Fibrosing Alveolitis

Synonym: idiopathic pulmonary fibrosis (IPF), cryptogenic fibrosing alveolitis
Fibrosing alveolitis is a chronic lung disease characterised initially by the presence of inflammatory cells within the alveoli. This is followed by thickening and fibrosis of the alveolar walls. The aetiology and pathogenesis is as yet unknown. A form called the Hammond-Rich syndrome has a particularly poor prognosis.

The condition is part of a spectrum of conditions known as interstitial lung disease. The term cryptogenic fibrosing alveolitis should be reserved for those patients in whom lung histology has shown to demonstrate the pathological changes termed 'usual interstitial pneumonitis' (UIP).¹ This is characterised by patchy interstitial changes, a honeycomb appearance to the lung tissue and eosinophilic infiltration.²

The incidence of fibrosing alveolitis appears to be rising, although it is not yet known why. A general practice-based study calculated an overall incidence of 4.6 per 100,000 person-years. The study confirmed the impression that the incidence was rising and found that it had doubled between 1990 and 2003. It was postulated that this could be due either to an ageing population or to increasing recognition of the condition.

Exposure to certain airborne agents such as asbestos and metal alloys may produce the condition and the great majority of people who develop fibrosing alveolitis are, or have been at some time, smokers. It is most common in people in their 50s and affects men to a slightly greater degree than women(M:F 1.7:1).

The disease may show familial clusters, but the genetic reason for this is not yet fully understood as it does not occur in a predictable fashion.

An American study found that mortality rates increased from 1992 to 2003.⁵

Risk factors

• The condition is common in certain occupations - e.g people who work with silica, asbestos, heavy metals or mouldy foliage.
• Environmental factors include pigeon breeding and contaminated ventilation systems.
• It can be an adverse effect of amiodarone.

Symptoms

• The commonest symptoms are progressively increasing shortness of breath and dry cough.
• 5% of patients diagnosed opportunistically have no initial symptoms.
• 50% of patients are systemically unwell and may have a flu like illness, fatigue or weight loss.
• Spontaneous remissions do not occur (in contrast to sarcoidosis).
• Extrapulmonary features may include arthralgia, muscle pains and skin rashes.

Signs

These may include:

• Exertional dyspnoea progressing to breathlessness at rest
• Tachypnoea
• Cough
• Clubbing (50%)
• Cyanosis
• Fine bilateral basal crepitations particularly at the end of expiration ("Velcro rales")
• Signs of cor pulmonale and right heart failure in the later stages

Due to the non-specific nature of the presenting symptoms and signs, there are many other diagnoses which must be considered ranging from very common disorders such as heart failure through to much rarer diseases.

Diagnoses to be considered include:

• Heart failure
• COPD
• Sarcoidosis
• Pulmonary embolism
• Lymphangitis carcinomatosis
• Extrinsic allergic alveolitis

Laboratory tests

• Full blood count may show mild anaemia or may be normal.
• ESR and CRP may be raised in 50% of patients.
• Anti nuclear factor and rheumatoid factor may be raised in up to a third of all patients.

Radio-imaging

• Chest X-ray will show abnormalities in 95% of patients. The commonest finding is bilateral basal and peripheral infiltrates. The fibrosis may also produce a honeycombing effect.
• High-resolution CT scanning (HRCT). The specificity of this has been questioned in recent years, but it is still a useful screening tool to decide whether or not to proceed to lung histology tests. Typically, a ground glass appearance is indicative of fibrosing alveolitis, whereas a reticular pattern is more predominant in other types of interstitial lung disease.^2,8

Lung function tests

These may show:

• A restrictive defect (FEV1 usually less than 80% predicted value, FVC usually less than 3 litres, FEV1/FVC ratio normal, because both are reduced)
• Reduced gas transfer
• Reduced lung volumes

Histology

Lung biopsy is the definitive method of arriving at the diagnosis, but as the lesions need to be separated both in time and space, a large biopsy e.g. open lung biopsy or several smaller biopsies may be required.

Fibrosing alveolitis may be found in association with several autoimmune disorders such as:

• Thyroid disease
• Systemic sclerosis
• Rheumatoid arthritis
• Autoimmune liver disease
• Systemic lupus erythematosis

There is no consensus regarding management.⁹

Non-drug

• Supportive therapy with oxygen and physiotherapy may be helpful.
• Regular exercise should be encouraged.
• Vaccinate against influenza and pneumococcus.
• Encourage to stop smoking if the patient continues to do so.

Drug

Medication should be initiated under specialist supervision.

• Steroids are the drugs of first choice, but will only benefit 20% of patients.
• Immunosuppressive drugs such as azathioprine or cyclophosphamide or antifibrotic agents such as colchicine or pirfenidone may be helpful in patients who do not respond to steroids.
• Interferon-gamma1b is being assessed for use in this condition. Promising results, in terms of improved survival, have been found in trials.¹⁰
• Bosentan, an endothelin receptor antagonist, is a promising antifibrotic therapy for this condition.¹¹

Surgical

Lung transplant may be required for patients who fail to respond to medical therapy.

These may include:

• Adverse drug effects (closely monitor)
• Cor pulmonale
• Pneumothorax
• Infection
• Lung cancer¹²
• Thromboembolic diseases
• Pulmonary hypertension¹³

It is hoped that the advent of Interferon-gamma1b therapy will improve the prognosis. Trials to assess the use of this treatment on morbidity and mortality are currently being conducted.

A more favourable prognosis is also associated with female sex, younger age and shorter duration of symptoms. The development of pulmonary hypertension indicates a poor prognosis.¹³

A blood test to assist in the diagnosis of fibrosing alveolitis is being investigated.¹⁴ Ongoing research is looking at the use of stem cells to help repair damaged lung tissue.¹⁵ There is a need for an international register to help gather data on diagnosis and the effectiveness of emerging therapies.¹⁶