Respiratory Flashcards
What is the pathophysiology associated with acute pulmonary embolism?
Occlusion of pulmonary artery results in ventilated areas without perfusion (V/Q mismatch)
Increased pulmonary vascular resistance results in increased pulmonary artery pressure, increased RV afterload resulting in RV dilatation and dysfunction
RV dysfunction results in reduced LV preload and cardiac output, resulting in RV ischaemia
How should a possible PE be assessed?
-Negative Wells criteria + negative PERC excludes PE
-Positive PERC perform D-dimer and use YEARS algorithm
- Positive Wells or raised d-dimer perform CTPA or imaging
Should asymptomatic or subsegmental PE be treated?
No, higher risk of 90-day mortality in anti-coagulated group
How long should a PE be treated for?
Provoked:
- transient risk factor = 3 months
- permanent risk factor = lifelong
Unprovoked: 3-6 months
- consider prophylactic NOAC
Submassive PE: 6-12 months
Massive PE: indefinite
When is thrombolysis indicated for PE?
Massive PE if SBP<90 or falls by 40 or
When is an IVC filter indicated for PE?
Patients with contraindication to anticoagulation:
Recent surgery
Haemorrhagic CVA
Active bleeding
Massive PE where recurrent embolism would be fatal
Recurrent PE despite anticoagulation
What follow up is indicated after a PE?
Massive PE or ongoing symptoms are 3-6 months: repeat CTPA and ECHO to rule out chronic disease
When should a thrombophilia screen be performed as part of work up for PE?
If under 40 and unprovoked PE
What should be included on a thrombophilia screen for PE?
Antithrombin 3
Protein C
Protein S
Factor 5 leiden
Plasminogen
Fibrinogen
Activated protein C resistance
Cardiolipin antibody
What is the pathological diagnosis of pneumonia?
Acute infection of lung parenchyma resulting in alveolar occlusion with inflammatory infiltrates
What are common pathogens that cause pneumonia?
Most common = Strep pneumonia
Others: mycoplasma pneumoniae, Staph aureus, Legionella pneumophilia, enterobacteriaceae, haemophilus influenzae
What therapies for COVID-19 infection have demonstrated a reduction in mortality?
Dexamethasone
Tocilizumab/baricitinib
What are the three most common causes of pleural effusions?
- Malignancy
- Heart failure
- Infection (including TB)
What medications can cause a pleural effusion?
MADCOPIN
Methotrexate
Amiodarone
Dasatinib
Clozapine
Ovarian stimulation
Phenytoin
Immunotherapy
Nitrofurantoin
What is the mode of essential imaging for suspected pleural effusion?
Point of care thoracic ultrasound
What is the first step in diagnosis of a new pleural effusion of unclear aetiology?
Diagnostic thoracocentesis
What are the contraindications to a diagnostic thoracocentesis?
- insufficient pleural fluid
- skin infection or wound at the needle insertion site
- severe bleeding risk
What are the common complications to thoracocentesis? Which is the most common?
Most common = pneumothorax
Pain at puncture site
Breathlessness, cough
Bleeding
Empyema
Soft tissue infection
Spleen or liver puncture
Re-expansion pulmonary oedema (rare)
What does “anchovy paste” pleural fluid indicate?
Amoebal abscess, can occure with Hepato-pleural fistula
What routine tests should be performed on pleural fluid?
Cell count and differential
Total protein (paired with serum)
LDH (paired with serum)
Glucose
Culture and gram stain
Cytology
What is a pleural fluid pH of < 7.2 indicative of?
Parapneumonic effusion
What is the difference between a transudate and an exudate?
Transudate = imbalance between hydrostatic and oncotic pressure in chest
Exudate = result from inflammation and impaired lymphatic drainage
What are causes for a transudative pleural effusion?
Heart failure (may present as exudate after long period of diuresis)
CSF leak
Atelectasis
Hepatic hydrothorax
Hypoalbuminaemia
Hypothyroidism (can also be exudate)
Nephrotic syndrome
Peritoneal dialysis
Urinothorax
What are common causes of exudative effusions?
