Gastroesophageal reflux (GER) is frequent in children with asthma, can induce bronchospasm, and increase airways reactivity. Children with asthma are often treated for GER with drugs to suppress gastric acid production. However, this treatment is expensive, and with unproven benefit. The primary objective in this proposal is to conduct a multi-site, randomized, clinical trial to test the hypothesis that treatment of GER with lansoprazole, an approved proton pump inhibitor, will decrease the frequency of exacerbations in children with poorly controlled asthma. The study will include 300 asthmatic children treated with inhaled corticosteroids, 6-16 years of age, with poor control defined by frequent symptoms, excessive beta agonist use, or frequent exacerbations. Participants will be randomly assigned to treatment with either lansoprazole or placebo for six months. The presence, severity, and relationship of GER to asthma symptoms will be determined with 24 hour esophageal pH monitoring, but randomization to treatment will not be influenced by the presences or severity of GER. The primary outcome measure is the proportion of participants who have exacerbations of asthma defined by diaries and interviews. Secondary outcome measures include asthma symptom and control scores, GER symptoms, lung function, and unscheduled health care contacts. Pre-defined subgroup analyses will examine the relationship between specific clinical features and the response to lansoprazole. Treatment response will also be evaluated with 3-hour post-dose plasma lansoprazole concentrations, and related to polymorphisms in CYP2C19, the cytochrome P450 pathway, and IL-1 beta, a pro-inflammatory cytokine. Tertiary studies will determine how the magnitude of GER impacts airways inflammation, as measured by the concentrations of H+ (pH) and NO in expired breath. The results of this trial should have a major impact on the understanding and treatment of GER in children with asthma.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL080450-05
Application #
7878064
Study Section
Clinical Trials Review Committee (CLTR)
Program Officer
Smith, Robert A
Project Start
2006-09-20
Project End
2011-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
5
Fiscal Year
2010
Total Cost
$466,849
Indirect Cost
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Lang, Jason E; Hossain, Jobayer; Holbrook, Janet T et al. (2016) Gastro-oesophageal reflux and worse asthma control in obese children: a case of symptom misattribution? Thorax 71:238-46
Quezada, Wilson; Kwak, Eun Soo; Reibman, Joan et al. (2016) Predictors of asthma exacerbation among patients with poorly controlled asthma despite inhaled corticosteroid treatment. Ann Allergy Asthma Immunol 116:112-7
Lang, Jason E; Holbrook, Janet T; Lima, John J et al. (2015) Reply: worsening asthma control in children taking lansoprazole: possible mechanisms. Ann Am Thorac Soc 12:1110-1
Lang, Jason E; Holbrook, Janet T; Mougey, Edward B et al. (2015) Lansoprazole Is Associated with Worsening Asthma Control in Children with the CYP2C19 Poor Metabolizer Phenotype. Ann Am Thorac Soc 12:878-85
Fitzpatrick, Anne M; Holbrook, Janet T; Wei, Christine Y et al. (2014) Exhaled breath condensate pH does not discriminate asymptomatic gastroesophageal reflux or the response to lansoprazole treatment in children with poorly controlled asthma. J Allergy Clin Immunol Pract 2:579-86.e7
Nguyen, Jessica M; Holbrook, Janet T; Wei, Christine Y et al. (2014) Validation and psychometric properties of the Asthma Control Questionnaire among children. J Allergy Clin Immunol 133:91-7.e1-6
Lang, Jason E; Dozor, Allen J; Holbrook, Janet T et al. (2013) Biologic mechanisms of environmental tobacco smoke in children with poorly controlled asthma: results from a multicenter clinical trial. J Allergy Clin Immunol Pract 1:172-80
Lang, Jason E; Holbrook, Janet T; Wise, Robert A et al. (2013) Obesity in children with poorly controlled asthma: Sex differences. Pediatr Pulmonol 48:847-56
Writing Committee for the American Lung Association Asthma Clinical Research Centers; Holbrook, Janet T; Wise, Robert A et al. (2012) Lansoprazole for children with poorly controlled asthma: a randomized controlled trial. JAMA 307:373-81