Proton Pump Inhibitors and the Risk of Community-Acquired Pneumonia: An Updated Meta-analysis

2021 ◽  
pp. 106002802110392
Author(s):  
Xuejiao Xun ◽  
Qifan Yin ◽  
Yuhao Fu ◽  
Xueru He ◽  
Zhanjun Dong
Keyword(s):  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Literature Search ◽  
Primary Outcome ◽  
Adverse Reactions ◽  
Meta Analysis ◽  
Community Acquired Pneumonia ◽  
Published Evidence ◽  
Increased Risk ◽  
Comprehensive Literature Search

Background: Some studies suggested an increased risk of community-acquired pneumonia (CAP) among proton pump inhibitors (PPI) users. However, the published evidence is inadequate to define the association between PPI use and the risk of CAP. Objective: The aims of our meta-analysis were to systematically assess the association between the risk of CAP and PPI use in adults to reduce the adverse effects of PPI and ensure the safety of medication for patients. Methods: A comprehensive literature search was conducted, published between January 1, 2004, and February 1, 2021. The primary outcome was the incidence of CAP. This meta-analysis was performed using odds ratios (ORs) with 95% CIs as effective measures; 13 studies including 2 098 804 patients were enrolled in our meta-analysis. Results: Our study revealed that the incidence of CAP was higher in PPI users than non -PPI users [OR = 1.37 (95% CI = 1.22–1.53)], especially for PPI duration < 30 days [OR = 1.49 (95% CI = 1.34–1.66)]. Compared with non-PPI use, PPI use increased the incidence of CAP in the stroke disease population [OR = 1.52 (95% CI = 1.33–1.75)], but not in the liver disease population [OR = 1.13 (95% CI = 0.98–1.30)]. Conclusions and Relevance: Using PPI could increase the risk of CAP when compared to not using PPI. PPI use increased the incidence of CAP in patients with stroke. Clinicians and clinical pharmacists should weigh the benefits before medication and strictly control the indication of the prescription, so as to reduce adverse reactions.

scholarly journals Meta-analysis of proton pump inhibitors induced risk of community-acquired pneumonia

2020 ◽  
Vol 32 (5) ◽  
pp. 292-299 ◽  
Author(s):  
Phung Anh Nguyen ◽  
Mohaimenul Islam ◽  
Cooper J Galvin ◽  
Chih-Cheng Chang ◽  
Soo Yeon An ◽  
...  
Keyword(s):  
Systematic Review ◽  
Random Effects ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Observational Studies ◽  
Meta Analysis ◽  
Community Acquired Pneumonia ◽  
Cochrane Library ◽  
High Dose ◽  
Increased Risk

Abstract Purpose Proton pump inhibitors (PPIs), one of the most widely used medications, are commonly used to suppress several acid-related upper gastrointestinal disorders. Acid-suppressing medication use could be associated with increased risk of community-acquired pneumonia (CAP), although the results of clinical studies have been conflicting. Data sources A comprehensive search of MEDLINE, EMBASE and Cochrane library and Database of Systematic Reviews from the earliest available online year of indexing up to October 2018. Study selection We performed a systematic review and meta-analysis of observational studies to evaluate the risk of PPI use on CAP outcomes. Data extraction Included study location, design, population, the prevalence of CAP, comparison group and other confounders. We calculated pooled odds ratio (OR) using a random-effects meta-analysis. Results of data synthesis Of the 2577 studies screening, 11 papers were included in the systematic review and 7 studies with 65 590 CAP cases were included in the random-effects meta-analysis. In current PPI users, pooled OR for CAP was 1.86 (95% confidence interval (CI), 1.30–2.66), and in the case of recent users, OR for CAP was 1.66 (95% CI, 1.22–2.25). In the subgroup analysis of CAP, significance association is also observed in both high-dose and low-dose PPI therapy. When stratified by duration of exposure, 3–6 months PPIs users group was associated with increased risk of developing CAP (OR, 2.05; 95% CI, 1.22–3.45). There was a statistically significant association between the PPI users and the rate of hospitalization (OR, 2.59; 95% CI, 1.83–3.66). Conclusion We found possible evidence linking PPI use to an increased risk of CAP. More randomized controlled studies are warranted to clarify an understanding of the association between PPI use and risk of CAP because observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding.

scholarly journals Association between Proton Pump Inhibitors and Respiratory Infections: A Systematic Review and Meta-Analysis of Clinical Trials

