Publications

Despite the equipoise regarding alcohol's cardiovascular effects and absence of relevant rigorous controlled trials, the lay press frequently portrays alcohol as "heart healthy." The public perception of alcohol's heart effects, the sources of those perceptions, and how they may affect behavior are unknown. We performed a cross-sectional analysis of data obtained from March 2013 to September 2014 from consecutive participants enrolled in the Health eHeart Study. Of 5,582 participants, 1,707 (30%) viewed alcohol as heart healthy, 2,157 (39%) viewed it as unhealthy, and 1,718 (31%) were unsure. Of those reporting alcohol as heart healthy, 80% cited lay press as a source of their knowledge. After adjustment, older age (odds ratio 1.11), higher education (odds ratio 1.37), higher income (odds ratio 1.07), US residence (odds ratio 1.63), and coronary artery disease (odds ratio 1.51) were associated with perception of alcohol as heart healthy (all p <0.003). Ever smokers (odds ratio 0.76, p = 0.004) and those with heart failure (odds ratio 0.5, p = 0.01) were less likely to cite alcohol as heart healthy. Those perceiving alcohol as heart healthy consumed on average 47% more alcohol on a regular basis (95% confidence interval 27% to 66%, p <0.001). In conclusion, of >5,000 consecutive Health eHeart participants, approximately 1/3 believed alcohol to be heart healthy, and the majority cited the lay press as the origin of that perception. Those with a perception of alcohol as heart healthy drink substantially more alcohol.

Acute respiratory distress syndrome (ARDS) is a devastating disorder characterized by increased alveolar permeability with no effective treatment beyond supportive care. Current mechanisms underlying ARDS focus on alveolar endothelial and epithelial injury caused by products of innate immune cells and platelets. However, the role of adaptive immune cells in ARDS remains largely unknown. In this study, we report that expansion of Ag-specific αβTh17 cells contributes to ARDS by local secretion of IL-17A, which in turn directly increases alveolar epithelial permeability. Mice with a highly restrictive defect in Ag-specific αβTh17 cells were protected from experimental ARDS induced by a single dose of endotracheal LPS. Loss of IL-17 receptor C or Ab blockade of IL-17A was similarly protective, further suggesting that IL-17A released by these cells was responsible for this effect. LPS induced a rapid and specific clonal expansion of αβTh17 cells in the lung, as determined by deep sequencing of the hypervariable CD3RβVJ region of the TCR. Our findings could be relevant to ARDS in humans, because we found significant elevation of IL-17A in bronchoalveolar lavage fluid from patients with ARDS, and rIL-17A directly increased permeability across cultured human alveolar epithelial monolayers. These results reveal a previously unexpected role for adaptive immune responses that increase alveolar permeability in ARDS and suggest that αβTh17 cells and IL-17A could be novel therapeutic targets for this currently untreatable disease.

BACKGROUND

The association between occupational exposure and autoimmune disease is well recognized for silica, and suspected for other inhalants. We used a large cohort to estimate the risks of rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and dermatomyositis associated with silica and other occupational exposures.

METHODS

We analyzed data for male Swedish construction industry employees. Exposure was defined by a job-exposure matrix for silica and for other inorganic dusts; those with other job-exposure matrix exposures but not to either of the 2 inorganic dust categories were excluded. National hospital treatment data were linked for International Classification of Diseases, 10(th) Revision-coded diagnoses of rheumatoid arthritis (seronegative and positive), systemic lupus erythematosus, systemic sclerosis, and dermatomyositis. The 2 occupational exposures were tested as independent predictors of prospective hospital-based treatment for these diagnoses using age-adjusted Poisson multivariable regression analyses to calculate relative risk (RR).

RESULTS

We analyzed hospital-based treatment data (1997 through 2010) for 240,983 men aged 30 to 84 years. There were 713 incident cases of rheumatoid arthritis (467 seropositive, 195 seronegative, 51 not classified) and 128 cases combined for systemic lupus erythematosus, systemic sclerosis, and dermatomyositis. Adjusted for smoking and age, the 2 occupational exposures (silica and other inorganic dusts) were each associated with increased risk of rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and dermatomyositis combined: RR 1.39 (95% confidence interval [CI], 1.17-1.64) and RR 1.31 (95% CI, 1.11-1.53), respectively. Among ever smokers, both silica and other inorganic dust exposure were associated with increased risk of rheumatoid arthritis (RRs 1.36; 95% CI, 1.11-1.68 and 1.42; 95% CI, 1.17-1.73, respectively), while among never smokers, neither exposure was associated with statistically significant increased risk of rheumatoid arthritis.

CONCLUSION

This analysis reaffirms the link between occupational silica and a range of autoimmune diseases, while also suggesting that other inorganic dusts may also impart excess risk of such disease.