Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy.
BACKGROUND
Daily azithromycin decreases acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but long-term side effects are unknown.


OBJECTIVE
To identify the types of exacerbations most likely to be reduced and clinical subgroups most likely to benefit from azithromycin, 250 mg daily, added to usual care.


METHODS
Enrollment criteria included irreversible airflow limitation and AECOPD requiring corticosteroids, emergency department visit, or hospitalization in the prior year or use of supplemental oxygen. Recurrent events and cumulative incidence analyses compared treatment received for AECOPD by randomization group, stratified by subgroups of interest. Cox proportional hazards models estimated treatment effects in subgroups adjusted for age, sex, smoking status, FEV1% predicted, concomitant COPD medications, and oxygen use.


RESULTS
Azithromycin was most effective in reducing AECOPD requiring both antibiotic and steroid treatment (n = 1,113; cumulative incidence analysis, P = 0.0002; recurrent events analysis, P = 0.002). No difference in treatment response by sex (P = 0.75), presence of chronic bronchitis (P = 0.19), concomitant inhaled therapy (P = 0.29), or supplemental oxygen use (P = 0.23) was observed. Older age and milder Global Initiative for Chronic Obstructive Lung Disease stage were associated with better treatment response (P = 0.02 and 0.04, respectively). A significant interaction between treatment and current smoking was seen (P = 0.03) and azithromycin did not reduce exacerbations in current smokers (hazard ratio, 0.99; 95% confidence interval, 0.71-1.38; P = 0.95).


CONCLUSIONS
Azithromycin is most effective in preventing AECOPD requiring both antibiotic and steroid treatment. Adjusting for confounders, we saw no difference in efficacy by sex, history of chronic bronchitis, oxygen use, or concomitant COPD therapy. Greater efficacy was seen in older patients and milder Global Initiative for Chronic Obstructive Lung Disease stages. We found little evidence of treatment effect among current smokers. Clinical trial registered with www.clinicaltrials.gov (NCT0011986 and NCT00325897).
1 University of Michigan Health System, Ann Arbor, Michigan.
MeiLan K
MK
Han
Nabihah
N
Tayob
Susan
S
Murray
Mark T
MT
Dransfield
George
G
Washko
Paul D
PD
Scanlon
Gerard J
GJ
Criner
Richard
R
Casaburi
John
J
Connett
Stephen C
SC
Lazarus
Richard
R
Albert
Prescott
P
Woodruff
Fernando J
FJ
Martinez
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017963:Azithromycin / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D017963:Azithromycin
azithromycin; chronic obstructive pulmonary disease; exacerbation; quality of life