Obesity, metabolic dysregulation and oxidative stress in asthma

Epidemiological data demonstrate an increased risk of developing incident asthma with increasing adiposity. While the vast majority of studies support the interaction between obesity and asthma, the causality is unclear. This article will review the current literature supporting the presence of an obese asthma phenotype and the possible mechanisms mediating the effects of obesity on asthma. Obesity is associated with poor asthma control, altered responsiveness to medications and increased morbidity. Obesity is characterized by systemic inflammation that may result in increased airway inflammation. However, this assertion is not supported by current studies that demonstrate a lack of significant airway inflammation in obese asthmatics. In spite this observation one must consider limitations of these studies including the fact that most subjects were treated with inhaled corticosteroids that would likely alter inflammation in the lung. Thus, it remains unclear if obesity is associated with alterations in inflammation in the airways of subjects with asthma. Hormones such as leptin and adiponectin are affected by obesity and may play a role in mediating innate immune responses and allergic responses, respectively. The role of oxidative stress remains controversial and the current evidence suggests that while oxidative stress is important in asthma, it does not fully explain the characteristics associated with this unique phenotype. Obesity related asthma is associated with increased morbidity and differential response to asthma therapies. Understanding the mechanisms mediating this phenotype would have significant implications for millions of people suffering with asthma. This article is part of a Special Issue entitled Biochemistry of Asthma. ► We review the literature supporting an obesity asthma phenotype. ► We present an overview of the possible mechanisms mediating obesity related increases in asthma. ► Obesity results in an increased risk of asthma, however, the mechanism is unclear. ► Further studies are required to delineate the mechanisms behind this association and increased understanding would have significant public health implications.