s-1743 and Pneumonia

Debate continues on whether a causal association exists between the use of proton pump inhibitors (PPIs) and the risk of respiratory tract infections, in particular pneumonia.. To investigate the occurrence of community-acquired respiratory tract infections, including pneumonia, in patients receiving esomeprazole.. A retrospective investigation of pooled data on adverse events related to respiratory tract infections, originally reported in 24 randomised, double-blind clinical studies, was conducted. The frequencies of respiratory tract infections and their relative risks were calculated retrospectively for the total patient population (9602 patients receiving esomeprazole and 5500 receiving placebo) and for sub-populations defined according to sex, age, esomeprazole dose, indication and geographical region. The cumulative frequency of first occurrence of events was calculated over 180 days.. Frequencies of respiratory tract infections were similar in patients receiving esomeprazole and in those receiving placebo (any respiratory tract infection or signs/symptoms potentially indicating an respiratory tract infection, 0.278 and 0.296 patients per patient-year; lower respiratory tract infections, 0.048 and 0.058 per patient-year; pneumonia, 0.006 and 0.009 per patient-year, respectively). The relative risk for any respiratory tract infection in patients receiving esomeprazole compared with placebo was 0.94 (95% CI, 0.86-1.04). For lower respiratory tract infections, the relative risk was 0.82 (95% CI, 0.65-1.03) and for pneumonia, 0.66 (95% CI, 0.36-1.22). Sub-analyses by demographics, dose and indication yielded similar results to the overall analysis. The occurrence of respiratory tract infections was evenly distributed over time and similar in the esomeprazole and placebo groups.. There is no causal association between treatment with esomeprazole and the occurrence of community-acquired respiratory tract infections, including pneumonia.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Child; Child, Preschool; Community-Acquired Infections; Dose-Response Relationship, Drug; Double-Blind Method; Esomeprazole; Female; Humans; Infant; Male; Middle Aged; Pneumonia; Proton Pump Inhibitors; Respiratory Tract Infections; Retrospective Studies; Sex Factors; Young Adult

Topics: Aged, 80 and over; Anti-Bacterial Agents; Blood Transfusion; Colitis; Colon; Cytomegalovirus; Cytomegalovirus Infections; Diarrhea; Esomeprazole; Gastrointestinal Hemorrhage; Gastrointestinal Tract; Humans; Immunocompetence; Male; Penicillanic Acid; Piperacillin; Pneumonia; Pulmonary Disease, Chronic Obstructive; Steroids; Tazobactam; Treatment Outcome; Viremia

The beneficial outcome associated with the use of proton pump inhibitors (PPIs) in idiopathic pulmonary fibrosis (IPF) has been reported in retrospective studies. To date, no prospective study has been conducted to confirm these outcomes. In addition, the potential mechanism by which PPIs improve measures of lung function and/or transplant-free survival in IPF has not been elucidated.. Here, we used biochemical, cell biological and preclinical studies to evaluate regulation of markers associated with inflammation and fibrosis. In our in vitro studies, we exposed primary lung fibroblasts, epithelial and endothelial cells to ionizing radiation or bleomycin; stimuli typically used to induce inflammation and fibrosis. In addition, we cultured lung fibroblasts from IPF patients and studied the effect of esomeprazole on collagen release. Our preclinical study tested efficacy of esomeprazole in a rat model of bleomycin-induced lung injury. Furthermore, we performed retrospective analysis of interstitial lung disease (ILD) databases to examine the effect of PPIs on transplant-free survival.. The cell culture studies revealed that esomeprazole controls inflammation by suppressing the expression of pro-inflammatory molecules including vascular cell adhesion molecule-1, inducible nitric oxide synthase, tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1β and IL-6). The antioxidant effect is associated with strong induction of the stress-inducible cytoprotective protein heme oxygenase-1 (HO1) and the antifibrotic effect is associated with potent inhibition of fibroblast proliferation as well as downregulation of profibrotic proteins including receptors for transforming growth factor β (TGFβ), fibronectin and matrix metalloproteinases (MMPs). Furthermore, esomeprazole showed robust effect in mitigating the inflammatory and fibrotic responses in a murine model of acute lung injury. Finally, retrospective analysis of two ILD databases was performed to assess the effect of PPIs on transplant-free survival in IPF patients. Intriguingly, this data demonstrated that IPF patients on PPIs had prolonged survival over controls (median survival of 3.4 vs 2 years).. Overall, these data indicate the possibility that PPIs may have protective function in IPF by directly modulating the disease process and suggest that they may have other clinical utility in the treatment of extra-intestinal diseases characterized by inflammatory and/or fibrotic phases.

Topics: Aged; Animals; Apoptosis; Biomarkers; Bleomycin; Cell Proliferation; Cell Separation; Collagen; Disease Models, Animal; Esomeprazole; Female; Fibroblasts; Gene Expression Regulation; Genetic Pleiotropy; Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Transplantation; Male; Middle Aged; Pneumonia; Proton Pump Inhibitors; Radiation, Ionizing; Rats, Inbred F344; Solubility; Survival Analysis; Transforming Growth Factor beta