Idiopathic fibrosing alveolitis
D E FI N I T ION
Inflammatory condition of the lung resulting in fibrosis of alveoli and
interstitium. Previously known as ‘cryptogenic fibrosing alveolitis’.
AE T IOLOGY
In a genetically predisposed host (e.g. with telomerase/surfactant protein
mutations), recurrent injury to alveolar epithelial cells may result in secretion of cytokines
and growth factors (e.g. TNF-a, IL-1 and MCP-1) which cause fibroblast activation,
recruitment, proliferation, differentiation into myofibroblasts and " collagen synthesis
and deposition. Profibrogenic molecules, e.g. PDGF and TGF-b, are secreted by inflammatory,
epithelial and endothelial cells.
Certain drugs can produce a similar illness (e.g. bleomycin, methotrexate and amiodarone).
Histological patterns: Usual interstitial pneumonia (UIP: patchy interstitial fibrosis, later:
‘honeycomb’ lung). Desquamative interstitial pneumonia (DIP: diffuse intra-alveolar
accumulation of macrophages, mild thickening of alveolar septa, lymphoid aggregates)
and non-specific interstitial pneumonia (NSIP).
Risk factors: Smoking (in 75%), occupational exposure to metal (steel, brass, lead) or wood
(pine) in 20% cases; chronic microaspiration, animal and vegetable dusts.
E P IDEMIOLOGY
Rare. Prevalence in UK is 6 in 100 000. <:, is 2 : 1. Mean age 67 years.
H ISTORY
Gradual onset of progressive dyspnoea on exertion.
Dry irritating cough. No wheeze.
Symptoms may be preceded by a viral-type illness.
Fatigue and weight loss are common.
Full occupational and drug history is important.
EXAMINA T I ON
Finger clubbing (50%).
Bibasal fine late inspiratory crepitations.
Signs of right heart failure in advanced stages (e.g. right ventricular heave, raised JVP,
peripheral oedema).
INVE S T I G A T IONS
Blood: ABG (normal in early disease, but # PO2 on exercise; normal PCO2 which rises in late
disease). One-third have rheumatoid factor or antinuclear antibodies.
CXR: Usually normal at presentation. Early disease may feature small lung fields and ‘ground
glass’ shadowing. Later, there is reticulonodular shadowing (especially at bases), signs of
cor pulmonale and eventually, in advanced disease, honeycombing.
High-resolution CT: More sensitive in early disease than CXR. Affecting mainly lower zones
and subpleural areas, with reticular densities, honeycombing and traction bronchiectasis.
Pulmonary function tests: Restrictive ventilatory defect (# FEV1, # FVC with preserved or
increased ratio), # lung volumes, # lung compliance and # TLCO.
Bronchoalveolar lavage: To exclude infections and malignancy.
Lung biopsy: Gold standard for diagnosis but may not be appropriate.
Echocardiography: To look for pulmonary hypertension.
MANAGEMENT
No curative treatment available.
Combination of azathioprine, oral glucocorticoids and high-dose acetylcysteine, reassess the
response (symptoms, lung function tests) every 3 months. After 3–6 months of treatment,
if there is no evidence of a response, treatment is discontinued. Immunosuppressant
therapy may not be offered to patients with severe loss of lung function or extensive
fibrosis on high-resolution chest CT.
Supportive care: Home oxygen may be necessary. Pulmonary rehabilitation. Opiates in
terminal stages for relieving distressing breathlessness. Psychosocial support is necessary
because of poor long-term prognosis.
Acute exacerbation: Broad-spectrum antibiotics and high-dose glucocorticoids.
Idiopathic fibrosing alveolitis (continued)
Surgical: Single lung transplantation. Lung transplantation may be an option for patients
with progressive disease and minimal comorbidities.
COMPL I C A T IONS
Right heart failure. Lung cancer (12%). Pulmonary embolus. Death
from respiratory failure.
P ROGNOSIS
Poor; mean survival is only about 3 years. Good prognostic factors:
Clinical: Young age, female, response to steroids.
Radiological: Predominantly ‘ground glass’ shadowing.
Histology: DIP and NSIP better response to treatment than UIP.
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