Shortfalls in imputing sarcoidosis to occupational exposures

The cause of sarcoidosis remains elusive. Reports of elevated sarcoidosis incidence in New York City firefighters and World Trade Center disaster responders have been advanced to support a causal relationship. This inference is open to question due to methodological differences in assessing and computing sarcoidosis incidence in populations versus putative occupational exposures. The magnitude of the odds ratio (OR; ca. 1.5) of causal candidates in the ACCESS case‐control study of occupational and environmental exposures is sufficiently small that it might easily be attributable to confounders. Additionally, multiplicity of comparisons, difficulty in assembling a valid control population and the potential for recall bias critically limit causal inferences. A possible explanation for etiological elusiveness and multiplicity of elevated OR is that individuals with sarcoidosis, lacking components of efficient cellular immunity, respond with systemic granulomas to a variety of ubiquitous, frequently unidentifiable environmental antigens. Epidemiological methods for the identification of sarcoidosis causal candidates are potentially misleading and are unlikely to prove useful. Am. J. Ind. Med. 56:496–500, 2013. © 2012 Wiley Periodicals, Inc.     

Premenstrual Asthma: The Effect of Estrogen on Symptoms,Pulmonary Function,and β2-Receptors

Study Objectives . To characterize asthma symptoms, pulmonary function, and responsiveness to β₂-agonist stimulation, and in vitro β₂-receptor density and cyclic adenosine 3′,5′-monophosphate (cAMP) response throughout the menstrual cycle in women with premenstrual asthma (PMA); and to examine the effect of exogenous estradiol administration on asthma symptoms, pulmonary function and responsiveness, and β₂-receptor density and function in these women. Design . Open-label, longitudinal, 9-week study. Setting . A university clinical research center. Patients . Seventeen women with mild to moderate asthma, of whom 14 completed the study. Interventions . Every morning on awakening during the entire 9-week study, each subject completed visual analog scales for asthma symptomatology (cough, wheezing, breathlessness, chest tightness) and measured and recorded her peak expiratory flow rate (PEFR) with a peak flow meter. Also measured at various times throughout the menstrual cycle were dyspnea index scores, pulmonary function (PEFR, forced expiratory volume in 1 sec [FEV₁]), pulmonary response to subcutaneous terbutaline, T lymphocyte β₂-receptor density (B_max) and function (cAMP), and estradiol, progesterone, and catecholamine concentrations, both with and without exogenous estradiol administration. Measurements and Main Results . At the time of enrollment, only 5 subjects reported premenstrual worsening of asthma symptoms, but all 14 had greater than 20% decrease in PEFR and/or increase in symptoms premenstrually during the study. Significant differences (p<0.05) existed in asthma symptoms and PEFR between day 13 (highest estradiol concentrations) and day 26 (lowest estradiol concentrations) of the menstrual cycle. Asthma symptoms and dyspnea index scores were significantly improved (p<0.05) after estradiol administration compared with baseline (premenstrual period without exogenous estrogen). Pulmonary response to terbutaline, β₂-receptor density and function, and catecholamine concentrations were not significantly altered after estradiol administration, but the trend was toward significant differences (0.05 < p < 0.2) in pulmonary function tests (PEFR, FEV₁). Conclusions . Even asthmatics not previously aware of PMA may experience premenstrual worsening of asthma symptoms and/or PEFR. Estradiol is associated with a significant improvement in asthma symptoms and dyspnea index scores. This ameliorating effect does not appear to be related to β₂-receptors.