Meta-analysisindependent cross-checkabstract checked I-PPI-114 standard review
Trials hint at a small pneumonia risk at most
The impact of proton pump inhibitor exposure on pneumonia: an updated meta-analysis based on randomized controlled trials.
Overview
Wu Z et al.. Front Pharmacol 2025 · PMID 41230098 · DOI 10.3389/fphar.2025.1713256
Pooling 20 randomised trials, PPI users had a 10% higher pneumonia rate, which was not statistically certain.
Does the study support the specific claim? Partly · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Pool RCTs on PPIs and pneumonia.
- How was the study done?
Meta-analysis.
- How many people, animals or samples were studied?
29,100 participants.
- What was actually found?
RR 1.10, borderline.
- How large was the observed effect?
1.10 (0.99-1.21).
- What do the results mean in everyday life?
Any pneumonia risk is likely small.
- What are the study's limitations?
Subgroup multiplicity.
- What does it say about Elawady's specific claim?
Neither confirms nor excludes a small effect.
- Do the results apply to Germany and Europe?
European subgroup null.
- What can explicitly not be concluded from this study?
Cannot prove causation.
Scientific in-depth review
1. Full reference
- Authors
- Wu Z et al.
- Journal
- Front Pharmacol
- Year
- 2025
- Identifier
- PMID 41230098 DOI 10.3389/fphar.2025.1713256
- Verification
- verified – PubMed efetch 2026-10-26 + Crossref 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
No conflicts declared
2. Research question
Does PPI exposure increase pneumonia incidence in randomised trials?
3. Study design and population
- Study design
- Meta-analysis – Systematic review and meta-analysis of RCTs
- Population
20 RCTs
- Country
International (subgroups Asia, Europe, America)
- Period
January 2000 - March 2025
- Sample size
20 RCTs; 29,100 participants
- Inclusion and exclusion criteria
RCTs comparing PPI with non-PPI
4. Methods and endpoints
- Exposure / intervention
PPI
- Comparator
No PPI
- Endpoints
Pneumonia (overall, HAP, VAP)
- Statistical methods
Pooled relative ratios; subgroup analyses
5. Actual results
- Results
Pneumonia RR 1.10 (0.99-1.21; P=0.07); HAP 1.12 (1.00-1.26; P=0.06); Asian population RR 1.30 (P=0.02); Europe 1.04; America 1.02; ICU 1.05.
- Absolute risks
Not reported
- Authors' conclusion
PPI use might increase pneumonia risk, especially in Asian populations.
6. Strengths
- RCT-only
7. Weaknesses
- Many subgroup analyses; multiplicity
- Overlaps with Omar 2026 (I-PPI-113)
8. Risk of bias
- Orienting tool
- AMSTAR 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Subgroup claims fragile.
9. Assessment of the statistical interpretation
Borderline overall; subgroup findings exploratory (stats/C-PPI-05_pneumonia.py).
10. Relevance to the specific claim
Randomised evidence compatible with at most a small pneumonia increase (upper limit ~21%).
11. Independent contrary findings
Omar 2026 OR 1.00.
12. Transferability to Germany and Europe
Applicable; European subgroup null.
13. Overall methodological judgement
Small effect possible, not established.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | moderate |
| Directness | direct |
| Reproducibility | partly replicated |
| Consistency with the overall evidence | mixed |
| Regional transferability | moderate |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Long-term outpatient use.
15. Linked fact checks
- Long-term acid suppression causes hip fractures and pneumonia. – Studies with mixed or unclear results