Malignancy
Infection
Autoimmune conditions
Chylothorax
Cholesterol effusion seen in TB, RA
ARDS
Asbestos pleural effusion
Pancreatitis, abdo infection
Hypothyroidism
Radiation therapy
PE
What is Light’s criteria for pleural effusions?
Exudate if any one positive:
-Fluid protein : serum protein > 0.5
-Pleural fluid LDH : serum LDH > 0.6
-Pleural LDH >2/3 serum LDH ULN
What is the pleural fluid only three test combination rule?
Exudate is defined as any one of:
-Pleural fluid protein > 30
- pleural fluid cholesterol > 55
- Pleural LDH >2/3 serum LDH ULN
What factors influence the management approach of a malignant pleural effusion?
Patient preference
Prognosis
Presence of non-expandable lung (means pleurodesis will not be effective)
What is a trapped lung and how is it determined?
Inability of lung to expand fully to fill the thoracic cavity usually due to presence of fibrinous restrictive pleural layer
Can be determined by post aspiration CXR
What is the most effective management strategy for malignant pleural effusions?
No evidence to support any one strategy being more effective than the other
What are the different management strategies for malignant pleural effusions?
-Repeated therapeutic pleural aspirations
-talc slurry pleurodesis via 12Fr intercostal catheter
-talc slurry pleurodesis via Large bore chest drain
- indwelling pleural catheter
- talc pouldrage pleurodesis via thorascopy
- video assisted thoracoscopic pleurodesis
What are the 3 pathophysiological features of asthma?
Variable airflow obstruction
Bronchial hyper-responsiveness
Airway inflammation
What reasons may someone with asthma have no bronchodilator reversibility on spirometry?
Baseline FEV1 is normal
Recent bronchodilator use
Poorly controlled asthma
What tests can be employed to diagnose asthma?
Two week peak flow monitoring at home
Exhaled nitric oxide
Raised blood eosinophilia
What is samter’s triad variant of asthma?
Asthma, aspirin intolerance, nasal polyps
What is the allergic bronchopulmonary aspergillosis variant of asthma?
Chronic asthma
Recurrent pulmonary infiltrates
Bronchiectasis
Very high total IgE (>1000)
Evidence of aspergillus senstivity
What is the EGPA (eosinophillic granulomatosis with polyangitis, previously Churg-Strauss) variant of asthma?
Necrotising vasculitis, granulomas, tissue eosinophilia
Asthma + blood eosinophils essential
30-50% ANCA positive
Cardiac disease accounts for 50% deaths
Often don’t involve kidneys
In what patients with asthma may long term oral steroids be required?
Those with adrenal insufficiency
Allergic bronchopulmonary aspergillosis varian
EGPA
What add on therapies can be used and when in severe asthma?
-Tiotropium: evidence of airflow obstruction,
exacerbations
- macrolides: exacerbations, cough + sputum
- monteleukast: aspirin sensitive asthma
- mAbs: exacerbations, type 2 biomarkers
What is the biggest risk factor for COPD? What are other risk factors?
Smoking - causal in 50% of cases
Air pollution, esp indoor cooking over open flame
Asthma
Infection
Occupational dusts
Low SES
What mABs are available for severe asthma? What are their benefits?
Omalizumab: targets IgE, used in allergic asthma
Mepolizumab: targets IL5R in eosinophilic asthma
Benralizumab: targets IL5R in eosinophillic asthma
Dupilumab: targets IL4/IL13R in allergic/eosinophillic asthma with ectopy
Steroid sparing therapies
Reduce exacerbations by 50%
How is COPD diagnosed ?
Persistent airflow limitation that is not fully reversible = post bronchodilator FEV1/FVC <0.7 (LLN)
What non-pharmacologic therapies are useful in COPD?
Minimise exposures
Pulmonary rehab programme = 2x/week 8 week programme
What pharmacological therapy is used in COPD?
SABA or SAMA PRN
THEN add regular LAMA or LABA
THEN combo LAMA/LABA
THEN add ICS
What interventions prevent disease deterioration in COPD?
Smoking cessation
Vaccinations: influenza, COVID and pneumococcal
What features define COPD exacerbations and how should they be managed?
