An Official American Thoracic Society Workshop Report: Obesity and Metabolism. An Emerging Frontier in Lung Health and Disease

Abstract

The world is in the midst of an unprecedented epidemic of obesity. This epidemic has changed the presentation and etiology of common diseases. For example, steatohepatitis, directly attributable to obesity, is now the most common cause of cirrhosis in the United States. Type 2 diabetes is increasingly being diagnosed in children. Pulmonary researchers and clinicians are just beginning to appreciate the impact of obesity and altered metabolism on common pulmonary diseases. Obesity has recently been identified as a major risk factor for the development of asthma and for acute respiratory distress syndrome. Obesity is associated with profound changes in pulmonary physiology, the development of pulmonary hypertension, sleep-disordered breathing, and altered susceptibility to pulmonary infection. In short, obesity is leading to dramatic changes in lung health and disease. Simultaneously, the rapidly developing field of metabolism, including mitochondrial function, is shifting the paradigms by which the pathophysiology of many pulmonary diseases is understood. Altered metabolism can lead to profound changes in both innate and adaptive immunity, as well as the function of structural cells. To address this emerging field, a 3-day meeting on obesity, metabolism, and lung disease was convened in October 2015 to discuss recent findings, foster research initiatives, and ultimately guide clinical care. The major findings arising from this meeting are reported in this document.

Figure 1.

The complex interactions between obesity-mediated metabolic dysregulation, systemic inflammation, and pulmonary function deficits in association with obesity-related asthma. Obesity-mediated metabolic dysregulation includes (1) insulin resistance and its downstream effects (blue arrows) and (2) dyslipidemia and its downstream effects (red arrows). Insulin resistance and dyslipidemia frequently coexist. Obesity is also associated with systemic inflammation, Th-cell polarization and monocyte activation (green arrows). Inflammation mediated by metabolic dysregulation and obesity is associated with pulmonary function deficits specific to obesity-related asthma. Insulin resistance itself is associated with reduced pulmonary function.