Interferon Gamma-1b for Pulmonary Fibrosis

Abstract

The recent trial of interferon gamma-1b for idiopathic pulmonary fibrosis, reported by Raghu et al. (Jan. 8 issue),¹ is a major accomplishment, despite the disappointing results. One may wonder, however, whether the selected end points were optimal. A decline in the forced vital capacity by at least 10 percent of the predicted value seems a robust criterion, but the criterion for the difference between alveolar and arterial oxygen tension (P(A–a)O₂), which accounted for 55 percent of the primary end-point events, is weak. Day-to-day variations in barometric pressure, the effective alveolar ventilation, and random errors in measurement can easily conspire to produce a rise of 5 mm Hg in the P(A–a)O₂ without an important or lasting physiological change in the patient. In addition, the report is unclear about when “progression of disease” was determined. A sophisticated assessment of gas exchange might not be feasible in a large, multicenter trial, but other means of evaluation (e.g., a six-minute walk, measurement of oxyhemoglobin desaturation during light exercise, or even a full cardiorespiratory exercise test) might prove practicable and informative. Data on systemic markers of inflammation and collagen metabolism would be of supplementary interest. We hope that this study will pave the way for additional large-scale trials of treatment for idiopathic pulmonary fibrosis and similar difficult diseases, such as unremitting sarcoidosis.