RESUMO
RATIONALE: Frequent chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of hospital admission and mortality and are associated with increased airway inflammation. Macrolides have airway antiinflammatory actions and may reduce the incidence of COPD exacerbations. OBJECTIVES: To determine whether regular therapy with macrolides reduces exacerbation frequency. METHODS: We performed a randomized, double-blind, placebo-controlled study of erythromycin administered at 250 mg twice daily to patients with COPD over 12 months, with primary outcome variable being the number of moderate and/or severe exacerbations (treated with systemic steroids, treated with antibiotics, or hospitalized). MEASUREMENTS AND MAIN RESULTS: We randomized 109 outpatients: 69 (63%) males, 52 (48%) current smokers, mean (SD) age 67.2 (8.6) years, FEV1 1.32 (0.53) L, FEV1% predicted 50 (18)%. Thirty-eight (35%) of the patients had three or more exacerbations in the year before recruitment, with no differences between treatment groups. There were a total of 206 moderate to severe exacerbations: 125 occurred in the placebo arm. Ten in the placebo group and nine in the macrolide group withdrew. Generalized linear modeling showed that the rate ratio for exacerbations for the macrolide-treated patients compared with placebo-treated patients was 0.648 (95% confidence interval: 0.489, 0.859; P = 0.003) and that these patients had shorter duration exacerbations compared with placebo. There were no differences between the macrolide and placebo arms in terms of stable FEV1, sputum IL-6, IL-8, myeloperoxidase, bacterial flora, serum C-reactive protein, or serum IL-6 or in changes in these parameters from baseline to first exacerbation over the 1-year study period. CONCLUSIONS: Macrolide therapy was associated with a significant reduction in exacerbations compared with placebo and may be useful in decreasing the excessive disease burden in this important patient population. Clinical trial registered with www.clinicaltrials.gov (NCT 00147667).
Assuntos
Antibioticoprofilaxia , Eritromicina/uso terapêutico , Macrolídeos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Humanos , Inflamação/fisiopatologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Escarro/microbiologiaRESUMO
BACKGROUND: Emerging evidence supports the role of cell-derived microparticles (MPs) in the pathophysiology of acute coronary syndrome (ACS). OBJECTIVES: To explore the relationship between coronary and systemic MP levels, investigate the correlation between MPs, inflammatory markers and Troponin T in patients with ACS. METHODS: Thirty seven patients with ACS scheduled for percutaneous coronary interventions (PCI) were studied. Eleven patients with stable angina (SA) were included as a control group. AnnexinV+MPs (AnV+MPs) and activated platelet-monocyte aggregates (PMA) from right atrium (RA) and culprit coronary artery (CO) distal to culprit lesion were measured using flow cytometry. High sensitivity C-reactive protein (CRP), Interleukin - 6 (IL-6), tumour necrosis factor - α (TNF-α), serum amyloid A (SAA) and Troponin T were assayed. RESULTS: Total and cell specific AnV+MP expression were higher in the ACS group in both the CO and RA, with greater levels detected in the CO. Platelet activation showed positive correlation with Troponin-T and platelet MP in both CO and RA of the ACS group (r=0.4 for both; p=0.04 & p=0.03 respectively). Inflammatory markers levels did not differ between the ACS and SA patients. CONCLUSIONS: Elevated coronary and systemic MP levels and positive correlation of platelet activation with Troponin-T and platelet MPs suggest a pathogenic role for MPs in ACS.