Background Asthma in obese individuals is poorly understood, these patients are often refractory to standard therapy. Objectives To gain insights into the pathogenesis and treatment of asthma in obese individuals by determining how obesity and bariatric surgery affect asthma control, airway hyperresponsiveness and markers of asthmatic inflammation. Methods A prospective study of (i) asthmatic and non-asthmatic bariatric surgery patients compared at baseline, and (ii) asthmatic patients followed for 12 months after bariatric surgery. Results We studied 23 asthmatic and 21 non-asthmatic patients undergoing bariatric surgery. At baseline, asthmatics had lower FEV1 and FVC, and lower levels of lymphocytes in bronchoalveolar lavage. Following surgery, asthmatic participants experienced significant improvements in asthma control (asthma control score 1.55 to 0.74, p < 0.0001) and asthma quality of life (4.87 to 5.87, p < 0.0001). Airways responsiveness to methacholine improved significantly (PC20 3.9 to 7.28, p = 0.03). There was a statistically significant interaction between IgE status and change in airways responsiveness (p for interaction term = 0.01), improvement in AHR was significantly related to change in BMI in those with normal IgE (p = 0.02, R2 = 0.46). The proportion of lymphocytes in bronchoalveolar lavage and production of cytokines from activated peripheral blood CD4+ T cells increased significantly. Conclusions Bariatric surgery improves airway hyperresponsiveness in obese asthmatics with normal serum IgE. Weight loss has dichotomous effects on airway physiology and T cell function typically involved in the pathogenesis of asthma, suggesting that obesity produces a unique phenotype of asthma that will require a distinct therapeutic approach.

Rationale: Obesity is a major risk factor for asthma; the reasons for this are poorly understood, although it is thought that inflammatory changes in adipose tissue in obesity could contribute to airway inflammation and airway reactivity in individuals who are obese. Objectives: To determine if inflammation in adipose tissue in obesity is related to late-onset asthma, and associated with increased markers of airway inflammation and reactivity. Methods: We recruited a cohort of obese women with asthma and obese control women. We followed subjects with asthma for 12 months after bariatric surgery. We compared markers in adipose tissue and the airway from subjects with asthma and control subjects, and changes in subjects with asthma over time. Measurements and Main Results: Subjects with asthma had increased macrophage infiltration of visceral adipose tissue (P , 0.01), with increased expression of leptin (P , 0.01) and decreased adiponectin (p , 0.001) when controlled for body mass index. Similar trends were observed in subcutaneous adipose tissue. Airway epithelial cells expressed receptors for leptin and adiponectin, and airway reactivity was significantly related to visceral fat leptin expression (rho ¼ 20.8; P , 0.01). Bronchoalveolar lavage cytokines and cytokine production from alveolar macrophages were similar in subjects with asthma and control subjects at baseline, and tended to increase 12 months after surgery. Conclusions: Obesity is associated with increased markers of inflammation in serum and adipose tissue, and yet decreased airway inflammation in obese people with asthma; these patterns reverse with bariatric surgery. Leptin and other adipokines may be important mediators of airway disease in obesity through direct effects on the airway rather than by enhancing airway inflammation.

Background and objective There appears to be two distinct clinical phenotypes of obese patients with asthma – those with early-onset asthma and high serum IgE (TH2-high) and those with late-onset asthma and low serum IgE (TH2-low). The aim of the present study was to determine in the two phenotypes of obese asthma the effect of weight-loss on small airway function. Methods TH2-low (n=8) and TH2-high (n=5) obese asthmatics underwent methacholine challenge before and 12 months following bariatric surgery. Dose response slopes as measures of sensitivity to airway closure and narrowing were measured as maximum %fall FVC and FEV1/FVC, respectively, divided by dose. Resting airway mechanics were measured by forced oscillation technique. Results Weight-loss reduced sensitivity to airway closure in TH2-low but not TH2-high obese asthmatics (pre-post mean change ± 95%CI: 1.8 ± 0.8 doubling doses vs −0.3 ± 1.7 doubling doses, p=0.04). However, there was no effect of weight loss on the sensitivity to airway narrowing in either group (p=0.8, TH2-low: 0.8 ± 1.0 doubling doses, TH2-high: −1.1 ± 2.5 doubling doses). In contrast, respiratory resistance (20Hz) improved in TH2-high but not in TH2-low obese asthmatics (pre-post change median [IQR]: 1.5 [1.3 – 2.8] cmH2O/L/s vs 0.6 [−1.8 – 0.8] cmH2O/L/s, p=0.03). Conclusions TH2-low obese asthmatics appear to be characterised by increased small airway responsiveness and abnormalities in resting airway function that may persist following weight loss. However, this was not the case for TH2-high obese asthmatics, highlighting the complex interplay between IgE status and asthma pathophysiology in obesity.

This study demonstrated that NNFs grown in culture under increased pressures undergo a transformation not seen in cells grown at atmospheric pressure. Cells grown under pressure demonstrated reduced growth rates, increased fibronectin production, and abnormal morphologies similar to fibroblasts isolated from venous ulcers. This study suggests that pressure elevations (like venous hypertension) can directly result in altered cell function and morphology that may contribute to the delayed wound healing seen in patients with venous ulcers. This model uses a pressurized incubator that may prove to be a valuable adjunct in studying the effects of venous hypertension.

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