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. 2025 Sep 29;15(10):e70920. doi: 10.1002/brb3.70920

Effect of Acupuncture on Pneumonia Risk in Stroke Patients using Proton Pump Inhibitors: A Retrospective Case‐Control Study

Shaokang Wang 1,2,3, Mi Ou 1,2,3, Haipeng Ban 1,2, Tianlong Yin 1,2,3, Yalu Meng 1,2,3, Sihan Sun 1,2,3, Lili Zhang 1,2, Yuzheng Du 1,2,✉
PMCID: PMC12480440  PMID: 41024508

ABSTRACT

Background

Stroke, the second leading cause of death globally, often requires the use of proton pump inhibitors (PPIs) to prevent gastrointestinal bleeding. However, the misuse of PPI can lead to pneumonia, and no current studies have explored the preventive effects of acupuncture on PPI‐induced pneumonia.

Methods

A case‐control study was conducted using data from the Tianjin Healthcare Bigdata Company covering stroke patients on PPI from January 1, 2016 to December 31, 2019. Patients with pneumonia during hospitalization from a stroke diagnosis were assigned to the case group, while those without pneumonia served as the control group. Propensity score matching was applied using a matching threshold set at 0.05. Matching characteristics included age, gender, dementia, Parkinsonism, gastric tube feeding, and oral disease. A logistic regression model was employed to evaluate the impact of acupuncture on the risk of pneumonia in stroke patients using PPI.

Results

In this case‐control study, pneumonia occurred in 6389 (11.11%) stroke patients. Risk factors for pneumonia included suctioning phlegm and hospital stays. When the number of acupuncture sessions was treated as a continuous variable, each additional acupuncture session after the first was associated with a 6% reduction in the risk of pneumonia (odds ratio [OR]: 0.94; 95% confidence intervals [CI]: 0.93–0.95; p < 0.001). Multivariable logistic regression revealed that, compared to patients receiving acupuncture less than three times per visit, the risk of pneumonia was significantly reduced by 64% (OR: 0.36; 95% CI: 0.24–0.45; p < 0.001) for those receiving acupuncture 7–11 times per visit and by 79% (OR: 0.21; 95% CI: 0.16–0.27; p < 0.001) for those receiving acupuncture more than 11 times per visit. The highest quartile pneumonia risk was one‐fifth of the lowest quartile.

Conclusion

In conclusion, this case‐control study suggested that acupuncture may reduce pneumonia risk in stroke patients using PPI. Within a single visit, the best preventive effect was observed with more than 11 acupuncture sessions.

Keywords: Acupuncture, Proton pump inhibitors, Pneumonia, Stroke

Stroke patients often require the use of proton pump inhibitors (PPIs) to prevent gastrointestinal bleeding. However, the misuse of PPI can lead to pneumonia. This case‐control study suggested that acupuncture may reduce pneumonia risk in stroke patients using PPI.

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Abbreviations

ATP4

H+/K+‐ATPase

CAP

community‐acquired pneumonia

CI

confidence intervals

GERD

gastroesophageal reflux disease

H2RA

Histamine H2 receptor antagonists

OR

Odds Ratio

PPI

Proton pump inhibitors

1. Introduction

As the second leading cause of death worldwide, stroke poses a significant threat to human life and health due to its high incidence and disability rate (Z. Wang et al. 2023). In China, the prevalence of stroke has surpassed that of ischemic heart disease, with an incidence rate of 2.6% (Tu et al. 2023), and continues to rise. This presented a considerable challenge to the country's healthcare system (S. Wu et al. 2019). During the early stages of stroke, patients experience acute stress and require secondary prevention medications (Shim and Kim 2016; Yasuda 2015), which can lead to digestive system symptoms such as vomiting blood and black stools within a week of stroke onset (Ogata et al. 2014), significantly impacting patient prognosis and safety (S. Liu et al. 2022; Yang et al. 2013).

Proton pump inhibitors (PPIs), which target gastric H+/K+‐ATPase (ATP4), are commonly used to treat gastrointestinal diseases related to gastric acid (El Rouby et al. 2018). However, the misuse of PPI by stroke patients often arises from the need to prevent stress ulcers in nonintensive care unit settings and to mitigate the risk of gastrointestinal bleeding in patients undergoing antiplatelet or anticoagulant therapy (B.‐L. Liu et al. 2013; Savarino et al. 2018). Misuse of PPI can lead to adverse outcomes. Recent evidence has suggested an increased risk of poststroke pneumonia and community‐acquired pneumonia (CAP) associated with PPI usage (Song and Kim 2019; Zirk‐Sadowski et al. 2018). Even after controlling for potential confounders, a moderate correlation between PPI dosage and pneumonia risk remains. The association between short‐term and long‐term PPI use and pneumonia risk is still controversial. Recent research indicated that the mechanism behind PPI‐related pneumonia may involve PPI altering gastric pH, which weakens bacterial growth inhibition and leads to bacterial colonization of the respiratory tract following aspiration of full column reflux, thus triggering pneumonia (Naito et al. 2018).

Acupuncture, as a traditional Chinese therapy, has unique advantages in improving limb function, cognitive function, dysphagia, and other aspects in stroke patients (J. Wang et al. 2020; Xiao et al. 2023; L. Li et al. 2023). Early acupuncture intervention after a stroke aims to prevent further stroke development and complications. The mechanism by which acupuncture may reduce the risk of pneumonia in stroke patients taking PPI could involve repairing the gastrointestinal barrier and decreasing the incidence of reflux aspiration. Therefore, this retrospective case‐control study was to assess the benefits of acupuncture in reducing the risk of pneumonia in stroke patients taking PPI in collaboration with the Tianjin Healthcare Big Data Company.

