Dataset Information

Macrolide therapy in adults and children with non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis.

ABSTRACT:

Background

A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of macrolide therapy in adults and children with bronchiectasis.

Methods

We searched the PUBMED, EMBASE, CENTRAL databases to identify relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcome was the number of bronchiectasis exacerbations. Secondary outcomes included exacerbation-related admissions, quality of life (QoL), spirometry, 6-minute walk test (6MWT) and adverse events.

Results

Nine eligible trials with 559 participants were included. Six were conducted on adults, and the remaining on children. Macrolide therapy significantly reduced the number of patients experiencing one or more exacerbation in adults [risk ratio (RR)?=?0.59; 95% CI, 0.40 to 0.86; P?=?0.006; I2?=?65%] and children [RR?=?0.86; 95% CI, 0.75-0.99; P?=?0.04; I2?=?0%], but not the number of patients with admissions for exacerbation. Macrolide therapy was also associated with reduced frequency of exacerbations in adults (RR?=?0.42; 95% CI, 0.29 to 0.61; P<0.001; I2?=?64%) and children (RR?=?0.50; 95% CI, 0.35 to 0.71; P<0.001). Pooled analyses suggested that spirometry, including FEV1 and FVC, were significantly improved in adults but not in children. Macrolide therapy improved the QoL (WMD, -6.56; 95% CI, -11.99 to -1.12; P?=?0.02; I2?=?86%) but no significant difference in 6MWT (WMD, 4.15; 95% CI, -11.83 to 20.13; P?=?0.61; I2?=?31%) and the overall adverse events (RR, 0.96; 95% CI, 0.82 to 1.13; P?=?0.66; I2?=?0%) in adults. However, reports of diarrhea and abdominal discomforts were higher with macrolide therapy.

Conclusions

Macrolide maintenance therapy, both in adults and children, was effective and safe in reducing bronchiectasis exacerbations, but not the admissions for exacerbations. In addition, macrolide administration in adults was associated with improvement in QoL and spirometry, but not 6WMT. Future studies are warranted to verify the optimal populations and clarify its potential effects on antimicrobial resistance.

SUBMITTER: Gao YH

PROVIDER: S-EPMC3946068 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Macrolide therapy in adults and children with non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis.

Gao Yong-Hua YH Guan Wei-Jie WJ Xu Gang G Tang Yan Y Gao Yang Y Lin Zhi-Ya ZY Lin Zhi-Min ZM Zhong Nan-Shan NS Chen Rong-Chang RC

PloS one 20140306 3

<h4>Background</h4>A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of macrolide therapy in adults and children with bronchiectasis.<h4>Methods</h4>We searched the PUBMED, EMBASE, CENTRAL databases to identify relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcome was the number of bronchiectasis exacerbations. Secondary outcomes included exacerbation-related admissions, quality of life (QoL), spirometry, ...[more]

PMID: 24603554

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Project description:Rationale: Non-cystic fibrosis bronchiectasis is characterized by airway mucus accumulation and sputum production, but the role of mucus concentration in the pathogenesis of these abnormalities has not been characterized.Objectives: This study was designed to: 1) measure mucus concentration and biophysical properties of bronchiectasis mucus; 2) identify the secreted mucins contained in bronchiectasis mucus; 3) relate mucus properties to airway epithelial mucin RNA/protein expression; and 4) explore relationships between mucus hyperconcentration and disease severity.Methods: Sputum samples were collected from subjects with bronchiectasis, with and without chronic erythromycin administration, and healthy control subjects. Sputum percent solid concentrations, total and individual mucin concentrations, osmotic pressures, rheological properties, and inflammatory mediators were measured. Intracellular mucins were measured in endobronchial biopsies by immunohistochemistry and gene expression. MUC5B (mucin 5B) polymorphisms were identified by quantitative PCR. In a replication bronchiectasis cohort, spontaneously expectorated and hypertonic saline-induced sputa were collected, and mucus/mucin concentrations were measured.Measurements and Main Results: Bronchiectasis sputum exhibited increased percent solids, total and individual (MUC5B and MUC5AC) mucin concentrations, osmotic pressure, and elastic and viscous moduli compared with healthy sputum. Within subjects with bronchiectasis, sputum percent solids correlated inversely with FEV1 and positively with bronchiectasis extent, as measured by high-resolution computed tomography, and inflammatory mediators. No difference was detected in MUC5B rs35705950 SNP allele frequency between bronchiectasis and healthy individuals. Hypertonic saline inhalation acutely reduced non-cystic fibrosis bronchiectasis mucus concentration by 5%.Conclusions: Hyperconcentrated airway mucus is characteristic of subjects with bronchiectasis, likely contributes to disease pathophysiology, and may be a target for pharmacotherapy.

