Association between proton pump inhibitor use and risk of pneumonia in children: nationwide self-controlled case series study in Sweden

Wang, Yun‐Han; Svanström, Henrik; Wintzell, Viktor; Ludvigsson, Jonas F.; Pasternak, Björn

doi:10.1136/bmjopen-2022-060771

Cited by 5 publications

(8 citation statements)

References 19 publications

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“…Some studies, although limited by sample size and design, suggested the increased risks of necrotizing enterocolitis, upper respiratory infections, pneumonia, sepsis, urinary tract infections, gastroenteritis, Clostridium difficile infections, and fractures (4,24). However, others did not observe these associations (25). The small cohort size in our study did not allow us to accurately evaluate the occurrence of safety events.…”

Section: Discussionmentioning

confidence: 99%

Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis: Predictive Factors and Long-Term Step-Down Efficacy

Gutiérrez-Junquera¹,

Fernández‐Fernández²,

Domínguez-Ortega³

et al. 2022

Journal of Pediatric Gastroenterology &Amp; Nutrition

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Objectives: To assess the short-and long-term efficacy of proton pump inhibitor (PPI) therapy for pediatric eosinophilic esophagitis (EoE) in realworld practice with a step-down strategy, and to evaluate factors predictive of PPI responsiveness. Methods: We collected data regarding the efficacy of PPIs during this crosssectional analysis of the prospective nationwide RENESE registry. Children with EoE treated with PPI monotherapy were included. Histological remission was defined as a peak eosinophilic count of <15 eosinophils (eos)/ high-power field (hpf). Factors associated with PPI responsiveness were identified using multivariate logistic regression analysis. Results: After induction therapy, histological and clinico-histological remission were observed in 51.4% (n = 346) and 46.5% of children, respectively. Normal endoscopic appearance of the esophagus was associated with a higher possibility [odds ratio (OR), 9.20; 95% confidence interval (CI), 2.10-40.16], and fibrostenotic phenotype was associated with a lower possibility (OR, 0.36; 95% CI, 0.18-0.74) of histological remission. Long-term therapy with a step-down strategy effectively maintained histological remission in 68.5% and 85.3% of children at 7 months (n = 108) and 16 months (n = 34), respectively. Complete initial histological remission (≤5 eos/hpf) was associated with a higher possibility of sustained histological remission (OR, 5.08; 95% CI, 1.75-14.68). Adverse events were infrequent and mild. Conclusions: We confirmed the efficacy of PPIs for a large cohort of children with EoE with sustained histological remission using a stepdown strategy. Children with fibrostenotic phenotypes are less likely to respond to induction therapy. Furthermore, patients with complete initial histological remission are more likely to experience long-term histological remission.

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Section: Discussionmentioning

confidence: 99%

Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis: Predictive Factors and Long-Term Step-Down Efficacy

Gutiérrez-Junquera¹,

Fernández‐Fernández²,

Domínguez-Ortega³

et al. 2022

Journal of Pediatric Gastroenterology &Amp; Nutrition

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“…Second, information was not available on breastfeeding or social interactions. Nevertheless, analyses were adjusted for other notable risk factors for infections, such as maternal comorbidities, prematurity, low birth weight, or cesarean delivery, which is a novelty compared with previous studies conducted in young children . In addition, we showed that residual confounding tended to be minimized, through calculation of E-values and use of a negative control outcome.…”

Section: Discussionmentioning

confidence: 95%

“…31,32 Three pediatric studies examined the risk of respiratory tract infections in children, with conflicting results 20,33,34 : PPI use was associated with a doubled risk in 1 cohort study, 33 whereas the results of 2 studies did not support an association. 20,34 One study showed a 2-fold increased risk of central nervous system infections associated with PPI in adults. 35 Two studies have investigated the risk of urinary tract or skin infections, also in adults: one found no association for these sites 36 while the other showed increased risks in PPI users, which was attributed to residual confounding.…”

Section: Discussionmentioning

confidence: 99%

“…We applied a 30-day lag on exposure because of the latency in the development of infection and to limit protopathic bias. In particular, protopathic bias was suspected of overestimating associations between pneumonia and PPI use …”

Section: Methodsmentioning

confidence: 99%

“…Nevertheless, analyses were adjusted for other notable risk factors for infections, such as maternal comorbidities, prematurity, low birth weight, or cesarean delivery, 42 which is a novelty compared with previous studies conducted in young children. 20,[31][32][33][34] In addition, we showed that residual confounding tended to be minimized, through calculation of E-values and use of a negative control outcome. Third, PPI use during hospital stays or over-the-counter use is not identifiable in the SNDS but is limited.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

