MED: Respiratory Flashcards
What features indicate a moderate acute asthma exacerbation?
PEFR >50-75% of the patient’s best or predicted score
What features indicate a severe acute asthma exacerbation?
- PEFR 33-50% of the patient’s best or predicted score
- RR ≥ 25
- HR ≥ 110
- Inability to complete sentences in one breath.
What features indicate a life-threatening acute asthma exacerbation?
- PEFR <33% of the patient’s best or predicted score.
- SpO₂ <92% - (PaCO₂ will be normal, if rises, then near-fatal)
- PaO₂ <8kPa.
- Absence of audible breath sounds over the chest (silent chest).
- Cyanosis (usually of the lips).
- Reduced respiratory effort.
- New-onset arrhythmia.
- Exhaustion.
- Reduced GCS
- Hypotension.
What features indicate a near fatal acute asthma exacerbation?
Raised PaCO₂ (>6kPa) and/or need for mechanical ventilation
What are the investigations for an acute exacerbation of asthma?
PEFR or FEV1:
- Used to assess severity and aid in decision making about treatment strategies / admitting to hospital.
- In an acute setting, PEFR is often easier.
SpO₂ measurement using a pulse oximeter:
- Normal is >94%
- SpO₂ <92% suggests exacerbation is life-threatening and requires urgent treatment
- Also associated with an increased risk of hypercapnia
ABG:
- Indicated if patient’s SpO₂ is <92% or PEFR is ≤30% of best or predicted
- ABG measurement includes PaO₂ and PaCO₂.
- Hypercapnia (PaCO₂ >6kPa) suggests that a patient’s attack is near-fatal
- Majority of patients will have a respiratory alkalosis, but if the patient becomes hypercapnic they are likely to become acidotic. In very severe cases this can result in metabolic acidosis.
- VBG may be used if ABG is not possible
Chest X-ray:
- Generally required unless another diagnosis such as pneumonia is suspected.
Describe the management of an acute exacerbation of asthma
Admission to hospital?:
- Near-fatal or life-threatening admitted
- Severe admitted if fail to respond to initial treatment
Oxygen therapy:
- If acutely unwell > 15L via a non-rebreathe mask
- Can then be titrated down to a flow rate where they are able to maintain a SpO₂ 94-98%
- Nasal cannulae and Venturi masks may also be used
High-dose inhaled short acting beta₂-agonist (SABA) e.g. salbutamol:
- NO features of life-threatening or near-fatal asthma > standard pressurised metered-dose inhaler (pMDI) or oxygen-driven nebulizer
- WITH features of a life-threatening exacerbation > nebulised
- If patient doesn’t respond to initial dose of SABA via inhaler, nebulisation should be considered
40-50mg prednisolone orally (PO) daily:,
- Continued for at least five days or until patient recovers from attack
- Also continue normal medication routine including inhaled corticosteroids.
Nebulised ipratropium bromide:
- In patients with severe or life-threatening asthma, or who have not responded to SABA and corticosteroid treatment
- Can be given 0.5mg 4-6 hourly
Magnesium sulphate // Aminophylline:
- IV or nebulised mag sulph is treatment option in severe or life-threatening exacerbation if haven’t responded to initial treatment
- IV aminophylline considered in near-fatal or life-threatening exacerbation
Mechanical ventilation:
- Severe fatigue, cardiovascular compromise and pneumothorax may be useful in decision making about mechanical ventilation
Follow up:
- RV patient situation and treatment plan including:
- Any possible triggers for the attack.
- Inhaler use and technique.
- Optimisation of treatment and a plan for preventing further exacerbations.
What are causes of an acute exacerbation of COPD?
- Bacterial infection - Haemophilus influenzae, Moraxella, Strep pneumoniae
- Viral infection - Rhinovirus, influenzae, RSV
- Eosinophilic inflammation
- Environmental factors such as air pollution
- Psychological factors such as anxiety and panic attacks
What is the modified Anthonisen criteria?
