The risk of community-acquired pneumonia in children using gastric acid suppressants

Abstract

With the increased use of acid suppressants, significant potential complications, such as community-acquired pneumonia are becoming more apparent. Paradoxically, in spite of an increased focus on potential complications, there is an increased use of acid suppressants in children and a lack of data specifically targeting the association between acid suppressants and community-acquired pneumonia. Our main objective was to evaluate the risk of community-acquired pneumonia in children using acid suppressants (proton pump inhibitors and/or histamine-2-receptor antagonists).We performed a cohort study using data from the Clinical Practice Research Datalink. All patients aged 1 month to 18 years with a prescription of acid suppressants were included and matched to up to 4 unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of community-acquired pneumonia. The cohort consisted of 84 868 exposed and 325 329 unexposed children.Current use of proton pump inhibitors and histamine-2-receptor antagonists was associated with an increased risk of community acquired pneumonia, adjusted hazard ratio 2.05 (95% CI 1.90 to 2.22) and 1.80 (95% CI 1.67 to 1.94), respectively. The risk was even greater in patients with respiratory disease. Long term use >211 days of proton pump inhibitors and histamine-2-receptor antagonists led to a significantly greater risk of community-acquired pneumonia compared to short term use <31 days. After cessation of therapy, the risk remained increased for the following 7 months.The use of acid suppressants in children was associated with a doubled risk of community-acquired pneumonia. This risk increased with chronic use, respiratory disease and remained increased after discontinuation of therapy.

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

“…Furthermore, recent evidence,7 8 especially a large-scale randomised controlled trial8 did not find a significant difference in risk of pneumonia between patients randomised to pantoprazole and placebo. Given the scarcity of previous data in children,9 10 our study substantially expands on the understanding of this drug safety concern in the paediatric population.…”

“…In children, only two population-based studies9 10 have examined this drug safety issue. A recent cohort study10 observed a twofold increased risk of pneumonia within the first 30 days of current use of PPIs, as compared with non-use, whereas a nested case–control study found a neutral association when comparing current PPI use to past use 9.…”

“…In children, only two population-based studies9 10 have examined this drug safety issue. A recent cohort study10 observed a twofold increased risk of pneumonia within the first 30 days of current use of PPIs, as compared with non-use, whereas a nested case–control study found a neutral association when comparing current PPI use to past use 9. The discrepancies between the two studies can probably be explained by sample variation, potential selection bias, or protopathic bias, which is particularly prone to contribute to a higher risk of pneumonia occurring in the immediate period after PPI initiation.…”

Associations of proton pump inhibitors with susceptibility to influenza, pneumonia, and COVID-19: Evidence from a large population based cohort study

“…For the past two decades, accumulating evidence indicates increased risks of pneumonia under the use of PPIs [7,8,20], whereas others failed to show such associations [9,10].…”

Tracheobronchitis in children with tracheostomy tubes: Overview of a challenging problem

“…These agents increase gastric pH, which in turn leads to increased survival and growth of microbes in the stomach. 17 Several studies in both adults and children 18,19 have suggested that the use of gastric acid suppression therapy increases the risk of respiratory infections, although the topic is controversial due to a lack of controlled trials.…”