Extrinsic allergic alveolitis (EAA, also known as hypersensitivity pneumonitis) is a condition caused by hypersensitivity induced lung damage due to a variety of inhaled organic particles.

Examples

• bird fanciers' lung: avian proteins
• farmers lung: spores of Saccharopolyspora rectivirgula (formerly Micropolyspora faeni)
• malt workers' lung: Aspergillus clavatus
• mushroom workers' lung: thermophilic actinomycetes*

It is thought to be largely caused by immune-complex mediated tissue damage (type III hypersensitivity) although delayed hypersensitivity (type IV) is also thought to play a role in EAA, especially in the chronic phase.

A thorough clinical history is essential. This must include an occupational history, as certain jobs are associated with exposure to agents that can cause EEA:

• 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

A particular focus on exposure at home or at work to moulds is important, including in ventilators, air conditioners, hay or wood as this is a common causative agent.

The presentation may be acute, with symptoms presenting 4-8 hours after exposure to causative agent and subsiding within 24-48 hours, or chronic, usually following long term low-exposure to a causative agent.

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

On auscultation of the lungs in both cases, bilateral midzone inspiratory crepitations will likely be heard to a greater or lesser extent depending on the severity of the condition.

The diagnosis of EEA is challenging as it can present insidiously, and there is no gold standard test. It is, therefore, a combination of clinical, radiological and lung function test findings.

Blood Tests
Routine tests reveal largely non-specific findings but are important to rule out an infectious process.

• Full blood count
  • May show a mildly increased WCC and normocytic anaemia
• Arterial blood gas
  • Patients with acute hypoxia secondary to EEA may develop 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
  • In other cases where the link with a precipitant is less clear, however, serum antibody is of less use

Imaging

• Chest X-Ray (CXR)
  • May show non-specific ground-glass changes, airspace consolidation, or interstitial opacities
• High-resolution CT (HRCT) chest. Suggestive clinical history and CXR should lead to a review by the respiratory team and further imaging with HRCT to investigate further. However, HRCT may be normal in 8-18% of patients with EEA. 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

• Lung function tests in acute EEA demonstrate a restrictive picture
  • A reduction in both FEV1 and FVC, but with FEV1/FVC>80% expected
• However, chronic EEA may show features of obstructive lung disease
• The diffusing capacity for carbon monoxide (DLCO) will also likely be decreased in EEA

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

Key differentials are from other forms of interstitial lung disease or infectious lung disease

• Idiopathic pulmonary fibrosis (IPF)
  • The most likely and clinically similar condition, that needs to be ruled out when EEA is suspected
  • EEA’s pattern of exposure correlating with symptomatic recurrence is a key differentiating feature on the history to help distinguish between the two conditions
  • Furthermore, BAL in IPF is less likely to demonstrate the typical leucocytosis of seen in EEA

• Pneumonia
  • Viral pneumonia is likely to be associated with a dry cough and fever, and should not recur in contrast to the natural history of EEA that is characterised by repeated short recurrences
  • Similarly, bacterial pneumonia will usually be accompanied by frank lobar consolidation on CXR and productive cough

• Chronic Obstructive Pulmonary Disease (COPD)
  • Chronic, progressive dyspnoea with cough and reduced exercise tolerance. No periods of symptoms improvement in the natural history of the disease.
  • Key risk factor is smoking, and age over 60 years
  • Typically a hyperinflated chest is seen on x-ray, with an obstructive picture on spirometry (FEV1/FVC <70%, reduced DLCO)

• Sarcoidosis
  • A rarer auto-immune condition
  • Clinical features of sarcoidosis may be very similar to EEA, but with the important addition of extra-pulmonary features associated with sarcoidosis
  • These include painless cervical lymphadenopathy, red and painful eye, and arthralgia

• Asbestosis
  • A rare condition following worldwide campaigns to remove asbestos from homes and workplaces
  • Clinical symptoms are likely very similar to EEA, but with a history of asbestos exposure
  • Imaging shows pathognomonic pleural plaques

British Thoracic Society (BTS) guidelines on interstitial lung disease (2008) underline the key factor in management is the identification and avoidance of the precipitating agent.

• Identification by a thorough clinical history including occupational hazards and correlation with symptom timeline of the patient.
  • A causative agent may not be able to be identified in up to 25% of cases
  • BAL cytology or antigen testing of the blood may confirm the causative agent

• Once identified, the removal of the causative agent is the most important part of management, and 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

Fibrotic and emphysematous changes following inflammation in the lung during an acute period may lead to fibrosis, which has long term effects. Studies have found that 20% of patients with farmer’s lung (EEA secondary to occupational exposure to hay dust or mould spores) developed emphysema.

• Chronic oxygen requirement
  • Widespread fibrosis may result in chronic hypoxaemia requiring long-term oxygen therapy at home
• Decreased lung function will lead to a reduced ability to carry out physical activities and activities of daily living