2008 ◽  
Vol 22 (9) ◽  
pp. 761-766 ◽  
Author(s):  
Nabil Sultan ◽  
Jose Nazareno ◽  
James Gregor
Keyword(s):  
Respiratory Infection ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Respiratory Infections ◽  
Bacterial Colonization ◽  
Meta Analysis ◽  
Gastrointestinal Diseases ◽  
Controlled Trials ◽  
High Dose ◽  
Increased Risk

BACKGROUND: Proton pump inhibitors (PPIs) have become the mainstay of treatment for and prevention of many serious gastrointestinal diseases. Laboratory and clinical evidence suggests that the increase in gastric pH caused by PPIs may be linked to increased bacterial colonization of the stomach and may predispose patients to an increased risk for respiratory infections.OBJECTIVE: To examine the association between PPI treatment and respiratory infections.METHODS: A literature search was conducted using PubMed, MEDLINE and Cochrane databases of randomized, placebo-controlled trials evaluating the efficacy of PPIs. Studies that listed and quantified the specific adverse events of ‘respiratory infection’ or ‘upper respiratory infection’ (or equivalent), and compared their rates between PPIs and placebo were included. The χ2analysis was used to calculate the significance of association in individual studies and a meta-analysis of the selected studies was performed.RESULTS: Of 7457 studies initially identified and 70 relevant randomized, controlled trials (RCTs) selected, seven studies met the inclusion criteria. A total of 16 comparisons for χ2analysis were possible given the multiple dosage arms used in several studies. PPIs included in the studies were esomeprazole, rabeprazole, pantoprazole and omeprazole. More than one-half of the studies showed a trend toward an association between PPI use and respiratory infections, although the majority of the studies failed to show a significant correlation. A single study using high-dose esomeprazole (40 mg) showed a significant association – 4.3% rate of respiratory infections in the active group compared with 0% in the placebo group (P<0.05). Meta-analysis showed a trend toward an association between PPIs and respiratory infections, although it failed to reach significance (OR 1.42, 95% CI 0.86 to 2.35; P=0.17).CONCLUSION: Although a trend was evident in both a χ2analysis of individual studies and a meta-analysis, the present review and meta-analysis failed to show a conclusive association between PPIs and respiratory infections. Very few RCTs actively sought out respiratory infections, which excluded the majority of RCTs identified. A well-structured, placebo-controlled prospective study would be needed to determine whether a true association between PPIs and respiratory infections exists.

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

2021 ◽  
pp. 2003229
Author(s):  
Linda J.T.M. van der Sande ◽  
Quirijn Jöbsis ◽  
Michiel A.G.E. Bannier ◽  
Ewoudt M.W. van de Garde ◽  
Jan J.M. Coremans ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Proportional Hazards ◽  
Community Acquired Pneumonia ◽  
Cox Proportional Hazards ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Receptor Antagonists ◽  
Increased Risk

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.

scholarly journals Long Term Use of Proton Pump Inhibitors: Where to Draw the Line

2018 ◽  
Vol 1 (1) ◽  
pp. 20-35
Author(s):  
M. Manzurul Haque
Keyword(s):  
Adverse Effects ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Community Acquired Pneumonia ◽  
Ulcer Disease ◽  
Increased Risk ◽  
Prospective Trials ◽  
Evidence Based Therapy ◽  
Clostridium Difficile Associated Diarrhea

Proton pump inhibitors are the leading evidence-based therapy for acid related upper gastrointestinal disorders including dyspepsia, GERD and peptic ulcer disease. These are among the most frequently prescribed drugs globally. However, PPIs have been subjected to studies and have been associated with increased risk of adverse effects like Clostridium difficile-associated diarrhea, community-acquired pneumonia, bone fracture, reduced intestinal absorption of vitamins and minerals, and more recently kidney damage and dementia etc. In this review the recent literature regarding these adverse effects and their association with long-term proton pump inhibitor treatment is discussed. The objective of this review is to analyse the potential adverse effects of long-term PPI use and summarize the clinical implications. We documented a considerable increase in the use of PPIs over the last decade. This increase is due to over-prescription and use of PPIs for inappropriate indications. On the other hand, some patients may have had PPI therapy discontinued abruptly or inappropriately due to safety concerns. However the patients with a proven indication for a PPI should continue to receive it in the lowest effective dose for a shortest possible time. Finally, in most cases and based on the available evidence, PPIs benefits seem to outweigh potential adverse effects. Large randomized prospective trials are required to more firmly establish direct cause and effect relationships between PPIs and adverse events.