2. Method

2.1 Database

This study is a secondary analysis based on the data acquired by Tianjin Healthcare Bigdata Company from 79 secondary and tertiary healthcare institutions in Tianjin, spanning from January 1, 2016 to December 31, 2020. The data encompassed comprehensive outpatient and inpatient records, comprising patient and visit details, medical orders, diagnosis information, and more. Random identification numbers were assigned to patients to protect their privacy. An application for an informed consent exemption was submitted. The study protocol was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (ethics number: TYLL2024[Z]字027) and was conducted following the legal requirements and tenets of the Declaration of Helsinki and its subsequent amendments.

2.1. Study Subjects

Our research included patients diagnosed with stroke who were also taking PPI from January 1, 2016 to December 31, 2019, with no restrictions based on age or gender. The first time we accessed the data was on April 26, 2024. Five types of PPI are available in Tianjin: omeprazole, pantoprazole, lansoprazole, esomeprazole, and rabeprazole. This study included only patients who had documented PPI prescriptions during each hospitalization. This study defined pneumonia using ICD codes, with patients diagnosed on admission day with ICD‐10‐J12.xx, 13, 14, 15.xx, 16.xx, 17.xx, or 18.xx classified as having pneumonia. Analysis was conducted for all included patient visits. After applying a series of inclusion and exclusion criteria, 57,497 subjects were included in the study. Patients diagnosed with pneumonia were assigned to the case group. Patients with a single hospitalization and no pneumonia diagnosis were assigned to the control group. To minimize the impact of confounding factors, the propensity score was used to match patients without pneumonia diagnoses, with a matching threshold set at 0.05. Matching characteristics included gastric tube feeding, dementia, Parkinsonism, oral diseases, age, and gender, as illustrated in Figure 1. Gastric‐tube feeding was identified as a risk factor for pneumonia in stroke patients taking PPI. While it is intended to ensure nutritional intake and prevent aspiration in stroke patients, studies suggested that compared to post‐pyloric feeding, gastric tube feeding may increase the risk of pneumonia due to mucosal irritation or injury in the pharyngeal area caused by gastric tube stimulation or improper nasogastric feeding procedure (Y. Liu et al. 2021; Alkhawaja et al. 2015). Additionally, critically ill patients may not be suitable candidates for gastric tube feeding (Huang et al. 2012). Dementia and parkinsonism were also considered as risk factors for pneumonia (Funayama et al. 2023; Won et al. 2020). These conditions often involve dysphagia, an impaired gag reflex, altered consciousness, and an increased risk of aspiration. Furthermore, oral hygiene was associated with respiratory tract infections. Microaspiration of oral bacteria is common, often occurring during sleep (Beal et al. 2004). Dental plaque may harbor respiratory pathogens, and oral microorganisms from periodontal disease may be aspirated into the lungs, triggering pneumonia (Winning et al. 2021).

FIGURE 1.

FIGURE 1

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Flowchart of case‐control study.

2.2. Study Design

This case‐control study investigated the association between acupuncture treatment and the occurrence of pneumonia in stroke patients taking PPI. The exposure group included various acupuncture modalities, such as body acupuncture, scalp acupuncture, and auricular acupuncture. To explore the effect of the sessions of acupuncture on the risk of pneumonia, we stratified the number of acupuncture treatments per visit. The study endpoint was defined as the occurrence of pneumonia in each visit. For accurate pneumonia diagnosis coding, outpatient information was excluded, and patients diagnosed with pneumonia on the day of hospital admission were not considered. Covariates included age, gender, diabetes, dementia, oral diseases, Parkinsonism, heart failure, gastroesophageal reflux disease (GERD), gastric tube feeding, suctioning phlegm, antipsychotics, statins, histamine H2 receptor antagonists (H2RA), and length of hospital stay. Detailed information on these covariates is provided in Table 1.

TABLE 1.

Baseline characteristics of the control group and case group before and after matching.

Variable Unmatched Matched
Control (n = 5,1106) Case(n = 6391) p value Control (n = 6389) Case (n = 6389) p value
n % n % n % n %
Gender 0.001 0.801
Women 21,921 42.9 2603 40.7 2588 40.5 2603 40.7
Men 29,185 57.1 3788 59.3
Age group
Mean (SD) 66.86 (11.81) 71.35 (12.81) < 0.001 71.44 (12.67) 71.34 (12.81) 0.662
< 60 11,798 23.1 1007 15.8 < 0.001 922 15.5 1007 15.8 0.935
60–75 24,433 47.8 2367 37.0 2372 37.1 2367 37.0
≥ 75 14,875 29.1 3017 47.2 3025 47.3 3015 47.2
Acupuncture 10,912 21.4 1050 16.4 < 0.001 1677 26.2 1050 16.4 < 0.001
Q1 2561 23.5 429 40.9 < 0.001 364 21.7 429 40.9 < 0.001
Q2 2723 25.0 268 25.5 336 20.0 268 25.5
Q3 2802 25.7 188 17.9 505 30.1 188 17.9
Q4 2826 25.9 165 15.7 472 28.1 165 15.7
Diabetes 22,106 43.3 2228 34.9 < 0.001 2655 41.6 2228 34.9 < 0.001
Dementia 2397 4.7 70 1.1 < 0.001 85 1.3 70 1.1 0.258
Oral diseases 576 1.1 33 0.5 < 0.001 20 0.3 33 0.5 0.099
Parkinson 948 1.9 110 1.7 0.483 98 1.5 110 1.7 0.442
Heart failure 8421 16.5 1401 21.9 < 0.001 1427 22.3 1400 21.9 0.579
GERD 1527 3.0 59 0.9 < 0.001 148 2.3 59 0.9 < 0.001
Gastric tube feeding 7457 14.6 3784 59.2 < 0.001 3779 59.1 3782 59.2 0.971
Suctioning phlegm 13,139 25.7 3557 59.7 < 0.001 3199 50.1 3555 55.6 < 0.001
Antipsychotics 1554 3.0 420 6.6 < 0.001 377 5.9 420 6.6 0.124
Statin 41,251 80.7 3391 53.1 < 0.001 4803 75.2 3390 53.1 < 0.001
H2RA 222 0.4 36 0.6 0.176 23 0.4 36 0.6 0.117
Length of hospital time < 0.001 < 0.001
Mean (SD) 13.29 (15.77) 19.61 (26.90) 17.57 (29.49) 19.61 (26.90)
≤ 14 days 32,286 63.2 2806 43.9 < 0.001 3562 55.8 2805 43.9 < 0.001
15–30 days 17,1113 33.5 2713 42.5 2227 34.9 2712 42.4
> 30 days 1707 3.3 872 13.6 599 9.4 872 13.6
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Notes: Q1–Q4 under Acupuncture are according to the number of acupuncture quarterback partitions. p value < 0.05 was considered statistically significant.

