Respiratory Flashcards
Flow loop - Pattern and differentials (3)
Fixed obstruction
- Tracheal carcinoma
- Tracheal stenosis
- Goitre
Flow loop
Pattern and differentials (4)
Variable extrathoracic
Differentials
-Vocal cord/fold paralysis
-extra-thoracic tracheomalacia
-Poly-chondritis
-Mobile tumours
Pattern and differentials (2)
Variable intrathoracic obstruction
Differenitals
-Tracheomalacia
-Malignant tumours
7 indicators of success for NIV
3 diagnostic criteria for insomnia
Absolute contraindications to lung transplantation (10)
AC (Assist Control) ventilation aka continuous mandatory ventilation (CMV)
Patient triggers ventilation
Ventilator delivers specific volume to the patient (500ml - 600ml)
-Aim 8ml/kg (ideal body weight)
Back up mode (Rate) - sets a baseline rate of ventilation if patient does not breathe. Patient cannot breathe less than this rate
Pressure and volume and volume have an inverse relationship
Compliance = Change in Volume/Change in Pressure
Therefore you can set a volume but depending on lung compliance - pressure achieved will vary
-low compliance = high pressure
-high compliance = low pressure
Advanced therapies in PH
-CCB
Vasoreactivity test - do before starting Rx ?respond
- Vasoreactivity testing is recommended in patients with IPAH, HPAH and PAH associated with drugs use to detect patients who can be treated with high doses of calcium channel blocker
- A positive response to vasoreactivity testing is defined as a reduction of mean PAP >10mmHg to reach an absolute value of mean PAP <40mmHg with an increased or unchanged cardiac output
- POSITIVE TEST = trial CCB, NEGATIVE = Rx with alternatives
CCB - prolong survival, functional and haemodynamic improvement
- nifedipine OR diltiazem
- Less than 10% of patients will respond to, or tolerate CCB long term
Advanced therapies in PH
-Endothelin antagonists
Mech - endothelin 1 promotes vasoconstriction, cell proliferation, vascular remodelling. This blocks that = vasodilation + improved exercise capacity
ADR - anaemia, flushing, peripheral oedema, headache, nasal issues, abdo pain, hepatic dysfunction
Examples = ambrisentan, Bosentan, Macitentan
Advanced therapies in PH
-Phosphodiesterase 5 inhibitors
- Mech - inhibit PDE5 = relaxation of smooth muscle in pulm vasc bed = vasodilation and reduction in pulm vascular resistance
- increase exercise capacity in pulmonary hypertension
- Examples - sildenafil, tadalafil
Advanced therapies in PH
-Prostacyclins
- Mech - inhibit platelet aggregation. Cause direct vasodilation of pulm arterial bed = improved haemodynamics and exercise capacity
- ADR - increased bleeding, vasodilation, hypotension, dizziness, headache, jaw pain, nausea, vom, diarhoea
- Examples - epoprostenol, Iloprost, Treprostinil
- Do not stop drug suddenly = rapid deterioration
Advanced therapies in PH - indications
Group 1 PAH (b/c nil primary therapies)
Symptoms
Group 4 if not operative candidate or bridge to surgery
Avoid:
Groups 2,3 - may be harmful in group 2, and no benefit proven with group 3
Unclear - group 5
Airway Hyperresponsiveness
Direct - methacholine, histamine
Indirect - mannitol, hypertonic saline
Alpha 1 anti-trypsin deficiency
- What does AAT do?
- How does it cause lung damage?
- How dose it cause liver damage? Which genotype is at highest risk?
- Inheritance?
- General principles of therapy?
- AAT is a serine protease inhibitor encoded by SERPINA1 (aka PI) on chromosome 14
- Classic presentation in COPD: panlobar (panacinar) basal emphysema in a young <45years patient
- null/null OR Z/null OR Z/Z - very high risk of COPD with
- ZZ also having high risk of liver disease
- SZ = increased risk of COPD + ?increase in lung disease
- M/null, M/Z - possible increase risk in COPD
Anti-muscarinic drugs in COPD
- Block bronchoconstrictor effects of acetylcholine on M3 muscarinic receptors expressed in airway smooth muscle
- SAMAs (ipratropium and oxitropium) also block the inhibitory neuronal receptor M2, which potentially can cause vagally induced bronchoconstriction
- LAMAs eg tiotropium, have prolonged binding to M3 muscarinic recptors, with faster dissociation from M2 muscarinic receptors = prolonged bronchodilation
- LAMAs improve symptoms, health status, effectiveness of pulmonary rehab, reduce exacs and related hospitalisations
- Nil impact on lung function decline
- ADRs - inhaled LAMAs/SAMAs are poorly absorbed = less symptomatic anticholingeric effects
- SE - dry mouth, bitter/metallic taste
- ?small increase in cardiovascular events with ipratropium
Antibiotics in STABLE COPD
Long term azithromycin and erythromycin Rx reduces exac over 1 year BUT
Azithromycin is associated with increased bacterial resistance and hearing impairments
Benefits of CPAP in OSA
Improves
- MVA
- Daytime sleepiness
- Depression
- Cognitive dysfunction
- Quality of life
- Systolic and Diastolic BP
NO improvement
- Cardiovascular mortality (no RCT data)
- Cardiovascular event rates (SAVE and RICADDSA 2016 studies)
- SAVE - maybe less stroke with CPAP
Benefits of NIV in COPD
(When commenced early)
- decreased mortality
- decreased intubation intiation and duration
- decreased ventilator associated pneumonia
- decreased ICU and hospital length of stay
- decreased treatment failure
- decreased symptoms of respiratory distress
Benefits of pulmonary rehab
Improves:
- Severity of dyspnoea
- Exercise capacity
- Health related QoL
Beta2agonists in COPD
- Relax airway smooth muscle by stimulating beta2-adrenergic receptors = increased cAMP = functional antagonism to bronchoconstriction = bronchodilation
- Have no effect on mortality or rate of decline of lung function
- Improve FEV1 and symptoms
- SABAs wear off after 4 - 6 hours
- LABAs work for >12 hours
- ADRs -sinus tachycardia, cardiac arrhythmias, tremor
Bronchiectasis
Causes of High and Low DLCO
Causes of hypoxia
Summary of causes
- Ventilation-perfusion mismatch is nearly always the cause of clinically significant hypoxia (increased A-a gradient; good response to increased FiO2)
- Hypoventilation -increased PaCO2, normal A-a gradient <15mmHg
- Right-to-left shunt - increased A-a gradient, poor response to increased FiO2
- Impaired diffusion - very rare
- Low inspired environmental O2 eg. high altitude
Note: destaturation of mixed venous blood (eg. shock) can worsen hypoxemia drom other causes
Causes of hypoxia with elevated A-a gradient
- Diffusion defect
- V/Q mismatch
- Right to left shunt
- Conditions of increased O2 extraction
Causes of hypoxia with normal A-a gradient
- Alveolar hypoventilation - But these patients have high PaCO2
- Low PiO2 - When FiO2 <0.21 or barometric pressure <760mmHg
Causes of pulmonary fibrosis
- Upper lobe: SCATO
- Lower lobe: RASHO
Cystic Fibrosis epidemiology in Australia
- 1 in 2800 live births
- 1 in 25 people are asymptomatic carriers of a CF gene mutation
- 50% of the CF population were hospitalised at least once in 2003
- Life expectancy is improving
CFTR modulator therapies
Ivacaftor - potentiator
- facilitates opening of Cl- channel and improves CFTR activity
- increases time open
Lumacaftor - corrector
- Improves CTFR production/processing
- puts more in
Tezacaftor combined with Ivacaftor
*
Cheyne-Stokes breathing in PSG
- 3 consecutive central respiratory events, separated by the characteristic crescendo-decrescendo respiratory pattern.
- on average >5/hour of sleep characteristic apneas or hypopneas must occur
- length of each crescendo-decrescendo cycle must be at least 40 seconds
- Longer cycle lengths are associated with more severe cardiac disturbance.
- Associated in CCF, neurologic diseases or use of sedative medications
Classification of Lung Ca
- NSCLC - 85%
- SCLC - 15%
- Remember EGFR and ALK - as have targetted agents
Classification of pulmonary HTN
-
Group 1 - Pulmonary arterial HTN (PAH)
- causes: idiopathic, inherited, drugs, CTD (scleroderma, RA, SLE), HIV, portal HTN, CongHD, schistosomiasis
- worst survival of all the groups
-
Group 2 - PH due to left heart disease (also have elevated LA pressure > 14mmHg)
- causes LV systolic/diastolic dysfunction, Mitral/aortic valve disease
- Group 3 - PH due to chronic lung disease and/or hypoxaemia
- Group 4 - PH due to chronic thromboembolic disease
- Group 5 - PH due to unclear multifactorial mechanisms
Classification of severity of COPD
Classification of Spontaneous Pneumothorax
Primary spontaneous vs Secondary Spontaneous
- Primary spontaneous: occurs in the absence of a precipitating event, in a person without known lung disease
- Secondary spontaneous: all other spontaneous pneumothoracies
Clinical severity scale for obstructive ventilatory defects
- Mild - FEV1% predicted >70%
- Moderate - FEV1% predicted 60 - 69%
- Moderately Severe - FEV1%predicted 50 - 59%
- Severe - FEV1% predicted 35 - 49%
- Very severe - FEV1% predicted <35%
- A similar scale can be applied for restrictive defects with FVC substituted
Combination Therapies in COPD
- Combinations of SABA + SAMA are more effective compared to either medication alone in improving FEV1 and Sx
- LAMAs>LABAs at reducing exacerbaions and decreasing hospitalisation
- LABA + LAMA increases FEV1, reduces Sx and exacs compared to monotherapy
- In summary combination therapies are more effective than the individual therapies
Complications of OSA
- Poor daytime functioning - sleepiness and fatigue = increased risk of accidents
- Psychiatric disorders
- Cardiovascular morbidity - increased risk of systemic HTN, pulm HTN, CAD, arrhythmias, CCF, stroke
- Metabolic syndrome and T2DM
- NAFLD
- Increased perioperative complications
- Mortality - all cause if severe and untreated
Conditions known to respond to NIV
- Exacerbations of crhonic obstructive pulmonary disease (COPD) that are complicated eby hypercapnic acidosis (PaCO2> 45mmHg or pH < 7.30)
- Cardiogenic pulmonary oedema
- Acute hypoxic respiratory failure
Connective tissue disorders related to interstitial lung disease
Of note:
- SLE - is LESS likely to cause ILD. More Pleural or serositis with diffuse alveolar damage (DAH) ie pulmonary haemorrhage
- RA - UIP pattern is common
- Scleroderma - NSIP pattern is common
Contraindications to NIV (8)
-AKA the need for emergent intubation is required
- cardiac or respiratory arrest
- Inability to cooperate, protect the airway, or clear secretions
- Severly impaired consciousness
- Nonrespiratory organ failure that is acutely life threatening
- Facial surgery, trauma or deformity
- High aspiration risk
- prolonged duration of mchanical ventilation anticipated
- Recent oesophageal anastomosis
CPAP (term used in NIV) = PEEP (term used in invasive vent)
Positive End Expiratory Pressure
- Continuous pressure - regardless of whether patient is inspiring or expiring
- Generally 5 to 20cmH2O (mmHg if PEEP)
Criteria for Anti-fibrotic drugs for interstitial lung disease
- HRCT consistent with IPF in ast 12 months
- FEV1/FVC >0.7 - not obstructed
- FVC > 50%
- DLCO > 30%
- MULTIDISCIPLINARY DIAGNOSIS
- Patient must not have ILD due to other known causes including domestinc and occupational environmental exposures, CTD or drug toxicity
- Must by treated by specialist respiratory physician
- *Chronic Thromboembolic Pulmonary Hypertension**
- epidemiology, 1 major RF
- cardinal symptom
- first test
- 3 steps of management - what is the definitive therapy?
Type 4 PAH
Current recommendations for treatment of IPF
*pretty much only antifibronlytics
CXR findings in PH
Enlargement of central pulmonary arteries with attenuation of peripheral vesels = oligemic lung fields
Also RV enlargement (diministed retrosternal space), RA dilation (prominent RH border)
+/- underlying cause = interstitial lung disease
Define: Apnoea, hyponpnoea and Respiratory effort-related arousals in PSG
- Apnoea - >90% decrease in airflow compared with preceding signals for >10 seconds
- Obstructive = continued respiratory effort throughout event
- Central = NO respiratory effort throughout the event
- Mixed = NO respiratory effort at the start, followed by respiratory effort at a later part of the apnoea
-
Hypnoea - reduction of airflow to a degree that is insufficient to be called an apnoea
- Airflow decreases >30% but (<90%) c/f baseline
- The diminished airflow lasts >10 seconds
- Associated with either a 3% O2 desat from baseline or an EEG arousal
-
RERA (respiratory effort related arousal) - change in ariflow that is insufficient to be called apnoea or hyponoea
- event >10sec with flattening of the nasal pressure waveform and/or evidence of increased respiratory effort terminating in arousal
Definition of Reversibility in Spirometry
- A >12% AND >200mL increase in FEV1 or FVC is a significant reversible response to bronchodilators
- If reversibility is substantial: >400ml then treat for asthma
Diagnosis of Cystic fibrosis
- Newborn screening program
- heel prick blood test 48 - 72 hours
- measures immunoreactive trypsin (high sens, low spec)
- If elevated samples are tested for mutations in CFTR gene (but >2000 mutations)
- homozygous or compound heterozygous mutations = assumed CF
- Sweat test for confirmation (sweat chloride > 60mmol/L)
- NB: compound heterozygote = 2 different mutant alleles at a particular gene locus
- Clinical presentation at birth with meconium ileus
Direct vs Indirect Bronchoprovocation Tests
- What does each detect, which is better for asthma
- What agents are for direct (2), indirect (3)
- What marks a positive test in each
- Which is more sensitive
- Which is more specific
Drugs shown to slow disease progression in idiopathic pulmonary fibrosis (IPF)
-
Pirfenidone - pleotrophic novel antifibrotic
- ADR: GIT (nausea, diarrhoea, dyspepsia, and vomiting), photosensitive rash, derranged LFTs
-
Nintendanib - intracellular TK inhibitor
- ADR: Diarrhoea also nausea, vomiting and decreased appeptite, derranged LFTs. Possible cardiovasculat risk and bleeding risk for those anticoagulated
- contraindicated if significant IHD
- As per FVC monitoring (ASCEND, IMPULSIS)
- trials included only patients with mild-mod disease
Easy formula for Aa gradient at sea level at room temp
PaCO2/0.8 = adding a quarter to it
ECG features of PE
Sinus tachycardia +
- peaked P waves
- right axis deviation (S waves in lead I)
- Tall R waves in lead Vi
- Right bundle branch block
- Inverted T waves in lead Vi (normal) spreading across to lead V2 or V3
- A shift to transition point ot the left, so that the R wave equals ths S wave in lead V5 or V6 rather than in lead V3 or V4 (clockwise rotation). A deep S wave will persist in lead V6
- Q wave in lead III resembling an inferior infarction
ECG findings of pulmonary HTN
Signs of RVH or strain
- Right axis deviation,
- R wave: S wave ratio > 1 in lead V1,
- complete or incomplete right BBB
- p pulmonale (peaked p wave in II)
Extrapulmonary manifestations of CF (10)
- Sinus disease - common
-
Pancreatic disease
- pancreatic insufficiency = 2/3 at birth 25% more during childhood.
