. 2018 Nov 22;13:3813–3829. doi: 10.2147/COPD.S181246

Table 1.

Characteristics of included studies

Study	Year	Country	Design	Sample size	Population characteristics (treatment/control)			Treatment arms	Duration of treatment (months)	Primary outcome	Secondary outcomes
Study	Year	Country	Design	Sample size	Mean age (years)	Men (%)	Mean FEV % predicted ¹	Treatment arms	Duration of treatment (months)	Primary outcome	Secondary outcomes
Albert et al²²	2011	USA	RCT	1,117	65/66	59/59	39/40	Azithromycin 250 mg once daily; placebo	12	The time to the first acute exacerbation of COPD	Quality of life, nasopharyngeal colonization with selected respiratory pathogens, adherence, SGRQ, SF-36, hearing
Banerjee et al²³	2005	UK	RCT	67	65.1/68.1	–	42.5/43.9	Clarithromycin 500 mg once daily; placebo	3	Health status	Sputum bacterial quantitative load, infective exacerbation rate, shuttle walk test, serum C-reactive protein levels
Berkhof et al²⁴	2013	the Netherlands	RCT	84	67/68	74/76	49.8/47.4	Azithromycin 250 mg once 3 days/week; placebo	3	Mean LCQ total and domain scores	SGRQ, SF-36, FEV₁, blood values, microbiology
Blasi et al²⁵	2010	Italy	RCT	22	72/73	91/82	–	Azithromycin 500 mg 3 days/week; standard care	6	The number of exacerbations and hospitalizations	Time to first exacerbation and hospitalization, steroid and antibiotic use, evaluation of the inflammatory cytokines values in the EBC, mortality, quality of life, safety
Brill et al²⁶	2015	UK	RCT	99	67.9/68.7	64/75	44/53	Azithromycin 250 mg once 3 days/week; placebo	3	The change in total cultured bacterial load in sputum from baseline	Bacterial numbers by 16S qPCR, sputum inflammatory markers, bacterial resistance, lung function, health status, adherence to therapy, exacerbations, adverse events, comparison of airway load measurements using quantitative culture and 16S qPCR
He et al²⁷	2010	China	RCT	36	68.8/69.3	83.3/88.9	44.3/42.1	Erythromycin 125 mg 3 times daily; placebo	6	Neutrophil number in sputum; exacerbations	Spirometry, quality of life, inflammatory markers in sputum, sputum bacteriology, adherence, safety
Naderi et al³³	2018	Canada	R	195	67.8/70.8	59.8/47.8	34.8/39.9	Azithromycin 250 mg once at least 3 times per week; placebo	≥6	Exacerbations and health service use	Changes in exacerbations according to patient and disease characteristics and adverse effects
Seemungal et al²⁸	2008	UK	RCT	109	66.5/67.8	62/64	49.3/50.6	Erythromycin 250 mg twice daily; placebo	12	Exacerbations and airway inflammation	Spirometry, sputum testing for bacteria, adverse events
Shafuddin et al²⁹	2015	New Zealand	RCT	191	67.6/66.7	85.6/71.3	33.9/35.8	Roxithromycin 300 mg once daily; placebo	3	COPD exacerbations over 48-week posttreatment period	COPD exacerbations over the 12-week treatment period, and the first and last 24-week posttreatment periods, FEV₁, FVC, CRQ scores, adverse events
Simpson et al³⁰	2014	Australia	RCT	30	71.7/69.9	60.0/66.7	56.5/51.1	Azithromycin 250 mg once daily; placebo	3	Airway bacterial load, sputum neutrophil proportion, levels of CXCL8	Exacerbations, symptom score, SGRQ, CCQ, lung function and CT scores, side effect
Suzuki et al³¹	2001	Japan	RCT	109	69.1/71.7	85.5/81.5	–	Erythromycin 200–400 mg once daily; riboflavin 10 mg once daily	12	The frequency of the common cold	The frequency of the subsequent exacerbation
Uzun et al³²	2014	the Netherlands	RCT	92	64.7/64.9	47/40	44.2/45.0	Azithromycin 500 mg once 3 days/week; placebo	12	Rate of exacerbations of COPD	Time to first exacerbation, hospital admission for acute exacerbations, change in the treatment of exacerbations, FEV₁, FVC, 6 minutes walking test, quality of life, macrolide-resistant microorganisms, adverse events

Abbreviations: CCQ, Clinical COPD questionnaire; CRQ, chronic respiratory disease questionnaire; CXCL8, a neutrophils chemokine; EBC, exhaled breath condensate; LCQ, Leicester Cough Questionnaire; R, retrospective cohort study; RCT, randomized controlled trail; SF-36, the Medical Outcomes Study 36-Item Short-Form Health Survey; SGRQ, St George’s Respiratory Questionnaire; qPCR, quantitative PCR.