Sputum metagenomics reveals a multidrug resistant Pseudomonas-dominant severe asthma phenotype in an Asian population.

Background And Objective: While the lung microbiome in severe asthma has been studied, work has employed targeted amplicon-based sequencing approaches without functional assessment with none focused on multi-ethnic Asian populations. Here we investigate the clinical relevance of microbial phenotypes of severe asthma in Asians using metagenomics.

Methods: Prospective assessment of clinical, radiological, and immunological measures were performed in a multi-ethnic Asian severe asthma cohort (N = 70) recruited across two centres in Singapore.

Characteristics of Severe Asthma Clinic Patients With Eosinophilic Granulomatosis With Polyangiitis.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis associated with varying clinical presentations and overlapping multiorgan involvement. Asthma is a predominant feature of EGPA, typically in its prodromal phase, often severe, and precedes vasculitic complications. However, there is paucity of studies describing the prevalence and characteristics of EGPA in the asthma population.

Residential exposure to spp is associated with exacerbations in COPD.

Background: Sensitisation to is linked to worse outcomes in patients with COPD; however, its prevalence and clinical implications in domestic (residential) settings remains unknown.

Methods: Individuals with COPD (n=43) recruited in Singapore had their residences prospectively sampled and assessed by shotgun metagenomic sequencing including indoor air, outdoor air and touch surfaces (a total of 126 specimens). The abundance of environmental and the occurrence of (Asp f) allergens in the environment were determined and immunological responses to allergens determined in association with clinical outcomes including exacerbation frequency.

Targeting respiratory microbiomes in COPD and bronchiectasis.

Introduction: This review summarizes our current understanding of the respiratory microbiome in COPD and Bronchiectasis. We explore the interplay between microbial communities, host immune responses, disease pathology, and treatment outcomes.

Areas Covered: We detail the dynamics of the airway microbiome, its influence on chronic respiratory diseases, and analytical challenges.

Predictors of persistent poor control and validation of ASSESS score: Longitudinal 5-year follow-up of severe asthma cohort.

Background: Longitudinal predictors of persistent poor asthma control in severe asthma (SA) cohort remain scarce. The predictive value of the asthma severity scoring system (ASSESS) in the SA cohort outside the original study and in the Asian population is unknown.

Objective: We sought to determine the 5-year longitudinal outcome of patients with SA and validate the use of ASSESS score in predicting future outcomes in SA.

RNA is a key component of extracellular DNA networks in Pseudomonas aeruginosa biofilms.

The extracellular matrix of bacterial biofilms consists of diverse components including polysaccharides, proteins and DNA. Extracellular RNA (eRNA) can also be present, contributing to the structural integrity of biofilms. However, technical difficulties related to the low stability of RNA make it difficult to understand the precise roles of eRNA in biofilms.

Applying Next-Generation Sequencing and Multi-Omics in Chronic Obstructive Pulmonary Disease.

Microbiomics have significantly advanced over the last decade, driven by the widespread availability of next-generation sequencing (NGS) and multi-omic technologies. Integration of NGS and multi-omic datasets allow for a holistic assessment of endophenotypes across a range of chronic respiratory disease states, including chronic obstructive pulmonary disease (COPD). Valuable insight has been attained into the nature, function, and significance of microbial communities in disease onset, progression, prognosis, and response to treatment in COPD.

The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi.

Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and infective exacerbations, however, in-vitro model systems for the study of host-pathogen interaction at the individual level are lacking. Here, we describe the establishment of nasopharyngeal and bronchial organoids from healthy individuals and COPD that recapitulate disease at the individual level. In contrast to healthy organoids, goblet cell hyperplasia and reduced ciliary beat frequency were observed in COPD organoids, hallmark features of the disease.

Managing adult asthma during the COVID-19 pandemic: A 2022 review and current recommendations.

Introduction: This review aims to examine asthma management during the COVID-19 pandemic.

Method: Relevant recommendations and articles were identified by respiratory professional societies and PubMed search using the terms "asthma" and "COVID-19", and examined for relevance and inclusion in this study.

Results: Recommendations for the management of asthma have remained similar but are now supported by new evidence between the years 2020 and 2022.

Healthcare utilization and health-related quality of life of severe asthma patients in Singapore.

Background: Notwithstanding unequivocal consensus on the disproportionate effect of severe asthma (SA) on asthma morbidity, healthcare utilization, quality of life, work impairment and socioeconomic burden, the burden of SA patients in Singapore has not been appraised.

Objectives: To determine the burden of disease and extent of quality of life impairment in SA patients in Singapore.

Methods: A cross-sectional analysis of SA patients seen in Singapore General Hospital (2020-2021) to investigate emergency healthcare utilization, oral corticosteroid (OCS) burden and health-related quality of life (HRQoL) with primary endpoint EuroQoL-5 Dimension three-level (EQ-5D-3L) scores.

Cluster phenotypes in a non-idiopathic pulmonary fibrosis fibrotic interstitial lung diseases cohort in Singapore.

Background: Non-idiopathic pulmonary fibrosis fibrosing interstitial lung diseases (F-ILDs) may demonstrate a progressive disease trajectory similar to idiopathic pulmonary fibrosis (IPF). We aimed to identify novel F-ILD phenotypes in a multi-ethnic South-East Asian population.

Methods: F-ILD subjects (n=201) were analysed using unsupervised hierarchical cluster analysis and their outcomes compared against IPF (n=86).