Diagnosis of exacerbation of COPD made if at least 2 major symptoms or at least one major and one minor symptom:
- Major symptoms - dyspnoea, increased sputum volume, increased sputum purulence
- Minor symptoms - cough, wheeze, nasal discharge, sore throat, pyrexia
What are the investigations for an acute exacerbation of COPD?
Bloods:
- FBC
- Urea and electrolytes
- Theophylline levels if the patient is on it
- Serial ABGs to monitor for the development of Type 2 respiratory failure
- A PaO2 of < 7 kPa and a pH level of < 7.35 are indications that the patient should continue to be managed in hospital
Chest X-ray:
- Overt changes such as opacification and oedema should prompt a reconsideration of the diagnosis
ECG:
- Helps to exclude acute ischaemia and/or comorbid cardiac dysfunction
Microbiological investigations:
- Sputum sample for microscopy and culture if sputum purulent
- Blood cultures if pyrexia present
In addition, the following tests should be done if the corresponding diagnosis is suspected:
- D-dimer – pulmonary embolism
- Cardiac troponins - myocardial infarction
- BNP - heart failure
Describe the management of an acute exacerbation of COPD
1. Provision of respiratory support
Prior to availability of ABG results, all patients provided with supplemental oxygen titrated to achieve target sats of 88-92%. Supplemental oxygen can be provided via either:
- A 24% Venturi mask at 2-3 L/min
- A 28% Venturi mask at 4 L/min
- Nasal cannulae at 1-2 L/min
ABG measurements should be taken upon arrival in hospital and repeated after 30-60 minutes. If the pCO2 and pH values are normal, target oxygen saturation can be adjusted to 94-98%. However, a target of 88-92% should be maintained if the patient has:
- History of previous Type 2 respiratory failure requiring NIV or intermittent positive pressure ventilation
- Oxygen saturation below 94% when clinically stable
- Long-standing hypercapnia – raised pCO2 but with a pH of ≥ 7.35 and/or a bicarbonate level of > 28 mmol/mol
Patients with persistent hypercapnia and respiratory acidosis despite optimal medical management need to be started on NIV. NIV is indicated if the following features are present 60 minutes after optimal supplemental oxygen and bronchodilation have been given:
- Acidosis - pH < 7.35
- Hypercapnia - pCO2 > 6.5
- Respiratory rate > 23
Improvement in pH and reduction of RR within the first 4 hours are key indicators of NIV success, otherwise, escalation to invasive mechanical ventilation (IMV) should be considered, especially if the following features are present:
- Imminent respiratory arrest
- Severe respiratory distress
- Failure of NIV - persistent acidosis (pH < 7.25) and tachypnoea (RR > 35)
- Persistent or worsening acidosis (pH < 7.15)
- Depressed consciousness (GCS < 8)
Escalation to IMV may be deemed inappropriate after considering the patient’s clinical status and wishes. In such cases, if NIV is adding to the patient’s discomfort it should be discontinued and palliative care measures started.
