Table 6. Randomized Trials of Second-Generation Macrolides/Azalides for Asthma: Exclusions, Outcomes, and Results
ReferenceExclusions*Outcomes ReportedResults of Macrolide Treatment
Shoji (1999)17SmokersBlood eosinophils and ECPDecreased eosinophils/ECP
Controller medicationSputum cell counts and ECPDecreased eosinophils/ECP
(No differences in sputum neutrophils)
Sulpyrine provocation testNot improved
(No patient-oriented outcomes reported)
Amayasu (2000)18SmokersBlood eosinophils and ECPDecreased eosinophils/ECP
Aspirin sensitivitySputum cell counts and ECPDecreased eosinophils/ECP
ARI for 6 weeksBHRImproved
Any asthma controller medicationPulmonary functionNot improved
Overall asthma symptomsImproved
Black (2001)19FEV1 <50% predictedPulmonary function(PEF)Improvement at end of prescription that waned after prescription
C. pneumoniae IgG < 1:64 and IgA < 1:16Pulmonary function(FEV1)Not improved
Smoking ≥20 pack-yearsAsthma symptomsNot improved
BronchiectasisAQLNot improved
Prednisone burst in previous month
Respiratory illness
Kraft (2002)20Smoking >5 pack yearsPCR+ for Mpn or Cpn31 of 55 were PCR+ for Mpn and/or Cpn
Any cigarette within 2 yearsPulmonary functionImproved FEV1 in PCR+ subject subgroup
Any lung comorbidityLung inflammationDecreased inflammatory cytokines
Any LRTi within 3 months(No patient-oriented outcomes reported)
Kostadima (2004)21Asthma diagnosis <1 year agoBHRDecreased BHR
Not on ICSPulmonary functionNot improved
Rescue inhaler >2 times weeklySerum free cortisolNot affected
Any smoking history(No patient-oriented outcomes reported)
Any other medication
FEV1 < 50% predicted
Any ARI or exacerbation within 4 weeks before or during the study
Hahn (2006)22NoneAQLNo improvement
Rescue medication useNo improvement
Cpn IgG and IgA antibodiesBaseline IgA predicted worsening symptoms
Overall asthma symptomsImproved at end of prescription and persisted after prescription
Piacentini (2007)23Oral steroids in the preceding 3 months or during the studyLung functionNo improvement
Signs of airway infection in the preceding month or during the studyBHRImproved
Lung inflammationReduced induced sputum neutrophils
Simpson (2008)24Current smokingSputum inflammatory markersDecreased airway IL-8 and neutrophils
History of smoking, >5 pack-yearsPulmonary functionNo improvement
Antihistamine medicationBHRNo improvement
Asthma controlNo improvement
Asthma symptomsDecreased wheezing after prescription
AQLImproved (NNT = 6 for ≥0.5 units improvement)
It was unclear whether the AQL was reported at the end of the prescription or after the prescription
Strunk (2008)25No controller medicationTime to inadequate control after steroid step-downNo improvement in asthma control (futility analysis)
FEV1 < 50%predRecruitment was discontinued early (292 screened, only 55 randomized)
>3 hospitalizations in past year
Sinus surgery in past year
Lung comorbidities
Sutherland (2010)26Exacerbation within 6 weeksAsthma controlNo differences in asthma control
ARI within 6 weeksPulmonary functionNo improvement
>2 exacerbations or ARI prior to entryExhaled nitric oxideNo improvement
History of smoking, ≥10 pack-yearsRescue medication useNo improvement
Lung comorbiditiesAQLNo improvement
Hahn (2012), current studyNoneOverall asthma symptomsRandomized: no improvements in any outcome
AQLOpen label: improved overall asthma symptoms and AQL score at end of prescription that persisted after prescription (improvements maximal at the 9-month study point)
  • * Other than for safety and logistics.

  • ACQ, asthma control questionnaire; ARI, acute respiratory illness; AQL, asthma quality of life; BHR, bronchial hyperresponsiveness; Cpn, Chlamydia pneumoniae; ECP, eosinophil cationic protein; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; Ig, immunoglobulin; IL, interleukin; LRTi, lower respiratory tract illness; Mpn, Mycoplasma pneumoniae; NNT, number needed to treat; PCR, polymerase chain reaction; PEF, peak expiratory flow.