The organism, Pneumocystis jiroveci (previously known as Pneumocystis carinii), seldom causes serious problems for normal hosts, but in people with suppressed immune systems, such as transplant patients or cancer patients undergoing chemotherapy, it can result in a deadly lung infection. For patients with HIV, Pneumocystis is the most common and most serious AIDS-defining opportunistic infection.
The study, conducted at the University of Pittsburgh School of Medicine, involved 68 patients with COPD and 44 patients with other lung diseases, such as cystic fibrosis. Pneumocystis was more prevalent in the COPD patients, especially those with the most advanced disease; and neither smoking history, number of packs of cigarettes smoked over time, age or gender correlated with the existence of the organism in the lungs.
"Pneumocystis colonization is associated with severity of COPD, and airway obstruction was significantly worse in patients whose lungs were colonized than in those patients who had no evidence of the organism. Moreover, colonization did not appear to be the result of other clinical factors or concomitant conditions," stated Alison Morris, M.D., M.S., assistant professor of medicine in the division of pulmonary and critical care medicine at the University of Southern California who conducted the study while completing a fellowship at the University of Pittsburgh under Karen A. Norris, Ph.D. Dr. Norris, the paper's senior author, is an associate professor of immunology at Pitt's School of Medicine.
The researchers looked for the presence of Pneumocystis in lungs that had been explanted during transplantation or removed in part during lung resection surgery. Using a technique called polymerase chain reaction that detects DNA, they found Pneumocystis colonization in 11, or 36.7 percent, of 30 patients classified with the most severe form of COPD, all of whom received lung transplants; two of these patients developed Pneumocystis pneumonia within six months of transplantation. Yet only two, or 5.3 percent, of the 38 other COPD patients with less severe forms of the disease were colonized. All 68 COPD patients in the study were previous smokers.
Colonization was also associated with worse lung function in the COPD patients. Using a standard test that evaluates lung function by measuring the percentage of forced expiratory volume (FEV1) in one second, patients with Pneumocystis colonization had a median FEV1 of 20 percent of the predicted normal value, versus a median FEV1 of 62 percent in the Pneumocystis-negative patients.
Of the 44 patients who were transplanted for reasons other than COPD, who served as a control group, 12, or 27 percent, had been smokers, and four, or 9.1 percent, were colonized with Pneumocystis. Only one of these four colonized patients was a smoker. Overall, their median FEV1 was 31 percent.
"The strong association between Pneumocystis colonization and severity of airflow obstruction in those with a history of smoking strongly suggests the pathogen is at play, most likely inducing an exaggerated lung inflammatory response by specific immune system cells that, interestingly, are the same cells that infiltrate the lungs in COPD," explained Dr. Norris.
"Only 10 to 15 percent of smokers develop COPD, so the question remains whether chronic colonization with Pneumocystis is an added risk factor for smokers," she added.
Other questions the current study did not address include how long colonization must occur for it to impact disease progression, and whether Pneumocystis colonization results in acceleration of COPD or if some factor unique to COPD creates the right environment for the organism to colonize.
"Further work will be necessary to clarify whether the presence of Pneumocystis contributes to worsening lung function or whether patients with the poorest lung function are predisposed to Pneumocystis. However the correlation between the two cannot be ignored," said Frank C. Sciurba, M.D., associate professor of medicine in the division of pulmonary, allergy and critical care medicine at Pitt's School of Medicine.
In addition to Drs. Morris, Norris and Sciurba, other authors include: from the University of Pittsburgh, Irina P. Lebedeva, department of immunology; and Andrew Githaiga, M.D., department of medicine; W. Mark Elliott, Ph.D., and James C. Hogg, M.D., both of the University of British Columbia in Vancouver, Canada; and Laurence Huang, M.D., of the University of California, San Francisco.
The study was supported by the National Institutes of Health and the Canadian Institute for Health Research.
Journal
American Journal of Respiratory and Critical Care Medicine