2. Pharmacological management
Bronchodilation
- SABA and/or SAMA should be used initially
- Can be delivered via inhaler or nebuliser driven by air
- Patients’ LABA, LAMA and/or ICS inhalers should be continued
- NICE recommends that IV theophylline may be used if the response is inadequate and levels should be checked 24 hours after commencing treatment
Corticosteroids
- 5-day course of oral prednisolone
Antibiotics:
- Given to patients who have all 3 of the major symptoms or have 2 major symptoms with increasing sputum purulence being one of them or require mechanical ventilation (invasive and non-invasive)
- Choice of antibiotic – penicillin e.g. amoxicillin, macrolides e.g. clarithromycin and tetracyclines e.g. doxycycline
3. Optimising the patient for discharge
- Measurement of spirometry
- Optimisation of maintenance bronchodilator therapy
- Satisfactory pulse oximetry and ABGs in patients who have had respiratory failure
- Confirmation that the patient has returned to their functional baseline
- Arrangement for follow-up and home care e.g. nurse visits
4. Prevention of exacerbations
- Smoking cessation
- Influenza and pneumococcal vaccination
- Pulmonary rehabilitation - integrated programme consisting of supervised exercise training, smoking cessation, nutritional counselling and educating patients about self-management of their disease
- Vitamin D supplementation
- Augmentation of long-acting bronchodilation with anti-inflammatory therapy - ICS, Roflumilast (alternative to ICS or added to patients already on a combination of LABA, LAMA and ICS if they have been hospitalised for an exacerbation in the past year)
- Long-term macrolide - Azithromycin has been shown to be effective especially among non-smokers but is associated with an increased risk of bacterial resistance
- Mucoregulators - Can be used as regular therapy in patients not receiving ICS - N-acetylcysteine and carbocysteine are common examples
What is Allergic bronchopulmonary aspergillosis?
A hypersensitivity reaction that occurs in response to colonisation of the respiratory tract with Aspergillus fumigatus.
It predominantly affects patients with a pre-existing medical condition like atopy, asthma, or cystic fibrosis
What are RFs for ABPA?
- Asthma
- CF
- Atopy
What are the clinical features of ABPA?
Presentation is variable and may range from mild respiratory symptoms to severe symptoms like a respiratory failure
Most commonly ABPA present as worsening of asthma or cystic fibrosis symptoms. Patients often present as:
- New or worsening cough
- Increased sputum production - brown-black mucus plugs
- Wheezing
- Haemoptysis
- Pleuritic chest pain
- Dyspnea
- Weight loss
- Fever
- In chronic advanced disease, finger clubbing, cyanosis, or features of cor pulmonale may be present.
What are the investigations for ABPA?
Skin test:
- Skin testing for hypersensitivity to Aspergillus fumigatus
- A positive skin test with a wheal and flare reaction alone is not specific
Blood tests:
- Serum-specific IgG and IgE against Aspergillus fumigatus
- The combination of increased total serum and specific IgE allows classic ABPA to be diagnosed
- Serum total IgE
- FBC - Eosinophilia
Imaging tests:
- Chest x-ray - Upper/middle lobe infiltrates. Mucus plugging and signs of bronchiectasis may also be noted.
- CT chest - Central bronchiectasis, mucus plugging, mucus impaction, pulmonary infiltrates and peribronchial thickening may be seen. Finger-in-glove sign showing mucoid impaction in bronchioles.
What is the criteria for diagnosing ABPA
1. Predisposing asthma or cystic fibrosis
2. Obligatory criteria
- Type I - positive Aspergillus skin test or elevated IgE levels against Aspergillus fumigatus and
- Elevated total IgE levels (value >1000 IU/mL)
3. Supportive criteria (minimum of two out of three):
- Presence of precipitating or IgG antibodies against Aspergillus fumigatus in serum
- Radiographic pulmonary opacities consistent with ABPA.
- Total eosinophil count over 500 cells/µl in glucocorticoid naïve patients
What is the management of acute ABPA?
Patients who are symptomatic with fever, cough, increased sputum production, haemoptysis, or chest pain and on investigation shows radiographic opacities and an elevated total serum IgE
Corticosteroids:
- Cornerstone therapy.
- Resolution of pulmonary inflammation, pulmonary infiltrates, and it prevents irreversible lung damage.
Anti-fungal drug: itraconazole/ voriconazole:
- Adjunctive but not primary therapy.
- Used in adults with severe, poorly controlled asthma and ABPA who are unable to taper oral corticosteroids.
What is the management of ABPA in remission?
Patients who have been treated with oral prednisolone for acute ABPA or exacerbation and are asymptomatic/stable asthma for greater than 6 months after stopping therapy. And also no infiltrates are seen on chest x-ray with normal or mildly elevated total IgE
- Maintenance therapy with inhaled glucocorticoids
- Management of underlying asthma or CF
What is the management of end-stage fibrosis?
