Flare-Ups of Chronic Lung Disease Associated with Specific Bacterial Strains, UB Researchers Find

BUFFALO, N.Y. -- University at Buffalo researchers have found an association between bacteria in the sputum of patients with chronic obstructive pulmonary disease (COPD) and exacerbations of the disease, answering a long-standing question about the role of pathogens and COPD flare-ups.

Results of the prospective study appear in the Aug. 15 issue of New England Journal of Medicine.

COPD is the fourth-leading cause of death in the U.S., according to the American Lung Association, and fatalities are closely linked to exacerbations. Up to 90 percent of cases of the disease are caused by long-term smoking.

"For years, people have hypothesized that bacteria played a role in COPD exacerbations, but studies performed decades ago found no difference in bacterial presence during stable periods and flare-ups," said Timothy Murphy, M.D., UB professor of medicine and microbiology and senior author on the study.

"Using the new technology of molecular typing, where you can look at turnover of bacteria in the respiratory tract in a more accurate way, we have shown that that hypothesis is correct."

Sanjay Sethi, M.D., UB associate professor of medicine, is first author of the study, which began in 1994. Sethi, Murphy and colleagues found that it is the particular strain within a bacterial species, not the volume of bacteria in general, that is associated with a COPD flare-up. This observation is a change in the way physicians have viewed the role of bacteria in COPD, Murphy noted. The three major pathogens implicated in causing exacerbations were H. influenzae, M. catarrhalis, and Strep. Pneumoniae, the study showed.

In addition to elucidating the role of bacteria in exacerbations, these findings are important because they point to novel ways of treating or preventing exacerbations, Murphy said.

"This information should lead to the development of vaccines to prevent colonization by the offending strains. It also provides a better understanding of what the bacteria are doing, which allows us to modulate the patient's immune response to the bacteria."

The findings are based on a total of 1,975 clinic visits by 81 patients over 56 months conducted at the Veterans Affairs (VA) Western New York Hospital System. Sputum samples were collected monthly and during exacerbations. Bacteria isolated from the samples were subjected to molecular typing.

Results showed that exacerbations were twice as likely to occur in conjunction with the appearance of a new bacterial strain. An exacerbation was diagnosed at 33 percent of the clinic visits that involved isolation of a new strain, compared to 15.4 percent of visits where no new strain was found, the researchers reported.

"Our findings don't prove that a new strain causes an exacerbation," Murphy said. "We also found that some patients had new strains without flare-ups and some had flare-ups without new strains. However, the results contribute to the growing body of evidence that bacteria cause a significant portion of exacerbations.

"This new information will act as an important guide in developing novel ways to treat and prevent exacerbations. More importantly, it is possible that such interventions could actually slow the progressive loss of lung function that occurs in COPD. That will be one of the goals of our ongoing research in the study clinic."

Additional researchers on the study were Nancy Evans, a research nurse with the VA Western New York Hospital System, and Brydon J.B. Grant, M.D., UB professor of medicine and physiology.