To identify the determinants of survival in patients with idiopathic pulmonary fibrosis (IPF), we performed a survival analysis on 74 subjects with IPF. The study subjects were on average 64 yr of age (range, 25 to 83 yr), 62% were male, and 29% were never smokers. A tissue diagnosis was made in 67 (91%) of our study subjects. These subjects were followed for a mean period of 4 yr (range, 1.4 to 118.8 months) after the onset of pulmonary symptoms. During the period of observation, 41 subjects died (median survival = 28.2 months) and 33 continue to survive (median follow-up period = 60.9 months). A univariate analysis demonstrated that diminished survival was significantly associated with male gender (hazard ratio = 1.98; 95% confidence interval [CI] = 1.01-3.85), a higher FEV1/FVC ratio (hazard ratio = 1.82 [per 10% increase in the FEV1/FVC ratio]; 95% CI = 1.21-2.73), a lower percent predicted FVC (hazard ratio = 0.74; 95% CI = 0.60-0.91), a lower percent predicted total lung capacity (TLC) (hazard ratio = 0.75; 95% CI = 0.60-0.94), a lower percent predicted diffusing capacity of carbon monoxide (DLCO) (hazard ratio = 0.69; 95% CI = 0.53-0.89), a higher ILO profusion category on chest radiograph (hazard ratio = 3.52; 95% CI = 1.58-7.87), and an enhanced release of prostaglandin E2 (PGE2) by cultured alveolar macrophages (hazard ratio = 1.32 [per 10 pm/ml of PGE2]; 95% CI = 1.07-1.62).(ABSTRACT TRUNCATED AT 250 WORDS)

To assess whether working in a swine confinement facility causes an excess or accelerated decline in lung function, we conducted a population-based study to evaluate the determinants of longitudinal changes in airflow in a population of swine confinement operators. Spirometric measures of lung function were compared between swine confinement operators (N = 168) and neighborhood farmer control subjects (N = 127). Study subjects were randomly selected from a cohort of swine confinement operators in eastern Iowa. The control farming population was matched by geographic location, age, and sex to the swine confinement operators. On average, the follow-up time was approximately 2 yr, with a range of follow-up between 56 and 1,900 d. Although swine confinement operators and neighborhood farmers had similar demographic characteristics (age, gender, racial background, smoking history, and atopy status), swine confinement operators tended to have less farming experience and were more extensively followed (more measures of lung function and longer periods of observation) than the neighborhood farmer control group. Swine confinement operators were also exposed to higher environmental dust concentrations and other irritants than the farmer control subjects. Interestingly, the cross-sectional data indicated that swine confinement operators tended to have slightly lower measures of airflow and greater workshift declines in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and mid-expiratory flow (FEF25-75) than the neighborhood farmer control group.(ABSTRACT TRUNCATED AT 250 WORDS)

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 (DLCO) during the period of observation. Although, on average, there was a 5.3% increase in the TLC and a 9.8% increase in DLCO 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 DLCO. Decrements in TLC were independently associated with severe dyspnea (p = 0.01) and treatment with cyclophosphamide (p = 0.03). Decrements in DLCO 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 DLCO in patients with IPF.(ABSTRACT TRUNCATED AT 250 WORDS)

To prospectively identify the determinants of persistent or accelerated loss of lung function among workers occupationally exposed to asbestos and assess the relative contribution of cigarette smoking, asbestos-induced pleural fibrosis, and specific findings from bronchoalveolar lavage and high resolution CT scans, we examined the determinants of lung function changes in 117 subjects occupationally exposed to asbestos for at least 1 yr in a high exposure setting. A minimum of 20 yr was required between the first exposure to asbestos and entry into the study. Baseline studies included an independent assessment of dyspnea, lung volumes, diffusing capacity of carbon monoxide (DLCO), a chest radiograph, a high resolution CT (HRCT) scan, and bronchoalveolar lavage (BAL). Subjects were observed for an average of 2 yr (range, 0.5 to 4.0 yr), and lung function was measured on at least two separate occasions (mean, 4.1 separate tests). During the period of observation, there was an average 1.5% decrease in the TLC and a 2.5% decrease in the DLCO. In this longitudinal data set, after controlling for age, height, pack-years of cigarette smoking, and follow-up time, persistently lower measures of TLC were independently related to moderate to severe dyspnea (p = 0.005), diffuse pleural thickening (p = 0.007), and higher concentrations of fibronectin in BAL fluid (p = 0.01). Interstitial lung disease either on the chest radiograph or HRCT scan was not independently associated with persistently lower measures of TLC during the period of observation. However, none of the clinical variables we examined were associated with an accelerated decline in TLC.(ABSTRACT TRUNCATED AT 250 WORDS)