- 15% remain sufficient = risk of pancreatitis
- CF related diabetes = 25% by 20 years, 50% of adults
- Meconium ileus - up to 20% of newborns
- Rectal prolapse - rare (more likely if pancreatic enzyme therapy not done)
- Hepatobiliary disease - common but rarely progressive
- Infertility - >95% of men most commonly due to absent vas deferens (Rx microsurgical epididymal sperm aspiration). CF women also less fertile than other women
-
MSK
- reduced bone mineral content = increased risk of fractures and kyphoscoliosis
- CF associated arthropathy - 2 to 9%
- hypertrophic osteoarthropathy (uncommon) 5%
- aquagenic wrinkling (wrinkling and nodules after immersion in water) - up to 80%
- Recurrent VTE - ?related to long term CVC
- Anaemia - 10% of children, more common with advancing age and declining lung function (Fe deficiency, chronic inflam)
- Nephrolithiasis and neprocalcinosis - common (27 - 92%)
Factors associated with accelerated decline in lung function in asthma
Factors associated with increased risk of flare ups in asthma
Factors associated with increased risk of life-threatening asthma
Factors associated with treatment-related adverse events in asthma
Features of life-threatening asthma (7)
- Reduced consciousness or collapse
- Exhaustion
- Cyanosis
- O2 saturation <90%
- Poor respiratory effort,
- Soft/absent breath sounds
- Can’t speak
Features that increase risk of recurrence of primary spontaneous pneumothorax
- Female gender
- Tall stature in men
- Low body weight
- Failure to stop smoking
Fleischner guidelines for follow up of solid pulmonary nodule
-What 6 features makes someone high risk?
Probabiity of malignancy
- Low <5%
- young, less smoking, no prior cancer, small nodule size, regular margins and non-upper lobe
- Intermediate (5-65%)
- mixture of low and high probability features
- High (>65%)
- older, heavy smoking, prior cancer, larger size, irregular margin, upper lobe location
Flying post pneumothorax
-When can patient’s fly
1 week post full resolution
Genetic Mutation of Cystic Fibrosis
Autosomal recessive mutation of cystic fibrosis transmembrane conductance regulator (CFTR) protein on Chromosome 7
- CFTR regulates Cl + Na channels - mutations lead to thickened secretions
- Most common mutation F508del AKA Delta F508 found in 70% Caucasian CF patients
There are categories of CFTR gene mutation
- Class I - defective protein production = 2 - 5% of cases worldwide
- Class II - defective protein procssing (inc Delta F508) = 70% in USA
- Class III - defective regulation
- Class IV - defective conduction
- Class V - Reduced amounts of functional CFTR
Human airways - anatomy
- Terminal bronchioles are the smallest airways without alveoli
- The conducting zone = anatomical dead space (nil gas exchange), vol 150ml
- Respiratory zone = where gas exchange occurs, vol 2 - 3L
Hypercapnic and Hypocapnic Central sleep apnoea
- Hypercapnic CSA = causes, phenotype
- Hypocapnic CSA = causes, phenotype
Indications for home O2
PaO2 <55mmHg OR <60mmHg if end organ disease
Indications for long-term O2 therapy in COPD
Indications for lung biopsy in interstitial lung disease (ILD)
PEARL - definite UIP does NOT need a biopsy
Indications for lung transplantation in IPF (7)
Lung Tx is the only definitive cure for IPF - refer all appropriate patients regardless of severity
Indications
- Desaturation to <88% or distance <250m on 6 min walk test
- >50m decline in 6 min walk test distance in 6 months
- Fall in FVC >10% or DLCO >15% during 6 month follow up
- Pulmonary HTN
- Hospitalisation for acute exacerbation
- Respiratory decline
- Pneumothorax
Indications for NIV (Non invasive ventilation) in COPD
Inhaled corticosteroids in COPD
- ICS + LABA is more effective than either as monotherapy at improving lung function, health status and reducing exacerbations
- However regular ICS therapy increases risk of pneumonia especially if severe disease
- Triple Rx - ICS + LABA + LAMA improves lung function, Sx and health status, reduces exacs compared to to monotherapy
- In summary triple therapy is great but prolonged use of ICS increases risk of pneumonia
-
Long term PO glucocorticoids have numerous SE an no benefits in stable COPD
- Have a role in acute exac only
- ICS alone do not modify long-term decline of FEV1 nor mortality in COPD
- ADRs of ICS
- PO candidiasis, hoarse voice, skin bruising, pneumonia
Initial treatment options in asthma
Intervention most likely to reduce exacerbations in COPD
Pulmonary Rehab
(no mortality benefit)
Ivacaftor - drug profile
- Indication: CF with G551D or other gating (Class III) mutation or an R117H mutation of the CFTR gene
- Mechanism of action: Improve Cl transport by potentiating CFTR
- Benefits G551D pts: Reduces number of pulmonary exacerbations, improves FEV1 and weight
- ?Benefits in R117H pts: improved lung function and QoL
- Cautions
- nil longterm safety data
- may cause cataracts in long term use
- drug interactions and hepatic metabolism
Light’s Criteria for Pleural Effusion
If clinical suspicion of transudate
-Serum:pleural protein gradient if >31g/L likely transudate
=Serum Protein - Pleural Protein
- *If <31** can do albumin gradient if >12 most likely transudate
- *Ratio <0.6 is the most senstive for transudate**
Lung Volume Reduction Surgery
Lung volume reduction surgery (LVRS) - reduction pneumoplasty is a surgical technique that involves reducing the lung volume by multiple wedge excision in areas where emphysematous changes are most marked. Typically the amount of tissue resected is 20 to 35 percent of the volume of each lung.
LVRS modestly improves spirometry, lung volumes, exercise capcity, dyspnoea and quality of life and may improve long-term survival among highly selected patients. Certain clinical features appear to influence the degree of risk and benefit.
Potential complications of LVRS include persistent air leak, intraoperative myocardial infarction, reintubation, prolonged mechanical ventilation, pneumonia, wound infection, arrythmias, DVT, PE and death.
Recommend NOT performing LVRS in high-risk patients (FEV1 20% of predicted or less and either a DLCO of 20% predicted or less or homogenous emphysema on CT)
Management of Pleural Infection
Management of Spontaneous Pneumothorax
Mask choice in NIV
- Face mask - greatest physiological improvement, poorly tolerated and difficult to monitor for aspiration
- Nasal mask - best tolerated, but risk of airleak through mouth
- Oronasal mask is preferred for initial use - if no benefit trial full face mask
Medication options in chemical pleurodesis
Tetracyclines vs Talc
Tetracycline (doxycycline or minocycline)
- SE: allergic reaction to ABx –> respiratory failure
Talc
- causes severe CP +/- chronic pain, ARDS
UTD prefers tetracyclines due to similar efficacy and no association with ARDS
Mepolizumab
- mechanism
- indication + factor which indicates likely response
- 3 benefits
- 1 Caution
Methylxanthines in COPD
Controversy re mechanism of action
-likely non-selective phosphodiesterase inhibitors
eg. Theophylline is metabolised by CYP450 mixed function oxidases
Clearance of drug declines with age, many other variables also alter drug metabolism
Improves FEV1 and Sx of breathlessness
ADRs - toxicity is dose related (bad because therapeutic levels are very close to toxic levels)
Fatal cardiac arrhythmias, grand mal convulsions (irrespective of prior epilepsy Hx), headaches, insomnia, nausea, heartburn (last 4 can occur in therapeutic range)
LOTS of drug interactions
Most common aetiologies for secondary pneumothorax
- COPD - most common, worse COPD = worse risk
- CF
- Primary or metastatic lung malignancy
- Necrotising pneumonia
- Lots of others less common
Nintedanib
Intracellular inhibitor that targets multiple TKs
- Effects
- Significant reduction in FVC decline (approx 109ml) aka slows progression
- NO change in time to first exacerbation or QOL
- ADR
- GI upset - 60% diarrhoea, nausea
- Similar efficiacy to Pirfenidone
- Possible cardiovascular risk
- Possible small increase in bleeding risk -avoid in those on anticoagulants
Non-specific interstitial pneumonia (NSIP) pattern
- More ground glass opacities
- Less honeycombing
- Better prognosis
- no subpleura involvement
Obesity Hypoventilation Syndrome
- define
- main RF
- main co-existing condition
- 2 pillars of therapy
- which Rx to avoid
- main cause of death
Omalizumab in Asthma
- *Mech -** recombinant humanised mAb directed against IgE = reduces immune system response to allergen exposure
- *Indication -** maintence of mod-severe allergic asthma in pts Rx with ICS and with raised serum IgE levels
- *ADR -** thrombocytopenia, bleeding, MSK pain, ?Churg Strauss, anaphylaxis
- *AKA - Xolair**
Only factors which improve survival in COPD
- Smoking Cessation - also slows decline in FEV1
- Oxygen Supplementation
Pathogens of CF
- Initial - Staph. aureus, Haem. influenzae
- During adolescence and adulthood - pseudomonas aeruginosa
- early pseudomonas is quite sensitive
- later mucoid phenotype develops = biofilm => resistance to ABx
- Other
- Burkholderia cepacia
- Stenotrophomonas maltophilia
- Achromobacter xylosoxidans
- nTB and fungi
Pathologic stages of ARDS
- Exudate stage - diffuse alveolar damage, then after 7 - 10 days
- Proliferative stage - resolution of pulmonary oedema, proliferation of type II alveolar cells, squamous metaplasia, interstitial infiltration by myofibroblasts, and early deposition of collagen
- Some progress to Fibrotic stage - obliteration of normal lung architecture, diffuse fibrosis and cyst formation
Pathological Findings in Asthma
- Airways are infilitrared by
- eosinophils
- Activated T lymphocytes
- Activated mucosal mast cells
- There is also
- thickening of the basement membrane due to collagen deposition in subepithelium
- Hypertrophy of airway smooth muscle
- In fatal asthma
- multiple airways occluded by mucous plugs
- Airway oedema
Pathophysiology of ARDS
- Alveolar injury leads to
- Release of inflammatory cytokines (TNF, IL1, IL6, IL8) these
- Recruit neutrophils to the lungs where they become activated and
- Release toxic mediators which
- Damage capillary endothelium and alveolar epithelium which
- Allows protein to escape vascular space which
- Changes the oncotic gradient which normally favours resorption of fluid so
- Fluid poors into interstitium, overwhelming lymphatics so
- Airspaces fill with blood, proteinaceous oedema fluid and debris (and functional surfactant is lost
- End result = alveolar collapse = impaired gas exchange, decreased complaince and increased pulm artery pressure
PFT algorithm
Pharmacological Management of IPF
Phosphodiesterase-4 (PDE4) inhibitors in COPD ?not yet available in Australia
- Mechanism - reduce inflammation by inhibiting the breakdown of intracellular cAMP
- E.g. Roflumilast - reduces moderate and severe exac
- ADRs
- GIT: Diarrhoea, nausea, reduced appetite –> LOW, abdo ppain
- Other- sleep disturbance, headache, ?depression
Pirfenidone
- Exact mechanism of action unknown - antifibrotic, antiinflammatory, antioxidant
- Regulates TGF B1 and TNF alpha in vitro
- Inhibits fibroblast proliferation and collagen synthesis
- Reduces cellular and histological markers of fibrosis (animal models)
- Effects
- Reduction in decline in FVC and 6MWT
- Improved progression free survival
- NO reduction in dyspnoea scores or death
- ADRs
- Photosensitivity - must wear sun protective clothing!!
- Nausea, diarrhoea
- Rash
Poor prognostic factors in pulmonary HTN (12)
- Age > 50 years
- Male gender
- WHO functional class III or IV
- Failure to improve WHO functional class during Rx
- RV dysfunction
- Reduced pulmonary arterial capacitance (SV/pa pulse pressure)
- Hypocapnia
- Comorbidities (COPD, DM)
- PAH associated with CTD
- SSRI use
- Low vWF levels
- Bone morphogenetic protein receptor type 2 BMPR2 mutations
Possible biomarker algorithm for pleural effusions
Pressure Control (PC) Ventilation
- Patient or time can trigger ventilation
- Can independently determine pressure delivered to lungs
- If low compliance of lungs = low lung volumes
- If high compliance of lungs = high lung volumes
Pressure Support Ventilation (PS)
- Patient initiates breaths
- Patient gets a specific pressure only on inhalation
Primary therapies in pulmonary HTN
- Group 1 (idiopathic/inherited) = no primary therapies
- Group 2 (2nd to LH disease) = Rx underlying heart disease
- Group 3 (2nd to lung disease causing hypoxaemia) = Rx undering hypoxia cause and supplemental O2 (mortality benefit)
- Group 4 (2nd of chronic TE of prox/distal pulmonary vasculature) = anticoagulation, surgical thromboendartectomy
- Group 5 (2nd to multifactorial) = Rx underlying
Principles of Pulmonary HTN treatment
- Assess severity (WHO functional classification + echo +/-RHC)
- Class I - no limitations of physical activity
- Class II - slight limitation of physical activity, comfortable at rest
- Class III - marked limitation of physical activity, comfortable at rest
- Class IV - inability to complete physical activity without Sx. Sx at rest
- Primary therapy - address underlying cause
- Advanced therapy - directed at PH
Prognostic markers in pleural infection
RAPID
Progression of Pulmonary Disease in Cystic Fibrosis
- Start - recurrent cough which becomes persistent
- recurrent respiratory tract infection due to inability to clear secretions
- chronic infection/inflammation –> progressive tissue damage in airways
- lysosomal enzymes released from infiltrating neutrophils contribute to progressive airway destruction
- airway becomes floppy + collapsible under conditions of high flow = air trapping +airway hyperreactivity
Pulmonary Function Testing in CF
Normal in newborns
Signs of deterioration by 6months
Overtime - develop obstructive pattern
Lung volumes (TLC and RV) will increase due to hyperinflation
FEV1 correlates with survival in CF
Pulmonary HTN - definition
Mean arterial pressure >25mmHg at rest of pulmonary artery
Normal ~ 20mmHg
Pulmonary Rehabilitation in COPD
- Multidisciplinary approach
- Optimum benefits achieved from programs lasting 6 - 8 weeks
- Supervised exercise training twice weekly is recommended
- Rehabilitation - shown to be the most effective therapeutic strategy to improve SOB, health status and exercise tolerance
- Education alone is not effective
Relative contraindications to lung transplantation (9)
Removal of inhaled particles from the body
- Large particles - filtered out in the nose
- Smaller particles - removed by muco-cillary escalator
- Even smaller particles that make it to alveoli - engulfed by macrophages –> removed via lymphatics/blood flow
Risk factors for pneumothorax
Primary spontaneous
- SMOKING (biggest)
- male gender
- cannabis smoking
- FHx
- Marfans
- Homocystinuria
- Thoracic endometriosis
Sg and Sx of pulmonary HTN
Symptoms - do not usually occur until pressure 2x normal (50mmHg)
- Initial - exterional dyspnoea, fatigue (because you can’t adequately increase CO during exercise)
- Later - develop evidence of severe PH with RVF - exertional CP/syncope (when O2 demand goes up), oedema, ascites, pleural effusion
Signs
- Initial - increased P2, palpable P2
- Later - as RV hypertrophy develops –> prominent a wave of JVP due to forceful contraction of RA
- Even later - wider splitting of S2, RV heave. Systolic ejection click, S4, pulmonary ejection murmur
- Systemically in very severe disease - tachypnoea, peripheral cyanosis, cold extremities
- Pulse - small volume (severe disease)
Spirometry Interpretation
First look at FEV1/FVC
- if > LLN then look at FVC - if FVC > LLN = normal study,
- if > LLN then look at FVC - if FVC< LLN = possible restrictive defect
- if < LLN or <0.70 then look at FVC - if FVC > LLN = obstructive defect
- if < LLN or <0.70 then look at FVC - if FVC < LLN = mixed: obstructive defect with possible restrictive defect or gas trapping
NOTE: post bronchodilator fixed ratio of FEV1/FVC < 0.70 = COPD type airflow limitation
Spirometry result which indicates air trapping and hyperventilation
- Airtrapping: FRC or RV increased >120% predicted
- Hyperventilation: TLC increased >120%
Stepwise management of Asthma
Stepwise Management of Stable COPD
Triple therapy may reduce rate of exac and reduce hospitalisations – for stable COPD patients
- In patients with a history of exacerbations during the previous year:
- Triple therapy with fluticasone furoate, umeclidinium and vilanterol (ICS/LABA/LAMA) resulted in:
- Lower rate of moderate or severe COPD exacerbations than
- Fluticasone furoate–vilanterol (ICS/LABA) or
- Umeclidinium–vilanterol (LAMA/LABA)
- Lower rate of hospitalisations due to COPD than
- Umeclidinium–vilanterol (LAMA/LABA)
- Lower rate of moderate or severe COPD exacerbations than
The primary causes of death post lung transplantation
- Within 30 days: Primary graft dysfunction (PGD)
- a form of ARDS/diffuse alveolar damage
- After the first year: Chronic lung allograft dysfunction (CLAD)
- bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome
- Less but still common at all time points
- infection EG bacterial bronchitis/pneumonia, also fungi, CMV, viral and mycobacteria
- Less common
- malignancy (most common overall: non-melanoma skin cancer, most common after 1 year posttransplant lymphoproliferative disease (PTLD))
The role of pharmacotherapy in stable COPD
There is no conclusive clinical trial evidence that any existing meds for COPD modify long-term decline in lung function
Theophyllines
- Mech - unclear ?sm musc relaxation, anti-inflam, increase diaphragm contractility, and CNS stimulation
- Many, many precautions + narrow therapeutic range
-
ADR - nausea, vom, diarhoea, GORD, headache, insomnia, anxiety, tremor
- +Rarely seizures, arrhythmias, tachycardia
Total ventilation, alveolar ventilation definitions, and physiological deadspace
- Total ventilation (total volume leaving lung/min) = TV x RR
- Alveolar ventilation (volume of air available for gas exchange/min) = (TV - anatomical deadspace) x RR
-
Physiological dead space - volume of gas that does not eliminate CO2
- Anatomical and physiological dead spaces are roughly equal in healthy pts
- Physiological increases in lung disease
TPA and DNase for empyema Mx
- name the 2 benefits
- what is the current role
TNA/Dnase may be an option for patients in whom standard therapy has failed and who are not a candidate for thoracic surgery
Treatment of OSA
- Weight loss
- CPAP
- Oral appliances
- Upper airway surgery
- Hypoglossal nerve stimulation
- Devices - nasal splints, expiratory valves, chin straps
Treatment of primary spontaneous pneumothorax
>2cm!
