Stimulated by Wang et al 2025.[1]
PPIs – proton pump inhibitors
IF – impact factor
CDI – Clostridium difficile infection
SIBO – small intestinal bacterial overgrowth
PD – Parkinson’s disease
GERD – gastroesophageal reflex disease
OR – odds ratio– key to acronyms
I have come to quite like the large retrospective cohort studies that have been published in the last decade or so. Most come from Taiwan or Korea, where the whole population is on a health insurance database, but now China is getting in on the action, or more specifically, Tianjin. I have written a paragraph on Tianjin (Heavenly ford) in a previous blog – Acupuncture for PSA 2024. Coincidentally, last week’s blog on PSD also came from a group based in Tianjin, although it seems to be an entirely different group at the same institution – Acupuncture for PSD 3 2025.
This paper is published in the open access journal Brain and Behaviour (IF 2.7), which started out in 2011.
To my knowledge, China does not have a single database with healthcare information as we find in Taiwan and Korea; however, Tianjin has developed a project to collect a large quantity of healthcare data over the last decade. It is called the Tianjin Health and Medical Big Data Company. Stroke appears to be one of the disease categories that this project has focussed on; presumably because in China, stroke prevalence has exceeded that of ischaemic heart disease.
This paper narrows its view to one particular adverse event related to PPI use in patients with stroke, that being pneumonia. I must confess that until I read the title of this paper, I had no idea that PPIs increased any risk of disease or illness; despite suspecting for years that it cannot be good to abolish gastric acid in the long term.
PPI use is associated with an increased risk of enteric infections, particularly CDI. It is also associated with SIBO, spontaneous bacterial peritonitis, community-acquired pneumonia, hospital-acquired pneumonia, hepatic encephalopathy, and adverse outcomes in inflammatory bowel disease.[2]
It seems logical that reduced gastric acid will result in alterations in the flora of the upper gastrointestinal tract. Perhaps this predisposes to a change in bacterial colonies in the respiratory tract as well and hence altering the risk of developing pneumonia.
During the period 2016 to 2019, the Tianjin Health and Medical Big Data Company recorded 244 102 patients with stroke. Of these, 57 497 were included in the study by virtue of having their first ischaemic stroke and being on PPIs, having no missing data or a diagnosis of pneumonia (or a related condition) on admission with the stroke.
6 391 patients developed pneumonia, and this cohort was matched with stroke patients who did not develop pneumonia through propensity score matching using the following characteristics: age, gender, dementia, PD, gastric tube feeding, and oral diseases. This resulted in two cohorts of 6 389 that were compared.
Several factors were associated with developing pneumonia (in patients with their first ischaemic stroke and taking PPIs). Before matching, age and gender were factors, with older males being at highest risk. After matching, acupuncture, diabetes, GERD, suctioning phlegm, statins, and length of hospital stay were all factors affecting risk. Acupuncture, diabetes, GERD, and statins all were associated with reduced risk, whereas suctioning phlegm and increased length of hospital stay were associated with increased risk.
There appeared to be a dose response relationship between the number of acupuncture sessions and the risk of developing pneumonia. The lowest risk was associated with receiving more than 11 sessions during the hospital inpatient stay OR 0.21. This increased slightly to 0.27 when adjusted for the length of hospital stay.
This is an interesting and rather novel paper, but it does leave us with a lot of questions when we consider the possible mechanistic relationships suggested by these odds ratios. Have a think and come along on Wednesday night to debate the possibilities.
References
1 Wang S, Ou M, Ban H, et al. Effect of Acupuncture on Pneumonia Risk in Stroke Patients using Proton Pump Inhibitors: A Retrospective Case-Control Study. Brain Behav. 2025;15:e70920. doi: 10.1002/brb3.70920
2 Naito Y, Kashiwagi K, Takagi T, et al. Intestinal Dysbiosis Secondary to Proton-Pump Inhibitor Use. Digestion. 2018;97:195–204. doi: 10.1159/000481813
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