Abbreviations: GERD, gastroesophageal reflux disease; H2RA: Histamine H2 receptor antagonists.

2.3. Statistical Analysis

Categorical variables were summarized using numbers and percentages, and differences between groups were assessed using Chi‐square tests. Continuous variables were first tested for normal distribution with the Kolmogorov–Smirnov test and were described with mean ± SD. Comparisons between groups were conducted using one‐way ANOVA. Multivariable logistic regression balanced intergroup differences and was applied to adjust for potential confounders such as underlying diseases and treatments that may affect pneumonia risk. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to identify risk factors and evaluate their effects. A p value < 0.05 was considered statistically significant. Statistical analyses were performed using R version 4.2.1.

3. Result

We performed propensity score matching for variables including age, gender, dementia, Parkinsonism, gastric tube feeding, and oral disease. This matched cohort comprised a case group (n = 6389) and the control group (n = 6389). Baseline characteristics of the participants are summarized in Table 1.

Several factors were associated with pneumonia among stroke patients using PPI but without pneumonia, including age, acupuncture, diabetes, heart failure, GERD, suctioning phlegm, antipsychotics, statins, H2RA, and length of hospital stay. After adjusting for these variables, suctioning phlegm and longer hospital stays were found to increase the risk of pneumonia. In the univariate analysis, age was not a risk factor for pneumonia induced by PPI use in stroke patients. In the multivariate analysis, diabetes was a protective factor. Conversely, acupuncture was found to be a protective factor against pneumonia (OR: 0.54, 95% CI: 0.50–0.60). Hospitalization for 15–30 days (OR: 1.55, 95% CI: 1.44–1.67) and for more than 30 days (OR: 1.85, 95% CI: 1.65–2.07) both elevated the risk of pneumonia. Detailed information is shown in Table 2

TABLE 2.

Odds ratio and 95% confidence intervals of pneumonia with acupuncture and covariates.

Univariable analysis Multivariable analysis
OR (95% CI) p Value OR (95% CI) p Value
Age group
< 60 ref —
60–74 0.98 (0.89–1.09) 0.748 —
≥ 75 0.98 (0.89–1.09) 0.723 —
Acupuncture 0.55 (0.51–0.60) < 0.001 0.54 (0.50–0.60) < 0.001
Diabetes 0.75 (0.70–0.81) < 0.001 0.79 (0.73–0.85) < 0.001
Heart failure 0.98 (0.90–1.06) 0.565 —
GERD 0.39 (0.29–0.53) < 0.001 0.42 (0.30–0.57) < 0.001
Suctioning phlegm 1.25 (1.17–1.34) < 0.001 1.11 (1.03–1.20) 0.006
Antipsychotics 1.12 (0.97–1.30) 0.116 —
Statin 0.37 (0.35–0.40) < 0.001 0.42 (0.39–0.45) < 0.001
H2RA 1.57 (0.93–2.68) 0.0925 —
Length of hospital time
≤ 14 days ref ref
15–30 days 1.55 (1.44–1.67) < 0.001 1.64 (1.52–1.78) < 0.001
> 30 days 1.85 (1.65–2.07) < 0.001 1.58 (1.40–1.79) < 0.001
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Note: p < 0.05 was considered statistically significant.

Abbreviations: GERD, gastroesophageal reflux disease; H2RA, Histamine H2 receptor antagonists;

In the univariable logistic analysis, when the number of acupuncture sessions was treated as a continuous variable, each additional acupuncture session after the first was associated with a 6% reduction in risk (OR: 0.94, 95% CI: 0.93–0.95). When the number of acupuncture sessions was treated as a categorical variable classified by quartiles, they were Q1: 1–3 sessions, Q2: 4–6 sessions, Q3: 7–11 sessions, and Q4: > 11 sessions. When acupuncture sessions were categorized and Q1 was used as the reference, Q2, Q3, and Q4 were significantly correlated with a lower risk of pneumonia (Q2, OR: 0.68, 95% CI: 0.55–0.84; Q3, OR: 0.32, 95% CI: 0.25–0.39; Q4, OR: 0.30, 95% CI: 0.24–0.37). Even after adjusting for length of hospital stay, acupuncture remained significantly linked to a reduced risk of pneumonia (Q2, OR: 0.67, 95% CI: 0.54–0.83; Q3, OR: 0.32, 95% CI: 0.26–0.40; Q4, OR: 0.27, 95% CI: 0.21–0.33). In the multivariable logistic analysis, Q3 and Q4 were significantly associated with a reduced risk of pneumonia (Q3, OR: 0.36, 95% CI: 0.24–0.45; Q4, OR: 0.21, 95% CI: 0.16–0.27). Detailed information is shown in Table 3.

