TY - JOUR T1 - Metabolic consequences of obesity as an “outside in” mechanism of disease severity in asthma JF - European Respiratory Journal JO - Eur Respir J SP - 291 LP - 293 DO - 10.1183/13993003.01132-2016 VL - 48 IS - 2 AU - Michael C. Peters AU - John V. Fahy Y1 - 2016/08/01 UR - http://erj.ersjournals.com/content/48/2/291.abstract N2 - The clinical features of asthma are highly varied. Most patients have relatively mild disease that is easily controlled with inhaled β-adrenergic agonists with or without low or medium doses of inhaled corticosteroids. However, a subset of patients has more severe disease, and many of these patients suffer persistent symptoms in spite of treatments that include high doses of inhaled corticosteroids. Furthermore, some asthma patients are exacerbation prone, and these patients require frequent treatment with systemic corticosteroids to control these exacerbations. Studies that have systematically examined the heterogeneity of disease severity in asthma have noted that older age and higher body weight are clinical features of patients with more severe disease [1, 2]. In addition, it has been noted that age has a greater effect than asthma duration on risk of severe asthma [3]. These clinical features provide clues about disease mechanisms of asthma, and work is now being done to understand how ageing and obesity lead to severe asthma. For example, it has recently been shown that systemic interleukin (IL)-6 inflammation occurs in a subset of patients with asthma who are characterised by older age, obesity and severe disease (low lung function and frequent exacerbations) [4]. Notably, increases in plasma IL-6 occur in some but not all obese patients, and obese patients with high IL-6 levels have more severe asthma than obese patients with low IL-6 levels. In addition, increases in plasma IL-6 remain strongly associated with asthma severity, even when controlling for body mass index and age in regression models. This means that systemic IL-6 inflammation is an independent predictor of disease severity in asthma and that the heterogeneity of asthma severity that occurs in obese patients with asthma can be explained at least in part by the presence or absence of low-grade systemic inflammation in these patients (figure 1). Low-grade systemic inflammation in obesity is characterised by increases in systemic levels of inflammatory cytokines such as IL-6, IL-1 and tumour necrosis factor-α, and adipokines such as leptin. These mediators originate in adipocytes and activated macrophages in adipose tissue, and contribute to mechanisms of metabolic dysfunction and metabolic syndrome in obese patients [5, 6]. These inflammatory cytokines could alter lung function in a variety of ways, including through activation of vascular endothelial cells, airway fibroblasts, airway smooth muscle cells or airway epithelial cells [7]. In addition, IL-6 influences the differentiation of naïve T-cells into Th17-cells and could indirectly affect lung function through the effects of IL-17 [8].“Outside in” asthma: inflammatory events that drive asthma severity arise in tissue compartments outside the lung http://ow.ly/aEcZ301mcLc ER -