Neisseria species as pathobionts in bronchiectasis.

Neisseria species are frequently identified in the bronchiectasis microbiome, but they are regarded as respiratory commensals. Using a combination of human cohorts, next-generation sequencing, systems biology, and animal models, we show that bronchiectasis bacteriomes defined by the presence of Neisseria spp. associate with poor clinical outcomes, including exacerbations. Neisseria subflava cultivated from bronchiectasis patients promotes the loss of epithelial integrity and inflammation in primary epithelial cells. In vivo animal models of Neisseria subflava infection and metabolipidome analysis highlight immunoinflammatory functional gene clusters and provide evidence for pulmonary inflammation. The murine metabolipidomic data were validated with human Neisseria-dominant bronchiectasis samples and compared with disease in which Pseudomonas-, an established bronchiectasis pathogen, is dominant. Metagenomic surveillance of Neisseria across various respiratory disorders reveals broader importance, and the assessment of the home environment in bronchiectasis implies potential environmental sources of exposure. Thus, we identify Neisseria species as pathobionts in bronchiectasis, allowing for improved risk stratification in this high-risk group.

High Frequency of Allergic Bronchopulmonary Aspergillosis in Bronchiectasis-COPD Overlap.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is associated with frequent exacerbations and poor outcomes in chronic respiratory disease, but remains underdiagnosed. The role of fungal sensitization in bronchiectasis-COPD overlap (BCO) is unknown. RESEARCH QUESTION: What is the occurrence and clinical relevance of Aspergillus sensitization and ABPA in BCO when compared with individuals with COPD or bronchiectasis without overlap? STUDY DESIGN: Prospective, observational, cross-sectional study. METHODS: We prospectively recruited 280 patients during periods of clinical stability with bronchiectasis (n = 183), COPD (n = 50), and BCO (n = 47) from six hospitals across three countries (Singapore, Malaysia, and Scotland). We assessed sensitization responses (as specific IgE) to a panel of recombinant Aspergillus fumigatus allergens and the occurrence of ABPA in relationship to clinical outcomes. RESULTS: Individuals with BCO show an increased frequency and clinical severity of ABPA compared with those with COPD and bronchiectasis without overlap. BCO-associated ABPA is associated with more severe disease, higher exacerbation rates, and lower lung function when compared with ABPA occurring in the absence of overlap. BCO with a severe bronchiectasis severity index (BSI; > 9) is associated significantly with the occurrence of ABPA that is unrelated to underlying COPD severity. CONCLUSIONS: BCO demonstrates a high frequency of ABPA that is associated with a severe BSI (> 9) and poor clinical outcomes. Clinicians should maintain a high index of suspicion for the potential development of ABPA in patients with BCO with high BSI.

Increased Chitotriosidase Is Associated With Aspergillus and Frequent Exacerbations in South-East Asian Patients With Bronchiectasis.

BACKGROUND: Chitinase activity is an important innate immune defence mechanism against infection that includes fungi. The 2 human chitinases: chitotriosidase (CHIT1) and acidic mammalian chitinase are associated to allergy, asthma, and COPD; however, their role in bronchiectasis and bronchiectasis-COPD overlap (BCO) is unknown. RESEARCH QUESTION: What is the association between chitinase activity, airway fungi and clinical outcomes in bronchiectasis and bronchiectasis-COPD overlap? STUDY DESIGN AND METHODS: A prospective cohort of 463 individuals were recruited across five hospital sites in three countries (Singapore, Malaysia, and Scotland) including individuals who were not diseased (n = 35) and who had severe asthma (n = 54), COPD (n = 90), bronchiectasis (n = 241) and BCO (n = 43). Systemic chitinase levels were assessed for bronchiectasis and BCO and related to clinical outcomes, airway Aspergillus status, and underlying pulmonary mycobiome profiles. RESULTS: Systemic chitinase activity is elevated significantly in bronchiectasis and BCO and exceed the activity in other airway diseases. CHIT1 activity strongly predicts bronchiectasis exacerbations and is associated with the presence of at least one Aspergillus species in the airway and frequent exacerbations (≥3 exacerbations/y). Subgroup analysis reveals an association between CHIT1 activity and the "frequent exacerbator" phenotype in South-East Asian patients whose airway mycobiome profiles indicate the presence of novel fungal taxa that include Macroventuria, Curvularia and Sarocladium. These taxa, enriched in frequently exacerbating South-East Asian patients with high CHIT1 may have potential roles in bronchiectasis exacerbations. INTERPRETATION: Systemic CHIT1 activity may represent a useful clinical tool for the identification of fungal-driven "frequent exacerbators" with bronchiectasis in South-East Asian populations.

The use of e-cigarettes among university students in Malaysia.

INTRODUCTION: E-cigarette use is an emerging phenomenon with increasing recognition and acceptance globally. This study aims to create a profile of e-cigarette users among university students in Malaysia. METHODS: The study was conducted using a cross-sectional research involving six universities in Malaysia. A semi-structured questionnaire was distributed to 1302 randomly selected students, who either smoked cigarettes and/or e-cigarettes. The 2011 version of Global Adult Tobacco Surveys (GATS) tool was used to record the respondents' sociodemographic data. RESULTS: The study revealed that 74.9% of the respondents smoked e-cigarettes; 40.3% used both cigarettes and e-cigarettes (dual users), and 34.5% were exclusive e-cigarette users. The exclusive use of e-cigarettes was related to gender (OR=0.18, 95% CI: 0.09-0.39). Also, male respondents were the majority users (95%). Of the respondents, 75.2 % were Malays, 98.0% single and most believed they have no health problems (92.1%). Further findings revealed the occurrence of adverse effects, dizziness 14.4%, cough 14.1%, and headaches 12.4%. Overall, 57.8% of the respondents used e-cigarettes as a smoking cessation tool, while others consider e-cigarettes a self-image enhancing tool or as part of social activities. CONCLUSIONS: Further research on the use of e-cigarettes should be conducted on a large number of respondents in other settings to augment the findings of this study, and also guide policy making on and prevention practice of e-cigarette use, among the general student population in Malaysia.

Metastatic melanoma: a rare cause of central airway obstruction.

A middle-aged woman with recurrent malignant melanoma presented initially with massive left pleural effusion. There was a complete obliteration of the left main bronchus on flexible bronchoscopy caused by a mass. Serial cryo-debulking of the tumour was done under rigid bronchoscopy; however, the outcome was not favourable due to the aggressive tumour growth. Vemurafenib was planned after thoracic radiation. She was not keen for the biologics treatment due to financial constraints. We report a case of central airway obstruction due to recurrent aggressive melanoma. More evaluations are needed on the role of interventional pulmonologist for bronchoscopic debulking of this rapidly growing tumour as well as the role of biological agents in treating such cases.

Low-dose intrapleural alteplase (without deoxyribonuclease) in complicated parapneumonic effusion: case series and literature reviews.

This case series reviews two cases of elderly patients who presented with fever, cough and shortness of breath. Clinical examinations and initial chest radiographs confirmed unilateral pleural effusion. Thoracenteses were consistent with exudative pleural effusion. We commenced intravenous antibiotics treating for parapneumonic effusions. The first case showed persistent effusion despite drainage, and the second case had a little aspirate from pleural tapping. Subsequent ultrasound of the thorax showed multiloculated effusions. We made the decisions for intrapleural fibrinolytic therapy using low-dose alteplase 2.5 mg each time, in view of the elderly patient as sacrosanct for risk of bleeding. Furthermore, DNase was not used, as it is not yet available in our setting. Both of our patients had good clinical and radiological outcomes, without the need for surgical interventions.