Table 5. Randomized Trials of Second-Generation Macrolides/Azalides for Asthma: Study Designs

Reference	Age Group	Sampling Frame	Asthma Severity	Subjects (n)	Design	R_X/Duration	Observation after R_X
Shoji (1999)¹⁷	Adults	Hospital asthma clinic	Mild/moderate	14	Single site; double-blind cross-over (4-week washout)	Roxithromycin, 300 mg daily or placebo/8 weeks	None
Shoji (1999)¹⁷	Adults	Hospital asthma clinic	Aspirin-intolerant asthma	14	Single site; double-blind cross-over (4-week washout)	Roxithromycin, 300 mg daily or placebo/8 weeks	None
Amayasu (2000)¹⁸	Adults	Not stated (hospital asthma clinic[s]?)	Mild/moderate	17	Single site; double-blind cross-over (4-week washout)	Clarithromycin, 200 mg daily or placebo/8 weeks	None
Black (2001)¹⁹	18–60 years old	Majority of subjects recruited from the general population; recruitment method(s) not specified	Moderate/severe	232	Multinational; double-blind, parallel groups (Australia, New Zealand, Italy, Argentina)	Roxithromycin, 300 mg daily or placebo/6 weeks	24 weeks
Kraft (2002)²⁰	Young adults	Subjects recruited from the general population via advertising	Not stated Mean FEV₁%pred = 69.3 35% were taking ICS	52	Single site; double-blind parallel groups All subjects underwent bronchoscopy before and after prescription	Clarithromycin, 1000 mg daily or placebo/6 weeks	None
Kostadima (2004)²¹	18–70 years old	Not stated (referral speciality setting)	Not stated, probably mild	63	Single site; double-blind, parallel groups	Clarithromycin, 500 or 750 mg daily or placebo/8 weeks	None
Kostadima (2004)²¹	18–70 years old	Not stated (referral speciality setting)	Mean FEV₁%pred ∼85% Subjects using albuterol >2 times weekly were excluded	63	Single site; double-blind, parallel groups	Clarithromycin, 500 or 750 mg daily or placebo/8 weeks	None
Hahn (2006)²²	≥18 years old	Community-based healthcare settings	Mostly mild/moderate	46	Multisite; double-blind, parallel groups	Azithromycin, 600 mg daily for 3 days then 600 mg weekly or placebo/6 weeks	12 weeks
Piacentini (2007)²³	Children	Inpatient setting	Not stated	16	Single site; double-blind, parallel groups	Azithromycin, 10 mg/kg/day for 3 of 7 days or placebo/8 weeks	None
Simpson (2008)²⁴	Adults	Specialty outpatient clinic	Severe refractory	45	Single site; double-blind, parallel groups	Clarithromycin, 1000 mg daily or placebo/8 weeks	4 weeks
Simpson (2008)²⁴	Adults	Specialty outpatient clinic	Severe refractory	45	Stratified by high (>61%)/low induced sputum neutrophil proportion	Clarithromycin, 1000 mg daily or placebo/8 weeks	4 weeks
Strunk (2008)²⁵	Children	Academic asthma centers	Moderate/severe	55	Multisite; 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 weeks	6 weeks
Sutherland (2010)²⁶	18–60 years old	Academic asthma centers	Suboptimally controlled asthma	92	Multisite; 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 weeks	None
Hahn (2012), current study	≥18 years old	Community-based healthcare settings	Mild/moderate (randomized)	75 randomized 22 open-label	Multisite; double-blind, parallel groups	Azithromycin, 600 mg daily for 3 days then 600 mg weekly or placebo/12 weeks	36 weeks
Hahn (2012), current study	≥18 years old	Community-based healthcare settings	Severe (open-label)	75 randomized 22 open-label	Multisite; double-blind, parallel groups		36 weeks

%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.