TABLE 3.

Odds ratio and 95% confidence intervals of pneumonia with acupuncture times and quartile interval.

Exposure Univariable analysis Model 1 Multivariable analysis
OR (95% CI) p Value OR (95% CI) p Value OR (95% CI) p Value
Acupuncture times 0.94 (0.93–0.95) < 0.001 0.94 (0.93–0.94) < 0.001 0.93 (0.92–0.94) < 0.001
Q1 reference reference reference
Q2 0.68 (0.55–0.84) < 0.001 0.67 (0.54–0.83) < 0.001 0.81 (0.64–1.01) 0.065
Q3 0.32 (0.25–0.39) < 0.001 0.32 (0.26–0.40) < 0.001 0.36 (0.24–0.45) < 0.001
Q4 0.30 (0.24–0.37) < 0.001 0.27 (0.21–0.33) < 0.001 0.21 (0.16–0.27) < 0.001
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Note: Model 1: Multivariate analysis after adjusting length of stay. Q1–Q4 under Acupuncture is according to the number of acupuncture quarterback partitions. p < 0.05 was considered statistically significant.

4. Discussion

To our knowledge, this study is the first to investigate the impact of acupuncture on pneumonia risk in stroke patients using PPI, based on a large‐scale case‐control study. The results indicated that acupuncture can reduce pneumonia risk associated with PPI usage in stroke patients, acting as a protective factor. Within a single visit, the best preventive effect occurred with acupuncture times exceeding 11 times. The cumulative effect of acupuncture sessions on the prevention of pneumonia remains a topic that warrants further investigation.

The use of PPI was often deemed inappropriate (Pasina et al. 2011; Jarchow‐Macdonald and Mangoni 2013). In stroke patients, PPIs were commonly administered preemptively to prevent gastrointestinal bleeding from ulcers. However, misuse of PPI may trigger a range of adverse reactions, including Clostridium difficile infection, cardiovascular diseases, and fractures (Xun et al. 2022; Melloni et al. 2015; Poly et al. 2019). Some observational studies suggested an increased risk of poststroke pneumonia in patients using PPI and H2RA, with a higher pneumonia risk associated with high‐dose PPI (Song and Kim 2019). Sarkar et al. (2008) found a significant correlation between PPI usage duration and the risk of CAP, with the highest risk occurring within 30 days of use. Additionally, dementia patients should use PPI cautiously (Ho et al. 2017). Mechanistically, there was still no definitive conclusion regarding the relationship between PPI usage and pneumonia. Studies indicated a significant correlation between the bacteria abundance in the stomach and duodenum and gastric pH (Thorens et al. 1996). An increase in pH led to an increase in bacterial abundance in the stomach, particularly acid‐sensitive bacteria such as streptococci and staphylococci (Rosen et al. 2014; Williams and McColl 2006). Suctioning phlegm is a common practice in the daily care of stroke patients and can also be used diagnostically to assist doctors to identify pathogens, diagnose pneumonia types, and determine the necessity of antibiotics (Sachdev et al. 2010). However, our findings indicated that phlegm suctioning could increase the risk of pneumonia, potentially due to inadequate adherence to aseptic techniques during the procedure. Additionally, the diagnostic use of phlegm suctioning needs careful consideration regarding its impact on pneumonia risk. Our study suggested that diabetes might reduce the risk of pneumonia associated with PPI use in stroke patients, contrary to previous research findings (Ho et al. 2017; Jiménez‐Trujillo et al. 2017). This could be attributed to diabetic patients being more vigilant about managing their blood sugar levels. Diabetes patients may be more concerned about blood sugar levels as a result. Regardless of diabetes status, You et al. (2019) demonstrated that higher fasting blood glucose levels upon admission are more likely to increase the risk of pneumonia in acute ischemic stroke patients. Our study indicated that elevated blood glucose levels, rather than diabetes itself, may be a significant risk factor for pneumonia, possibly due to stress‐induced hyperglycemia at the time of admission (Roberts et al. 2023).

Some observational studies suggested microbial community exchange between the stomach and lungs with species overlap between the microbial communities in the stomach and oral cavity. This indicates that the gastric microbiota induced by aspiration of full column reflux may influence the upper respiratory tract microbiota (Rosen et al. 2015; Segal et al. 2006). In stroke patients, PPI elevated gastric pH, significantly increasing streptococci and enterococci. Following aspiration of full column reflux, these bacteria may become potential pathogens for upper respiratory tract infections and pneumonia. Additionally, changes in the symbiotic bacteria between the stomach and lungs may alter the microbial environment, potentially increasing the risk of pulmonary pathogen infection and reducing the benefit of acid‐suppressing medications (Rosen et al. 2014; Sakwinska et al. 2014). An experimental study suggested that PPI inhibited ATP4 function in the mature mucociliary epithelium, impairing the function of the mucociliary epithelium in the airways and increasing susceptibility to pulmonary infections (Walentek et al. 2015).

