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.

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.

Accelerated Lung Function Decline and Mucus-Microbe Evolution in Chronic Obstructive Pulmonary Disease.

Progressive lung function loss is recognized in chronic obstructive pulmonary disease (COPD); however, no study concurrently evaluates how accelerated lung function decline relates to mucus properties and the microbiome in COPD. Longitudinal assessment of mucus and microbiome changes accompanying accelerated lung function decline in patients COPD. This was a prospective, longitudinal assessment of the London COPD cohort exhibiting the greatest FEV decline ( = 30; accelerated decline; 156 ml/yr FEV loss) and with no FEV decline ( = 28; nondecline; 49 ml/yr FEV gain) over time.

Airway "Resistotypes" and Clinical Outcomes in Bronchiectasis.

Chronic infection and inflammation shapes the airway microbiome in bronchiectasis. Utilizing whole-genome shotgun metagenomics to analyze the airway resistome provides insight into interplay between microbes, resistance genes, and clinical outcomes. To apply whole-genome shotgun metagenomics to the airway microbiome in bronchiectasis to highlight a diverse pool of antimicrobial resistance genes: the "resistome," the clinical significance of which remains unclear.

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.

Microbial Dysregulation of the Gut-Lung Axis in Bronchiectasis.

Emerging data support the existence of a microbial "gut-lung" axis that remains unexplored in bronchiectasis. Prospective and concurrent sampling of gut (stool) and lung (sputum) was performed in a cohort of  = 57 individuals with bronchiectasis and subjected to bacteriome (16S rRNA) and mycobiome (18S Internal Transcribed Spacer) sequencing (total, 228 microbiomes). Shotgun metagenomics was performed in a subset ( = 15; 30 microbiomes).

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.

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.

Aspergillus-Associated Endophenotypes in Bronchiectasis.

Bronchiectasis is a chronic condition of global relevance resulting in permanent and irreversible structural airway damage. Bacterial infection in bronchiectasis is well studied; however, recent molecular studies identify fungi as important pathogens, either independently or in association with bacteria. species are established fungal pathogens in cystic fibrosis and their role is now increasingly being recognized in noncystic fibrosis bronchiectasis.

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.

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.

Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa.

Estrogen, a major female sex steroid hormone, has been shown to promote the selection of mucoid in the airways of patients with chronic respiratory diseases, including cystic fibrosis. This results in long-term persistence, poorer clinical outcomes, and limited therapeutic options. In this study, we demonstrate that at physiological concentrations, sex steroids, including testosterone and estriol, induce membrane stress responses in This is characterized by increased virulence and consequent inflammation and release of proinflammatory outer membrane vesicles promoting persistence of the bacteria.

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.

Metagenomics Reveals a Core Macrolide Resistome Related to Microbiota in Chronic Respiratory Disease.

Long-term antibiotic use for managing chronic respiratory disease is increasing; however, the role of the airway resistome and its relationship to host microbiomes remains unknown. To evaluate airway resistomes and relate them to host and environmental microbiomes using ultradeep metagenomic shotgun sequencing. Airway specimens from 85 individuals with and without chronic respiratory disease (severe asthma, chronic obstructive pulmonary disease, and bronchiectasis) were subjected to metagenomic sequencing to an average depth exceeding 20 million reads.

Gender differences in bronchiectasis: a real issue?

Unlabelled: Gender differences in chronic respiratory disease, including cystic fibrosis and non-cystic fibrosis bronchiectasis are clinically apparent and of increasing importance. Differences in disease prevalence, severity and outcome are all described, however, the precise cause of the gender dichotomy and their associated underlying mechanisms have been poorly characterised. A lack of dedicated clinical and epidemiological research focused in this area has led to a paucity of data and therefore a lack of understanding of its key drivers.

The Microbial Endocrinology of Pseudomonas aeruginosa: Inflammatory and Immune Perspectives.

Pseudomonas aeruginosa is a major pathogen responsible for both acute and chronic infection. Known as a colonising pathogen of the cystic fibrosis (CF) lung, it is implicated in other settings such as bronchiectasis. It has the ability to cause acute disseminated or localised infection particularly in the immunocompromised.