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Non-antimicrobial airway management of non-cystic fibrosis bronchiectasis.

ABSTRACT: Bronchiectasis are often encountered in clinical practice, and are characterized by abnormal airway dilatation and distortion associated with impaired mucociliary clearance and mucous plugging, which are frequently associated with recurrent infections. Numerous etiologies can underlie the development of bronchiectasis, but the most important distinction in research and clinical practice is between bronchiectasis due to cystic fibrosis (CF) and bronchiectasis due to all other reasons (non-CF bronchiectasis). The causes of non-CF bronchiectasis are varied and often unclear. Patients disease severity and phenotypes of non-CF bronchiectasis also varied, which can influence disease trajectory, frequency of exacerbations and mortality. This article reviews the published evidence and suggests interventions to enhance airways clearance in patients with non-CF bronchiectasis, which are key components of an individualized therapeutic program in order to achieve symptomatic relief and prevention of exacerbations and functional decline.

SUBMITTER: Egan AM

PROVIDER: S-EPMC6830171 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Non-antimicrobial airway management of non-cystic fibrosis bronchiectasis.

Egan Ashley M AM Clain Jeremy M JM Escalante Patricio P

Journal of clinical tuberculosis and other mycobacterial diseases 20171212

Bronchiectasis are often encountered in clinical practice, and are characterized by abnormal airway dilatation and distortion associated with impaired mucociliary clearance and mucous plugging, which are frequently associated with recurrent infections. Numerous etiologies can underlie the development of bronchiectasis, but the most important distinction in research and clinical practice is between bronchiectasis due to cystic fibrosis (CF) and bronchiectasis due to all other reasons (non-CF bron ...[more]

PMID: 31720381

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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 ).

Dataset Information

Non-antimicrobial airway management of non-cystic fibrosis bronchiectasis.

Publications

Non-antimicrobial airway management of non-cystic fibrosis bronchiectasis.

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