Serum leptin and adiponectin levels correlate with exercise-induced bronchoconstriction in children with asthma

doi:10.1016/j.anai.2011.03.013

Annals of Allergy, Asthma & Immunology

Volume 107, Issue 1, July 2011, Pages 14-21

https://doi.org/10.1016/j.anai.2011.03.013 Get rights and content

Background

Exercise-induced bronchoconstriction (EIB), a form of bronchial hyperresponsiveness (BHR), is common in children with asthma or obesity. Epidemiological studies have shown that asthma and obesity are increasing in parallel, but obesity- and adipokine-related effects on inflammation and BHR have not yet been demonstrated in the human airway.

Objective

To address the relationship between leptin and adiponectin and EIB in children with asthma.

Methods

Eighty-five prepubertal children between the ages of 6 and 10 years were included in our study. They comprised obese with asthma (n = 19), normal weight with asthma (n = 23), obese without asthma (n = 23), and healthy (n = 20). We measured seum leptin and adiponectin levels. We also performed pulmonary function tests: baseline, postbronchodilator inhalation, methacholine inhalation, and exercise. The area under the forced expiratory volume in 1 second (FEV₁)–time curve quantified the severity of EIB over a 20-minute period after exercise (AUC₂₀).

Results

The obese children had significantly elevated levels of leptin and reduced levels of adiponectin. The maximum decreases in %FEV₁ and AUC₂₀ after exercise were positively correlated with leptin levels and negatively with serum adiponectin levels in children with asthma. The odds for having EIB were incrementally and significantly higher for children with higher levels of serum leptin.

Conclusions

Levels of the adipocyte-derived hormones leptin and adiponectin are significantly correlated with BHR induced by exercise challenge in children with asthma. Further studies are needed to elucidate whether the changes in leptin and adiponectin levels bear a causal relationship to the EIB/BHR.

Introduction

Exercise-induced bronchoconstriction (EIB) refers to a condition in which vigorous physical exertion triggers acute airway narrowing in individuals with heightened bronchial hyperresponsiveness (BHR). Exercise-induced bronchoconstriction occurs in approximately half of children with asthma.¹

Epidemiological studies have shown that the prevalence of asthma is increasing concomitantly with obesity.² Emerging data suggest a link between asthma and obesity³ and indicate that the mechanical, immunological, hormonal and inflammatory effects of obesity play a role in the development and persistence of asthma.2, 4, 5, 6 Adipose tissue releases a variety of proinflammatory adipokines, including leptin, adiponectin, interleukin (IL) 6, tumor necrosis factor alpha (TNF-α), plasminogen activator inhibitor 1, eotaxin, vascular endothelial growth factor, and monocyte chemotactic protein (MCP)-1.3, 7 Studies in mouse models8, 9, 10, 11 have demonstrated that obesity and adipokines enhance BHR, airway inflammation, and allergic responses. However, obesity- and adipokine-related effects on inflammation and BHR have not yet been demonstrated in the human airway. The aim of this study was to address the relationship between the adipocyte-derived hormones leptin and adiponectin and EIB in children with asthma.

Section snippets

Subjects and Protocol

The subjects were recruited from the outpatient clinics in Hanyang University Hospital, Korea. Study participants were 85 prepubertal children between the ages of 6 and 10 years who were classified into one of the following groups: obese subject with asthma (n = 19), normal-weight subject with asthma (n = 23), obese subject without asthma (n = 23), and healthy (n = 20). Age- and sex-specific body mass index (BMI) percentiles were calculated based on raw height and weight according to the

Characteristics of Study Subjects

The demographic data for the 85 subjects are shown in Table 1. Of the 42 subjects with asthma, 7 had mild intermittent asthma (3 obese and 4 normal-weight), 14 had mild persistent asthma (7 obese and 7 normal-weight), and 21 had moderate asthma (10 obese and 11 normal-weight) according to the Global Initiative for Asthma guidelines. No significant differences were seen in asthma severity between the obese and normal-weight subjects with asthma. Mean values of age, height, and sex distribution

Discussion

We have shown that levels of the adipocyte-derived hormones leptin and adiponectin were higher and lower, respectively, in obese subjects with asthma than in normal-weight subjects with asthma, and were significantly correlated with BHR induced by exercise challenge.