Type 1 vs Type 2 Respiratory Failure
-
Type 1 - Oxygenation failure
- Examples: ARDS, Pneumonia, CCF
-
Type 2 - Ventilation failure
- Examples: COPD, Asthma
Usual interstitial pneumonia - CT findings
UIP - RASH
- Reticular abnormality
- Absence of inconsistent features
- Subpleural, basal predominance
- Honeycombing with or without traction bronchiectasis
Vaccinations for stable COPD
- Influenza - reduces serious illness and death in COPD patients
- 23-valent pneumococcal polysaccharide vaccine (PPSV23) reduces CAP in COPD pts <65yrs with FEV1 <40% predicted + have comorbidities
- In the general population of adults >65years the 13-valent conjugated pneumococcal vaccine (PCV13) reduces bacteraemia and serious invasive pneumococcal vaccines
Value of FEF 25-75
- It is the mean forced expiratory flow between the 25% and 75% of the FVC
- Reflects flow in smaller, peripheral airways
- May be reduced in early obstructive disease
VO2 max formula
VO2 = maximum rate of oxygen consumption measured during incremental exercise; that is, exercise of increasing intensity.
What are the benefits of the different advanced therapies for pulmonary HTN?
Soluble Guanylate Cyclase (sGC) Stimulators
- Soluble guanylate cyclase (sGC) is an enzyme in the cardiopulmonary system and the receptor for nitric oxide (NO). Pulmonary arterial hypertension (PAH) is associated with endothelial dysfunction, impaired synthesis of NO, and insufficient stimulation of the NO-sGC-cGMP pathway.
- eg of GC simulatant riocguat
What factors shifts O2 dissociation curve to the RIGHT
- *CADET face RIGHT**
increased: CO2, Acidity (decreased pH), 2-3 DGP, Exercise, Temperature
What is the airflow at FRC
No airflow
What is the full Aa gradient formula
Which genetic mutation is associated with PAH
BMPR2 - Bone morphogenetic protein receptor 2 inactivation = inhibition of vascular proliferation
A patient presents with PFTs showing a mixed obstructive/restrictive deficit that resolves with bronchodilators
What is the likely aetiology?
Pure obstructive disease with air trapping
Are ABGs and VBGs equivalent in COPD?
No evidence they’re an acceptable alternative, shouldn’t be used
Are corticosteroids of benefit in CAP? In which group?
- Yes, demonstrated in a meta analysis of 13 RCTs
- Pneumonia severity index (PSI) 4 and 5 have been shown to most benefit
- NNT of 18 to prevent 1 death
- 3% reduced mortality, 5% reduced need for mechanical ventilation, LOS reduced by 1 day
Another study IPD (more thorough review – gold standard) of the same studies (minus a few that wouldn’t share their data)
- More conservative conclusions than Cochrane review regarding benefits of steroids
- No difference in mortality
- Reduces LOS ~ 1 day
- Reduced time to clinical stability
- Increased hyperglycaemia requiring insulin
- Increased CAP related readmissions (NNH 45)
So… steroids in CAP?
- Not at this stage
Are steroid sparing agents of use in asthma?
No for the classic ones, multiple have been tried with no benefit
- methotrexate, cyclosporin, azathioprine, gold, IVIg
Omalizumab
- neutralises circulating IgE without binding to cell-bound IgE
- reduces exacerbations in severe asthma, allows lower dose ICS, improves symptom control
- requires high IgE levels to qualify
- very expensive
- may be continued in pregnancy
Mepolizumab/reslizumab
- anti IL-5 which blocks eosinophil recruitment and activation in steroid resistant eosinophilic asthma
- reduces exacerbations 50%, improves FEV1, symptom control, and QOL
- requires peripheral eosinophilia to qualify
Benralizumab (CALIMA, Lancet Sept 2016)
- anti IL-5r inducing rapid eosinophil depletion
- Phase III RCT in those with severe uncontrolled asthma on ICS/LABA with >=2 exac in last yr and peripheral eos >300 cell/uL
- Improves exacerbation rate, FEV1
Dupilumab (Wenzel et al, Lancet April 2016)
- anti IL-4r, inhibiting IL-4/13 signalling
- Phase IIb RCT in those with uncontrolled asthma already on ICS/LABA
- improves FEV1 and reduces exacerbations regardless of baseline eosinophil count
By what is IPF mediated? What are the treatment considerations?
- Aberrant wound healing thought to be the important underlying cause
- Nintedanib and pirfenidone both slow disease progression but don’t affect dyspnoea or survival
- Supplemental oxygen and pulmonary rehabilitation improve QOL
Describe the distribution of inflammation typical of asthma and the cells that mediate it
Trachea to terminal bronchioles with predominance in bronchi
Mediated by airway hyperresponsiveness
Chronic inflammation punctuated by episodes of acute inflammation
Mast cells
- Found in airway surface in asthmatics, where none are normally
- Initiate acute bronchoconstrictor response to allergens or other stimuli
- IgE dependent activation mechanism
- Histamine, prostaglanding D2, cysteinyl leukotreines, other cytokines, chemokines, growth factors
Macrophages/dendritic cells
- Present antigen to uncommitted T lymphocytes
- Usually promote TH2 differentiation, require IL-12 or TNFa to differentiate to TH1
- Thymic stromal lymphopoetin instructs dendritic cells to attract TH2 into airways
Eosinophils
- Infiltration a characteristic feature of asthmatic airways
- Oxygen derived free radicals and basic proteins drive hyperreactivity
- Survive longer by adhering to vascular endothelial walls
Neutrophils
- Increased activated neutrophils may be found in some with severe asthma
- Some with mild asthma can have neutrophil predominance
T Lymphocytes
- Coordinate inflammatory response by recruiitng eosinophils and mast cells with specific cytokines
- TH2 phenotype overexpressed in naive and asthmatic immune system, which release IL-5 for eosinophilic inflammation and IL-4/13 for IgE formation
- TH1 predominate in normal airways
- Regulatory T cells play a role in expression of other cells
Structural cells
- May be more important than immune cells in chronic inflammation due to predominance
- Important source of inflammatory mediators
Does coal dust increase risk of lung cancer?
Nope
Does CPAP alter cardiovascular outcomes in OSA?
No
SAVE study in Sept 2016 NEJM
45-75yo with mod-sev OSA + coronary or cerebrovascular disease
- CPAP + usual care vs usual care alone
Primary end point
- death from cardiovascular causes, MI, stroke
- hospitalisation for UA, HF, TIA
AHI decreased from 29.0 -> 3.7 events per hour in the CPAP group
- *No difference in primary endpoint** (1.10; 0.91-1.32)
- **significant reduction in snoring and daytime sleepiness
- improved health related QOL and mood**
Does immunotherapy (desensitisation therapy) help in asthma?
Yes
Does snoring necessitate the presence of OSA? What is the prevalence of OSA?
Not necessarily, but is correlated
~23% women
~50% men
Go through PFT interpretation
- *?Obstruction**
- FEV1/FVC <70% = obstruction
- *?Severity**
- mild >70%
- mod 60-69%
- mod-sev 50-59%
- sev 35-49%
- very sev <35%
- *?Reversible**
- Increase in FEV1 or FVC >12% and 200mL
- no SABA for 4hrs, no LABA for 12hrs, no LAMA for >24hrs prior
- *?Inducible**
- Direct = MetacholinE = SensitivE. Positive if >20% reduction in FEV1 with <=4mg/mL
- Indirect = Mannitol = Specific. Positive if >15% reduction in FEV1 at <=635mg cumulative
- *- Exercise** = treadmill = specific and sensitive for exercise induced bronchconstriction but not asthma. Positive if >=10% reduction in FEV1 or FVC over any two consecutive time points
?Specific volume loop pattern Variable Extrathoracic (pharynx, larynx, extrathroacic trachea)
DLCO interpretation
?Diffusion
- DLCO high = polycythaemia, asthma, increased blood volume, L->R shunt, alv haemorrhage
- DLCO low = thick membrane, decreased surface area, decreased blood volume, decreased lung volume
- DLCO:VA (KCO) = gas exchange per unit volume. Low in pulm causes, high in extrinsic causes
- DLCO very low compared with TLC -> think pulmonary hypertension
Go through the algorithm for approach to treatment of pulmonary arterial hypertension (group 1)
Go through the various anatomical locations of insterstitum in the lungs
How are SCLC and NSCLC staged? Are they different? Why? What’s the mortality like for the two subtypes of SCLC?
Both require imaging and tissue sampling
NSCLC staged with TNM
- CTCAP first
- If mets then no PET. If no mets then PET
- PET upstages 20%, avoiding unnecessary surgery
How are the interstitial lung diseases (ILD) subclassified? How might they behave?
Varying presentations/clinical course
- Self limiting inflammation
- Inflammation with risk of progression to fibrosis
- Stable fibrosis
- Progressive fibrosis with stabilisation posisble
- Inexorably progressive fibrosis
How bad is second hand smoke?
Third leading cause of preventable death in the USA
- *Increases risk of:**
- *- heart disease** 23%
- *- lung cancer** 17-30%
- COPD; asthma exacerbations; meningococcal meningitis
All cause mortality increased by 15% in lifetime non-smokers who live with smokers
How can central sleep apnoea (CSA) be differentiated from OSA on polysomnography?
CSA (due to instability of respiratory controller)
- minimal hypoxia
- minimal snore
- gets better in REM
OSA (due to anatomical obstruction)
- hypoxia
- loud snore
- gets worse during REM
>80% of apnoeas have to be central to diagnose
- i.e. no flow and no chest or abdo muscular effort
How can severity of pneumonia be categorised? What is the mortality associated with various scores?
CURB65
• Confusion
• Urea >7mmol/L
• Respiratory rate >30
• BP <90mmHg systolic or 60mmHg diastolic
• Age >65
Risk of death at 30 days (0-1 = outpatient; 2 = consider short stay in hospital or close observation as OP; 3-5 requires hospitalisation and consideration of ICU)
- 0 – 0.6%
- 1 – 2.7%
- 2 – 6.8%
- 3 – 14%
- 4 – 27.8%
- 5 – 27.8%
SMART-COP is probably the better score to use as it identifies those which may deteriorate rather than those who are clinically obviously severe
How can the severity of cystic fibrosis be predicted based on genetic abnormality?
Severe - F508del homozygotes
- more often associated with pancreatic insufficiency
- more often associated with OP
- more often associated with DM
Less severe - F508del + other
Least severe - other + other
How can you think of the asthma epitypes and their management?
90-95% of asthmatics are sorted out by ICS +- LABA
Of that 5-10% separate into:
- refractory with eosinophilia or high IgE
- in which case you go to the appropriate mab (omalizumab IgE, mepolizumab IL-5, with new ones coming)
- refractory non-eosinophilic
- in which case no good treatment but maybe dupilumab against IL-4r will be the go to in coming years
How do ICS work in asthma? When are they of benefit? What are their side effects?
Reduce inflammatory cells and their activation
- eosinophils, surface mast cells, activated T lymphocytes
- switch off transcription of multiple genes that encode inflammatory proteins
Of benefit in any age and severity
- prevent symptoms and exacerbations
- reduce AHR
- minimise irreversible changes
- don’t cure, only suppress
ADR: Hoarseness and oral candidiasis most common
- no convincing evidence of impaired growth in children or OP in adults
How do inhaled anticholinergics act? Are they well tolerated?
Muscarinic receptor antagonists
- Prevent cholinergic induced bronchoconstriction and mucous secretion
- less effective than beta agonists as they only affect the cholinergic reflex aspect
Slower than SABAs so should be used only after
Well tolerated
- most commonly dry mouth
- the elderly more likley to get urinary retention or glaucoma
How does chronic eosinophilic pneumonia differ from acute?
- More indolent, never presents with acute respiratory failure and hypoxaemia
- 90% have peripheral eosinophilia
- Classic ‘photographic negative pulmonary oedema’
- >50% relapse after treatment with corticosteroids
How does hypersensitivity pneumonitis present? How is it diagnosed? What is the strongest predictor of HP?
Variable presentation, strongest predictor is exposure to an antigen known to cause HP
Acute
- 4-8hrs following exposure with intense fevers, chills, malaise, dyspnoea
- resolves within hours/days without further exposure
- note that usually no wheezing
Subacute
- Gradual onset over weeks
- May occur as culmination of intermittent episodes of acute HP
- Resolves over weeks/months without further exposure
Chronic
- Insidious onset makes diagnosis a challenge
- Progressive dyspnoea, cough, fatigue, weight loss, clubbing
- Can have irreversible component
- May mirror IPF
- Fibrotic phenotypes may be associated with bird antigens
- Emphysematous phenotypes may be seen in farmer’s lung (actinomycetes; fungus)
Chronic HP with parenchymal changes is associated with poorer prognosis
- Chronic pigeon breeder’s lung has similar mortality to IPF
Diagnosis
- Careful occupation and home exposure history
- May have ill defined micronodular or ground glass opacities on CXR
- HRCT may be normal in acute; subacute characterised by groundglassing and centrilobular nodules; chronic may show reticular changes and traction bronchiectasis
- May have subpleural honeycombing similar to IPF; but spares the bases unlike IPF
- PFTs can be restrictive or obstructive
- Useful for categorising physiologic impairment and gauging response to therapy
- DLCO may be significantly impaired, especially in chronic HP with fibrotic changes
- Serum precipitins
- Assays for precipitating IgG antibodies against specific antigens
- Often provide false negatives
- Bronchoscopy
- For BAL, which may show lymphocytosis which is characteristic but not specific to HP
- note that there’s no eosinophilia
- Biopsy
- Not necessary
- Loose and poorly defined non-caseating granulomas
- Differ from sarcoid where the granulomas are well defined
- Mixed cellular infiltrate with lymphocytic predominance in alveolar spaces/interstitium
How does inhaled nitric oxide affect pulmonary physiology? In which conditions might it be useful? In which harmful?
- Localised dilation of vasculature associated with ventilated alveoli.
- Useful in pulmonary hypertension or in severe ARDS, where optimisation of V/Q mismatch can be helpful to improve oxygenation and ventilation.
- Can worsen oxygenation/ventilation in COPD due to significant number of partially ventilated alveoli to which flow is directed
How does pulmonary sarcoidosis present?
