Effect Of Low-Dose Erythromycin On Patients With Stable Chronic Obstructive Pulmonary Disease

Objective:To understand the effects of long-term treatment with low-dose erythromycin on pulmonary function,respiratory symptoms,life quality,exercise tolerance,and airway neutrophil function in stable chronic obstructive pulmonary disease.Methods:A total of thirty-six subjects with moderate-to-severe stable COPD were recruited.They were divided into two groups[erythromycin group (n=18)and control group(n=18)]with a prospective randomised,self-controlled method.All parameters were estimated and compared before treatment and after three and six months of treatment.All subjects with COPD were required to continue their previous treatment.Erythromycin(375mg/d)was added on those patients of erythromycin group.All subjects were measured pulmonary function and six-minute walking distance(6MWD),and recorded the frequency of acute respiratory exacerbations.The British Medical Reserch Council(MRC)dyspnea scale was used to assess the degree of dyspnea.St.George's Respiratory Questionnaire(SGRQ)and Medical outcomes study Short Form 36 item Questionnair(SF-36)were used for evalue heath-related quality of life(HRQoL) evaluation.The total and differential leucocyte counts were measured in induced sputum.The concentrations of neutrophil elastase(NE)and macrophageinflammatory protein 2(MIP-2)in the sputum supernate were respectively detected by Enzyme-linked immunosorbent assay(ELISA).The plasm concentrations of NE and MIP-2 were also detected by the same assay.Chemotactic chamber assay was used to investigate the chemotaxis of neutrophils.Results:Thirty-six subjects with COPD were recruited(5 female)of mean(SD)age 68.87(7.56)years and initial forced expiratory volume in 1 second(FEV₁)42.79(14.37)%predicted.The result of erythromycin treatment were as follows:(1)Pulmonary function:compared with the control group,the erythromycin group inspiratory capacity(IC)was higher(1.97±0.69L vs 1.51±0.44L,P=0.05).(2)HRQoL:Compared with these parameters before treatment,the erythromycin group showed significant improvement for the parameters of general health status(GH)and social function(SF)either at the end of three months or at the end of six months.(3)Erythromycin therapy can significantly increase 6MWD after six months(372.364±76.16 m vs 349.764±67.95 m,P＜0.05).There were no significant difference in MRC score(P＞0.05).The number of acute respiratory exacerbations approach statistic significance between two groups in six months of therapy(P=0.052).(4)At the end of three or six months,sputum leucocyte total counts were significantly reduced in subjects with erythromycin(both P＜0.05).Neutrophil counts were significantly reduced compared with pretreatment counts[after 3 months:(25.65±11.97)×10⁸ cells/L vs(36.57±13.35)×10⁸ cells/L,P＜0.05;after 6 months: (24.61±12.27)×10⁸ cells/L vs(36.57±13.35)×10⁸ cells/L,P＜0.05)] Neutrophil proportion was also reduced in two time points(both P＜0.01).(5)The concentrations of NE in sputum or blood were significantly lower than their pretreatment concentrations(P＜0.05,P＜0.01).Sputum MIP-2 levels were significantly reduced after three or six months of erythromycin therapy (both P＜0.01).(6)The chemotaxis of neutrophils was reduced at the end of six months of erythromycin therapy(P＜0.05).Conclusion:1.Long-term low-dose erythromycin therapy can reduce airway neutrophil counts and inhibit activity of neutrophils in pations with moderate-to-severe stable COPD.2.Erythromycin therapy can increase significantly inspiratory capacity(IC)and 6MWD,reduce the number of acute exacerbations,and improve quality of life.