Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial

被引：376

作者：

Brusselle, Guy G. ^{[1
]}

VanderStichele, Christine ^{[1
]}

Jordens, Paul ^{[2
]}

Deman, Rene ^{[3
]}

Slabbynck, Hans ^{[4
]}

Ringoet, Veerle ^{[5
]}

Verleden, Geert ^{[6
]}

Demedts, Ingel K. ^{[7
]}

Verhamme, Katia ^{[8
]}

Delporte, Anja ^{[1
]}

Demeyere, Benedicte ^{[1
]}

Claeys, Geert ^{[9
]}

Boelens, Jerina ^{[9
]}

Padalko, Elizaveta ^{[9
]}

Verschakelen, Johny ^{[10
]}

Van Maele, Georges ^{[11
]}

Deschepper, Ellen ^{[11
]}

Joos, Guy F. P. ^{[1
]}

机构：

[1] Ghent Univ Hosp, Dept Resp Med, B-9000 Ghent, Belgium

[2] Onze Lieve Vrouw Hosp, Dept Resp Med, Aalst, Belgium

[3] AZ Groeninge, Dept Resp Med, Kortrijk, Belgium

[4] ZNA Middelheim, Dept Resp Med, Antwerp, Belgium

[5] Acad Hosp St Jan, Dept Resp Med, Brugge, Belgium

[6] Univ Hosp Gasthuisberg, Dept Resp Med, B-3000 Louvain, Belgium

[7] Heilig Hart Ziekenhuis, Dept Resp Med, Roeselare, Belgium

[8] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[9] Ghent Univ Hosp, Dept Microbiol Clin Chem & Immunol, B-9000 Ghent, Belgium

[10] Univ Hosp Gasthuisberg, Dept Radiol, B-3000 Louvain, Belgium

[11] Ghent Univ Hosp, Dept Publ Hlth, Biostat Unit, B-9000 Ghent, Belgium

来源：

THORAX | 2013年 / 68卷 / 04期

关键词：

OBSTRUCTIVE PULMONARY-DISEASE; CHLAMYDIA-PNEUMONIAE; EOSINOPHILIC ASTHMA; CLINICAL-PRACTICE; CYSTIC-FIBROSIS; CLARITHROMYCIN; THERAPY; BRONCHIECTASIS; IDENTIFICATION; ROXITHROMYCIN;

D O I：

10.1136/thoraxjnl-2012-202698

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

100201 [内科学];

摘要：

Background Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides. Methods We performed a randomised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting beta(2) agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). Results The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma (blood eosinophilia <= 200/mu l): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci. Conclusions Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study.

引用

页码：322 / 329

页数：8

共 32 条

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Azithromycin for Prevention of Exacerbations of COPD [J].