Antibiotic Reverses Deadly Airflow Obstruction in Lung Transplant Patients
Low doses of the antibiotic azithromycin can halt and reverse lung function decline in lung transplant patients who suffer from the deadly and previously untreatable condition Bronchiolitis Obliterans Syndrome (BOS), according to an article published in the second issue of the September 2005 American Thoracic Society's peer-reviewed American Journal of Respiratory and Critical Care Medicine.
Paul A. Corris, M.B., B.S., F.R.C.P., of the William Leech Centre for Lung Research at FreemanHospital in High Heaton, Newcastle upon Tyne, United Kingdom, along with eight associates, studied 10 male and 10 female patients with BOS.
According to the researchers, after 3 months of azithromycin therapy (250 mg every other day), patients showed a significant increase in lung function after taking a common lung function test, forced expiratory volume in one second (FEV1). These increases averaged 110 ml with a range from -70 to 730 ml, although the higher figure was only seen in one patient.
"This improvement was sustained beyond 3 months in the majority of patients who had initially benefited from azithromycin, as demonstrated over 11 months of follow-up," said Dr. Corris.
Lung transplant patients who have BOS experience a persistent decline in lung function test results in the absence of acute rejection, infection or bronchial complications. To date, the only way physicians have been able to manage this problem is by transplanting a new lung.
Recently, several small pilot studies have stirred up interest in the role of macrolide antibiotics in the management of BOS. Macrolides are any of several antibiotics (including erythromycin) used as antibacterial agents. Azithromycin is derived from erythromycin.
Since BOS leads to deteriorating graft function and limited long-term survival, transplant physicians have tried using multiple strategies in an effort to manage the condition. These strategies include switching immunosuppressive regimens, augmenting treatment with corticosteroids and initiating therapy designed to destroy certain cells. None of these approaches has worked.
"The International Transplant Registry data shows a 50 percent prevalence of BOS at 5 years after transplantation," said Dr. Corris. "This is associated with a reduction in quality of life and increased morbidity and mortality, limiting 7-year mean survival to only 31 percent."
In an editorial on the study in the same issue, Trevor J. Williams, M.D., of Alfred Hospital and Monash University Clinical School in Mebourne, Australia, and Geert M. Verleden, M.D., of University Hospital in Gasthuisberg, Leuven, Belgium, wrote that the researchers: "describe a case series of 20 patients with post-transplant BOS where the use of the neomacrolide antibiotic azithromycin (250 mg on alternate days) led to improved lung function. The improvement was modest (median 110 ml) and the follow-up short (mean 6.25 months). Nevertheless, indicative of our collective frustration with present therapeutic options, these results are very exciting."
In speculating on how azithromycin might work, the editorialists felt that, among other possibilities, one potential mechanism was through the suppression of important pathogens, such as Pseudomonas aeruginosa. Another theory was that it might exert anti-inflammatory effects against traditional immune responses associated with transplanted tissue from another individual. Moreover, it might work against more primitive innate immune responses in the body. They also said that the antibiotic also seemed to significantly reduce neutrophilia (an excessive number of a certain type of white cell) after 3 months of treatment. According to the editorial, this latter effect might be an important mechanism of action since cystic fibrosis, chronic obstructive pulmonary disease and panbronchiolitis are classified as neutrophilic airway diseases.
(Neutrophils are the body's primary cellular defense against bacteria and fungi.