Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) is the most common form of idiopathic interstitial pneumonia, corresponding to progressive pulmonary fibrosis and predominantly in male smokers. Symptoms of idiopathic pulmonary fibrosis develop over months to years and include dyspnea on exertion, cough, and fine wheezing.

Diagnosis is made by history, physical examination, chest radiography, and pulmonary function tests, and is confirmed by HRCT, lung biopsy, or both when necessary. No specific treatment has been shown to be effective for idiopathic pulmonary fibrosis, but glucocorticoids, cyclophosphamide, azathioprine, or combinations of these are often used. Most patients deteriorate despite treatment; median survival is less than 3 years from diagnosis.

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Causes of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis, defined histologically as usual interstitial pneumonia, accounts for 50% of cases of idiopathic interstitial pneumonia and occurs in both men and women aged 50 to 60 years in a ratio of 2:1. Current or previous smoking is strongly associated with the disease. There is some genetic predisposition: a family history is noted in 3% of patients.

Although idiopathic pulmonary fibrosis is referred to as pneumonia, inflammation probably plays a relatively minor role. Environmental, genetic, or other unknown factors are thought to initially cause alveolar epithelial injury, but proliferation of specific and aberrant interstitial fibroblasts and mesenchymal cells (with collagen deposition and fibrosis) probably underlie the clinical development of the disease. Key histologic features are subpleural fibrosis with foci of fibroblast proliferation and areas of marked fibrosis interspersed with areas of normal lung tissue. Widespread interstitial inflammation is accompanied by lymphocytic, plasmacytic, and histiocytic infiltration. Cystic dilatation of the peripheral alveoli ("honeycombing") is found in all patients and increases with disease progression. This histologic pattern is uncommon in IBLAR of known etiology; the term usual interstitial pneumonia is used for idiopathic lesions with no obvious cause.

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Symptoms of Idiopathic Pulmonary Fibrosis

Symptoms of idiopathic pulmonary fibrosis typically develop over 6 months to several years and include dyspnea on exertion and nonproductive cough. Systemic symptoms ( subfebrile fever and myalgia) are rare. The classic sign of idiopathic pulmonary fibrosis is sonorous, dry, bilateral basal inspiratory fine bubbling rales (similar to the sound of Velcro opening). Clubbing of the terminal phalanges of the fingers is present in approximately 50% of cases. The rest of the examination findings remain normal until the end-stage of the disease, when manifestations of pulmonary hypertension and right ventricular systolic dysfunction may develop.

Diagnosis of idiopathic pulmonary fibrosis

Diagnosis is based on history, imaging, pulmonary function tests, and biopsy. Idiopathic pulmonary fibrosis is commonly misdiagnosed as other conditions with similar clinical manifestations, such as bronchitis, asthma, or heart failure.

Chest X-ray usually reveals diffuse enhancement of the pulmonary pattern in the lower and peripheral zones of the lung. Small cystic enlightenments ("honeycomb lung"), dilated airways due to the development of bronchiectasis may be additional findings.

Pulmonary function tests typically show restrictive changes. Diffusing capacity for carbon monoxide (DI_CO) is also reduced. Arterial blood gas testing reveals hypoxemia, which is often aggravated or detected by physical exertion and low arterial CO concentrations.

HRCT reveals diffuse or focal subpleural enhancement of the pulmonary pattern with asymmetrically thickened interlobular septa and intralobular thickening; subpleural honeycombing and traction bronchiectasis. Ground-glass opacities involving more than 30% of the lung suggest an alternative diagnosis.

Laboratory studies play a minor role in diagnosis. Elevated ESR, C-reactive protein levels, and hypergammaglobulinemia are common. Antinuclear antibody or rheumatoid factor levels are elevated in 30% of patients and, depending on specific values, may exclude connective tissue diseases.

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Treatment of idiopathic pulmonary fibrosis

No specific treatment option has demonstrated efficacy. Supportive care for idiopathic pulmonary fibrosis consists of oxygen inhalation for hypoxemia and antibiotics for pneumonia. Terminal disease may require lung transplantation in selected patients. Glucocorticoids and cytotoxic agents (cyclophosphamide, azathioprine) have traditionally been given empirically to patients with idiopathic pulmonary fibrosis in an attempt to halt the progression of inflammation, but limited data support their efficacy. However, it is common practice to try prednisolone (orally at a dose of 0.5 mg/kg to 1.0 mg/kg once daily for 3 months, then tapering to 0.25 mg/kg once daily for the next 3 to 6 months) in combination with cyclophosphamide or azathioprine (orally at a dose of 1 mg/kg to 2 mg/kg once daily and N-acetylcysteine 600 mg 3 times daily orally as an antioxidant). Clinical, radiographic, and physical assessments and drug dosage adjustments are performed every 3 months to once a year. Treatment of idiopathic pulmonary fibrosis is discontinued if there is no objective response.

Pirfenidone, a collagen synthesis inhibitor, may stabilize lung function and reduce the risk of exacerbations. The efficacy of other antifibrotic agents, in particular those that inhibit collagen synthesis (relaxin), profibrotic growth factors (suramin), and endothelin-1 (angiotensin receptor blocker), has only been demonstrated in vitro.

Interferon-y-lb showed good effect when given with prednisone in a small study, but a large double-blind, multinational randomized trial found no effect on disease-free survival, lung function, or quality of life.

Lung transplantation is successful in patients with end-stage idiopathic pulmonary fibrosis who do not suffer from concomitant pathology and are aged no older than 55 years (which accounts for <40% of all patients with idiopathic pulmonary fibrosis).

Forecast

Most patients have moderate to severe clinical manifestations of the disease at diagnosis; idiopathic pulmonary fibrosis often progresses despite treatment. Normal values of PaO2 at diagnosis and fewer fibroblastic foci detected by histological examination of biopsy material improve the prognosis of the disease. In contrast, the prognosis is worse in old age and even worse in those with decreased lung function at diagnosis and severe dyspnea. The median survival is less than 3 years from diagnosis. An increase in the frequency of hospitalizations for sudden respiratory tract infections and pulmonary failure indicates an imminent fatal outcome in the patient, which requires care planning. Lung cancer is more common in patients with idiopathic pulmonary fibrosis, but the cause of death in them is usually respiratory failure, respiratory tract infections, or heart failure with ischemia and arrhythmia.

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