Public Release:  P. aeruginosa bacteria associated with increased hospitalizations in COPD patients

American Thoracic Society

ATS 2012, SAN FRANCISCO - Patients with chronic obstructive pulmonary disease (COPD) who become infected with the bacterium Pseudomonas aerguinosa are more likely to have worse clinical outcomes and experience more hospitalizations during the course of their disease than COPD patients who are not infected, according to researchers from Buffalo, N.Y.

The study will be presented at the ATS 2012 International Conference in San Francisco.

Bacterial bronchial infection plays a key role in the course of COPD, causing chronic inflammation as well as acute exacerbations of symptoms, and is related to increased levels of illness and mortality among COPD patients.

"Previous studies have shown that infection with P. aeruginosa is more common in patients with more severe COPD ," said study researcher Sanjay Sethi, MD, FACP, chief of the Pulmonary/Critical Care/Sleep Medicine Division at the University at Buffalo, SUNY. "In this study, we wanted to determine if infection with P. aeruginosa was associated with poorer clinical outcomes, such as hospitalizations, need for intensive care, and greater numbers of exacerbations."

The study focused on 177 patients who participated in a COPD study at the Buffalo Veterans Affairs Medical Center from March 1994 to January 2011. Study participants had clinic visits every month and additional visits during exacerbations. During each visit, clinical information and sputum samples were taken. Patients with less than six months of follow-up were excluded from the study.

For this analysis, study participants were divided into two groups: those whose sputum samples showed evidence of P. aeruginosa (PA+) infection and those whose samples showed no evidence of the bacteria (PA-). In addition, follow-up times were divided into two phases, Phase 1 denoting the time period prior to acquiring P. aeruginosa and Phase 2 covering the time period after the bacteria had been identified in the sputum.

"As COPD progresses, hospitalizations and exacerbations tend to increase and we had to account for that in our analysis. Therefore, we matched PA+ subjects with PA- subjects having similar duration of follow-up in the study," Dr. Sethi said. "Rates of events, including hospitalizations, ICU admissions and COPD exacerbations, and relative risks of having at least one event were compared in the two phases within and between the two groups."

In the study's final analysis, 55 PA+ study participants were matched with 55 PA- control subjects. Although the two groups were well matched in terms of age, sex, pack years of smoking and lung function, the rates of hospitalization in the PA+ group after P. aeruginosa infection were significantly higher than those in the control group, and the relative risk of having at least one hospitalization, intensive care admission or exacerbation also were all greater.

"Similar analyses are being performed with other bacterial pathogens identified in our COPD study clinic data to determine if this observation is unique to P. aeruginosaor extends to other bacterial pathogens," Dr. Sethi said.

"The possibility exists that, in our study, P. aeruginosa may be simply a 'colonizing bacteria' - a marker for worsening COPD- rather than a cause of the worse clinical outcomes," he added. "However, we and others have shown that P. aeruginosa behaves as an infectious pathogen in COPD. Also, in related chronic airway diseases, such as cystic fibrosis, Pseudomonas infection is a major cause of morbidity and mortality."

Dr. Sethi noted that to date, P. aeruginosa infection has received little attention as an important pathogen in COPD. As a result, studies of specific treatments to eradicate or contain this infection have not been conducted in COPD.

"This study suggests that we should pay more attention to these bacteria in COPD, and treatments to deal with this pathogen in COPD should be developed," he said.

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"Acquistion Of Pseudomonas Aeruginosa Is Associated With Adverse Clinical Outcomes In COPD" (Session D105, Wednesday, May 23, 2:00-4:30 p.m., Room 2024, Moscone Center; Abstract 27711)

* Please note that numbers in this release may differ slightly from those in the abstract. Many of these investigations are ongoing; the release represents the most up-to-date data available at press time.

Abstract 27711
Acquistion Of Pseudomonas Aeruginosa Is Associated With Adverse Clinical Outcomes In COPD
Type: Scientific Abstract
Category: 09.09 - COPD: Outcomes (CP)
Authors: M.O. Jamil1, J. Yin1, N. Nag1, E. Eberhardt2, L. Grove2, I. Parameswaran1, T. Murphy1, S. Sethi3; 1SUNY at Buffalo - Buffalo, NY/US, 2VA Western NY Healthcare System - Buffalo, NY/US, 3University of Buffalo, SUNY - Buffalo, NY/US

Abstract Body

Rationale: Pseudomonas aeruginosa (PA) is isolated from the sputum of 4-15% of patients with COPD. In cross-sectional studies it has been shown that PA isolation is more frequent with increasing severity of COPD. However the association of PA acquisition to adverse clinical outcomes in COPD has not been characterized in a longitudinal study.

Methods: We conducted a prospective longitudinal study of a cohort of 177 subjects with COPD at the Buffalo Veterans Affairs Medical Center. The subjects were enrolled from Mar 1994 to Jan 2011. They had clinic visits monthly and during exacerbations. At each visit clinical information and expectorated sputum samples were obtained. Patients with less than 6 months of follow-up were excluded from this analysis. We categorized the subjects who had at least one sputum culture positive for P aeruginosa as PA+. We divided their follow-up period into phase1 (before acquiring PA) and phase2 (after acquiring PA). To account for disease progression with time PA+ subjects were matched with PA- subjects having similar duration of follow-up, and the follow up period for each patient was divided into phases with similar duration of time. Rates of events (hospitalizations, ICU admissions and COPD exacerbations) and relative risks of having atleast one event were compared in the two phases within and between the two groups.

Results: There were 55 subjects in the PA+ group. They were matched with an equal number of PA- controls. There were no statistically significant differences between the two groups in terms of age, sex, pack years of smoking and FEV1 % predicted. The rates of hospitalization in PA+ group increased significantly in phase2 as compared to phase1 and the increase was significantly greater than PA- controls.

The difference in proportions of patients having at least one event (hospitalization, ICU admission or COPD exacerbation) between phase1 and phase2 of both groups were statistically significant but the differences between PA+ and PA- controls were not statistically significant.

Conclusions: In patients with COPD the morbidity increases significantly after the acquisition of Pseudomonas aeruginosa. This could be directly related to the P aeruginosa infection and/or P aeruginosa infection could be a marker of progressive immunocompromise and a harbinger of poor prognosis.

Funded by: VA Merit Review

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