Sensitisation to recombinant allergens and clinical outcomes in COPD.

Background: Variable clinical outcomes are reported with fungal sensitisation in chronic obstructive pulmonary disease (COPD), and it remains unclear which fungi and what allergens associate with the poorest outcomes. The use of recombinant as opposed to crude allergens for such assessment is unknown.

Methods: A prospective multicentre assessment of stable COPD (n=614) was undertaken in five hospitals across three countries: Singapore, Malaysia and Hong Kong.

Clinical Signatures in COPD and Bronchiectasis.

Pulmonary mycoses remain a global threat, causing significant morbidity and mortality. Patients with airways disease, including COPD and bronchiectasis, are at increased risks of pulmonary mycoses and its associated complications. Frequent use of antibiotics and corticosteroids coupled with impaired host defenses predispose patients to fungal colonization and airway persistence, which are associated with negative clinical consequences.

Spillover Effects of COVID-19 on Essential Chronic Care and Ways to Foster Health System Resilience to Support Vulnerable Non-COVID Patients: A Multistakeholder Study.

Objectives: Little empirical research exists on how key stakeholders involved in the provision of care for chronic conditions and policy planning perceive the indirect or "spillover" effects of the COVID-19 on non-COVID patients. This study aims to explore stakeholder experiences and perspectives of the impact of COVID-19 on the provision of care for chronic conditions, evolving modalities of care, and stakeholder suggestions for improving health system resilience to prepare for future pandemics.

Design: Qualitative study design.

The current understanding and future directions for sputum microbiome profiling in chronic obstructive pulmonary disease.

Purpose Of Review: Next-generation sequencing (NGS) has deepened our understanding of the respiratory microbiome in health and disease. The number of microbiome studies employing sputum as an airway surrogate has continued to increase over the past decade to include multiple large multicentre and longitudinal studies of the microbiome in chronic obstructive pulmonary disease (COPD). In this review, we summarize the recent advances to our understanding of the bacteriome, virome and mycobiome in COPD.

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.

Heterogeneity of non-cystic-fibrosis bronchiectasis in multiethnic Singapore: A prospective cohort study at a tertiary pulmonology centre.

Introduction: Non-cystic fibrosis bronchiectasis (NCFB) is a highly heterogenous disease. We describe the clinical characteristics of NCFB patients and evaluate the performance of Bronchiectasis Severity Index (BSI) in predicting mortality.

Methods: Patients attending the bronchiectasis clinic between August 2015 and April 2020 with radiologically proven bronchiectasis on computed tomography were recruited.

Integrative microbiomics in bronchiectasis exacerbations.

Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( https://integrative-microbiomics.ntu.

Respiratory Mycoses in COPD and Bronchiectasis.

Chronic obstructive pulmonary disease (COPD) and bronchiectasis represent chronic airway diseases associated with significant morbidity and mortality. Bacteria and viruses are commonly implicated in acute exacerbations; however the significance of fungi in these airways remains poorly defined. While COPD and bronchiectasis remain recognized risk factors for the occurrence of Aspergillus-associated disease including chronic and invasive aspergillosis, underlying mechanisms that lead to the progression from colonization to invasive disease remain uncertain.

The airway microbiome in COPD, bronchiectasis and bronchiectasis-COPD overlap.

Objective: To review the airway microbiome in chronic obstructive pulmonary disease (COPD), bronchiectasis and bronchiectasis-COPD overlap (BCO).

Data Source And Study Selection: Relevant studies were selected from PubMed, Google scholar, EMBASE and Web of Science. All studies involving human microbiomes, published in the English language, and using the search terms "COPD", "Chronic Obstructive Pulmonary Disease", "Bronchiectasis", "BCO" or "Bronchiectasis and COPD overlap", AND "microbiome", "mycobiome" or "metagenomics" were included.

A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD.

Introduction: The chronic obstructive pulmonary disease (COPD) bacteriome associates with disease severity, exacerbations and mortality. While COPD patients are susceptible to fungal sensitisation, the role of the fungal mycobiome remains uncertain.

Methods: We report the largest multicentre evaluation of the COPD airway mycobiome to date, including participants from Asia (Singapore and Malaysia) and the UK (Scotland) when stable (n=337) and during exacerbations (n=66) as well as nondiseased (healthy) controls (n=47).

Evaluation of Droplet Digital Polymerase Chain Reaction (ddPCR) for the Absolute Quantification of species in the Human Airway.

Background: Prior studies illustrate the presence and clinical importance of detecting species in the airways of patients with chronic respiratory disease. Despite this, a low fungal biomass and the presence of PCR inhibitors limits the usefulness of quantitative PCR (qPCR) for accurate absolute quantification of in specimens from the human airway. Droplet digital PCR (ddPCR) however, presents an alternative methodology allowing higher sensitivity and accuracy of such quantification but remains to be evaluated in head-to-head fashion using specimens from the human airway.

Environmental fungal sensitisation associates with poorer clinical outcomes in COPD.

Introduction: Allergic sensitisation to fungi such as are associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis; however, clinical relevance in COPD remains unclear.

Methods: Patients with stable COPD (n=446) and nondiseased controls (n=51) were prospectively recruited across three countries (Singapore, Malaysia and Hong Kong) and screened against a comprehensive allergen panel including house dust mites, pollens, cockroach and fungi. For the first time, using a metagenomics approach, we assessed outdoor and indoor environmental allergen exposure in COPD.