Abstract 15722: Proton Pump Inhibitors and Risk of Myocardial Infarction: A Systematic Review and Meta-analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ahmed Ullah Mishuk ◽  
Shahariar Mohammed Fahim ◽  
Richard Hansen ◽  
Li Chen ◽  
Philippe Gaillard ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Systematic Review ◽  
Clinical Trials ◽  
Quality Assessment ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Observational Studies ◽  
Meta Analysis ◽  
Pharmacovigilance System ◽  
Increased Risk

Introduction: Proton Pump Inhibitors (PPIs) are generally considered safe, but recent evidence suggests otherwise. Objective: This systematic review and meta-analysis assessed the association between PPIs and the risk of myocardial infarction (MI), using both clinical trials and observational studies. Methods: A systematic search was performed in December 2019 to retrieve all potential studies using PubMed, PsycInfo, International Pharmaceutical Abstracts, Web of Science, and Clinicaltrials.gov. This search initially identified any published studies describing any adverse event (AE) or outcomes related to PPI. Records were included in this study if 1) studies were published in English, 2) study design was clinical trials or observational studies, 3) PPI use was the exposure or treatment, and 4) study outcome was the incidence of MI. Two researchers independently reviewed all identified records, performed full article review, extracted data into structured evidence table, and conducted quality assessment using Newcastle-Ottawa Scale and Quality Assessment Tool for Quantitative Studies. Meta-analysis was performed using the RStudio software to assess the risk of MI with PPI use. Results: A total of 4,507 abstracts meeting the inclusion criteria were identified, and 20 full articles were included in this study, among which 10 were cohort, 3 were case-control, 3 were RCT post-hoc analysis, and 4 were RCT studies. The pooled Odds Ratio (OR)=1.40 with 95% CI=1.20-1.63 for all studies indicated the presence of an association between PPI use and increased risk of MI compared to PPI non-users. Meta-analysis found a similar association between PPI use and increased risk of MI in observational studies (OR=1.40; 95% CI=1.20, 1.64) but no association (OR=0.90; 95% CI=0.47, 1.73) in RCT-studies. Heterogeneity was high (I 2 > 75%) for all analyses except for RCTs (I 2 =0%). Conclusion: Although our meta-analysis identified the association between PPI use and increased risk of MI, results from RCTs did not agree with observational studies. Due to the mixed findings by study designs and high variation of heterogeneity among studies, the pharmacovigilance system should evaluate different levels of evidence to support decision making in safety of drug products.

scholarly journals Proton Pump Inhibitors and Fractures in Adults: A Critical Appraisal and Review of the Literature

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Silvia Irina Briganti ◽  
Anda Mihaela Naciu ◽  
Gaia Tabacco ◽  
Roberto Cesareo ◽  
Nicola Napoli ◽  
...  
Keyword(s):  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Bone Health ◽  
Meta Analysis ◽  
Fragility Fractures ◽  
High Dose ◽  
Case Control Studies ◽  
Number Of Patients ◽  
Increased Risk

Despite the large number of patients worldwide being on proton pump inhibitors (PPIs) for acid-related gastrointestinal disorders, uncertainty remains over their long-term safety. Particularly, the potential side effects of these drugs on bone health have been evaluated in the last years. The purpose of our narrative review is to gather and discuss results of clinical studies focusing on the interactions between PPIs and fracture risk. Data generated mainly from nested case-control studies and meta-analysis suggest that long-term/high-dose PPIs users are characterized by an increased risk of fragility fractures, mainly hip fractures. However, in these studies, the PPIs-induced bone impairment is often not adjusted for different confounding variables that could potentially affect bone health, and exposure to PPIs was reported using medical prescriptions without adherence evaluation. The mechanisms of the PPI-related bone damage are still unclear, but impaired micronutrients absorption, hypergastrinemia, and increased secretion of histamine may play a role. Clinicians should pay attention when prescribing PPIs to subjects with a preexistent high risk of fractures and consider antiosteoporotic drugs to manage this additive effect on the bone. However, further studies are needed to clarify PPIs action on the bone.

scholarly journals Association of IL-6 −174 G>C Polymorphism with Susceptibility to Colorectal Cancer and Gastric Cancer: a Systematic Review and Meta-Analysis

