Shore Stephanie A, Johnston Richard A
Physiology Program, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Pharmacol Ther. 2006 Apr;110(1):83-102. doi: 10.1016/j.pharmthera.2005.10.002. Epub 2005 Nov 17.
Obesity is an important public health problem. An increasing body of data supports the hypothesis that obesity is a risk factor for asthma. These data include numerous large cross-sectional and prospective studies performed in adults, adolescents, and children throughout the world. With few exceptions, these studies indicate an increased relative risk of asthma in the obese and overweight and demonstrate that obesity antedates asthma. Obesity appears to be a particularly important issue for severe asthma. Studies showing improvements in asthma in subjects who lose weight, as well as studies showing that obese mice have innate airway hyperresponsiveness (AHR) as well as increased responses to certain asthma triggers also suggest a causal relationship between obesity and asthma. The mechanistic basis for this relationship has not been established. It may be that obesity and asthma share some common etiology, such as a common genetic predisposition, common effects of in utero conditions, or that obesity and asthma are both the result of some other predisposing factor such as physical activity or diet. However, there are also plausible biological mechanisms whereby obesity could be expected to either cause or worsen asthma. These include co-morbidities such as gastroesophageal reflux, complications from sleep-disordered breathing (SDB), breathing at low lung volume, chronic systemic inflammation, and endocrine factors, including adipokines and reproductive hormones. Understanding the mechanistic basis for the relationship between obesity and asthma may lead to new therapeutic strategies for treatment of this susceptible population.
肥胖是一个重要的公共卫生问题。越来越多的数据支持肥胖是哮喘危险因素这一假说。这些数据包括在全球范围内针对成人、青少年和儿童开展的大量大型横断面研究和前瞻性研究。几乎毫无例外,这些研究表明肥胖和超重人群患哮喘的相对风险增加,并证明肥胖先于哮喘出现。肥胖对于重度哮喘似乎是一个尤为重要的问题。那些显示体重减轻的受试者哮喘症状改善的研究,以及那些表明肥胖小鼠存在先天性气道高反应性(AHR)以及对某些哮喘触发因素反应增强的研究,也提示了肥胖与哮喘之间存在因果关系。这种关系的机制基础尚未明确。可能是肥胖和哮喘存在一些共同的病因,比如共同的遗传易感性、子宫内环境的共同影响,或者肥胖和哮喘都是其他一些易感因素(如体力活动或饮食)导致的结果。然而,也存在一些合理的生物学机制,据此推测肥胖可能会引发哮喘或使哮喘病情加重。这些机制包括诸如胃食管反流等合并症;睡眠呼吸紊乱(SDB)的并发症、低肺容量呼吸、慢性全身炎症以及内分泌因素,包括脂肪因子和生殖激素等。了解肥胖与哮喘之间关系的机制基础可能会为治疗这一易感人群带来新的治疗策略。