Exam Review Flashcards
3 side effects of Singulair (not allergy or rash).
Nausea, headache, abdominal pain, vivid dreams, increased risk of depression, aggression, suicidality, nightmares, personality changes
Where does TB get reactivated in the lungs? Why?
Reactivation favors the upper lung lobes especially within the lung apex. This is likely due to the higher oxygen tension in these upper pulmonary segments, as discussed in ventilation-perfusion ratio distribution, which facilitates growth of the obligate aerobe M. tuberculosis.
- Higher oxygen tension
- Lympho-hematogenous spread from the initial infection.
Foci of primary pulmonary tuberculosis favor the lower and middle lung lobes since infective respiratory droplets tend to deposit there
In Canada, reactivation more common than reinfection
List 3 features of the primary complex in TB. Where does this occur in the lungs?
The triad of: 1) primary focus 2) local tuberculous lymphangitis (basically inflammation of surrounding lymphatic channels) 3) enlarged regional lymph nodes = the primary complex.
Ghon focus = happens when cellular infiltrates continue to the site of infection, the center for the granuloma because caseous (or necrotizing) and you can see a fibrocalcific residua on imaging
Ghon complex = Ghon focus + calcified granulomatous focus in a draining lymph node
Some reasons for low VO2 max
1) Deconditioning
2) CV limitation
3) Resp limitation
4) MSK
5) Anxiety
How to decide a maximal test for a CPET
RER ≥ 1 HR = max (>90% max) Borg exhaustion >9/10 VO2 plateau Evidence of ventilatory limitation
CPET variables (VO2, O2, dead space, eCO2, HR reserve) for a healthy patient
VO2 max: normal HR reserve: absent to small Sat: stable Dead space: decreases eCO2: Decrease
CPET variables (VO2, O2, dead space, eCO2, HR reserve) for a patient with CV limitation
VO2 max: Decreased HR reserve: absent to small Sat: stable Dead space: Decrease eCO2: Decrease
CPET variables (VO2, O2, dead space, eCO2, HR reserve) for a patient with obstructive lung disease
VO2 max: Decreased HR reserve: present Sat: decreases Dead space: Decrease eCO2: Increase or stable
CPET variables (VO2, O2, dead space, eCO2, HR reserve) for a patient with pulmonary vascular disease
VO2 max: Decreased HR reserve: present (small) Sat: decreases Dead space: Increase or stable eCO2: Decrease
CPET variables (VO2, O2, dead space, eCO2, HR reserve) for a patient with NM disease
VO2 max: Decreased HR reserve: large Sat: stable Dead space: Decrease eCO2: Increase or stable
4 reasons for a false positive D-dimer (kid with sudden onset chest pain)
Infection Cardiovascular disease Cancer Trauma Pregnancy Recent surgery.
8 risk factors for teen GIRL for PE.
OCP Obesity Pregnancy Smoking Immobility post surgery eg scoliosis Trauma and immobility Inherited Thrombophilia: eg menorrhagia in teens SLE; increased in Girls Central lines Inflammatory bowel disease F slightly more common ALL M>F Nephrotic syndrome M>F
Equation for static compliance
C = Vt/Pplat - PEEP
What is dynamic compliance?
Change in volume of lungs / change in alveolar distending pressure during the course of a breath.
Complaince decreases with increasing resp rate and with increasing airway resistance
Equation for dynamic compliance
C = Vt/PIP-PEEP
Patient with query PCD, normal ciliary ultrastructure. List 3 other tests you can use to diagnose PCD.
1) Nasal nitric oxide
2) Genetics
3) Digital high speed videomicroscopy
4) Immunofluorescence of dynein proteins
5) Transmission electron microscopy (normal in this question)
Causes of bronchiectasis
1) Impaired immune function
- SCID, CVID, AT, HIV etc
2) Ciliary dyskinesia (Primary, functional)
3) Abnormal mucus (CF)
4) Clinical syndromes
- Young’s syndrome, Yellow nail lymphedema syndrome, Marfan syndrome, Usher syndrome
5) Congenital tracheobronchomegtly
- Mounier-Kuhn syndrome, Williams-Campbell, Ehlers-Danlos
6) Aspiration syndromes
- Recurrent small volume, primary aspiration, TEF, GERD
7) Obstructive bronchiectasis (FB, tumour, LN)
8) Other pulmonary disease association
- ILD, BO, ABPA, BPD, Tracheobronchomalacia
9) Others
- Alpha-1 antitrypsin deficiency, post transplant, autoimmune, posttoxic fumes, eosinophilic lung disease
List 2 evidence based medicine ways to treat a new PsA infection in a CF patient
ELITE: Inhaled tobramycin 300mg BID for 28 days
EPIC: Inhaled tobramycin 300mg BID for 28 days and oral ciprofloxacin 14 days –>addition of cirpo didn’t make a difference to rate of eradication
What is closing volume? How does it differ from a young child to a 70 year old healthy person?
Closing volume is the lung volume at which the small airways at the dependent regions of the lungs start closing
In an infant, the closing volume is more than FRC ; in childhood, the closing volume decreases less than FRC ; towards older age the closing volume again increases and FRC and RV also increases.
FRC and RV increases with age while TLC remains constant and Closing volume increases with age and crosses FRC around 50s
List 2 reasons why drowning causes ARDS.
1) Surfactant washout and dysfunction due to both freshwater and salt water drowning
2) Neurogenic pulmonary edema- due to asphyxial brain injury
3) Negative pressure pulmonary edema due to inspiration against a closed glottis
List 2 mechanisms for why compliance is reduced in ARDS
1) Alveolar flooding with protein rich fluid due to epithelial and endothelial injury due to inflammation causes surfactant dysfunction and decreases lung compliance
2) Decreased FRC due to non aerated or consolidated/atelectatic lung more in the dependent lung regions
Kid with aspergillus in the home, list 3 disease this can cause and the associate immunoglobulin.
Allergic bronchopulmonary aspergillosis- IgE
Hypersensitivity pneumonitis (farmer’s lung, composter’s lung etc ) -IgG
If immunocompromised - Invasive pulmonary aspergillosis , aspergillus tracheobronchitis , invasive rhinosinusitis , disseminated aspergillosis–>CGD, HSCT and low neutrophils, HIV, SCID
Bone marrow transplant is more of an issue for invasive aspergillosis than solid organ like lung
Kid sick with asthma, give 3 important components of the mechanical ventilation strategies for asthma patients and why.
1) Low tidal volumes as there is already hyperinflation
2) Lower I:E ratio - I:E ratios 1:3 and more as there is need for more time for expiration due to increased expiratory time constant (Which means low respiratory rates and long expiratory times). (Of note, a normal I:E ratio is 1:2)
3) Can have high peak airway pressures (VOLUME CONTROL) but limit plateau pressures to <30(as that is the true distending pressure of the lungs )
What is LCI?
LCI is the ratio of cumulative exhaled volume to FRC (number of lung turnovers) while washing out an inert gas from the lung to its 1/40th concentration during tidal breathing.
LCI is calculated as the cumulative expired volume (CEV) normalized by FRC (LCI = CEV/FRC)
The value of LCI indicates the overall lung ventilation homogeneity at the point when the test gas is cleared from the lungs
Normal = <7-7.5
In a CF kid, do you expect the LCI to be normal/abnormal? Is abnormal a higher or lower value than normal?
Abnormal = Higher
If the patient has a complete left main stem bronchus obstruction, how does this affect LCI?
FRC measured with MBW is lower, as it only measures ventilated lung
CEV would be lower
Therefore ? no change to LCI
3 determinants of RV in a healthy person.
Expiratory muscle strength
Chest wall compliance and shape
Lung elasticity
It is determined by the force generated by the muscles of expiration
and the inward elastic recoil of the lungs as they oppose the outward elastic recoil of the chest wall.
Dynamic compression of the airways during the forced expiratory effort may also be an important determinant of the RV as airway collapse occurs, thus trapping gas in the alveoli
DMD - indications for nocturnal ventilation?
Baseline SpO2 <95% or end tidal CO2 >45 when awake
AHI >10 on PSG OR 4 + episodes of SpO2 <92% OR drops in SpO2 of at least 4% /hr of sleep
DMD - Indications for cough assist?
Respiratory infection present and peak cough flow <270lpm
Baseline peak cough flow <160 or max expiratory pressure <40cm H20
Baseline FVC <40% predicted OR <1.25L in older teen/adult
CF patient with B. cepacia – Genomovar II - are you worried?
No, we are not worried because B multivorans only rarely, if ever, causes cepacia syndrome
**worry about Cenocepacia - genomovar III
Which B. cepacia genomovar is worrying?
B cenocepacia
What are the clinical manifestations of B cenocepacia?
Severe decline in CF lung function possibly developing into a life-threatening systemic infection known as cepacia syndrome.
Extremely difficult to treat because of virulence and resistance
Cepacia syndrome is characterized by a rapidly progressive fever, uncontrolled bronchopneumonia, weight loss, and in some cases, death.
List 2 investigations used to confirm a diagnosis of CF.
Sweat chloride (>=60mmol/L) Cystic Fibrosis Transmembrane Conduction Regulator (CFTR) mutation analysis
If initial CF investigations are indeterminate, list 4 investigations that can help to make a diagnosis of CF.
- Nasal potential difference
- Intestinal current measurement (from rectal biopsy)
- Fecal elastase to assess for pancreatic insufficiency
- Ultrasound to assess for pancreatic echogenicity and
- Congenital bilateral absence of the vas deferens
- Chest CT for assessment of bronchiectasis
Viral pre-school wheeze:
What cell type predominates in the BAL?
What cytokine activates this cell?
Neutrophils
IL-8, (Il-1, IL-17)
Atopic pre-school wheezer – what cell type predominates on BAL?
Eosinophil
IL-5
Bronchogenic cyst: most likely location? Histology?
Bronchogenic (foregut) cyst are closed epithelium lined sacs developing abnormally in the thorax from the primitive developing upper gut and respiratory tract. Typically single and unilocular.
50% are situated in the mediastinum close to the carina (less frequently adjacent to the esophagus and alongside tracheobronchial tree), more common on the right.
Cyst lined by respiratory-type epithelium. Wall is often fibrous and inflamed, may contain seromucous glands and cartilage plates.
Peripheral chemoreceptors – location? What do they respond to?
Peripheral chemoreceptors are located in
(1) the carotid bodies (at the division of the common carotid artery into its external and internal branches) and (2) the aortic bodies (between the ascending aorta and pulmonary artery).
They respond primarily to changes in PO2. They are also responsive to changes in arterial pH (carotid but not aortic bodies) and CO2.
Central chemoreceptors – location? What do they respond to?
Central chemoreceptors are located in the ventral lateral medulla. Increases in PCO2 or H+ concentration produce an increase in ventilation.
Characteristics of PTLD
PTLD is a broad term describing B cell proliferation post transplant, often related to EBV
Can occur in patients with solid organ (eg. Lung transplant) and HSCT. For our purposes, more common amongst lung than HSCT
Pathophysiology: EBV positive B cell proliferation because of T cell suppression
A late complication >6 months in lung transplant and within the first year (more so in first 1-5 months) post HSCT
Risk factors for PTLD
Lung transplant, as compared to other solid organ transplants, since higher level of immunosuppression
More common in CF patients with lung transplant partially due to age of patients, but also CF specific risk factors
Children, since more likely to be EBV negative
HSCT: allogenic, T cell depleted graft, EBV negative recipient with EBV positive donor
Imaging in PTLD
- Mediastinal lymphadenopathy
- Pleural effusion
- Pulmonary nodule
- Pulmonary mass
- Consolidation
3 Treatment options for PTLD
Decrease immunosuppression, though increased risk of rejection
Rituximab if CD20+
Chemotherapy (CHOP protocol – cyclophosphamide, doxorubicin, vincristine, prednisone) or radiation therapy
Sarcoidosis - 3 common CXR findings.
- Bilateral lymphadenopathy
- Normal CXR
- Reticular opacity
- Ground glass opacity
- Volume loss (in stage 4)
Sarcoidosis - 3 common CT findings.
- Thickening of interlobular septa
- Beaded or irregular thickening of the bronchovascular bundles
- Nodules along bronchi, vessels (peribronchovascular), and subpleural regions
- Bronchial wall thickening
- Ground glass opacification
- Parenchymal masses or nodular consolidation, occasionally with cavitation
- Parenchymal bands
- Cysts
- Fibrosis with distortion of the lung architecture and traction bronchiectasis
- CT findings show upper to mid lung zone predominance
Stages of sarcoidosis
Stage 0: normal CXR
Stage 1: bilateral lymphadenopathy
Stage 2: bilateral lymphadenopathy + interstitial infiltrate
Stage 3: parenchymal infiltrate with no bilateral lymphadenopathy
Stage 4: pulmonary fibrosis
2 lab tests for sarcoidosis – describe the abnormality.
Increased ESR, CRP
Hypercalcemic, hypercalciuria—in 10-30% of cases
Increased angiotensin converting enzymes (ACE), in case 60-80% of cases —>so ACE is more sensitive than high calcium levels
Anemia
Hypergammaglobulinemia
Granulomatosis with Polyangitis:
6 pulmonary/lower airways manifestations?
Upper airway: Sinusitis Nasal septal ulceration Otitis media Mastoiditis Oral ulcer Saddle nose deformity Subglottic stenosis Epistaxis
Lower airway: Diffuse alveolar haemorrhage Nodules, which may or may not be cavitating Mediastinal lymphadenopathy Pleural effusion Tracheal stenosis
Specific blood test for Dx of GPA
PR3 ANCA
What is the breathing abnormality you see in Rett’s and when does it occur?
Abnormal breathing while awake
- Hyperventilation and hypocapnea alternating with hypoventilation/apnea during which they may have oxygen desaturation
- Breathing is normal in between episodes
- Hypoventilation/apnea can last 20-120 seconds
- During hyperventilatoin: child is excited or agitated
- During hypoventilation/apnea: child doesn’t appear distressed, they may even be calm and smiling
- No associated bradycardia
- There can be severe cyanosis and EEG seizures
Baby on HFO with oxygen saturation in the right hand of 93% and in the left foot of 88%. Explain the difference.
Difference = differential cyanosis
difference in oxygen saturation (O2 sat) of at least 5% or a difference in partial pressure of oxygen (Pao2) of at least 20 mm Hg between the arms and legs associated with congenital heart disease or persistent pulmonary hypertension of the newborn
2 causes of differential cyanosis
PPHN - with shunting primarily or exclusively across PDA. (If shunting was primarily from right atrium to left atrium, then were would be cyanosis as opposed to differential cyanosis)
Critically obstructive left sided cardiac disease, where there is enough antegrade flow to provide right subclavian flow, but distal flow is supplied across ductus arteriosus, critical aortic stenosis, critical coarctation, interrupted aortic arch
What is the mechanism of iNO?
Inhaled nitric oxide selectively dilates pulmonary vasculature in ventilated areas of the lung.
Mechanism of action: NO activates soluble guanylyl cyclase (sGC) to produce cyclic guanosine monophosphate (cGMP) leading to decrease vascular smooth muscle tone (ie, vasodilation)
Histology for old BPD
- saccular stage
- thinning of interstitium
- increased airspaces (sacs)
- vascular expansion
- fibroproliferative changes
Histology for new BPD
- canalicular stage
- undifferentiated epithelial cells
- paucity of capillaries
- vascular expansion
- reduced SA
2 abnormalities on autopsy of T21 kid’s lungs, who was otherwise healthy
Alveolar simplification
Subpleural cysts
Newborn with BPD on home oxygen. Give 1 advantage and 2 disadvantages of oxygen concentrator vs. cylinder. How does a concentrator work?
Oxygen concentrator:
- Filter room air and removes nitrogen so that purified O2 can be delivered
- Concentration of up to 95%
- Large , needs electrical source (immobile) or small battery powered( mobile).
- Need back up cylinder.
- Noisy
- Higher up-front cost, but very little long-term maintenance cost
- Safer, create oxygen as needed, limiting the concern for oxygen leaks
Oxygen Cylinder:
- Metal tanks containing pressurized oxygen or liquid oxygen released at specific flow rates to provide oxygen to the patient (
- Concentration of up to 100%
- Lighter, more portable
- Quiet
- Lower initial cost. However, greater cost over time as they need to be refilled or replaced frequently
- Small possibility of a leak causing safety concerns due to an increased chance of fire ignition
Mother with child with TB, she heard steroids will reduce fever. She wants steroids.
List two situations/indications where steroids are used in TB.
TB meningitis
TB pericarditis
Causes of localized bronchiectasis
FB, lung malformation, TB, obstructive (external compression), aspiration, tumour, infection (pneumonia)
CCHS: what gene?
PHOX 2B
How does the gene in CCHS affect/lead to non- respiratory complications?
The gene is typically responsible for expression regulation of genes involved in the development of the autonomic nervous system
List 3 non-respiratory complications of CCHS
Hirschsprung Abnormal pupillary response Cardiac asystole, sinus pauses Development of neural crest tumours ANS dysregulation
List the 6 classes of CF genetic mutations. Briefly describe each.
Class 1: Protein synthesis defect (BLUEPRINT for making a door, for example) - premature termination codons (PTC)
Class 2: Protein maturation defect (MANUFACTURER)
misfolding, premature degradation and impaired protein biogenesis
Classic example: delF508
Class 3: Gating defect (DOOR NO OPEN)
impair the regulation of the CFTR channel, resulting in abnormal gating characterized by a reduced open probability
Example: G551D
Class 4: Conductance defect (DOOR TOO SMALL)
conductance defect-alter the channel conductance by impeding the ion conduction pore, leading to a reduced unitary conductance
eg R117H with 5T
Class 5:Reduced quantity (TOO LITTLE PRODUCTION)
Alter its abundance by introducing promoter or splicing abnormalities
Class 6: Reduced stability (POOR QUALITY MATERIAL)
destabilize the channel in post-ER compartments and/or at the plasma membrane by reducing its conformational stability
Sarcoidosis; list the distinctive lesion on histopathology.
Non-caseating granulomas
Other presentations (non-lung) of Sarcoidosis
Granulomatous lesions can occur in any organ but most commonly in lung, lymph nodes, eyes, skin, liver, heart
Non-specific symptoms are common (fatigue, weight loss, fever)
Lofgren syndrome is less common in children (acute arthritis, BHL, erythema nodosum)
Can have cardiac, ocular, neurological, renal involvement and hypercalcemia/hypercalciuria
Common skin lesions include papules, plaques, nodules, changes in old scars, erythema nodosum, hyperpigmented lesions, and hypopigmented lesions.
Central nervous system involvement may present with headache, seizures, cranial nerve palsies, motor signs, hypothalamic dysfunction, and hydrocephalus.
Early onset sarcoidosis (<4yo) → skin rash, uveitis, arthritis, absence of lung disease
PFT Findings in Sarcoidosis
often normal, advanced = restriction with low DLCO
Bronch Findings in Sarcoidosis
Specific changes of waxy yellow mucosal nodules and nonspecific changes → erythema, edema, granularity and cobblestoning of the airway mucosa and bronchial stenosis (typically in the lobar and segmental bronchi).
BAL Findings in Sarcoidosis
lymphocytosis in >85%, normal or low neutrophils (except in late disease) and CD4:CD8 is increased
Diagnosis in Sarcoidosis
Diagnosis is established when typical clinical features are supported by a tissue biopsy showing noncaseating granulomas
Prognosis in Sarcoidosis
Generally adults do quite well - 2/3 spontaneous remission in 2 years
consider steroids for severe cases
When to consider steroids in Sarcoidosis
Pulmonary: worsening symptoms, decreasing lung function, progressive imaging findings
Any of: cardiac, ocular, renal, CNS, hypercalciuria
Severe clinical symptoms
What is Harrison sulcus/groove?
A horizontal groove along the lower border of the thorax corresponding to the costal insertion of the diaphragm. It reflects increased work of breath against airflow resistance eg Asthma
Describe 2 pathophysiologies that can lead to Harrison sulcus.
Asthma
Bronchiolitis Obliterans
Rickets - soft ribs drawn in by diaphragm under tension
Tends to be more common in infancy when the chest wall is softer
Why the low oxygen saturation with methemoglobinemia?
Hemoglobin converted from ferrous(Fe2+) to ferric state (Fe 3+) by oxidation by MetHb. The presence of ferric heme molecules causes a structural change in the hemoglobin molecule, resulting in reduced oxygen-carrying capacity and impaired unloading of oxygen at the tissue. This left shift in the oxygen saturation curve results in functional anemia.
The low saturation is due to the waveband of the saturation monitor. Pulse oximetry can only measure two frequencies, oxyhemoglobin and reduced Hb. As MEtHb rises the saturation falls and plateaus at 85%. Despite normal Arterial PO2. So called saturation gap
How do you test for Methemoglobinemia and how do you confirm it?
Arterial Blood is chocolate brown colour
Measure blood level of MetHb (blood gas)
Evelyn Malloy method
Co-oximeter–>gives a print out of various hemoglobin
Features of Pierre Robin Syndrome
Micrognathia
Big tongue posterior, glossoptosis
Airway obstruction
+/-Cleft palate
Management of Pierre Robin Syndrome
Airway obstruction: ONO, Cap Gas, PSG Feeding difficulties: OT assessment, formal feeding study Airway Obstn Non-Surgical: - Lateral or prone positioning. - Nasopharyngeal airway - CPAP/BIPAP Surgical: Tongue-Lip adhesion to increase oropharyngeal gap Floor of mouth release Mandibular distraction Tracheostomy* Feeding: NG or G tube
List 3 ways a history of TEF can contribute to airway inflammation and bronchospasm.
Asthma is seen in TEF
Patients with a history of EA/TEF have an abnormally high prevalence of bronchial hyperreactivity, suggesting that airway reactivity in these individuals may be due to events in early childhood such as chronic aspiration, rather than atopy
Airway malacia
Allergy/Atopy more common
Aspiration/Reflux
Protracted bronchitis - (more prominent in younger children with TEF)
Recurrent TEF
Cytokine for:
1) TH1
2) TH2
Th-1 =IL-12
TH1 — IFNg, IL-2, TNF-a = Cell mediated immunity
Th-2 = IL-4
TH2—IL-4, IL-5, IL-13 = Allergy, IgE, eosinophilia, AHR
BPD going on home O2. What is the goal of oxygen saturation according to Current BTS criteria?
More than or equal to 93% for 95% of the recording time if continuous oxymetry (BTS 2009 ) If BPD + PHT- more than 94% In CF more than or equal to 90% Sickle more than or equal to 94 % In ATS 2018- BPD MORE THAN 93 % AHA- BPD with PH - 92-95%
Equation for shunt calculation
QS/QT=CcO2-CaO2/CcO2-CvO2 x 100 %
Normal values for a shunt
Up to 5% is accepted
Other than Idiopathic PAP. List one congenital PAP.
Surfactant protein B deficiency, ABCA3 deficiency , NKX2 deficiency , Lysinuric protein intolerance , Meth Transfer RNA synthetase deficiency (MARS) etc
Definition of congenital PAP
This term is usually used when they present early in newborn or infancy . Most of the findings and pathology is due to interstitial changes though alveolar proteinosis is also seen
List one acquired PAP- presents after 2 years
autoimmune PAP (GMCSF receptor antibody)
Causes of primary PAP
Primary= Autoimmune PAP (GMSCF receptor antibody) Hereditary PAP (receptor deficiency)
List 2 treatments options for PAP.
Whole lung lavage for primary PAP
GMCSF -inhaled or s/c
Immunosuppression : steroids/Hydroxychloroquine
Lung transplant in congenital PAP and acquired PAP
Child previously healthy. No history of trauma. CXR shows raised left hemidiaphragm.
Eventration left diaphragm
Volume loss left lung due to hypoplasia or collapse
Unilateral Diaphragmatic palsy (many causes are idiopathic if no trauma/surgery ) - eg. due to left mediastinal mass causing phrenic nerve compression
Subpulmonic pleural effusion
(with diaphragmatic hernia, you shouldn’t be able to actually see the diaphragm)
Abdominal mass - eg. splenic
Patient with raised hemidiaphragm. How does this affect his VC? Why?
VC is decreased since abdominal organs push on the lung affecting compliance of the lung
List 2 causes for unilateral VC paralysis
More common than bilateral
Birth trauma, cardiac surgery ( PDA ligation, coarctation repair ), neck surgery , idiopathic (all causes of unilateral can theoretically cause bilateral)
List 2 causes for bilateral VC paralysis.
Birth trauma, Chiari malformation, idiopathic , hereditary neuropathies
What is the nerve that controls the motor part of the larynx? From which major nerve does it originate from?
Recurrent laryngeal nerve supplied all muscles of larynx except cricothyroid which is supplied by superior laryngeal nerve
Originates from Vagus nerve
Describe/name the 6 classes of CF mutations
Class I: protein synthesis defect
frameshift, splicing, or nonsense mutations that introduce premature termination codons (PTC), resulting in severely reduced or absent CFTR expression.
Class II: maturation defect misfolding, premature degradation by the endoplasmic reticulum (ER) quality-control system, and impaired protein biogenesis, severely reducing the number of CFTR molecules that reach the cell surface. Prototype is Phe508del(although this mutation also can have additional class 3 and class 6 function if escapes ER degradation)
Class III: gating defect
impair the regulation of the CFTR channel, resulting in abnormal gating characterized by a reduced open probability ie. G551D
Class IV: conductance defect-alter the channel conductance by impeding the ion conduction pore, leading to a reduced unitary conductance eg R117H with 5T (also has some class 3) → with 5T makes it more significant for CF (without 5T is unknown significance)
Class V: reduced quantity- do not change the conformation of the protein but alter its abundance by introducing promoter or splicing abnormalities
Class V1: Reduced stability
Components of Ivacaftor
Kalydeco -Gating potentiator ) approved for class 3 and one class 4 mutation(R1117) approved more than 6 months of age
Components of Lumacaftor
(Corrector) partially partially reverts the ΔF508-CFTR functional expression defect by stabilizing the NBD1-MSD1/2 interface, by alone no action but modest effect in combination (Orkambi) with Ivacaftor in homozygous df508 - approved for more than 2 years
Components of Symdeko
Tezacaftor + ivacaftor -for homozygous df 508 and one residual function - approved for more than 6 years , symdeko has less side effects than orkambi and less drug interactions. (Not that much more efficacious than orkambi)
Components of Trikafta
Teza+Iva+elazacaftor(next generation corrector) -for homo and hetero df 508
How do the combination of 2 CFTR modulators work for improving CFTR function?
Ivacaftor is a CFTR gating potentiator which is fda approved for use in class 3 and one class 4 mutation(R1117) ,more than 6 months of age
Lumicaftor is a CFTR corrector which partially reverts the ΔF508-CFTR functional expression defect by stabilizing the NBD1-MSD1/2 interface, by alone no action in homozygous df 508 . When ivacaftor used in combination with lumicaftor (Orkambi) it has modest effects in homozygous df 508.
Df508 is mainly class 2 but even with lumacaftor, only about 1/3rd of the structurally normal protein reaches the cell surface; addition of ivacaftor keeps the channel open for a longer time and also works on the class 3 action of df508 .
Child on symbicort you want to change them to Advair – give the dose equivalents of the steroid and the LABA.
Symbicort TURBUHALER comes in three strengths - 100 BUDESONIDE / 6 FORMOTEROL and 200 BUDESONIDE /6 FORMOTEROL, Forte 400 Budesonide /12 Formoterol
Advair MDI comes in two strengths - Fluticasone 125/ Salmeterol 25 Fluticasone 250 /Salmeterol 25
Equivalent dose of Budesonide DPI 200 = 125 Fluticasone MDI and discus
Equivalent dose of Formoterol 12 = 50 Salmeterol (multiple head to head comparison studies have used these dose )
While converting from symbicort 200/6 1 inhalation = Advair MDI 125/25 1 puff
Patient with asthma, worsening clinical picture .. reasons (other than adherence and accurate diagnosis)
Wrong inhaler technique Presence of environmental triggers Smoking - active and passive ABPA complicating asthma Neutrophilic asthma Presence of un addressed comorbidities like obesity, OSA, allergic rhinitis, GERD, VCD ,anxiety
At what dose do you see systemic side effects of high dose fluticasone?
> 500mcg per day
What are the CTS operational criteria for diagnosis of asthma in pre-schoolers?
