An open-label study examining the effect of pharmacological treatment on mannitol- and exercise-induced airway hyperresponsiveness in asthmatic children and adolescents with exercise-induced bronchoconstriction

BMC Pediatrics

Jörg D Leuppi⁵  Bruno Knöpfli⁴  Anne B Taegtmeyer³  Prashant N Chhajed²  Alexandra Goll⁴  Sabine Sauter⁴  Ladina Joos Zellweger²  Anja Jochmann¹  David Miedinger²  Thomas Mueller²  Salome Schafroth Török² 

[1] University Childrens Hospital Basel, Basel, Switzerland;Internal Medicine, University Hospital Basel and University of Basel, Basel, Switzerland;Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland;Alpine Childrens Hospital Davos, Davos, Switzerland;University Clinic of Internal Medicine, Kantonsspital Baselland, Liestal, Switzerland

关键词: Mannitol challenge test;    Exercise challenge test;    Children;    Airway hyperresponsiveness;    Exercise-induced bronchoconstriction;   

Others  :  1138444
DOI  :  10.1186/1471-2431-14-196

 received in 2014-05-05, accepted in 2014-07-09,  发布年份 2014

【 摘 要 】

Background

Mannitol- and exercise bronchial provocation tests are both used to diagnose exercise-induced bronchoconstriction. The study aim was to compare the short-term treatment response to budesonide and montelukast on airway hyperresponsiveness to mannitol challenge test and to exercise challenge test in children and adolescents with exercise-induced bronchoconstriction.

Methods

Patients were recruited from a paediatric asthma rehabilitation clinic located in the Swiss Alps. Individuals with exercise-induced bronchoconstriction and a positive result in the exercise challenge test underwent mannitol challenge test on day 0. All subjects then received a treatment with 400 μg budesonide and bronchodilators as needed for 7 days, after which exercise- and mannitol-challenge tests were repeated (day 7). Montelukast was then added to the previous treatment and both tests were repeated again after 7 days (day 14).

Results

Of 26 children and adolescents with exercise-induced bronchoconstriction, 14 had a positive exercise challenge test at baseline and were included in the intervention study. Seven of 14 (50%) also had a positive mannitol challenge test. There was a strong correlation between airway responsiveness to exercise and to mannitol at baseline (r = 0.560, p = 0.037). Treatment with budesonide and montelukast decreased airway hyperresponsiveness to exercise challenge test and to a lesser degree to mannitol challenge test. The fall in forced expiratory volume in one second during exercise challenge test was 21.7% on day 0 compared to 6.7% on day 14 (p = 0.001) and the mannitol challenge test dose response ratio was 0.036%/mg on day 0 compared to 0.013%/mg on day 14 (p = 0.067).

Conclusion

Short-term treatment with an inhaled corticosteroid and an additional leukotriene receptor antagonist in children and adolescents with exercise-induced bronchoconstriction decreases airway hyperresponsiveness to exercise and to mannitol.

