Twin towers, twin epidemics: Obesity and asthma

Twin epidemics are on the rise: obesity and asthma. Obese patients with asthma, in particular, tend to have more severe symptoms, be less responsive to glucocorticoid treatment, and have a greater number of acute exacerbations than do their leaner counterparts. The only available treatment for these patients, other than current standard-of-care asthma therapy, is weight loss. Fortunately, research into the pathogenic mechanisms of asthma in the obese host is beginning to unravel the puzzle, opening doors to potential novel therapies. Fernandez-Boyanapalli et al. investigated the effects of obesity on immune manifestations of asthma in adult patients. The authors hypothesized that impairment in the clearance of apoptotic inflammatory cells by airway macrophages—an important anti-inflammatory process called “efferocytosis”—would be associated with altered airway inflammation, reduced glucocorticoid sensitivity, and systemic oxidative stress in obese asthmatic patients. Their findings showed that airway macrophage efferocytosis was 40% lower in obese than nonobese subjects, with a similar reduction of efferocytosis in blood monocytes. The macrophage efferocytosis index (a measure of efferocytosis) in peripheral blood monocytes was significantly correlated with dexamethasone sensitivity. Obese patients also had an increased percentage of macrophages and a reduced percentage of eosinophils in their sputum. In addition, the authors noted an altered pattern of macrophage programming in obese patients, with a reduction in the markers of the alternative (M2) relative to classical (M1) activation. M1 activation is thought to be proinflammatory, whereas M2 programming is associated with expression of efferocytic receptors and suppression of inflammation. Systemic oxidative stress was increased in obese patients as compared with nonobese patients with asthma and was inversely correlated with the macrophage efferocytosis index. The authors concluded that obese asthma patients show evidence of impaired macrophage/monocyte efferocytosis and M1/M2 reprogramming, reduced glucocorticoid responsiveness, and increased systemic oxidative stress. This is the first report comparing efferocytosis in macrophages/monocytes in obese and nonobese patients with asthma and linking it to corticosteroid responsiveness and oxidative stress. On the basis of these data, the authors propose that impaired efferocytic responses by airway macrophages contribute to increased asthma severity in the obese host. Moreover, airway macrophages may be a central inflammatory cell type in patients with asthma and obesity, linking the oxidative stress seen in obesity to the airway inflammation and glucocorticoid insensitivity of severe asthma. This work refocuses our attention on the role of macrophages/monocytes in asthma complicated by obesity, opening yet another door for targeted cell-specific therapies. However, the answer to the rising public health burden of asthma and obesity lies in a multipronged therapeutic approach. These diseases are ripe for additional research, with complex interactions we are just beginning to understand. R. Fernandez-Boyanapalli et al ., Obesity impairs apoptotic cell clearance in asthma. J. Allergy Clin. Immunol. , published online 12 Nov 2012 (10.1016/j.jaci.2012.09.028). [[Abstract]][1] [1]: http://www.jacionline.org/article/S0091-6749(12)01550-3/abstract