>90% of those with sarcoidosis
CTchest more sensitive but CXR preferred for characterising and following up
- peribronchial thickening, reticular nodular changes, predominantly subpleural
Stage 0 = normal
Stage 1 = hilar adenopathy alone
Stage 2 = hilar adenopathy plus infiltrates
Stage 3 = infiltrates alone
Stage 4 = fibrosis
PFTs
- DLCO the most sensitive test for ILD
- Restrictive defect can be seen but 1/3 with abnormal CXR and dyspnoea have normal volumes
- ~50% have obstructive defect
PAH in >=5%
- Found in 70% of those with end stage awaiting transplant
- Sarcoidosis related PAH can respond to therapy
How does sleep progress throughout the night?
Normal sleep in adults is consistently organised from night to night
- Progress through stages of non-REM
Have bouts of REM in cycles of 90-110 minutes
- 4-6 episodes per night
- get progressively longer
- associated with dreaming if awoken
Slow wave = used to be called stage 3/4
- Slow wave sleep may be completely absent in older adults
Sleep duration associated with weight gain and mortality
- <6hrs associated with more weight gain at 4yrs compared to more sleep
- <6hrs associated with increased mortality, seems to be mediated by inflammation
How is allergic bronchopulmonary aspergillosis (ABPA) managed?
- *Oral steroids for >=12 weeks**
- induce remission
- long term doesn’t prevent relapse
- slight increase in risk of invasive aspergillus
- *Itraconazole**
- improves IgE, radiology, QOL, symptoms
- reduces prednisolone use
- use for 4 months in those who’re steroid dependent
- *Omalizumab**
- overall limited evidence
- decreases exacerbations and steroid use; reduces IgE and FeNO
IgE level a marker of disease severity and treatment response
How is bronchiectasis managed?
Manage underlying disease if modifiable
- nontuberculous mycobacteria
- IgG deficiency of whatever cause
- ABPA
- COPD
Acute exacerbations
- decisions made based on symptom changes rather than investigations
- increased sputum, more viscous, darker, dyspnoea, haemoptysis
- sputum MCS prior to abx to guide therapy
- consider eradication of pseudomonas when first isolated (80% successful initially; free at median 14months f/u in 50%)
Prevention
- Positive expiratory pressure therapy (chest physio): improves QOL/FEV1/FVC; reduces sputum/inflammatory markers
- azithromycin reduces rates of exacerbation (use in frequent exacerbators >=3/yr or 2 hosp in 12 months)
- need to ensure no MAC colonisation first
- immunisations
- inhaled aminoglycacides not clear in non-CF bronchiectasis
- nebulised saline improves sputum bacteriology and QOL
- nebulised dornase increases exacerbation frequency, hospitalisation, steroid/antibiotic use
- inhaled steroids only with concommitant asthma/wheeze
How is COPD severity classified?
Severe complications without severe obstruction unlikley solely due to COPD
How is eosinophilia with pulmonary infiltrates classified? Name some of the causes
How is non-cardiogenic pulmonary oedema defined? What is its main underlying pathophysiology?
Radiographic evidence of alveolar fluid accumulation without haemodynamic evidence of cardiogenic aetiology (PAWP <= 18mmHg)
How long is it recommended to wait before flying after pneumothorax?
Most airlines recommend 6 weeks, though it has been shown to be safe to fly 2 weeks after radiological resolution of pneumothorax.
How may asthma be differentiated from COPD clinically and on PFTs?
Clinically
- COPD has less variability in symptoms
- COPD never completely remits
- COPD has less reversibility with bronchodilators
- ~10% of COPD have features of asthma: eosinophils and response to OCS
PFTs (>20% improvement psot bronchodilators quite specific for asthma over COPD)
- Asthma often fully reversible with bronchodilators
- COPD may have increased TLC and decreased RV, indicated gas trapping and hyperinflation
How much does weight loss improve OSA? What effect does CPAP have on weight?
Improves symptoms but very few are cured of mod-sev OSA with weight loss
- degree of weight loss doesn’t predict
- significant improvement in sleep symptoms with weight loss
- weight loss better than CPAP for metabolic benefits (CRP, insulin resistance, TGs)
- both weight loss and CPAP improve hypertension in those with OSA
Mod-sev OSA patients treated with CPAP tend to gain weight
- thought due to feeling better -> more of an appetite
Note that weight loss is an important adjunctive treatment when initiating CPAP for the metabolic benefits
How ought COPD exacerbations be managed?
Bronchodilators and corticosteroids the mainstay
Bronchodilators
- SABAs: No evidence nebuliser more efficacious than MDI and spacer in asthma. Not extended to COPD but makes sense.
- Neb = 10-12 puffs ventolin
- Evidence for adding ipratropium mixed
Systemic corticosteroids
- Improve symptoms, FEV1, PaO2 in mod-sev exac
- Reduced treatment failure, relapse, length of stay
- SEs: insomnia, anxiety, depression, BSLs
- 30-50mg/day
- No advantage to IV. May be useful in first 24hrs in those in extremis and unable to take orals
- No benefit beyond 2 weeks
- 5 days likely adequate (no tapering needed)
Antibiotics
- Controversy
- Most benefit in those with all 3 symptoms: SOB, volume, purulence
- More and more evidence that sputum purulence and ?CRP are the most important
- ?CRP >40 indication for antibiotics
- In severe exacerbations decreases mortality and length of stay
- Most only require oral antibiotics
- Not unreasonable to start intravenous in the most severe exacerbations
Oxygen
- Use low concentrations aiming 88-92% SaO2. Use Prongs at 0.5-2L/min
- ideally all patients with significant exacerbation need ABGs
- Risk of worsening hypercapnoea: Alter V/Q matching, haldane effet, decrease hypoxic drive
- High flow oxygen associated with increased HDU admission, NIV and LOS
NIV
- Indicated in hypercapnoeic respiratory failure
- Use early in RR >30 and pH <7.35
- Improves biochemical markers
- Decreases failure, length of stay, rates of intubation
- Needs experienced nurses +/- HDU
- Start at low pressures
- Aim to fix RR and pH within an hour
Intubation
- Mortality 10-50%. Varying with QOL, age, acuity, comorbidities, length of ventilation, previous episodes
- Weaning may be facilitated by NIV
How should empyema be managed?
Thoracotomy the gold standard
- associated with considerable morbidity and mortality as patients usually unwell and with comorbidities
Drain size
- small bore drains effective
- bigger drains = more pain and lower patient satisfaction
DNAse/tPA
- MIST-2 showed that DNase + tPA intrapleurally decreases need for surgical intervention (study endpoint was radiological and not mortality)
- note that the study did this after standard drainage deemed ineffective
- DNase alone -> higher treatment failure
How should patients with possible PAH be risk stratified based on PFT and TTE screening?
In what forms is CO2 carried in the blood?
- *Dissolved**
- 10% of CO2 in alveoli from blood from dissolved form
Bicarbonate
- *Carbamino compounds**
- CO2 combined with terminal amine groups of blood proteins
- Most importan globin of Hb, giving carbaminohaemoglobin
In which group with pulmonary hypertension is there a mortality benefit to oxygen?
Is exercise training of use? In whom should the pulmonary vasodilators be used?
Those with pulmonary cause have oxygen benefit
Exercise training improves 6MWT more than any other management option
- *Pulmonary vasodilators**
- Good for group 1 (pulmonary artery hypertension)
- Maybe in 3,4,5
- NEVER in group 2 (cardiac cause)
In which patients is lung resection contraindicated due to mortality risk? What can indicate patients that will tolerate pneumonectomy and lobectomy?
MI within 3 months
- 20% will die of reinfarction
- within 6 months relative contraindication
Uncontrolled arrhythmia
FEV1 <1L
Hypercapnoea
Severe pulmonary htn
DLCO <40%
FEV1 >2L can tolerate pneumonectomy
FEV1 >1.5L can tolerate lobectomy
Is adaptive servo ventilation (ASV) of benefit in those with central sleep apnoea and heart failure?
No, harmful (note that CPAP also doesn’t alter outcomes but is not harmful)
SERVE-HF trial in September 2015 NEJM
- LVEF <=45% + AHI >=15/hr and predominance of central events
- Treatment: ASV + usual care vs usual care alone
- Primary outcome - death from any cause, lifesaving cardiovascular intervention, unplanned hospitalisation for worsening HF
AHI -> 6.6/hr in ASV group
All cause mortality (1.28; 1.06-1.55) and Cardiovascular mortality (1.34; 1.09-1.65) significantly higher in ASV group
Is drug induced liver injury more common in those with underlying CLD?
No, but severity of outcome may be amplified
Exceptions in presence of hepatitis C
- Aspirin
- Methotrexate
- Isoniazid
- HAART for HIV
Is HRCT better than CXR in immunocompromised patients?
Yes, very much so
HRCT is a good, sensitive test. Not overly specific.
- can give clues as to the cause of the infiltrate, e.g. fungal
Is immunosuppression of benefit in IPF?
What did the PANTHER trial show?
NOO - is harmful!
Landmark study in IPF
Is nocturnal ventilation of benefit in neuromuscular Central Sleep Apnoea (CSA)?
E.g.
- muscular dystrophy
- MND
- Kyphoscoliosis
- Diaphragm paralysis
MIPS (maximal inspiratory pressure) on PFTs can be a good predictor of noctural hypoventilation
- MIPS <15-20 strongly predicts
Of benefit
- decreases mortality, hospitalisations, infections, symptoms
Is smoking cessation of use in COPD? What about vaccinations? Long term antibiotic therapy?
Smoking = Intervention with the greatest mortality/FEV1 impact
Flu - Reduction in number/severity of exacerbations
Pneumococcal - Reduces invasive disease
- *Antibiotics**
- Azithromycin has not become standard of care
- Signficantly increases time to first exacerbation
- Increased macrolide resistance
- No change in hospitalisations
Simvastatin doesn’t reduce exacerbation frequency (NEJM 2014)
Is there a difference between continuous and intermittent ICS in mild intermittent asthma? What about mild persistent asthma? What about moderate persistent asthma already on ICS?
No for mild intermittent
- Boushey et al NEJM 2005
- RCT of 225 pts
- 200 budesonide BD vs placebo vs 20 BD zafirlukast
- Exacerbation rescue: 800 budesonide BD for 10 days or 0.5mg/kg pred for 5 days
- No difference between groups
- exacerbation rate, QOL, rate of FEV1 decline over a year
Yes for persistent
- Pauwels et al Lancet 2003
- RCT of 7241 pts
- 400 daily >11yrs, 200 daily <11yrs budesonide vs placebo
- 44% reduction in risk of hospital or ED treatment of asthma
- Improved FEV1 from baseline prebronch 1.71% and postbronch 0.88% at 3yrs
- Fewer courses of oral steroids and more symptom free days
Addition of LABA for mod persistent already on ICS
O’Byrne et al Am J Respir Crit Care Med 2001
From POV of exacerbations per year
- bud 200 = bud 400
- bud 200 + eform ~30% reduction in exacerbations (vs 200 bud)
- bud 400 + eform ~60% reduction in exacerbations (vs 400 bud)
List the main causes of obstructive pulmonary defect
Asthma
COPD
Bronchiectasis
Bronchiolitis obliterans
Alpha1 antitrypsin disease
Cystic fibrosis
Name the major causes of non-cardiogenic pulmonary oedema
ARDS
Neurogenic
Altitude
Re-expansion
Opioid
PE
Eclampsia
TRALI
Of what should you be suspicious with groundglass nodules?
Lung adenocarcinoma that is not yet apparent
- need to keep a close eye on them
- shouldn’t be dismissed as infection
To what does primary and advanced therapy refer in the management of pulmonary hypertension and that are the options in the different groups?
All
- Pulmonary rehab improves 6MWT, QOL, WHO class, VO2max but not haemodynamics
- Exercise training improves aerobic capacity and endurance
- Diuretics have no RCT evidence but are used
- Oxygen if hypoxic has no evidence but is used
- anticoagulation for (retro observational data): IPAH, drug induced PAH, hereditary PAH, CTEPH (not in CTD group)
Primary = at underlying disease
- group 1: CTD and HIV if the cause
- group 2: OMT of heart failure
- group 3: underlying disease. Continuous oxygen (>16hrs/day) if baseline PaO2<55 confers survival benefit
- group 4: anticoagulation for 3 months, if no improvement then surgical thrombendarterectomy which may result in dramatic and sustained response (both lacking good data)
- group 5: variable at specific aetiologies
Advanced = pulmonary vasodilators
- in WHO functional class II-IV despite treatment of underlying cause
- definite in group 1, almost never in group 2, case-by-case in 3-5
- group 1: Improved survival, 6MWT, functional class, delayed disease progression, improved pulmonary haemodynamics
- group 2: increase mortality
- group 3: thought to worsen due to worsened V/Q mismatch
- group 4: could consider after thrombendarterectomy or if they’re not fit for it or to bridge to surgery
- group 5: unknown role
Agents
- *- CCBs if vasoreactive on RHC**
- improved survival, function, haemodynamics
Prostacyclin pathway
- epoprostenol IV: first line in class IV (only medication with prospective evidence of improved survival)
- improves function, haemodynamics and survival in IPAH, unclear if in other group 1
- iloprost inh: improves functional class and 6MWT but needs 6-9x/day
- selexipag: improves progression free survival and decreases hospitalisations, no change in mortality
- Endothelin receptor antagonists
- nonselectives: bosentan, macitentan
- bos delays clinical worsening, improves haemodynamics and exercise capacity with mortality favourable to historical controls
- maci delayed clinical worsening, improves functional class and exercise capacity, improves combined morbidity/mortality endpoint
- selective against A: ambrisentan
- improves exercise tolerance, functional class, haemodynamics and QOL
NO-cGMP enhancers
- PDE5 inhibitors: sildenafil, tadalafil
- sild: improves haemodynamics and exercise capacity
- tada: improves time to clinical worsening and exercise capacity
Riociguat
- Stimulates soluble guanylate cyclase
- increases sensitivity of sGC to endogenous NO; direct stimulation of NO receptor
- improves 6MWT, WHO class, symptoms, PVR
- unknown if mortality benefit
End stage
- lung transplant and creation of R->L shunt
To what does vasodilator response refer and how does it change management options in pulmonary hypertension?
During RHC
- short duration vasodilator administered
- decrease in PAMP >=10mmHg to an absolute level of <=40mmHg without decrease in CO or BP
In these patients long term treatment with a dihydropyridine or diltiazem CCB confer survival, functional, and haemodynamic benefit
- use outside of vasoreactivity worsens outcomes
What are desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis interstitial lung disease (RBILD)?
DIP
- Smoking related form of ILD (one of the rarest forms)
- Diffuse groundglass opacities, usually basal and peripheral
- pigment laden macrophages fill alveoli on histology
- good prognosis with smoking cessation and steroids
RBILD
- related to DIP, some feel that DIP is just end stage RBILD
What are some of the infectious causes of pulmonary eosinophilia?
What are the adverse effects of OSA?
Cardio/pulmonary/vascular risk
- doubles CV risk
Sleepiness and QOL
Noise pollution
Post-operative risk
What are the age related changes to the respiratory system?
Loss of elastic tissue
- enlarged alveolar ducts -> loss of surface area for gas exchange
- decreased lung recoil -> maximal exercise limit to expiratory flow and produces dynamic lung hyperinflation
Increased stiffness of the chest wall
Flattened and less efficient diaphragm
Physiology
- DLCO decreases 5%/decade
- increased V/Q mismatching
- increase in A-a gradient
- decreased response to hypoxaemia and hypercapnoea
- decreased mucociliary clearance
What are the aims of asthma therapy? What are the features of controlled/partly controlled/uncontrolled asthma? Is education important?
Aims of asthma therapy
- minimal chronic symptoms, ncluding nocturnal
- minmal exacerbations
- no emergency visits
- minimal use of SABA
- no limitations on activities, inclduign exercise
- Peak exp flow circadian variation <20%
- normal peak flow exp flow
- minmal ADR from medicine
Education improves compliance, especially with ICS
- also helps to recognise worsening asthma and how to step up
- Written action plans reduce admissions and morbidity in adults and children
What are the benefits of auto-CPAP compared to fixed pressure CPAP in OSA?
What about BiPAP vs CPAP in OHS?
Some studies show higher patient preference and adherence
- no benefit regarding apnoea/hypopnoea and oxygen desaturations
CPAP equally effective compared with BiPAP in OHS
- both improve daytime hypercapnoea in those without severe nocturnal hypoxaemia
What are the broad categories of aetiology for bronchiectasis?
