DETERMINANTS OF SURVIVAL IN IDIOPATHIC PULMONARY FIBROSIS

To identify the determinants of survival in patients with idiopathic p ulmonary fibrosis (IPF), we performed a survival analysis on 74 subjec ts with IPF. The study subjects were on average 64 yr of age (range, 2 5 to 83 yr), 62% were male, and 29% were never smokers. A tissue diagn osis was made in 67 (91%) of our study subjects. These subjects were f ollowed for a mean period of 4 yr (range, 1.4 to 118.8 months) after t he onset of pulmonary symptoms. During the period of observation, 41 s ubjects died (median survival = 28.2 months) and 33 continue to surviv e (median follow-up period = 60.9 months). A univariate analysis demon strated that diminished survival was significantly associated with mal e gender (hazard ratio = 1.98; 95% confidence interval [CI] = 1.01-3.8 5), a higher FEV(1)/FVC ratio (hazard ratio = 1.82 [per 10% increase i n the FEV(1)/FVC ratio]; 95% CI = 1.21-2.73), a lower percent predicte d FVC (hazard ratio = 0.74; 95% CI = 0.60-0.91), a lower percent predi cted total lung capacity (TLC) (hazard ratio = 0.75; 95% CI = 0.60-0.9 4), a lower percent predicted diffusing capacity of carbon monoxide (D L(CO)) (hazard ratio = 0.69; 95% CI = 0.53-0.89), a higher ILO profusi on category on chest radiograph (hazard ratio = 3.52; 95% CI = 1.58-7. 87), and an enhanced release of prostaglandin E(2) (PGE(2)) by culture d alveolar macrophages (hazard ratio = 1.32 [per 10 pm/ml of PGE(2)]; 95% CI = 1.07-1.62). In fact, after controlling for age, Cox's regress ion analyses demonstrated that diminished survival was independently a ssociated with male gender (hazard ratio = 9.05; 95% CI = 1.84-44.5), a higher FEV(1)/FVC ratio (hazard ratio = 3.91 [per 10% increase in th e FEV(1)/FVC ratio]; 95% CI = 1.68-8.07), and an enhanced release of P GE(2) by cultured alveolar macrophages (hazard ratio = 1.45 [per 10 pm /ml of PGE(2)]; 95% CI = 1.14-1.83). Survival was not found to be inde pendently associated with the concentration of cells in the ravage flu id or other cytokines (tumor necrosis factor alpha [TNF alpha] and int erleukin-1 beta [IL-1 beta]) released by alveolar macrophages. Limitin g our analysis to subjects closely followed in our SCOR Program (n = 4 1), Cox's regression analysis (adjusted for age) demonstrated that dim inished survival was independently associated with male gender (hazard ratio = 8.21; 95% CI = 1.30-50.6), a higher ILO profusion category (h azard ratio = 4.00; 95% CI = 1.43-11.42), and a lower concentration of lymphocytes in bronchoalveolar ravage fluid (hazard ratio = 0.95; 95% CI = 0.91-0.99). In aggregate, our findings suggest that adverse prog nosticators in IPF include male gender, advanced disease (restrictive lung function, abnormal gas exchange, and increased interstitial abnor malities on the chest radiograph), and, possibly, increased release of PGE(2) from cultured alveolar macrophages.