Sanjay H. Chotirmall
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View article: Stress-induced toxic genomic R-loops support biofilm extracellular matrix formation
Stress-induced toxic genomic R-loops support biofilm extracellular matrix formation Open
Self-aggregation into biofilms is a bacterial stress response that promotes antimicrobial resistance because biofilms comprise viscous extracellular polymeric matrices that impede antimicrobial diffusion. Extracellular DNA (eDNA) is typica…
View article: Economic burden of asthma multimorbidity in Singapore: Shadow costs of steroid use
Economic burden of asthma multimorbidity in Singapore: Shadow costs of steroid use Open
Background: In some countries including Singapore, biologic therapies are not routinely available. Instead, oral corticosteroid (OCS) is commonly used for severe asthma management, which could lead to substantial adverse health events. Obj…
View article: Multidrug-resistant <i>Haemophilus influenzae</i> cluster of severe asthma from sputum bacteriome-resistome
Multidrug-resistant <i>Haemophilus influenzae</i> cluster of severe asthma from sputum bacteriome-resistome Open
Background Severe asthma encompasses heterogeneous inflammatory phenotypes and airway bacteriome diversity but the state of its airway resistome remains understudied. We therefore evaluated the link between the airway microbiome and the an…
View article: Design and rationale of the AIR-NET trial: a randomised, open-label, multifactorial, multicentre, adaptive platform trial using a range of repurposed anti-inflammatory treatments to improve outcomes in patients with bronchiectasis within the EMBARC clinical research network
Design and rationale of the AIR-NET trial: a randomised, open-label, multifactorial, multicentre, adaptive platform trial using a range of repurposed anti-inflammatory treatments to improve outcomes in patients with bronchiectasis within the EMBARC clinical research network Open
Background Neutrophilic airway inflammation is associated with disease severity and exacerbation frequency in bronchiectasis. Neutrophil protease inhibition significantly reduced exacerbation rates in phase II and III trials in bronchiecta…
View article: Symptoms, risk of future exacerbations, and response to long-term macrolide treatment in bronchiectasis: an observational study
Symptoms, risk of future exacerbations, and response to long-term macrolide treatment in bronchiectasis: an observational study Open
EU, European Federation of Pharmaceutical Industries and the Associations Innovative Medicines Initiative Inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society.
View article: Ethnic variation in South East Asian patients with severe asthma: A first look at the Singapore Severe Asthma Registry (SSAR) and implications on clinical practice
Ethnic variation in South East Asian patients with severe asthma: A first look at the Singapore Severe Asthma Registry (SSAR) and implications on clinical practice Open
This study provided the first look into data from the Singapore Severe Asthma Registry; ethnic differences were observed, especially in comorbidity risks.
View article: A peek into the pipeline: Expert views on emerging therapies
A peek into the pipeline: Expert views on emerging therapies Open
Alzheimer's disease (AD) trials: A field in (r)evolution AD remains a major societal challenge, but more than a century of research is gradually leading to an exciting (r)evolution in AD and other tauopathy trials. Initially, amyloid-beta-…
View article: A gut <i>Eggerthella lenta</i> –derived metabolite impairs neutrophil function to aggravate bacterial lung infection
A gut <i>Eggerthella lenta</i> –derived metabolite impairs neutrophil function to aggravate bacterial lung infection Open
The composition of the gut microbiota in patients with bronchiectasis has been proven to be distinct from that of healthy individuals, and this disrupted gut microbiota can exacerbate lung infections. However, the responsible microbes and …
View article: Targeting neutrophil serine proteases in bronchiectasis
Targeting neutrophil serine proteases in bronchiectasis Open
Persistent neutrophilic inflammation is a central feature in both the pathogenesis and progression of bronchiectasis. Neutrophils release neutrophil serine proteases (NSPs), such as neutrophil elastase (NE), cathepsin G and proteinase 3. W…
View article: Fungal lung disease
Fungal lung disease Open
Fungal lung disease encompasses a wide spectrum of organisms and associated clinical conditions, presenting a significant global health challenge. The type and severity of disease are determined by underlying host immunity and infecting fu…
View article: Residential exposure to<i>Aspergillus</i>spp<i>.</i>is associated with exacerbations in COPD
Residential exposure to<i>Aspergillus</i>spp<i>.</i>is associated with exacerbations in COPD Open
Background Sensitisation to Aspergillus fumigatus 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)…
View article: Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF, a phase II randomised, double-blind, placebo-controlled, dose-finding study
Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF, a phase II randomised, double-blind, placebo-controlled, dose-finding study Open
Background Bronchiectasis is characterised by uncontrolled neutrophil serine protease (NSP) activity. Cathepsin C (CatC; dipeptidyl peptidase 1) activates NSPs during neutrophil maturation. CatC inhibitors can potentially reduce neutrophil…
View article: A severe asthma phenotype of excessive airway <i>Haemophilus influenzae</i> relative abundance associated with sputum neutrophilia
A severe asthma phenotype of excessive airway <i>Haemophilus influenzae</i> relative abundance associated with sputum neutrophilia Open
Background Severe asthma (SA) encompasses several clinical phenotypes with a heterogeneous airway microbiome. We determined the phenotypes associated with a low α‐diversity microbiome. Methods Metagenomic sequencing was performed on sputum…
View article: Host–microbial interactions differ with age of asthma onset
Host–microbial interactions differ with age of asthma onset Open
The host immune response to pathogens differs between early- and late-onset asthma https://bit.ly/3xSa4Fe
View article: Bronchiectasis in Asia: a review of current status and challenges
Bronchiectasis in Asia: a review of current status and challenges Open
Recent bronchiectasis studies from large-scale multinational, multicentre registries have demonstrated that the characteristics of the disease vary according to geographic region. However, most perspectives on bronchiectasis are dominated …
View article: The Precision Medicine Era of Bronchiectasis
The Precision Medicine Era of Bronchiectasis Open
Bronchiectasis, originating from the Greek words bronkhia (“airway”) and ektasis (“distortion”), is a permanent, irreversible airway dilatation described in 1819 by René Laennec (1) (Figure 1A). Key work by Sir William Osler followed in th…
View article: A systematic literature review of the clinical and socioeconomic burden of bronchiectasis
A systematic literature review of the clinical and socioeconomic burden of bronchiectasis Open
Background The overall burden of bronchiectasis on patients and healthcare systems has not been comprehensively described. Here, we present the findings of a systematic literature review that assessed the clinical and socioeconomic burden …
View article: Infection and the microbiome in bronchiectasis
Infection and the microbiome in bronchiectasis Open
Bronchiectasis is marked by bronchial dilatation, recurrent infections and significant morbidity, underpinned by a complex interplay between microbial dysbiosis and immune dysregulation. The identification of distinct endophenotypes have r…
View article: Effects of intermittent fasting on periodontal inflammation and subgingival microbiota
Effects of intermittent fasting on periodontal inflammation and subgingival microbiota Open
Background Studies on the impact of intermittent fasting on periodontal health are still scarce. Thus, this study evaluated the effects of long‐term intermittent fasting on periodontal health and the subgingival microbiota. Methods This pi…