1) Recurrent (>/=2) episodes of asthma like symptoms or exacerbations even when triggered by virus
2) Objective documentation of airway obstruction ( or convincing report of symptoms )
3) Objective documentation of reversibility (or convincing and repeated response report by parent ) of airway obstruction with treatment with SABA/steroid when documented/reported obstruction or convincing parental report of improvement in symptoms to 3 month of medium dose ICS)
4) No alternative diagnosis
Low and Medium dose of Fluticasone for Preschoolers
Low = 100-125 mcg/day Med = 200-250 mcg/day
Characteristics of Intralobular Pulmonary Sequestration
- Shares visceral pleura
- More common with infections
- Doesn’t usually have associated anomalies
- Blood supply = Aorta, Venous usually to left atrium but can also be to right side
Characteristics of Extralobular Pulmonary Sequestration
- Own visceral pleura
- Usually detected incidentally on imaging
- More common to have associated anomalies
- Blood supply = Aberrant vessel from Aorta, Venous drainage to right atrium
End-expiratory volume is volume left at end-expiration vs FRC, these are same in children/adults, but not in infants. Why?
Expiratory breaking by diaphragm keeps the end expiratory volume above FRC- this is because of very compliant chest wall . FRC is determined when lung recoil is balanced by chest wall recoil. Hence FRC is more closer to residual volume.
Airway closure is above FRC so need to have a higher end expiratory volume, above FRC
How is the closing volume different in an obese person. Explain why.
Because the operating volume of the lung is small (low FRC ) , airways close early
In normal health, closing capacity is less than FRC (closing capacity = closing volume +RV)
In obesity , because FRC is reduced and the residual volume (RV) is not, ERV declines. ERV reduction is greatest in the supine position when the diaphragm ascends in the chest, and the weight of the lower thorax and the abdomen is applied to the lungs. At this point, the ERV may approach or be exceeded by the closing volume and gas may be trapped in the chest.
Effect of obesity on lung volumes
Compliance - lung chest wall and resp system compliance is reduced
TLC - very little effect
FRC- low
ERV- decreased
RV - very little effect
RV/TLC - normal to slightly increased
DLCO increased due to increased pulmonary capillary blood volume
Spirometry - Usually normal in adults ; airway dysynapsis in children ( FVC disproportionately increased to FEV1 , decreased FEV1/FVC ratio in children )
6 Long term complications of TEF
Tracheomalacia with brassy TEF cough
TEF recurrence
Recurrent aspiration leading to bronchitis and bronchopneumonia
Gastroesophageal reflux ( –>Barrett’s esophagus)
Esophageal stricture
Dysphagia
Obstructive and restrictive ventilatory defects
Airway hyperreactivity
4 causes of eosinophilic pleural effusion
Pneumothorax
TB
Acute/Chronic Eosinophilic pneumonia
Hydatid disease
FEV1 decline for exercise induced bronchospasm
10%
Components of the Starling equation
Qf = Kf[(Pc − Pis) − σ(πpl − πis)]
where Qf = net flow of fluid
Kf = capillary filtration coefficient; this describes the permeability characteristics of the membrane to fluids and the surface area of the alveolar-capillary barrier
Pc = capillary hydrostatic pressure
Pis = hydrostatic pressure of the interstitial fluid
σ = reflection coefficient; this describes the ability of the membrane to prevent extravasation of solute particles such as plasma proteins
πpl = colloid osmotic (oncotic) pressure of the plasma
πis = colloid osmotic pressure of the interstitial fluid
Note that the surface area of the alveolar-capillary barrier is included in the Kf.
The Starling equation is very useful in understanding the potential causes of pulmonary edema, even though only the plasma colloid osmotic pressure (πpl) can be measured clinically.
In a CF patient, what are 4 meds that are QT prolonging?
PPIs
Bronchodilators (e.g, albuterol, formoterol, salmeterol)
Anti-inflammatory (e.g., Azithromycin)
Fluoroquinolone (e.g, Ciprofloxacin)
Anti-fungal (e.g., voriconazole)
Anti-mycobacterial medications (e.g,. Bedaquiline, Clofazamine)
Motility agents (Domperidone, Cisapride)
An adolescent girl wants to take Orkambi. What are 5 meds that are made less effective due to its induction effects.
Macrolide Antibiotics (clarithromycin, erythromycin)–generally, need to dose adjust
Antifungals (voriconazole, ketoconazole, itraconazole, posoconazole)–generally, need to dose adjust
PPIs, H2 blockers, antacids (ranitidine, omeprazole, esomeprazole, lansoprazole)
Hormonal contraceptives
Immunosuppressants (cyclosporine, tacrolimus)
Steroids (Prednisone/Methylprednisolone)–practically, don’t need to dose adjust
Anti-inflammatories (ibuprofen) Montelukast Benzodiazopines (midazolam) Anti-depressants (Citalopram, Escitalopram, Sertraline) Oral hypoglycemics Warfarin
Ivacaftor is metabolized by cytochrome CYP3A. (don’t use a strong inducer with Ivacaftor. If it’s a strong inhibitor, you can still use the drug, but you need to do a dose adjustment). Since ivacaftor is part of all the CF drugs, this is very relevant.
strong CYP3A inducers(not recommended) and inhibitors(need dose adjustment except rifabutin which is not recommended)
4 pulmonary complications of Duchenne’s
Hypoventilation: + obstructed Sleep disordered breathing
Recurrent infections: poor cough clearance,
Aspiration: swallowing dysfunction
Scoliosis
Cor pulmonale:
Tracheostomy, small number of patient
One advantage and one disadvantage of transcutaneous CO2
Advantage of PTCCO2 monitoring compared to PETCO2 is that the accuracy of transcutaneous measurements is not degraded by mouth breathing, supplemental oxygen, or mask ventilation
The signal has a longer response time than the PETCO2 to acute changes in ventilation. PTCCO2 will not provide data for breath-by-breath changes, e.g., changes in the first few breaths after an apnea.
Poor seal on skin pick up
V/Q mismatch of lung disease
One advantage and one disadvantage of end tidal CO2
Nasal prongs , side stream measurement Advantage Reflects alveolar gas concentration, ventilation during sleep Breath by Breath changes Real time
D:
Mouth breathing and occlusion of the nasal cannula can impair the ability of end-tidal PCO2 monitoring to detect apnea
Low tidal volume and fast respiratory rates will impact ability to measure accuracy
Leak in circuit, or mouth
Poor signal may be obtained with poor positioning of the cannula, rapid respiratory rates without stable exhaled CO2 levels, mouth breathing, simultaneous delivery of oxygen, and blockage of the cannula with secretions or humidity
Hydatid lung disease. What are 5 features on CT.
Location: periphery, centre or hilum Pulmonary cyst Regular shaped cyst Thin walled cyst, Water lily sign Meniscus, crescent sign Bronchial displacement Pericentric emphysema Air fluid level
Hydatid lung cyst: surgeon wants to resect. Do you agree and why?
No - Risk of rupture and seeding, anaphylaxis
Percutaneous drainage
Medical treatment with albendazole (alone has limited success)
2 features of pulmonary emboli on CT
Lack of flow distal to pulmonary artery
Filling defect in Pulmonary artery
Non-Specific = Parenchymal infiltrates, Atelectasis
Asthmatic on continuous inhaled salbutamol in ICU. 5 other steps to take before intubation.
Atrovent 3 doses IV Magnesium IV Aminophyline IV Methly prednisone IV salbutamol BIPAP Heliox
Support
O2
Steroids
Child with suspected histoplasmosis. You hear right sided wheeze. Why does he have this?
“classical sign” due to bronchial compression
Child with airway papillomatosis. Name two serotypes that cause this.
HPV 6 and 11
What are 4 long term complications of airway papillomatosis
Airway obstruction
Distal involvement including the tracheal and tracheobronchial tree
Requirement for tracheostomy
Pulmonary cavitation
Malignant transformation: esp with HPV 11
Abbreviated A-a gas equation
PAO2 = PiO2 - (PaCO2/R)
List four pulmonary complications of Hurler’s syndrome
Recurrent respiratory infections Upper airway obstruction Obstructive sleep apnea Alveolar hypoventilation Atelectasis
Causes of upper airway obstruction in Mucopolysaccharidosis
An enlarged tongue and bone
Craniofacial abnormalities, namely micrognathia, result in predominant nasal breathing and oral
snoring.
Upper airway obstruction and OSAS, combined with thoracic cage deformity and tracheal distortion due to shortened spinal height = frequent total airway collapse.
List four anatomical anomalies or conditions associated with complete tracheal rings
Pulmonary artery sling (most common) Double aortic arch (and many other CV) Tracheal bronchus Pulmonary hypoplasia Down syndrome Pfeiffer syndrome VACTERL
Very rare - there is a segment of the trachea, often distal, where the tracheal rings are
truly complete. Most common cause of congenital tracheal stenosis. Complete tracheal rings
result from a defect in embryogenesis after the eighth week of gestation causing a complete
cartilaginous ring with absence of the usual posterior membranous portion of the trachea.
List four non-infectious pulmonary complications of AIDS
Lymphoid interstitial pneumonitis Pulmonary tumours Bronchiolitis obliterans Bronchiectasis Immune reconstitution inflammatory syndrome (IRIS) Airway hyperreactivity/asthma Aspiration pneumonitis Pulmonary HTN (limited data in children) Upper airway disease
Respiratory disease is the most common complication occurring in human immunodeficiency virus (HIV)-infected children.
Acute disease = most likely to be infectious
List 4 histological findings in surfactant protein B deficiency
1) Alveolar type 2 epithelial cell hyperplasia
2) Interstitial thickening (same as mesenchymal thickening)
3) Finely granular lipoproteinaceous material and macrophages in alveoli distal air spaces
4) Abnormal lamellar body with large whirls and vacuolar inclusions
Child with CT finding of cavitating nodules diffusely. List four non-infectious etiologies
Inflammatory, such as granulomatous with polyangitis, rheumatoid arthritis, sarcoid
Fat emboli
Malignancy, such as squamous cell carincoma
Langerhans cell histiocytosis
Differential for cavitary lung lesions
CAVITY is the acronym to remember
C = cancer, such as squamous cell carcinoma
A = autoimmune, such as GPA, rheumatoid arthritis (rheumatoid nodules)
V = vascular, such as septic pulmonary emboli or
I = infection, such as bacterial or fungal, such as pulmonary abscess, pulmonary TB, NTAM, aspergillus
T = trauma, such as pneumatoceles
3 long term respiratory complications of marijuana use
?impaired lung function - increased FVC
Hyperinflation
Chronic cough, SOB, wheeze
Peripheral bullae and case reports of pneumomediastinum
Increased risk of pulmonary aspergillosis
3 acute respiratory complications of marijuana use
Acute irritation of the airway Cough Sputum production Wheeze, chest tightness Can also produce bronchodilation
3 complications of vaping
E-cigarette or vaping produce use associated lung injury (EVALI)—which has a very broad definition and varies pathologies including diffuse alveolar damage, acute eosinophilic pneumonia, hypersensitivity pneumonitis.
Suspected compounds: THC containing products, vitamin E. Other mechanisms of injury: pyrolysis, thermal injury, release of metals
Chronic:
- Chronic bronchitis
- Chronic decline in FEV1
- Chronic airflow obstruction and possible bronchiolitis obliterans –at least 1 case report, which was in a Canadian youth
Criteria of severe pulmonary disease associated with E-cigarette use
1) Use of an e-cigarette in 90 days before symptoms onset
AND
2) Pulmonary infiltrate on CXR or CT
AND
3) Absence of pulmonary infection including (at minimum) negative viral and influenza
4) No evidence of alternate diagnosis
5 long term non-infectious pulmonary complications of HIV
Bronchiectasis Bronchiolitis obliterans Aspiration Interstitial lung disease: Lymphoid interstitial pneumonia Malignancy—eg. Kaposi sarcoma Asthma Pulmonary hypertension
4 pulmonary complications of IBD
Tracheal stenosis
Bronchiectasis
Pulmonary nodules—including necrobiotic nodules
Colobronchial fistula
Hypersensitivity pneumonitis from medications such as mesalazine
Interstitial lung disease
What cell predominates in the airways of viral induced wheezing?
What is the cytokine MOST responsible for this?
Neutrophilia
IL17
What cell predominates in wheezing in an atopic individual?
What is the cytokine MOST responsible for this?
Eosinophils
IL5
IL4
IL13
What are four absolute contraindications to the live attenuated flu vaccine. What age group is this most effective for?
History of severe allergic reaction to any vaccine component or after previous dose of any influenza vaccine
Concomitant aspirin or salicylate-containing therapy in children and adolescents;
Children aged 2 through 4 years who have received a diagnosis of asthma or whose parents or caregivers report that a health care provider has told them during the preceding 12 months that their child had wheezing or asthma or whose medical record indicates a wheezing episode has occurred during the preceding 12 months;
Children and adults who are immunocompromised due to any cause (including immunosuppression caused by medications or by HIV infection);
Close contacts and caregivers of severely immunosuppressed persons who require a protected environment;
Pregnancy;
Receipt of influenza antiviral medication within previous 48 hours.
3 intrinsic immunity features of the respiratory system
1) Aerodynamic filtering done by the nose, including nasal turbinates, adenoids and tonsils – based on particulate size
2) Respiratory mucous, airway surface liquid layer and mucociliary clearance
3) Airway reflexes: eg. Sneezing, coughing and bronchoconstriction
4) Macrophages
Which immunoglobulin is most responsible for immunity in mucus?
Ig A.
Secretory IgA is the most predominant Ig isotype present in airway secretions and important for the mucosal response. Functions include: neutralising viruses & exotoxin, enhancing lactoferrin & lactoperoxidase activities and inhibits microbial growth.
4 histological and ultrastructural changes that are seen in surfactant protein B deficiency
1) Alveolar type II epithelial cell hyperplasia
2) Interstitial fibrosis
3) Poorly organised lamellar bodies (loosely packed lamellae and vacuolar inclusions, or fused lamellar bodies and multivesicular bodies)
4) Absence of tubular myelin
5) Lobular remodeling
6) Alveolar proteinosis
Acute complications of pulsed steroid therapy
CVS: BP changes - Hypotension/Hypertension, arrhythmias, circulatory collapse, cardiac arrest, sudden death, flushing
CNS: Headaches, seizures, altered behaviour (mood alteration, hyperactivity, psychosis, disorientation), sleep disturbances
Metabolic: Hyperglycemia, Hypokalemia
Immune: increased risk of infections
Anaphylactic shock (ass’d with the succinate ester of methylprednisolone)
Working up a kid with pulmonary hemorrhage. When would hemosiderin laden macrophages be positive (in how many days)?
First seen to be positive in the first 2 – 3 days after acute bleeding.
Oncology patient cannot tolerate Septra. Name 3 alternatives.
Trimethoprim-sulfamethoxazole (TMP-SMZ) is the preferred agent for both prophylaxis and treatment in children as well as adults.
- Pentamidine
Nebulised form - usually well tolerated. Main side-effects are coughing & wheezing, which can be prevented by the use of inhaled beta-agonists. Avoid in patients < 5 yrs old or if there is a history of asthma. - Dapsone
CI in patients with G6PD deficiency or those who experienced severe side-effects with TMP-SMX.
Adverse reactions: agranulocytosis, aplastic anaemia, rash, nausea and sulfone syndrome (rash, fever, hepatitis, lymphadenopathy and methemoglobinaemia) - Atovaquone
Most common side-effects include rash, nausea, diarrhoea, elevated transaminases and headache, which are usually mild. used in malaria as well!
Two types of CDH and where do they occur?
- Bochdalek - BACK (posterolateral) – 80% occur through the left pleuroperitoneal canal. Defect is in the diaphragm itself and usually there’s no associated membranous sac.
- MorgAgni (Anterior diaphragmatic hernia) - rare anterior defect of the diaphragm, also referred to as a retrosternal, or parasternal hernia. Accounting for ~ 23% of all CDH cases. Characterized by herniation through the foramina of Morgagni which are located immediately adjacent and posterior to the xiphoid process of the sternum
23 weeker. Describe the stage of formation their lungs are in.
Canalicular Phase (17 – 26 wks):
Respiratory bronchioles developing
- By the end of this stage each ends in a terminal sac (also termed a saccule).
- The glandular appearance is lost as the interstitium has less connective tissue and the lung develops a rich vascular supply that is closely associated with the respiratory bronchioles.
- The canalicular stage comprises the differentiation of the epithelia that allows the morphological distinction between conducting and respiratory airways. This distinction permits the recognition of the acinus/ventilatory unit for the first time.
What defines the primary acinus at 23 weeks?
That portion of lung distal to a terminal bronchiole and supplied by a first-order respiratory bronchiole or bronchioles.
Stages of lung development
“Every Pulmonologist Can See Alveoli”
1) Embryonic 4-7 wks
2) Pseudoglandular 5-17 wks
3) Canalicular 16-26 wks
4) Saccular 24 wks- term
5) Alveolarization 36 wks to 21 years
Structural events that happen during the Embryonic stage of lung development (3-7 weeks)
Lung buds; trachea, main stem, lobar, and segmental bronchi; trachea and esophagus separate
Structural events that happen during the Pseudoglandular stage of lung development (6–17weeks)
Subsegmental bronchi, terminal bronchioles, and acinar tubules; mucous glands, cartilage, and smooth muscle
Structural events that happen during the Cannalicular stage of lung development (16–26 weeks)
Respiratory bronchioles, acinus formation and vascularization; type I and II AEC differentiation
Structural events that happen during the Saccular stage of lung development (26-36 weeks)
Dilation and subdivision of alveolar saccules, increase of gas-exchange surface area, and surfactant synthesis
Structural events that happen during the Alveolar stage of lung development (36 weeks on)
Further growth and alveolarization of lung; increase of gas-exchange area and maturation of alveolar capillary network; increased surfactant synthesis
Causes of pleural fluid eosinophilia
Drugs Idiopathic Infection (bacteria, fungi, mycobacteria, parasites, virus) Inflammation (acute/chronic eosinophilic pneumonia, Churg-strauss, Rheumatoid effusion) Malignancy (lymphoma) PE Toxicity Trauma
Common causes of exudative pleural effusions
Infection Inflammatory/connective tissue disease Malignancy Lymphatic malformation/Chylothorax Post op surgical complications PE Abdominal Pathology Endocrine
Common causes of transudative pleural effusions
Cardiac disease Hepatic Cirrhosis Renal disease Hypoalbuminemia SVC obstruction
The criterion for the percent fall in FEV1 used to diagnose Exercise Induced Bronchospasm
10% decline
Grading of severity for Exercise Induced Bronchospasm
The severity of EIB can be graded as mild, moderate, or severe if the percent fall in FEV1 from the pre-exercise level is >10% but < 25%, >25% but <50%, and >50%, respectively.
Components of the Starling equation
Qf = Kf[(Pc − Pis) − σ(πpl − πis)]
where Qf = net flow of fluid
Kf = capillary filtration coefficient; this describes the permeability characteristics of the membrane to fluids and the surface area of the alveolar-capillary barrier
Pc = capillary hydrostatic pressure
Pis = hydrostatic pressure of the interstitial fluid
σ = reflection coefficient; this describes the ability of the membrane to prevent extravasation of solute particles such as plasma proteins
πpl = colloid osmotic (oncotic) pressure of the plasma
πis = colloid osmotic pressure of the interstitial fluid
Factors contributing to chronic lung disease in AIDS (Ex: LIP, chronic infection, IRIS, malignancies, bronchiectasis, BO, asthma)
Direct influences of HIV Immune dysregulation with increased inflammation Recurrent/severe infections ART Environmental exposures
ART may halt progression of lung damage but will not reverse established chronic disease
No ART = LIP, chronic/recurrent infections with bronchiectasis, BO, decreased lung function
Use of early ART prevents lung damage
Chronic lung disease = persistent bronchovascular reticular markings x 6 mos or more or consolidation/nodules x 3 mos or more
Characteristics in Lymphoid Interstitial Pneumonia (LIP)
in AIDS
Diffuse infiltration of lymphocytes and scattered nodules of mononuclear cells
Unclear etiology → ?lymphoproliferaton with response to the HIV alone or co-infection with another virus
EBV = common co-infection
Insidious course and slowly progressive
Median age = 2.5-3yrs
Dx = lung biopsy
Tx = non-specific → bronchodilators, oxygen, steroids
Some may progress to lymphoproliferative disease with polyclonal, polymorphic B-cell content with extranodal systemic and prominent pulmonary involvement or to malignant lymphoma
Most common pulmonary malignancy in AIDS
Non-Hodgkin Lymphoma
Factors relating to the risk of Aspiration Pneumonitis from AIDS
Esophagitis related to Candida, HSV, CMV etc. can be associated with swallowing difficulties and increased risk of pulmonary aspiration
Neurological impairment secondary to HIV encephalopathy can further increase this risk
Characteristics of Bronchiectasis in AIDS
May be focal or bilateral
May be associated with LIP or LRTI
Associated with severity of immunosuppression
Tx = optimizing ART, physio (airway clearance), treat intercurrent infections
Characteristics of Immune Reconstitution Inflammatory Response in AIDS
Described with myobacterial species: TB, M.bovis, MAC
TB IRIS may occur weeks to mos after initiation of ART and can happen either from unrecognized mycobacterial infection or an immune response directed against antigen in those on therapy
Characterized by paradoxical worsening in signs with increased lymphadenopathy and new clinical/radiologic respiratory signs
Must be distinguished from other infections
To minimize risk, those with probable or confirmed TB should start tx 2 weeks prior to ART if possible
Don’t stop ART or TB meds
May use steroids if severe
Factors relating to Upper Airway Involvement in AIDS
Recurrent infections
Lymphoid proliferation with tonsillar and adenoidal hypertrophy and pharyngeal infiltration → upper airway obstruction
Can get Candida epiglottitis
Function of surfactant B
One of the surfactant proteins, which include A-D
Promotes adsorption and organization of lipids in surfactant
Clinical presentation of surfactant B deficiency
Full term neonate with severe bilateral lung disease, similar to infant with RDS:
Respiratory distress is rapid, within minutes to hours
Hypoxemic respiratory failure and may even need HFOV or ECMO
May initially respond to exogenous surfactant, but this is not a sustained response and they will respond less to subsequent doses of surfactant
Name the 6 classes of CF mutations
1 = protein synthesis defect 2 = maturation defect 3 = gating defect 4 = conductance defect 5 = reduced quantity 6 = reduced stability
What is considered a minimal function CFTR mutation?
Class 1-3
Minimal function mutations = produced either no protein or a defective protein that is unresponsive to CFTR modulators
Includes: nonsense mutation, insertion and deletion mutations, canonical/canonical splicing mutations and certain severe protein misfiling mutations
What is considered a residual function CFTR mutation?
Class 4-5
Symdeko is Tezacaftor + Ivacaftor = for homozygous delF 508 and one residual function - approved for more than 6 years
How does the combination CFTR modulators work?
Ivacaftor is a CFTR gating potentiator which is fda approved for use in class 3 and one class 4 mutation(R1117) ,more than 6 months of age
Lumicaftor is a CFTR corrector which partially reverts the ΔF508-CFTR functional expression defect by stabilizing the NBD1-MSD1/2 interface, by alone no action in homozygous df 508 . When ivacaftor used in combination with lumicaftor (Orkambi) it has modest effects in homozygous df 508.
Df508 is mainly class 2 but even with lumacaftor, only about 1/3rd of the structurally normal protein reaches the cell surface; addition of ivacaftor keeps the channel open for a longer time and also works on the class 3 action of dF508 .
What is the interaction concern with some of the CFTR modulators?
Ivacaftor is metabolized by cytochrome CYP3A. (don’t use a strong inducer with Ivacaftor. If it’s a strong inhibitor, you can still use the drug, but you need to do a dose adjustment).
strong cyp3a inducers = Rifampin, Rifabutin, Phenytoin Phenobarb, herbal supplements (St Johns wort) is not recommended for use with Ivacaftor.
strong cyp3a inhibitors -azoles,erythro clarithro telithromycin- needs dose adjustment
seville orange, grapefruit-to avoid
caution when co administering other cyp3a substrates -tacrolimus, cyclosporine ,digoxin
Equation for Diurnal Variation
Diurnal variation = maximum PM pre-bronchodilator PEF - minimum AM pre-bronchodilator PEF/recent maximum x 100%
Diurnal Variation = day’s highest PEF - day’s lowest PEF/ mean of day’s highest and lowest PEF
> 10 (>13 in children) is considered to be significant
Criteria for positive methylcholine challenge
PC20 <4mg/ml
4-16 = borderline, >16 = negative
Asthma control criteria
Daytime sx <4 days/week Nighttime sx < 1 day /week Normal physica activity Ventolin use <4 times per week No school absences Mild, infrequent exacerbations FEV1 or PEF ≥ 90% personal best Diurnal variation <10-15% Sputum eosinophils <2-3%
5 Causes of pulmonary hypoplasia
Intrathoracic abnormality, e.g, Congenital diaphragmatic hernia, CPAM
Pulmonary hypoplasia associated with oligohydramnios
Genetic syndrome, e.g., Trisomy 21, Trisomy 13, Trisomy 18, Cerebrocostomandibular syndrome
Chest wall development, e.g., Asphyxiating thoracic dystrophy/Jeune syndrome
Giant omphalocele
5 pulmonary complications of trauma
Flail chest → pain control, no splinting Traumatic pneumothorax Hemothorax Tracheal or bronchial rupture Pulmonary compression injury (e.g., explosive blast causing pulmonary contusion, pathologically see edema, hemorrhage, atelectasis). Post-obstructive pulmonary edema Post-traumatic atelectasis Diaphragmatic rupture
Who would be at increased risk of exposure of TB in Canada (not new immigrants)
Foreign born individuals and Aboriginal people in particular are disproportionately affected by TB
Incarcerated
Homeless
Higher among males 1:0.8
Highest age-specific rate 75+ age group
Higher incidence in Northern Territories (3 most populous provinces, with 75% of population, make up 69% TB cases - BC, ON, QC)
5 causes of Hypersensitivity pneumonitis (not allergic reaction related)
Drug-induced HP (ie. MTX, cyclosporine)
Avian antigen exposure (ie. pigeon) - most common!
Bagassosis ( mold exposure)
Aspergillus fumigatus (organic compost)
Ventilation pneumonitis (air conditioner)
Farmer’s lung (moldy hay)
3 classes of medications post lung transplant – immunosuppressive therapy
Corticosteroids (eg. Prednisone)
Calcineurin inhibitors (eg. Tacrolimus, Cyclosporine)
Cell cycle inhibitors (eg. Mycophenolate {MMF}, Azathioprine)
3 criteria in the cath lab for pulmonary HTN diagnosis
Mean Pulmonary arterial pressure at rest ≥ 20 mmHg
Pulmonary artery wedge pressure (<15mmHg)
Elevated Pulmonary Vascular Resistance > 3 woods units x m2
Gold standard test for the diagnosis of Pulmonary HTN
Cardiac cath
Necessary:
(1) to confirm the diagnosis and assess the severity of PH
(2) to exclude other potentially treatable conditions, such as pulmonary thromboembolic disease
(3) to rule out left heart disease
(4) to assess response to vasodilators before starting therapy (and to reassess on therapy to determine need for escalation or change in treatment)
(5) to determine operability in patients with APAH-CHD
(6) to determine suitability for lung transplantation.
3 classes of meds used in PHTN and their mechanism of action
Nitric Oxide: Activates guanylate cyclase → production of cyclic GMP and subsequent smooth muscle relaxation
Selectively relaxes pulmonary vasculature without affecting arterial pressure
Also has antiproliferative effects on smooth muscle and inhibits platelet adhesion
Phosphodiesterase inhibitors (eg. Sildenafil): Prevent degradation of cyclic GMP → potentiates the effect of NO activity by inhibiting PDE 5
Endothelin Receptor Antagonists (eg. Bosentan-dual receptor): Block ET receptors (found in smooth muscle and endothelial cells) thus promoting vasodilation and prevents proliferation
Prostacyclin Analogs/receptor agonists (eg. Epoprostenol, Iloprost, Trepostinil): Acts as a pulmonary vasodilator, inhibits vascular smooth muscle proliferation, inhibits platelet aggregation, improves endothelial dysfunction and can also act as a possible cardiac inotrope
Ca channel blockers (eg. Nifedipine): Pulmonary vasodilator - by inhibiting Ca influx through slow channel in cardiac and vascular smooth muscle cells
Explain the mechanism of action of PEP therapy in CF
PEP may have an effect on the peripheral airways and collateral channels of ventilation (Opens collaterals)
Increase in lung volume may allow air to get behind the secretions and assist in mobilizing. (Air behind secretions is pushed)
The increase in pressure is transmitted to airways creating back pressure stenting them during exhalation , therefore preventing premature airway closure thus reducing gas trapping .