Some studies have concluded that obesity is a risk factor for BHR to methacholine,20, 21 but others have reported no increase in BHR to methacholine with increasing BMI.22, 23 The studies that used exercise challenge to examine BHR

Acknowledgments

We thank our pediatric patients and their parents for generous donation of study samples, Mr. Soon-H.O. Koo for technical assistance, and Professor Yeong-Gwan Im and Mr. Han-Sang Baek for data management. We also thank Aerocrine for their support of NIOX MINO for eNO measurement.

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Citation Excerpt :
Furthermore, in a study including obese and non-obese asthmatic children, leptin was positively and adiponectin negatively associated with a decrease in FEV1 after a standardised exercise challenge [26]. In the present study, leptin increased by higher BMI, in accordance with other studies [8, 14, 26]. The results from our previous study and from others, suggest that BMI and accelerated growth in early life, at least up to a given threshold, are positively associated with lung function [4–6].
Both inflammatory and mechanical effects have been proposed to explain the increased risk of asthma and reduced lung function observed in obese children and adults. The evidence regarding the potential role of obesity in the aetiology of atopy and allergy is more conflicting. The adipokines leptin and adiponectin are inflammatory markers of fat metabolism which may be involved in explaining the increased risk of asthma and reduced lung function in obese children and adults. In this cross-sectional study, we aimed to study how adiponectin and leptin were associated with lung function and atopic sensitisation in adolescents.
The study included 384 children at mean age 12.9 years with measurements of adiponectin, leptin, lung function and atopic sensitisation. Adiponectin and leptin levels were measured in serum, lung function was measured by spirometry and atopic sensitisation was measured by serum specific Immunoglobulin E.
In linear regression models, leptin was negatively associated with forced vital capacity (FVC) (Beta: −4.13; 95% Confidence Interval: −5.83, −2.44, P < 0.001) and forced expiratory volume in the first second (FEV₁) (−3.74; −5.39, −2.09, P < 0.001) after adjusting for body mass index (BMI) and other covariates. No associations were observed between adiponectin and lung function or between leptin or adiponectin and atopic sensitisation.
In this cross-sectional analysis of adolescents in all weight classes, leptin was negatively associated with FEV₁ and FVC independent of BMI, but no associations were found between adiponectin and lung function. The results suggest that leptin may have a functional role in the airways of healthy children.
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: Funding Sources: Self-funded.

: Disclosures: The authors have nothing to disclose.

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Original articleAsthma, lower airway diseaseSerum leptin and adiponectin levels correlate with exercise-induced bronchoconstriction in children with asthma

Background

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Subjects and Protocol

Characteristics of Study Subjects

Discussion

Acknowledgments

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Chest

J Allergy Clin Immunol

Allergol Immunopathol (Madr)

Metabolism

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

Lancet

Exercise-induced bronchospasm in children: effects of asthma severity

Am J Respir Crit Care Med

Obesity and the lung: 4Obesity and asthma

Thorax

Obesity and asthma

Am J Respir Crit Care Med

Obesity and asthma: lessons from animal models

J Appl Physiol

Obesity, adipokines and asthma

Allergy

Responses to ozone are increased in obese mice

J Appl Physiol

Allergic airway responses in obese mice

Am J Respir Crit Care Med

Dietary cholesterol enhances pulmonary eosinophilic inflammation in a murine model of asthma

Int Arch Allergy Immunol

Prevalence and trends in overweight among US children and adolescents, 1999-2000

JAMA

Guidelines for methacholine and exercise challenge testing-1999This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999

Am J Respir Crit Care Med

Global strategy for asthma management and prevention: GINA executive summary

Eur Respir J

Original article
Asthma, lower airway disease
Serum leptin and adiponectin levels correlate with exercise-induced bronchoconstriction in children with asthma