Association Between Proton Pump Inhibitor Use and Risk of Asthma in Children

Abstract

To evaluate if proton pump inhibitor (PPI) use is associated with risk of asthma in children.Children and adolescents ≤17 years included in several national registries in Sweden from January 1, 2007, to December 31, 2016.Data sources from this study included the following: (1) the National Patient Register, which contains complete records of disease diagnoses and surgical procedures from all inpatient and outpatient hospital and emergency department encounters; (2) the Prescribed Drug Register, which contains data on medications dispensed at all pharmacies in Sweden, and (3) the Total Population Register at Statistics Sweden, which provides details on demographic and socioeconomic characteristics. From these sources, all children who initiated PPI use, defined as patients prescribed their first PPI during the study period and who had no PPI prescription in the year previous. Patients with history of asthma, defined as a diagnosis of asthma within 5 years before the index date or a prescription for an asthma medication within 1.5 years before the index date, were excluded. Those who initiated PPI use and those who did not were matched (1:1 ratio) on the basis of propensity score and age group to control for potential confounding. The primary outcome was incident asthma, defined as a first diagnosis of asthma (primary or secondary diagnosis) captured from hospital records and specialist outpatient care or ≥2 independent prescriptions for any asthma medication filled within 90 days. The propensity score was derived by using multivariable logistic regression on the basis of several covariates including patient demographic and socioeconomic characteristics, comorbidities in the 2 years before the index date, and use of health care resources and comedications in the year before the index date.Among the 80 870 pairs (63.0% girls; mean age: 12.9 [SD: 4.8] years), those who initiated PPI use had a higher incidence rate of asthma (21.8 events per 1000 person-years), compared with those who did not initiate PPIs (14.0 events per 1000 person-years), with a hazard ratio (HR) of 1.57 (95% confidence interval [CI]: 1.49 to 1.64). The risk of asthma was significantly increased across all age groups and was the highest for infants and toddlers with an HR of 1.83 (95% CI: 1.65 to 2.03) in the group <6 months of age and 1.91 (95% CI: 1.65 to 2.22) in the 6 months to <2 years of age group (P < .001 for interaction). The association was consistent through all sensitivity analyses, including high-dimensional propensity score matching (HR: 1.48 [95% CI: 1.41 to 1.55]). In addition, the association between initiation of PPI use and risk of asthma was significantly different in subgroup analyses, according to history of atopic disease (HR for history: 1.22 [95% CI: 1.04 to 1.43]; HR for no history: 1.60 [95% CI: 1.52 to 1.68]; P = .001 for interaction).Using data from a national registry in Sweden, the authors of this study report an 57% increased risk of asthma among children (across all age groups) who initiated PPI uses, compared with that of those who did not.With this study, the authors add to a growing body of literature in both pregnant women and young infants that questions the safety of PPI use. Specifically, it is one of the first in which researchers look at PPI use and risk of asthma across all age groups, not just infants and toddlers. It is interesting to note that those without a history of atopy had higher HR to developing asthma, possibly identifying that PPI-mediated interference in the balance between the symbiotic and pathologic microbial species may cause asthma in those without genetic predispositions. Notably, however, data using large registries can only identify possible associations and further studies that can confirm asthma diagnosis, severity, PPI use, indication for use as well as several other important covariates would be needed to confirm these findings.