Prolonged Exhalation with huff breathing helps mobilize secretions
Name 2 common mechanism of PCD
1) Ultrastructural
2) Functional (30%)
Common aetiologies for diaphragm paralysis
Diaphragm paralysis generally results from injury to the phrenic nerve during thoracic or neck surgery. Tumors of the mediastinum, peripheral neuropathy, and agenesis of the phrenic nerve are less likely causes. In the newborn, stretching of the root C3–C5 during breech delivery is a frequent cause, most often in association with brachial plexus injuries (Erb’s paralysis).
Most diaphragm paralyses are on the right side, with bilateral paralysis occurring in only 10% of cases. Bilateral diaphragm paralysis can be responsible for a severe restrictive syndrome, with total lung capacity often below 50% of predicted value
How may someone with a unilateral diaphragm paralysis present?
In unilateral diaphragm paralysis (UDP), it is believed that the non-paralyzed hemidiaphragm increases in strength to compensate for the dysfunction of the paralyzed hemidiaphragm; therefore, most of these patients are able to maintain appropriate ventilatory conditions at rest and during mild exercise.
However, this is not true for all patients, because many of them have unexplained dyspnea, exercise limitations, and a reduction in inspiratory muscle capacity
Elevation of the paralyzed diaphragm is greater in the supine position, due to pressure from the abdominal content, and can be responsible for orthopnea.
On chest x-ray, unilateral paralysis of the right hemidiaphragm should be suspected if it is more than two rib spaces higher than the left hemidiaphragm; on the left side, it results in an elevation of the hemidiaphragm of at least one rib space above the right hemidiaphragm. Contralateral mediastinal shift also can be observed in severe cases.
Imaging besides CXR for investigating possible diaphragm paralysis
Fluoroscopy with a sniff test and ultrasonography in a spontaneously breathing patient show a paradoxical inspiratory upward motion of the paralyzed hemidiaphragm compared to the contralateral side.
Electromyography in association with percutaneous stimulation of the phrenic nerve can confirm the paralysis.
Repeated evaluations by fluoroscopy, ultrasonography, or electromyography can aid in assessing diaphragmatic function.
Reasons for BIPAP asynchrony
Leak, inappropriate trigger sensitivity, inappropriate settings, anxiety
Patient-ventilator asynchrony (PVA) describes the poor interaction between the patient and the ventilator and is the consequence of the respiratory muscle activity of the patient being opposed to the action of the ventilator. A mismatch between the breaths demanded by the patient and those delivered by the ventilator.
Advantages of nasal NO
Cheap
Easy to use/maintain
Directly measures all aspects of inflammation
Rapid results
Evidence of benefit of clinical outcome (Can be used to titrate steroid dosage, less side effects, better control
Identifies adherence)
Advantages of have high flow oxygen on the ward
Non invasive way of respiratory support Safe Easy to apply Quick to start Minimal morbidity, Reduce PICU admission On ward support Sedation not needed May support oral enteral feeding
Intentions of high flow oxygen
Eliminate most of the anatomic dead space
Create a reservoir with high FiO2 in the nasal cavity
Improve gas exchange
Significantly reduce the work of breathing
Positive effect of humidified high flow oxygen
Using humidified (warmed) gas keeps mucus more fluid and aids airway recovery (eg, after surgery)
Reduced respiratory rate
Less dyspnoea (laboured breathing or shortness of breath / breathlessness) and mouth dryness, and greater overall comfort
Ease of set-up – easier to fit a nasal cannula than an oxygen mask
Low level of patient compliance needed (sedation possible but not required)
Patients say it is very comfortable and allows them to communicate
Most common organisms causing necrotizing pneumonia
Strep Pneumo, Staph aureus, Pseudomonas aeruginosa
Strep Pyogenes
Defn: Necrosis and liquefaction of consolidated lung
Usually single lobe
can lead to: BP fistula, Abscess, Air fluid level, Pneumatocele
Necrotizing pneumonia usually follows pneumonia caused by particularly virulent bacteria
When to suspect necrotizing pneumonia
Clinical manifestations of necrotizing pneumonia are similar to those of uncomplicated pneumonia, but they are more severe.
Necrotizing pneumonia should be considered in a child with prolonged fever or septic appearance.
The diagnosis can be confirmed by chest radiograph (which demonstrates a radiolucent lesion) or contrast-enhanced computed tomography (CT); the findings on chest radiograph may lag behind those of CT.
In asthma, what happens to compliance with hyperinflation?
With hyperinflation, compliance decreases and work of breathing increases (this effect is more predominant and bad for these hyperinflated asthma patients).
What is the reason for barrel chest in asthma exacerbation?
Hyperinflation can decrease airway resistance by the tethering effect of parenchyma on airway
Barrel chest is due to air trapping and hyperinflation in an asthma exacerbation.
What are two criteria for an acceptable PFT in preschoolers?
Rapid rise to peak
Smooth curve with no glottic closure within measured time for FEV
Don’t need back extrapolation volume in preschoolers
At least 2 acceptable curves with FEVt and FVC are within 0.1L or 10% of highest value
No maximum number of maneuvers, while being attuned to their fatigue level (min 3)
Why should acceptability criteria for preschoolers differ from adult criteria?
1) Smaller absolute lung volumes and large airway size relative to lung volume
2) Forced expiration is therefore completed in a shorter time
3) VBE in children is typically lower than in adults, whereas VBE/FVC is higher. Both findings can be simply explained by the much smaller absolute lung volumes of very young subjects
6 pulmonary complications of IBD
Bronchiectasis (most common) Tracheal stenosis Ileobronchial colobronchial fistula COP (Cryptogenic organizing pneumonia) granulomatous and necrobiotic nodules ILD Pulmonary Vasculitis Drug induced disease (Sulfasalazine and Mesalamine can cause HP) Opportunistic infection Malignancy Pulmonary thromboembolism
Name two ways to reduce CO2 while on HFOV
1) Decrease frequency
2) Increase amplitude
3) Increase I:E ratio
HFOV→ you avoid the cyclical application of high distending airway pressures (barotrauma) and the associated cyclical delivery of large tidal volumes (volutrauma) so you keep the alveoli open and recruited more consistently with minimal lung damage.
Ways to reduce CO2 while on HFJV
Increase PIP (increase delta p) → primary way to regulate PaCO2 Increase frequency
HFJV is a form of time-cycled, pressure-limited ventilation such that if ventilator parameters are held constant, a decrease in chest wall or lung compliance will result in a reduction in minute ventilation. The driving pressure, rather than the respiratory frequency, is most influential for CO2 elimination.
Which is better for patients with airway obstruction: slow or fast VC?
In patients with airway obstruction, SVC > FVC. Using the larger volume would enable the FEV1/VC ratio to most sensitive to detection of airflow obstruction
In normal subjects, SVC = IVC = FVC are about the same
The embryological origin of the pulmonary artery. At what embryonic age does it develop?
Pulmonary arteries originate from 6th branchial arch arteries at 7 weeks gestation (end of embryonic, early pseudoglandular stage)
Pulmonary trunk arises from truncus arteriosus, which divides at 8 weeks
Central controllers of breathing
Medullary respiratory centre:
o Pre-botzinger complex: essential for generation of respiratory rhythm
o Dorsal respiratory group – associated with inspiration
o Ventral respiratory group – associated with expiration. This group is usually quiet during normal breathing, but is active during active exhalation, such as exercise.
Pons:
o Apneustic centre: has an excitatory effect on inspiratory area of medulla. Unclear if this area plays a role in normal human respiration. Activity of this area is seen in brain injury
o Pneumotaxic centre: switches off/inhibits inspiration and thereby, affects inspiratory volume and respratory rate. It’s not needing for basic rhythm, but it “fine tunes” the respiratory rhythm
What is the Henderson Hasselbach Equation?
pH = pKA + log (HCO3-/CO2) pH = 6.1 + log([HCO3-]/0.03 x pCO2)
2 Chest x ray features in neonatal RDS
Low volume lung , bilateral diffuse air space opacification
4 chemicals biomarkers of Chylothorax
Triglycerides >1.1 mmol/dl
Total count >1000 cells;>80% lymphocytes
Chylomicrons + –not usually tested for though
Sudan 3 + staining for fat globules
Exudate- Pleural fluid LDH > 2/3rd of upper limit of normal or > 0.6 of serum LDH, Pleural fluid Protein > 0.5 of serum protein (2-6 g/dl) (Lyte’s)
Electrolytes and glucose same as plasma
GPA 4 respiratory complications and two antibodies?
Upper respiratory tract - chronic sinusitis , nasal septal perforation/ulcer , oral ulcers, subglottic stenosis
Lower respiratory tract- tracheal or bronchial stenosis, diffuse alveolar hemorrhage , granulomas (nodules)
Antibodies - PR3 and MPO ANCA, mostly PR3 which is more specific.
3 reasons why PEF is not use in paediatrics
1) It is effort dependent
2) It has high variability
3) PEF is less sensitive than standard spirometry in detecting reversibility of airflow obstruction after bronchodilator administration
IPHT 3 clinical finding in exam apart HR and RR
Loud P2
Pan systolic murmur in right sternal border ( TR murmur) and ejection murmur in pulmonic area
HEPATOMEGALY/raised JVP
left parasternal heave
CFSPID criteria (one), your hospital has the 35 panel shows 1 dF508, is it enough to call it? mention 2 genetic tests to do?
CFSPID
1 - CFSPID if NBS shows high IRT and one mutation (inconclusive screen) with intermediate sweat x 2
2 - CFSPID if screen positive with two mutations (only one CF causing) and negative sweat
Follow in CF clinic with repeat CF testing at 2 months and 6 months , a small % may turn out to be CF (becomes sweat pos with symptoms of CF )
2 genetic tests may be: Sanger sequencing or next generation sequencing of the whole CFTR gene. Sanger sequencing: looking at a small sequence of genome, cheaper. Next generation: faster, looks at a wider section of genome, amplifies multiple areas at the same time. Next generation is mostly used currently
Salt and fresh water drowning, how each cause respiratory distress
Both types of nonfatal drowning result in decreased lung compliance, ventilation-perfusion mismatching, and intrapulmonary shunting, leading to hypoxemia that causes diffuse organ dysfunction.
Key mechanism: surfactant dysfunction and inflammation
2 types of bronchial casts
Bronchial casts are characterized by the formation of obstructive airway plugs that may be large enough to fill the branching pattern of an entire lung.
Type I – Inflammatory casts – contain fibrin and eosinophilic infiltrate , e.g.,CF, asthma
Type II – noninflammatory casts – acellular containing mucin and fibrin without inflammatory infiltrated e.g., plastic bronchitis in post-Fontan patient
2 conditions in which you will prefers BiPAP over CPAP and why?
1) Central sleep apnea – can provide rate so ventilation will occur despite central apnea
2) Neuromuscular disorder – inspiratory pressure required to provide ventilation
What is P50?
P50 is the PO2 at which 50% of the hemoglobin present in the blood is in the deoxyhemoglobin state and 50% is in the oxyhemoglobin state.
(At a temperature of 37C, a pH of 7.4 and PCO2 of 40mmHg, normal human blood has a P50 or 26 or 27mmHg. If the oxyhemoglobin dissociation curve is shifted to the right, the P50 increases. If it is shifted to the left, the P50 decreases).
3 causes that shift the Hb -Sat curve to the right
Increased temperature Reduced pH Increased 2,3 DPG Increased PCO2 Memory tool: think of exercising muscles--hot, acidosis
Down syndrome, 4 lower respiratory complications
Recurrent Aspiration Recurrent pneumonia Wheeze secondary to asthma Pulmonary hypertension chILD appears to be more common in children with Down Syndrome
BAL, proteinaceous secretions, PAS positive. Diagnosis? 2 differentials?
Pulmonary Alveolar Proteinosis
Fungal infection (PAS positive) ILD (Pulmonary fibrosis, sarcoidosis can be PAS positive)Surfactant protein deficiency (proteinaceous secretions) Surfactant protein deficiency (proteinaceous secretions)
Obesity, what do you expect in PFT?
reduced FVC reduced TLC reduced ERV, FRC normal FEV1 and FEV1/FVC (although increased risk of asthma) reduced MIP/MEP increased DLCO
What is a normal shunt?
< 5%
Equation: CcO2-CaO2/CcO2-CvO2
NEHI, what is the staining, what do you see on pathology?
No specific diagnostic features of disease, with an absence of extensive inflammation, reactive injury, architectural distortion, and fibrosis seen on lung biopsy
Minor and nonspecific changes involving the distal airways including:
- Mildly increased airway smooth muscle
- Mildly increased numbers of alveolar macrophages
- Increased number of ‘ clear cells’ within bronchioles
- Patchy mild periairway lymphocytic inflammation and fibrosis commonly seen
Stain = Bombesin stain
One or more bronchioles with > 10% of airway epithelial cells immunopositive
PCD: What is the ultrastructure of cilia? What is the commonest defect. Name 2 diseases caused by sensory ciliopathy
Cilia Ultrastructure – Classic 9+2 Arrangement
Commonest defect - Outer dynein arm defect
Diseases due to sensory ciliopathy: PCKD, Bardet-Biedl Syndrome, Alstrom Syndrome, Joubert, Retinitis pigmentosa
Foreign body in the left lung, what do you see in each lung on both rt and left lateral decubitus positions
Affected dependant lung will be hyperlucent. Normal lung will compress and partially collapse and appear denser (Normal).
This debucitus technique is helpful when kids can’t do inspiratory/expiratory
CT with bronchiectasis: mention 3 findings that suggest that
Enlarged internal bronchial diameter
Signet ring sign (bronchi : vessel ratio >1.0)
Failure of airway to taper in lung periphery
Bronchial wall thickening ( Tram track)
Mucus plugging / impaction ( Tree in bud pattern)
Mosaic perfusion
Air trapping on expiration
Air-fluid levels in distended bronchi
3 criteria for periodic breathing
*Think of 3s!
3 episodes of apnea
>3 seconds each
separated by continued breathing for ≤ 20 seconds
Asthma, 3 cytokines targeted for treatment.
IL-4, IL-5, IL-13
CF girl with osteopenia, 6 causes why might CF get that.
Prolonged steroids Pancreatic insufficiency (both exocrine and endocrine) Low weight bearing exercises Delayed puberty Chronic pulmonary infections Malnutrition
Palivizumab - What is it?
Palivizumab = a humanized murine monoclonal immunoglobulin G-1 directed against an epitope on the F glycoprotein of RSV
It is produced by recombinant DNA technology and directed against an epitope of the F glycoprotein of RSV.
Palivizumab binds to this glycoprotein and prevents viral invasion of the host cells in the airway. This reduces viral activity and cell-to-cell transmission, and blocks the fusion of infected cells
Post transplant pt, on Cyclosporin, mention 2 side effects
Hypertension
Nephropathy
Also: Hirsutism, gingival hyperplasia, neurologic toxicity, seizures, headache, and sleep disturbance, diabetes
Pt. Post BMT with invasive Aspergillus
Name a sign on CT and explain
Blood Galactomannan was +ve how does that help your management.
Classic = “halo sign” (distinct nodular lesion with surrounding areas of decreased attenuation)
“air crescent sign” (late finding of nodular cavitation, occurring after recovery of neutrophil counts)
Galactomannan = double sandwich EIA to detect galactomannan (polysaccharide cell wall antigen of Aspergillus)
Best validated for neutropenic patients with hematologic malignancy or HSCT
Blood less sensitive than pulmonary Galactomannan from BAL - if shows up in blood - more likely to be a severe infection.
ABPA in a CF patient mention 3 criteria
Treatment name and dose and course
IgE >500 (minimum), >1000 = classic
positive skin prick test with Aspergillus
worsening lung function
increased Aspergillus serum specific IgE and IgG
Radiographic changes on CXR or CT not cleared with antibiotics or physio
Additional:
Increase in blood eosinophilia when not on steroids (>40 ug/L)
Aspergillus species specific precipitating antibodies
central bronchiectasis
Aspergillus species specific containing mucus plugs
1st = steroids -> Prednisone 0.5-2mg/kg.day 1-2 weeks then taper within 2-3 mos
2nd = antifungal: oral Itraconazole 5mg/kg/day x 3-6 mos (therapeutic drug monitoring and LFTs)
add -> BD, inhaled steroids etc only if indicated for asthma
TEF: mention 4 complications
Tracheomalacia (Overall, tracheomalacia improves with age)
Recurrent bronchitis/ pneumonia due to poor secretion clearance
Aspiration due to esophageal stricture
GERD due to poor esophageal peristalsis
Recurrence of fistula
Chest wall deformities due to surgery predominantly (but Could also be related to vertebral anomalies with VACTERL association)
TB, TST: Mention 4 FN other than technical stuff
Live virus vaccination: measles, mumps, polio (recent)
Immunosuppressive drugs: corticosteroids, tumour necrosis factor (TNF) inhibitors, and others
Metabolic disease: chronic renal failure, severe malnutrition, stress (surgery, burns)
Diseases of lymphoid organs: lymphoma, chronic lymphocytic leukemia, sarcoidosis
Age: infants <6 months, the elderly
Infections: Active TB (especially if advanced) HIV infection (especially if CD4 count <200) Other viral infection (measles, mumps, varicella)
TB TST: 2 FP other than Technical stuff
Non tuberculosis mycobacterium infection
Recent BCG vaccine ( within 12 months )
Allergic reaction at the injection site
Mycobacterium abscessus mention 4 medication
Intensive + continuation phase
Intensive = 3-12 weeks of IV Amikacin PLUS 1 of: Tigecycline, Imipenum, Cefoxitin (consider adding macrolide)
- “For ABS you need to do CIT-ups”
Continuation = Inhaled Amikacin with 2-3 of: PO Minocycline, Moxifloxacin, Linezolid, Clofazimine
Characteristics of Burkholderia cenocepacia and Cenocepacia syndrome
severe decline in CF lung function possibly developing into a life-threatening systemic infection known as cepacia syndrome.
extremely difficult to treat because of virulence and resistance
cepacia syndrome is characterized by a rapidly progressive fever, uncontrolled bronchopneumonia, weight loss, and in some cases, death.
Differential for unilateral hyperlucent lung
Foreign body Congenital: CLO, CPAM Swyer James PTX Compensatory: Lung collapse – Pulmonary Hypoplasia Ventilator associated (deep ETT)
In CF what is the mechanism of PEP and mention one side effect
With the PEP device, there is normal inhalation, but there is resistance during exhalation, which results in the creation of back pressure (positive expiratory pressure)
This results in build up of gas pressure behind mucous through collateral ventilation.
Through forced expiratory maneuvers, the mucous can be moved from peripheral to central airways. Coughing maneuvers enables expectoration of mucus
Side effects:
- Hemoptysis
- Nausea
In CF what is the mechanism of Hypertonic Saline and mention one side effect
Hypertonic saline acts directly as an osmotic agent and may increase airway surface liquid volume
Side effects:
Bronchoconstriction (give with ventolin)
Cough
Dislodgement of GT tube, rupture of the tube
Less likely worsening Pulmonary functions
In CF what is the mechanism of Pulmozyme and mention one side effect
Inhaled recombinant DNAse treats CF lung disease by reducing sputum viscosity and increasing mucus clearance, attacks neutrophil DNA
Side effects:
- voice alteration
- sore throat
- laryngitis
- rash
- chest pain
Pt with PE Mention 1-2 advantages for each :
Enoxaparin
Warfarin
Enoxaparin adv: less doses more effective longer half life 4 hrs No need for close monitoring
dis: expensive bruising at injection site only partially reversed with vitamin k higher half life increase risk of bleeding
Warfarin Adv: Oral reverse with vitamin k once daily dosing very low cost
dis: Slow onset of action requires monitoring for INR narrow therapeutic window difficult control preoperative might interact with food and other drugs
2 causes of unilateral vocal cord paralysis
Unilateral more common on the left (due to longer course of the recurrent laryngeal nerve, and generally due to a nonfunctioning peripheral nerve) → cardiac surgery
Peripheral nerve pathology
Mediastinal lesions (tumours, vascular malformations or thoracic surgery)
Birth trauma often cause of transient palsies (for both unilateral and bilateral)
Acquired VC paralysis → usually a unilateral condition coming from iatrogenic injury to the recurrent laryngeal nerve (L > R)
Risk factors = PDA repair, Norwood cardiac repair + esophageal surgery (TEF), older children with thyroid surgery
May have spontaneous recovery months after injury (only if nerve is intact)
2 causes of bilateral vocal cord paralysis
Bilateral palsies → lesions of the CNS Arnold-Chiari malformation Hydrocephalus Meningoceles Myasthenia gravis Can also be idiopathic
Most common cause is congenital (as opposed to acquired which is seen with unilateral)
Most with bilateral paralysis present with significant airway compromise (with good voice)
What nerve is responsible for vocal cord movement and from what root
Recurrent laryngeal nerve → which comes from the vagus nerve (CN 10). (It supplies both adductor and abductor muscles of larynx
Side effects of Flovent
Local: thrush, dysphonia
- Adrenal insufficiency: hypoglycemia, altered mental status, fatigue, weakness, anorexia, Cushingoid features, growth failure, or weight loss
(Adrenal crisis–pediatric deaths related to fluticasone)
- Height: decreased growth velocity in prepubertal children in first 1-2 years of treatment, but this is not progressive or cumulative. Final result of 0.7% decrease in adult height (GINA 2019, page 140)
How to take MDI with a mouthpiece
As per Kendig’s chapter 16, page 260, with use of MDI: take a slow breath over 4-5 seconds, then 10 second breath hold.
- Infants use the MDI with tidal breathing and they require 5-10 breaths. (chapter 16, page 266 upper left hand corner)
- Ensure the inhaler isn’t empty, based on counted doses
How to know when an MDI is empty
Unless there is an external dose counter, there is no way of knowing if it’s empty without counting dose. Take note of date that inhaler was first used and count number of daily doses to get a sense of when inhaler needs to be replaced, or count individual doses.
Non-infectious pulmonary complications post BMT
Pulmonary edema (1-2 mos) VOD (1-2 mos) DAH (1-2 mos) Idiopathic pneumonia syndrome (1-6 mos) GVHD (acute and chronic) - 2mos on ILD (3 mos on) PTLD (3 mos on) BO (3 mos on)
Infectious pulmonary complications post BMT
Early (<30 days)
- Pseudomonas, other G+ and G- species, Candida
Late (>30 days)
- Staph aureus, PJP, Aspergillus, CMV, Toxo, VZV, EBV, Adenovirus
Late (>100 days)
- Encapulated gram positive (H. flu, S pneumo)
Causes of pneumonia unique to immunocompromised patients
Gram negative:
- PJP
- Legionella
- Capnocytophagia
Gram positive:
- Listeria
- Corynebacterium
Treatment of PJP
Septra for both treatment and prophylaxis
Treatment dose: Septra 15-20 mg/kg/day IV or oral in 3-4 divided doses x 21 days
Prophylaxis: One DS tablet daily or 3x/week or as one single strength tablet daily
Second line:
- Combo of Clindamycin + Primaquine
- Dapsone
- Atovaquone
If PJP + mild-moderate hypoxemia = Septra + steroids
PFT acceptability criteria
1) Must have BEV <5% of FVC or <0.100 L (whichever is greater)
2) Must have no evidence of faulty zero flow setting
3) Must have no cough in first second of expiration
4) Must have no glottic closure in first second of expiration
5) Must have no glottic closure after first second of expiration
6) Must achieve one of 3 EOFE indicators:
- Expiratory plateau
- Expiratory flow >15 s
- FVC is within repeatability tolerance or is greater than the largest prior FVC
7) No evidence of obstructed mouthpiece or spirometer
8) Must have no evidence of a leak
9) If max inspiration = more than FVC, then FIVC - FVC must be ≤ 0.100L or 5% of FVC, whichever is greater
PFT repeatability criteria
≥6yo: difference between largest FVC or FEV1 ≤ 0.150L
≤6yo difference between largest FVC or FEV1 ≤ 0.100L
Differences between child and adult thorax
1) The pediatric chest is typically more rounded with less developed musculature
2) More flexible and elastic rib cage (combo of 2 = very compliant chest)
3) The ribs and sternum of a child can thus support a significant amount of blunt force without fracture BUT the visceral structures may still have sustained serious injury.
4) Increased mediastinal mobility, together with the absence of preexisting vascular disease in children, make injuries to the mediastinum and great vessels less frequent
5) Conditions such as tension pneumothorax or hemothorax are very poorly tolerated and must be recognized and addressed emergently.
Physical exam findings consistent with sternal fractures
- Local tenderness
- Ecchymosis
- Sometimes a concavity or paradoxical respiratory movement.
- The sternal segments are typically well aligned without much displacement.
- Dyspnea, cyanosis, arrhythmias (most commonly sinus tachycardia), and hypotension may be evidence of an underlying cardiac contusion.
- Radiographic demonstration of fractures is most commonly by chest x-ray or CT scan
Children with traumatic injury of the sternum should be admitted to the intensive care unit given the increased risk for arrhythmias.
Cardiac tamponade and blunt myocardial damage must be ruled out
Mechanism behind tension pneumothorax
The creation of a tension pneumothorax requires a valvular mechanism through which the amount of air entering the pleural space exceeds the amount escaping it.
The positive intrapleural pressure is initially dissipated by a mediastinal shift, which compresses the opposite lung and can result in ipsilateral pulmonary collapse and angulation of the great vessels entering and leaving the heart.
Causes of tension pneumothorax
Chest wall and lung trauma Rupture of the esophagus Pulmonary cyst Emphysematous lobe Postoperative bronchial fistula.
Dangers with open pneumothorax (second thoracic emergency after tension pneumothorax)
If a considerable segment of chest wall is open, more air is exchanged at this site than through the trachea, because the pressures are similar.
Inspiration collapses the ipsilateral lung and drives its alveolar air into the opposite side. During expiration, the air returns across the carina.
The mediastinum becomes a widely swinging pendulum compressing the uninjured lung on inspiration and the lung on the injured side during expiration.
Under these circumstances, little effective ventilation is taking place because of the tremendous increase in the pulmonary dead space and the decrease in tidal volumes.
Most common sequel of thoracic trauma
Hemothorax
Possible sequelae from esophageal rupture
Esophageal injury is more commonly associated with penetrating trauma
The most common cause of esophageal injury is iatrogenic during instrumentation of the esophagus
Can lead to abscess
Basic management of esophageal perforation
Adequate pleural space drainage
IV antibiotics
Maintenance of adequate nutrition
Complications of MgSO4
Hypotension
Flushing
CNS depression
Hypermagnesemia
Complications of IV Ventolin
Tachycardia
Arrhythmia
Myocardial injury
Hypokalemia
What to do for acute asthma after back to back Ventolin and Atrovent:
Steroids- either oral (eg. Dexamethasone) or IV (methylpred)
MgSO4
Continuous ventolin/IV Ventolin
(Amiopylline) –ICU, with severe exacerbation failed to improve despite maximal therapy.
Side effects of Amiophylline
Nausea
Vomiting
Tachycardia
Complications of intubation for asthmatic
Hypotension (since many patients have relative hypovolemia combined with decrease in preload due to positive pressure ventilation and reduced vascular tone caused by anaesthetic agents)
Hypoxia
Bronchospasm, Cardiac Arrest
Difficulty with ventilation
Ventilator strategy for Asthmatics
Minimize dynamic hyperinflation and air trapping. Adequate oxygenation Permissive hypercarbia Goal pH >7.2 Strategy: - Slow ventilator rate with prolonged expiratory phase - Minimal end expiratory pressure - Short inspiratory time
Which severe asthmatics get hypoxemia?
