ABSTRACT
Aims: Exposure to dusts/bioaerosols in concentrated animal feeding operations (CAFOs) results in inflammatory lung diseases in workers. Hog CAFOs dust extract (HDE) increases expression of intercellular adhesion molecule-1 (ICAM-1), neutrophil adhesion, and TNFα release in bronchial epithelial cells. Alcohol consumption is increasingly recognized to impair lung immunity. We hypothesized that alcohol impairs HDE-induced TNFα, ICAM-1 expression and neutrophil adhesion by directly inhibiting TNFα converting enzyme (TACE) activity. METHODS: Bronchial epithelial cells (BEAS-2B) and primary human bronchial epithelial cells were pretreated with ethanol (EtOH) or TACE inhibitor. ICAM-1 surface expression, TNFα release, and TACE activity were analyzed following HDE stimulation. The effect of alcohol and TACE inhibition on HDE-regulated epithelial cell/neutrophil adhesion interactions was investigated. Finally, utilizing an established animal model, C57BL/6 mice were fed ad libitum ethanol (20%) in drinking water for 8 wk followed by daily intranasal inhalation of HDE or saline during the final two weeks. Mice were sacrificed and lung sections immunostained for ICAM-1. RESULTS: Pretreatment with alcohol or TACE inhibitor significantly decreased HDE-induced ICAM-1 expression and TNFα release. HDE augmented neutrophil adhesion to epithelial cells, which was decreased with alcohol (32% decrease) or TACE inhibitor (55% decrease) pretreatment. TACE activity increased following HDE exposure, but TACE activity was inhibited following alcohol pretreatment. Alcohol-fed mice demonstrated decreased HDE-induced airway epithelium ICAM-1 expression. CONCLUSIONS: Alcohol diminishes HDE-induced ICAM-1 expression, TNFα release, and neutrophil adhesion via inhibition of TACE activity. These results suggest that alcohol may be an important modulator of lung innate immune responses following CAFO exposure.
ABSTRACT
The objective of this study was to examine the association between body mass index (BMI) and the incidence of pulmonary complications (PCs) after hematopoietic stem cell transplant (HCT). We reviewed 398 adult patients with non-Hodgkin lymphoma (NHL) who received autologous or allogeneic HCT between 1993 and 1997. BMI was classified as normal (18.5 < BMI ≤ 24.9), overweight (24.9 < BMI ≤ 30) and obese (BMI > 30). Multivariate logistic regression was used to analyze the relationship between BMI and presence of PCs within 100 days post-HCT while adjusting for patient-, disease- and transplant-related variables. The incidence of PCs within 100 days post-HCT was 32% (n = 129). Median BMI was 25.4 (range: 18.6-52.2). Median age was 48.8 years (range: 19.5-73.6 years). Multivariate analysis failed to show significant association between BMI and PCs. However, a total body irradiation (TBI)-based conditioning regimen was associated with lower rate of PCs.