Patients have impaired respiratory function and chronic scarring on imaging studies
- Treatment is daily oral corticosteroids given indefinitely
What are the complications of ABPA?
Acute complications:
- Acute invasive pulmonary aspergillosis
- Recurrent exacerbation of underlying disease namely asthma and CF
Long term complications:
- Bronchiectasis
- Mostly central bronchiectasis resulting in recurrent bacterial infections, haemoptysis, and chronic respiratory insufficiency.
- Pulmonary fibrosis
- Chronic pulmonary aspergillosis
- Respiratory failure
- Pulmonary hypertension
Treatment-related complications:
- Side effects of long-term corticosteroid therapy
- Includes diabetes, osteopenia, and hyperlipidaemia, immune suppression, cataracts, and growth retardation
What are the RFs for asthma?
- Personal or family history of atopy
- antenatal factors: maternal smoking, viral infection during pregnancy (especially RSV)
- low birth weight
- not being breastfed
- maternal smoking around child
- exposure to high concentrations of allergens (e.g. house dust mite)
- air pollution
- ‘hygiene hypothesis’: studies show an increased risk of asthma and other allergic conditions in developed countries. Reduced exposure to infectious agents in childhood prevents normal development of the immune system resulting in a Th2 predominant response
What are the investigations for asthma?
FeNO:
- In adults level of >= 40 parts per billion (ppb) is considered positive
- In children a level of >= 35 parts per billion (ppb) is considered positive
Spirometry:
- FEV1/FVC ratio less than 70% (or below the lower limit of normal if this value is available) is considered obstructive
Reversibility testing:
- In adults, a positive test is indicated by an improvement in FEV1 of 12% or more and increase in volume of 200 ml or more
- In children, a positive test is indicated by an improvement in FEV1 of 12% or more
Describe the management of asthma
Step 1: Newly diagnosed asthma
- SABA
Step 2: *Not controlled on step 1 or newly-diagnosed with symptoms >= 3 / week or night-time waking
- SABA + low dose ICS
Step 3:
- SABA + low dose ICS + LRTA
Step 4:
- SABA + low-dose ICS + LABA
Step 5:
- SABA +/- LTRA
- Switch ICS/LABA for a maintenance and reliever therapy (MART), that includes a low-dose ICS
Step 6:
- SABA +/- LTRA + medium-dose ICS MART
- OR consider changing back to a fixed-dose of a moderate-dose ICS and a separate LABA
Step 7:
- SABA +/- LTRA + one of the following options:
- Increase ICS to high-dose (only as part of a fixed-dose regime, not as a MART)
- Trial additional drug (for example, a long-acting muscarinic receptor antagonist or theophylline)
- Seeking advice from a healthcare professional with expertise in asthma
What is bronchiectasis?
A chronic lung disease, characterised by irreversibly dilated bronchi alongside chronic bronchial inflammation and infection
What are the causes of bronchiectasis?
- Idiopathic (45%)
- Post-infection (30%)
- Immunodeficiency (5%)
- COPD (4%)
- Connective tissue diseases (4%)
- Allergic bronchopulmonary aspergillus (2.5%)
- Ciliary dysfunction (2.5%)
- Asthma (1.5%)
- Inflammatory bowel disease (1%)
- Obstruction (1%)
- Aspiration/oesophageal reflux (1%)
- Congenital malformation (<1%)
- Alpha-1 antitrypsin deficiency (<1%)
- Diffuse panbronchiolotis (<1%)
- Pink’s disease (<1%)
- Yellow nail syndrome (<1%)
What are the clinical features of bronchiectasis?
