Respiratory Disease Flashcards
— asthma —
Describe the pathology of asthma.
- asthma is a chronic disorder of the conducting airways caused by an immunologic reaction
- bronchoconstriction is reversible
- atopic asthma is mediated by IgE (type I hypersensitivity)
- remodelling of the airway occurs with repeated allergen exposure, including hypertrophy and hyperplasia of smooth muscle, epithelial injury, increased vascularity, mucus gland hypertrophy, and deposition of collagen
Describe the clinical presentation of asthma.
- Asthma is characterised by wheezing, dyspnoea, chest tightness, and cough.
- Symptoms are often diurnal (worst in the early morning and at night)
- There may be a history of other atopic conditions, such as eczema or allergic rhinitis
Describe the rationale behind investigating asthma.
- diagnosis is based on clinical assessment, and can be supported by tests. NICE guidelines have recently advocated moving toward more objective tests.
- spirometry with bronchodilator reversibility testing (BDR)
- fractional exhaled nitric oxide test (FeNO)
Describe the mechanism by which asthma causes remodelling of the airway.
Bronchoconstriction, chronic inflammation (eosinophils, by IgE hyp1), and airway hyperresponsiveness.
Describe the stepwise management of asthma.
- SABA + ICS (if 3+ symptoms/week or night-time waking)
- SABA + ICS (low-dose)
- SABA + ICS + LTRA (e.g. montelukast)
- SABA + ICS + LABA (+ LTRA in adults if responsive previously)
- SABA (+ LTRA), and switch to a MART (low-dose ICS)
- SABA (+ LTRA) and increase steroid dose component of MART
- Specialist territory; options include high-dose steroid (fixed regime only, not as part of a MART), adding theophylline, and seeking advice from a professional
NB steroid dosing classification from NICE has recently changed:
- low dose: <400ug equiv.
- moderate dose: 400-800ug equiv.
- high dose: >800ug equiv.
Describe the types of inhaler available.
- pressurised metered dose inhaler (pMDI): available with spacer (yellow or blue), and can be used in all ages
- breath actuated (BAI): used only in school-aged children
- dry powdered inhaler (DPI): should only be used in older children (e.g. 12+)
Compare the types of steroid available for airway disease, and how they may be administered.
Firstly, it is important to note steroids are compared by considering the beclomethasone dipropionate (BDP) equivalent dose. Steroid dosing is based on the BDP dose being ‘standard’ potency (e.g. BDP = 1).
- there are three main ICS available: beclomethasone (BDP), budesonide, and fluticasone.
- budesonide = BDP
- fluticasone is twice as potent as BDP (e.g. 0.5 fluticasone = 1 BDP)
ICS inhalers are available as either monotherapies with brand names, or as combination therapies with a LABA (formoterol or salmeterol), which constitutes a MART
- BDP: clenil modulite, kelhale etc.; fostair is a MART with formeterol
- budesonide: easyhaler, pulmicort, turbohaler, symbicort (+ formeterol)
- fluticasone: flixotide, accuhaler, evohaler, seretide (+ salmeterol)
new NICE dosing is as follows:
- very low: 200ug/day BDP equiv.
- low: 400ug/day BDP equiv.
- medium: 800ug/day BDP equiv.
- high: >800ug/day BDP equiv.
Describe the features that constitute life-threatening asthma.
Remember 33 92 CHASE (not CHEST!):
- PEFR <33% expected
- SpO2 <92%
- cyanosis
- hypotension
- arrhythmia/altered consciousness
- silent chest
- exhaustion
Describe the role of CO2 concentrations in assessing severity of acute asthma.
- acidosis with a normal PaCO2 indicates exhaustion, and is a feature of life-threatening asthma
- acidosis with a raised PaCO2 indicates near-fatal asthma
Describe the management of acute asthma.
The mnemonic ‘O SHIT ME’ may be used to remember the key drugs, but does not fully represent the order in which they should be given.
The following should be given to all patients simultaneously:
- O2: 15L non-rebreather, titrated down to a flow rate when patient is able to maintain a normal SpO2
- Salbutamol (back-to-back nebulisers intially)
- Hydrocortisone (prednisolone is now recommended)
The following should be given additionally if required and with senior input:
- Magnesium sulphate (IV over 20 minutes as a one-off dose), given before theophylline
- Theophylline (aminophylline infusion)
- Escalate care (intubation and ventilation)
What criteria are required to diagnose a patient after an episode of acute asthma?