Bronchial obstruction
- tumours
- hilar lymphadenopathy
- COPD
- mucoid impaction (ABPA)
Immunodeficiency
- IgG: bruton’s, CVID, subclass deficiency
- IgA: selective, ataxia telangiectasia
- CGD
Abnormal clearance
- ciliary defects: ciliary dyskinesia
- cystic fibrosis
- Young’s: obstructive azoospermia with sinopulmonary infections
Miscellaneous
- A1AT
- infections: childhood, bacterial, viral, other
- recurrent aspiration pneumonia
- CTD: RA/Sjogren’s
- IBD
- chronic rejection post transplantation
What are the categories of causes of restrictive lung defects? Name some examples from each category
Parenchymal
- IPF
- Drugs
- Amiodarone, bleomycin, methotrexate, nitrofuraontoin
- CTD
- SLE, systemic sclerosis, RA, sarcoid, vasculitidis
- Environmental
- Asbestosis, silicosis, hypersensitivity pneumonitis
- Radiation
Neuromuscular Weakness
- GBS, ALS, muscular dystrophy, myasthenia gravis
Chest wall/pleural
- Kyphoscoliosis
- Ankylosing spondylitis
- Effusion
- Morbid obesity
What are the causes of a fixed obstructive defect on flow-volume loop? What is its appearance?
Tracheal stenosis and goitre
What are the causes of clubbing?
Idiopathic
- pachydermoperiostosis, familial clubbing, hypertrophic osteoarthropathy
Pulmonary
- lung cancer, pulmonary metastases, pleural mesothelioma
- ILDs, sarcoidosis, cryptogenic fibrosing alveolitis
- lung hydatids
Cardiac
- cyanotic congenital heart disease
- any right to left shunt
- IE
Gastrointestinal
- IBD
- PBC, cirrhosis, hepatopulmonary syndrome
- achalasia, peptic ulceration of the oesophagus
Skin
- Bureau-Barrière-Thomas syndrome, Fischer syndrome, palmoplantar keratoderma, and Volavsek syndrome
Malignancies
- Thyroid
- Hodgkins, disseminated CML, POEMS
Miscellaneous
- acromegaly, thyroid acropachy, severe secondary hyperparathyroidism
- sickle cell
- pregnancy
What are the changes to pulmonary function testing (PFT) with aging?
Increased:
- residual volume and FRC
- V/Q mismatching
- airway reactivity
- compliance
Decreased
- FEV1
- FVC
- DLCO
- respiratory drive in response to hypoxia and hypercapnoea
Unchanged
- TLC
What are the characteristic radiographic findings in silicosis, coal worker’s pneumoconiosis, and asbestosis?
- *Asbestosis**
- Irregular linear opacities in lower lung fields
- Groundglassing
- Curvilinear lines parallel to the pleural surface
- Pleural thickening
- *Silicosis**
- Crazy paving pattern
- Calcified hilar nodes
- Small, rounded upper lobe opacities
- May coalesce as disease progresses and form large, non-segmental conglomerates of irregular masses
- Simple = small, rounded opacities without PFT change
- Complicated = coalescing
- Progressive massive fibrosis = large masses
- *Coal worker’s pneumoconiosis**
- Identified in 10% of all coal miners
- Nodules similar to silicosis
- May cause chronic bronchitis and COPD
- May progress to PMF as in silicosis
What are the clinical features of bronchiectasis? Radiological? Distribution aetiology associations?
- *Cough with daily production of mucopurulent and tenacious sputum for months/years the classics**
- dyspnoea, wheeze, pleuritic chest pain less so
- urinary incontinence common
- *Look for some underlying cause**
- infective, obstructive, immunodeficiency, etc
- *Imaging**
- CT preferred
- airway dilatation (>1.5x diameter of adjacent vessel)
- *- signet ring** sign classic
- *Distribution**
- *- perihilar: ABPA**
- upper: cystic fibrosis
- ML/LL: primary ciliary dysfunction
- ML/lingular of LUL: nontuberculous mycobacteria
- LL: idiopathic
What is physiological shunt and deadspace?
- Shunt: Perfusion to non-ventilated alveoli
- Deadspace: Ventilation to non-perfused areas
What are the major risk factors for fatal asthma?
What is the mechanism behind cyanosis?
Hb is purple, so decrease in bound O2 results in purple colour
Why does 2,3 DPG have lower binding affinity to HbF?
2,3 DPG best binds to the beta subunit, so HbF has less 2,3 DPG.
- Results in an oxygen dissociation curve shifted to the left (HbF has higher affinity for oxygen)
** DPG - promotes hemoglobin transition from a high –> LOW-oxygen-affinity state (shifts curve to the right)
What is the definition of an obstructive defect on PFT? How is severity categorised?
What is the definition of a reversible obstructive defect?
FEV1/FVC <70% predicted
Severity is categorised based on FEV1
- Mild >70%
- Mod 50-69%
- Severe <50%
Reversible
- Increase in FEV1 by >=12% and >=200mL after bronchodilators
- Asthma typically fully reversible, COPD not.
Which medications need to be withheld prior to PFT?
SABA for 4hrs
LABA for 12hrs
Tiotropium for >24hrs
What is inducibility PFT? When is it performed? What is used? What constitutes a positive test?
Either direct stimulation of bronchoconstriction, or activity to induce release of histamine.
Performed to rule out exercise or allergen induced asthma when standard PFTs normal
- Inhaled metacholine (direct challenge: cause direct constriction via receptors on smooth muscle)
- Highly sensitive but not specific
- >=20% reduction in FEV1 with 4mg/mL metacholine is positive
- Inhaled mannitol (indirect challenge: cause activation of mast cells -> histamine + bronchoconstrictor release)
- Highly specific but but not sensitive
- >=15% reduction in FEV1 with <=635mg inhaled mannitol
- Exercise challenge
- Excellent spec and sens for exercise induced bronchoconstriction
- Baseline spirometry followed by 80-90% maximum HR treadmill held for 8mins
- >=10% decline in FEV1 or FVC over any two consecutive timepoints at 1, 3, 5, 10, 15, 20, 30, 45 mins
What is the typical appearance of an extrathoracic obstruction on flow-volume loop? Why does it look the way it does?
NORMAL expiration flow
LIMITED inspiratory flow
What is the typical appearance of intrathoracic obstruction on pfts? Why does it appear the way it does?
LIMITED expiratory flow (as the obstruction moves IN with expiratory as it INTRAthoracic pushs IN on it)
PRESERVED inspiratory flow (as the obstruction moves out with inspiration as it is INTRAthoracic)
What is this flow-volume loop pattern indicative of? Differentials?
Indicative of fluctuating upper airway obstruction
- Neuromuscular weakness
- Parkinson’s disease
- OSA
- Upper airway burns
- Pedunculated tumours
- Laryngeal dyskinesia
lable diagram
What is the definition of a restrictive defect on PFT? What does RV:TLC tell you?
TLC<lln> defines a <strong>restrictive defect. </strong>FVC<lln>TLC is required in the definition</lln></lln>
RV (residual volume):TLC (Total lung capacity) tells you the ratio of unusable lung
- Increased RV:TLC points toward extrinsic restrictive defect
- normal RV:TLC points toward intrinsic restrictive defect
What is DLCO in relation to PFTs? Name the categories and causes for increase and decrease
Amount of CO that can bind to Hb
Decrease
- Diffusion problem
- Thickened membrane
- Fibrosis, alveolitis, vasculitis
- Decreased surface area
- COPD
- Thickened membrane
- Decreased capillary blood volume
- Anaemia
- PE
- HF
- Decreased lung volume (previous lobectomy)
Increase
- Polycythemia
- Asthma
- Increased blood volume
- Left->right shunt
- Alveolar haemorrhage
- Suspect if DLCO intially high then decreased subsequently
What is DLCO:VA? What does it mean?
KCO shows gas exchange per unit volume of lung, accounting for change in lung volume
Low in pulmonary causes of decreased DLCO
- ILD, fibrosis, pulmonary vascular disease
High in extrapulmonary causes of decreased DLCO
- Resection, thoracic wall abnormalities
Run through the algorithm to interpret PFTs
What type of genetic disorder is cystic fibrosis? On which chromosomes are the mutations? What is the most common mutation? Does any drug target it? Are there any other common mutations for which medications are available?
Autosomal recessive exocrinopathy due to mutations on chromosome 7
F508del most common
- 70% defective alleles
- 90% individuals carry >=1 F508del mutation
Ivacaftor of benefit in individuals with G551D stop mutation (~4% of CF)
- ~8% have this mutation
- improves FEV1 7-10%, reduces exacerbation by 55%, reduces hospitalisation, gains BMI
Lumacaftor-ivacaftor of minor benefit in individuals homozygous for F508del
- lumacaftor partially corrects misfolding
- ivacaftor improves channel gating activity
- 3% increase in FEV1, reduced exacerbation freq by 39%, small improvements in BMI and QOL
- similar benefit to that of inhaled tobramycin
What is the defective ion channel in cystic fibrosis? Where is it located? What happens when it’s defective?
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
- epithelial ion channel
- apical plasma membrane of acinar and epithelial cells
Inability to transport chloride ions, affecting different tissues in different ways
- Overriding principle is that of thickened secretions due to lack of periciliary layer caused by decrease in water
How many classes of CFTR defects are there?
6
- Class I
- Absence of synthesis
- Class II
- Defective protein maturation and premature degradation
- F508del accounts for ~70% of defective alleles
- 90% individuals carry >=1 F508del mutation
- Class III
- Disordered gating/regulation
- Class IV
- Defective conductance through the ion channel pore
- Class V
- Reduced number of CFTR transcripts due to promoter/splicing abnormality
- Class VI
- Accelerated turnover from cell surface
In whom is cystic fibrosis most common? What percentage carry a CF mutation? Incidence?
Caucasians
- 1/25 carry
- 1/3,300 live births in caucasians
- 1/33,000 live birth in asians
Why do individuals with cystic fibrosis get lung injury? What particular pattern does it follow?
What can be done to assist with mucous clearance?
Thick sputum is difficult to clear which leads to chronic infection and inflammation.
This then leads to bronchiectasis, typically in the upper lobes.
Chest physiotherapy
- daily required
Mucolytics
- DNase and hypertonic saline of benefit
- inhaled steroids and bronchodilators only of benefit in those with asthma phenotype
What are the extrapulmonary manifestations of cystic fibrosis? Their prevalence and treatment?
Pancreatic
- exocrine insufficiency
- 80-90% of those with CF
- due to blockage of ducts due to thickened and inspissated mucous
- fat soluble vitamin replacement
- pancreatic enzyme replacement
- requires PPI as they don’t function in acidic environment
- endocrine insufficiency
- >30% of adults with CF
- features of type 1 and 2
- yearly oral GTT recommended to screen (fasting BGL and HbA1c low sens)
- treated with insulin, never with diabetic diet
- decreased nutrition decreases BMI which worsens PFTs
Liver
- CF related liver disease usually develops before 18yrs of age
- ~10% CF patients develop cirrhosis
- hepatic steatosis most common at ~60%
- multilobar or focal biliary cirrhosis may be associated with portal hypertension and splenomegaly
- no benefit to ursodeoxycholic acid
- may progress to failure requiring transplantation
GORD
- requires aggressive treatment with PPI to reduce microaspirations
Gallbladder
- microgallbladder in 25-30%
- cholestasis and cystitis
Intestinal
- meconium ileus in 10-20% newborns with CF
- distal intestinal obstructive syndrome in adults
- c. difficile infection presents atypically, not usually with diarrhoea but with pain
Genitourinary
- involution of vas deferens in 99% males
- functioning spermatogenesis
- amenorrhoea and anovulation in females
Renal
- diabetic nephropathy
- oxalate nephrolithiasis
Haematological
- anaemia of chronic disease
- functional iron deficiency
- hypersplenism
- high INR
Musculoskeletal
- clubbing
- seronegative arthropathy
- pANCA positivity
What are the major predictors of poor outcome in cystic fibrosis? What about predictors of decline?
When is lung transplantation indicated?
Major predictors
- FEV1. Expected decline 2%/yr
- WCC
- Low BMI
- High CO2
- Female gender
Decline
- new bacteria
- especially pseudomonas, MRSA, MAC, burkholderia cepacia, stenotrophomonas
- diabetes
- ABPA
- poor social situation or poor compliance
- poor nutrition
- *Lung transplant indicated when 5yr survival <30%, best proxied by FEV1 <30%**
- 60% survival at 5yrs after transplant
May also be indicated with precipitous decline, especially when female or diabetic; massive haemoptysis or malnutrition; or pulmonary hypertension in the absence of hypoxaemic exacerbation
What is the most common bacterial pathogen in cystic fibrosis? What percentage of adults with cystic fibrosis are chronically infected with p. aeruginosa? How should acute pseudomonal exacerbations of cystic fibrosis be treated? What if any prophylactic therapy is appropriate? What is significant about burkholderia cepacia complex and mycobacterium avium complex?
Staph aureus most common
- MRSA becoming increasingly common, up to 25% prevalence
- MRSA independent risk factor for death
~70% of adults chronically infected with p. aeruginosa
- prolonged infection results in conversion to mucoid phenotype due to production of alginate
- chronic infection an independent risk factor for <fev1></fev1>
</fev1>
Dual anti-pseudomonal cover
- antipseudomonal beta lactam + one of fluoroquinolone, aminoglycacide (tobramycin preferable), or colistin
- utilise past sensitivities
Azithromycin and inhaled anti-pseudomonals (aztreonam, tobramycin) have been demonstrated to improve number of exacerbations and FEV1 when administered chronically in those colonised with pseudomonas
Burkholderia cepacia complex is associated with accelerated decline in PFT and decreased survival
- treated with bactrim
- contraindication to transplant in some centres
Isolation of MAC should result in immediate cessation of azithromycin prophylactic therapy to preserve sensitivity
What is the leading cause of cancer related death? What is the lifetime risk? How much risk does the largest risk factor confer?
Lung Ca
8% men, 6% women
- note that incidence in men has fallen dramatically whereas woman is plateauing/slightly going up
- *10x risk smokers** compared to never smokers
- *20x risk in continuin**g smokers
- stopping in middle age ameliorates 90% of the additional risk
What are the subsets of lung cancer? What are some basic pathological features?
Small Cell
- Neuroendocrine markers
- CD56, neural cell adhesion molecule, synaptophysin, chromogranin
- ~100% association with smoking
Non-Small Cell
- 90% of epithelial lung cancers
-
Adenocarcinoma
- Most common subtype
- Glandular differentiation or mucin production
- Thyroid transcription factor-1 positve in 70%
- Napsin-A positive in >90%
-
Squamous
- Morpholigcally identical to those outside the lung
- Sheets of cells with keratinisation or intercellular bridges arising from bronchial epithelium
- more likely to be cavitating than the others
-
Large cell
- <10% of all lung cancers
-
Adenocarcinoma
Which subtypes of lung cancer are most associated with smoking?
Small cell and squamous
- ~100% of SCLC is associated with smoking
All lung cancer subtypes can occur in smokers
Who should be screened for lung cancer?
Not currently recommended in Australia
High risk patients
- Current smokers 55-80yrs old with >30pck/yr smoking Hx
- Ex smokers of <15yrs and 55-80yrs old
As per the National Lung Screening Trial in NEJM 2011
- 53,454 pts 55-74yrs with >30pck/yr smoking and no symptoms
- 3x annual LDCT vs 3x annual CXR, primary endpoint all cause mortality
- Annual screening decreased mortality by 20%, despite 96% false positive rate
- 27% of initial LDCT had a nodule >4mm
In which subtype of lung cancer is paraneoplastic syndrome most common? Is it exclusive to this subtype? What are the common syndromes and their natural history?