Acupuncture has been shown to help prevent infections. A meta‐analysis showed that in patients with swallowing difficulties due to Parkinson's disease, acupuncture significantly reduced the incidence of pulmonary infections compared to those who did not receive acupuncture (J. Wu et al. 2023). Additionally, a cohort study demonstrated that acupuncture reduced the risk of pneumonia in stroke patients, especially in women and younger individuals (Chang et al. 2018). However, there is currently no research exploring the preventive effects of acupuncture on pneumonia caused by PPI use in stroke patients. Our finding indicated that each additional acupuncture session during a single visit was associated with a 6% reduction in pneumonia risk, with the most significant preventive effect occurring after more than 11 sessions. Previous studies have shown that four or more acupuncture sessions were moderately correlated with a reduction in pneumonia risk (Chang et al. 2018), which aligns with our results. Our study indicated that the more acupuncture sessions received, the lower the risk of pneumonia. Multivariate analysis showed that the protective effect of > 11 acupuncture sessions during a single hospitalization remained robust (OR = 0.21) after controlling for comorbidities. When further adjusting for length of stay, the OR increased to 0.27. Model 1 indicated no difference in hospitalization duration between the two groups. The positive correlation between length of stay and number of acupuncture sessions suggested that > 11 sessions per hospitalization might require a longer inpatient period to complete treatment. Evidence shows that prolonged hospitalization alone increases pneumonia risk due to cumulative exposure to hospital pathogens (Roberts et al. 2023). Extended length of stay is an independent risk factor for pneumonia (Table 2: 15–30 days OR: 1.55, > 30 days OR: 1.85) because the risk of nosocomial infections escalates with hospitalization duration.

There were several proposed mechanisms regarding the potential pathways through which acupuncture may affect pneumonia induced by PPI use. First, some studies suggested that the gastrointestinal barrier is an essential component of gastrointestinal defense, and acupuncture may help repair this barrier through neuroendocrine pathways and anti‐inflammatory effects (H. Li 2015). In patients with functional gastrointestinal disorders, acupuncture at CV‐12 may help restore the gastrointestinal barrier via the somatic sympathetic nervous pathway (Takahashi 2006). Evidence suggests that acupuncture can alleviate damage to the gastrointestinal mucosal barrier caused by stress and metabolic changes in stroke patients, thereby improving gastrointestinal function (Qin et al. 2022). Additionally, it can regulate the intestinal flora structure in patients with ischemic stroke, mitigate inflammatory responses, and accelerate the repair of the gastrointestinal barrier (Jiang et al. 2024). The gut–brain axis links the central nervous system and the gastrointestinal tract, regulating gastrointestinal function (Bonaz and Sabate 2009). Acupuncture has bidirectional regulatory effects and may improve gastric secretion in gastrointestinal systems with insufficient gastric acid, promoting gastric acid secretion and maintaining an acid‐base balance in the digestive system (Rehfeld 2021; Gao et al. 2007; Dickman et al. 2007). Second, while studies indicated that PPI could improve reflux diseases caused by excessive gastric acid, some viewpoints suggested that the association between PPI use and pneumonia may be related to reflux aspiration. Dickman et al. (2007) suggested that acupuncture combined with PPI might be more effective in treating GERD when standard doses of PPI fail to control symptoms. A randomized controlled trial demonstrated that thread‐embedded acupuncture effectively alleviated gastric burning and reflux symptoms in GERD patients, resulting in lower scores on the Gastroesophageal Reflux Disease Questionnaire (Trinh et al. 2023). According to traditional Chinese medicine theory, PC6, SP4, and DU20 were commonly used acupoints to alleviate symptoms like nausea, vomiting, and abdominal distension, providing a potential pathway for reflux inhibition (Ouyang 2007). Acupuncture can enhance the coordination of fine movements in the tongue and pharyngeal muscles, increase the activity of oropharyngeal muscle groups, and thereby reduce aspiration (H. Li et al. 2024).

This study is the first to investigate the impact of acupuncture on the risk of pneumonia in stroke patients using PPIs, based on a large‐scale case‐control study. The database contains extensive information on patients' inpatient and outpatient records, which can provide a reliable guarantee for the derivation of evidence‐based evidence. However, this study has several limitations. First, due to the high number of missing values of PPI dosage in the database, we did not explore the association between acupuncture and pneumonia risk related to PPI dosage. There was a dose‐dependent relationship between PPI use and pneumonia risk, with the defined daily dose representing the average maintenance dose recommended by the World Health Organization for adults as the primary indication for this medication (Sinnott et al. 2016). High doses of PPI can increase the risk of pneumonia. Second, our study did not investigate the effects of individual acupoints or combinations of acupoints on pneumonia. In practice, acupoint selection and techniques vary among acupuncturists based on the severity of the stroke and different complications. Third, patients may also receive other traditional Chinese medicine therapies, such as moxibustion and herbal medicine, which could overestimate acupuncture's efficacy. Finally, due to difficulties accurately labeling this field, we did not include dysphagia as a covariate in this study. Dysphagia is often considered an important confounding factor in PPI‐induced pneumonia.

In conclusion, a case‐control study suggested that acupuncture might reduce pneumonia risk in stroke patients using PPI, with the most significant preventive effect occurring after more than 11 acupuncture sessions with a single visit. Therefore, it is crucial in clinical practice to recognize the risks associated with PPI misuse in stroke patients and to consider the preventive benefits of acupuncture treatment.

Author Contributions

Shaokang Wang: writing – original draft. Mi Ou: writing – original draft, data curation, methodology. Haipeng Ban: writing – review and editing, conceptualization. Tianlong Yin: writing – review and editing, conceptualization. Yalu Meng: writing – review and editing, formal analysis. Sihan Sun: writing—review and editing, formal analysis. Lili Zhang: writing—review and editing, formal analysis. Yuzheng Du: writing—review and editing, supervision, resources, funding acquisition.

Ethics Statement

An application for informed consent exemption was submitted. The study protocol was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (ethics number: TYLL2024[Z]字027) and was conducted following the legal requirements and tenets of the Declaration of Helsinki and its subsequent amendments.

Conflicts of Interest

The authors declare no conflicts of interest.

Peer Review

The peer review history for this article is available at https://publons.com/publon/10.1002/brb3.70920

Acknowledgments

This research was supported by the National Key R&D Program of China (2018YFC1706004 and 2019YFC084070) and also by the Tianjin Science and Technology Project (18PTLCSY00060).

