Azithromycin reverses airflow obstruction in established bronchiolitis obliterans syndrome.
BACKGROUND
A recent pilot study noted clinical benefit of macrolide therapy in the management of six lung transplant recipients with bronchiolitis obliterans syndrome (BOS), a condition previously regarded as irreversible.


OBJECTIVE
To examine the effect of low-dose macrolides on lung function in lung allograft recipients with established BOS and to assess whether this benefit is sustained.


METHODS
We retrospectively evaluated the effect of azithromycin (250 mg alternate days) on clinical status and lung function in 20 allograft recipients with established BOS, confirmed by decline in FEV(1) or FEF(25-75); consistent high-resolution computed tomography findings; and exclusion of acute rejection, infection, or anastomatic complications. Azithromycin was introduced at mean 82 months after transplantation. BOS staging at initiation of treatment was BOS 3 (10), BOS 2 (2), BOS 1 (6), and BOS0-p (2). All patients were on maintenance immunosuppression comprising cell-cycle inhibitor, oral corticosteroids, and calcineurin inhibitor.


RESULTS
There was a significant increase in FEV(1) of median 110 ml (range, -70 to 730 ml) between baseline and 3 months of azithromycin therapy (p = 0.002). This improvement was sustained beyond 3 months in the majority of patients, who had initially benefited from azithromycin (up to 11 months follow up).


CONCLUSIONS
This case series confirms the benefit of azithromycin in not only halting, but reversing the declining lung function seen in patients with BOS. This benefit appears to be maintained over time. Low-dose macrolides offer a new and exciting therapeutic strategy for the treatment of progressive BOS, and further clinical and translational mechanistic studies are required.
Yates
Bryan
B
The William Leech Centre for Lung Research, The Freeman Hospital, High Heaton, Newcastle upon Tyne, NE7 7DN, UK.
Murphy
Desmond M
DM
Forrest
Ian A
IA
Ward
Chris
C
Rutherford
Robert M
RM
Fisher
Andrew J
AJ
Lordan
James L
JL
Dark
John H
JH
Corris
Paul A
PA
D000328:Adult; D000402:Airway Obstruction / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D001989:Bronchiolitis Obliterans / Q000150:complications*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013577:Syndrome; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D017963:Azithromycin