- stable on discharge medication (e.g. oral prednisolone)
- no nebulisers or O2 for 12-24hr
- inhaler technique checked and recorded
- PEFR >75% recorded
— COPD —
Describe the pathophysiology of COPD.
COPD is a condition which consists of emphysema and chronic bronchitis.
- emphysema is characterised by irreversible enlargement of airspaces distal to the terminal bronchioles, plus destruction of the walls without obvious fibrosis.
– centriacinar emphysema is seen in ~95% of cases of emphysema COPD
– panacinar emphysema is typically seen in a1-antitrypsin deficiency
- chronic bronchitis: defined as persistent cough + sputum production for >3 months in >2 consecutive years. hypertrophy of tracheal and bronchial cells leads to mucus hypersecretion as a protective reaction against smoke, smog etc.
What are the clinical differentiating signs of asthma?
Reversible (asthma) vs non-reversible (COPD) obstruction. Non-smoking vs smoking. Wheeze vs no wheeze. Diurnal variation (PEFR) vs not.
Describe the clinical features of COPD.
- progressive dyspnoea (especially on exertion), cough with sputum production, wheeze, frequent winter ‘bronchitis’
- less common: weight loss, waking at night, ankle oedema
- on examination: poor chest expansion, hyperinflated lungs, hypercapnic flapping tremor of hands, absence of clubbing
Describe the diagnosis of COPD.
- NICE recommend considering a diagnosis of COPD in patients >35 who are smokers, or ex-smokers, and have symptoms such as exertional dyspnoea, chronic cough, regular sputum production; the following investigations are recommended in patients with COPD:
– post-bronchodilator spirometry to demonstrate airflow obstruction; FEV1/FVC <70%
– CXR: hyperinflation, bullae, flat hemidiaphragm and to exclude of lung cancer
– FBC: exclude secondary polycythaemia
– BMI calculation
Describe the pharmacological management of stable COPD.
- SABA (initial therapy)
- assess whether the patient has steroid responsive features:
– previous diagnosis of asthma or atopy
– high eosinophil count
– variation in FEV1 (>400ml)
– diurnal variation in PEFR (>20%) - steroid responsive: SABA + ICS + LABA
- non-responsive: SABA + LABA + LAMA
After patients have been escalated through triple therapy:
- oral theophylline
- roflumilast (PDE4 inhibitor), if disease is severe (FEV <50%) and 2+ exacerbations despite triple therapy
- prophylactic macrolide (azithromycin) with the following criteria:
– CT thorax (exclude bronchiectasis)
– sputum culture (exclude atypical infection + TB)
– ECG (exclude QTc prolongation)
– 4+ exacerbations, requiring hospital admission at least once
- mucolytic (carbocysteine)
Describe the presentation and management of an acute exacerbation of COPD not requiring hospital admission.
- H influenzae is the most common pathogen overall, with others including S pneumoniae, M catarrhalis, and respiratory viruses (e.g. human rhinovirus)
- features include acute worsening of COPD symptoms (e.g. increased sputum production), hypoxia, and sometimes acute confusion
- management consists of three main aspects:
– antibiotics (amoxicillin, doxycycline, clarithromycin): NICE advocate not giving these routinely, only for production of purulent sputum or clinical signs of pneumonia
– oral steroids (30mg prednisolone for 5 days)
– increased frequency of bronchodilators (SABA, SAMA) and consider giving via nebuliser
What are the admission criteria for a patient with an acute exacerbation of COPD?
- severe dyspnoea
- acute confusion or impaired consciousness
- cyanosis or SpO2 <90%
- social (e.g. unable to cope at home or living alone)
- significant comorbidity (e.g. cardiac disease)
Describe the management of an acute exacerbation of COPD in secondary care.
Oxygen therapy
- oxygen: prior to the availability of ABG results, use 28% Venturi at 4l/min with a SpO2 target of 88-92%
- patients who develop type 2 respiratory failure should be given BiPAP with an EPAP of 4-5cm H2O and an IPAP of 10-15cm H2O
- severely acidotic patients (pH <7.25) may be given BiPAP but should be monitored more frequently (e.g. in HDU) and with a lower threshold to intubate and ventilate
Additional therapies
- nebulised SABA/SAMA
- steroid therapy: oral prednisolone (30mg OD 5 days, or IV hydrocortisone)
- IV theophylline if not responding to nebulisers
Why are airway spacers sometimes used instead of straight inhalers?