Common, especially in SCLC but not exclusive
PTH
- Mostly with squamous
ADH/ANP
- SIADH (classic for SCLC)
- Usually resolves within a month of chemotherapy
- Look for ANP if hyponatraemia doesn’t resolve with fluid restriction
ACTH (think SCLC)
- Usually with electrolyte disturbances rather than Cushing’s
- Usually resolves with chemo
- Can perform bilateral adrenalectomy if extreme
Skeletal/connective tissue
- Clubbing ~30%, HPOA 1-10% (think SCC)
- Neurologic-myopathic syndromes (think SCLC) ~1%
CNS
- Anti-hu, anti-CRMP5, ANNA-3
Anorexia, cachexia, immunosuppression, fever, weight loss
How are SCLC and NSCLC staged? Are they different? Why? What’s the mortality like for the two subtypes of SCLC?
Both require imaging and tissue sampling
NSCLC staged with TNM
- CTCAP first
- If mets then no PET. If no mets then PET
- PET upstages 20%, avoiding unnecessary surgery
SCLC staged with limited vs extensive disease
- CTCAP + MRIB +/- bone scan
- hepatic/adrenal disease common
- CNS involvement in 10% asymptomatic
- MRI spine in those with cord compression signs/symptoms for consideration of palliative resection/radiotherapy
Limited disease confined to a ipsilateral thorax within a tolerable radiation port
- median survival 12-20months, 5yr ~10%
Extensive disease overt metastatic disease by imaging or clinical exam
- median survival 7-11months, 5yr ~1%
Significant implication for survival and cure rates
Which lung cancers require surgical resection? What are the contraindications to curative lung resection in NSCLC?
Stage I-II NSCLC require resection if patient amenable and appropriate for surgery
IIIa NSCLC can be considered with mediastinal clearance in certain patients
Surgical resection not recommended in SCLC due to micrometastases even in early stage.
May be considered in clinical stage I when invasive mediastinal staging clear and with adjuvant chemotherapy
Contraindications to curative resection in NSCLC
- Extrathoracic metastases, metastases to supraclavicular node, contralateral lung/mediastinum
- SVC syndrome
- Malignant effusion
- Tamponade
- Tumour within 2cm of carina
- Involvment of main pulmonary artery
Is adjuvant chemotherapy of benefit in NSCLC? In which populations? Is any particular chemotherapy regimen or duration recommended?
Worsens outcomes in Ia
Possibly improves in Ib
Definitely improves in II-IIIa
- LACE study 5.4% improved survival at 5yrs with chemo + surgery compared to solo surgery
- No evidence of benefit to >4 cycles
- *Platinum based** but no particular regimen optimal
- *- Cisplatin or carboplatin** +/- other depending on subtype
- EGFR erlotinib or gefitinib
- ALK crizotinib
- If neither then bevacizumab (shouldn’t be used in squamous or CNS involement due to bleeding risk)
What are the rough 5yr survival rates associated with NSCLC?
What proportion of NSCLC present with metastatic disease? What is its median survival? What is the management of metastatic NSCLC?
~40% present with metastatic disease
Mean survival 4-6months
Symptom control very important
- *Chemotherapy** improves s**ymptoms, quality of life, and survival
- appropriate in ECOG <=2 with few comorbidities**
Look for specific mutation
-
EGFR
- gefitinib/erlotinib
- Doesn’t work if RAS present
-
ALK crizotinib
- mutually exclusive with EGFR
Platinum based first line
- cisplatin/carboplatin + either vinorelbine, paclitaxel/docetaxel, gemcitabine
- response rate ~30%
- increases meadian survival from 6 to 9 months
Addition of anti-VEGF (bevacizumab) improves survival
- HTN (predicts response), haemorrhage (especially in squamous or CNS), impaired healing, GI, skin, leukopoenias
Non-squamous has better outcomes with cisplatin + pemetrexed
Squamous has better outcomes with cisplatin + gemcitabine
What is the treatment for SCLC? Does it differ depending on staging? What are the median survival and 5 yr survival rates?
Surgical resection not recommended even in stage I disease due to prevalence of micrometastases
Chemotherapy
-
platinum based
- cisplatin/carboplatin + etoposide, ironotecan
- or cyclophosphamide, doxorubicin, vincristine if not tolerated
- Response rates ~80% but survival still abysmal (LD median 12-20months, 5yr 6-12%)(ED median 7-11months, 5yr ~1%)
Radiotherapy (60Gy in 30#)
- Standard part of induction in LD with good performance status
- Improves survival by 5% compared to sole chemo
- Better toxic profile with cisplatin + etoposide
- Prophylactic cranial given in complete response due to 100% 2yr CNS disease
Extended stage = palliative RTx and chemotherapy
What symptoms are characteristic of hyperventilation syndrome? What breathing patterns?
Dizziness, dry mouth, parasthesias in hands/feet, chest pain
Rapid, shallow, irregular breathing with frequent sigh breaths
When do respiratory symptoms tend to develop in myasthenia gravis? Is it a common presenting symptom?
Late in the disease process.
Very rare to present with respiratory weakness as the first symptom
What is the prevalence of asthma? Does disease severity vary within patients? What are the main risk factors for death?
10-12% adults
Usually each patient sticks within their own severity
Risk factors for death:
- Poorly controlled
- Poor compliance with ICS
- Previous near fatal asthma
- ICU admission or intubations
What are the main risk factors for developing asthma? What about triggers for those with asthma?
Risk factors
- Atopy the major one
- Those without unlikely to develop asthma
- Genetics
- Polygenic
- ADAM-33, DPP-10, ORMDL3, Arg-Gly-16 for decreased beta ag response, 5-lipooxygenase repeats for decrease leukotreine antagonist response
- Hygeine hypothesis
- Lack of exposure to infections pushes toward TH2 cell bias which is allergenic response
- Exposure associated with TH1 cell bias
- Obesity
- Independent risk factor for development
- Occupational
- Common, 10% young adults
- Suspect when symptoms abate on weekends and holidays
- Removal from exposure within 6 months usually results in complete resolution without airway damage
- Intrinsic
- ~10%
- Normal IgE and negative skin prick
- Usually more severe and persistent with later onset
Triggers
- Pollutants
- Allergens
- Activate mast cells with bound IgE
- Exercise
- Physical
- Cold air, hyperventilation, laughter, perfumes
- Infections
- Rhinovirus, coronavirus, RSV most common triggers of acute exacerbations
- Occupational exposure
- Drugs
- beta blockers, aspirin
Don’t make a difference
- diet
- GORD
- ACEI
What are the structural changes to the airway associated with asthma?
Epithelial shedding
- Loss of barrier function and exposure of sensory neurons
- Loss of enzymes for degrading inflammatory mediators
- Loss of relaxant factors
Thickening of basement membrane
- subepithelial type III and V collagen deposition
- feature of eosinophilia
- In severe the airway itself may be thickened, leading to irreversible narrowing
Oedematous and thickened airway wall
- especially in fatal
Mucous hypersecretion and plugging
- glycoproteins from increased number of goblet cells and plasma protein exudate
- Hyperplasia of submucosal glands in large airways
Vasodilation and angiogenesis
- VEGF involved
Airway smooth muscle hypertrophy/hyperplasia
- PDGF, endothelin 1
- Reduced response to beta agonism, likely resulting from uncoupling of receptors or chronic inflammation altering resting membrane potential
Altered neural regulation
- Secondary effect
- Reflexive cholinergic activation
- Inflammatory activation of sensory neurons
- Reflex cholinergic bronchoconstriction, release of inflammatory neuropeptidases
- Hyperalgesia
- Neurotrophin release, sensitising and proliferating
- Release of substance P
When might fractional exhaled NO (FENO) be useful in asthma?
NO is derived from airway epithelium and promotes dilation of blood vessels and airways
- vasodilation -> promotes oedema -> worsen obstruction
Measurement can be useful to determine compliance with ICS
- high NO implies active inflammation, which points toward non-compliant or not working
No convincing evidence that using NO to titrate ICS improves outcomes
What is the stepwise approach to asthma therapy?
Biologicals for severe asthma
Asthma type
Target
Molecule
Allergic asthma
IgE
Omalizumab
Eosinophiliac asthma
Il-5 or Il-5 receptor
Mepolizumab, benralizumab
- These monoclonal Abs are used in addition to ICS + LABA.
- In appropriately selected patients, mABs induce ~50% reduction in exacerbations
- Oral steroid sparing
- Modest improvements in lung function
Add on therapies for severe asthma
- Long term oral steroids should be avoided where possible
What do beta 2 agonists do? Do they affect inflammatory cells? What are their common side effects? Do patients develop tolerance? Are they safe?
Beta 2 receptors coupled via G proteins to adenyl cyclase, increasing intracellular cAMP
- relax SM, inhibit mast cells, reduce plasma exudate, reduce neural stimulation
- inflammatory cells rapidly downregulate their receptors, so little effect on AHR
SABAs
- 3-6hr duration
- Increased use indicates poor control
LABAs
- >=12hr duration
- Use without comcommitant ICS worsens outcome (doesn’t treat underlying inflammation)
- Improve control and reduce exacerbations when added to ICS
Side effect mainly tremors, mainly in the elderly
Large reserve of beta 2 receptors in smooth muscle means even with downregulation they’re still effective
- less so with mast cells, where ICS helps counteract downregulation
When is theophylline used in asthma? How does it act? What are its common side effects?
- Non-selective PDE inhibitor relaxing smooth muscle
- Used rarely as an adjunct when on maximal other medications
- Arrhythmias associated with higher levels >10mg/L - rarely observed below this
- Most commonly nausea, vomiting, headaches
- Largely inactivated by the liver
When are OCS required in asthma? How should they be dosed? What percentage of patients require maintenance treatment? What are their side effects?
During moderate-severe exacerbations
- oral equivalent to IV
- 30-45mg daily for 5-10days, no taper required
~1% require maintenance
- should be titrated to the minimum dose required to suppress symptoms and avoided when possible!
Multiple side effects
- truncal obesity, bruising, OP, diabetes, HTN, gastric ulcers, proximal myopathy, depression, cataracts
- monitoring of bone density allows for treatment with bisphosphonates
When are antileukotreines used in asthma?
May be added in those not controlled on low dose ICS
- less effective than LABA
Inhibit cyc-LT1 receptors
LUNG VOLUMES
What shifts the oxygen dissociation curve left or right?
What is aspirin sensitive asthma? Does it have a defined phenotype? How is it managed?
Called aspirin exacerbated respiratory disease (AERD)
7% of asthma sufferers get worse with COX inhibitors
- 14% with severe asthma
- need to ensure it’s not to a single agent, as that may be IgE mediated allergy
Phenotype (clinical diagnosis the rule)
- perennial rhinitis
- nasal polyps
- non atopic
- late onset
80% have upper or lower airway reactions to alcoholic drinks
NSAID reaction
- 30mins-3hrs after ingestion
- dose related, can be as bad as fatal
- urticaria/angioedema in 15%
Pathophysiology
- due to baseline dysregulation in arachidonic acid metabolism with balance shifted toward leukotrienes
- primary cell producing it is bronchial mast cells
- COX-1 inhibition exaggerates the dysregulation, thought to be by reducing PGE2 which is a ‘brake’ on leukotrienes
Triggered by COX inhibitors but present even in their absence
Safe to use COX2 inhibitors
- some exquisitely sensitive people may be triggered by them
Management
- Asthma as per usual guidelines
- COX-1 avoidance unless being desensitised
- leukotriene antagonists vastly improve airway symptoms and exacerbation rate
What is the natural history of asthma in pregnancy?
1/3 get better, 1/3 stay the s with mod/sev asthma
Prednisone better than prednisolone as foetal liver can’t convert prednisone to prednisolone
Breastfeeding safe
What percentage of asthmatics smoke? How bad is it?
~20%
More severe disease, more frequent admission, faster decline in PFTs, higher risk of death
Interferes with anti-inflammatory action of corticosteroids, requiring higher doses
Cessation improves PFTs and reduced steroid resistance
What is hypersensitivity pneumonitis? Name some of the pathogens that cause it
Exposure and sensitisation to an antigen leading to inflammation of the alveoli and small airways.
Sensitisation is necessary but not sufficient for developing HP; many sensitised individuals don’t develop HP.
TH1 inflammatory pattern with emerging evidence of TH17 subsets involved
Fungal, bacterial, mycobacterial, bird-derived, and chemical causes.
What is the treatment for hypersensitivity pneumonitis? Is any pharmacotherapy helpful?
- Antigen removal the mainstay
- Corticosteroids may help in decreasing duration of symptoms but don’t change outcomes
- 0.5-1mg/kg for 1-2/52 followed by 2-6/52 taper
- Fibrotic changes associated with chronic HP may be irreversible
What are the diagnostic criteria for acute eosinophilic pneumonia? Who is the prototypical patient? Is it associated with peripheral eosinophilia? What does HRCT show?
- Males 20-40 with no history of asthma
- Not associated with peripheral eosinophillia, not typically not until 7-30 days
-
HRCT is always abnormal or reticular opacities with small pleural effusions
- characterised by high pH with marked eosinophilia
- bilateral groundglassing
What are the general causes of an increased A-a gradient?
- *R->L intrapulmonary shunt**
- CCF
- ARDS
- Pneumonia
- *V/Q mismatch**
- PE
- Atelectasis
- Pneumonia
- Obstruction
- Pneumothorax
- *Alveolar hypoventolation**
- ILD
- *Hypoventilation**
- Neuromuscular disorders
- CNS disorders
What is methaemoglobinaemia? Why does it matter?
- *Ferric (3+) iron in heme**
- due to oxidation of Fe2+ -> Fe3+
- Unable to bind O2
- Affinity of the remaining ferrous heme groups is increased
- Functional anaemia!
- *Congenital**
- May be asymptomatic
- Cyanotic, slate blue skin and mucous membranes
- *Acquired**
- Drugs usually
Acquired treated with cessation of the cause and methylene blue or hydroxycobalamin.
Congenital best treated by avoiding medications that induce methaemoglobin
What are the risk factors for pulmonary embolism? What are the most common mutations causing prothrombotic states?
Prothrombotic states
- Common
- Factor V leiden: causes resistance to activated protein C
- Prothrombin gene mutation: increases plasma prothrombin concentration
- Antiphospholipid syndrome - most common acquired cause of thrombophilia
-
Rare
- Deficiency of: antithrombin, protein C, protein S
What is Well’s Criteria (wells score)?
d-dimer increased in those >70yrs
- not affected by smoking
- false positives in: sepsis, AMI, cancer, pneumonia, post-operative state, 2nd/3rd trimesters of pregnancy
What is McConnell’s sign on TTE?
Describes a regional pattern of acute right ventricular dysfunction - Hypokinesis of RV free wall with normal or hyperkinetic RV apex.
Best known indirect sign of PE
What percentage of adult asthma/COPD is a result of occupational factors?
15 - 20%
What are the syndromes associated with organic and inorganic dusts?
What is the risk of lung cancer in smokers with asbestos exposure? Is mesothelioma associated with smoking?
60 x baseline risk, synergistic risk
Mesothelioma doesn’t appear related to smoking. Even short term exposures of asbestos in the distant past can be associated with development of mesothelioma
Does silicosis affect risk of infection? How? Which? Does it have any rheumatological associations?
Silica is toxic to alveolar macrophages
Result in higher risk of infections requiirng these as primary defence
- **TB, atypical mycobacteria, fungi
- Treatment of latent TB is longer**
May develop connective tissue disorder
- *- RA or systemic** sclerosis
- Caplan syndrome is the combination of seropositive RA with pneumoconiotic nodules in the lung
- First described in coal workers
How does berylliosis present? How does it differ from sarcoidosis?
May present with acute pneumonitis
More commonly it presents with a chronic granulomatous disease similar to sarcoidosis
- Differs by evidence of specific cell mediated response to beryllium
- Delayed hypersensitivity reaction
Beryllium lymphocyte proliferation test
- Compares in vitro proliferation of lymphocytes from blood or BAL in the presence of beryllium salts to unstimulated cells
- Usually measured by uptake of radiolabelled thymidine
In beryllium sensitised individuals non-caseating granulomas or monocytic infiltration on lung biopsy establishes the diagnosis
What is diacetyl used for? With what is it associated?
Used to provide butter flavour to popcorn
Has been associated with bronchiolitis obliterans
What characterises COPD? What is its prevalence? What are the COPDX guidelines?
