A Meta-Analysis On Effectiveness And Safety Of Macrolides For Treatment Of Neutrophil-Dominated Airwaydiseases

Background Neutriphil-dominated airway diseases are a kind of inflammatory disease, characterized by massive neutrophils accumulation in airway, including chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), bronchiectasis, bronchiolitis obliterans syndrome (BOS) and noneosinophilic asthma, diffuse panbronchiolitis (DPB). At present, these neutrophil-dominated airway diseases result in acute exacerbation repeatedly, decline in lung function, numerous hospitalizations and increased risk of death, and reduce the quality of life. It presents a significant medical problem lacking adequate therapy. Macrolides which may possess anti-inflammatory and immunoregulatory functions beyond their antimicrobial effect has been used in the treatment of these disorders. However, the efficacy and safety of the macrolides across available randomized controlled trials (RCT) are disputed. Unfortunately, there was no evidence-based treatment of macrolides on the neutrophil-dominated airway diseases. We perform a meta-analysis to assess the effectiveness and safety of macrolides in neutrophil-dominated airway disease.Methods We searched the PUBMED, EMBASE, MEDLINE, Cochrane library, Cochrane clinical trials databases to identify relevant studies. Two reviewers evaluated the studies and extracted data independently. The outcome was the number of exacerbations, pulmonary function, hospitalization and the adverse event. The meta-analysis was performed using Rev-Man5.1 and STATA12.0.Results 24 eligible trials with 3064 patients were included. The duration of treatment ranged from 2 month to 12 month.6 were conducted on children,16 with adults and other 2 studies are mixed. Macrolides therapy significantly reduced the number of patients experiencing one or more exacerbation in 3 month group [RR=0.53,95%C1 (0.38,0.72), P< 0.0001],6 month group [RR=0.65,95% Cl (0.51,0.84), P=0.0008],12 month group [RR=0.74,95% C1 (0.62,0.88), P=0.0008]. The number of patients with hospitalization related to exacerbation showed the significant reduction [RR=0.56,95% C1 (0.38,0.84), P=0.005]. The significant difference showed in pulmonary function including predicted FEV1% [WMD=2.88,95%C1(1.14,4.62), P=0.001] and predicted FVC% [WMD=3.27,95%C1 (1.61,4.94), P=0.0001], especially in adults. No significant difference in the overall adverse events [RR=1.01,95%C1 (0.85, 1.91), P=0.93]. However, reports of diarrhea [RR=2.44,95%C1 (1.55,3.84), P=0.0001] were higher with macrolides therapy, especially after 6 month.Conclusions Macrolides maintenance therapy in 3 month,6 month and 12 month were effective in reducing the risk of exacerbations, and the hospitalization related with exacerbation was decreased of the macrolides therapy. Pulmonary function was improved in the overall effect. Macrolides can be recommended to the cure neutrophil-dominated airway diseases and the optimal duration is 3month to 6 month.