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Background: Several studies have investigated single nucleotide polymorphisms (SNP) in candidate genes associated with susceptibility, severity or outcome in patients with community-acquired pneumonia (CAP) with conflicting results., Methods: Multi-centre, prospective observational study. We studied 1162 white Spanish patients with CAP and 1413 controls. Severe forms of sepsis were recorded in 325 patients. Subjects were genotyped for the following polymorphisms: TNF -238 and -308, LTA +252, IL6 -174, IL1RN 86bp variable number of tandem repeats and TNFRSF1B+676 (TNFR2 M196R)., Results: No significant differences in genotype or allele frequencies were seen among patients and controls. We did not find any association between TNF, LTA, IL6 and IL1RN polymorphisms with disease severity or outcome. Analysis of 28-day mortality showed a significant difference in the distribution of TNFRSF1B+676 G/T genotypes (p=0.0129). Sequential Kaplan-Meier survival analysis of TNFRSF1B+676 G/T polymorphism showed a protective role of the GT genotype. Cox regression analysis adjusted for age, gender, hospital of origin and comorbidities showed that patients with GT genotypes had lower mortality rates compared to patients with GG or TT genotypes (p=0.02; HR 0.53; 95% CI 0.31-0.90 for 90-day survival; p=0.01; HR 0.41; 95% CI 0.21-0.81 for 28-day survival and p=0.049; HR 0.48; 95% CI 0.23-0.997 for 15-day survival)., Conclusions: Our study does not support a role for the controversial studied polymorphisms of the TNF, LTA, IL6 and IL1RN genes in the susceptibility or outcome of CAP. A protective role of heterozygosity for the functionally relevant TNFRSF1B+676 polymorphism in the outcome of CAP was observed., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Usually, mortality due to mild community-acquired pneumonias (CAP) (Pneumonia severity index (PSI) classes I-III) is low (<3%), but the appearance of hypoxemia significantly increases mortality. Our aim was to determine the clinical parameters associated with risk factors of developing hypoxemia in subjects with mild CAP (PSI I-III) and the clinical outcomes of the hypoxemic group. We analyzed clinical characteristics and the outcomes of patients with mild CAP and hypoxemia (PaO2/FiO2<300), in a prospective, multicenter cohort study of 1195 patients. Mild pneumonias (PSI I-III) were found in 645 cases (53.9%), of which 217 (33.6%) presented hypoxemia according to a PaO2/FiO2<300. Patients with PaO2/FiO2<300 required more ICU admissions, mechanical ventilation, and developed septic shock than other PSI I-III patients. The clinical parameters associated with hypoxemia were: COPD, bilateral chest X-ray involvement, and hypoalbuminemia. We conclude that patients with COPD, those with bilateral chest X-ray involvement, or hypoalbuminemia were significantly more likely to have hypoxemia in mild CAP. Hypoxemic patients with low-risk pneumonia have worse clinical outcomes, including more ICU admission, need for mechanical ventilation and presence of septic shock than non-hypoxemic low-risk patients.