Progressive chronic airflow limitation which is not fully reversible
5th leading cause of death worldwide, almost equal burden between genders
Prevalaence by spirometry
- 7.5% in >40yrs
- 29% in >75yr
Prevalence by symptoms
- 30% describe wheeze, 25% SOBOE in past 12 months
COPDX
- Confirm diagnosis
- Optimise function
- Prevent deterioration
- Develop support
- X - manage exacerbations
What defines a COPD exacerbation? What are the underlying aetiologies? Who ought to be hospitalised?
No universally accepted definition
Change in symptoms out of keeping of their normal variation
- Dyspnoea
- Purulence
- Volume
No objective diagnosis in 50%
Respiratory infection (50-70%)
- Bacterial: h influenzae, s pneumo, m catarrahalis, mycoplasma, chlamydia; pseudomonas, staph in more advanced
- Viral: influenza, rhinovirus, RSV, metapneumovirus
Non-infectious:
- Pollution
- PE: ~1 in 4 exacerbations without clear cause
- CCF
- Pneumothorax
- Sedation
- Anxiety
Hospitalisation
- Failed OP management
- Unable to manage at home due to breathlessness: Mobilising, sleeping, eating
- Severe comorbidities
- Confusion
- Worsening gas exchange
- New arrhythmia
What are the risk factors for developing COPD?
Cigarettes
- Accounts for >95% burden of diease
- Only 10-20% develop clinical disease
- ~50% have some airflow limitation
Organic/inorganic dusts (cadmium, coal, cotton, cement, grain)
Smoke from cooking
Bronchial hyperresponsivenes
Genetics
- alpha 1 antitrypsin
- 1-2% of population
Infections/mucous hypersecretion
What is the stepwise management of stable COPD? Do pharmacologic therapies improve survival or slow decline in FEV1?
Pharmacologic therapies useful in reducing symptoms, improving QOL, and reducing exacerbations but not improving survival or slowing decline of FEV1
Mild (FEV1 >60%)
- SABA only: terbutaline, salbutamol
Moderate (FEV1 <60%)
- Anticholinergic (LAMA): ipratropium; tiotropium, glycopyrronium, aclidinum, umeclidium
- LABA: salmeterol, eformeterol
- VLABA: indacterol, olodaterol
- Reduced dyspnoea, improved QOL, reduced exacerbations
- Longer acting and newer medications probably better than salmeterol/eformeterol
- Some concerns about CV effects of tiotropium, with risk/benefit usually falling on benefit side
- Multiple combination medications: ICS + LABA, LAMA + LABA/VLABA
Mod/sev (FEV1 <50%) with frequent exacerbations
- Addition of inhaled corticosteroids (ICS) reduces symptoms, improves QOL, reduces exacerbations
- Combination with LABA may slow decline in FEV1
- SEs: increased pneumonia, easy bruising, cataracts, ?OP
- budesonide doesn’t seem to increase pneumonia, fluticasone dose
Others
- Theophylline: Modest bronchodilator effect. New data indicating low dose may have anti-inflammatory and immunomodulatory effects
- PDE4 inhibitors: Anti-inflammatory with moderate fficacy as add on to LABA. Not TGA approved
- Mucolytics: May improve clearance and decrease exacerbations. High dose NAC shows promise
Severe with respiratory failure
-
Continuous oxygen therapy: Improves mortality
- PO2 <55 or <60 with pulm HTN or RHF
- Only beneficial if used >=16hrs a day
- Portable oxygen not shown to have mortlaity benefit
Beta blockers are safe in COPD
-
LVRS: Rarely in Australia. Predominant upper lobe emphysema benefit the most.
- Overall early increased mortality with no change at 2yrs, with increased exercise capacity
- Bronchoscopic techniques: valves, plugs, steam, airway bypass
- Transplant: Young with severe disease casuing significant morbidity
Additional
- QOL: Questionnaires, self reported dyspnoea
- Exercise tolerance
- Bone density: Significant number of mod/sev COPD population have OP, and do worse
What tend to be the causes of death in COPD? How does pulmonary hypertension and RHF affect this?
Generally don’t die of COPD, even in severe disease.
Top are CVS and cancer
What are the distinctive clinical and radiological findings in legionella pneumonia?
- *pneumophila** = cooling towers and humidifiers
- *longbeachae** = potting mix
Risk factors
- older, smokers
- immunocompromised
- chronic cardiac, resp, renal disease
- Diarrhoea, neurologic findings,* and temp >39
- *Hyponatraemia,** elevated LFTs, haematuria
Distinctive rounded, nodular opacities
- Especially in the immunosuppressed
Management
- azithromycin, moxifloxacin
What are the risk factors for developing non-tuberculous mycobacterial infection?
- Underlying lung diseases
- Bronchiectasis, pneumoconiosis, COPD, CF, alpha 1 antitrypsin deficiency, primary ciliary dyskinesia
What is the pattern of resistance as you progress through the airway generations? Which have tracheal rings?
First 7 generations have cartilage rings
What are the mechanisms of small airway narrowing?
What are the defining characteristics of asthma?
Air flow variability
- diurnal and between day variability
- gold standard for diagnosis of occupational asthma is day to day variability with bad days while at work (measured with peak flow)
Reversibility
- pre and post bronchodilator
- >12% and 200mL
Airway tests of airway hyperresponsiveness
- direct = metacholine test, sensitive BUT NOT specific. Good to look for perisistent airway remodelling
- indirect = mannitol, hypertonic saline. good measure of the inflammatory component. specific BUT NOT sensitive
What’s the definition of bronchiectasis? What’s it caused by?
Abnormal irreversible bronchial dilation
- HRCT gold standard
>=1 dilated bronchi
- internal luminal diameter exceeding diameter of adjacent arteries
Clinically characterised by small airway obstruction,
Causes - see list, but think ‘chronic infection and airway destruction’
What is constrictive bronchiolitis? Pathology? Causes? Clinical?
Also known as obliterative bronchiolitis and bronchiolitis obliterans
Pathology
- peribronchiolar fibrosis
- cicatrization of the bronchiolar lumen
- fibrosing inflammatory process surrounding the lumen
- extrinsic compression and obliteration of the airway
Causes (result of immunological injury)
- Allograft (lung, heart-lung, SCT)
- Postinfectious
- Connective tissue
- Inhalational injury
- Drugs
Clinical
- Severe, progressive small airway obstruction with dynamic hyperinflation
- CXR is normal or nonspecific
- On HRCT mosaic decreased attenutation. Evidence of gas trapping variability between neighbouring airways on expiration
What are the defenses against respiratory infection?
- Upper airway reflexes
- Cilia
- nonspecific and specific. e.g. smoking vs cilia diskinesis syndrome
- Mucous
- nonspecific and specific. e.g. chronic bronchitis from smoking vs CF
- Cough
- Immune
What proportion of those with COPD who have a viral infection develop secondary bacterial infection over the next week?
36% - Experimental infection of COPD patients with rhinovirus induces bacterial infection
Coinfection causes greater decline in lung function and prolonged hospital stay
What is a halo sign on HRCT? What does it represent?
- *Groundglass opacity** surrounding a pulmonary nodule/mass, representing haemorrhage
- *- Typically in fungal infection**
- *- May represent neoplasm or vasculitis**
What are the problems with empiric treatment, especially in opportunistic infections?
What is the yield on bronchoscopy in immunocompromised patients presenting with possible pneumonia?
Use of bronchoscopy in immunocompromised:
- diagnosis in 65%
- sensitivity 75% and spec 86%
- 80% accuracy
What is galactomannan?
Found in the cell wall of aspergillus
- antigen can be done in BAL or blood. Better in BAL
- Sens 79%, spec 86%, accuracy 89%
- Get false positives in
- contamination
- tazocin, amoxicillin, plasmalyte*
Corss sensitive with:
- penicillium, alternari, cladosporium, trychphyton, histoplasmosis, cryptococcus
- *Get false negatives with antifungal treatment**
- sens 52% vs 89%
What CT finding is characteristic of cystic fibrosis?
- Bronchiectasis that spares the peripheries
- Mosaic attenuation
Is oestradiol related to pseudomonas? How?
Oestradiol levels are related to alginate production of pseudomonas
- - testosterone not, placed on OCP not
Exacerbations correlate with the cycle phase in patients with cystic fibrosis
How is OSA classified?
CV risk begings to climb around 30 events/hr
What is the physiology underlying Obesity Hypoventilation Syndrome (OHS)?
What are the different types of Central Sleep Apnoea (CSA)? What are some examples of each subtype?
What is a secondary pulmonary lobule?
What are the key findings on HRCT in ILD?
- Honeycombing
- Traction bronchiectasis
- Reticulation
What is the best predictor of mortality on PFT in IPF? What’s a significant change in FVC or DLCO?
Does 6MWT have a role in measuring chane in disease severity?
FVC trends predict mortality better than other parameters
10% change in FVC or 15% in DLCO is considered significant
6MWT has no role in measuring change in disease severity
What are the diseases associated with specific BAL findings? When is it indicated?
Not indicated in the majority
- Most importantly to exclude hypersensivity pneumonitis
When should lung biopsy be performed for ILD? Which type of biopsy?
What is usual interstitial pneumonia (UIP)?
Describes a histopathological pattern on biopsy
- *- heterogeneity!**
- hallmark is fibroblastic foci (demonstrate ongoing damage)
Also used to describe a radiological pattern on HRCT.
Especially absence of groundglass
Causes
- IPF
- Asbestosis
- CT related ILD
Why does IPF need to be differentiated from NSIP?
Different prognosis and treatment options
Basically if IPF and appropriate to should refer for transplant
What did the ASCEND trial in IPF show?
NOT a CURE, slows down decline of RFT but minimal QoL benefit
What did the IMPULSIS trial in IPF show?
RCT for nintedanib
What is interstitial pnuemonia with autoimmune features?
ILD with features of CTD that don’t meet specific classification criteria for a given autoimmune disease
What particular infections are those with lung transplant predisposed to?
Early
- Pneumonia very common. 66% in one series
- Given prophylactic broad spectrum antibiotics in the initial days
- Mediastinitis more common than in cardiac transplant
Middle
- Incidence of CMV 75-100% if either donor or recipient is seropositive
- Most severe in cardiac and lung transplant for unknown reasons
- High incidence of HSV pneumonitis
Late
- PCP incidence high in lung and cardiac transplant
What is alpha-1 antitrypsin? What does it do?
What are the phenotypes of deficiency? With what other diseases is deficiency associated?
Glycoprotein in the family of serine protease inhibitors, controlling inflammatory cascades
- Produced in hepatocytes
Inherited in an autosomal co-dominant pattern
Phenotypes
- Normal
- Normal alleles are classed M, normal genotype = MM/PiMM
- Deficient
- Plasma AAT <35% of normal
- Most common deficient allele associated with emphysema is Z, carried by 2-3% of Caucasians
- Null
- No detectable AAT protein
- Least common, highest risk of lung disease, no risk of liver disease
- Dysfunctional
- Produce a normal quantity of protein that is defective
- Z and M(malton) the two common ones
Hepatic Disease
- Chief cause of liver disease in children
- Z and M(malton) alleles most well known to confer risk, autosomal recessive
- Due to accumulation of dysfunctional AAT protein in the hepatocyte, seen as intrahepatocyte inclusions with +ve acid Schiff stain
- 10-15% of newborns and adults develop hepatic disease
- Most are PiZZ
Pulmonary Disease
- Loss of function and imbalance between neutrophil elastase and the elastase inhibitor AAT. Protects against proteolytic degradation of elastin
- Cigarette smoking and infection increase elastase production, therefore greatly increase risk of progression
- Polymers of Z antitrypsin are chemotactic to neutrophils
- Deficiency = early onset emphysema.
- Bullous changes more prominent in bases than apices. Can be apical or diffuse in 1/3
- Test in persistent obstruction despite bronchodilator, early onset emphysema in non-smoker, and family history of emphysema/liver disease
Other
- Necrotising panniculitis; vasculitis, psoriasis, urticarial, angiodema
- Aneurysms and arterial fibromuscular dysplasia
- IBD
- GN
- ANCA +ve vasculitis
What underlies hepatopulmonary syndrome?
- Systemic vasodilation resulting in V/Q mismatch
-
Presentation
- orthodeoxea: decreased O2 saturation when upright, increased when lying
- platypnoea: dyspnoea when upright, better when lying flat
- Above due to dilation resulting in worsening of V/Q mismatch when sitting upright (blood pools to poorly ventilated bases)
What are the Fleischer Society Guidelines for incidental pulmonary nodules? What clinical and radiological features predict malignancy in pulmonary nodules?
- Clear growth = resect
- Groundglass = annual CT (higher risk of malignancy but usually slower growing)
- Stable over 2yrs without groundglassing = discharge
- PET in >=1cm with intermediate risk. Sensitivity 95%, specificity 75%
High risk features
- age > 60, current smoker, corona radiata or spiculated nodule margins
- volume doubling of mass 20-100 days, upper lobe calcification, spiculation.
What features carry the highest likelihood ratio of malignancy?
- >16mm cavity wall thickness
- spiculated edge
- Age > 70
- size > 3cm
- History of other malignancy
- Smoking > 40 ciggs/day
What carries a 0 likelihood ratio of being malignant?
- growth < 7 days and no growth > 465 days
- benign pattern of calcification
What patient factors predict EGFR mutation in NSCLC? What can you do about it?
Mutation present in 15% of lung adenocarcinoma
- Women>men
- Non-smokers>smokers
- Asian>non-asian
EGFR TKIs approved for 1st line treatment of EGFR +ve NSCLC - shown to be equivalent to chemotherapy
1st generation: erlotinib, gefitin and 2nd gen Afatinib
- Acne, diarrhoea, rare: pneumonitis/hepatitis
3rd generation: osimertinib (less rahs, designed for drug resistance)
What are the findings indicating mild/moderate, severe, or life threatening acute asthma? Go through the algorithm for approach to acute asthma, including secondary severity assessment
What clinical sign would indicate diaphragmatic paralysis?
Paradoxical movement of the abdomen inward with inspiration
Bilateral -> has mod-sev restriction of TLC
This gets worse on lying down
- decrease in VC of 30-50% when supine supports the diagnosis
What is the Bohr effect?
CO2 and acidosis preferentially stabilise the deoxygenated form of haemoglobin, resulting in release of oxygen from haemoglobin
This is desirable in the tissues
What is the mutation associated with familial pulmonary arterial hypertension (PAH)?
- *Bone morphogenetic protein receptor type-2 (BMPR2)**
- BMPR2 inhibits smooth muscle proliferation and induces apoptosis
- abnormalities -> proliferation of pulmonary vascular cells -> remodelling
- mutation confers 15-20% chance of developing PAH during lifetime
- accounts for 70-80% of familial PAH
What is the most sensitive test in one suspected to have active pulmonary tuberculosis?
Sputum culture
What are the Light Criteria for differentiating transudate from exudate?
Pleural fluid:serum protein >0.5
Pleural fluid: serum LDH >0.6
Pleural fluid LDH >2/3ULN of serum LDH
If all false then transudate
If >=1 true then exudate
What proportion of those post lung transplant develop brochiolitis obliterans (constrictive bronchiolitis)? Risk factors?
50% at 5yrs
75% at 10yrs
Major impediment to long term graft and patient survival
Hard to demonstrate on transbronchial biopsy
- decline in FEV1 used as a surrugate marker
Risk factors
- acute rejection the major one
- GORD or silent aspirations may contribute in some
Retransplant the only definitive management
- systemic immunosuppression doesn’t really work
- aerosolised cyclosporine has shown potential efficacy
- fundoplication to control reflux has been associated with improved PFTs in some with BOS
What’s the classic presentation of allergic bronchopulmonary aspergillosis (ABPA)? What’s the pathognomonic chest xray finding?
Virtually all have long-standing atopic asthma
Classically in 4th-5th decade
- chronic asthma, recurrent pulmonary infiltrate, and bronchiectasis
- long Hx of intermittent wheezing with evolution into more chronic and symptomatic: fever, chills, pulmonary infiltrates, productive cough
- *Segmental infiltrate or atelectasis in the upper lobes**
- branching, finger-like shadows of mucoid impaction of dilated central bronchi are pathognomonic.
What is pulmonary alveolar proteinosis?