Typical presentation = chronic productive cough on background of recurrent chest infections. Often lifelong non-smokers and more likely to be female
Key features:
- Persistent productive cough (90-96%)
- Daily sputum production (75%)
- Sputum may be mucopurulent or purulent
- Haemoptysis (25-50%)
- Recurrent chest infections
Other associated features:
- Rhinosinusitis symptoms (65-75% patients)
- Dyspnoea (60% patients)
- Chest pain (20-50% patients)
- GORD (20-40% patients) - common co-morbidity in patients with bronchiectasis
O/E:
- Crackles (70-75%)
- Wheeze (20-35%)
- Clubbing (2-3%)
Co-morbid conditions associated with the development of bronchiectasis:
- Joints: rheumatoid arthritis
- GI manifestations: inflammatory bowel disease, cystic fibrosis (malabsorption, pancreatitis), GORD
What are the initial investigations for suspected bronchiectasis?
Sputum culture:
- May show colonising pathogens, most commonly Haemophilus influenzae and Pseudomonas aeruginosa.
Chest X-ray:
- Majority of X-rays will be abnormal but findings are non-specific and further imaging is required
- Also useful for ruling out other possible causes such as TB or malignancy.
Post-bronchodilator spirometry:
- Most commonly an obstructive pattern is seen, although mixed, restrictive, and normal results are also possible.
What is the gold standard to diagnose bronchiectasis?
High-resolution CT scan or a thin section CT scan: Shows bronchial dilation:
- Bronchoarterial ratio > 1: the internal airway lumen is larger than the adjacent pulmonary artery
- This is often referred to as the ‘signet ring sign’
- Lack of tapering: bronchi should taper in diameter as they travel distally from the lung hila to the periphery
- Bronchus visible within 1cm of pleural surface: normal, non-dilated airways cannot usually be seen within 2cm of the pleura
Once bronchiectasis is confirmed:
- FBC, serum total IgE and assessment of sensitisation to Aspergillus fumigatus - to investigate for ABPA
- Serum IgG, IgA and IgM - to investigate for immunodeficiency
Dependant on the clinical features, further tests to help elucidate the underlying cause may be conducted including:
- Investigations for reflux and aspiration
- Cystic fibrosis test
- Primary Ciliary Dyskinesia test
- Specific antibody levels against capsular polysaccharides of Streptococcus pneumoniae
What is the initial management of bronchiectasis?
- Identifying and treating underlying cause
- Airway clearance techniques +/- pulmonary rehabilitation
- Annual influenza vaccine
- Antibiotics for exacerbations
- Self-management plan
What is the management of infective exacerbations of bronchiectasis?
- Collect a sputum sample - Send for microscopy, culture and sensitivity prior to commencing antibiotics.
- Prescribe a 7-14 day course of antibiotics - follow local prescribing guidelines or prescribe amoxicillin 500mg tds or clarithromycin 500mg bd
- Prescribe a short acting inhaled beta-2 agonist if the patient has wheeze or breathlessness in the acute phase
- Check airway clearance technique
- Review the patients response to antibiotics
- If the patient is not responding to treatment, change to a different antibiotic using the sputum culture and sensitivity results as a guide
≥ 3 exacerbations in one year despite following the initial management = treatment should be escalated in a stepwise manner. The second step in management is a physiotherapy reassessment and consideration of mucoactive treatment. Beyond this, specialists may consider prescribing long-term antibiotic therapy
Describe the surgical management of bronchiectasis
When medical therapies fail to control symptoms despite being optimised by specialists, surgical management may be considered.
- For those with localised disease, lung resection may be considered.
- For diffuse bilateral disease, a lung transplant may be considered.
BTS specify the following criteria for lung transplantation:
- Aged 65 years or less and
- FEV is <30% predicted with significant clinical instability or
- Rapid progressive deterioration despite optimal medical management
How is COPD diagnosed?
- Post-bronchodilator spirometry to demonstrate airflow obstruction: FEV1/FVC ratio less than 70%
- Chest x-ray: hyperinflation, bullae, flat hemidiaphragm. Also important to exclude lung cancer
- Full blood count: exclude secondary polycythaemia
- Body mass index (BMI) calculation
How is the severity of COPD graded?