【 授权许可】

   
2014 Török et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Sterk PJ, Fabbri LM, Quanjer PH, Cockcroft DW, O’Byrne PM, Anderson SD, Juniper EF, Malo JL: Airway responsiveness: standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults: report working party standardization of lung function tests, European community for steel and coal: official statement of the European respiratory society. Eur Respir J Suppl 1993, 16:53-83.
• [2]Leuppi JD, Brannan JD, Anderson SD: Bronchial provocation tests: the rationale for using inhaled mannitol as a test for airway hyperresponsiveness. Swiss Med Wkly 2002, 132(13–14):151-158.
• [3]Anderson SD: Provocative challenges to help diagnose and monitor asthma: exercise, methacholine, adenosine, and mannitol. Curr Opin Pulm Med 2008, 14(1):39-45.
• [4]Leuppi JD: Bronchoprovocation tests in asthma: direct versus indirect challenges. Curr Opin Pulm Med 2014, 20(1):31-36.
• [5]Haby MM, Anderson SD, Peat JK, Mellis CM, Toelle BG, Woolcock AJ: An exercise challenge protocol for epidemiological studies of asthma in children: comparison with histamine challenge. Eur Respir J 1994, 7(1):43-49.
• [6]Haby MM, Peat JK, Mellis CM, Anderson SD, Woolcock AJ: An exercise challenge for epidemiological studies of childhood asthma: validity and repeatability. Eur Respir J 1995, 8:729-736.
• [7]Anderson SD: Issues in exercise-induced asthma. J Allergy Clin Immunol 1985, 76(6):763-772.
• [8]Gotshall RW: Exercise-induced bronchoconstriction. Drugs 2002, 62(12):1725-1739.
• [9]Anderson SD, Brannan J, Spring J, Spalding N, Rodwell LT, Chan K, Gonda I, Walsh A, Clark AR: A new method for bronchial-provocation testing in asthmatic subjects using a dry powder of mannitol. Am J Respir Crit Care Med 1997, 156:758-765.
• [10]Brannan JD, Anderson SD, Perry CP, Freed-Martens R, Lassig AR, Charlton B: 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. BioMed Central Full Text
• [11]Brannan JD, Koskela H, Anderson SD, Chew N: Responsiveness to Mannitol in asthmatic subjects with exercise- and hyperventilation-induced asthma. Am J Respir Crit Care Med 1998, 158:1120-1126.
• [12]Subbarao P, Brannan JD, Ho B, Anderson SD, Chan HK, Coates AL: Inhaled mannitol identifies methacholine-responsive children with active asthma. Pediatr Pulmonol 2000, 29:291-298.
• [13]Brannan JD, Koskela H, Anderson SD, Chan HK: Budesonide reduces sensitivity and reactivity to inhaled mannitol in asthmatic subjects. Respirology 2002, 7:37-44.
• [14]Leuppi JD, Leuppi JD, Salome CM, Jenkins CR, Anderson SD, Xuan W, Marks GB, Koskela H, Brannan JD, Freed R, Andersson M, Chan HK, Woolcock AJ: Predictive markers of asthma exacerbation during stepwise dose-reduction of inhaled corticosteroids. Am J Respir Crit Care Med 2001, 163:406-412.
• [15]American Thoracic Society: Standardization of spirometry, 1994 update. Am J Respir Crit Care Med 1995, 152(3):1107-1136.
• [16]Weng TR, Levison H: Standards of pulmonary function in children. Am Rev Respir Dis 1969, 99(6):879-894.
• [17]Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wagner JS, Anderson SD, Wockcroft DW, Fish JE, Sterk PJ: 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.
• [18]Scichilone N, Morici G, Zangla D, Arrigo R, Cardillo I, Bellia V, Bonsignore MR: Effects of exercise training on airway closure in asthmatics. J Appl Physiol (1985) 2012, 113(5):714-718.
• [19]Anderson SD, Charlton B, Weiler JM, Nichols S, Spector SL, Pearlman DS: Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma. Respir Res 2009, 10:4. BioMed Central Full Text
• [20]Clearie KL, Williamson PA, Vaidyanathan S, Short P, Goudie A, Burns P, Hopkinson P, Meldrum K, Howaniec L, Lipworth BJ: Disconnect between standardized field-based testing and mannitol challenge in Scottish elite swimmers. Clin Exp Allergy 2010, 40(5):731-737.
• [21]Anderson SD: Indirect challenge tests: airway hyperresponsiveness in asthma: its measurement and clinical significance. Chest 2010, 138(2 Suppl):25S-30S.
• [22]Holzer K, Anderson SD, Chan HK, Douglass J: Mannitol as a challenge test to identify exercise-induced bronchoconstriction in elite athletes. Am J Respir Crit Care Med 2003, 167(4):534-537.
• [23]Brannan JD, Anderson SD, Gomes K, King GG, Chan HK, Seale JP: Fexofenadine decreases sensitivity to and montelukast improves recovery from inhaled mannitol. Am J Respir Crit Care Med 2001, 163:1420-1425.