In terms of mechanism for hypoxemia:
- V/Q mismatch causes intra-pulmonary shunt (atelectasis) and dead space (due to airway over distension)
- Patients have hypoxemia and hypercarbia
- Atelectasis due to small airway obstruction = decreased ventilation, but adequate perfusion
- Dynamic hyperinflation will stretch pulmonary vasculature = increased pulmonary vascular resistance, increased RV afterload and compromising RV function
- Large negative intrathoracic pressure after inspiration = increased LV afterload = systolic BP decreases during inspiration = pulsus paradoxus (decreased BP on inspiration)
BAL findings of DAH
Alveolar hemorrhage is confirmed when lavage aliquots are progressively more hemorrhagic, a finding characteristic of DAH from all causes
Hemosiderin-laden macrophages -> Prussian blue staining
When greater than 20 percent of 200 macrophages stain positive for hemosiderin, a diagnosis of DAH is usually made.
It’s normal to have up to 3%. It’s normal to have up to 3% of macrophages stain positive for iron.
it takes 50 hours after a bleed for the macrophages to become positive for iron staining. If there is no further bleeding, the iron will clear in 12-14 days
In general: hemosiderin laden macrophages at day 3 post hemorrhage, peak at day 7-10 post hemorrhage
Management of hemorrhage during bronchoscopy
First choice: Application of ice cold saline → gentle instillation of 10-15 mL aliquots from a fully wedge bronchoscopy
Second choice: epinephrine 1:100,000 dilution with small aliquots of 2 mL (maximum adult dose of 0.6 mg)
Could think about otrivin drops down the scope
CF kid - can use foley catheter and blow up the balloon to tamponade it while waiting for other management
Causes of Pulmonary Hemorrhage in Children
Infection Lung Abscess Pneumonia Trauma Vascular Disorders Coagulopathy Congenital Lung Malformations Miscellaneous (catamenial, factitious, neoplasm) DAH
Causes of Immune Mediated Diffuse Alveolar Hemorrhage
Idiopathic Pulmonary Capillaritis GPA Microscopic Polyangiitis Anti-GBM disease SLE HSP Behcets Cryoglobuminemic Vasculitis JIA COPA syndrome
Causes of Non-Immune Mediated Diffuse Alveolar Hemorrhage
Idiopathic pulmonary hemosiderosis Acute idiopathic pulmonary hemorrhage of infancy Heiner’s syndrome Asphyxiation/abuse Cardiovascular causes Pulmonary vein atresia/stenosis Total anomalous pulmonary venous return Pulmonary veno-occlusive disease Mitral stenosis Left-sided heart failure Pulmonary capillary hemangiomatosis Pulmonary telangiectasia
General investigations for Pulmonary Hemorrhage
CT chest with contrast to look for PE, AVM
Test for coagulation defects
Bronchoscopy to look for foreign body, airway hemangioma, tumor, presence of hemosiderin laden macrophages
Infection: blood and sputum cultures, TB testing with purified protein derivative
If diffuse alveolar opacities—>echo to look for cardiac disease, CT with contrast, cardiac cath
If systemic involvement (eg. renal disease, rash, joint disease)—>ANA, ANCA, CBC, ESR, CRP, urinalysis, metabolic panel, d-dimer, von willebrand factor, anti-phospholipid antibody, lupus anticoagulant
If DAH and no cardiac, renal or systemic disease with negative antibodies (ANA, ANCA, anti-GBM)—>transthoracic biopsy either through open approach (mini-thoracotomy) or VATS
What is Orthodexoxia?
Drop in oxygen saturation by 2% of more when going from supine to upright.
Another definition: decrease in the arterial oxygen tension (by more than 4 mmHg [0.5 kPa]) or arterial oxyhemoglobin desaturation (by more than 5 percent) when the patient moves from a supine to an upright position.
This is caused by conditions where being in the upright position causes more blood flow through an intrapulmonary shunt such as AVM (AVM has predilection for lower lobes in 50-70% of cases), or increased blood flow through intrapulmonary vascular dilatations (which are preferentially in dependent position) in hepatopulmonary syndrome, or increased flow through an inter-atrial shunt such as PFO
Pulmonary AVM: first line is echo (bubble) to screen,can also look for desat on CPET
What is Platypnea?
Platypnea = dyspnea in the upright position, which is better in the supine position
Pulmonary AVM appearance of CXR
Pulmonary varix (dilated vessel) may be apparent as a non-specific soft tissue mass, often with a relatively unusual orientation compared to adjacent vessels. More than one raises the possibility of hereditary hemorrhagic telangiectasia
Pulmonary AVM appearance of CT
The characteristic presentation of a PAVM on non-contrast CT is a homogeneous, well-circumscribed, non-calcified nodule up to several centimeters in diameter or the presence of a serpiginous mass connected with blood vessels
CT is often the diagnostic imaging modality of choice.
Follow-up/Surveillance for Pulmonary AVM
1) Lifelong antibiotic prophylaxis prior to dental and other potentially non sterile procedures.
2) When receiving intravenous fluids or medications, meticulous care should be taken to avoid the introduction of air bubbles (eg, use of intravenous in-line filters).
3) Avoid scuba diving
4) If PAVM is >=3 -> embolization
5) For patients with asymptomatic PAVMs in whom the feeding artery is <2 mm = yearly clinical observation, and a non-contrast CT every three to five years.
6) PAVMs that progressively enlarge or become symptomatic during follow-up should undergo evaluation for embolotherapy with pulmonary angiography
7) Consider genetic testing for HHT
HHT work up for Pulmonary AVM
Brain MRI at infancy and at puberty
Bubble echo at diagnosis, every 3-5 years, at puberty. If AVM, then CT chest.
HHT - should sibling check genetics, what to do on physical exam.
You should consider checking the sibling for HHT by doing genetics
HHT physical exam:
- Vitals: saturation, orthodeoxia in supine and upright position
- Epistaxis–>endonasal telangiectasia
- Retinal telangiectasia and hemorrhage
- Telangiectasia on lips, oral mucosa, finger tips. Can use a hand held illuminator to look for vascular anomalies on digits
- Resp: thoracic bruit is heard in ½ of HHT patients with cyanosis, clubbing (association between cyanosis and clubbing with cerebral abscess and stroke)
- CNS: Bruit if cerebrovascular malformation and open fontanelle
- GI:
· High-output heart failure
· Hepatomegaly
· Portal hypertension
· Encephalopathy
· Right-upper-quadrant pain and jaundice
What is Heliox, and explain why its use is beneficial.
Helium has the lowest specific gravity of any gas = Low specific gravity is associated with low density
Combining helium and oxygen gas (Heliox) results in a gas with a similar viscosity to air but with a substantially lower density.
Laminar flow is the most efficient way in which oxygen is delivered to the more distal parts of the bronchial tree.
How does Heliox lower the resistance to gas flow within the airways?
1) Breathing Heliox leads to a reduction in the Reynolds number, converting turbulent flow into more efficient laminar flow.
2) Because of its low density, Heliox decreases the pressure gradient needed to achieve a given level of turbulent flow and this in theory reduces the work of breathing.
The use of Heliox in asthma and upper airways obstruction is not for the treatment of the underlying disease, but is used to reduce airways resistance and respiratory muscle work until definitive treatments act
Uses of Heliox
Upper airway obstruction
Croup
Asthma
COPD
What is one disadvantage of Heliox?
To be effective at reducing airways resistance by significant amounts the concentration of helium must be high, ideally greater than 70% of the inhaled gas mixture. This will limit the amount of oxygen that can be delivered simultaneously.
More commonly (practically): croup and post-extubation stridor), need to be on <30% fiO2 to use heliox
It’s also expensive!
Viral triggered preschooler with wheeze (non-atopic)
BAL cell type
Chemokine that is the most important in accumulating this cell in the airways
Relatively increased levels of neutrophils in viral preschool wheeze
Airway neutrophilia has been associated with the release of the potent neutrophil attractants IL‐8 and leukotriene (LT)B4
Atopic wheezer
BAL cell type
Cytokine most important in accumulating this cell in the airways
Relatively higher eosinophils
Even during relatively asymptomatic periods, atopic wheezers in the study below still had higher eosinophil counts
IL13, IL5, IL4, GM-CSF. Eosinophils release leukotrienes. (In general, IL5 is the most important)
The Role of Eosinophils in the Development of Allergic Inflammation
- Initiation of events that lead to Th2 inflammation
- Suppression of Th1 mediated immunity
- Recruitment of Th2 cells to the lung
- Release of growth factors that contribute to the development of airway remodeling
Which cytokine is responsible for induction and recruitment of eosinophils from the peripheral circulation to the airways?
IL-5
IL-5 also promotes eosinophil differentiation, growth, and survival
How do steroids reduce airway eosinophilia?
Glucocorticoids increase eosinophil apoptosis and block the survival effect of interleukin-5, resulting in a reduction in airway eosinophilia
Give 3 early (0-30 days post) complications of HSCT?
- Oral mucositis (peak 1–2 weeks after)
- Pulmonary edema ( rapid onset, usually within the 2–3 weeks following HSCT)
- Peri-Engraftment Respiratory Distress Syndrome (first 14 days following HSCT)
- Idiopathic Pneumonia syndrome )initial peak approximately 2 weeks and a later peak 6–7 weeks post-HSCT.)
- Diffuse Alveolar Hemorrhage (within 30 days)
The preengraftment or early phase, from day 0 to day 30 or sooner, encompasses the time of marrow recovery leading to normalization of the peripheral neutrophil count
What is the blood glucose value for diagnosis of CFRD?
≥11.1
What is the blood glucose value(s) for diagnosis of impaired glucose tolerance?
7.8-11.1
What is the blood glucose value(s) for diagnosis of impaired fasting glucose?
6.1-6.9
Organisms that need airborne precautions
Anthrax Varicella Measles TB Smallpox Cryptococcus
Describe the histopathology of the lamellar bodies in SP-B?
Poorly organized, with loosely packed lamellae and vacuolar inclusions, having the appearance more of multivesicular or composite bodies.
Describe the histopathology of the lamellar bodies in ABCA3?
Absent or small, abnormally formed lamellar bodies
Eccentrically placed electron-dense inclusions within the abnormal lamellar bodies give them a “fried-egg” appearance.
Name the 3 common causes of upper lobe predominant non-CF bronchiectasis
TB non-TB mycobacterial (more rare) post-TB scarring Sarcoidosis Chronic hypersensitivity pneumonitis, Post radiation fibrosis ABPA
Causes of lower lobe predominant bronchiectasis
Most common zonal predilection in bronchiectasis
Mostly idiopathic
Post infective bronchiectasis (recurrent childhood infections)
Aspiration - Pulmonary aspiration diseases
In association with immunodeficiency (Hypogammaglobulinemia)
Primary ciliary dyskinesia
As a sequelae of bronchiolitis obliterans in the setting of posttransplantation rejection
Broad causes of Bronchiectasis
- Infection or aspiration
- Congenital conditions
- Fibrosing Diffise Lung Disease
- Endobronchial/peribronchial lesions
- Other (BO)
Define: Arterial oxygen saturation
Oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the blood
Define: Arterial oxygen content
Amount of oxygen in blood- includes oxygen bound to Hb and dissolved in blood
O2 content = sats/100 x Hb (g/dl )x 1.39 + PaO2 X 0.003 in ml/dl of blood
If Hb is in g/L divide it by 10 (generally the case with Canadian units)
Normal is 20 ml O2 per 100 ml of blood
Define: Oxygen delivery
Amount of oxygen delivered to tissues per minute
O2 DELIVERY = Cardiac output (Stroke volume x HR) x (arterial oxygen content) in ml/min
Normal = 1000 ml O2/min for 5 litres/min CO
2 bacterial causes for neuromuscular disease and chest wall weakness
Campylobacter jejuni ,Mycoplasma
Viruses- CMV, EBV, HIV, Influenza, Enterovirus D68
Name two congenital lung diseases known to be associated with TEF?
CHARGE and VACTERL (more common)
Name 3 long term respiratory complications of TEF
Tracheomalacia Aspiration Recurrent respiratory infections Wheeze Chronic cough Recurrence of fistula
At what gestational age does the trachea and esophagus separate?
5th week (during the embryonic stage: 3-8 weeks)
Respiratory system starts as a median outgrowth, the laryngotracheal groove, which appears in the floor of the caudal end of the anterior foregut in the 4th week - this protrudes as lung bud which develops into the tracheobronchial tree
Tracheoesophageal septum forms a partition between the trachea and esophagus at the end of 5th week.
Stages of lung embryogenesis
Embryonic phase (3-7 weeks) Pseudoglandular (6-16 weeks) Canalicular (16- 26 weeks) Saccular (26- 36 weeks) Alveolar (from 36 weeks)
Key features of Embryonic stage of lung development
3-7 weeks
Lung buds; trachea, main stem, lobar, and segmental bronchi; trachea and esophagus separate
LUNG BUD
Key features of Pseudoglandular stage of lung development
6-17 weeks
Subsegmental bronchi, terminal bronchioles, and acinar tubules; mucous glands, cartilage, and smooth muscle
BRONCHIAL TUBULES
Key features of Canalicular stage of lung development
16-26 weeks
Respiratory bronchioles, acinus formation and vascularization; type I and II AEC differentiation
ACINAR TUBULES
Key features of Saccular stage of lung development
26-36 weeks
Dilation and subdivision of alveolar saccules, increase of gas-exchange surface area, and surfactant synthesis
TERMINAL SACCULES
Key features of Alveolar stage of lung development
36 - maturity
Further growth and alveolarization of lung; increase of gas-exchange area and maturation of alveolar capillary network; increased surfactant synthesis
ALVEOLI
Lung malformations in Embryonic phase
Laryngeal, tracheal, esophageal, and bronchial atresia
Tracheoesophageal and bronchoesophageal fistulas Tracheal and bronchial stenosis
Bronchogenic cysts
Ectopic lobes
Extrapulmonary sequestration
Pulmonary agenesis
Lung malformations in Pseudoglandular phase
Tracheomalacia and bronchomalacia
Intralobar bronchopulmonary sequestration
CPAM
Acinar aplasia or dysplasia
ACD-MPV
Congenital pulmonary lymphangiectasia, and other pulmonary vascular malformations
Hypoplasia with CDH
Lung malformations in Canalicular phase
Congenital alveolar dysplasia
Alveolar capillary dysplasia
Pulmonary hypoplasia
Good stats test to use for categorical, non-parametric variables
Chi square
Fisher’s exact test
Good stats test to use for continuous, parametric variables
T-test for two groups
ANOVA for more than 2 groups
Good stats test to use for continuous, non-parametric variables
Mann Whitney (Wilcoxon-rank sum) for 2 groups Kruskal Wallis for more than 2 groups
Pathological characteristics of old BPD (pre-surfactant era)
Alternating atelectasis with hyperinflation
Severe airway epithelial lesions (e.g., hyperplasia,
squamous metaplasia)
Marked airway smooth muscle hyperplasia
Extensive, diffuse fibroproliferation
Hypertensive remodeling of pulmonary arteries Decreased alveolarization and surface area
Pathological characteristics of new BPD (post-surfactant era)
Less regional heterogeneity Rare airway epithelial lesions Mild airway smooth muscle thickening Rare fibroproliferative changes Fewer arteries but “dysmorphic” Fewer, larger and simplified alveoli
Two microorganisms causing pneumonia in children with CGD and with neutropenia
Most common = ASPERGILLUS ,staph
Also: Burkholderia C ,Serratia, Nocardia
2 diseases that can cause low nasal NO apart from PCD
Cysic fibrosis = nNO is reduced in some patients with CF
Viral illness = transiently decreased nasal nitric oxide
Sinusitis = transiently decreased nasal nitric oxide
Caveats around nasal NO
Cooperative child > 5 years of age (diagnostic accuracy in children <5 years has not been established)
- Clinical phenotype of PCD
- Exclude CF
- Ideally more than one nNO test (on two separate occasions, at least two weeks apart) since viral illness and sinusitis can transiently lower nasal NO
Low = <77nl/min
Two causes of false positive sweat test
Endocrine: adrenal insufficiency, pseudohypoaldosteronism, hypothyroidism, hypoparathyroidism
Skin: eczema, ectodermal dysplasia
Malnutrition
Renal: Nephrogenic DI
Metabolic: G6PD, glycogen storage disease type 1
Two causes of false negative sweat test
Insufficient sweat quantity due to incorrect technique or low weight (>2 kg and >2 weeks are the recommendations for sweat chloride in Kendig’s) Malnutrition Hyponatremia Edema Dilution
Respiratory complications of Hunter syndrome
Hunter’s syndrome is type II mucopolysaccharidosis, which is a type of lysosomal storage disorder
Deposition of glycosaminoglycans in throat and trachea = airway obstruction, OSA (they frequently need CPAP)
Tracheobronchomalacia from deposition of GAG in tracheal/bronchial cartilage - this can affect airway clearance and cause recurrent infection infection,
Restrictive lung disease due abnormal shape of ribs, scoliosis, pectus carinatum, enlargement of abdominal organs which affects diaphragm excursion
Recurrent pneumonia due to above mechanisms
General respiratory features of MPS
- Airway Obstruction
- Restrictive Lung Disease
- Other (Disproportional length of trachea and spine, spinal cord compression, cardiac and CNS disease)
Spirometry: Within test acceptability criteria
- Start of test criteria:
- If maximum inspiration after end of test is greater than FVC, then FIVC – FVC must be ≤0.100 L or 5% of FVC, whichever is greater
- Back extrapolated volume ≤ 5% of FVC or ≤0.100 L, whichever is greater - During test:
- No cough in first second
- No glottic closure in the first second or after the first second
- No obstruction of mouthpiece
- No leak - One of the following end of test criteria should be achieved:
- Plateau = ≤ 25 mL/s in the last second of expiration
- Expiratory time ≥ 15 seconds
- FVC is within the repeatability tolerance or greater than the largest prior observed FVC
Spirometry: Between test repeatability criteria
Repeatability criteria depend on age
a) If above 6 years of age: the difference between the two largest FEV1 and the two largest FVC must each be within 150 mL
b) If 6 year or younger: the difference between the two largest FEV1 and FVC must within 100 mL or 10% of highest value, whichever is greate
Spirometry: If acceptable, which FVC and FEV1 to report?
The largest FEV1 and the largest FVC show up on the report. Other indices come from the maneuver with the largest sum of FVC and FEV1.
Three ways to provide daytime lung recruitment in NMD children
1) Glossopharyngeal breathing
2) Delivery of stacked breaths using a resuscitation bag with a one-way valve and mouthpiece
3) Mechanical inspiration through a mechanical insufflator or volume cycled ventilator
One location for cough receptors
Carina (anywhere from pharynx to terminal bronchiole)
Mechanical receptors in airway
Chemical receptors in GI tract
Afferent nerve of cough reflex
Vagal and glossopharyngeal nerve
Cough reflex centre in the brain
Upper brainstem and Pons
Efferent nerve of cough reflex
Vagus, Phrenic, and Spinal motor nerves to diaphragm, abdominal wall and muscles.
Neurological pathway of cough
- Afferent receptors: anywhere from pharynx to terminal bronchioles
- Afferent receptor is stimulated
- Afferent neuron (glossopharyngeal and vagus to cough centre in brainstem and pons
- Signal from brainstem sent via efferent signal to larynx, diaphragm, chest wall muscles, abdominal muscles, pelvic floor
- Cortical influence can voluntarily initiate or suppress cough
Gold standard test for diagnosis of PE
CT with pulmonary angiography
Risk factors for PE in an adolescent male
Factor V Leidein Prothrombin gene mutation Recent surgery, trauma, immobilization Active malignancy Heavy cigarette smoking Obesity Drugs
Two common side effects of IV Tobramycin
Ototoxicity
Nephrotoxicity
Neurotoxicity (neuromuscular blockade)
3 categories of pulmonary hypertension as per WHO and list one example for each
- PAH - idiopathic, heritable, PPHN, drugs and toxins
- PH due to left heart disease
- PH due to chronic lung disease (ILD, COPD, BPD)
- Chronic Thromboembolic PH (CTEPH)
- Unknown/Multifactorial: heme, systemic inflammatory, metabolic, CHD
One medication for sialorrhea and one side effect
1) Anticholinergics: Transdermal scopolamine, glycopyrrolate, atropine
S/E: Irritability, restlessness, sedation, and delirium from central effects of the drugs. Also, the inhibition of sweat glands has caused significant inhibition of temperature regulation.
Inhibition of GI motility has resulted in worsening constipation in a population already plagued with such difficulties.
Photophobia, urinary retention, and facial flushing also result from these medications.
2) Botox injections
Botulinum toxin A inhibits the release of acetylcholine at the nerve terminal by inactivation of the 25-kDa synaptosome-associated protein SNAP-25, a protein essential for the fusion and release of acetylcholine-containing vesicles at the cell membrane.
Adverse effects:
Pain, dry mouth, difficulties swallowing, speech impairment.
Explain the vascular relation to trachea and esophagus
Vasculature in front of trachea which is in front of esophagus
Aortic arch encircles left mainstem
What do you expect to see on upper GI contrast study for Double aortic arch?
Bilateral indentation of Esophagus
What do you expect to see on upper GI contrast study for Aberrant right subclavian?
AP: oblique defect upward to right
Lat: small defect on right posterior wall
What do you expect to see on upper GI contrast study for PA sling?
± Anterior indentation above carina between trachea and esophagus (course behind trachea and in front of esophagus)
What do you expect to see on upper GI contrast study for Anomalous Innominate?
Normal
CCHS mutation
PHOX2B
How ‘s this mutation associated with non-respiratory complications?
The PHOX2B gene mutation, consisting primarily of increased polyalanine expansions, manifests an autosomal-dominant mode of inheritance and de novo mutations at the first generation.
This gene is critical for embryologic development of the autonomic nervous system
3 long term risks of CCHS
Tumors of autonomic neural crest derivatives such as Neuroblastoma and Ganglioneuroblastoma.
Pulmonary hypertension
Cardiac ( Heart Block, Prolonged Sinus Pauses )
Risks related to prolonged use of non invasive ventilation
SIDS
List three conditions that require airborne precautions
1- Suspected or confirmed active pulmonary, laryngeal or miliary Mycobacterium tuberculosis
2- Extrapulmonary Mycobacterium tuberculosis until pulmonary disease ruled out
3- VZV
4- Measles
5- Small pox
CF BAL - predominant cell
Neutrophils
Major cytokine = IL8, IL1B, IL6, TNF alpha
Why is resistance low at high lung volumes?
Resistance decreases as lung volume rises because th airways are pulled open
Airway resistance = highest in the medium-sized bronchi, low in very small airways (large cross-sectional area)
When you give a gas in the upright position, which lobes receive more gas and why?
The lower lobes
In an upright position, due to a greater intrapleural pressure gradient in the upper lung, the alveoli in the upper zone are already more distended. When gas is administered, the lower lobes receive a greater portion of gas.
Any change in the transpulmonary pressure during a normal respiratory cycle will cause a greater change in volume in the alveolus in the lower, gravity-dependent region of the lung than it will in the alveolus in the nondependent region of the lung, as shown by the arrows in the figure.
Because the alveoli in the lower parts of the lung have a greater change in volume per inspiration and per expiration, they are better ventilated than those alveoli in nondependent regions (during eupneic breathing from the FRC).
Two situations when rigid bronch is preferred
- Foreign body removal
2. Assessment of posterior trachea (e.g., tracheoesophageal fistula) and larynx (e.g,. laryngeal cleft)
Two limitations of rigid bronch
Limited ability to access more distal areas of the lung, and those requiring a flexible curve to reach, e.g., right upper lobe
Limited ability to obtain bronchoalveolar lavage specimens
List 5 factors that affect diffusion as per Fick’s law
Fick’s Law: Diffusion= [surface area x diffusion coefficient x (P1-P2)]/thickness
- Surface area
- Thickness of the alveolar-capillary diffusion barrier
- Solubility of the gas
- Molecular weight of the gas
- Partial pressure difference
The volume of gas per unit of time moving across the alveolar-capillary barrier is directly proportional to the surface area of the barrier, the diffusivity, and the difference in concentration between the two sides, but is inversely proportional to the barrier thickness.
What are the variables that make up the diffusion constant for a gas?
Directly proportional to the solubility of the gas and inversely proportional to the sq root of the molecular weight
Explain the underlying physiology for differential cyanosis
There is a difference in pre and post-ductal saturation. There is right to left shunt of de-oxygenated blood from the pulmonary artery to the aortic arch via the patent ductus arteriosus, distal to the take off of the right brachiocephalic artery, and prior to the take off of the left subclavian artery.
2 causes:
- Persistent pulmonary hypertension of the newborn
- Interrupted aortic arch, aortic coarctation
Name two common causes of respiratory death caused by Diphtheria.
- Airway obstruction (laryngeal diphtheria – extension of pharyngeal diphtheria, or dislodgement of pharyngeal membrane)
- Secondary pneumonia?
Deaths are usually as a result of airway obstruction, myocarditis/cardiomyopathy, or sepsis
Characteristics of Diphtheria
Corynebacterium diphtheriae
Primarily involves tonsils, pharynx, larynx, nose, skin, occasionally other mucous membranes
Mild catarrhal form or severe membranous form
Incubation: 1-6d
Clinical presentation:
3-4d URTI. Fever, membranous pharyngitis, fetor oris, cervical adenopathy, may have bull neck appearance secondary to edema of surrounding soft tissue.
Adherent gray-white membrane, surrounded by inflammation, toxin causes local tissue destruction which promotes multiplication and transmission of bacteria. Can bleed with removal. Pharyngeal membrane, can have laryngeal extension. Disruption of membrane can cause airway obstruction.
“membranous pharyngitis”
Complications of Diphtheria
Secondary pneumonia Toxin-mediated disease Myocarditis or cardiomyopathy Neuritis or paralysis Adrenal failure with hypotension
Treatment of Diphtheria
Diphtheria antitoxin to neutralize circulating toxin (administer before lab confirmation).
Antibiotics (penicillin, erythromycin x 14d) to eradicate the organism, stop toxin production and reduce transmission, but do not replace antitoxin.
Prevention: vaccination, prophylaxis for close contacts
Name four expiratory muscles of respiration.
- Rectus abdominus
- Transversus abdominis
- External and internal oblique
- Internal intercostal muscles (depresses rib cage downwards, opposite of external intercostals)
What is the mechanism of PEP for airway clearance?
- PEP may have an effect on the peripheral airways and collateral channels of ventilation (Opens collaterals)
- Increase in lung volume may allow air to get behind the secretions and assist in mobilizing. (Air behind secretions is pushed)
- The increase in pressure is transmitted to airways creating back pressure stenting them during exhalation , therefore preventing premature airway closure thus reducing gas trapping .
- Prolonged Exhalation with huff breathing helps mobilize secretions
3 malignant mediastinal masses based on their location (1 each for anterior, middle, posterior)
Anterior: Thymoma, teratoma
Middle: lymphoma, metastatic disease
Posterior: neuroblastoma, pheochromocytoma, rhabdomyosarcoma
3 benign mediastinal masses based on their location (1 each for anterior, middle, posterior)
Anterior: thymus (cyst, enlargement), thyroid goiter
Middle: lymphadenopathy, bronchogenic cyst
Posterior: hemangioma, ganglioneuroma, neurofibroma
Three Light criteria for pleural exudate
Pleural protein to serum protein > 0.5
Pleural LDH to serum LDH > 0.6
Pleural LDH >2/3 upper limit normal serum LDH
You saw young boy with chronic cough, his parents are pigeon breeders. What interstitial lung disease do you suspect?
Hypersensitivity Pneumonitis (Bird Fancier’s lung)
What is the underlying immune pathophysiology of Hypersensitivity Pneumonitis?
Hypersensitivity Pneumonitis known as extrinsic allergic alveolitis = an immune mediated lung disease occurring in response to repeated inhalation of an antigen.
The initial event involves sensitization to an inhaled antigen in the distal airway, but the level and duration of antigen exposure that is required for sensitization is unknown.
After antigen exposure in a sensitized individual, an acute alveolitis develops with an increase in neutrophils. This typically peaks at 48 hours and is followed by an increase in the number of macrophages and lymphocytes. Typically CD8+ T cells predominate, but CD4+ T cells can also be found distinguishing HP from sarcoidosis.
For your asthmatic patient, what would be the best particle size for aerosol delivery?
5-10 μm - More likely to deposit in the upper airways. However this can be avoided to achieve lower airway penetration by a slower respiratory flow.