2019 ◽  
Vol 62 (4) ◽  
pp. 137-146 ◽  
Author(s):  
Jamal Jafari-Nedooshan ◽  
Seyed Alireza Dastgheib ◽  
Saeed Kargar ◽  
Mohammad Zare ◽  
Ali Raee-Ezzabadi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Literature Search ◽  
Meta Analysis ◽  
Case Control ◽  
Case Control Studies ◽  
Pooled Data ◽  
Increased Risk ◽  
Strength Of Association ◽  
Larger Sample ◽  
Comprehensive Literature Search

Background: The −174G>C (rs1800795) polymorphism at interleukin 6 (IL-6) gene has been reported to be related with the occurrence of colorectal (CRC) and gastric (GC) cancers. However, the results had been conflicting and controversial. In order to give a comprehensive and precise result, we summarized available data to analyze the association of this polymorphism with CRC and GC risk. Methods: A comprehensive literature search on PubMed, Elsevier Science Direct, and CNKI database was performed to identify all eligible studies up to May 15, 2019. The strength of association was assessed by odds ratios (ORs) with 95% confidence intervals (CI). Results: A total of 29 case-control studies including 16 studies with 7,560 cases and 9,574 controls on CRC and 13 studies with 1,445 cases and 2,918 controls on GC were selected. Overall, pooled data showed that the IL-6 −174G>C polymorphism was not significantly associated with increased risk of CRC and GC in overall. When stratified by ethnicity, we found a statistically significant association between the IL-6 −174 G>C polymorphism and CRC risk in Asians (CC vs. GG: OR = 1.860, 95% CI 1.061–3.258, p = 0.030; and CC vs. CG+GG: OR = 1.941, 95% CI 1.131–3.331, p = 0.016). Conclusion: The meta-analysis suggests that IL-6 −174G>C polymorphism was not significantly associated with the increased risk of CRC and GC in overall population. However, the results showed that IL-6 −174G>C polymorphism may be associated with risk of GC in Asians. Further studies including a larger sample size will be necessary to clarify these results.

scholarly journals Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis

2021 ◽  
Vol 14 ◽  
pp. 175628482110514
Author(s):  
Daniel Segna ◽  
Nele Brusselaers ◽  
Damian Glaus ◽  
Niklas Krupka ◽  
Benjamin Misselwitz
Keyword(s):  
Gastric Cancer ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Meta Analysis ◽  
Random Effect ◽  
Significant Risk ◽  
Case Control ◽  
Cochrane Library ◽  
Increased Risk ◽  
Statistical Heterogeneity

Introduction: The use of proton-pump inhibitors (PPI) may be associated with an increased risk of gastric cancer (GC). Objective: To review and meta-analyse available literature investigating the association between PPI use and GC risk. Methods: Two independent reviewers systematically searched Ovid MEDLINE, EMBASE, and Cochrane Library (inception to July 2020) for case-control and cohort studies assessing the association between PPI use and GC according to a predefined protocol in PROSPERO (CRD42018102536). Reviewers independently assessed study quality, extracted data, and meta-analysed available and newly calculated odds ratios (ORs) using a random-effects model, and stratified for GC site (cardia versus non-cardia) and PPI duration (<1 year, 1–3 years, >3 years). Results: We screened 2,396 records and included five retrospective cohort and eight case-control studies comprising 1,662,881 individuals in our meta-analysis. In random-effect models, we found an increased GC risk in PPI users [OR: 1.94, 95% confidence interval (95% CI): 1.47–2.56] with high statistical heterogeneity ( I2 = 82%) and overall moderate risk of bias. Stratified analyses indicated a significant risk increase in non-cardia (OR: 2.20, 95% CI: 1.44–3.36, I2 = 77%) with a similar non-significant trend in cardia regions (OR: 1.77, 95% CI: 0.72–4.36, I2 = 66%). There was no GC increase with longer durations of PPI exposure (<1 year: OR: 2.29, 95% CI: 2.13–2.47, I2 = 0%; 1–3 years: OR: 1.46, 95% CI: 0.53–4.01, I2 = 35%; >3 years: OR: 2.08, 95% CI: 0.56–7.77, I2 = 61%). Conclusion: We found a twofold increased GC risk among PPI users, but this association does not confirm causation and studies are highly heterogeneous. PPI should only be prescribed when strictly indicated.

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