DETERMINANTS OF PROGRESSION IN IDIOPATHIC PULMONARY FIBROSIS

Idiopathic pulmonary fibrosis (IPF) is a progressive form of lung disease with a median survival of less than 5 yr. To address the progressive nature of this disease process, we investigated the determinants of decrements in lung function in patients with IPF. We prospectively evaluated 39 subjects with IPF. Our study subjects were followed for an average of 2 yr (range, 49 to 1,883 days) and lung function was measured on at least two separate occasions (mean = 9.1 separate tests) during the follow-up period. Since IPF is characterized by reduced lung volume and abnormal gas exchange, our analysis focused on the determinants of total lung capacity (TLC) and diffusing capacity of carbon monoxide (DL(CO)) during the period of observation. Although, on average, there was a 5.3% increase in the TLC and a 9.8% increase in DL(CO) between the first and last measure of lung function, 25% of the study population experienced a decline in the TLC and 28% of the study population experienced a decline in the DL(CO). Decrements in TLC were independently associated with severe dyspnea (p = 0.01) and treatment with cyclophosphamide (p = 0.03). Decrements in DL(CO) were significantly and independently associated with more pack-years of cigarette smoking (p = 0.02), moderate (p = 0.03) or severe (p = 0.02) dyspnea, and treatment with cyclophosphamide (p = 0.0002). These findings indicate that several clinical characteristics are independently associated with subsequent declines in TLC and DL(CO) in patients with IPF. These results raise the possibility of using these prognostic factors (clinical symptoms, smoking history, and need for immunosuppressive therapy) to assess the risk for disease progression in patients with IPF.