Obesity, smooth muscle, and airway hyperresponsiveness

Harvard University, Cambridge, Massachusetts, United States
Journal of Allergy and Clinical Immunology (Impact Factor: 11.48). 06/2005; 115(5):925-7. DOI: 10.1016/j.jaci.2005.01.064
Source: PubMed


Both asthma and obesity are large and growing public health issues. Mounting evidence now implicates obesity as a major risk factor for asthma, thus linking these 2 major epidemics. Moreover, both in human subjects and in mice, obesity appears to predispose toward airway hyperresponsiveness. This review describes potential mechanisms whereby obesity might modify airway smooth muscle function to explain these observations. These mechanisms include both static and dynamic mechanical factors attributable to decreases in functional residual capacity and decreases in tidal volume that are observed in the obese. They include also obesity-related changes in lung development, chronic systemic inflammation (including increased serum levels of inflammatory cytokines and chemokines), and adipocyte-derived factors, including leptin, adiponectin, and plasminogen activator inhibitor.

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    • "Obesity is a risk factor for asthma and airway hyper-reactivity. Shore et al. explained that airway function could be altered by chronic systemic inflammation and adipokines, including leptin and adiponectin [63]. These effects have been shown to be directly on airway smooth muscle for some but not all adipokines. "
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    ABSTRACT: Obesity is a major health problem worldwide. The prevalence of obesity is increasing in both developed and developing countries. In the UK, for example, 60% of adults are overweight and 25% are obese. Obesity is associated with many pathological complications including respiratory, cardiovascular and endocrine, but it also affects fertility and is associated with many reproductive complications. This has led us and others to investigate links between women with high BMI, pregnancy outcome and uterine function. These studies in turn have led investigators to ask how obesity can have such an impact on reproduction and, as part of this, to consider the role of the adipokines released from adipose tissue. Our focus in this short review is on adipokines and myometrial activity, and for completeness we overview their effects on other smooth muscles. To date four adipokines (leptin, visfatin, apelin and ghrelin) have been investigated and all affect myometrial contractility, but some more potently than others. We consider the possible mechanisms involved in how adipokines may modify uterine contractility, and discuss the potential impact on labour and delivery. Copyright © 2015. Published by Elsevier Inc.
    Preview · Article · Feb 2015 · Life Sciences
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    • "Recent epidemiological studies have demonstrated that the prevalence of asthma and obesity are both increasing concomitantly, suggesting that these factors may be causally related [28]. Accumulating evidence has implicated systemic changes in immune function in the development of obesity; several obesity-related hormones and cytokines may lead to airway hyper-responsiveness [1,29,30]. In our study there was no difference between the BMIs of asthmatic and non-asthmatic children, so we could eliminate the effect of obesity on the serum levels of leptin. "
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    ABSTRACT: Appetite-modulating hormones ghrelin and leptin might be relevant to asthma with their pro-inflammatory effects, and calprotectin has been recognized as a promising marker of inflammation. The purpose of this study was to explore whether asthma, atopy and lung functions has a relation with serum levels of leptin, ghrelin and calprotectin as inflammatory markers in children. A cross-sectional study was performed by searching the doctor diagnosed asthma through questionnaires filled in by parents who were phoned, and children were invited to supply fasting blood samples in order to measure serum levels of leptin, ghrelin and calprotectin, and to perform skin prick test and spirometry. Participants were divided into Group 1, children with previous diagnosis of asthma, and Group 2, children without previous diagnosis of asthma. One thousand and two hundred questionnaires were distributed and 589 of them were returned filled in. Out of 74 children whose parents accepted to participate in the study, 23 were in Group 1 and 51 were in Group 2. There was no statistical difference in serum levels of leptin, ghrelin, calprotectin, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) , forced expiratory flow between 25 and 75% of vital capacity (FEF25-75) values , and skin prick test results between the two groups (p values are 0.39, 0.72, 0.5, 0.17, 0.5, 0.27, 0.18, and 0.81 respectively). In this study the inflammation in asthmatic children could not be shown by using serum leptin, ghrelin and calprotectin levels and this is possibly due to the low number of children with ever asthma and equal skin prick test positivity in both groups. This study is the first study aimed to show the relation between serum calprotectin levels and inflammation in asthma. As this study was a cross-sectional study, further prospectively designed randomized controlled studies are necessary to show the association of these markers and inflammation in asthma.
    Full-text · Article · Sep 2013 · Multidisciplinary respiratory medicine
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    • "Serum adiponectin has important anti-inflammatory effects in obesity that inhibits proinflammatory cytokines (TNF-a, IL-6, and nuclear factor-kB) and induces anti-inflammatory cytokines (IL-10 and IL-1 receptor antagonist) [7, 10]. Thus, leptin and adiponectin could have a role in the pathogenesis of asthma as supported by animal studies [11, 12], and only few studies have been done in humans to convincingly establish a link between adipokines and asthma [13–15]. "
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    ABSTRACT: There is growing evidence of a positive correlation between asthma and obesity in children and adults. Leptin and adiponectin regulate several metabolic and inflammatory functions. This study aims to evaluate serum leptin and adiponectin concentrations in asthmatic school children to investigate their association with obesity and the degree of asthma control. Obese asthmatic (OA) and nonobese asthmatic (NOA) children, aged 7 to 14, were randomly enrolled in this prospective study. Data on demographic, anthropometric, serum lipids, and spirometric measures and allergy status were collected and analyzed. Serum leptin was significantly higher (25.8 ± 11.1 versus 8.7 ± 11.1; P < 0.0001) and adiponectin levels were lower (2.5 ± 1.2 versus 5.4 ± 2.9; P < 0.0001) in OA compared to NOA children. The uncontrolled group had higher leptin and lower adiponectin levels compared to well and partially controlled asthma. BMI was positively correlated with leptin (r = 0.79; P < 0.001) and negatively with adiponectin (r = -0.73; P < 0.001). Mean BMI and leptin levels were observed to be higher in girls compared to boys. Stepwise multiple linear regression analysis showed that higher BMI and female gender had significant effect on serum leptin levels. Among asthmatic children higher serum leptin and lower adiponectin levels were significantly associated with obesity and showed no significant association with degree of asthma controls.
    Full-text · Article · Aug 2013 · Journal of Allergy
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