Airway 'Resistotypes' and Clinical Outcomes in Bronchiectasis.

INTRODUCTION: Application of whole-genome shotgun metagenomics to the airway microbiome in bronchiectasis highlights a diverse pool of antimicrobial resistance genes: the 'resistome', the clinical significance of which remains unclear. METHODS: Individuals with bronchiectasis were prospectively recruited into cross-sectional and longitudinal cohorts (n=280) including the international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis 2 study (CAMEB 2; n=251) and two independent cohorts, one describing patients experiencing acute exacerbation and a further cohort of patients undergoing P. aeruginosa eradication treatment. Sputum was subjected to metagenomic sequencing and the bronchiectasis resistome evaluated in association with clinical outcomes and underlying host microbiomes. RESULTS: The bronchiectasis resistome features a unique resistance gene profile and elevated counts of aminoglycoside, bicyclomycin, phenicol, triclosan and multi-drug resistance genes. Longitudinally, it exhibits within-patient stability over time and during exacerbations despite between-patient heterogeneity. Proportional differences in baseline resistome profiles including increased macrolide and multi-drug resistance genes associate with shorter intervals to next exacerbation, while distinct resistome archetypes associate with frequent exacerbations, poorer lung function, geographic origin, and the host microbiome. Unsupervised analysis of resistome profiles identified two clinically relevant 'resistotypes' RT1 and RT2, the latter characterized by poor clinical outcomes, increased multi-drug resistance and P. aeruginosa. Successful targeted eradication in P. aeruginosa-colonized individuals mediated reversion from RT2 to RT1, a more clinically favourable resistome profile demonstrating reduced resistance gene diversity. CONCLUSION: The bronchiectasis resistome associates with clinical outcomes, geographic origin, and the underlying host microbiome. Bronchiectasis 'resistotypes' link to clinical disease and are modifiable through targeted antimicrobial therapy. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Dysfunctional Bronchial Cilia Are a Feature of Chronic Obstructive Pulmonary Disease (COPD).

Impaired mucociliary clearance may increase COPD exacerbation risk. We aimed to compare bronchial ciliary function and epithelial ultrastructure of COPD patients to healthy controls and explore its relationship to exacerbator phenotypes (frequent [FE] and infrequent [IFE] exacerbator). In this cross-sectional study, 16 COPD patients and 12 controls underwent bronchial brushings. Ciliary beat frequency (CBF) and dyskinesia index (DI; % of dyskinetic cilia) were assessed using digital high-speed video microscopy, and epithelial ultrastructure using transmission electron microscopy (TEM). Bronchial epithelium in COPD showed lower CBF and higher DI, compared to controls (median [IQR] CBF: 6.8 (6.1-7.2) Hz vs 8.5 (7.7-8.9) Hz, p<0.001 and DI: 73.8 (60.7-89.8) % vs 14.5 (11.2-16.9) %, p<0.001, respectively). This was true for FE and IFE phenotypes of COPD, which were similar in terms of bronchial CBF or DI. Subgroup analyses demonstrated lower CBF and higher DI in FE and IFE COPD phenotypes compared to controls, irrespective of smoking status. TEM showed more loss of cilia, extrusion of cells, cytoplasmic blebs and dead cells in COPD patients versus controls. Profound dysfunction of bronchial cilia is a feature of COPD irrespective of exacerbation phenotype and smoking status, which is likely to contribute to poor mucus clearance in COPD.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2021.1963695 .

Ministry of Health Clinical Practice Guidelines: Chronic Obstructive Pulmonary Disease

The Ministry of Health (MOH) has updated the Clinical Practice Guidelines on Chronic Obstructive Pulmonary Disease (COPD) to provide doctors and patients in Singapore with evidence-based treatment for COPD. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH Clinical Practice Guidelines on COPD, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: https://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of granulomatous mediastinal lymphadenopathy

<p><b>INTRODUCTION</b>This study assessed the clinical utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of suspected granulomatous mediastinal lymphadenopathy.</p><p><b>MATERIALS AND METHODS</b>Retrospective chart review of all patients who underwent EBUS-TBNA for suspected granulomatous mediastinal lymphadenopathy at Singapore General Hospital between December 2008 and December 2011 inclusive.</p><p><b>RESULTS</b>Over a period of 3 years, a total of 371 patients underwent EBUS-TBNA of whom 33 (9%) had the procedure performed for evaluation of suspected granulomatous mediastinal lymphadenopathy - 18 for suspected tuberculosis (TB) and non-tuberculous mycobacterial (NTM) lymphadenitis, and 15 for suspected sarcoidosis. EBUS-TBNA was diagnostic in 9 of the 13 patients with a final diagnosis of TB/NTM. EBUS-TBNA cultures were positive in 6 of them (46%), 1 showed acid-fast bacilli (AFB) although cultures were negative, and 2 had necrotising granulomatous inflammation from EBUS-TBNA biopsies and sputum cultures grew TB. EBUS-TBNA was diagnostic in 9 of the 14 patients with a final diagnosis of sarcoidosis through histology showing non-caseating granulomatous inflammation. The sensitivities of EBUS-TBNA for diagnosis of TB/NTM, sarcoidosis and overall granulomatous mediastinal lymphadenopathy were 69%, 64%, 64%; the negative predictive values were 56%, 17%, 33%; and accuracies were 78%, 67%, 70%, respectively.</p><p><b>CONCLUSION</b>EBUS-TBNA can be useful in the diagnosis of suspected granulomatous mediastinal lymphadenopathy with sensitivities and accuracies of >60%.</p>