Recurrent Community-acquired Pneumonia in Patients Starting Acid-suppressing Drugs

Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
The American journal of medicine (Impact Factor: 5). 01/2010; 123(1):47-53. DOI: 10.1016/j.amjmed.2009.05.032
Source: PubMed


Several studies suggest that proton pump inhibitors (PPIs) and histamine 2-receptor antagonists (H2s) increase risk of community-acquired pneumonia. To test this hypothesis, we examined a prospective population-based cohort predisposed to pneumonia: elderly patients (> or =65 years) who had survived hospitalization for pneumonia.
This study featured a nested case-control design where cases were patients hospitalized for recurrent pneumonia (> or =30 days after initial episode) and controls were age, sex, and incidence-density sampling matched but never had recurrent pneumonia. PPI/H2 exposure was classified as never, past, or current use before recurrent pneumonia. The association between PPI/H2s and pneumonia was assessed using multivariable conditional logistic regression.
During 5.4 years of follow-up, 248 recurrent pneumonia cases were matched with 2476 controls. Overall, 71 of 608 (12%) current PPI/H2 users had recurrent pneumonia, compared with 130 of 1487 (8%) nonusers (adjusted odds ratio [aOR] 1.5; 95% confidence interval [CI], 1.1-2.1). Stratifying the 608 current users according to timing of PPI/H2 initiation revealed incident current-users (initiated PPI/H2 after initial pneumonia hospitalization, n=303) bore the entire increased risk of recurrent community-acquired pneumonia (15% vs 8% among nonusers, aOR 2.1; 95% CI, 1.4-3.0). The 305 prevalent current-users (PPI/H2 exposure before and after initial community-acquired pneumonia hospitalization) were equally likely to develop recurrent pneumonia as nonusers (aOR 0.99; 95% CI, 0.63-1.57).
Acid-suppressing drug use substantially increased the likelihood of recurrent pneumonia in high-risk elderly patients. The association was confined to patients initiating PPI/H2s after hospital discharge. Our findings should be considered when deciding to prescribe these drugs in patients with a recent history of pneumonia.

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Available from: Cheryl Sadowski, Apr 28, 2015
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    • "We have highlighted to the possibility of confounding-by-indication in the use of PPIs, which needs to be addressed in future studies. An intriguing possibility, which will require additional investigation, is that control of acid aspiration improves QOL, but that the association of GERD with increased exacerbation frequency relates less closely to acid aspiration than to changes in the community structure of the lung microbiome [32], as suggested by findings of higher frequency of pneumonia among PPIs users in the general population [33,34]. "
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    ABSTRACT: Background The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes. Methods Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD. Physician-diagnosed GERD was ascertained by questionnaire. Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD. We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models. Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs). To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score. Results GERD was reported by 29% of subjects with female predominance. Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs. 13.4.0%, p < 0.0001). Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs. 1.8, p < 0.0001), and poorer quality of life (QOL) scores (St. George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs. 34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs. 41.4, p < 0.0001). In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006). During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included. PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association. Conclusions In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up. These associations are maintained after controlling for PPI use. The PPI-exacerbations association could result from confounding-by-indication.
    Full-text · Article · Jun 2014 · Respiratory Research
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    • "Studies of PPI therapy in asthma have inconsistently demonstrated beneficial effects [11,12], and retrospective studies in idiopathic pulmonary fibrosis suggest stabilization of lung function and improved survival with acid suppression [13,14] , Among individuals with CF , PPIs are likely initiated for a variety of reasons including improved efficacy of pancreatic enzymes in a higher pH environment, as well as treatment of cough or other respiratory or gastrointestinal complaints thought to be possibly caused by GER. Use of these agents however, may be associated with risk [15,16]. Use of PPIs in both hospitalized and ambulatory patients has been shown to be associated with an increased risk of pneumonia [15-18]. "
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    ABSTRACT: Gastro esophageal reflux (GER) is common in cystic fibrosis (CF) and may contribute to lung disease. Approximately 50% of patients with cystic fibrosis are being treated with proton pump inhibitors (PPIs). In a randomized controlled study in adults, we compared treatment with esomeprazole 40 mg twice daily versus placebo in patients with CF and frequent respiratory exacerbations over a thirty-six week treatment period to determine effect on time to first exacerbation and other health related outcomes. 17 patients without symptoms of GER were randomized and 15 completed the study. 13 subjects underwent 24 hour ambulatory pH probe monitoring; 62% had pH probe evidence of GER. Forty one percent of subjects had a pulmonary exacerbation during the study. There was no significant difference in time to first pulmonary exacerbation (log rank test p = 0.3169). Five of nine subjects in the esomeprazole group compared with 2 of eight subjects in the placebo group experienced exacerbations (esomeprazole vs. placebo: odds ratio = 3.455, 95% CI = (0.337, 54.294), Fisher's exact test: p = 0.334). There was no change in Forced Expiratory Volume in one second, Gastroesophageal Symptom Assessment Score or CF Quality of Life score between the two treatment groups. There was a trend to earlier exacerbation and more frequent exacerbations in subjects randomized to esomeprazole compared with placebo. The effect of proton pump inhibitors on pulmonary exacerbations in CF warrants further investigation.Clinical trials registration:, NCT01983774.
    Full-text · Article · Feb 2014 · BMC Pulmonary Medicine
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    • "Pantoprazole inhibits gastric acid secretion more effectively in patients admitted to the ICUs and may lead to higher bacterial colonization (9). Some other studies have shown that pantoprazole is associated with increased rates of community-acquired pneumonia compared with ranitidine (10–12), while other studies have not confirmed such findings (13).Higher risk of hospital acquired pneumonia in patients on pantoprazole without mechanical ventilation has also been reported (3). We only found a historical cohort study in the literature comparing the effect of ranitidine and pantoprazole and reporting the incidence of VAP to be three times higher in patients receiving pantoprazole (14). "
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    ABSTRACT: Background Acid suppressive medications are used to prevent stress ulcers in critically ill patients. Few studies have been done to evaluate the effect of ranitidine and pantoprazole on stress ulcers. We aimed to compare the effects of ranitidine and pantoprazole on Ventilator Associated Pneumonia (VAP). Materials and Methods In this double-blind randomized controlled trial, we enrolled 120 traumatic patients with trauma admitted to the intensive care unit (ICU) of Besat Hospital in Hamadan Province located in northwest Iran. The patients were divided into two equal groups receiving either intermittent intravenous ranitidine or pantoprazole to prevent stress ulcers. The incidence of VAP, duration of tracheal intubation, length of ICU stay, duration of hospital stay, and the outcome of treatment including mortality or hospital discharge were compared in both groups. Results The incidence of VAP was 10% and 30% in patients receiving ranitidine and pantoprazole, respectively (P=0.006). There was no significant difference between the two groups with respect to the duration of tracheal intubation. However, the patients treated with pantoprazole stayed at the hospital two days longer than the other patients (P=0.027). Although patients with VAP stayed at the hospital for 12 more days, the two groups had almost equal mortality rates (P=0.572). Conclusion ICU patients using pump inhibitors have a three-fold increased risk of developing VAP in comparison to H2-blocker receivers. Thus, prevention of stress ulcers should be limited to its own specific indications.
    Full-text · Article · Feb 2013 · Tanaffos
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