Antielastin autoimmunity in tobacco smoking-induced emphysema.

Chronic obstructive pulmonary disease and emphysema are common destructive inflammatory diseases that are leading causes of death worldwide. Here we show that emphysema is an autoimmune disease characterized by the presence of antielastin antibody and T-helper type 1 (T(H)1) responses, which correlate with emphysema severity. These findings link emphysema to adaptive immunity against a specific lung antigen and suggest the potential for autoimmune pathology of other elastin-rich tissues such as the arteries and skin of smokers.

Lung myeloid dendritic cells coordinately induce TH1 and TH17 responses in human emphysema.

Exposure to tobacco smoke activates innate and adaptive immune responses that in long-term smokers have been linked to diseases of the lungs, cardiovascular system, joints, and other organs. The destruction of lung tissue that underlies smoking-induced emphysema has been associated with T helper 1 cells that recognize the matrix protein elastin. Factors that result in the development of such autoreactive T cells in smokers remain unknown but are crucial for further understanding the pathogenesis of systemic inflammatory diseases in smokers. Here, we show that lung myeloid dendritic cells were sufficient to induce T helper 1 and T helper 17 responses in CD4 T cells. T helper 1 and 17 cells are invariably present in lungs from patients with emphysema but not in lungs from normal individuals. Interleukin-17A, a canonical T helper 17 cytokine, enhanced secretion of CCL20, a chemoattractant for dendritic cells, and matrix metalloproteinase 12, a potent elastolytic proteinase, from lung macrophages. Thus, although diverse lung factors potentially contribute to T helper effector differentiation in vivo, lung myeloid dendritic cells direct the generation of pathogenic T cells and support a feedback mechanism that sustains both inflammatory cell recruitment and lung destruction. This mechanism may underlie disease in other elastin-rich organs and tissues.

Abdominal obesity and the risk of Barrett's esophagus.

BACKGROUND: The association between overweight/obesity and the risk of Barrett's esophagus (BE) is unclear. Further, the association between body fat distribution and the risk of BE is unknown. METHODS: We conducted a retrospective case-control study in patients who underwent endoscopy at a single large VA Medical Center between 2000 and 2003. Cases were patients with documented BE who had an abdominal CT scan within 1 yr of the endoscopy, whereas controls were patients without BE (with or without erosive esophagitis) who also had an abdominal CT scan. The surface areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated from CT scan images at level of intervertebral disc between L4 and L5, and body mass index (BMI) in kg/m2 at the time of endoscopy was also recorded. Cases and controls were compared in univariate and multivariable analyses. RESULTS: We identified 36 cases and 93 controls. There were no significant differences between cases and controls in age (mean 63 yr), gender (98% men), or race (71% white Caucasian). BMI was significantly greater in cases than controls (27 vs 24; p= 0.006). BMI >30 kg/m2 was associated with a greater risk of BE than lower BMI (odds ratio 4.0; 95% CI: 1.4-11.1, p= 0.008). VAT was approximately 1.5-fold greater in cases than controls (183 vs 115 cm2; p < 0.0001), whereas SAT was less different (248 vs 200 cm2; p= 0.03). We estimated that each 10-cm2 increase in VAT was associated with 9% increase in risk of BE. Interestingly, VAT remained independently associated with BE in the model that adjusted for BMI, and in that model, BMI was not significantly associated with BE. CONCLUSIONS: Obesity seems to be associated with an increased risk of BE. Abdominal visceral adiposity might mediate most of this risk.