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      The microbiome in bronchiectasis

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          Abstract

          Bronchiectasis is increasing in prevalence worldwide, yet current treatments available are limited to those alleviating symptoms and reducing exacerbations. The pathogenesis of the disease and the inflammatory, infective and molecular drivers of disease progression are not fully understood, making the development of novel treatments challenging. Understanding the role bacteria play in disease progression has been enhanced by the use of next-generation sequencing techniques such as 16S rRNA sequencing. The microbiome has not been extensively studied in bronchiectasis, but existing data show lung bacterial communities dominated by Pseudomonas, Haemophilus and Streptococcus, while exhibiting intraindividual stability and large interindividual variability. Pseudomonas- and Haemophilus-dominated microbiomes have been shown to be linked to severe disease and frequent exacerbations. Studies completed to date are limited in size and do not fully represent all clinically observed disease subtypes. Further research is required to understand the microbiomes role in bronchiectasis disease progression. This review discusses recent developments and future perspectives on the lung microbiome in bronchiectasis.

          Abstract

          Studies of the microbiome in bronchiectasis demonstrate an association between Pseudomonas, Haemophilus and other genera with exacerbations. Lower microbiome diversity correlates with greater disease severity. Larger studies are needed. http://bit.ly/2xwROOR

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          Most cited references80

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          Disordered Microbial Communities in Asthmatic Airways

          Background A rich microbial environment in infancy protects against asthma [1], [2] and infections precipitate asthma exacerbations [3]. We compared the airway microbiota at three levels in adult patients with asthma, the related condition of COPD, and controls. We also studied bronchial lavage from asthmatic children and controls. Principal Findings We identified 5,054 16S rRNA bacterial sequences from 43 subjects, detecting >70% of species present. The bronchial tree was not sterile, and contained a mean of 2,000 bacterial genomes per cm2 surface sampled. Pathogenic Proteobacteria, particularly Haemophilus spp., were much more frequent in bronchi of adult asthmatics or patients with COPD than controls. We found similar highly significant increases in Proteobacteria in asthmatic children. Conversely, Bacteroidetes, particularly Prevotella spp., were more frequent in controls than adult or child asthmatics or COPD patients. Significance The results show the bronchial tree to contain a characteristic microbiota, and suggest that this microbiota is disturbed in asthmatic airways.
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            European Respiratory Society guidelines for the management of adult bronchiectasis.

            Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines.The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature.A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy.These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes.
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              Nanopore metagenomics enables rapid clinical diagnosis of bacterial lower respiratory infection

              The gold standard for clinical diagnosis of bacterial lower respiratory infections (LRIs) is culture, which has poor sensitivity and is too slow to guide early, targeted antimicrobial therapy. Metagenomic sequencing could identify LRI pathogens much faster than culture, but methods are needed to remove the large amount of human DNA present in these samples for this approach to be feasible. We developed a metagenomics method for bacterial LRI diagnosis that features efficient saponin-based host DNA depletion and nanopore sequencing. Our pilot method was tested on 40 samples, then optimized and tested on a further 41 samples. Our optimized method (6 h from sample to result) was 96.6% sensitive and 41.7% specific for pathogen detection compared with culture and we could accurately detect antibiotic resistance genes. After confirmatory quantitative PCR and pathobiont-specific gene analyses, specificity and sensitivity increased to 100%. Nanopore metagenomics can rapidly and accurately characterize bacterial LRIs and might contribute to a reduction in broad-spectrum antibiotic use.
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                Author and article information

                Journal
                Eur Respir Rev
                Eur Respir Rev
                ERR
                errev
                European Respiratory Review
                European Respiratory Society
                0905-9180
                1600-0617
                30 September 2019
                04 September 2019
                : 28
                : 153
                : 190048
                Affiliations
                Scottish Centre for Respiratory Research, University of Dundee, Dundee, UK
                Author notes
                James D. Chalmers, Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK. E-mail: j.chalmers@ 123456dundee.ac.uk
                Article
                ERR-0048-2019
                10.1183/16000617.0048-2019
                9489022
                31484665
                527c0f6a-eff0-4a8f-aee4-0c98025f01dc
                Copyright ©ERS 2019.

                This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

                History
                : 28 April 2019
                : 01 July 2019
                Categories
                Lung Science Conference Review
                3

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