Wang, S. , Ou M., Ban H., et al. 2025. “Effect of Acupuncture on Pneumonia Risk in Stroke Patients using Proton Pump Inhibitors: A Retrospective Case‐Control Study.” Brain and Behavior 15, no. 10: e70920. 10.1002/brb3.70920

Funding: This research was supported by the National Key R&D Program of China (2018YFC1706004 and 2019YFC084070) and also by the Tianjin Science and Technology Project (18PTLCSY00060).

Shaokang Wang, Mi Ou, and Haipeng Ban contributed equally to this study.

Data Availability Statement

Data are available upon reasonable request. The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Alkhawaja, S. , Martin C., Butler R. J., et al. 2015. “Post‐Pyloric Versus Gastric Tube Feeding for Preventing Pneumonia and Improving Nutritional Outcomes in Critically Ill Adults.” Cochrane Database of Systematic Reviews 2015, no. 8: Cd008875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beal, M. , Chesson A., Garcia T., Caldito G., Stucker F., and Nathan C.‐A.. 2004. “A Pilot Study of Quantitative Aspiration in Patients With Symptoms of Obstructive Sleep Apnea: Comparison to a Historic Control Group.” Laryngoscope 114, no. 6: 965–968. [DOI] [PubMed] [Google Scholar]
  3. Bonaz, B. , and Sabate J. M.. 2009. “Brain–Gut Axis Dysfunction.” Gastroenterologie Clinique Et Biologique 33, no. S1: S48–S58. [DOI] [PubMed] [Google Scholar]
  4. Chang, C.‐C. , Chen T.‐L., Lin C.‐S., et al. 2018. “Decreased Risk of Pneumonia in Stroke Patients Receiving Acupuncture: A Nationwide Matched‐Pair Retrospective Cohort Study.” PLoS ONE 13, no. 5: e0196094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dickman, R. , Schiff E., Holland A., et al. 2007. “Clinical Trial: Acupuncture vs. Doubling the Proton Pump Inhibitor Dose in Refractory Heartburn.” Alimentary Pharmacology & Therapeutics 26, no. 10: 1333–1344. [DOI] [PubMed] [Google Scholar]
  6. El Rouby, N. , Lima J. J., and Johnson J. A. 2018. “Proton Pump Inhibitors: From CYP2C19 Pharmacogenetics to Precision Medicine.” Expert Opinion on Drug Metabolism & Toxicology 14, no. 4: 447–460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Funayama, M. , Koreki A., Takata T., et al. 2023. “Pneumonia Risk Increased by Dementia‐Related Daily Living Difficulties: Poor Oral Hygiene and Dysphagia as Contributing Factors.” American Journal of Geriatric Psychiatry 31, no. 11: 877–885. [DOI] [PubMed] [Google Scholar]
  8. Gao, X. , Yuan J., Li H., et al. 2007. “Clinical Research on Acupuncture and Moxibustion Treatment of Chronic Atrophic Gastritis.” Journal of Traditional Chinese Medicine 27, no. 2: 87–91. [PubMed] [Google Scholar]
  9. Ho, S.‐W. , Teng Y.‐H., Yang S.‐F., et al. 2017. “Association of Proton Pump Inhibitors Usage With Risk of Pneumonia in Dementia Patients.” Journal of the American Geriatrics Society 65, no. 7: 1441–1447. [DOI] [PubMed] [Google Scholar]
  10. Huang, H.‐H. , Chang S.‐J., Hsu C.‐W., Chang T.‐M., Kang S.‐P., and Liu M.‐Y.. 2012. “Severity of Illness Influences the Efficacy of Enteral Feeding Route on Clinical Outcomes in Patients With Critical Illness.” Journal of the Academy of Nutrition and Dietetics 112, no. 8: 1138–1146. [DOI] [PubMed] [Google Scholar]
  11. Jarchow‐Macdonald, A. A. , and Mangoni A. A.. 2013. “Prescribing Patterns of Proton Pump Inhibitors in Older Hospitalized Patients in a Scottish Health Board.” Geriatrics & Gerontology International 13, no. 4: 1002–1009. [DOI] [PubMed] [Google Scholar]
  12. Jiang, Z. , Liu L., Zhang L., et al. 2024. “Effects of ‘Brain–Gut Coherence’ Method of Acupuncture on Motor Function and Intestinal Microflora in the Patients With Cerebral Ischemic Stroke.” Zhongguo Zhen Jiu 44, no. 7: 740–748. [DOI] [PubMed] [Google Scholar]
  13. Jiménez‐Trujillo, I. , Jiménez‐García R., De Miguel‐Díez J., et al. 2017. “Incidence, Characteristic and Outcomes of Ventilator‐Associated Pneumonia Among Type 2 Diabetes Patients: An Observational Population‐Based Study in Spain.” European Journal of Internal Medicine 40: 72–78. [DOI] [PubMed] [Google Scholar]
  14. Li, H. 2015. “Acupuncture and Regulation of Gastrointestinal Function.” World Journal of Gastroenterology 21, no. 27: 8304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Li, H. , Li J., Wang X., and Zhang Z.. 2024. “A Systematic Review and Meta‐Analysis of Acupuncture in Aspiration Caused by Post‐Stroke Dysphagia.” Frontiers in Neurology 15: 1305056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Li, L. , Xu F., Yang S., et al. 2023. “Tongue Acupuncture for the Treatment of Post‐Stroke Dysphagia: A Meta‐Analysis of Randomized Controlled Trials.” Frontiers in Neuroscience 17: 1124064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Liu, B.‐L. , Li B., Zhang X., et al. 2013. “A Randomized Controlled Study Comparing Omeprazole and Cimetidine for the Prophylaxis of Stress‐Related Upper Gastrointestinal Bleeding in Patients With Intracerebral Hemorrhage.” Journal of Neurosurgery 118, no. 1: 115–120. [DOI] [PubMed] [Google Scholar]
