Rationale: Evidence suggests that tumor necrosis factor (TNF)-α plays an important role in the pathophysiology of sarcoidosis. Objectives: To assess the efficacy of infliximab in sarcoidosis. Methods: A phase 2, multicenter, randomized, double-blind, placebo-controlled study was conducted in 138 patients with chronic pulmonary sarcoidosis. Patients were randomized to receive intravenous infusions of infliximab (3 or 5 mg/kg) or placebo at Weeks 0, 2, 6, 12, 18, and 24 and were followed through Week 52. Measurements and Main Results: The primary endpoint was the change from baseline to Week 24 in percent of predicted FVC. Major secondary efficacy parameters included Saint George's Respiratory Questionnaire, 6-min walk distance, Borg's CR10 dyspnea score, and the proportion of Lupus Pernio Physician's Global Assessment responders for patients with facial skin involvement. Patients in the combined infliximab groups (3 and 5 mg/kg) had a mean increase of 2.5% from baseline to Week 24 in the percent of predicted FVC, compared with no change in placebo-treated patients (p = 0.038). No significant differences between the treatment groups were observed for any of the major secondary endpoints at Week 24. Results of post hoc exploratory analyses suggested that patients with more severe disease tended to benefit more from infliximab treatment. Conclusions: Infliximab therapy resulted in a statistically significant improvement in % predicted FVC at Week 24. The clinical importance of this finding is not clear. The results of this Phase 2 clinical study support further evaluation of anti–TNF-α therapy in severe, chronic, symptomatic sarcoidosis.

Air pollution has been associated with impaired health, including reduced lung function in adults. Moving to cleaner areas has been shown to attenuate adverse effects of air pollution on lung function in children but not in adults. We conducted a prospective study of 9651 adults (18 to 60 years of age) randomly selected from population registries in 1990 and assessed in 1991, with 8047 participants reassessed in 2002. There was complete information on lung volumes and flows (e.g., forced vital capacity [FVC], forced expiratory volume in 1 second [FEV₁], FEV₁ as a percentage of FVC, and forced expiratory flow between 25 and 75% of the FVC [FEF_25–75]), smoking habits, and spatially resolved concentrations of particulate matter that was less than 10 μm in aerodynamic diameter (PM₁₀) from a validated dispersion model assigned to residential addresses for 4742 participants at both the 1991 and the 2002 assessments and in the intervening years. Overall exposure to individual home outdoor PM₁₀ declined over the 11-year follow-up period (median, −5.3 μg per cubic meter; interquartile range, −7.5 to −4.2). In mixed-model regression analyses, with adjustment for confounders, PM₁₀ concentrations at baseline, and clustering within areas, there were significant negative associations between the decrease in PM₁₀ and the rate of decline in FEV₁ (P=0.045), FEV₁ as a percentage of FVC (P=0.02), and FEF_25–75 (P=0.001). The net effect of a decline of 10 μg of PM₁₀ per cubic meter over an 11-year period was to reduce the annual rate of decline in FEV₁ by 9% and of FEF_25–75 by 16%. Cumulative exposure in the interval between the two examinations showed similar associations. Decreasing exposure to airborne particulates appears to attenuate the decline in lung function related to exposure to PM₁₀. The effects are greater in tests reflecting small-airway function.

Pulmonary hypertension during exercise is common in severe chronic obstructive pulmonary disease (COPD). It was hypothesised that the use of the endothelin-receptor antagonist bosentan can improve cardiopulmonary haemodynamics during exercise, thus increasing exercise tolerance in patients with severe COPD.In the present double-blind, placebo-controlled study, 30 patients with severe or very severe COPD were randomly assigned in a 2:1 ratio to receive either bosentan or placebo for 12 weeks. The primary end-point was change in the 6-min walking distance. Secondary end-points included changes in health-related quality of life, lung function, cardiac haemodynamics, maximal oxygen uptake and pulmonary perfusion patterns.Compared with placebo, patients treated with bosentan during 12 weeks showed no significant improvement in exercise capacity as measured by the 6-min walking distance (mean±sd331±123versus329±94 m). There was no change in lung function, pulmonary arterial pressure, maximal oxygen uptake or regional pulmonary perfusion pattern. In contrast, arterial oxygen pressure dropped, the alveolar–arterial gradient increased and quality of life deteriorated significantly in patients assigned bosentan.The oral administration of the endothelin receptor antagonist bosentan not only failed to improve exercise capacity but also deteriorated hypoxaemia and functional status in severe chronic obstructive pulmonary disease patients without severe pulmonary hypertension at rest.

The association between passive exposure to tobacco smoke and respiratory symptoms was examined in a sample of 4,197 never-smoking adults. They constituted the never-smoking subsample of a random sample of 9,651 adults (age, 18 to 60 yr) in eight areas in Switzerland. Information on passive smoking exposure and standardized questions on respiratory symptoms were obtained via a questionnaire administered by trained examiners. After controlling for age, sex, body mass index (BMI), study area, atopy, and parental and sibling history, passive smoking exposure was associated with an elevated risk of wheezing apart from colds (odds ratio [OR] = 1.94, 95% CI = 1.39 to 2.70), an elevated risk of bronchitis symptoms (OR = 1.59, 95% CI = 1.17 to 2.15), an elevated risk of symptoms of chronic bronchitis (OR = 1.65, 95% CI = 1.28 to 2.16), an elevated risk of dyspnea (OR = 1.45, 95% CI = 1.20 to 1.76), and an elevated risk of physician diagnosed asthma (OR = 1.39, 95% CI = 1.04 to 1.86). It was not associated with any increased risk of allergic rhinitis including hayfever. Adding a variable for low educational level, excluding subjects whose mother ever smoked or subjects with end-expiratory CO levels > or = 7 ppm, and controlling for paternal smoking during childhood or occupational exposure had little impact on the association. The association of passive smoking exposure with dyspnea, wheeze, and asthma showed evidence of a dose-dependent increase with hours per day of exposure, whereas association with symptoms of bronchitis was stronger with years of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)