Increased SOB and/or cough that worsens in < 14 days
70% are caused by infection but need to work up other causes such as cardiac, anaemia, anxiety
Inhaled bronchodilators
PO steroids - short course
PO antibiotics
Oxygen aiming sats 88-92%, NIV
PT and airway clearance
Smoking cessation
Inhaler technique
What is the COPD=X guideline for management of COPD?
Confirm diagnosis with spirometry
Optimise function with pulmonary rehab and inhalers
Prevent deterioration with smoking cessation and vaccination
Develop plan of care with self-management action plan
Manage exacerbations
What is bronchiectasis?
Permanent dilatation of bronchi and bronchioles due to destruction of airway muscles and elastic connective tissue
What are common causes of bronchiectasis?
- post infection
- ABPA = allergic bronchopulmonary aspergillosis
- COPD
- traction secondary to fibrosis
- aspiration
- obstruction
- immunodeficiencies
- congenital (Marfans, ciliary defects, A1AT deficiency)
- Inflammatory (RA, coeliac, DPB, SLE, IBD)
- Young’s syndrome (Male chronic rhinosinusitis, infertility, bronchiectasis)
- Amyloidosis
- cystic fibrosis
What investigations should be used in the work up of bronchiectasis?
CT chest
3 sputums for AFBs
IgE, Aspergillus precipitin
Immunoglobulins
Functional assessment
What is the main bacteria that affects people with bronchiectasis? What makes it challenging to treat?
Pseudomonas aeruginosa
Forms biofilms (pili)
Intrinsic resistance to beta-lactams
What are non-pseudomonal bacteria that cause exacerbations in bronchiectasis?
Non-tuberculous mycobacteria
Aspergillus
Atenotrophomonas maltophilia
Staphylococcus aureus
What antibiotics do you treat acute bronchiectasis exacerbations with?
Guided by sputum culture: 10 days PO ABx
If pseudomonas then 14 days ciprofloxacin
How should chronic inflammation in bronchiectasis be managed?
Macrolides (erythromycin)
OR
oral steroids
Through what 8 mechanisms do macrolides reduce inflammation in bronchiectasis?
- impair production of pro-inflammatory cytokines such as TNF-a
- inhibit neutrophil adhesion to cells
- inhibit respiratory burst of neutrophils
- reduce mucus secretion from airways
- improve macrophage clearance of apoptotic cells
- inhibit quorum sensing signals decreasing pseudomonal biofilm development
- decrease reflux and microaspiration
- impair epithelial cell growth and fibroblast migration
What are potential harms of macrolides used to treat bronchiectasis?
- Increased resistance
- Impairs intracellular killing of mycobacteria in macrophages, possibly increasing NTM infections
- QTc prolongation (Avoid concurrent ciprofloxacin prescription)
How are chronic infections treated in bronchiectasis?
-Inhaled antibiotics such as tobramycin
- trial other PO antibiotics
- macrolide or doxycycline
How are NTM infections treated in bronchiectasis?
First need to ensure they are pathogenic
MAC = ERClar = ethambutol + rifampicin + clarithromycin 12 months
M. Abscessus = cefotoxitin + amikacin IV for 1 month then clarithromycin + doxycycline + ciprofloxacin for 12 months
What is the commonest genetically life limiting inherited condition in caucasians?
Cystic fibrosis
What is the the pathological basis of cystic fibrosis? What is the inheritance pattern of cystic fibrosis?
Defect in CFTR on Chr7 = non-functioning Na/K pump results in dehydration of mucus, reducing mucocilliary clearance, leading to bacterial colonisation and airway inflammation + destruction
Most commonly is class II due to CFTR-trafficking defect = no functional protein
Autosomal recessive
What classification of CFTR protein defect is ivacaftor used in? How does it work?
Class III = defective channel regulation (G551D mutations)
CFTR potentiator and allows channel to open
How is CF diagnosed?
Clinical presentation usually at birth with meconium ileus
Heel prick test = immunoreactive trypsinogen (high sensitivity, low specificity)
To confirm diagnosis then sweat test with Cl > 60 mmol/L (borderline 40-60)
Gene testing
What therapies are effective for cystic fibrosis?
- CFTR modulators
- Inhaled DNase
- macrolides (azithromycin)
- hypertonic saline
- Lung transplantation