  18. Liu, S. , Wang Y., Gao B., and Peng J.. 2022. “A Nomogram for Individualized Prediction of Stress‐Related Gastrointestinal Bleeding in Critically Ill Patients With Primary Intracerebral Hemorrhage.” Neuropsychiatric Disease and Treatment 18: 221–229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Liu, Y. , Wang Y., Zhang B., Wang J., Sun L., and Xiao Q.. 2021. “Gastric‐Tube Versus Post‐Pyloric Feeding in Critical Patients: A Systematic Review and Meta‐Analysis of Pulmonary Aspiration‐ and Nutrition‐Related Outcomes.” European Journal of Clinical Nutrition 75, no. 9: 1337–1348. [DOI] [PubMed] [Google Scholar]
  20. Melloni, C. , Washam J. B., Jones W. S., et al. 2015. “Conflicting Results Between Randomized Trials and Observational Studies on the Impact of Proton Pump Inhibitors on Cardiovascular Events When Coadministered With Dual Antiplatelet Therapy: Systematic Review.” Circulation Cardiovascular Quality and Outcomes 8, no. 1: 47–55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Naito, Y. , Kashiwagi K., Takagi T., Andoh A., and Inoue R.. 2018. “Intestinal Dysbiosis Secondary to Proton‐Pump Inhibitor Use.” Digestion 97, no. 2: 195–204. [DOI] [PubMed] [Google Scholar]
  22. Ogata, T. , Kamouchi M., Matsuo R., et al. 2014. “Gastrointestinal Bleeding in Acute Ischemic Stroke: Recent Trends From the Fukuoka Stroke Registry.” Cerebrovascular Diseases Extra 4, no. 2: 156–164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ouyang, A. 2007. “Holistic Acupuncture Approach to Idiopathic Refractory Nausea, Abdominal Pain and Bloating.” World Journal of Gastroenterology 13, no. 40: 5360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pasina, L. , Nobili A., Tettamanti M., et al. 2011. “Prevalence and Appropriateness of Drug Prescriptions for Peptic Ulcer and Gastro‐Esophageal Reflux Disease in a Cohort of Hospitalized Elderly.” European Journal of Internal Medicine 22, no. 2: 205–210. [DOI] [PubMed] [Google Scholar]
  25. Poly, T. N. , Islam M. M., Yang H.‐C., Wu C. C., and Li Y.‐C.. 2019. “Proton Pump Inhibitors and Risk of Hip Fracture: A Meta‐Analysis of Observational Studies.” Osteoporosis International 30, no. 1: 103–114. [DOI] [PubMed] [Google Scholar]
  26. Qin, L. , Zhang X. X., Jin X., et al. 2022. “The Effect of Acupuncture on Enteral Nutrition and Gastrointestinal Dynamics in Patients Who Have Suffered a Severe Stroke.” Current Neurovascular Research 19, no. 3: 275–281. [DOI] [PubMed] [Google Scholar]
  27. Rehfeld, J. F 2021. “Gastrin and the Moderate Hypergastrinemias.” International Journal of Molecular Sciences 22, no. 13: 6977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Roberts, G. , Chang L., Park J.‐M., and Thynne T.. 2023. “The Occurrence of Hospital‐Acquired Pneumonia Is Independently Associated With Elevated Stress Hyperglycaemia Ratio at Admission but Not Elevated Blood Glucose.” Diabetes Research and Clinical Practice 205: 110955. [DOI] [PubMed] [Google Scholar]
  29. Rosen, R. , Amirault J., Liu H., et al. 2014. “Changes in Gastric and Lung Microflora With Acid Suppression: Acid Suppression and Bacterial Growth.” JAMA Pediatrics 168, no. 10: 932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rosen, R. , Hu L., Amirault J., Khatwa U., Ward D. V., and Onderdonk A.. 2015. “16S community Profiling Identifies Proton Pump Inhibitor Related Differences in Gastric, Lung, and Oropharyngeal Microflora.” Journal of Pediatrics 166, no. 4: 917–923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sachdev, A. , Chugh K., Sethi M., Gupta D., Wattal C., and Menon G.. 2010. “Diagnosis of Ventilator‐Associated Pneumonia in Children in Resource‐Limited Setting: A Comparative Study of Bronchoscopic and Nonbronchoscopic Methods.” Pediatric Critical Care Medicine 11, no. 2: 258–266. [DOI] [PubMed] [Google Scholar]
  32. Sakwinska, O. , Bastic Schmid V., Berger B., et al. 2014. “Nasopharyngeal Microbiota in Healthy Children and Pneumonia Patients.” Journal of Clinical Microbiology 52, no. 5: 1590–1594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sarkar, M. , Hennessy S., and Yang Y. X. 2008. “Proton‐Pump Inhibitor Use and the Risk for Community‐Acquired Pneumonia.” Annals of Internal Medicine 149, no. 6: 391–398. [DOI] [PubMed] [Google Scholar]
  34. Savarino, V. , Marabotto E., Zentilin P., et al. 2018. “Proton Pump Inhibitors: Use and Misuse in the Clinical Setting.” Expert Review of Clinical Pharmacology 11, no. 11: 1123–1134. [DOI] [PubMed] [Google Scholar]
  35. Segal, R. , Pogoreliuk I., Dan M., Baumoehl Y., and Leibovitz A.. 2006. “Gastric Microbiota in Elderly Patients Fed via Nasogastric Tubes for Prolonged Periods.” Journal of Hospital Infection 63, no. 1: 79–83. [DOI] [PubMed] [Google Scholar]
  36. Shim, Y. K. , and Kim N. 2016. “Nonsteroidal Anti‐Inflammatory Drug and Aspirin‐Induced Peptic Ulcer Disease.” Korean Journal of Gastroenterology 67, no. 6: 300. [DOI] [PubMed] [Google Scholar]