< 1 μm exhaled ( they have low inertia and settling velocity)
<3 µm will deposit in the lower and smaller airways
Particles greater than 5 µm generally deposit in the oropharynx or upper airways.
1–7 µm considered as a “ respirable range”
Therefore minimizing the particle size of aerosolized drugs is essential for targeted deposition in the smaller airways
Device and Formulation-Related Factors that influence Determinants of Aerosol Deposition
Particle size Particle velocity Hygroscopic properties Drug viscosity and surface tension Suspension vs solution
Patient related Factors that influence Determinants of Aerosol Deposition
Age Inspiratory flow rate Breathing pattern (inspiratory volume, rate) Nasal vs mouth breathing Anatomy (upper and lower airways) Disease severity Physical and cognitive ability Adherence, contrivance
4 pulmonary complications of SLE (lupus)
- Pleuritis with pleural effusion
- Acute lupus pneumonitis
- Chronic lupus ILD
- Pulmonary hemorrhage
- Pulmonary HTN
- Shrinking lung syndrome
Explain the method of obtaining LCI
Derived from the multiple breath washout (MBW) test which involves following the washout of an inert tracer gas from lungs during relaxed tidal breathing.
With each successive breath of the washout, there’s a fall in the peak concentration of the exhaled tracer gas and the LCI is the number of ‘lung turnovers’ required for the end-tidal tracer gas concentration to fall to 1/40th (2.5%) of it’s initial concentration.
LCI = Cumulative Expired Volume/FRC Normal = <7
In obstructive disease, why is LCI elevated?
LCI reflects abnormalities of the smaller airways and is increased in the presence of airway narrowing caused by either inflammation, mucus plugging/retention and airway wall structural damage. Thus in the presence of obstructive disease washout of the tracer gas will take longer to complete requiring a greater number of breaths resulting in an elevated LCI.
Because of inhomogeneity of ventilation / time constants.
Long term effect on lung from hydrocarbon aspiration
Residual injury to the peripheral airways
Small airway obstruction and gas trapping- increased FEV1 and increased RV/TLC
3 elements of severe asthma definition per CTS statement
- Asthma diagnosis confirmed by history and objective measures
- Treatment needed: high dose ICS and second controller for previous year / oral steroids >50% last year -asthma either uncontrolled despite these or needing the above for prevention of loss of control
- Environmental factors, comorbidities, adherence and inhaler technique addressed before labelling as severe asthma
Definition of uncontrolled asthma
- CTS asthma control criteria ACQ >1.5 or ACT or cACT >20
- Frequent(>2) exacerbation needing oral steroids
- 1 or more Severe exacerbation needing ICU or mechanical ventilation
- FEV1<80% with low ratio
CTS asthma control criteria
Daytime symptoms <4 days/week, Night-time symptoms <1 night/week, Physical activity Normal, Exacerbations Mild, infrequent Absence from work or school due to asthma None Need for a fast-acting b2-agonist <4 doses/week FEV1 or PEF >90% personal best PEF diurnal variation <10–15% Sputum eosinophils* <2–3%
List the diagnostic criteria for ABPA in CF; which test distinguishes classic from minimal?
IgE levels >1000 IU/ml needed in classic ; only>500 needed for minimal criteria
If 200-500 repeat test
Criteria:
- Acute or subacute clinical deterioration that is not attributable to another etiology
- A serum total IgE level >1000 unless receiving systemic steroids
- Presence of IgE antibodies to A. fumigatus or immediate cutaneous hypersensitivity to Aspergillus
- Precipitating antibodies to Aspergillus or serum IgG antibody to Aspergillus by an in vitro test
- New or recent infiltrates on CXR or CR That do not respond to antibiotics or physio
CT findings that might suggest ABPA
Central varicose bronchiectasis AND high attenuation mucus plugs in CT suggests ABPA
Normal FeNO in patient with confirmed asthma, name one cause.
- Adequately treated with steroids - no symptoms
- Technical faults - constant expiratory flow is not maintained - will have symptoms
- Smoking can cause lower FENO levels - can have symptoms
- Non eosinophilic asthma(steroid resistant) - will have symptoms
Cutoffs for FeNO
Delta of 10 for values <50 and delta of 20% for values more than 50 are considered significant changes in between visits
Lower cutoffs are 20 and 25 (>12 yrs)
Upper cutoffs are 35 (<12 yrs) and 50
In between cutoffs the values are interpreted according to clinical context (20-35 in children and 25 to 50 in adults)
What is FeNO?
FENO can be used to
a) diagnose eosinophilic airway inflammation
b) predict steroid responsiveness and
c) to monitor treatment and
d) to indicate nonadherence to steroid therapy
Three isoforms of NOS (nitric oxidate synthetase)- nNOS (neuronal), INOS (inducible) (both in airway epithelIum) and eNOS (endothelia)l
iNOS has the capacity to generate large quantities of NO when transcriptionally upregulated by inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin 1 (IL-1)-beta, interferon (IFN)-gamma, IL-4, and IL-13 . In vitro evidence suggests that this upregulation can be abolished by glucocorticoids in vitro and in vivo .
The majority of exhaled NO originates from the lower airways.
A FENO less than 25 ppb in adults and less than 20 ppb in children younger than 12 years of age implies the absence of eosinophilic airway inflammation and non responsiveness to glucocorticoids
Hydatid disease - organism
Echinococcus genus
Hydatid disease - transmission
Transmission - eating water and food contaminated by echinococcus eggs in the faeces of the definite host or close contact with canine,sheep No human to human transmission - Humans are accidental hosts Definite host (adult sexually mature worms are seen in the intestine) - canines For E multilocularis which causes alveolar form - fox is the definitive host
Intermediate host (maintain larval forms) = sheep and livestock Eggs are present in the faeces of definitive host- these eggs once swallowed by humans, hatch and embryos penetrate intestine and are hematogenously spread to mainly liver and lungs where they grow into 3 layered cysts
Symptoms of Hydatid disease
Cough (coughs up grape cysts) Chest pain Hemoptysis Fever Bronchospasm
Radiographic signs of Hydatid disease
- Meniscus sign /crescent sign
- Cumbo sign (double air layer appearance or onion peeL or double arch)
- Water Lilly or camellote sign
- Ultrasound signs- same as xray plus - honeycomb appearance , ball of wool sign, cyst wall calcification
3 major forms of Hydatid disease
- Cystic (predominant form affecting lungs)
- Alveolar
- Polycystic echinococcosis (least common)
Treatment of Hydatid disease
Surgery ,USS guided aspiration and chemotherapy
USS guided aspiration if single cyst (Puncture, aspiration, injection and reaspiration) has widely replaced surgery and chemo
Pretreat with albendazole before percutaneous drainage /surgery
Lung resection is not advised - cystectomy is advised if going for surgery
Chemo for upto 1 month after removal is controversial
In asymptomatic patients, multiple cysts in >1 organs, recurrence - chemo alone can be tried
Chemo - albenadazole or mebendazole , can add praziquantel after surgery for synergy
Bipap and not tolerating it, what are the causes?
Blowing into the eyes Poor mask and headgear fit High leak Inappropriate settings Not densitised with mask Poor sensing - dyssynchony Lack of humidification
Acute flaccid paralysis, 4 causes of lung disease
AF = clinical syndrome characterized by rapid onset of weakness, including weakness of muscles of respiration and swallowing, progressing to max severity within days to weeks. Flaccid = absence of spasticity or other signs of disordered CNS tracts
Causes: Enterovirus D68, West nile, Adenovirus, Guillan barre, Botulism, Tetanus, Spinal cord compression
Mechanisms:
- Atelectasis
- Aspiration
- Hypoventilation/respiratory muscle weakness
- Secondary infection
- GB -> autonomic neuropathy -> cardiac failure -> pulmonary edema
Risk factors for acute chest syndrome in sickle cell
- Age, in particular pediatric age group and highest incidence at 2-4 years of age
- Pulmonary infection such Mycoplasma pneumonia
- Fat embolism
- Post operative atelectasis
- Lower concentration of fetal haemoglobin
- Bronchospasm due to asthma
- Higher WBC count
- Previous ACS (most important)
6 causes for chronic or persistent cough in 3 year old.
Dry:
o Allergic rhinitis and post nasal drip
o Asthma
o GERD
o Tracheobronchomalacia +/ - an associated abnormality like vascular ring
o Habit cough
o Interstitial lung disease – eg. Eosinophilic lung disease
o Post infectious cough: Pertussis and Mycoplasma pneumonia (Kendig’s)
o Drugs like ACEi
Wet:
o Cystic fibrosis
o Primary ciliary dyskinesia
o Retained foreign body – consider in child<5 years, typically wet cough, but could be dry. Associated: wheeze, halitosis.
o Aspiration
o Immunodeficiency
o Chronic endobronchial suppurative disease:
§ Non-CF bronchiectasis- eg. Immunodeficiency
§ Persistent bacterial bronchitis
Other:
- Chronic infection: TB (cough, monophasic wheeze from hilar lymphadenopathy or tuberculoma), fungal (histoplasmosis, cocciodoides), Chlamydia pneumonia, Mycoplasma pneumonia, non-tuberculous mycobacteria
- Chalmydia trachomatis, CMV can cause “afebrile pneumonia of infancy”
- Non-infective bronchitis: from exposure to environmental pollutants - environmental tobacco smoke, biologic pollutants (eg, dust mite, mold, pets), nitrogen dioxide from unvented gas heating, and particulate matter from wood stoves and cooking
- Mediastinal mass
Effects on DLCO with Mueller maneuver
Mueller maneuver = inhalation against closed glottis decreases intrathoracic pressure and increases blood return to the lungs
= Increased DLCO
Effects on DLCO with pulmonary HTN
Decreased DLCO
Effects on DLCO with lobar resection
decreased V = decreased DLCO (normal if DLCO is corrected for volume)
Effects on DLCO with pulmonary hemorrhage
low Hb–>decreased DLCO (normal if DLCO if corrected for Hb)
Pulmonary hemorrhage –>increased DLCO
Effects on DLCO with Smoking
High carboxyhemoglobin–>decreased DLCO
Equation for DLCO
DLCO = [VA x Pulm cap blood volume x Hgb] / [A-C membrane thickness x COHb]
Five PARDS diagnostic criteria.
- Exclude patients with perinatal lung disease
- Within 7 days of known clinical insult
- Respiratory failure not fully explained by cardiac failure or fluid overload
- Chest imaging findings of new infiltrate(s) consistent with acute pulmonary parenchymal disease
- Oxygenation
CPAP ≥ 5, P/F ≤ 300, SpO2/FiO2 ≤ 264
Mild = 4 ≤ OI ≤8
Moderate = 8 ≤ OI ≤ 16
Severe = OI ≥ 16
Equation for Oxygenation index
mean airway pressure MAP × FiO2 × 100÷PaO2
Tidal volumes suggested for ARDS
~6ml/kg
Obesity changes on lung function test (TLC, RV, FRC, ERV)
TLC: reduced
RV: may increase due to air trapping
FRC: decreased
ERV: decreased
Pneumothorax: When can they fly after radiographic resolution ?
The BTS air travel guidelines recommend that complete resolution of the pneumothorax and that then a minimum 7 days should elapse prior to flying.
In patients with underlying conditions longer periods are required = CF, the consensus is recommending at least 2 weeks from resolution.
If in a CF patient with severe disease, what 2 tests would you order to assess safety for flight
- Spirometry (wait 2 weeks post pneumo)
if FEV1 <50% predicted - do HCT - Hypoxic challenge testing: If SpO2 falls below
90%, in-flight oxygen is advised
Chronic Pulmonary disease in HIV AIDS
- Immune Reconstitution Inflammatory Syndrome
- ILD
- Pulmonary HTN
- Recurrent infections
- Bronchiectasis/BO
- Malignancy
What is Immune Reconstitution Inflammatory Syndrome?
A syndrome that develops in the context of recovery of CD4 cell counts following the initiation of Antiretroviral therapy (ART).
IRIS is believed to represent an excessive inflammatory response to an antigen, most frequently a subclinical or recently treated opportunistic infection. It is most commonly seen in conjunction with such infections as TB, PCP, MAC, and Cryptococcus
Most cases occur in the first few weeks after starting ART, though cases of IRIS have been reported up to 12 months following the initiation of therapy. Risk factors include low CD4 count prior to initiation of ART and opportunistic infection treatment proximal in time to ART initiation.
What disease gives you a fried egg appearance on electron microscopy?
ABCA3
Tx = Oxygen/supportive, steroids, hydroxycholorquine
Pathology findings in chronic hypersensitivity pneumonitis
- Giant cells, granulomas, or Schaumann bodies
- Interstitial pneumonia (UIP)–like Pattern.
- A nonspecific interstitial pneumonia (NSIP)–like pattern or a bronchiolitis obliterans organizing pneumonia like disease can also be seen in chronic HP
Pathology findings in sub-acute hypersensitivity pneumonitis
The classic triad of
- Interstitial lymphocytic-histiocytic cell infiltrate.
- Bronchiolitis obliterans.
- Scattered poorly formed non-necrotizing granulomas.
Pathology findings in acute hypersensitivity pneumonitis
- Interstitial mononuclear cell infiltrate.
2. Granulomas and macrophages with foamy cytoplasm have also been reported.
Why shouldn’t you use PEF in children?
A peak flow reading will only be as good as your effort. Numbers can be artificially high with tongue thrusts or spitting.
Or they may be artificially low due to not enough effort or poor technique
Three reasons why can’t a 6 year old can’t get a 6 second plateau on spirometry
- High elastic recoil results in exhalation of FVC prior to 6 seconds
- Require coaching specific to their developmental level, with possible incentive display.
- Restrictive lung disease
Blood gas findings if bubble in a venous sample (effect on pH, PO2, PCO2, HCO3)
pH unchanged
pO2 increased
pCO2 decreased
HCO3 unchanged
Components of the Starling Equation
Qf = Kf[(Pc − Pis) − σ(πpl − πis)]
where Qf = net flow of fluid
Kf = capillary filtration coefficient; this describes the permeability characteristics of the membrane to fluids and the surface area of the alveolar-capillary barrier
Pc = capillary hydrostatic pressure
Pis = hydrostatic pressure of the interstitial fluid
σ = reflection coefficient; this describes the ability of the membrane to prevent extravasation of solute particles such as plasma proteins
πpl = colloid osmotic (oncotic) pressure of the plasma
πis = colloid osmotic pressure of the interstitial fluid
The Starling equation describes the movement of liquid across the capillary endothelium
What effects would the Starling equation (on which variable, and effect on flow) would protein losing enteropathy have?
Decreased colloid osmotic pressure
What effects would the Starling equation (on which variable, and effect on flow) would left heart failure have?
Increased capillary hydrostatic pressure
4 causes of vascular ring and what symptoms would you expect?
- Double aortic arch (most common)
- Aberrant left subclavian and right aortic arch (second most common)
- Circumflex aorta (rare)
- Persistent 5th aortic arch (rare)
- Cervical aortic arch
- Pulmonary artery sling (not a true vascular ring)
Symptoms:
Respiratory: noisy breathing, barking cough, wheeze, frequent URTI, apneic episodes, intermittent cyanosis (from tracheal compression)
GI: difficulty swallowing (solids) – sensation of food being stuck, slow eating, hyperextension during feeds (from esophageal compression)
2 surgical causes of unilateral vocal cord paralysis
- Thoracic surgery with iatrogenic injury to recurrent laryngeal nerve (e.g., PDA repair, Norwood cardiac repair, esophageal surgery especially TEF repair, thyroid surgery)
- Peripheral nerve pathology
- Mediastinal lesion (e.g., tumor)
2 congenital causes of bilateral vocal cord palsy
- Idiopathic (usually)
- Arnold-Chiari malformation
- Hydrocephalus
- Meningocele
- Myasthenia gravis
- Birth trauma (may be transient)
What side is most commonly affected in unilateral vocal cord paralysis?
Left due to the path of the recurrent laryngeal nerve
Symptoms of Unilateral vocal cord paralysis
Usually left side
Breathy voice
Acceptable airway
Risk of aspiration
Symptoms of Bilateral vocal cord paralysis
Normal voice
Biphasic stridor
Airway compromise
Alpha-1 antitrypsin deficiency, mom diagnosed with PiZZ genetics. How is this inherited? Should you test the son?
What is the most important thing he can do?
Autosomal co-dominant
Yes - Yes if symptomatic. Discuss predispositional testing if asymptomatic.
Avoid smoke exposure to reduce risk of emphysematous changes.
What is the role of Alpha-1 Antitrypsin?
AAT inhibits the activity of a number of proteolytic enzymes, the most important of which is neutrophil elastase
Lung disease in AAT deficiency occurs primarily secondary to loss of function, resulting in an imbalance between levels of AAT relative to the amount of neutrophil elastase. Neutrophil elastase degrades elastin and extracellular matrix elements located within the lower respiratory tract that normally function to maintain the structural integrity of the lung.
Major role = inhibit neutrophil elastase -> degrades elastin (also basement membrane + matrix)
Synthesized by hepatocytes
Categories of Alpha-1 Antitrypsin deficiency
- Normal (>200umol/L)
- Deficiency (<20), Z-variant = most common
Z variant = normal mRNA and synthesis rate, ~15% released into circulation (85% blocked in the terminal secretory pathway of hepatocytes)
- Null - no detectable circulating AAT
- Dysfunction - AAT Pittsburgh (thrombin inhibitor), PI*F (decreased association with elastin)
Most common abnormal alleles in Alpha-1 Antitrypsin deficiency
Most common abnormal alleles = S and Z
S = associated with a mild decrease in circulating levels and no hepatocyte accumulation of AAT
Z = substantial decrease of circulating levels and hepatocyte accumulation of AAT
Highest to lowest levels = PIMS, PISS, PIMZ, PISZ, PI*ZZ
PI*ZZ = autosomal co-dominant gene
PIMS and PISS have levels that are above what is needed to protect the lungs -> no increased risk of lung disease
Null allele -> no detectable levels and pts are at the highest risk of lung disease (but no liver disease as AAT is not produced and therefore not accumulated in hepatocytes)
Alpha-1 Antitrypsin deficiency genotypes at increased risk for Emphysema
Deficiency/null + homozygous or heterozygous
Characteristics of Emphysema in Alpha-1 Antitrypsin deficiency
Permanent dilation of the air spaces distal to the terminal bronchioles secondary to destruction of alveolar wall and without fibrosis
?secondary to protease-antiprotease imbalance
Imbalance between antielastase defenses and excess leukotriene elastase -> elastase degradation
*major pathogenic factor = cigarette smoke (capable of inactivating AAT and recruits inflammatory cells)
When should you consider doing quantitative testing of AAT?
Confirm absence of AAT peak
Early onset pulmonary emphysema
Family history of AAT
Dyspnea and cough in multiple family members
Liver disease NYD
COPD
Bronchiectasis with no evident etiology
Asthma that doesn’t reverse with treatment
Unexplained panniculitis and anti-protease 3 vasculitis
Pulmonary clinical features of Alpha-1 Antitrypsin deficiency
Panacinar emphysema with basal predominance
PFT
- Decreased FEV1, normal (or decreased) FVC, decreased FEV1/FVC (loss of elastic recoil from parenchymal disease with dynamic collapse of normal airways)
- Increased compliance = hyperinflation with increased RV and TLC (pleth>dilution), air trapping
- Decreased DLCO (impairment of gas exchange)
○ More advanced disease -> MIPS/MEPS
CXR -> usually normal initially
Advanced: hyperinflation and increased radiolucency (especially in the lower segments
Treatment for Alpha-1 Antitrypsin deficiency
- Bronchodilator: if helpful, add ICS if evidence of bronchial hyperreactivity
- Antibiotics with bronchitis or URTI -> beta lactams or quinolones
- Oxygen if desats with exercise
- Nutrition
- Augmentation Treatment
Role of Augmentation Treatment in Alpha-1 Antitrypsin deficiency
- IV human plasma-derived augmentation therapy
- Inhalation
- Recombinant AAT
- Synthetic elastase inhibition
Indications:
Based on the presence and level of obstructive lung disease = FEV1 30-65% or normal lung function with rapid decline (change >120mls/yr)
Non-pulmonary complications of Alpha-1 Antitrypsin deficiency
- Liver disease - neonatal cholestasis -> resolves by adolescence (30-40% -> cirrhosis, carcinoma >50yo)
- Necrotizing panniculitis
- Multisystem vasculitis
What is Hepatopulmonary syndrome?
Characterized by the triad of:
- Abnormal arterial oxygenation caused by intrapulmonary vascular dilatations (IPVDs) in the setting of liver disease
- Portal hypertension
- Congenital portosystemic shunts
DDx for PE
Pneumonia Atelectasis Chest trauma Alveolar hemorrhage Malignancy.
Diagnostic criteria of HHT
- Spontaneous recurrent epistaxis
- Multiple telangiectasias (in multiple sites)
- Visceral lesions (AVMs -> GI bleeding, or pulmonary, cerebral or spinal hemorrhage)
- First degree relative with diagnosed HHT
Need 3/4
Investigations to confirm the diagnosis of HHT
- CBC + diff
- Ferritin, stool for occult blood
- Brain Angiography, endoscopy, chest CT, bubble echo
- Genetics
6 mo, asymptomatic, normal chest X-ray. Had BCG at birth. Contact with grandparent with TB.
TST or IGRA in the 6 month old and why?
TST - IGRA has not been validates in <2yrs
** TST can be false negative <2
When can BCG vaccination be ignored as a cause for a positive TST?
- BCG given in infancy and the person tested in now ≥ 10yo
- High probability of TB infection: close contacts, aboriginal Canadians from a high-risk community or immigrants/visitors from a country with high TB incidence
- There is a high risk of progression from TB infection to disease
4yo, asymptomatic, normal chest X-ray. Had BCG at birth. Contact with grandparent with TB.
Negative TST - what is the next step?
Treat as latent TB until repeat TST 8 weeks later is done (The rifampin may be discontinued if, after a period of 8 weeks after the last contact, the repeat TST is negative, and the child remains asymptomatic and is immunocompetent and more than 6 months of age)
NEJM paper on rifampin x 4 months equivalent to INH x 9 months
6yo, asymptomatic, normal chest X-ray. Had BCG at birth. Contact with grandparent with TB.
TST <5mm, what do you do for him?
No further treatment needed
12yo, asymptomatic, normal chest X-ray. Had BCG at birth. Contact with grandparent with TB.
TST 7mm and is diagnosed with latent TB. What are risk factors to ask about for conversion to disease?
Conversion = a TST of 10 mm or greater when an earlier test resulted in a reaction of less than 5 mm.
Original between 5-9:
An increase of 6 mm or more - this is a more sensitive criterion, which is suggested for those who are immune compromised with increased risk of disease or for an outbreak.
An increase of 10 mm or more - this is a less sensitive but more specific criterion. In general, the larger the increase, the more likely that it is due to true conversion
TST conversion occurs within 8 weeks of exposure.
Certain medical conditions will increase risk of conversion as well as drugs (steroids, anti-TNF)
Systemic corticosteroids at daily doses of ≥15 mg prednisone equivalent for 1 month or longer should first be tested for LTBI.
High risk medical factors that increase risk for TB reactivation
AIDS HIV Transplantation SIlicosis Chronic renal failure requiring hemodialysis Recent TB infection (within last 2 years) Abnormal CXR (fibronodular disease) Carcinoma of the head and neck
Definition of TB exposure
Significant contact with a person with suspected of confirmed contagious pulmonary TB
Asymptomatic, normal CXR, normal TST
Definition of TB infection
Asymptomatic, normal CXR, but positive TST
Definition of TB disease
Disease in person wth TB infection in whom signs and symptoms or radiographic manifestations are apparent
People considered positive TST with 0-4mm
Child under 5 years AND high risk of TB infection
People considered positive TST with ≥5mm
HIV (well)
Close contact with active contagious case (past 2 years)
Presence of fibronodular disease on CXR (healed TB)
Organ transplant
TNF-alpha inhibitors
Other immunosuppressive medications
End stage renal disease
People considered positive TST with ≥10mm
All others including:
- TST conversion (within 2 years)
- Diabetes, malnutrition
- Hematologic malignancies
Reasons for positive TST
Mycobacterium TB infection
NTM Infection
BCG in the past
Incorrect technique
Reasons for false negative TST
Incorrect technique Active TB (esp if disseminated) Steroids Young age Malnutrition Viral infections (measles, varicella, influenza) Live vaccines
Advantages of IGRA for TB testing
Interferon Gamma Release Assays
Measures T-cell release of IFN-gamma in response to M. TB
A:
More specific for M. Tuberculosis (does cross react with BCG and most NTM)
Does not require follow-up visit in 48-72 hours
Most useful for latent TB diagnosis in BCG recipients
Cavets to IGRA testing in TB
Cross reacts with some NTM species
Limited S&S for active TB diagnosis
(cannot tell LTBI from active, sensitivity decreased by temporary anergy of acute illness, reduced sensitivity in immune compromised individuals)
Diagnosis of Pulmonary TB
- TST and IGRA done BUT do not distinguish LTBI from active disease and do not “rule out” Pulmonary TB
- CXR
- Gastric aspirates (3 consecutive mornings, taken before ambulation or feeding)
- BAL in select cases
- Microbiology (acid fast staining, DNA probes, PCR)
Side effects of Isoniazid
Hepatotoxicity Peripheral Neuropathy (interferes with pyridoxine metabolism)
Side effects of Rifampin
Hepatotoxicity Hypersensitivity reactions Memory Impairment Drug interactions Body fluid turns orange
Side effects of Pyrazinamide
Hepatotoxicity
Increased uric acid levels
Side effects of Ethambutol
Optic neuropathy (decreased acuity, decreased visual fields, colour blindness)
3 meds and one side effect of each for M abscessus intense phase.
Intensive = 3-12 weeks of IV Amikacin PLUS 1 of: Tigecycline, Imipenum, Cefoxitin (IV) (consider adding macrolide)
“For ABS you need to do CIT-ups”
Amikacin: diarrhea, hearing loss vertigo
Tigecycline: nausea/vomiting, diarrhea
Cefoxitin: nausea/vomiting, diarrhea
Meds fo continuation phase of M. abscesses treatment
Inhaled Amikacin with 2-3 of: PO Minocycline, Moxifloacin, Linezolid, Clofazimine
Side effect of Tacrolimus (x2) and MMF (x1)
Tac: peripheral neuropathy, HTN, nephropathy, diarrhea
MMF: leukopenia, thrombocytopenia
4 airway manifestations of SLE
- PLeuritis with pleural effusion
- ILD
- Pulmonary hemorrhage
- Pulmonary HTN
- Shrinking lung syndrome
- Acute pneumonitis
Most common PFT abnormality in SLE
Restriction + low DLCO
Central sleep apnea on PSG, what are two tests you’d do in a 3 month old?
Brain MRI
?genetics (CCHS)–but might be more convinced if hypoventilation
Other: metabolic work up, infectious work-up
4 critical components in emergency trach kit at home
2 trach tubes, one size and one size below Obturator from current trach tube Portable Suction and catheter Syringes for sterile water If vented - ventilator and bagger
Others:
Two clean trach tubes with holders attached and obturators in place:
One tube that’s the same size as the tube your child has in place
One tube that’s a size smaller than the tube your child has in place
Trach ties and noses
Spare inner cannula
Small blanket or towel roll
Sterile water and water soluble lube
Portable suction
Luer-Lock syringe (if trach tube is cuffed)
Instructions for CPR and how to troubleshoot an obstructed tube
Oxygen
Emergency phone numbers
4 absolute or relative contraindications of NIV
NIV should not be used in patients:
- After recent facial or upper airway surgery
- In the presence of facial abnormalities such as burns or trauma
- If there is fixed obstruction of the upper airway
- If the patient is vomiting.
Contraindications to NIV include:
- Recent upper gastrointestinal surgery
- Inability to protect the airway
- Copious respiratory secretions
- Life threatening hypoxaemia
- Severe co-morbidity
- Confusion/agitation
- Bowel obstruction
- Poor glottic function
- Inability to achieve adequate ventilation noninvasively
- Patient preference
- Lack of caregiver expertise.
What class is Tiotropium (Spiriva)?
Anticholinergic - a long-acting muscarinic receptor antagonist
What receptor does Tiotropium (Spiriva) work on?