Traps particles that cause thrush, reduces particle size/velocity.
— Bronchiectasis —
Name the risk factors for bronchiectasis.
- congenital and hereditary conditions: cystic fibrosis, immunodeficiency, Kartagener’s
- infections: pneumonia, measles, pertussis, TB
- bronchial obstruction: tumour, foreign bodies
- COPD
- autoimmune conditions: RA, SLE, IBD, post-transplant
Describe the pathophysiology of bronchiectasis.
- destruction of smooth muscle and elastic tissue by chronic necrotising infections, leading to permanent dilation of bronchi and bronchioles
- normal clearing mechanisms are impaired, leading to pooling of secretions distal to obstruction
- pooled secretions lead to infection, inflammation, necrosis, fibrosis, and dilatation
- obliteration of bronchioles occurs progressively (bronchiolitis obliterans)
Describe the clinical and radiological findings of bronchiectasis.
- severe, persistent cough with large volumes of foul smelling and occasionally bloody sputum (haemoptysis) and dyspnoea
- coarse crackles and wheeze
- clubbing may be present
- HRCT is the imaging modality of choice and may demonstrate ‘signet rings’ and a tram-track appearance
Describe the management of bronchiectasis.
- physical training, such as inspiratory muscle training, which has a good evidence base for patients with non-CF bronchiectasis
- airway clearance: options include devices (Flutter, Acapella) or nebulised saline
- long-term rotating antibiotics: azithromycin is useful for long-term prophylaxis + ciprofloxacin for Pseudomonas
- surgery/transplantation
— Oxygen therapy —
When should liberal oxygen therapy overtake conservative?
In cluster headaches, poisoning, and tension pneumothorax
— additional oxygen therapy cards —
— spirometry —
Describe the peak expiratory flow rate curves for obstructive and restrictive disease.
Obstructive - peak is lower and not as long. Restrictive - peak reaches top but not as long.
— Lung cancer —
What are the two main presentations of lung cancer?
Primary and paraneoplastic
Describe some of the main symptoms of lung cancer.
Cachexia, cough, dyspnoea, persistant haemoptysis, hoarseness, recurrent pneumonia
Describe the histological classification and features of lung cancer.
SCLC
- arises from APUD cells
- typically central in location
- associated with SIADH, Cushing’s syndrome, and Lambert-Eaton
NSCLC
- adenocarcinoma
– most common type in both smokers and non-smokers
- squamous (SCC)
– Central location
– Cigarettes
– Cavitating
– Clubbing
– Calcium (hypercalcaemia)
- large cell: peripheral, anaplastic tumours which may secrete B-hCG
Describe the main benign tumours of the lung.
- hamartoma: most common benign tumour; ‘popcorn’ calcification is virtually diagnostic
- bronchial adenoma: resembles an intestinal carcinoid tumour, but does not secrete serotonin (instead secretes ACTH)
- additional benign tumours include cylindroma, chondroma, and lipoma
Describe the investigations for lung cancer.
- bloods: may show raised platelets
- CXR: often the first investigation; may be normal in ~10% of cases
- CT: investigation of choice, allows staging via TNM
- bronchoscopy: histological diagnosis
- PET-CT: lymph nodes and metastasis
Describe the main paraneoplastic effects of lung cancer.
SCLC
- SIADH (ADH secretion)
- Cushing’s syndrome (ACTH secretion): hypertension, hyperglycaemia, hypokalemic alkalosis, muscle weakness
- Lambert-Eaton syndrome: antibodies block calcium channels that enable acetylcholine release in the neuromuscular junction
Adenocarcinoma
- gynaecomastia
- HPOA + clubbing
SCC
- hypercalcaemia
- HPOA + clubbing
- hyperthyroidism due to ectopic TSH secretion (controversial)
Pancoast tumour
- Horner’s syndrome
Which two treatments may be used for lung cancer?
Surgery/radiotherapy
Describe the referral criteria for suspected lung malignancy.