The severity of COPD is categorised using the FEV1
Describe the management of COPD
General management:
- Smoking cessation advice: including offering nicotine replacement therapy, varenicline or bupropion
- Annual influenza vaccination
- One-off pneumococcal vaccination
- Pulmonary rehabilitation to all people who view themselves as functionally disabled by COPD
Bronchodilator therapy:
- SABA or SAMA is first-line treatment
- For patients who remain breathless or have exacerbations despite using short-acting bronchodilators the next step is determined by whether the patient has ‘asthmatic features/features suggesting steroid responsiveness’
No asthmatic features/features suggesting steroid responsiveness:
- Add LABA + LAMA
Asthmatic features/features suggesting steroid responsiveness:
- LABA + inhaled corticosteroid (ICS)
- If patients remain breathless or have exacerbations offer triple therapy i.e. LAMA + LABA + ICS
Oral theophylline:
- NICE only recommends theophylline after trials of short and long-acting bronchodilators or to people who cannot used inhaled therapy
Oral prophylactic antibiotic therapy:
- Azithromycin prophylaxis is recommended in select patients
- Patients should not smoke, have optimised standard treatments and continue to have exacerbations
Mucolytics:
- ‘considered’ in patients with a chronic productive cough and continued if symptoms improve
PDE-4 inhibitors:
- Oral PDE-4 inhibitors such as roflumilast reduce the risk of COPD exacerbations in patients with severe COPD and a history of frequent COPD exacerbations
- NICE recommend if: the disease is severe, defined as a FEV1 after a bronchodilator of less than 50% of predicted normal, and the person has had 2 or more exacerbations in the previous 12 months despite triple inhaled therapy with a long-acting muscarinic antagonist, a long-acting beta-2 agonist and an inhaled corticosteroid
What criteria determines whether a COPD patient has asthmatic/steroid responsive features?
- any previous, secure diagnosis of asthma or of atopy
- a higher blood eosinophil count
- substantial variation in FEV1 over time (at least 400 ml)
- substantial diurnal variation in peak expiratory flow (at least 20%)
Describe cor pulmonale in COPD
Features include peripheral oedema, raised jugular venous pressure, systolic parasternal heave, loud P2
Use a loop diuretic for oedema, consider long-term oxygen therapy
Describe the use of LTOT in COPD
Patients who receive LTOT should breathe supplementary oxygen for at least 15 hours a day.
Assess patients if any of the following:
- Very severe airflow obstruction (FEV1 < 30% predicted). Assessment should be ‘considered’ for patients with severe airflow obstruction (FEV1 30-49% predicted)
- Cyanosis
- Polycythaemia
- Peripheral oedema
- Raised jugular venous pressure
- Oxygen saturations less than or equal to 92% on room air
Assessment is done by measuring ABGs on 2 occasions at least 3 weeks apart in patients with stable COPD on optimal management
Offer LTOT to patients with a pO2 of < 7.3 kPa or to those with a pO2 of 7.3 - 8 kPa and one of the following:
- Secondary polycythaemia
- Peripheral oedema
- Pulmonary hypertension
In terms of smoking, NICE advise the following:
- Do not offer LTOT to people who continue to smoke despite being offered smoking cessation advice and treatment, and referral to specialist stop smoking services.
NICE suggest that a structured risk assessment is carried out before offering LTOT, including:
- The risks of falls from tripping over the equipment
- The risks of burns and fires, and the increased risk of these for people who live in homes where someone smokes (including e‑cigarettes)
What are the complications of COPD?
Respiratory:
- Acute Exacerbations
- Pneumothorax: due to abnormal lung parenchyma and formation of bulla
- Respiratory Failure
Cardiovascular:
- Pulmonary Hypertension: Chronic hypoxia and vascular remodeling can lead to the development of pulmonary hypertension in individuals with COPD, increasing the risk of right-sided heart failure (cor pulmonale).
