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.
