Published online Mar 31, 2014.
https://doi.org/10.4168/aard.2014.2.1.30
Serum leptin levels correlate with bronchial hyper-responsiveness to mannitol in asthmatic children
Abstract
Purpose
Epidemiological data indicate that obesity is a risk factor in asthma, however effects related to obesity and adipokines on airway inflammation and bronchial hyper-responsiveness (BHR) have not yet been demonstrated in the human airway. The aim of this study was to investigate the relationship between serum adipokine levels and BHR to mannitol in asthmatic children.
Methods
Serum adipokine levels were measured and pulmonary function tests were perfomed: baseline, postbronchodilator inhalation, methacholine inhalation, and mannitol inhalation. The response to mannitol was expressed as the dose causing a 15% decrease in forced expiratory volume in one second (FEV1) (PD15), and as the response-dose ratio (RDR) (% fall in FEV1/cumulative dose).
Results
Sixty-nine prepubertal children between the ages of 6 and 10 years were participated in the study. They comprised asthmatic children (n=40) and healthy (n=29). Twenty-two subjects (55.5%) with asthma had a positive mannitol bronchial provocation test (BPT) result. The body mass index (BMI) was higher in those asthmatics with positive mannitol BPTs than in asthmatics with negative mannitol BPTs and in the control group (19.30 kg/m2 vs. 17.60 kg/m2 vs. 17.93 kg/m2,P=0.035, P=0.046). Serum leptin levels were also significantly higher in asthmatics with positive mannitol BPTs than in asthmatics with negative mannitol BPTs and in the control group (10.58 ng/mL vs. 5.49 ng/mL vs. 6.75 ng/mL, P=0.002, P=0.016). Leptin values were significantly associated with a PD15 (r=-0.498, P=0.022) and RDR to mannitol (r=0.346, P=0.033) in asthmatic children after adjustment for BMI.
Conclusion
Serum leptin levels were significantly associated with BHR to mannitol in asthmatic children.
Fig. 1
Relationship between serum leptin and PD15 and RDR to mannitol in children with asthma. (A) Serum leptin levels were significantly related to PD15 (r=-0.498, r=partial correlation coefficient adjusted for BMI, P=0.022) in both obese (n=9, r=-0.327, P=0.042) and normal-weight asthmatics (n=13, r=-0.322, P=0.048). (B) Serum leptin levels were significantly related to RDR to mannitol (r=0.346, r=partial correlation coefficient adjusted for BMI, P=0.033) in both obese (n=11, r=-0.302, P=0.039) and normal-weight asthmatics (n=29, r=-0.318, P=0.043). PD15, cumulative provocative dose causing a 15% fall in FEV1; RDR, response-dose ratio (% fall in FEV1/cumulative dose of mannitol); FEV1, orced expiratory volume in one second; BMI, body mass index.
Table 1
Characteristics of the subjects included in the study.
Table 2
Characteristics of the asthmat subjects
Table 3
Serum leptin and adiponectin levels of the study subjects
Table 4
Correlation coefficients between serum leptin levles and lung function or markers of atopy
Table 5
Odds ratios for association between sex, age, BMI, atopy, adipokines and BHR to mannitol
This work was supported by a grant from the 2011 MSD Research Grant Award, The Korean Academy of Pediatric Allergy and Respiratory Disease.
References
-
del Río-Navarro B, Cisneros-Rivero M, Berber-Eslava A, Espinola-Reyna G, Sienra-Monge J. Exercise induced bronchospasm in asthmatic and non-asthmatic obese children. Allergol Immunopathol (Madr) 2000;28:5–11.
-
-
Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, et al. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med 2000;161:309–329.
-
-
American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med 2005;171:912–930.
-
-
Human IL-6 quantikine ELISA kit [Internet]. Minneapolis (MN): R&D systems; 2014 [cited 2011 Apr 30].Available from: http://www.rndsystems.com/Products/D6050.
-
-
Theoharides TC, Makris M, Kalogeromitros D. Allergic inflammation and adipocytokines. Int J Immunopathol Pharmacol 2008;21:1–4.
-
-
Bäck M, Sultan A, Ovchinnikova O, Hansson GK. 5-Lipoxygenase-activating protein: a potential link between innate and adaptive immunity in atherosclerosis and adipose tissue inflammation. Circ Res 2007;100:946–949.
-
-
O'Sullivan S, Roquet A, Dahlen B, Larsen F, Eklund A, Kumlin M, et al. Evidence for mast cell activation during exercise-induced bronchoconstriction. Eur Respir J 1998;12:345–350.
-
-
Porsbjerg C, Brannan JD, Anderson SD, Backer V. Relationship between airway responsiveness to mannitol and to methacholine and markers of airway inflammation, peak flow variability and quality of life in asthma patients. Clin Exp Allergy 2008;38:43–50.
-