Haematological:
- Secondary polycythaemia: overproduction of red blood cells as a result of hypoxia
Other:
- Anxiety and Depression
- Muscle Wasting and Weakness
What is Eosinophilic granulomatosis with polyangiitis (EGPA) ?
Now the preferred term for Churg-Strauss syndrome.
It is an ANCA associated small-medium vessel vasculitis.
What are the features of EGPA?
- Asthma
- Blood eosinophilia (e.g. > 10%)
- Paranasal sinusitis
- Mononeuritis multiplex
- pANCA positive in 60%
What is extrinsic allergic alvelolitis?
// Also known as hypersensitivity pneumonitis
A condition caused by hypersensitivity induced lung damage due to a variety of inhaled organic particles.
Describe the classification of EAA
- Bird fanciers’ lung: avian proteins
- Farmers lung: spores of Saccharopolyspora rectivirgula (formerly Micropolyspora faeni)
- Malt workers’ lung: Aspergillus clavatus
- Mushroom workers’ lung: thermophilic actinomycetes
What occupations are associated with EAA?
- Farmers - particularly mushroom and potato workers, compost workers
- Animal cleaning/breeding - particularly avian species
- Chemical industry - working with paints, powders
- Smelters and hard metal workers
What are the clinical features of EAA?
Acute EEA:
Typically presents, alongside a suggestive occupational/exposure history, with:
- Cough (productive or non-productive)
- Dyspnoea
- Fever
- Malaise
- Chest tightness
- Acute type 1 respiratory failure may develop in severe cases
Chronic EEA:
Presents more insidiously, alongside a suggestive occupational/exposure history, with:
- Insidious cough/dyspnoea symptoms
- Weight loss
- Clubbing (50% of cases)
- More widespread fibrotic changes mimicking idiopathic pulmonary fibrosis
O/E:
- Bilateral midzone inspiratory crepitations
What are the investigations for EAA?
Blood Tests:
- FBC- mildly increased WCC and normocytic anaemia
- ABG - acute hypoxia secondary to EEA may cause type 1 respiratory failure
- Serum precipitant antibodies - if there is a known, probable precipitant (e.g. suggestive symptoms in a pigeon farmer), then measuring serum IgG antibody of the precipitant can confirm humoral response to it, and diagnosis of EEA. It can also be used to track response to treatment
Imaging:
- CXR - may show non-specific ground-glass changes, airspace consolidation, or interstitial opacities
- High-resolution CT chest - may be normal / common features include patchy, diffuse, symmetrical ground glass opacities, small (<5mm) centrilobular nodules, patchy air trapping on expiratory imaging, airspace consolidation
- Changes are typically bilaterally in the mid-zones
Lung function tests:
- In acute EEA demonstrate a restrictive picture
- A reduction in both FEV1 and FVC, but with FEV1/FVC>80% expected
- Chronic EEA may show features of obstructive lung disease
Bronchoalveolar lavage (BAL):
- Fluid from BAL can be analysed for causative agents and antigens to that agent
- A negative BAL does not rule out EEA in the presence of positive lung function testing, HRCT and clinical history
- There is also generalised lymphocytosis on BAL culture
Describe the management of EAA
Identification and avoidance of precipitating agent:
- Symptoms should resolve following this
- Liaison with the employer and occupational health if the agent is work-related, and with the provision of respiratory masks and other protective equipment may be necessary
Corticosteroids:
- A trial of corticosteroids e.g. oral prednisolone can help with symptoms, mostly in patients with equivocal clinical presentation, as EEA tends to be steroid-responsive, whereas idiopathic pulmonary fibrosis does not
- This should then be tapered over a period of several weeks
- Patients with chronic EEA may benefit from long-term low dose prednisolone
What is granulomatosis with polyangiitis?
// Formerly known as Wegener’s granulomatosis
An ANCA-associated systemic vasculitis, typically affecting small and medium sized blood vessels.
