Table 5. Randomized Trials of Second-Generation Macrolides/Azalides for Asthma: Study Designs
ReferenceAge GroupSampling FrameAsthma SeveritySubjects (n)DesignRX/DurationObservation after RX
Shoji (1999)17AdultsHospital asthma clinicMild/moderate14Single site; double-blind cross-over (4-week washout)Roxithromycin, 300 mg daily or placebo/8 weeksNone
Aspirin-intolerant asthma
Amayasu (2000)18AdultsNot stated (hospital asthma clinic[s]?)Mild/moderate17Single site; double-blind cross-over (4-week washout)Clarithromycin, 200 mg daily or placebo/8 weeksNone
Black (2001)1918–60 years oldMajority of subjects recruited from the general population; recruitment method(s) not specifiedModerate/severe232Multinational; double-blind, parallel groups (Australia, New Zealand, Italy, Argentina)Roxithromycin, 300 mg daily or placebo/6 weeks24 weeks
Kraft (2002)20Young adultsSubjects recruited from the general population via advertisingNot stated
Mean FEV1%pred = 69.3
35% were taking ICS
52Single site; double-blind parallel groups
All subjects underwent bronchoscopy before and after prescription
Clarithromycin, 1000 mg daily or placebo/6 weeksNone
Kostadima (2004)2118–70 years oldNot stated (referral speciality setting)Not stated, probably mild63Single site; double-blind, parallel groupsClarithromycin, 500 or 750 mg daily or placebo/8 weeksNone
Mean FEV1%pred ∼85% Subjects using albuterol >2 times weekly were excluded
Hahn (2006)22≥18 years oldCommunity-based healthcare settingsMostly mild/moderate46Multisite; double-blind, parallel groupsAzithromycin, 600 mg daily for 3 days then 600 mg weekly or placebo/6 weeks12 weeks
Piacentini (2007)23ChildrenInpatient settingNot stated16Single site; double-blind, parallel groupsAzithromycin, 10 mg/kg/day for 3 of 7 days or placebo/8 weeksNone
Simpson (2008)24AdultsSpecialty outpatient clinicSevere refractory45Single site; double-blind, parallel groupsClarithromycin, 1000 mg daily or placebo/8 weeks4 weeks
Stratified by high (>61%)/low induced sputum neutrophil proportion
Strunk (2008)25ChildrenAcademic asthma centersModerate/severe55Multisite; double-blind, parallel groups
This was a study of macrolide as a “steroid-sparing” agent, not as an antimicrobial
Azithromycin, 250–500 mg daily or montelukast 5–10 mg daily of placebo/24 weeks6 weeks
Sutherland (2010)2618–60 years oldAcademic asthma centersSuboptimally controlled asthma92Multisite; double-blind, parallel groups
Stratified on Mpn or Cpn PCR± (bronchoscopic sampling) The study was underpowered to test PCR+ cases
Clarithromycin, 1000 mg daily or placebo/16 weeksNone
Hahn (2012), current study≥18 years oldCommunity-based healthcare settingsMild/moderate (randomized)75 randomized 22 open-labelMultisite; double-blind, parallel groupsAzithromycin, 600 mg daily for 3 days then 600 mg weekly or placebo/12 weeks36 weeks
Severe (open-label)
  • %pred, percent of the predicted value; Cpn, Chlamydia pneumoniae; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; Mpn, Mycoplasma pneumoniae; PCR, polymerase chain reaction.