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Randomized Controlled Trial
. 2015 Jun;12(6):878-85.
doi: 10.1513/AnnalsATS.201408-391OC.

Lansoprazole Is Associated with Worsening Asthma Control in Children with the CYP2C19 Poor Metabolizer Phenotype

Jason E Lang  1   2 , Janet T Holbrook  3 , Edward B Mougey  2 , Christine Y Wei  3 , Robert A Wise  4 , W Gerald Teague  5 , John J Lima  2 ; American Lung Association-Airways Clinical Research Centers
Collaborators, Affiliations
Randomized Controlled Trial

Lansoprazole Is Associated with Worsening Asthma Control in Children with the CYP2C19 Poor Metabolizer Phenotype

Jason E Lang et al. Ann Am Thorac Soc. 2015 Jun.

Abstract

Rationale: Gastric acid blockade in children with asymptomatic acid reflux has not improved asthma control in published studies. There is substantial population variability regarding metabolism of and response to proton pump inhibitors based on metabolizer phenotype. How metabolizer phenotype affects asthma responses to acid blockage is not known.

Objectives: To determine how metabolizer phenotype based on genetic analysis of CYP2C19 affects asthma control among children treated with a proton pump inhibitor.

Methods: Asthma control as measured by the Asthma Control Questionnaire (ACQ) and other questionnaires from a 6-month clinical trial of lansoprazole in children with asthma was analyzed for associations with surrogates of lansoprazole exposure (based on treatment assignment and metabolizer phenotype). Groups included placebo-treated children; lansoprazole-treated extensive metabolizers (EMs); and lansoprazole-treated poor metabolizers (PMs). Metabolizer phenotypes were based on CYP2C19 haplotypes. Carriers of the CYP2C19*2, *3, *8, *9, or *10 allele were PMs; carriers of two wild-type alleles were extensive metabolizers (EMs).

Measurements and main results: Asthma control through most of the treatment period was unaffected by lansoprazole exposure or metabolizer phenotype. At 6 months, PMs displayed significantly worsened asthma control compared with EMs (+0.16 vs. -0.13; P = 0.02) and placebo-treated children (+0.16 vs. -0.23; P < 0.01). Differences in asthma control were not associated with changes in gastroesophageal reflux symptoms. Recent upper respiratory infection worsened asthma control, and this upper respiratory infection effect may be more pronounced among lansoprazole-treated PMs.

Conclusions: Children with the PM phenotype developed worse asthma control after 6 months of lansoprazole treatment for poorly controlled asthma. Increased exposure to proton pump inhibitor may worsen asthma control by altering responses to respiratory infections. Clinical trial registered with www.clinicaltrials.gov (NCT00604851).

Keywords: child; lansoprazole; phenotype; polymorphism (genetics).

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Figures

Figure 1.
Figure 1.
Change in Asthma Control Questionnaire (ACQ) score in children with uncontrolled asthma by level of lansoprazole exposure. Higher scores indicate worse asthma control. Error bars indicate 95% confidence intervals. There is zero suppression on the y axis. EM = lansoprazole-treated extensive metabolizer; Plb = placebo; PM = lansoprazole-treated poor metabolizer.
Figure 2.
Figure 2.
Difference in Asthma Control Questionnaire (ACQ) scores between patients with recent upper respiratory infection (URI) and those without (calculated as ACQURI – ACQno URI). Shown is the difference by metabolizer phenotypes over the 6-month treatment period. EM = lansoprazole-treated extensive metabolizer; Plb = placebo; PM = lansoprazole-treated poor metabolizer.
See this image and copyright information in PMC

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References

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