Rare condition characterised by alveolar accumulation of surfactant
- several causes
- *Autoimmune in 90%**
- antibodies against GM-CSF -> no activation of alveolar macrophages -> accumulation of surfactant
- *Presentation varies considerably**
- everything from asymptomatic and spontaneously remiting to severe respiratory failure
- *HRCT**
- crazy paving pattern*
- *Lavage**
- grossly turbid exudate
- periodic acid-Schiff positive*
Whole lung lavage the most effective therapy
With which genetic mutation is lymphangioleimyomatosis associated?
Occurs in ~30% of women with tuberous sclerosis
- TSC1 encodes hamartin, TSC2 encodes tuberin
Sporadic LAM also associated with mutation of tuberous sclerosis genes
Characterised by smooth muscle cell infiltration and cystic destruction of the lung
- express markers of smooth muscle and melanocytic differentiation
Presentation
- progressive SOBOE, recurrent pneumothoraces, abdominal/thoracic lymphadenopathy, abdominal tumours
- angiomyolipomas, lymphangiomyomas
May present with just abdominal disease, mimicing lymphoma/ovarian cancer
- very rare
Rx: sirolimus
When is CTPA of greatest accuracy? When is V/Q helpful as an addition?
- Most sensitive for the main and lobar pulmonary arteries
- decreases in the segmental and sub-segmental vessels
- Normal V/Q rules out pulmonary hypertenion due to chronic thromboembolic disease
What’s tracheomalacia? What kind of airflow obstruction does it cause?
Variable intrathoracic obstruction
What are the two types of alveolar cells and what do they do?
Type 1 = squamous
- cover 90-95% of alveolar surface
- involved in gas exchange
- unable to replicate, susceptible to toxic insults
Type 2 = surfactant secreting
- <5% of alveolar surface
- can divide and differentiate into type 1 cells if lung tissue is damaged
When is elevated PaCO2 and low PaO2 expected in COPD?
PaO2 usually remains near normal until FEV1 <50% predicted
- ventilation-perfusion mismatching accounts for essentially all of the reduction
PaCO2 usually not elevated until FEV1 <25%
- may not even occur then
Which disorders cause predominant upper zone vs lower zone fibrosis?
- *Upper (think allergens)**
- hypersensitivity pneumonitis
- coal worker’s pneumoconiosis (+ progressive massive fibrosis)
- silicosis
- sarcoidosis
- tuberculosis
- histiocytosis
- ankylosing spondylitis (rare)
- *Lower (think immune and drug)**
- IPF
- CTD related
- Drug: amiodarone, bleomycin, methotrexate
- Asbestosis (fibres are heavy)
What are the main differential diagnoses for cavitating lung lesion?
- Abscess
- s aureus, klebsiella, pseudomonas
- Squamous cell lung cancer (others can do but less common)
- Tuberculosis
- Granulomatosis with polyangiitis (GPA, Wegener’s)
- Rheumatoid arthritis
- Other infection
- aspergillosis, histoplasmosis, coccidiodomycosis
What is Kartegener’s Syndrome?
-
Primary ciliary dyskinesia
- respiratory tract (including eustachian tube and inner ear), fallopian tube, flagella of sperm = infertility
- Rare autosomal recessive disorder resulting in defective outer/inner dynein arms (give cilia motility)
- Only known as Kartagener’s when associated with situs inversus
- ~50% of the time
What are the presentations of the altitude related disorders?
Descent is a required part of management of all
Acute mountain sickness
- generally self limiting
- headache, nausea, fatigue
- starts above 2500m, develops gradually over 6-12hrs, may last days
- acetazolamide to prevent, gain altitude at <500m/day
High altitude pulmonary oedema
- classic pulmonary oedema features
- nifedipine, dexamethasone, acetazolamide, PDE5 inhibitors
- oxygen if available
High altitude cerebral oedema
- dexamethasone
What makes up surfactant?
Dipalmitoyl phosphatidylcholine
Which form of asbestos is most dangerous?
Crocidolite (blue)
What is Combined Pulmonary Fibrosis and Emphysema Syndrome?
Usually patients have either disorder predominating
- as they have dissimilar physiologic effects
- emphysema: reduced recoil, increased compliance, increased volumes, reduced maximal exp flow
- fibrosis: increased recoil, decreased compliance, reduced volumes, normal/increased maximal exp flow
Features
- male (90%), smoking history (98%), dyspnoea, pulmonary hypertension
- upper lobe emphysema
- lower lobe fibrosis, predominance of UIP
- relatively normal spiro/lung volumes with severely impaired DLCO
Diagnosis
- consensus definition doesn’t exist
- HRCT showing typical features + above hx/RFs
Complications
- pulm HTN more frequent and severe than in IPF alone
- significantly increased risk of lung cancer, with worse outcomes if they get it
Prognosis
- median survival 2-8yrs
- if pulmn HTN 1yr survival 60%
- seem to have similar outcomes to pulm fibrosis alone
Management
- smoking cessation
- lung transplantation the only definitive
What are the commonly isolated pathogens in bronchiectasis?
Viral
- coronavirus, rhinovirus, influenza
Bacterial
- haemophilus influenzae
- moraxella catarrhalis
- staph aureus
- pseudomonas aeruginosa
- strep pneumoniae
What is the recommended diet for cystic fibrosis?
High calorie, high fat
- used to be low fat to reduce steatorrhoea
- now recognised important to get enough fat intake
Supplementation with vitamin A, D, E, K
90% need pancreatic enzymes
Which supplements increase the risk of lung cancer in smokers?
Beta carotene and vitamin E
What is graft survival like comparing the different transplanted organs?
What’s the definition of Acute Respiratory Distress Syndrome (ARDS)?
Within 1 week of a known insult, or new/worsening respiratory symptoms
Bilateral opacities not explained by effusions, collapse/consolidation, nodules
Hypoxia not explained by CCF or overload
- do a TTE in those with no risk factors for ARDS to look at LV function
Phases
- acute exudative phase
- fibrosing alveolitis (days to weeks after)
- recovery phase
Management
- low volume ventilation (6mL/kg ideal bodyweight)
- prone ventilation decreases mortality (PROSEVA study NEJM 2013; 23.6% vs 41% 90 day mortality proning 16hrs/day vs not)
- supportive care
- nothing works to fix it
What is eosinophilic bronchitis?
Not synonymous with asthma
- lacks airway hyperresponsiveness
- have the same frequency of atopy as the general population
Causes a steroid responsive chronic cough
- responds to oral or ICS
Diagnosed with >2.5% eosinophils in induced sputum
What did the FLAME trial of ICS/LABA vs LAMA/LABA in COPD show? What about the LANTERN study?
Summary
- LABA/LAMA > LABA/ICS
- Fewer exacerbations in the LABA/LAMA group
LANTERN study in Int J Obstruct Pulm Dis 2015
- looked at the same population with <=1 exacerbation in the last 12 months
- showed non-inferiority
What markers can help prognosticate in COPD?
- *BODE** Index - higer the score the worse prognosis
- Better predicts mortality, hospitalisation, survival post LVRS
- *BMI -** < 21 = 1 point
- *Obstruction -** FEV1
- *Dyspnoea -**on dyspnoea scale score
- *Exercise -** distance walked in 6 minutes
What is acute interstital pneumonitis (AIP)?
Also known as Hamman-Rich syndrome
Rapidly progressive non-infectious ILD
- the only acute process of the idiopathic interstitial pneumonias
- effectively looks like and follows a similar course to ARDS
Typically occurs in middle aged adults without pre-existing lung disease
- presents with productive cough, fever, dyspnoea that often requires mechanical ventilation within weeks of onset
Radiology - same as ARDS
What is the pulmonary embolism severity index (PESI)? What are the risk stratifying parameters in acute PE?
PESI useful to identify low risk patients suitable for outpatient management
Imaging
- RV dysfunction due to PE = 2x mortality
- RV thrombus = ~doubled mortality
- Co-existent DVT = 2x mortality
Laboratory
- low BNP predicts uncomplicated course
- raised troponin OR 5 for short term mortality
- hyponatraemia <130 OR 3 for mortality
- lactate >2 predicts mortality
Who should be tested for inherited thrombophilia?
Routine screening for those presenting with VTE not recommended
Family history +ve
- 1st degree relative with VTE <45yrs
- protein C, S, antithrombin III deficiency, factor V leiden, prothrombin gene mutation
Family history -ve
- <45yrs and recurrent VTE = thrombophilias and APLS
- thrombosis in multiple or unusual sites (portal*, hepatic*, mesenteric, cerebral veins) = thrombophilias and APLS
- warfarin induced skin necrosis = look for protein C deficiency (rarely protein S or FVL)
- arterial thrombosis = look for APLS
* = also test for JAK2 mutation and PNH
At what weight should NOACs be avoided?
BMI >=40 or weight >120kg
- lack of data to guide dosing
When should those with pulmonary embolism (PE) be thrombolysed?
PE with hypotension (‘massive’) = thrombolyse
- RR 0.20 for mortality
- 9.4% vs 19% risk of recurrent VTE or death
PE without hypotension = don’t thrombolyse
- no difference in mortality
PE without hypotension but with RV dysfunction and elevated troponin (‘submassive’) = not standard
- no difference in mortality (Meyer et al NEJM 2014)
- reduced cardiovascular collapse but increased bleeding
Which medications are associated with development of group 1 pulmonary hypertension?
What are the important prognostic factors in pulmonary hypertension?
Poor prognosis
- male
- CTD
- older
- NYHA class
What are the two types of endothelin receptor and what do they do?
- *Endothelin-1 has A and B receptors**
- levels increased in plasma and lungs in PAH
- levels correlate with disease activity and mortality
Both present on smooth muscle
- activation -> vasoconstriction
Endothelin B present on vascular endothelium
- activation -> NO release and vasodilation
What are the mandatory minimum investigations on diagnosis of bronchiectasis?
- FBE + immunoglobulin level
- Culture of airway secretions, including for non-tuberculous mycobacteria
- if first isolation of pseudomonas attempt eradication
- Spirometry
- Serological tests for aspergillus
What should be the approach to respiratory infections in cystic fibrosis?
- *Routine sputum MCS 3 monthly to guide therapy**
- base antibiotic choice on prior isolates with exacerbations
- *Pseudomonas aeruginosa**
- initial isolation -> attempt to prevent colonisation with aggressive antibiotic therapy
- >70% of adults chronically infected, once mucoid phenotype develops impossible to eradicate
- mucoid -> worsening lung function
- in chronic infection antibiotic susceptibility doesn’t affect outcome
- chronic azithromycin beneficial (decreases exacerbations, increases FEV1)
- contact precautions and masks for healthcare workers; patients shouldn’t congregate together
- *Burkholderia cepacia complex**
- chronic infection -> accelerated decline in lung function
- usually multi drug resistant
- contraindication to lung transplantation (due to worse outcomes)
- *Non-tuberculous mycobacteria**
- MAC not associated with worse transplant outcomes
- Abscessus associated with worse transplant complications
- only treat is symptoms, worsening lung function, or nodular infiltrates/cavitating disease
- *Antibiotics**
- one antibiotic for each organism isolated on culture
- two antibiotics if possible for each gram -ve isolated
- no role for routine tune-ups
- no role for chronic/cyclical antibiotics other than azithromycin
What are the two biggest predictors of cigarette dependence?
- Smoking within minutes of waking predicts stronger dependence
- Increased number of cigarettes smoked per day predicts stronger dependence
Is there any evidence to support reduction of number of cigarettes smoked per day as a method of smoking cessation?
NO
What are primary and secondary spontaneous pneumothorax (PSP; SSP), what are their risk factors and rates of recurrence? Management?
- *Primary =** no underlying lung disease. Recurrence 25-50%
- Smoking the biggest: >22cpd -> 102x RR; <12 cpd 7x RR
- FHx in 10%
- others: Marfan’s, homocystinuria, thoracic endometriosis
- *Secondary =** underlying lung disease. Recurrence >50% (depends on aetiology)
- usually more dangerous than PSP due to decreased reserve. M**ortality 16%
- COPD responsible for 50-70%**
- 5-10% of PCP will get SSP
- up to 20% of CF >18yo will develop SSP
- others: TB, lung cancer, necrotising pneumonia, ankylosing spondylitis, LAM, ILD, histiocytosis, CTD
- *Management** (2cm (at the level of hilum) the cutoff for small vs large; symptoms more important than size)
- SP of any size with significant dyspnoea -> active intervention
- SSP of any size should be intervened upon (only 60% spontaneously close)
- needle aspiration equivalent to large bore + reduced admission rates and LOS
- never repeat needle aspiration unless technical difficulties caused it to fail (insert small bore drain rather than repeat)\
- *Recurrence prevention**
- thoracotomy + pleurectomy -> 1% recurrence
- VATS pleuradesis -> <5% recurrence
- Talc pleuradesis -> 5-8% recurrence + 2% risk of ARDS
- smoking cessation
What factors are associated with poor outcome in pleural infection?
RAPID score
What did the REDUCE trial show with regard to use of glucocorticoids in exacerbations of COPD?
RCT of 5 days vs 14 days of 40mg prednisolone in those presenting with acute exacerbation of COPD
- 314 patients, 92% admitted to hospital
5 days non-inferior to 14 days
- predefined non-inferiority criterion was upper limit of 15% increase in re-exacerbation rates
- no difference in time to death; combined exacerbation, death, or both; recovery of lung function
What is the concept of ‘frequent exacerbators’ in COPD?
Phenotype is distinct as some with COPD are prone to frequent exacerbations
- Generally defined as >=2 exacerbations per year
Rate of exacerbation in the past year predicts risk in the next year
Frequent exacerbations lead to more rapid decline of lung function, more rapid functional decline, greatest risk of AMI
Targets for interventions to reduce exacerbations
- LAMAs reduce exacerbations, most data for tiotropium
- LABA/LAMA superior to LABA/ICS for exacerbation prevention
- indacterol, vilanterol, olodaterol superior to salmeterol
- add ICS in those with significant reversibility or frequent exacerbations
- pneumonia risk least with budesonide
What is the significance of OSA in those with COPD?
Those with both are more likely to have pulmonary hypertension or hypercapnoea than with either alone
OSA (untreated) in those with COPD predicts worse survival and severe exacerbations
- risk abolished by treatment of the OSA
What did the FLORALI study find when comparing high flow nasal oxygen with non-invasive ventilation in those with acute hypoxaemic respiratory failure?
HIGH FLOW BETTER!
- less required intubation at 28 days
- decreased rates of death at 90 days
When is tiotropium of benefit in asthma?
RCT of addition of tiotropium vs placebo in those with poorly controlled asthma on ICS/LABA
- 912 patients
Outcomes (improves PFTs, symptoms, exacerbations)
What is the dominant immune pattern in asthma vs COPD?
Asthma
- eosinophilic and TH2 driven
COPD
- neutrophilic and CD8 driven
Note that there’s an overlap
- longstanding asthma can move toward a neutrophil/CD8 predominance
- a portion with COPD have TH2 pathway and eosinophils
What are the expected values to assess for degree of compensation in respiratory acidosis and alkalosis?
When is pulmonary rehab useful?
Involve all with COPD early, even with mild symptoms
Grade A evidence
- improves exercise capacity
- reduces breathlessness
- improves health related QOL
- reduces hospitalisations and LOS
- improves recovery after hospitalisation for an exacerbation
- reduces anxiety/depression associated with COPD
Grade B evidence
- benefits extend well beyond immediate period of training
- improves survival
- enhances effect of LABA
What are the complications and their associated mortality in IPF? When should they be referred for transplant?
- Progressive respiratory failure - 39%
- Cardiovascular disease - 24%
- RV hypertrophy, cor pulmonale due to PH+RHF, LV due to concurrent IHD
- Bronchogenic carcinoma - 10%
- 14:1 excess risk c/w general population
- same histologic distribution as the general population
- Pulmonary embolism - 3-7%
- Pulmonary infection - 2-4%
- Pneumothorax
- less often than in other ILDs
- Complications of therapy
- Referral for transplant
- should be referred early if appropriate
- DLCO <40%, FVC <80%, any dyspnoea or functional limitation due to IPF, decrease in sats to <89% even if only during exertion
- decline in FVC >=10% or DLCO >=15% during 6 months of f/u, pulmonary hypertension