GPA can affect any organ, but classically involves a triad of upper- and lower- respiratory tract symptoms and glomerulonephritis.
What are the clinical features of GPA
The classic triad of organ involvement includes:
1) Upper respiratory tract
- Sinusitis
- Nasal crusting, nasal discharge, epistaxis, nasal septal perforation, saddle nose deformity
- Subglottic stenosis
- May present as hoarseness or stridor.
- Otitis media, hearing loss, ear pain.
2) Lower respiratory tract
- Dyspnoea
- Cough
- Pleuritis
- Haemoptysis
- Pulmonary infiltrates or nodules may be seen on imaging
3) Glomerulonephritis
- Microscopic haematuria
- Urinary sediment
- Typically causes a pauci-immune rapidly progressive glomerulonephritis (RPGN) leading to chronic kidney disease
Patients commonly experience a prodrome of non-specific systemic inflammatory symptoms such as fever, malaise, arthralgias and weight loss. This often precedes the development of more organ-specific symptoms such as rhinosinusitis, cough, dyspnoea, hearing loss, purpura, urinary sediment or neurological dysfunction
Other common organ manifestations:
1) Ocular (60%)
- Scleritis/episcleritis
- May present as eye pain, redness and tearing.
- Orbital mass (often as an extension of sinus disease)
- May present as proptosis, diplopia or visual loss.
2) Cutaneous (50%)
- Skin lesions including leukocytoclastic angiitis (lower extremity purpura and ulceration), petechiae, nodules and vesicles
3) Neurological (15%)
- Mononeuritis multiplex
- Peripheral sensorimotor polyneuropathy
- Cranial neuropathy
What are the investigations for GPA?
- cANCA positive in > 90%, pANCA positive in 25%
- chest x-ray: wide variety of presentations, including cavitating lesions
- renal biopsy: epithelial crescents in Bowman’s capsule
Describe the management of GPA
Induction of remission:
- Initial immunosuppression with a corticosteroid and a second immunosuppressive agent.
- The choice of therapy is determined by the severity of the disease and the threat to organs and life.
For life/organ-threatening disease:
First-line therapy:
- Methylprednisolone IV for 3-5 days (followed by oral prednisolone) and cyclophosphamide.
- This therapy is typically given for 3-6 months to induce remission.
- Therapy adjunct: plasmapheresis (in selected patients with severe organ involvement and non-responsive to initial induction therapy).
Second-line therapy:
- Methylprednisolone IV for 3-5 days (followed by oral prednisolone) and rituximab IV.
For non-life/organ- threatening disease:
First-line therapy:
- Methylprednisolone IV for 3-5 days (followed by oral prednisolone) and methotrexate (with folic acid).
Second-line therapy:
- Oral prednisolone and cyclophosphamide.
- Oral prednisolone and rituximab.
Maintenance of remission:
First-line therapy:
- Prednisolone and methotrexate (with folic acid).
- Prednisolone and azathioprine.
All therapy options should be complemented with osteoporosis prophylaxis and pneumocystis jiroveci prophylaxis.
What are the complications of GPA?
Complications as a result of active GPA:
- Chronic kidney disease - Dialysis or renal transplant may be indicated
- Saddle nose deformity
- Conductive or sensorineural deafness
- Venous thromboembolism
Treatment-related complications:
- Infection
- Osteoporosis
- Bone marrow toxicity
- Diabetes mellitus
- Malignancy - Cyclophosphamide increases the risk of bladder cancer, skin cancer, leukaemia and lymphoma.
- Gonadal failure - Related to cyclophosphamide use.
- Pulmonary fibrosis
What is idiopathic pulmonary fibrosis?
A chronic lung condition characterised by progressive fibrosis of the interstitium of the lungs.
The term IPF is reserved when no underlying cause exists.
What are the clinical features of IPF?
- progressive exertional dyspnoea
- bibasal fine end-inspiratory crepitations on auscultation
- dry cough
- clubbing