There are five subtypes of muscarinic receptors, three of which are found in human airways (M 1 , M 2 , M 3 ).
All three types of muscarinic receptors mediate neurally induced bronchoconstriction.
Tiotropium has a high affinity for M receptors but dissociates very slowly from type M1 and M3 receptors, resulting in prolonged prevention of bronchoconstriction and a 24-hour bronchodilatation effect.
How does Tiotropium work? Airway effects?
The effect on lung function is comparable to that of salmeterol, and there may also be acute bronchodilatation in patients with poorly controlled symptoms.
What is the duration of action of Tiotropium?
Tiotropium has a high affinity for M receptors but dissociates very slowly from type M1 and M3 receptors, resulting in prolonged prevention of bronchoconstriction and a 24-hour bronchodilatation effect.
One advantage of PRN LABA use
Longer acting than ventolin so more convenient to use
Two disadvantages of PRN LABA use
- Tolerance and reduced sensitivity to the bronchodilator effects of salbutamol
- Increased risk of exacerbation, serious adverse effects and death
What is Direct Bronchial challenge testing?
Methacholine mimics the neurotransmitter acetylcholine to directly interact with muscarinic receptors on airway smooth muscle, resulting in contraction and airway narrowing.
Similar direct airway responses can be demonstrated with histamine. When the muscarinic receptors are directly stimulated, the response is felt to reflect a property of the airway smooth muscle, but airway structure and geometry also influence the response.
Methods:
- Methacholine challenge
- Histamine
What is Indirect Bronchial challenge testing?
Bronchoconstriction can be elicited through exercise or other stimuli to the airways that act indirectly to cause airway narrowing.
Both exercise and eucapnic hyperventilation cause airway drying and cooling, and the stimulus to bronchoconstriction is now recognised to involve the osmolar change in the airway epithelium resulting from water loss.
An osmolar stimulus can also be induced by inhalation of hypertonic saline or, in a more recently developed test, by inhalation of mannitol powder.
Other indirect challenge tests causing bronchoconstriction by stimulation of inflammatory cells and mediators and/or sensory nerves include adenosine monophosphate and allergen challenge.
Methods:
- Exercise
- Mannitol
- Hypertonic saline - osmotic stimulus
- Allergen challenge
Max dose of pancreatic enzyme in PERT, what side effects can it cause, what are 2 other reasons for diarrhea other than not having enough enzyme
Limit to 2500 lipase units per kg per meal or 10,000 lipase units per kg per day
Side effects: fibrosing colonopathy
What are 2 other reasons for diarrhea other than not having enough enzyme in CF?
Small bowel bacterial overgrowth
C-diff
Celiac
Calculate static compliance
Cs = VT/Pplat-PEEP
Calculate dynamic compliance
Cd = VT/PIP-PEEP
Decreases with increasing RR or airway resistance
An increase in respiratory rate will result in an increase in venous return. (and increased airflow)
Long-term PFT findings of BPD
PFTs frequently show decreased forced expiratory volume in one second (FEV1) and decreased ratios of FEV1 to forced vital capacity (FEV1/FVC), consistent with airflow limitation and small airway obstruction
Two histopathology features of new BPD
- Less regional hetergeneity
- Mild airway smooth muscle hypertrophy
- Rare fibroproliferation
- Alveolar simplification
- Fewer arteries, but “dysmorphic’
- Rare airway epithelial lesions
Unvaccinated asthma patient, currently on oral prednisone course. Exposed to sister with confirmed diagnosis of varicella. How do you manage.
1-If there is evidence of immunity, nothing. Observe clinically , if developed disease treat with antiviral
2-If no evidence of immunity , then depend on steroid route/dose and duration .
Definition of high dose steroid in regard to immunosuppression: Receiving daily corticosteroid therapy at a dose ≥15 mg (or >2 mg/kg/day for patients weighing <10 kg) of prednisone or equivalent for ≥14 days;
3- The timing to vaccine if patient is on high dose steroid is 4 weeks after stopping
4 hepatobiliary manifestations of CF.
Neonatal cholestasis Focal biliary cirrhosis Multilobular cirrhosis Non-cirrhotic portal hypertension Hepatic steatosis Gallstones
4 mechanisms that High flow supports respiration
HIFLOW Heat and humidification of secretions Decrease inspiratory effort FRC increases (CPAP effect with PEEP) Lighter - more tolerable Oxygen dilution (can minimal oxygen dilution by meeting flow demands) Washout of dead space
3 complications of CCHS (other than apnea and pulmonary hypertension) and how you would screen for them.
- Cardiac ( Heart Block – Prolonged Sinus Pauses ) ECG – Seventy-two-hour continuous electrocardiography (Holter monitoring)
- Ophthalmic (meiosis, strabismus, and convergence insufficiency) – Ophthalmologic assessment , Pupillometry (measurement of pupil size and reactivity)
- Malignancy (CCHS is associated with tumors of neural crest origin, primarily neuroblastomas) risk is strongly associated with PHOX2B genotype
- GI (Hirschsprung) – Clincaly monitoring [Delayed passage of meconium (failure to pass meconium within the first 48 hours of life), Constipation, Abdominal distension, Tight anal sphincter, or symptoms of enterocolitis (fever, vomiting, abdominal distension, and explosive diarrhea).
Contrast enema and rectal suction biopsy. - Neurobehavioral - Cognitive deficits in children with CCHS, including learning disabilities, limitations in perceptual skills, vocabulary and abstract reasoning,
Neurocognitive testing – Annual neurodevelopmental screening is recommended, to monitor for progressive dysfunction (which might be caused by insufficient ventilation, recurrent hypoxemia, or by the underlying disorder), and to optimize support services
Surveillance for neural crest tumors in CCHS
- For patients with PHOX2B NPARMs, close surveillance for neuroblastoma is recommended, consisting of chest and abdominal imaging and urine catecholamines (every three months until age two years, then every six months until age seven years).
- For patients with longer PARMs (20/28 and longer), surveillance for ganglioneuromas and ganglioneuroblastomas is recommended, consisting of annual chest and abdominal imaging.
- For patients with short PARMs (24 through 27 repeats), surveillance is not required.
2 situations/indications where steroids are used in TB.
Tuberculous meningitis
Constrictive pericarditis, and patients at high risk of constrictive tuberculous pericarditis.
Nitric oxide in pulmonary hypertension - mechanism of action?
Inhaled nitric oxide selectively dilates pulmonary vasculature in ventilated areas of the lung.
Mechanism of action:
NO activates soluble guanylyl cyclase (sGC) to produce cyclic guanosine monophosphate (cGMP) leading to decrease vascular smooth muscle tone (ie, vasodilation)
Additional effects of NO include suppression of both smooth muscle proliferation and platelet aggregation
2 side effects of iNO
- Hemodynamic deterioration
- Methemoglobulinemia
- Rebound pulmonary HTN
Weaning approach:
Can wean rapidly to 5 ppm
After 5 ppm, need to wean slower to b/c of rebound pulmonary hypertension
Why can you see barrel shaped chest in asthma?
Chronic Hyperinflation - chronic pulmonary disease
Air trapping in obstructive disease results in increased residual volume
Explain how does hyperinflation affects compliance or oxygenation?
Compliance decreases in obstructive disease (if there is hyperinflation)
Hypoxemia : V/Q mismatch ( stretched alveoli and narrow extra alveolar vessels)
3 aspects of management of severe asthma
Ipratropium bromide IV steroids IV MgSO4 Start BIPAP IM epinephrine IV Ventolin
Cardiology wants to give as asthmatic patient B-blockers for his long QT syndrome. What do you want to do for management? list 3 things.
Avoid triggers
Compliance with LTRA (Preferred) or ICS
Consider use of ipratropium bromide as reliever
Consideration should be given to use of ipratropium bromide as a reliever medication. If this is ineffective, beta-agonist reliever should be added. If symptoms are severe enough to require a preventer medication then consider starting a leukotriene antagonist as first line. The aim here would be to avoid the potential corticosteroid related increase in cardiac event risk. Failure to achieve control on a leukotriene anatagonist could lead to addition of low-dose inhaled corticosteroids.
11 yrs old boy on ICS- LABA single dose maintenance and reliever - Why do we use formeterol?
LABA with rapid onset
Formoterol has a rapid onset of action comparable with albuterol (within three to five minutes), in addition to being long-acting (up to 12 hours of bronchodilation).
Why is combination ICS-LABA preferred on ICS- intermittent SABA in certain patients?
More consistent use (for reliever therapy) results in improved ICS use ( increased compliance).
Decreases in asthma exacerbation and emergency visits.
If the patient is African Canadian are you concerned to put them on ICS/LABA ? and why ?
Not concerned
The SMART trial initially showed worse outcomes in african americans. The results have been controversial because there were differences in baseline asthma characteristics between white and african american patients (lower baseline peak exp flow, more nocturnal symptoms, more emergency department visits and hospitalisations).
Mother has chondolymata. Papillomatosis in newborn, describe how do they look on bronchoscopy?
Papillomas: Macroscopically visible “cauliflower-like” exophytic lesions
Location: Larynx
Less often, affects the oral cavity, trachea and bronchi.
4 yrs old Child adopted from Ukraine, CT shows RML + RLL bronchiectasis. List 6 differentials. (Localized bronchiectasis)
FB Lung malformation TB Obstructive (external compression) Aspiration Tumour Infection
CCHS: what gene?
PHOX 2B
How does PHOX2B affect/leads to non- respiratory complications in CCHS?
The gene is typically responsible for expression regulation of genes involved in the development of the autonomic nervous system
List 3 non-respiratory complications of CCHS
Hirschsprung Abnormal pupillary response Cardiac asystole, sinus pauses Development of neural crest tumours ANS dysregulation
List the 6 classes of CF genetic mutations. Briefly describe each
Class 1: Protein synthesis defect (blueprint for making a door, for example)
Class 2: Protein maturation defect (manufacturer)
Class 3: Gating defect (door doesn’t open)
Class 4: Conductance defect (door too small)
Class 5: Reduced quantity (production vs demand)
Class 6: Reduced stability (poor quality material)
Sarcoidosis; list the distinctive lesion on histopathology.
Non-caseating granulomas
Staging of Sarcoidosis
Stage 0: Normal imaging
Stage 1: Bilateral hilar infiltrates
Stage 2: Parenchymal infiltrates + hilar infiltrates
Stage 3: Parenchymal infiltrates without hilar infiltrates
Stage 4: Fibrosis
Other presentations of Sarcoidosis
Granulomatous lesions can occur in any organ but most commonly in lung, lymph nodes, eyes, skin, liver, heart
Non-specific symptoms are common (fatigue, weight loss, fever)
Lofgren syndrome is less common in children (acute arthritis, BHL, erythema nodosum)
Can have cardiac, ocular, neurological, renal involvement and hypercalcemia/hypercalciuria
Common skin lesions = papules, plaques, nodules, changes in old scars, erythema nodosum, hyperpigmented lesions, and hypopigmented lesions.
Central nervous system involvement may present with headache, seizures, cranial nerve palsies, motor signs, hypothalamic dysfunction, and hydrocephalus.
Early onset sarcoidosis (<4yo) → skin rash, uveitis, arthritis, absence of lung disease
PFT Findings in Sarcoidosis
Often normal
Advanced = restriction with low DLCO
Bronch and BAL Findings in Sarcoidosis
Specific changes of waxy yellow mucosal nodules and nonspecific changes → erythema, edema, granularity and cobblestoning of the airway mucosa and bronchial stenosis (typically in the lobar and segmental bronchi).
BAL: lymphocytosis in >85%, normal or low neutrophils (except in late disease) and CD4:CD8 is increased
Diagnosis of Sarcoidosis
Typical clinical features are supported by a tissue biopsy showing noncaseating granulomas
Pulmonary prognosis in Sarcoidosis
The clinical course is chronic or progressive in 10%–30%, and fatalities occur in 1%–5% of patients, typically due to progressive pulmonary fibrosis or central nervous system or cardiac involvement
Pulmonary involvement may lead to progressive pulmonary fibrosis and end stage chronic lung disease; this seems to be more likely with stage III pulmonary disease at the onset in both adults and children.
What is Harrison sulcus/groove? Describe 2 pathophysiologies that can lead to Harrison sulcus.
A horizontal groove along the lower border of the thorax corresponding to the costal insertion of the diaphragm. It reflects increased work of breath against airflow resistance
Ex: Asthma, BO
Also seen in rickets as soft ribs drawn in by diaphragm under tension (Tends to be more common infancy when the chest wall is softer)
Why the low oxygen saturation in Methemoglobulinemia?
Hemoglobin converted from ferrous(Fe2+) to ferric state (Fe 3+) by oxidation by MetHb. The presence of ferric heme molecules causes a structural change in the hemoglobin molecule, resulting in reduced oxygen-carrying capacity and impaired unloading of oxygen at the tissue. This left shift in the oxygen saturation curve results in functional anemia.
The low saturation is due to the waveband of the saturation monitor. Pulse oximetry can only measure two frequencies, oxyhemoglobin and reduced Hb. As MEtHb rises the saturation falls and plateaus at 85%. Despite normal Arterial PO2 - saturation gap
How do you test for Methemoglobulinemia and how do you confirm it?
Arterial Blood is chocolate brown colour
Measure blood level of MetHb (blood gas)
Evelyn Malloy method
Co-oximeter–>gives a print out of various hemoglobin
Features of Pierre Robin Syndrome
Micrognathia
Big tongue posterior, glossoptosis
Airway compromise
+/-Cleft palate
Management of Pierre Robin Syndrome
Airway obstruction: ONO, Cap Gas, PSG
Feeding difficulties: OT assessment, formal feeding study
Airway Obstruction
Non-Surgical:
Lateral or prone positioning.
Nasopharyngeal airway
CPAP/BIPAP
Surgical: Tongue-Lip adhesion to increase oropharyngeal gap
Floor of mouth release
Mandibular distraction
Tracheostomy*
Feeding: NG or G tube
List 3 things how his history of TEF can contribute to airway inflammation and bronchospasm.
Asthma is seen in TEF
Patients with a history of EA/TEF have an abnormally high prevalence of bronchial hyperreactivity, suggesting that airway reactivity in these individuals may be due to events in early childhood such as chronic aspiration, rather than atopy
Airway malacia
Allergy/Atopy more common
Aspiration/Reflux
Protracted bronchitis - (more prominent in younger children with TEF)
Cytokine to go toward TH1 , cytokine to go toward TH2.
TH1: IL-12
TH1->IFNg, IL-2, TNF-a: Cell mediated immunity
TH2: IL 4
TH2->IL-4, IL-5, IL-13: allergy, IgE, eosinophilia, AHR
BPD going on home O2. What is the goal of oxygen saturation according to Current BTS criteria?
≥ 93% for 95% of the recording time if continuous oximetry
Pulmonary AVM. Patient just had embolization. Calculate shunt in percentage.
QS/QT=CcO2-CaO2/CcO2-CvO2 x 100 %
Normal = 2-5%
List one congenital PAP (Other than idiopathic)
Surfactant protein B deficiency
This term is usually used when they present early in newborn or infancy .
List one acquired PAP
Autoimmune PAP (GMCSF receptor antibody)
Primary vs Secondary PAP
PAP can also be classified as primary and secondary
primary (Alveolar proteinosis is the main abnormality) or secondary to other disorders
Primary is Autoimmune PAP (GMSCF receptor antibody) or hereditary PAP (receptor deficiency)
Secondary could be due to connective tissue disease , infection, immunodeficiency, malignancy, chemical inhalation
List 2 treatments options for PAP.
Whole lung lavage for primary PAP
GMCSF -inhaled or s/c
Immunosupression : steroids/Hydroxychloroquine
lung transplant in congenital PAP and acquired PAP
DDx of raised left hemidiaphragm.
Eventration left diaphragm
Volume loss left lung due to hypoplasia or collapse
Unilateral Diaphragmatic palsy (many causes are idiopathic if no trauma/surgery ) - eg. due to left mediastinal mass causing phrenic nerve compression
Subpulmonic pleural effusion
(with diaphragmatic hernia, you shouldn’t be able to actually see the diaphragm)
Abdominal mass - eg. splenic
Raised left hemidiaphragm, now in supine position. How does this change VC?
Would reduce vital capacity due to the effects of posture/gravity on static lung volumes plus a paralyzed diaphragm that can lead to ineffective ventilation and paradoxical breathing exaggerating the normal physiologic response.
List 2 causes for unilateral VC paralysis
Birth trauma
Cardiac surgery ( PDA ligation, coarctation repair )
Neck surgery
Idiopathic (all causes of unilateral can theoretically cause bilateral)
List 2 causes for bilateral VC paralysis.
Birth trauma
Chiari malformation
Idiopathic
Hereditary neuropathies
What is the nerve that controls the motor part of the larynx? From which major nerve does it originate from?
Recurrent laryngeal nerve supplied all muscles of larynx except cricothyroid which is supplied by superior laryngeal nerve
Originates from Vagus nerve
Post lung transplant: list 3 acute complications (< 6 mos)
Surgical complications:
1- Dehiscence of the airway anastomosis
2- Dehiscence of the vascular anastomosis
3- recurrent laryngeal nerve injury
Non surgical
1- Hyperacute rejection
2- Bacterial infection
3- Fungal infection
Post lung transplant: list 3 chronic complications (>6 mos)
1-Acute humoral rejection 2- Posttransplant Lymphoproliferative Disease 3- Chronic Lung Allograft Dysfunction 4- Renal dysfunction 5- infection( viral/Bacterial/Fungal)
How does flail chest affect respiration?
Multiple rib fractures resulting in the destruction of the integrity of the thoracic skeleton can cause paradoxical movement of the “flail chest”
The unsupported area of the chest moves inward with inspiration and outward with expiration which leads to dyspnea. The explosive expiration of coughing is dissipated and made ineffective by the paradoxical movement and intercostal pain. This can lead to airway obstruction, atelectasis and pneumonia.
List 2 management options for flail chest.
Mechanical positive pressure ventilation.
Surgical stabilization in severe flail chest (has shown to lower the incidence of pneumonia, shorten ICU stay, reduce ventilatory requirement, reduce overall hospital cost)
Pain control to allow unrestricted respiration. With severe fractures, the alleviation of pain and the restoration of cough are important and can be provided by analgesics
Name genetic disorder that leads to SIDS
CCHS
Genes encoding cardiac ion channels, such as SCN5A, KCNQ1, KCNH2, or RYR2], or proteins involved in myocardial conduction – These account for less than 5 percent of SIDS cases
Serotonin transporter gene, or monoamine oxidase A (MAOA) gene, which affects serotonergic and noradrenergic transmission.
Fatty acid oxidation defect
4 complications related to second hand smoking.
Risks to unborn babies:
- Stillbirth, and premature birth.
- Low birth weight
- Increase risk of developing later: leukemia, lymphomas, or brain tumours.
Risks to children and infants:
- Sudden infant death syndrome (SIDS),
- Asthma
- Pneumonia
- Bronchitis
- Ear infection.
- Breathlessness and coughing.
How does High frequency oscillation help in ARDS ?
HFOV achieves effective gas exchange while avoiding high peak airway pressures and the inflation deflation cycles characteristic of conventional ventilation.
Lung volume (and hence oxygenation) is maintained by the application of a high continuous mean airway pressure.
CO2 removal is achieved despite small tidal volumes (2–4 mL/ kg) by imposing a breath frequency of 300–900 (5–15 Hz) per minute, resulting in large minute volumes.
Therefore HFOV involves the application of the open lung strategy accompanied by small swings in pressure and volume in the distal airways and alveoli.
Increased CO2 on High frequency oscillation - changes to make?
- Decrease Frequency of Oscillations; can help with minute ventilation and decrease CO2
- Increase amplitude of oscillations- DELTA P or power ; can help with minute ventilation and decrease CO2
- Increase I:E ratio
Pectus excavatum ( labeled as moderate) referred to you by surgeon. whats the MOST COMMON finding you see on PFT.
Normal
How do you measure pectus excavatum ( best method to measure severity) and how do you calculate it ?
Haller index
CT chest - AP: transverse diameter (measured at deepest point of deformity)
The Haller index is calculated by dividing the transverse diameter of the chest by the anterior-posterior distance on CT of the chest on the axial slice that demonstrates the smallest distance between the anterior surface of the vertebral body and the posterior surface of the sternum.
Patient with recurrent pneumonia is now found to have chronic granulomatous disease ( CGD). List 3 bugs common in CGD.
Aspergillus S. aureus Burkholderia cepacia Nocardia Serratia
Duchene muscular dystrophy on BIPAP. When do you consider tracheostomy? List 3.
- Patient and clinician preference
- Patient cannot successfully use NIV
- Inability of local infrastructure to support NIV
- 3 extubation failures during critical illness despite optimal use of NIV and cough assist
- Failure of cough assist to prevent aspiration and drops in SpO2<95% requiring frequent suctioning
Steps in respiratory care of DMD
Step 1: Volume recruitment/Deep lung inflation technique
Step 2: Manual and Mechanically Assisted Cough techniques
Step 3: Nocturnal ventilation
Step 4: Daytime ventilation
Step 5: Tracheostomy
CF patient in severe respiratory distress and known to have severe lung disease. Now almost getting intubated. List 2 things you want to consider in your decision to intubate.
- Reversibility of acute deterioration and/or lung transplant eligibility (Options for bridge to transplant)
- Patient/family wishes, goals of care
Yes or no for hypoallergenic dog for a kid with a positive dog skin test
Recommend caution if considering adopting a dog (hypoallergenic or otherwise), as dog protein is still present which could worsen asthma symptoms (principle of identifying and eliminating exacerbating or aggravating factors). (Be cautious)
Why are the saline and histamine on the allergen prick test ?
Positive (histamine) and negative (saline) control tests should be included to detect inherent skin factors that may affect the reaction to allergen, such as dermatographism and extensive dryness or eczema.
Child on Nocturnal BIPAP. He doesn’t like it. He is not using it. List 3-4 things that can help.
Ensure appropriate mask and headgear fit to avoid pain, skin breakdown, mid-face hypoplasia and mask leak, which can lead to asynchrony
Come up with a desensitization plan
Adjust trigger sensitivity if unable to trigger (increase trigger sensitivity) or if there is autocycling (decrease trigger sensitivity)
Adjust rate
Consider adjusting the pressure by 1-2 units, as he becomes desensitized
Adjust humidity setting–>maybe too much or too little humidity
Consider a ramp
What’s the best way to calculate AT? And why this method is used?
Anaerobic threshold = when you switch from predominantly aerobic to anaerobic metabolism–>lactate production exceeds removal–>high CO2 production as your try and buffer presence of acid–>big increase in ventilation–>VCO2 production increases relative to oxygen consumption (VO2)
ATS CPET statement: use a combination of V slope and ventilatory equivalence (PETCO2, PETO2): since abnormal ventilation pattern and acute hyperventilation can invalidate the noninvasive measurements of anaerobic threshold.
Method 1: V-slope method
- VCO2 increases relative to VO2 -> there’s a huge amount of CO2 production since you’ve switched to anaerobic metabolism, low oxygen consumption size you aren’t using as much aerobic metabolism
Method 2: PETO2 and PETCO2 versus workload - loos for where the lines separate
Give 3 differences between the 13 valent and the 23 valent pneumococcal vaccines.
PCV 13 (prevnar) versus pneumococcal polysaccharide 23 vaccine (pneumovax):
- They are both polysaccharide vaccines, but prevnar has a conjugated protein to stimulate response in infant (<2 years of age). Infants can’t mount an immune response to pure polysaccharide vaccine
- Prevnar is part of routine immunization schedule
- Pneumovax is additional pneumococcal coverage, indicated for individuals with chronic respiratory disease, above 2 years of age
Three differences for PCV 13 versus Pneumovax 23:
<2 years
Conjugated
Less strains
Polysaccharide versus conjugate vaccines
Both have polysaccharide antigens of the bacteria, but in the conjugate vaccine, the polysaccharide antigen is attached to a protein
Young infants cannot mount an immune response to just the polysaccharide antigen, so the protein is required
List 2 risk factors for MRSA in Canada.
Cases are most frequently described within reasonably well-defined populations, such as:
- Children
- Military recruits
- Incarcerated people
- Men who have sex with men
- Sports teams
- Native populations
Common risk factors that have been identified in CA-MRSA outbreaks include:
- Overcrowding
- Frequent skin-to-skin contact between people
- Participation in activities that result in abraded or compromised skin surfaces
- Sharing of potentially contaminated personal items
- Challenges in maintaining personal cleanliness
- Hygiene
- Limited access to health care
3 classes of medications post lung transplant immunosuppressive therapy
Calcineurin inhibitors (Tacrolimus or Cyclosporine)
Cell cycle inhibitors (Azathioprine or MMF)
Steroids
Induction immunotherapy → polyclonal agent (antilymphocyte or antithrombocyte)
IL-2 receptor antagonist (daclizumab or basiliximab)
2 signs of PTLD and 2-3 treatment options
Most common malignancy post transplant
EBV-driven lymphoma
Most common site in the first post transplant year = allograft
Typical symptoms = cough, fever, dyspnea (all B symptoms as well)
CXR: single or multiple round or ovoid pulmonary nodules
After the first year, incidence of extra pulmonary PTLD increases
Other sites = GI, skin, lymphatic tissue (lymph nodes, nasopharynx)
EBV PCR: S/S marker for PTLD
Tx (early): reduction in immunosuppression
Also: rituximab (anti-CD20 monoclonal antibody), low dose cyclophosphamide and prednisone
When to suspect PTLD
New EBV PCR positive –>very important to include EBV in an answer since this would be the most specific feature
Persistently low lung function
Radiological findings
3 pulmonary complications of radiation therapy
Radiation pneumonitis
Pulmonary fibrosis
Interstitial pneumonitis
Factors associated with radiation induced lung injury
Dosimetric factors: Measurement, calculation and assessment of the ionizing radiation dose absorbed by the human body Treatment factors (radiation dose, chemo) → Radiation >10 Gy Patient factors (female, smoking, age) → Younger age at irradiation Medical history: including atopy
3 most common organisms in chronic granulomatous disease
Aspergillus species S. aureus Burkholderia (Pseudomonas) cepacia complex (Serratia marcescens) (Nocardia species)
The organisms that infect patients with CGD are catalase producing. Catalase is an enzyme that inactivates the hydrogen peroxide normally produced by some bacteria and fungi during growth. Although most microorganisms produce hydrogen peroxide, some do not. It was thought that CGD phagocytes could use the hydrogen peroxide produced by catalase-negative microbes to generate reactive oxidants, thereby bypassing the intrinsic CGD defect.
2 side effects of tacrolimus (different organ systems)
Nephrotoxicity: acute increase in plasma creatinine
Hypertension, which is related to nephrotoxicity
Neurotoxicity: mild tremor. Severe headache, visual abnormality and seizure with posterior leukoencephalopathy on brain imaging, pain syndrome
Glucose intolerance and diabetes
Hyperlipidemia
Risk of infection such as bacterial, viral (eg. CMV), fungal
Risk of malignancy — Both cyclosporine and tacrolimus are associated with an increased risk of squamous cell skin cancer and benign or malignant lymphoproliferative disorders
GI: anorexia, nausea, vomiting, diarrhea
Cyclosporine: hirsutism and gingival hyperplasia
Additional: TTP/HUS
Side effects of MMF
Diarrhea – most common S/E
Bone marrow suppression with cytopenia (eg. Leukopenia). Regular CBC (at least every 6-8 weeks)
Patient with RUL atelectasis with a normal oxygen saturation (O2 sat 97%). Describe how this is physiological possible?
Atelectasis–>low ventilation, but ongoing perfusion–>shunt, so venous admixture, but effect on saturation would depend on shunt fraction.
As well, hypoxemia in acute respiratory disease is due to VQ mismatch, but there are compensatory mechanisms like hypoxic pulmonary vasoconstriction
How does an oximeter work?