Urgent referral (2-week wait pathway)
- CXR findings suggesting lung cancer
- aged 40+ with unexplained haemoptysis
Offer CXR (2-week wait) if aged 40+ with either 2+ of the following, or if ever smoked with 1+ of the following:
- cough
- fatigue
- dyspnoea
- chest pain
- weight loss
- anorexia
Consider CXR (2-week wait) if aged 40+ with any of the following:
- persistent or recurrent chest infections
- finger clubbing
- supraclavicular lymphadenopathy
- persistent cervical lymphadenopathy
- thrombocytosis
What is the factor that decides whether a lung biopsy should be a bronchoscope or CT guided?
Proximity to the hilum.
— TB —
What is the main pathogen that causes TB?
Mycobacterium tuberculosis
Mycobacterium bovis is contracted from unpasteurised milk
What are the main symptoms of TB?
Haemopytsis, night sweats, weight loss
What are the risk factors for TB?
- immunosuppression: HIV, IVDU, solid organ transplant, haematological malignancy, chemotherapy
- age <5
- gastric surgery: jejunoileal bypass, gastrectomy
- comorbidities: CKD/haemodialysis, diabetes, silicosis
- biologics: e.g. anti-TNFa agents
Describe the histology of TB infection development.
- TB enters macrophages, replicating within them and seeding multiple sites
- activation of TH1 cells produces interferon gamma (IFN-y), which differentiates macrophages into epithelioid histiocytes, which aggregate to form granulomas
- the initial granuloma is known as the Ghon focus
- if the infection is not controlled within this site, it spills over to local pulmonary lymph nodes
- Ghon focus + lymph node infection = Ghon complex
Describe the investigations that should be undertaken to diagnose latent TB.
The Mantoux test remains the test of choice to diagnose latent TB. It is considered positive with an induration of 5+mm, regardless of BCG history.
- close contacts aged 18-65 should be offered a Mantoux test
- a positive Mantoux test should prompt assessment for active TB
- positive Mantoux test + no active TB: offer interferon gamma release assay (IGRA) if more evidence of infection is needed to decide on treatment
- inconclusive Mantoux: refer to a TB specialist
Describe the investigations that should be undertaken to diagnose active TB.
- CXR -> CT thorax
- sputum samples (3 deep cough samples, ideally including 1 early morning sample) for microscopy and culture
– these should be sent prior to treatment, or within 7 days if treatment is initiated in life-threatening disease
– if spontaneous samples cannot be produced consider gastric lavage, induction of sputum, or bronchoscopy and lavage - NAAT should be offered for all children and in adults whom
– have HIV
– care would be altered with rapid information about mycobacterial species
– need for large contact-tracing initiative is being explored
Describe the treatment of both latent and active TB.
Latent
- 3 months of RI (concerns re hepatotoxicity)
- 6 months of I alone
Active
- RIPE therapy for 2 months, then
- RI therapy for 4 months (10 months with CNS involvement)
Describe the side effects that may be observed with the 4 main drugs used for treating TB.
Rifampicin
- potent liver enzyme inducer
- hepatitis
- orange secretions (‘rifam-pissin’)
- flu-like symptoms
Isoniazid
- peripheral neuropathy (‘I’m-so-numb-azid’); requires co-prescription of pyridoxine (vitamin B6)
- agranulocytosis
Pyrazinamide
- hyperuricaemia (precipitates gout)
- arthralgia, myalgia
Ethambutol
- optic neuritis (E = eyes)
— Pneumonia —
Which clinical symptoms may suggest pneumonia?
Cough, high fever, chest pain, tachypnoea, pleural rub, crackles.
Describe the classification of pneumonia.
- community-acquired pneumonia (CAP)
- hospital-acquired pneumonia (HAP): requires being in hospital for a minimum of 48 hours
- aspiration pneumonia
- ventilator-acquired pneumonia (VAP)
Briefly describe the microbiology of pneumonia.
- S pneumoniae: 80% of cases
- H influenzae: most common in COPD
- M catarrhalis: elderly patients and second-most common in COPD
- S aureus: IVDU, following viral infection
- Klebsiella: malnourished, debilitated, alcoholics
- Pseudomonas: immunocompromise, CF
- Legionella: contaminated water and air conditioning units
- P jiroveci: HIV infection
- Zoonoses: Coxiella burnetti (Q fever), C psittaci (avian proteins)
