Treatment of patients with COPD and recurrent exacerbations: the role of infection and inflammation

Figures & data

Table 1 Clinical studies of antibiotic treatment for COPD in the stable phase

Study	Design and treatment groups	Patient population	Results
Gómez et al^Citation56	Nonrandomized, open, comparative study of 94 patients: 54 treated with azithromycin 500 mg/day for 3 days every 3 weeks from September to May, and 40 receiving standard care	Mean age 67.6 years, recruited after admission due to exacerbation and a mean of six exacerbations in the previous year	Significant reduction in exacerbations and hospital admissions in the azithromycin group
Suzuki et al^Citation57	Randomized, nonblind study in 109 patients: 55 treated with erythromycin 200–400 mg/day and 54 in the control group, for 1 year	Mean age 70 years, mean FEV1 between 1.3 and 1.47 L	Significant reduction in common infections and exacerbations in the antibiotic-treated group
Seemungal et al^Citation58	Randomized, double-blind, placebo-controlled study. 109 patients: 53 treated with erythromycin 250 mg twice daily, and 56 with placebo for 1 year	Mean age 67.2 years, mean FEV1 50%	Significant reduction in the frequency of exacerbations with antibiotics (35%, P=0.006). The mean time to first exacerbation was 271 versus 89 days in the placebo arm (P=0.02). Significant reduction in the duration of the exacerbation with macrolide
Pomares et al^Citation59	Retrospective study of 24 patients with COPD treated with azithromycin 500 mg three times per week for 1 year	Mean age 70.9 years, mean FEV1 32.2%, mean of 3.3 hospitalizations and seven exacerbations in the previous year	58.9% reduction in exacerbations and 61.2% reduction in hospitalizations compared to the previous year without macrolides
He et al^Citation60	Randomized, double-blind, placebo-controlled study of 36 patients: 18 treated with erythromycin 125 mg three times daily, and 18 with placebo	Mean age 69 years, mean FEV1 43%	Significant reduction in the total number of cells in sputum and neutrophil elastase. Significant reduction (44%) in the relative risk of exacerbation with antibiotics. Significant delay in time to first exacerbation with macrolide
Blasi et al^Citation61	Open, randomized, noncontrolled study of 22 patients with COPD and tracheostomy: 11 receiving azithromycin 500 mg 3 days per week for 6 months, and 11 in the usual care group	Mean age 72 and 73 years. No information on lung function. 91% and 73% were colonized	Time to first exacerbation was significantly longer with the macrolide. Hazard ratio for the first exacerbation associated with usual care was 5.41 (95% CI: 1.67–17.5). Significant reduction in hospitalizations with azithromycin
Albert et al^Citation14	Randomized, double-blind, placebo-controlled clinical trial in 1,142 patients: 570 received azithromycin 250 mg daily, and 572 received placebo	Mean age 66 years. Mean FEV1 39%–40%; >50% had required hospital visits for exacerbation in the previous year	Significantly reduced risk of exacerbations with azithromycin (P<0.001). Median time to first exacerbation was significantly prolonged: 174 days with placebo and 266 with macrolide. Hazard ratio for time to first exacerbation was 0.71 (95% CI: 0.61–0.83; P<0.001)
Uzun et al^Citation16	Randomized, double-blind, placebo-controlled clinical study in 92 patients with COPD: 47 treated with azithromycin 500 mg 3 days a week for 1 year, and 45 with placebo	COPD with at least three exacerbations in the previous year. No significant bronchiectasis	Significant reduction (42%) in the rate of exacerbations in the azithromycin group compared to placebo
Sethi et al^Citation17	Randomized, double-blind, placebo-controlled study of 1,157 patients: 573 received moxifloxacin 400 mg once a day for 5 days, repeated cycles every 8 weeks for a total of six cycles, compared to placebo	Mean age 66 years, mean FEV1 40%, with at least two exacerbations in the previous year	Significant reduction (25%) of exacerbations with moxifloxacin (P=0.046). 45% reduction in exacerbations in patients with purulent/mucopurulent sputum at the time of inclusion (OR =0.55, 95% CI: 0.36–0.84; P=0.006)

Abbreviations: FEV₁, forced expiratory volume in 1 second; CI, confidence interval; OR, odds ratio.

Table 2 Risk factors for Pseudomonas aeruginosa infection in COPD

Study	Risk factors
Allegra et al^Citation62	FEV1 <35%
Eller et al^Citation63	FEV <35%
	Pretreatment with antibiotics
Miravitlles et al^Citation6	FEV1 <50%
Lode et al^Citation64	FEV1 <35%
	Use of systemic corticosteroids
	Antibiotics in the previous 3 months
Monsó et al^Citation65	Low FEV1
	Use of oral corticosteroids
	Antibiotics in the previous 3 months
	Protective effect of influenza vaccine
García-Vidal et al^Citation66	Use of systemic corticosteroids
	High BODE index
	Hospital admission in the previous year
	Previous isolation of P. aeruginosa
Gallego et al^Citation49	Presence and extent of bronchiectasis
	Prior exposure to antibiotics

Abbreviation: FEV₁, forced expiratory volume in 1 second.

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