Idiopathic Pulmonary Fibrosis

Abstract

SUMMARY Idiopathic pulmonary fibrosis is a precise syndrome defined by clinical, roentgenographic, physiologic, and histopathologic features. Clinically, most patients have a nonproductive cough and dyspnea on exertion. The most common physical finding is the presence of crackles over the lower portions of both lungs; also, there may be clubbing, cyanosis, and evidence of pulmonary hypertension. The chest roentgenogram may be normal but generally shows a reticular or reticulonodular pattern of interstitial lung disease. Vital capacity and lung compliance may be normal in early disease but typically become reduced as the disease progresses. Other physiologic alterations included reduced diffusing capacity, elevation in the proportion of wasted ventilation, normal maximum breathing capacity, exercise-induced arterial oxygen desaturation, and pulmonary hypertension (particularly during exercise). The earliest pathologic changes following injury to the alveolarcapillary unit is fibrinous exudation into the alveolar spaces and proliferation of type II alveolar epithelial cells. Also characteristic of the early tissue reaction is an alveoli tis, with the influx of inflammatory and immune effector cells into the distal lung parenchyma. If the alveolitis continues unchecked, connective tissue alterations result in marked thickening of the alveolar walls and finally in severe derangement of the lung parenchyma. The natural history of idiopathic pulmonary fibrosis varies considerably. Some patients progress to end-stage disease within a few months, and some patients survive more than 15 years with this syndrome. However, the average survival is around four years. An important determinant of survival is the responsiveness to therapy. Corticosteroids are the mainstay of treatmeht, but an objective response is evident in only a minority of patients. To be successful, therapy must be started while there is an active alveolitis. Commonly used methods of staging the disease, such as chest roentgenograms and pulmonary function tests, are not sensitive to the presence of alveolitis. Current investigation mainly involves the utility of new methods for detecting and monitoring alveolitis. Also, progress is being made in understanding the basic immunologic alterations responsible for idiopathic pulmonary fibrosis. These advances in basic and clinical research offer the hope of improved therapy and prognosis for patients with this syndrome.