Oximeter has 2 different wavelengths of light (660 nm and 940 nm)
Oxygenated Hb absorbed light at 660 nm
Normal Hb (without oxygen) absorbs light at 940 nm
Oximeter calculates HbO2/Hb + HbO2
The oximeter measurements are timed with arterial pulse so you get an arterial oxygen saturation
Limitations of pulse oximetry:
Does NOT detect COHb or methemologlobin or dyshemoglobin
Perfusion
Technical issues: skin pigmentation, nail polish, motion artifact
Features of Methemoglobulinemia
PaO2 normal
SaO2 - normal (since on the ABG this is calculated from PaO2)
SpO2 - abnormal (often 85%) - this is the one measured from saturation
Methemoglobin on blood gas is the key way of detecting
Hypoxemia in TAPVR ? and Explain mechanism ?
Shunt
In TAPVR, the heart has no direct pulmonary venous connection into the left atrium. The pulmonary veins may drain above the diaphragm into the right atrium directly, into the coronary sinus, or into the superior vena cava via a “vertical vein,” or they may drain below the diaphragm and join into a “descending vein” that enters into the inferior vena cava or one of its major tributaries, often via the ductus venosus.
All forms of TAPVR involve mixing of oxygenated and deoxygenated blood before or at the level of the right atrium (total mixing lesion).
This mixed right atrial blood either passes into the right ventricle and pulmonary artery or passes through an atrial septal defect (ASD) or patent foramen ovale into the left atrium, which will be the only source of systemic blood flow.
Primary muscles that open and close the vocal cords
Posterior cricoarytenoid (abduction) Lateral cricoarytenoid (add) Transverse arytenoid (add)
Which cord is most likely to be affected in unilateral VC palsy?
Left
Which position are the vocal cords resting in in bilateral VC paralysis?
Adduction
Name 4 muscles of expiration
Rectus abdominis
External and internal oblique muscles
Transversus abdominis
Internal intercostal muscles.
Differential for CF deterioration
- Inappropriate treatment
- Drug resistance
- New bugs
- Non-infectious:
- ABPA
- CF related diabetes
- Poor nutrition
Investigations to do with unexplained CF deterioration
- Sputum sample with antibiotic susceptibility testing
- CF bacteria, AFB smear and culture (at least 2 samples to actually diagnose NTM), fungal.
- Fasting glucose and 2 hour post prandial glucose x 48 hours in hospital
- IgE, IgE to aspergillus
- Bronchoscopy
- CXR, CT scan
Diagnostic criteria for MAC disease in CF
Clinical (both are required):
- Pulmonary symptoms, nodular or cavitary opacities on CXR or CT showing multifocal bronchiectasis with multiple small nodules
- Appropriate exclusion of other diagnoses
Micro criteria (need one)
- Positive culture results from at least 2 separate expectorated sputum samples
- Postive culture results from at least one bronchial wash or lavage
- Transbronchial or other lung bx with mycobacterial histopath features and postive cx for NTM
Treatment for MAC
If MAC that is macrolide susceptible with NO cavitation (non-cavitary): macrolide (ideally azithromycin), rifampin, ethambutol (MAC ARE)
Azithro is the preferred macrolide because:
Less interactions with CYP3A enzyme system, which is also affected by rifampin
Immunomodulatory benefits of azithro in patients with CF
Treatment in CF patient with macrolide resistant MAC, systemically ill, AFB smear positive, or cavitary lesion on imaging:
1-3 months of amikacin at the start of the treatment course, along with standard 3 oral antibiotics
Duration of therapy — Treatment should be continued until sputum cultures are consecutively negative for at least 12 months.
Classic CT findings for MAC
Nodules Tree-in-bud opacities Cavities Bronchiectasis Consolidation
When do you screen for MAC in CF?
Annual sputum culture or BAL for NTM, not a swab sample
Differential diagnosis for chronic wet cough
Acute infection – TB, viral, bacterial, atypical, fungal, parasites
Protracted bacterial bronchitis
Bronchiectasis: o Immunodeficiency o Primary ciliary dyskinesia o Cystic fibrosis o Aspiration o ABPA
Investigations for chronic wet cough
Immunoglobulins – IgG, A, M, E. Vaccine titres – IgG for diptheria, tetanus, HiB; HIV CBC Sweat chloride Sputum culture PFTs (complete + bronchodilator) CXR Mantoux
How to interpret nasal nitric oxide?
Low nasal nitric (<77 nL/min) is quite consistent in PCD, though other things can also result in low nasal nitric oxide (viral illness, sinusitis, cystic fibrosis)
Low nasal NO is relatively sensitive (90% range) and specific (90% range) for PCD
Recommendation: in a child >=5 years of age with a clinical phenotype of PCD and CF excluded, low NO on 2 separate occasions can make a presumptive diagnosis of PCD
Subtypes of PCD
Ultrastructural (most common = dynein arm defect)
Other U/S = radial spoke defects, microtubular transposition defects
Functional
Management of PCD
Pulmonary:
- Regular airway clearance
- Consider antibiotics during pulmonary exacerbations, regular sputum cultures
- Ensure appropriate nutrition and growth
- Immunizations–>influenza, routine, pneumovax
- Avoid smoking
- ENT: audiology assessment, ?hearing aids, referral to ENT physician
- Genetic testing and counselling
- Sibling screening
What are the parameters for assessing good asthma control?
History:
Daytime symptoms <4 days per week (daytime symptoms >3 days per week)
No night time symptoms
SABA doses <4 doses per week (>3 doses per week)
No physical activity limitation
Not missing any work or school
Mild, infrequent exacerbations
Objective testing:
FEV1>=90% of personal best
Diurnal variation of PEF <10-15% (but CTS didn’t recommend use of diurnal variation for diagnosis in children, so this would be more so for >=12years)
Sputum eosinophils <2-3% (adults)
GINA criteria for uncontrolled asthma
- Retrospective assessment over the last 4 weeks
- Daytime symptoms > 2 days per week (3 days or greater is too many days)
- Any night time symptoms
- Reliever use >2 times per week (not including pre-exercise)
- any activity limitation due to asthma (since this will decrease the probability of having symptoms)
- Based on the above, patients can be classified as well controlled, partly controlled or not controlled
What are the key features of a good asthma education program?
- Explain pathophysiology at a level appropriate to developmental status of child
- Demonstrate technique for use devices like MDI or turbohaler
- Provide a written action plan, with additional instructions for yellow zone or red zone
- Discussion about environmental triggers like pets and smoking
- Ideally education provided in patient’s native language
- Ability to monitor adherence such as with pharmacy data
What are the risk factors for asthma hospitalization?
Non-adherence
Poor technique
Having a severe exacerbation, defined as need for oral steroid, in the last year
Prior ICU admission
Significant BD response while on treatment
Low lung function, FEV1<60%
Ongoing exposure to triggers like smoking
Risk factors for asthma exacerbation, as per GINA:
- Poor asthma control
- Low lung function (FEV1<60%)
- High BD reversibility
- > = 1 severe exacerbation in the last 12 months (as per CTS, severe exacerbation is where oral steroids are needed)
- Ever being intubated or in ICU for asthma
- high blood eosinophils
- elevated FeNO
- comorbiities: GERD, food allergy, pregnancy
Approach to severe asthma
- Seek confirmation for the diagnosis of asthma–>review of prior spirometries, methacholine challenge
- Differentiate between severe asthma versus uncontrolled asthma and explore adherence, medication technique and triggers
3. Ensure no red flags suggesting an alternate primary diagnosis or significant co-morbidities: o Bronchiectasis—CF, PCD o Aspiration o Immunodeficiency o Foreign body o ABPA o Tracheobronchomalacia o Obesity o Co-morbidities: GERD, rhinitis, VCD (inducible laryngeal obstruction)
- If severe asthma, then consider:
o Treat co-morbidities like GERD, rhinitis
o Tiotropium
o Symbicort maintenance and reliever therapy
o Biologic – eg. Xolair
Criteria for Omalizumab initiation
o IgE is in target range (30-1300 for 6-11 years, 30-700 for >=12 years)
o Evidence of sensitization either via in vitro or skin testing to an aeroallergen
Omalizumab is dosed every 2-4 weeks, depending on IgE and patient weight
Side effects of Omalizumab
o. Injection site reaction
o No association with lymphoma has been found
o Risk of anaphylaxis – 0.09%, more so after first 3 doses and within first 2 hours.
o All doses are given subcutaneously in a monitored environment
Patients need to be monitored for 2 hours after first 2 doses and for ½ hour after subsequent doses
Differential diagnosis of early respiratory distress of neonate needing mechanical ventilation on high pressures
- Surfactant dysfunction mutation: surfactant protein B, ABCA 3, NKX2.1, pulmonary alveolar proteinosis
- Diffuse developmental disorder such as ACD-MPV
- Growth abnormalities such as pulmonary hypoplasia +/- T21, associated with congenital heart disease, filamin A mutation
- Condition of undefined etiology: PIG, NEHI
- Immunodeficiency – PJP
- Infection – eg. GBS sepsis, RSV, TB
Initial investigations for early respiratory distress of neonate needing mechanical ventilation on high pressures
- Genetics: surfactant protein B, C, ABCA 3, NKX2.1, FOXF1
- Tracheal aspirate for infectious pathogens such as Chlamydia trachomatis, pertussis, viral, bacterial
- CT chest with contrast
For early respiratory distress of neonate needing mechanical ventilation on high pressures what do you send lung biopsy for?
Microbiology Histopathology Immunohistochemistry Immunofluorescence EM
Diagnosis confirmed to be SP-B def, what would you expect on path?
AEC2 hyperplasia
Interstitial fibrosis
Alveolar proteinosis
Large and loosely packed lamellar bodies with vacuolar inclusions
Management of Acute Chest Syndrome
Oxygenation Antimicrobials: broad spectrum abx (including macrolide) Blood transfusion/exchange transfusion Fluids Bronchodilators Incentive spirometry Analgesia
What is the long term pulmonary management for children with sickle cell disease?
Regular evaluation for cardiorespiratory symptoms
PH: screening echo at age 3 years, repeated every 5 years and more often if symptomatic
Asthma and OSA: only investigate if there are symptoms
Consider hydroxyurea
Vaccines: Amoxicillin
PFT and lung volumes annually starting at age 6 (Spiro with every visit if they have asthma)
Lung volumes q5 years in children with no asthma or ACS episodes
Bronchodilator challenge should be done in those with obstruction on PFT
Differential Diagnoses for Restrictive Lung Disease
Interstitial lung diseases
Neuromuscular weakness
Chest wall disease
What are the changes that occur in the PFT in DMD
Low Forced vital capacity with normal FEV1:FVC ratio, Low TLC , normal to increased RV/TLC ratio ,since TLC is more reduced than RV in a generalized neuromuscular disease
Also low MIP and MEP and normal DLCO/VA
What medication is recommended for using in DMD patients and when?
Deflazacort (steroid)- there is no consensus on age of starting according to AAN practice guidelines 2016;
Most of the studies started it between 5-15 years average 8 years ref: ATS DMD guidelines
At the time of motor skills plateau ~5-8 years
Name 2 advantages of using deflazacort and 4 side effects for DMD
Steroids help by anti inflammatory effect and delayed depletion of muscle progenitor cells
Improved muscle strength and lung function
delays cardiomyopathy and scoliosis
Side effects- cataract, bone demineralisation and fractures , excess weight gain, behavioural changes
When is resp fxn decelerated in DMD?
When there is loss of ambulation
When does FVC max plateau occur in DMD?
Around 10-12 years after which it declines
How do you monitor these resp fxn in DMD?
Ambulatory yearly, early non ambulatory 6 monthly FVC, MIP, MEP , Peak cough flow , sats PCO2 in clinic visit , Either PSG or overnight oxymetry with end tidal or tCO2 annually when FVC <60%
Why do DMD patients develop restrictive lung disease?
Respiratory muscle weakness
Scoliosis
what are your resp management strategies for these patients?
Pneumococcal and influenza vaccine to prevent respiratory infections
Start Lung volume recruitment when FVC < 40%- <60% in the 2018 update
Start manually assisted cough or MIE device when FVC <40 (<50% in 2018 update) or Peak Cough Flow <270 with respiratory infections (<160 when well) or MEP<40 (<60 in 2018 update)
Start Nocturnal BIPAP
Symptoms or signs of hypoventilation when awake sats <95 , PCO2 >45
An apnea-hypnea index >10/h on polysomnography OR four or more episodes of SpO2< 92% OR drops in SpO2 of at least 4%/ h of sleep
2018 update - PSG- petCO2 or ptcCO2 of more than 50 mm Hg for at least 2% of sleep time, a sleep-related increase in petCO2 or ptcCO2 of 10 mm Hg above the awake baseline for at least 2% of sleep time, an SpO2 of 88% or less for at least 2% of sleep time or for at least 5 min continuously, or AHI >5
Also FVC <50% and MIP <60% IN THE 2018 UPDATE
Start day time mouthpiece ventilation when patient self extends into daytime NIV or is dyspneic or
Nocturnal NIV not enough to keep day time sats and CO2 normal or cannot speak a sentence without breathlessness
When do you consider trach in DMD?
Failed NIV
Cannot successfully use NIV
No infrastructure for NIV
Patient and clinician preference
3 failed extubation after needing acute ventilation
Failed non invasive methods of cough assist
DMD with severe scoliosis - What cobb angle is best to detect restriction?
Restriction - cobb >50
Nocturnal hypovent- cobb>60
Cardioresp failure - cobb >90
In DMD, >20 cobb angle and FVC 40% is indication for surgical management since bracing is not effective in these patients
Will scoliosis surgery change FVC in DMD?
Surgery doesn’t improve FVC , in fact there is evidence to indicate it might decrease FVC temporarily
The decrease in vital capacity usually lasts for 6 weeks to 3 months after fusion but can persist for up to 1 year
ATS/CDC recommendations on vaccination in DMD
Individuals with DMD should receive yearly immunization with the inactivated influenza vaccine (ie, the injectable vaccine, not the live, attenuated nasal vaccine) and pneumococcal vaccines (including PCV13 and PPSV23), according to guidelines available from the US Centers for Disease Control and Prevention
DMD has normal PCO2 in the daytime but sleep study showed significant hypoventilation and increased PCO2 (they did not give sleep study). What is the next treatment? What are the initial settings?
Nocturnal BIPAP -
Initial settings- S/T mode , IPAP 8/4 (min delta 4) to get chest rise and adequate tidal volume, EPAP minimum 4 BUR just below baseline (2-4 below)
DMD FVC=20% and he has daytime increase of PCO2. What are the methods of ventilation/treatment?
24/7 non invasive ventilation - Start day time Mouthpiece ventilation in addition to night time BIPAP
Trach and 24/7 vent are option based on patient preference and effectiveness of MIE in clearing secretions
Provide 2 explanations for change in VC in patients with DMD
Decreased respiratory muscle strength with progression
Scoliosis causing chest wall restriction
What should you assess for on pre operative assessment of scoliosis for DMD?
FVC, MIP, MEP, PCF Overnight oximetry, PTCO2/TCO2 Echo PSG Optimize respiratory care by making sure you have LVR, cough assist or NIV as indicated by stage of the disease before the surgery CXR
Term baby , born 1 hr ago, with some mild resp distress. - What would you like to do at this point if this baby needs frequent suctioning?
Try to insert OG tube and Get Chest Xray with OG tube in situ
Name 4 different types of TEF. And which is the most common type?
Type A Esophageal atresia alone
Type C- Esophageal atresia with proximal eso pouch and distal fistula (most common 84%)
Type B- Proximal TE fistula with distal esophageal atresia
Type D - TEF with distal connection
Type E: H-type fistula (no EA)
At which developmental stage does TEF occurs?
Embryonic stage
What are associations with TEF?
2/3rd have associated anomalies
VACTERL (Vertebral anomaly, anorectal malformation, TE fistula, cardiac , renal and limb anomaly
CHARGE (coloboma, heart defects, atresia choanae, retarded growth, genital and ear abnormalities )
Potter syndrome ,Pierre Robin, Di George
How do babies with TEF usually present?
Immediately after birth with Increased secretions, choking and respiratory distress and inability to feed if there is esophageal atresia (95% of the time)
Those without esophageal atresia present later with recurrent pneumonia and failure to thrive
What’s the Definitive Rx for TEF?
Surgical ligation of the fistula with anastomosis of the esophageal segments
Reanastomosis might not be possible if the esophageal remnants are far apart in which case a staged approach might be needed.
Name 3 long term complications of TEF/Repair
Recurrent aspiration Tracheomalacia Recurrence of fistula Esophageal stenosis GERD Asthma and wheeze
Term baby born with significant resp distress from birth , with choking, apneas, and resp failure requiring mechanical ventilation. Also has PHTN. No prenatal/antenatal care. Give 3 differential diagnoses
Obstructed TAPVC Congenital Diaphragmatic Hernia Alveolocapillary dysplasia with MPV Sepsis and PPHN Surfactant protein B deficiency with pulmonary hypertension MAS (meconium aspiration)
How could you work up a CDH?
Chest Xray
Echo to look at cardiac anatomy and assess pulmonary hypertension
Ultrasound thorax and abdomen might be needed if there is doubt
CT abdomen might be needed in some cases preoperatively
Name2 types of CDH and name 3 differences for each
Bochdalek (posterior)-95% and Morgagni (anterior)
Bochdalek- posterolateral herniation, Most common, presents earlier and is more severe
Morgagni- Anterior, presents later and milder
Eighty-six percent of Bochdalek defects are left-sided, 13% right-sided, and up to 2% bilateral
What is the definitive treatment option for CDH and when would you consider it ?
Surgical repair(closing defect and reducing abdominal viscera back to abdomen) - after medically stabilizing and controlling pulmonary hypertension
In patients without pulmonary hypertension and who are medically stable, repair is done at 48-72 hours of life
Name 5 possible complications/long term outcomes of CDH
Lung hypoplasia Pulmonary hypertension Neurodevelopmental delay Recurrence of diaphragmatic hernia Chronic lung disease GERD Chest wall deformities Hearing loss Long term ventilator dependence
What is the best prognostic indicator for CDH in the antenatal period?
Observed/expected LHR -ratio of the lung area divided by the head circumference, compared to a reference value for that gestational age
Best survival predictor = Lung Head Ratio value >1.0
Name 2 good and 2 bad prognostic factors for CDH
Good- Isolated left-sided hernias, an intra abdominal stomach, and diagnosis after 24 weeks are favorable prognostic factors
Bad- Syndromic CDH, Prematurity, right CDH, bilateral hernia, associated major cardiac anomalies, presence of liver in thorax
What’s 1 risk factor for higher mortality risk in CDH?
Pulmonary hypertension
Name 1 abnormality you would expect on PFT when pt is older for CDH
Obstruction (Low FEV1 FVC FEV1/FVC ratio and increased RV/TLC)
What is Fetal endotracheal Balloon occlusion (FETO)
Intrauterine occlusion of trachea with a balloon , so that lung fluid stays and promotes lung growth
Tracheal occlusion at 24-28 weeks gestation for severe and 30 weeks for moderate CDH, leads to accumulation of lung fluid which in turn causes lung stretch. This activates a pathway that leads to proliferation and increased growth of the airways and pulmonary vessels, nicely summarized in the acronym PLUG: “Plug the Lung Until it Grows”
Now a plug-unplug sequence,” and reversal of occlusion around 34 weeks is an important component in the fetal treatment strategy.
Name 3 categories of scoliosis and which one is the most common type?
Congenital ,
Idiopathic - (infantile , juvenile and adolescent)
Scoliosis associated with neuromuscular disease
Most common is the idiopathic scoliosis (85%)
What is the prevalence of idiopathic adolescent scoliosis in the general population?
2-3% (Cobb angle more than 10 = scoliosis)
Lower prevalent with higher Cobb angles ( 0.5% cobb more than 20 and 0.2% cobb more than 30)
How do you assess the severity of scoliosis?
Cobb angle
Identify the vertebra whose endplates are most tilted towards each other- Lines are then drawn along the endplates, and the angle between the two lines, where they intersect, measured.
Name 1 respiratory complication and 1 cardiac complication that you expect to see from Scoliosis
Restrictive lung disease and pulmonary hypertension
Cardiopulmonary insufficiency
At what Cobb Angle do you expect to see Restriction? And what angle predisposes to cardio-resp failure, and what angle predispose to nocturnal hypoventilation?
Restriction - cobb >50
Nocturnal hypovent- cobb>60
Cardioresp failure - cobb >90
What determines Restriction severity in scoliotic patients? Name 2.
Cobb angle
Presence of associated neuromuscular problems
Age of onset (lung hypoplasia)
What are the PFT abnormalities that you expect to see and what is the most sensitive marker of reduced thoracic cage and mobility?
Decreased FVC,normal ratio , TLC and normal or increased RV/TLC since TLC is more decreased than RV
You can also see obstruction if there is obstruction of the bronchus due to distortion
Most sensitive marker of reduced thoracic cage mobility is FVC
When performing a PFT , is there something you need to consider when you input the patients information into the system before starting PFT if they have scoliosis?
Predicted values based on arm span instead of standing height , can also use height predicted based on ulnar length if arm span can’t be used
Name 2 modalities for treating scoliosis, and when you would consider each in a 14 year old.
Bracing is mainly used in idiopathic scoliosis
Bracing - only if Cobb angle is more than 25 - 50 and non progressive
Surgical when cobb angle is more than 50 or progress despite bracing in idiopathic scoliosis - growth friendly distraction or spinal fusion
The surgical threshold will also depend on the category of scoliosis whether it is idiopathic or neuromuscular and type of surgery on whether the spine growth is complete or not
If the 14 year old has DMD - surgery is considered if cobb >20 and FVC <40%
Key points re: scoliosis
Cobb Less than 20 and non progressive , wait and watch
Surgery- Growth friendly distraction technique before bone growth is complete and spinal fusion after spine growth is complete
In congenital scoliosis - serial casting until 5 years followed by growth friendly distraction surgery
In idiopathic scoliosis - bracing between 20-50 - surgery choice based on spine growth
In neuromuscular disease - bracing avoided, surgery when Cobb >20 and FVC <40%
7 yr old with scoliosis, cobb angle 30 degrees and is non progressive, what do you do?
Assuming that it is juvenile idiopathic scoliosis answer is bracing
Bracing is advised if >20 or progressive
Indication for growth friendly distraction is more than 40 at time of diagnosis or progressive despite bracing in juvenile scoliosis ;
If cobb less than 20; wait and watch
In adolescent idiopathic scoliosis the threshold is 25 for bracing ; more than 50 for spinal fusion
In congenital scoliosis - serial casting up to 5 years of age followed by distraction devices are used as they do not respond to bracing
If underlying neuromuscular disease- treatment is growth friendly distraction
Name 3 respiratory/cardiac investigations that you would order pre-op for scoliosis surgery
Chest Xray
PFT
Echo
Name 5 possible complications post-op scoliosis surgery
Bleeding Fluid shifts causing pulmonary edema Pneumonia Atelectasis Multifactorial respiratory failure related to pain, sedation, analgesia, restriction, fat embolism etc
BPD - His O2 requirements are 1 Litre by Nasal prongs, FiO2 28%. How severe is his BPD based on this information?
Moderate BPD = At 36 weeks needing FiO2 <30%
Name 4 Risk Factors for developing BPD?
Endogenous risk factors for BPD:
- gestational immaturity
- lower birth weight
- male sex
- white/non-black race
- family history of asthma
- SGA
Prenatal risk factors for BPD:
- maternal smoking
- Pre-eclampsia
- placental abnormalities
- Chorioamnionitis
- IUGR
- no maternal steroids
- perinatal asphyxia
Post natal risk factors for BPD:
- lower Apgars
- RDS
- PDA
- higher weight -adjusted fluid intake
- earlier use of IV lipid
- light exposed TPN
- duration of O2 therapy
Risk factors for BPD in at-risk infants
Duration and approach of mechanical ventilation (increased O2, PIP, rate decreased PEEP) Hypocarbia Colonization with ureaplasma urealyticum Post-natal CMV Post-natal sepsis
Differences b/n new and old BPD
Features of “old” BPD (6)
1) alternating atelectasis with hyperinflation
2) severe airway epithelial lesions
3) marked airway smooth muscle hyperplasia
4) extensive diffuse fibroproliferation
5) hypertensive remodeling of pulmonary arteries
6) decreased alveolarization and overall surface area
Features of “new” BPD (6)
1) less regional heterogeneity
2) rare airway epithelial lesions
3) mild airway smooth muscle thickening
4) rare fibroproliferative changes
5) fewer arteries but “dysmorphic”
6) fewer, larger, and simplified alveoli
Name 3 factors that may worsen or increase severity of BPD.
High PIP, high volumes Hypocarbia High oxygen or duration of oxygen Co-morbidities: PPHN, PDA, IVH, prolonged ventilation, sepsis Invasive Ventilation
What are features of BPD on an infant PFT?
Obstruction
Airway hyperreactivity
What happens to the compliance curve in BPD?
Compliance decreases in BPD due to less surfactant thus increased surface tension
Dynamic lung compliance is markedly reduced in infants with established BPD, even in those who no longer require oxygen therapy.
The reduction in compliance is due to small airway narrowing, interstitial fibrosis, edema, and atelectasis. Established BPD is primarily characterized by reduced surface area and heterogeneous lung units in which regional variations in airway resistance and tissue compliance lead to highly variable time constants throughout the lung.
How does pulm HTN develop in BPD?
Increased muscularization of smooth muscle leads to increased pulmonary vascular resistance
Decreased compliance
What ventilator strategies would you recommend for a patient with early BPD?
Once there is BPD established: Longer I time Large tidal volume High PEEP Lower rate
For RDS (want to prevent BPD): Lower PIP Higher PEEP Increased RR with lower tidal volumes Tolerating higher CO2
Name 3 long term treatments available for BPD
Oxygen Non-invasive ventilation RSV immunization Trach and vent (sajith will do this) Nutrition
You are preparing to send the baby home, what saturation does the BTS currently recommend for the patient to maintain at home?
BTS = ≥ 93%
How long in general would you expect a BPD pt to need home O2 therapy for, and what is the outcome that you expect for their pulmonary function in the future?
Majority are off by 2 years.
PFT could show some obstruction.
What is Pulmonary interstitial emphysema (PIE)?
It refers to the abnormal location of gas within the pulmonary interstitium and lymphatics usually due to positive pressure ventilation. It typically results from rupture of overdistended alveoli following barotrauma in infants with respiratory distress syndrome.
What is the role of antenatal steroids and what is its effect on the incidence of BPD?
Antenatal steroids are used to help increase lung maturation in premature babies. It has been shown to decrease the morbidity/mortality of BPD but not necessarily the incidence.
The use of antenatal steroids in mothers at high risk of delivering a premature infant has reduced the incidence of neonatal death and RDS by 50% but failed to decrease the incidence of BPD, even in combination with postnatal surfactant
What is the role of surfactant and its effect on BPD?
Exogenous surfactant is used in premature babies to decrease the surface tension and increase compliance. It has been shown to decrease mortality from BPD but not the incidence.
Surfactant reduces the combined outcome of death and BPD but not BPD alone
Is there any evidence for inhaled steroids? iNO? Caffeine?
No evidence for inhaled steroids
iNO is a pulmonary vasodilator and has shown some effects in BPD.
In clinical studies, inhaled nitric oxide (iNO) therapy acutely lowered PVR and improved oxygenation in patients with PH in various settings, including premature infants with severe RDS and established BPD. Experimental data have demonstrated that iNO therapy may be lung-protective in several animal models of experimental BPD and, importantly, may be associated with increased alveolar and vascular growth
Caffeine has been shown to help with decreasing airway resistance and postulated to have an additive effect to diuretics but does have undesirable side effects. More evidence for helping with the prevention of BPD.
Comment on the harm vs benefit in the use of Systemic steroids early vs later in a BPD pt.
Benefit: Has shown to help those with BPD successfully extubate (DART protocol) but does not have any effect with reducing the overall incidence or morbidity of BPD. Some evidence as well for short pulses for use with acute lung deterioration.
Acute treatment with steroids improves lung mechanics and gas exchange and reduces inflammatory cells and mediators in tracheal samples of patients with BPD
Harm is substantial and would include: HTN, osteoporosis, increased risk of IVH, poor head growth, neurodevelopmental concerns
Other side effects include systemic hypertension, hyperglycemia, cardiac hypertrophy, intestinal perforation, poor somatic growth, sepsis, intestinal bleeding, and myocardial hypertrophy. Currently the routine use of early high-dose steroids in premature newborns is strongly discouraged
CPS: Avoid early steroids, DART after day 7
What is your differential diagnosis of round pneumonia?
