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ABSTRACT: Pseudomonas aeruginosa (PA) is isolated in advanced stages of chronic obstructive pulmonary disease (COPD). The aim of our study was to determine whether PA isolation during hospitalization for COPD exacerbation was associated with a poorer prognosis after discharge. We prospectively studied all patients with COPD exacerbation admitted between June 2003 and September 2004. A sputum culture was obtained at admission. Comorbidity, functional dependence, hospitalizations during the previous year, dyspnea, quality of life and other variables previously associated with mortality in COPD were studied. Spirometry and a 6-min walking test were performed 1 month after discharge. Mortality was evaluated 3 years after discharge. A total of 181 patients were included in the study. Of these, 29 (16%) had PA in the sputum. The mean age was 72 years, and mean basal postbronchodilator forced expiratory volume in 1 s was 45.2% predicted (SD 14.4). The mean point value on the BODE index was 5.1 (SD 2.5). At 3 years, 17 of 29 patients (58.6%) in the PA group had died, compared to 53 of the 152 non-PA patients [34.9%; p < 0.004; hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.29-3.86]. In the multivariate analysis, PA remained statistically related to posthospital mortality (p = 0.02; HR 2.2, 95% CI 1.2-4.2) after adjustment for age (p < 0.02; HR 1.04, 95% CI 1.007-1.07), BODE index (p < 0.02; HR 1.15, 95% CI 1.02-1.3) and comorbidity (p < 0.02; HR 1.24, 95% CI 1.03-1.5). PA isolation in sputum in patients hospitalized for acute exacerbation of COPD is a prognostic marker of 3-year mortality. Poor prognosis is independent of other significant predictors of mortality such as BODE index, age and comorbidity, as measured by the Charlson index.