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Proton Pump Inhibitor Use and Risk of Serious Infections in Young Children

Lassalle¹,

Zureik

Dray‐Spira³

2023

JAMA Pediatr

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ImportanceProton pump inhibitor (PPI) use may lead to infections through alteration of the microbiota or direct action on the immune system. However, only a few studies were conducted in children, with conflicting results.ObjectiveTo assess the associations between PPI use and serious infections in children, overall and by infection site and pathogen.Design, Setting, and ParticipantsThis nationwide cohort study was based on the Mother-Child EPI-MERES Register built from the French Health Data System (SNDS). We included all children born between January 1, 2010, and December 31, 2018, who received a treatment for gastroesophageal reflux disease or other gastric acid–related disorders, namely PPIs, histamine 2 receptor antagonists, or antacids/alginate. The index date was defined as the first date any of these medications was dispensed. Children were followed up until admission to the hospital for serious infection, loss of follow-up, death, or December 31, 2019.ExposurePPI exposure over time.Main Outcomes and MeasuresAssociations between serious infections and PPI use were estimated by adjusted hazard ratios (aHRs) and 95% CIs using Cox models. PPI use was introduced as time-varying. A 30-day lag was applied to minimize reverse causality. Models were adjusted for sociodemographic data, pregnancy characteristics, child comorbidities, and health care utilization.ResultsThe study population comprised 1 262 424 children (median [IQR] follow-up, 3.8 [1.8-6.2] years), including 606 645 who received PPI (323 852 male [53.4%]; median [IQR] age at index date, 88 [44-282] days) and 655 779 who did not receive PPI (342 454 male [52.2%]; median [IQR] age, 82 [44-172] days). PPI exposure was associated with an increased risk of serious infections overall (aHR, 1.34; 95% CI, 1.32-1.36). Increased risks were also observed for infections in the digestive tract (aHR, 1.52; 95% CI, 1.48-1.55); ear, nose, and throat sphere (aHR, 1.47; 95% CI, 1.41-1.52); lower respiratory tract (aHR, 1.22; 95% CI, 1.19-1.25); kidneys or urinary tract (aHR, 1.20; 95% CI, 1.15-1.25); and nervous system (aHR, 1.31; 95% CI, 1.11-1.54) and for both bacterial (aHR, 1.56; 95% CI, 1.50-1.63) and viral infections (aHR, 1.30; 95% CI, 1.28-1.33).Conclusions and RelevanceIn this study, PPI use was associated with increased risks of serious infections in young children. Proton pump inhibitors should not be used without a clear indication in this population.

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A review of proton pump inhibitor use in cystic fibrosis and considerations for deprescribing

Omecene,

Wilcox,

Cox

et al. 2024

Pediatric Pulmonology

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Use of proton‐pump inhibitors (PPIs) is common among people with cystic fibrosis (pwCF) both for the management of suspected GERD, as well as pancreatic enzyme replacement therapy augmentation. Despite their use, limited data exist to demonstrate a clinically significant impact of PPIs on key endpoints in pwCF. Furthermore, the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy may modify the need for use. These notions, coupled with the potential for adverse outcomes associated with long‐term PPI use in pwCF, should facilitate re‐evaluation of long‐term PPI use in pwCF and promote potential deprescribing. Despite limited data on PPI deprescribing in pwCF, it intuitively mirrors the existing guidance in adults in the general population, but with added consideration given to tapering strategy, and monitoring for CF‐specific outcomes such as nutritional and respiratory status. The development of a monitoring and re‐initiation plan is key to reducing deprescribing inertia. This review aims to summarize the evidence that details the concern for long‐term use of PPIs and provide CF clinicians with rationale and guidance on how to approach deprescribing in their practice.

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Association between proton pump inhibitor use and risk of pneumonia in children: nationwide self-controlled case series study in Sweden

Cited by 5 publications

References 19 publications

Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis: Predictive Factors and Long-Term Step-Down Efficacy

Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis: Predictive Factors and Long-Term Step-Down Efficacy

Proton Pump Inhibitor Use and Risk of Serious Infections in Young Children

A review of proton pump inhibitor use in cystic fibrosis and considerations for deprescribing

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