Project description:BackgroundBoth cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis are characterized by permanent bronchial dilation, impaired mucociliary clearance, and development of chronic colonization and infection. Although the major airway microbiota in both CF and non-CF bronchiectasis may be similar, there are some differences in clinical and microbiologic features. There may also be differences in antibiotic susceptibility patterns between the CF and non-CF populations. Therefore, analysis and comparison of the microbiota and antibiotic susceptibility pattern in CF bronchiectasis versus non-CF bronchiectasis would help to improve the management of both conditions.MethodsTwo authors will independently search the electronic databases PubMed, EMBASE, the Cochrane Library, and LIVIVO, for studies reporting bacterial colonization of the respiratory tract in adults and children diagnosed with bronchiectasis in either CF or non-CF. We will include studies examining any respiratory tract specimen, using conventional bacterial culture or other specialized techniques such as molecular methods. We will also examine the antimicrobial susceptibility patterns in people with CF bronchiectasis versus non-CF bronchiectasis. The authors will independently assess the risk of bias in each included study using the Newcastle Ottawa Scale (NOS). We will present the data with descriptive statistics and provide pooled estimates of outcomes, wherever it is feasible to perform meta-analysis. Heterogeneity in studies will be explored by visual inspection of forest plots as well as using the Higgins and Thompson I2 method. We will contact the corresponding authors of studies where data is/are missing and try to obtain the missing data. We will undertake sensitivity analysis to explore the impact of study quality and subgroup analysis based on pre-set criteria. We will prepare a summary of findings' table and assess the confidence in the evidence using the GRADE methodology.DiscussionTo date, there are no locally applicable evidence-based guidelines for antimicrobial treatment of non-CF bronchiectasis patients. In general, treatment is based on extrapolation of evidence in people with CF bronchiectasis. An insight into the microbiota and antimicrobial susceptibility patterns in the two conditions would facilitate appropriate rather than empiric antimicrobial therapy and hopefully reduce the burden of antimicrobial resistance created by rampant usage of antibiotics.Systematic review registrationThe protocol has been registered in PROSPERO on July 26, 2020 (PROSPERO registration number: CRD42020193859 ).

Project description:BackgroundMacrolide maintenance treatment remains controversial for patients with noncystic fibrosis (non-CF) bronchiectasis, we performed a meta-analysis to estimate the benefits and safety of macrolides therapy in adults and children with non-CF bronchiectasis.MethodsPubMed, Embase, the Cochrane Library, and Web of Science databases were searched for all the randomized controlled trials of macrolides for treating non-CF bronchiectasis. The primary outcome was improvement of bronchiectasis exacerbations. Secondary outcomes included adverse events and macrolide resistance.ResultsA total of 10 studies involving 602 patients were included in the analysis. Pooled results showed that macrolide therapy significantly reduced the number of patients who suffered from exacerbations (RR?=?1.56, 95% CI?=?1.14-2.14, P?=?.006, I?=?72%), number of patients who experienced at least 3 exacerbations (RR?=?0.55, 95% CI?=?0.39-0.77, P?=?.0005, I?=?40%), average exacerbations per patient during the observation time (SMD?=?-0.69, 95% CI?=?-1.06 to -0.32, P?=?.0002, I?=?60%), and bronchiectasis exacerbation-related admissions (RR?=?0.46, 95% CI?=?0.23-0.96, P?=?.04, I?=?0%). Specified subgroup analyses of the number of patients free from exacerbations were further performed; macrolide therapy showed a significant benefit in both children (RR 5.03, 95% CI 2.02-12.50, P?=?.0005, I?=?45%) and adults (RR?=?1.66, 95% CI?=?1.37-2.02, P?<?.00001, I?=?79%); azithromycin showed a significant reduction on the number of patients who suffered from exacerbations (RR?=?2.25, 95% CI?=?1.67-3.02, P?<?.00001, I?=?0%), was different from erythromycin (RR?=?1.33, 95% CI?=?0.92-1.94, P?=?.13, I?=?0%) and roxithromycin (RR?=?1.14, 95% CI?=?0.97-1.35, P?=?.11, I?=?0%). The pooled results also showed no higher risk of adverse events (RR?=?0.98, 95% CI?=?0.85-1.13, P?=?.80, I?=?8%), even a lower risk of severe adverse events (RR?=?0.53, 95% CI?=?0.33-0.85, P?=?.009, I?=?0%). However, a higher risk of macrolide resistance (RR?=?3.59, 95% CI 2.6-4.96, P?<?.00001, I?=?0%) was observed.ConclusionFor both children and adults with non-CF bronchiectasis, macrolide maintenance therapy can effectively reduce bronchiectasis exacerbations, especially for patients with more frequent exacerbations and needing hospital treatment. Azithromycin was more effective than other macrolides. Macrolide maintenance therapy did not increase the risk of adverse events, but may increase the risk of macrolide resistance.

Dataset Information

Macrolide therapy in adults and children with non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis.

Background

Methods

Results

Conclusions

Publications

Macrolide therapy in adults and children with non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis.

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