  37. Sinnott, S.‐J. , Polinski J. M., Byrne S., and Gagne J. J.. 2016. “Measuring Drug Exposure: Concordance Between Defined Daily Dose and Days' Supply Depended on Drug Class.” Journal of Clinical Epidemiology 69: 107–113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Song, T. J. , and Kim J. 2019. “Risk of Post‐Stroke Pneumonia With Proton Pump Inhibitors, H2 Receptor Antagonists and Mucoprotective Agents: A Retrospective Nationwide Cohort Study.” PLoS ONE 14, no. 5: e0216750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Takahashi, T 2006. “Acupuncture for Functional Gastrointestinal Disorders.” Journal of Gastroenterology 41, no. 5: 408–417. [DOI] [PubMed] [Google Scholar]
  40. Thorens, J. , Froehlich F., Schwizer W., et al. 1996. “Bacterial Overgrowth During Treatment With omeprazole Compared With cimetidine: A Prospective Randomised Double Blind Study.” Gut 39, no. 1: 54–59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Trinh, D.‐T. T. , Tran A. H., Bui M.‐M. P., and Vuong N. L.. 2023. “Thread‐Embedding Acupuncture May Improve Symptom Resolution in Patients With Gastroesophageal Reflux Disease: A Randomized Controlled Trial.” Integrative Medicine Research 12, no. 3: 100971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Tu, W.‐J. , Zhao Z. , Yin P., et al. 2023. “Estimated Burden of Stroke in China in 2020.” JAMA Network Open 6, no. 3: e231455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Walentek, P. , Beyer T., Hagenlocher C., et al. 2015. “ATP4a is Required for Development and Function of the Xenopus Mucociliary Epidermis—A Potential Model to Study Proton Pump Inhibitor‐Associated Pneumonia.” Developmental Biology 408, no. 2: 292–304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wang, Z. , Liu W., Y.i Ren,, et al. 2023. “Loss of Life Expectancy due to Stroke and Its Subtypes in Urban and Rural Areas in China, 2005–2020.” Stroke and Vascular Neurology 8, no. 5: 349–357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wang, J. , Tian L., Zhang Z., et al. 2020. “Scalp‐Acupuncture for Patients With Hemiplegic Paralysis of Acute Ischaemic Stroke: A Randomized Controlled Clinical Trial.” Journal of Traditional Chinese Medicine 40, no. 5: 845–854. [DOI] [PubMed] [Google Scholar]
  46. Williams, C. , and McColl K. E. 2006. “Review Article: Proton Pump Inhibitors and Bacterial Overgrowth.” Alimentary pharmacology & therapeutics 23, no. 1: 3–10. [DOI] [PubMed] [Google Scholar]
  47. Winning, L. , Lundy F. T., Blackwood B., Mcauley D. F., and El Karim I.. 2021. “Oral Health Care for the Critically Ill: A Narrative Review.” Critical Care 25, no. 1: 353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Won, J. H. , Byun S. J., Oh B.‐M., Kim H.‐J., Park S. J., and Seo H. G.. 2020. “Pneumonia Risk and Its Associated Factors in Parkinson's Disease: A National Database Study.” Journal of the Neurological Sciences 415: 116949. [DOI] [PubMed] [Google Scholar]
  49. Wu, J. , Wang Y.i, Wang X., Xie Y., and Li W.. 2023. “A Systematic Review and Meta‐Analysis of Acupuncture in Parkinson's Disease With Dysphagia.” Frontiers in Neurology 14: 1099012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wu, S. , Wu B., Liu M., et al. 2019. “Stroke in China: Advances and Challenges in Epidemiology, Prevention, and Management.” Lancet Neurology 18, no. 4: 394–405. [DOI] [PubMed] [Google Scholar]
  51. Xiao, J. , Wang T., Ye B., and Tang C.. 2023. “Scalp Acupuncture and Computer Assisted Cognitive Rehabilitation for Stroke: A Meta‐Analysis of Randomised Controlled Trials.” Heliyon 9, no. 7: e18157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Xun, X. , Yin Q., Fu Y., He X., and Dong Z.. 2022. “Proton Pump Inhibitors and the Risk of Community‐Acquired Pneumonia: An Updated Meta‐Analysis.” Annals of Pharmacotherapy 56, no. 5: 524–532. [DOI] [PubMed] [Google Scholar]
  53. Yang, T.‐C. , Li J.‐G., Yu D.‐M., et al. 2013. “Gastrointestinal Bleeding After Intracerebral Hemorrhage: A Retrospective Review of 808 Cases.” American Journal of the Medical Sciences 346, no. 4: 279–282. [DOI] [PubMed] [Google Scholar]
  54. Yasuda, H. 2015. “Treatment and Prevention of Gastrointestinal Bleeding in Patients Receiving Antiplatelet Therapy.” World Journal of Critical Care Medicine 4, no. 1: 40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. You, S. , Ou Z., Zhang W., et al. 2019. “Combined Utility of White Blood Cell Count and Blood Glucose for Predicting In‐Hospital Outcomes in Acute Ischemic Stroke.” Journal of Neuroinflammation 16, no. 1: 37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Zirk‐Sadowski, J. , Masoli J. A., Delgado J., et al. 2018. “Proton‐Pump Inhibitors and Long‐Term Risk of Community‐Acquired Pneumonia in Older Adults.” Journal of the American Geriatrics Society 66, no. 7: 1332–1338. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Data are available upon reasonable request. The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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