Infectious (bacterial most likely, viral, fungal) pneumonia Underlying congenital lung lesion Foreign body Abscess - lower on differential Aspiration pneumonitis/pneumonia TB/NTM Atelectasis - lower on differential
Why do children develop round pneumonia vs adults?
Underdeveloped pores of Kohn and Lambert’s channels that may cause the centrifugal spread of fluid or bacteria
Mostly children <8
Name 5 common causative agents of pneumonia in children
S. pneumoniae S. Aureus H. Influenzae Mycoplasma (M. pneumoniae) Chlamydia pneumoniae Moraxella Viral
Name 2 bacteria common in ages 1-3 months; 2 bacteria up to 1 yr age
1-3 mos: GBS, E.coli, Chlamydia trachomatis
Up to 1 yr: S. pneumoniae, S. aureus
Name 5 viruses that can cause pneumonia
Adenovirus Influenza RSV Human metapneumovirus Enterorhinovirus
Most common cause of CAP and treatment
S. pneumoniae - PO Amoxicillin or IV Ampicillin if ++ unwell
CAP develops an air fluid level. What 3 bugs would you be expecting that he could have as a causative agent? and what would you call this CXR finding?
Air fluid level = Abscess
Staph aureus, S. pneumonia, Pseudomonas
What test will you perform to confirm or that may help with further management of a potential abscess?
CT chest with contrast
How will you treat a clinically stable patient now with a confirmed abscess?
IV antibiotics: Ampicillin-sulbactam, Cephalosporin with Clinda x 4-6 weeks
Name 3 possible complications of lung abscess.
BP fistula
Empyema
Pyothorax
Pneumothorax
The abscess turns into a significant hemithorax empyema.. how will you proceed now?
U/S
Chest tube with thoracentesis
Consider TPA if clinically indicated and no BP fistula
What is Light’s Criteria? Name 2 examples for each.
3 criteria:
Pleural LDH/Serum LDH >0.6
Pleural protein/Serum Protein >0.5
Pleural LDH > ⅔ upper limit of normal for serum LDH
1 criteria = exudate
Exudates = Infectious, Chylothorax Transudates = CHF, cirrhosis, renal
What will you request the lab to check for on your thoracocentesis sample?
LDH Protein Glucose pH Cell count Culture/gram stain TB
When do you expect the CXR to normalize?
90% by 6 mos, nearly all by 12 mos (empyema as per Kendig)
Side effects of the various TB meds
Hepatotoxicity Neuropathy Retinopathy Bodily fluids may turn orange Supplementation with pyridoxine (with isoniazid) certain populations
When can BSG be ignored as a positive TST?
1) BCG vaccination was given in infancy, and the person tested is now aged 10 years or older;
2) There is a high probability of TB infection: close contacts of an infectious TB case, Aboriginal Canadians from a high-risk community or immigrants/visitors from a country with high TB incidence;
3) There is high risk of progression from TB infection to disease.
Primary immunodeficiencies that can give you pneumonia
Aggammaglobulinemia CVID CGD Hyper IGE syndrome IgA deficiency
Differential for bilateral diffuse infiltrates in an HIV patient
Top list: viral, PJP, LIP
Viral; RSV, influenza, parainfluenza, human metapneumovirus, and adenovirus. Influenza, Measles and varicella Bacterial(25%)infection; strep, Staph, H Infl, E coli, Salmonella Opportunistic infection PJP (4%) Fungal infection TB(10%) CMV Co-infection NTM: MAC uncommon Chronic lung disease LIP as persistent. Kaposi sarcoma
Treatment for PJP who needs oxygen
Oxygen
High dose Septra for 21 days step down if improvement to oral
As Hypoxic Prednisone 5 day then taper over 10-14 days
How would you treat Lymphoid Interstitial pneumonitis/Pulmonary lymphoid hyperplasia?
Confirm diagnosis, Immunoglobulins are usually elevated
Lung biopsy
Bronchodilators
O2
Steroids oral
Masses in the posterior mediastinum
Malignant schwannoma
Tumors of sympathetic origin
- Neuroblastoma
- Ganglioneuroma
- Ganglioneuroblastoma
- Pheochromocytoma
Chemodectoma
Possibly:
Partial right sided Eventration
Right sided diaphragmatic hernia (possibly to posterior)
CPAM
Sequestration
Esophageal Duplication cyst (foregut cyst)
Anterior mediastinum masses
Malignant lymphoma (Hodgkin and non-Hodgkin) - most common Teratoma - common Thymus (benign enlargement) - common Thyroid (retro- or sub-sternal extension) Thymic cyst Angioma Langerhans cell histiocytosis Mesenchymal tumors Lymphangioma (cystic hygroma)
Middle mediastinum masses
Foregut duplication cyst (bronchogenic, enteric, and neuroenteric) - most common; bronchogenic cyst is more common
Lymphadenopathy
Vascular malformations
Pulmonary risks with Radiation therapy
Radiation pneumonitis: Within 30-90 days, steroids, low DLCO, normal lung function, fever chest pain ,dyspnea, hypoxia. Crackles. CXR diffuse hazy opacities and ground glass changes
Radiation Fibrosis: 6 months to 24 months. Progressive dyspnea, Irreversible, restrictive defect, low DLCO , chronic. CXR: there may be streaky densities, decreased lung volume or atelectasis, or pleural thickening
Pulmonary risks with BMT
Early:
- Pulmonary oedema
- VOD
- Diffuse alveolar hemorrhage
- Idiopathic pneumonia syndrome
Medium to long term
- Idiopathic pneumonia syndrome
- Infection
- ILD
- GVHD
- PTLD
- Bronchiolitis obliterans
Severe BO: Lung transplant
15 year old with CF is on the ward one day after a bronchial artery embolization and develops an oxygen requirement.
What are you concerned about and what will you do?
Post op atelectasis Pneumothorax Lung infarct ABC, Examination/history/CXR Vitals Airway clearance
Pleuritic pain post BE - differential?
Analgesia
Can get pleuritic chest pain post embolisation (not uncommon)
?lung infarct
?PE
CT with contrast, D-dimer, thrombotic screen
Complications post bronchial embolization
Spinal artery thrombosis –paraplegia
Severe chest pain–>analgesia
How is DLCO measured?
DLCO is a measure of transfer of Carbon Monoxide (CO) from the gaseous phase into the red blood cells - ease of uptake of oxygen across the alveolar/capillary membrane. Dependent on ventilation and perfusion of the lung.
It provides information on the rate at which the oxygen is transferred via passive diffusion from the lungs to the circulation The diffusion across the alveolar-capillary interface can be impaired by both structural and functional changes of the alveoli or the capillaries
Can be measured by single breath or steady state. Measured by breathing a known concentration of CO and calculating the absorption.
CO is negligible concentration in blood and so allows a measure of true diffusion down its partial pressure gradient between alveoli and capillaries.
Why do patients with interstitial lung disease desaturate during exercise?
V/Q mismatch
Lung fibrosis
Poor diffusion less effective gas exchange due to abnormal alveolar/capillary membrane.
Less time for oxygen to diffuse, transfer of oxygen is diffusion limited
Management of Hypersensitivity Pneumonitis
Serum preciptating antigen to bird
Inhalational challenge
Kill the cockatiel, still may have environmental exposure
Steroids
Major criteria for HP (6)
- Symptoms compatible with HP
- Evidence of exposure to antigen
- Radiographic characteristics consistent with HP
- BAL fluid lymphocytosis (CD8 > CD4)
- Lung biopsy demonstrates histology consistent with HP
- Positive natural challenge that produces symptoms and objective abnormalities after reexposure to the offending antigen
Histology consistent with HP on lung biopsy
Alveolitis, noncaseating granulomas, giant cells, foamy alveolar macrophages or fibrosis
DDx for hyperlucent lung
Congenital lobar overinflation (emphysema)
Other congenital pulmonary abnormalities (e.g., CPAM)
Congenital diaphragmatic hernia (no clear bowel seen in left hemidiaphragm, although gastric bubble not clear)
Foreign body (age dependent)
Bronchial obstruction (e.g., endobronchial tumor, infection)
Filamin A deficiency
Contralateral Agenesis
Most common location for CLE
LUL (42%), RML (35%), RUL (21%), lower lobes (2%)
Caused by deficiency of bronchial cartilage, occasionally partial obstruction (e.g., mucosal flap or twisting of lobe on pedicle)
Management for CLE
Options for Investigations:
Bronchoscopy – may reveal causes of intrinsic obstruction and permit removal of foreign body or inspissated secretions
Echo – to assess heart and great vessels
V/Q – useful if unclear if pathologically distended lobe on one side or congenitally small contralateral lung with secondary physiology expansion
Management - dependent on symptoms
- Conservative management – if no respiratory compromise
- Surgical resection (lobectomy) – if respiratory distress (rarely develops beyond neonatal period)
- Ventilation – low pressure, high frequency oscillation to prevent barotrauma to affected lobe and further respiratory compromise to adjacent lung
Causes of CLE
1) Idiopathic 50%
2) Bronchial cartilage absence, hypoplasia or dysplasia 25%
3) Parenchymal diseases
– Polyalveolar lobe
– Pulmonary alveolar glycogenosis
4) Internal bronchial obstruction – Bronchial stenosis – Bronchomalacia – Meconium aspiration – Hypertrophic mucosa membranes – Mold mucous plaques – Foreign body aspiration – Bronchial polyp
5) External bronchial obstruction – Pulmonary artery sling anomaly – Pulmonary rotation anomaly – Bronchogenic cyst – Lymphadenopathy – Mediastinal mass – Duplication of esophagus
Management of intralobar sequestration.
1) Surgical excision (open vs thorascopic)
- Preferred if infected or suspected malignancy
2) Embolization
- Reduces shunt and risk of high output cardiac failure,
- Leaves residual tissue
- consider “unquantifiable” risk of malignancy
Key points re: Intralobar sequestration
84% – usually posterior LLL, encircled by visceral pleura, no pleural separation from rest of the lobe
Key points re: Extralobar sequestration
beneath LLL (15% abdominal), male 4x, increased association with malformations
Key points re: pulmonary sequestration in general
CT appearances variable – solid 49%, cystic 29%, cavitating 12%, pneumonia 8%
Most common LLL (66%), posterior basal (20%)
Arterial supply – thoracic (77%) or abdominal (19%) aorta, may have at least two arterial supplies
Drainage by pulmonary venous system in 90%
Nonspecific presentation
Most common organisms Aspergillus fumigatus and pseudomonas aeruginosa
Ventilation strategies with CDH
Avoidance of IPPV to limit gastric and bowel distention, intubation at birth if respiratory distress present
Sedation all mechanically ventilated infants with CDH, deep sedation and NMB selective for greater ventilation needs or O2 requirement.
Lung protective ventilation of particular importance given pulmonary hypoplasia associated with CDH.
- T piece with ventilator to avoid peak inspiratory pressure >25cm H2O
- target pH 7.25-7.40, pCO2 45-60mmHg
- supplemental O2 for SpO2>85, but not >95% - initial ventilation mode: gentle, intermittent mandatory ventilation (HFOV if PIP required is >25cmH2O)
Hemodynamic support of CDH
Hemodynamic support:
-treatment of poor perfusion (judicious crystalloid not >20cc/kg, ionotropic agents -dopamine or epinephrine, hydrocortisone), if persistent assess cardiac function
Echo (2 standard)
- w/i 48h birth
- one at 2-3wk life
Management of pulmonary hypertension
- iNO for suprasystemic PAH without LV dysfunction. Stop if no clinical/echo response.
- Sildenafil if refractory, or when weaning iNO
- milrinone for cardiac dysfunction, especially if association PHTN
- PGE1 for PDA patency and R afterload reduction if RV failure/closing ductus
ECMO
- can be considered, should be discussed during prenatal counselling
- no survival benefit in currently available evidence
- avoid OR until decannulated, if unable to wean off consider surgery or palliation
Surgical repair of CDH
- Surgical consultation
- criteria before surgery: U/O>1ml/kg/hr, FiO2 <0.5., SpO2 85-95%, normal MAP for age, lactate <3mmol/L, PA pressure < systemic.
- failure to meet criteria by 2 weeks; consider attempted repair or palliation
- patch repair if not amenable to primary repair
- open repair (high recurrence with minimally invasive technique)
How can you estimate the severity of CDH?
The severity of congenital diaphragmatic hernia (CDH) can be estimated prenatally using observed-to-expected lung–head ratios (by ultrasound) and total fetal lung volumes (by magnetic resonance imaging), as well as fetal liver position.
L CDH LHR <25% poor outcome, R CDH LHR <40% predicts poor outcome
DDx for unilateral cystic densities on CXR
BPD
PIE
chILD (disorders more prevalent in infancy)
o ACDMPV (FOXF1, increased risk associated malformations)
o Lung Growth abnormalities
§ Brain, thyroid, lung (NKX2.1)
§ Filamin A (FLNA)
o PIG
o Surfactant deficiency
§ ABCA3
§ TTF-1 (NKX2.1)
§ Surfactant protein B
§ Surfactant protein C
Congenital cardiac disease
Chronic aspiration – reflux, congenital abnormality, e.g,. TEF)
Congenital cystic lung abnormality (although very diffuse)
CDH
Post-infectious
Right pulmonary hypoplasiaVentilator strategy for PIE
HFJV
Minimize barotrauma and volutrauma
There is no definitive treatment for PIE. Management is supportive and directed at providing adequate gas exchange and minimizing the risk of further air leak. This is best accomplished by decreasing the mean airway pressure as much as possible, which is achieved by reducing the peak inspiratory pressure, positive end expiratory pressure, and inspiratory duration. The inspired oxygen concentration should be increased to compensate for the decreased mean airway pressure. We often use high frequency ventilation in infants with PIE to avoid large cyclic swings in tidal volume, although trials of this intervention are not available
Positioning the infant with the affected side down, minimal chest physiotherapy and endotracheal suctioning, and if possible, decreasing ventilator pressure and inspiratory times
What is PIE?
Pulmonary interstitial emphysema (PIE) consists of air trapped in the perivascular tissues of the lung. This results in decreased compliance and overdistention of the lung. The interstitial air also compresses airways, resulting in increased airway resistance.
PIE typically affects mechanically ventilated extremely low birth weight infants and may involve one or both lungs. It usually presents within 96 hours of birth with gradually worsening hypoxemia and hypercarbia. Ventilator settings are often increased in response to the poor gas exchange, which may exacerbate air trapping and lead to further worsening of oxygenation and ventilation. Overdistention of the lung may cause vascular compression, resulting in decreased venous return and impaired cardiac output. PIE may precede the development of pneumothorax or other air leak.
Acute management of chILD
Minimize volutrauma, barotrauma, atelectrauma
Avoid oxygen toxicity (e.g., SpO2 goal 92-95% as in BPD)
Consideration of HFOV
iNO for pulmonary hypertension
potential of need for ECMO if deterioration
4 indications for intubation in the patient with a near fatal asthma exacerbation.
1- Exhaustion , with development of metabolic acidosis , decreasing pH in the presence of a normal or rising PCO2
2- Breath sounds start as audible , bilateral wheezes and become distant as air trapping increases
3- Severe hypoxemia while receiving oxygen
5- Altered mental status
6- Life threatening dysrhythmia
7- PCO2 rises while pH declines
8- Cardiac or respiratory arrest
Describe key elements to the approach to mechanical ventilation in an asthmatic
1- Keep peak and Pplat minimized ( alveolar plateau pressure must still be kept low ( <30cmH2O) despise high PIP
2- Maintain FiO2 as needed to keep PaO2 60-100mmHg
3- Permissive hypercapnia ( PaCO2 45 -80mmHg) is acceptable as long as pH range is acceptable ( 7.10 - 7.20)
4- Ventilator cannot be matched to patient needs ( use of sedatives and paralytics) particularly in the 1st 24 hours
5- Avoid increasing air trapping (auto-PEEP - put their PEEP below auto PEEP) by providing longer expiratory time:
Vt 4-8ml/Kg ; I:E 1:3 Low RR- Inspiratory flow 80-100L/min
Auto PEEP - expiratory hold in patient not spont breathing on vent
What volume constitutes massive hemoptysis?
> 240 mL in 24 hours
What is the most common cause of pediatric hemoptysis?
Infection (in those without underlying conditions)
List 5 ways to help distinguish hematemesis from hemoptysis.
History
- no nausea or vomiting
- Lung disease
- Asphyxia possible with hemoptysis
Sputum
- frothy
- liquid or clotted appearance
- bright red or pink
Lab
- alkaline pH
- macrophages and neutrophils
Differential diagnosis for chest pain and SOB
Trauma Exposure to inhalation injury Smoking Pneumothorax History of syncope, cyanosis, heart disease? Previous pneumothorax? ID: History of fever? Cough? infection? PE risk factors: OCP use, pregnancy menses - catamenial hemoptysis, pneumothorax IV drugs, cocaine Vaping - EVALI Cannabis Rib fracture (Anxiety) Costochondritis Cardiac--pericarditis, myocarditis GERD - hiatus hernia Boerhaave syndrome - esophageal rupture
Causes of pneumothorax
1) Spontaneous - primary or secondary (underlying lung disease - COPD, asthma, CF, infection, ILD, CTD, scleroderma, Marfan’s, malignancy)
2) Traumatic
3) Iatrogenic
What are indications for insertion of a chest tube in a patient with PTX?
Patients who fail aspiration treatment because of a persistent air leak, or those who present with a recurrent spontaneous pneumothorax, and many patients with SSP should be managed with a thoracostomy tube or pigtail catheter
When would you consider pleurodesis in PTX?
1) A first PSP and an air leak that fails to resolve after approximately five days of thoracostomy drainage. This is the time period typically suggested for adults but is based on panels of experts rather than empiric evidence
2) Recurrence of PSP (either ipsilateral or contralateral).
PH and new difficulty with exertion - what investigations?
1- Blood gas, oxygen saturation
2- CXR
3- PFT including : 6-minute walk distance (6MWD) test and DLCO
4- ECG
Other investigations to be arranged urgently:
5- ECHO to assess RV function and PH
6- Cardiac Cath with acute vasoreactivity testing (AVT)
7- BNP and PRO BNP
8- MRI can be useful as part of the diagnostic evaluation and during follow-up to assess changes in ventricular function and chamber dimensions
Cardio consult
Management of PH after medical management optimized
Refer for lung transplant evaluation
Consider atrial septostomy
5 indications for lung transplant in Pediatrics
1- CF with end stage lung disease 2- Severe pulmonary hypertension with failure of all medical therapies 3- Congenital interstitial lung diseases 4- Bronchiolitis obliterans 5- alveolar capillary dysplasia 6- Retransplant 7- Severe Pulmonary fibrosis
Absolute contraindications for lung transplant
Active malignancy within 2 years Sepsis Active TB Severe NM disease Documented refractory nonadherence Multiple organ dysfunction Acquired immunodeficiency Syndrome Hepatitis C with histiologic liver disease
Relative Contraindications for lung transplant
Pleurodesis Renal insufficiency Markedly abnormal body mass infex Mechanical ventilation Scoliosis Poorly controlled DM Osteoporosis Chronic airway infection with multiple resistant organisms Hepatitis B surface antigen positive
One of the major limitations of pediatric lung transplant is limited organ availability. List 2 surgical techniques utilized to increase the donor pool in pediatrics.
Donor downsizing using linear stapling devices or lobectomy and lobar transplant.
Ex-vivo lung perfusion
Living donor lobar lung transplantation is still happening in Japan
What is the general 5 year survival after lung transplant?
50%
In cystic fibrosis what is the FEV1 at which lung transplantation should be considered? Why is this number generally used?
• FEV1 is <50% predicted and rapidly declining (>20% relative decline in FEV1 within 12 months)
OR
• FEV1 is <50% predicted with markers of shortened survival
OR
• FEV1 is <40% predicted
Markers of shortened survival in CF
low FEV1.
6-min walk test (6MWT) distance < 400 m
Room air hypoxemia (SpO2 b 88% or PaO2 b 55 mmHg, at rest or with exertion; at sea level)
Pulmonary hypertension (PA systolic pressure N 50mmHg on echocardiogram or evidence of right ventricular dysfunction in the absence of a tricuspid regurgitant jet),
Hypercarbia (PaCO2 N 50 mmHg, confirmed on arterial blood gas)
BMI <18 kg/m2 for adults (or BMI less than 5th percentile for children)
Increased frequency of pulmonary exacerbations (N2 exacerbations per year requiring IV antibiotics or one exacerbation requiring positive pressure ventilation)
Massive hemoptysis
Pneumothorax
14 y.o girl with history of CF, is day 7 post double lung transplant. She was extubated on day 5, but is now developing increasing oxygen requirements, respiratory distress and hypercapnia.
List three things on your differential diagnosis for her respiratory deterioration.
Infection – bacterial, viral and less likely fungal
Rejection – likely ACR (acute cellular rejection) at this point in time
Pulmonary edema
Other:
Anastomotic leak
Aspiration
Post lung transplant deterioration with intact anastomosis and no organisms on BAL - next step?
Transbronchial biopsy
Then IV pulse steroid for 3 days
1.5 years post lung transplant the child presents with declining pulmonary function and progressive shortness of breath. List 4 things on your differential diagnosis.
Chronic lung allograft dysfunction – BO/BOS, RAS
Antibody mediated rejection
Infection – viral/bacterial/fungal
Posttransplant lymphoproliferative disease
Tests: PFT’s (spiro with BDR, lung volumes) CXR Sputum sample CT chest BAL Transbronchial biopsy DSA (Donor Specific HLA antibodies) Open lung biopsy CMV/EBV
What are 3 treatment options for BO/BOS post transplant?
Consider switching immunosuppression meds
Azithromycin
Treat any concurrent infection ( bacterial/Viral or fungal)
Re-transplant
Ensure adherence to medication
Post lung transplant BO (combination of rejection + CMV + other stuff) : azithro, re-transplant
Post infectious BO: pulse steroids, (likely extrapolate FAM)
Post HSCT BO: pulse steroids, FAM
OSA severity scale in children
1.5-5 mild
5-10 moderate
>10 severe
Name 5 physical exam findings you may see in PH.
loud single P2
pan-systolic murmur from TR
diastolic murmur from pulmonary insufficiency
RV gallop
Evidence of RV failure – elevated JVP, hepatomegaly, peripheral edema
Cyanosis
Left parasternal heave
List 3 pulmonary vasodilators that can be used as an outpatient and their mechanism of action.
Phosphodiesterase inhibitors (eg. Sildenafil) Prevent degradation of cyclic GMP → potentiates the effect of NO activity by inhibiting PDE 5
Endothelin Receptor Antagonists (eg. Bosentan-dual receptor)
Block ET receptors (found in smooth muscle and endothelial cells) thus promoting vasodilation and prevents proliferation
Prostacyclin Analogs/receptor agonists (eg. Epoprostenol, Iloprost, Trepostinil)
Acts as a pulmonary vasodilator, inhibits vascular smooth muscle proliferation, inhibits platelet aggregation, improves endothelial dysfunction and can also act as a possible cardiac inotrope
Ca channel blockers (eg. Nifedipine)
Pulmonary vasodilator - by inhibiting Ca influx through slow channel in cardiac and vascular smooth muscle cells
What are side effects of iNO?
Methemoglobinemia
platelet dysfunction
Rebound PH
Please outline the classification of pulmonary hypertension
- PAH (includes PPHN and PVOD)
- PH secondary to left heart disease
- PH secondary to chronic lung disease
- CTEPH
- Multifactorial
4 potential respiratory complications of chronic liver disease/portal hypertension.
Porto-pulmonary hypertension
Hepato-pulmonary syndrome
Fluid overload – pulmonary edema/pleural effusions
Portal HTN → consumptive thrombocytopenia → pulmonary hemorrhage
Infection, including pneumonia, due to immunoglobulin loss/decreased production
Lymphocytic pneumonitis (primary biliary cirrhosis) Aspiration pneumonitis ( with patient in hepatic encephalopathy ) Restrictive lung function from mass effect of ascites
Tests:
CXR – assess for pulmonary edema/pleural effusions/small lung volumes (from ascities)
Echo + bubble study – assess for pulmonary hypertension and for intra-pulmonary shunt
ABG – assess PaO2
CT chest angio – assess for AVM
Macro-Aggregated Albumin Lung Perfusion Scan = radioactive lung perfusion scan
Bubble echo was done. Describe what you would expect if the patient had an intra-pulmonary shunt.
Bubbles from right side of heart would enter left heart within 3 – 6 cardiac cycles (< 3 cycles c/w intracardiac shunt)
< 3 cycles suggest intracardiac and 3 – 6 cycles suggest intra-pulmonary)
R-L shunt:
Extra-cardiac (intra-pulmonary) – AVM (isolated pulmonary AVM or in context of HHT)
Of note, the non-pulmonary shunts (cerebral, liver) are actually left to right shunts
What are the diagnostic criteria for HPS?
Oxygenation defect – PaO2 < 80 mmHg or A-a gradient > 15 mm Hg in room air
Pulmonary vascular dilatation – positive contrast echocardiography (bubble echo)
Portal hypertension +/- cirrhosis
List the three mechanisms of hypoxemia in HPS
Widened barrier to diffusion - bc of pulmonary edema and vessel dilation
R-L shunt
V/Q mismatch - bc of atelectasis
What is the definitive therapy for HPS?
Liver Transplant
What are the physiological causes of hypoxemia
Hypoventilation – global neurological disease with hypotonia (ie. T21, PWS), SCI, anterior horn injury (SMA), peripheral neuropathy (GBS), NMJ (MG), muscular (DMD/BMD etc), hypoventilation syndromes (CCHS, ROHAAD etc), Meds - opioid for pain relief
V/Q mismatch – ie. airways obstruction (asthma, CF, PCD, bronchiectasis), alveolar hemorrhage, pneumonia, alveolar edema etc à unlikely all result in respiratory symptoms (cough, SOB, wheeze etc).
Widened barrier to diffusion – ILD, interstitial edema, ACD/MPV etc
R-L shunt:
Intra-cardiac – CHD
Extra-cardiac (intra-pulmonary) – AVM (HHT), HPS
reduced Patm – not issue
Investigations for hypoxemia
Blood gas – assess for hypoventilation, hypoxemia (if arterial)
CXR - assess for causes of V/Q mismatch
CT chest contrast - vascular anomalies, shunting, PE
PFT’s – for V/Q mismatch/widened barrier to diffusion
Bubble echocardiography –assess for shunting
Pertinent points for HHT
FHx of HHT Telangiectasias? History of epistaxis Sx/Sx consistent with visceral AVMs Cyanosis, SOB, SOBOE, exercise intolerance, hemoptysis; embolic phenomenon – TIA, stroke, cerebral abscess GI bleed History of portal HTN H/A, seizure, focal neurological deficits, intra-cranial hemorrhage
How do you confirm a diagnosis of HHT?
Clinical diagnosis:
- Epistaxis
- Telangiectasias
- AVMs (visceral lesions)
- Family history
2 positive = suspected HHT
>3 = Confirmed HHT
Or
Genetic testing
If +ve confirms the diagnosis
If -ve doesn’t rule out the disease
What are the gene mutations known to cause HHT?
ENG gene – HHT type 1
ACVRL1 (also called ALK1) gene – HHT type 2
SMAD4 gene – HHT in association with juvenile polyposis (JPHT)
GDF2
What is the indication for embolization of a pulmonary AVM?
Progressive enlargement of the lesions
Symptomatic hypoxemia
Presence of paradoxical embolization
Feeding vessels of 3 mm or larger
DDx for narrow trachea
Extrinsic compression: Anterior mediastinal mass, lympadenopathy, Vascular ring
Intraluminal: hemangioma, web, cyst, papilloma, malignancy
Airway: tracheomalacia, tracheal stenosis
Which vascular abnormality results in anterior compression of esophagus?
PA sling
Vascular rings tend to cause posterior esophagus compression
What is another associated anatomical abnormality with a PA sling?
Complete tracheal rings and associated tracheal stenosis
What is the treatment for PA sling?
Surgical management if symptomatic
Translocate the anomalous left pulmonary artery onto main pulmonary artery
What are the treatment options for tracheal stenosis?
Slide tracheoplasty, to be discussed with ENT
4 ethical principles
Do no harm
Patient autonomy
Best interest of the patient
Justice (equal distribution)
