Allergy Asthma Respir Dis. 2014 Mar;2(1):30-37. Korean.
Published online Mar 31, 2014.
© 2014 The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma, Allergy and Clinical Immunology
Original Article

Serum leptin levels correlate with bronchial hyper-responsiveness to mannitol in asthmatic children

Jung-Kyung Yoo,1 Jae Young Shin,2 Jueng-Sup You,1 Soo-In Jeong,1 Joon-Sup Song,1 Seong Yang,1 Il-Tae Hwang,1 Ha-Baik Lee,3 and Hey-Sung Baek1
    • 1Department of Pediatrics, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea.
    • 2Department of Pediatrics, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea.
    • 3Department of Pediatrics, Hanyang University Medical Center, Seoul, Korea.
Received July 12, 2013; Revised August 26, 2013; Accepted August 27, 2013.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/).

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.

Keywords
Asthma; Leptin; Mannitol; Bronchial hyper-responsiveness; Child; Obesity

Figures

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.

Tables

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

Notes

This work was supported by a grant from the 2011 MSD Research Grant Award, The Korean Academy of Pediatric Allergy and Respiratory Disease.

References

    1. Hargreave FE, Ryan G, Thomson NC, O'Byrne PM, Latimer K, Juniper EF, et al. Bronchial responsiveness to histamine or methacholine in asthma: measurement and clinical significance. J Allergy Clin Immunol 1981;68:347–355.
    1. Brannan JD, Gulliksson M, Anderson SD, Chew N, Kumlin M. Evidence of mast cell activation and leukotriene release after mannitol inhalation. Eur Respir J 2003;22:491–496.
    1. Litonjua AA, Gold DR. Asthma and obesity: common early-life influences in the inception of disease. J Allergy Clin Immunol 2008;121:1075–1084.
    1. Sood A, Ford ES, Camargo CA Jr. Association between leptin and asthma in adults. Thorax 2006;61:300–305.
    1. Bustos P, Amigo H, Oyarzun M, Rona RJ. Is there a causal relation between obesity and asthma? Evidence from Chile. Int J Obes (Lond) 2005;29:804–809.
    1. Schachter LM, Salome CM, Peat JK, Woolcock AJ. Obesity is a risk for asthma and wheeze but not airway hyperresponsiveness. Thorax 2001;56:4–8.
    1. 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.
    1. Lopes WA, Radominski RB, Rosario Filho NA, Leite N. Exercise-induced bronchospasm in obese adolescents. Allergol Immunopathol (Madr) 2009;37:175–179.
    1. Baek HS, Kim YD, Shin JH, Kim JH, Oh JW, Lee HB. Serum leptin and adiponectin levels correlate with exercise-induced bronchoconstriction in children with asthma. Ann Allergy Asthma Immunol 2011;107:14–21.
    1. Sin DD, Sutherland ER. Obesity and the lung: 4. Obesity and asthma. Thorax 2008;63:1018–1023.
    1. Jartti T, Saarikoski L, Jartti L, Lisinen I, Jula A, Huupponen R, et al. Obesity, adipokines and asthma. Allergy 2009;64:770–777.
    1. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009;360:1509–1517.
    1. Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005;115:911–919.
    1. Shore SA, Schwartzman IN, Mellema MS, Flynt L, Imrich A, Johnston RA. Effect of leptin on allergic airway responses in mice. J Allergy Clin Immunol 2005;115:103–109.
    1. Shore SA, Terry RD, Flynt L, Xu A, Hug C. Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice. J Allergy Clin Immunol 2006;118:389–395.
    1. Johnston RA, Zhu M, Rivera-Sanchez YM, Lu FL, Theman TA, Flynt L, et al. Allergic airway responses in obese mice. Am J Respir Crit Care Med 2007;176:650–658.
    1. Kim KW, Shin YH, Lee KE, Kim ES, Sohn MH, Kim KE. Relationship between adipokines and manifestations of childhood asthma. Pediatr Allergy Immunol 2008;19:535–540.
    1. Jang AS, Kim TH, Park JS, Kim KU, Uh ST, Seo KH, et al. Association of serum leptin and adiponectin with obesity in asthmatics. J Asthma 2009;46:59–63.
    1. 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.
    1. Chai H, Farr RS, Froehlich LA, Mathison DA, McLean JA, Rosenthal RR, et al. Standardization of bronchial inhalation challenge procedures. J Allergy Clin Immunol 1975;56:323–327.
    1. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J 2005;26:319–338.
    1. 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.
    1. Human IL-6 quantikine ELISA kit [Internet]. Minneapolis (MN): R&D systems; 2014 [cited 2011 Apr 30].
    1. Brannan JD, Anderson SD, Perry CP, Freed-Martens R, Lassig AR, Charlton B, et al. The safety and efficacy of inhaled dry powder mannitol as a bronchial provocation test for airway hyperresponsiveness: a phase 3 comparison study with hypertonic (4.5%) saline. Respir Res 2005;6:144.
    1. Anderson SD, Charlton B, Weiler JM, Nichols S, Spector SL, Pearlman DS, et al. Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma. Respir Res 2009;10:4.
    1. Brannan JD, Gulliksson M, Anderson SD, Chew N, Seale JP, Kumlin M. Inhibition of mast cell PGD2 release protects against mannitol-induced airway narrowing. Eur Respir J 2006;27:944–950.
    1. Ford ES. The epidemiology of obesity and asthma. J Allergy Clin Immunol 2005;115:897–909.
    1. Beuther DA, Weiss ST, Sutherland ER. Obesity and asthma. Am J Respir Crit Care Med 2006;174:112–119.
    1. Shore SA. Obesity and asthma: possible mechanisms. J Allergy Clin Immunol 2008;121:1087–1093.
    1. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011;29:415–445.
    1. Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444:860–867.
    1. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796–1808.
    1. Theoharides TC, Makris M, Kalogeromitros D. Allergic inflammation and adipocytokines. Int J Immunopathol Pharmacol 2008;21:1–4.
    1. Liu J, Divoux A, Sun J, Zhang J, Clement K, Glickman JN, et al. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med 2009;15:940–945.
    1. Mito N, Kitada C, Hosoda T, Sato K. Effect of diet-induced obesity on ovalbumin-specific immune response in a murine asthma model. Metabolism 2002;51:1241–1246.
    1. 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.
    1. Taildeman J, Perez-Novo CA, Rottiers I, Ferdinande L, Waeytens A, De Colvenaer V, et al. Human mast cells express leptin and leptin receptors. Histochem Cell Biol 2009;131:703–711.
    1. 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.
    1. 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.
    1. Anderson SD. Indirect challenge tests: Airway hyperresponsiveness in asthma: its measurement and clinical significance. Chest 2010;138 2 Suppl:25S–30S.

Metrics
Share
Figures

1 / 1

Tables

1 / 5

PERMALINK