David F. Choy
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View article: Airway tryptase levels inform the lack of clinical efficacy of the tryptase inhibitor <scp>MTPS9579A</scp> in asthma
Airway tryptase levels inform the lack of clinical efficacy of the tryptase inhibitor <span>MTPS9579A</span> in asthma Open
Background Tryptase, a mast cell protease, has been identified as a potential therapeutic target in managing patients with refractory asthma. We assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of MTPS9579A, an anti‐tr…
View article: The effects of inhaled corticosteroids on healthy airways
The effects of inhaled corticosteroids on healthy airways Open
Background The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined. Objectives To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease‐related genes…
View article: A targeted amplicon next-generation sequencing assay for tryptase genotyping to support personalized therapy in mast cell-related disorders
A targeted amplicon next-generation sequencing assay for tryptase genotyping to support personalized therapy in mast cell-related disorders Open
Tryptase, the most abundant mast cell granule protein, is elevated in severe asthma patients independent of type 2 inflammation status. Higher active β tryptase allele counts are associated with higher levels of peripheral tryptase and low…
View article: Alternative Splicing Is a Major Factor Shaping Transcriptome Diversity in Mild and Severe Chronic Obstructive Pulmonary Disease
Alternative Splicing Is a Major Factor Shaping Transcriptome Diversity in Mild and Severe Chronic Obstructive Pulmonary Disease Open
The role of alternative splicing in chronic obstructive pulmonary disease (COPD) is still largely unknown. We aimed to investigate the differences in alternatively splicing events between patients with mild-to-moderate and severe COPD comp…
View article: The effects of inhaled corticosteroids on healthy airways
The effects of inhaled corticosteroids on healthy airways Open
Rationale The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined. Objectives To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease-related genes …
View article: S91 The effects of inhaled corticosteroids on healthy airways
S91 The effects of inhaled corticosteroids on healthy airways Open
Background The effects of inhaled corticosteroids (ICS) on healthy airways are poorly described. Delineating their effects on gene expression in health, without the confounding changes generated by changes in disease-related genes, will en…
View article: A bronchial gene signature specific for severe COPD that is retained in the nose
A bronchial gene signature specific for severe COPD that is retained in the nose Open
Introduction A subset of COPD patients develops advanced disease with severe airflow obstruction, hyperinflation and extensive emphysema. We propose that the pathogenesis in these patients differs from mild–moderate COPD and is reflected b…
View article: A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling
A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling Open
Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes acro…
View article: Early plasma angiopoietin-2 is prognostic for ARDS and mortality among critically ill patients with sepsis
Early plasma angiopoietin-2 is prognostic for ARDS and mortality among critically ill patients with sepsis Open
Angiopoietin-2 (Ang-2) is associated with vascular endothelial injury and permeability in the acute respiratory distress syndrome (ARDS) and sepsis. Elevated circulating Ang-2 levels may identify critically ill patients with distinct patho…
View article: Targeting interleukin-33 and thymic stromal lymphopoietin pathways for novel pulmonary therapeutics in asthma and COPD
Targeting interleukin-33 and thymic stromal lymphopoietin pathways for novel pulmonary therapeutics in asthma and COPD Open
Interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP) are alarmins that are released upon airway epithelial injury from insults such as viruses and cigarette smoke, and play critical roles in the activation of immune cell populati…
View article: A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling
A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling Open
Summary Altered myeloid inflammation and lymphopenia are hallmarks of severe infections, including SARS-CoV-2. Here, we identified a gene program, defined by correlation with EN-RAGE ( S100A12 ) gene expression, which was up-regulated in p…
View article: Integrated systems modeling of severe asthma: Exploration of <scp>IL</scp>‐33/<scp>ST2</scp> antagonism
Integrated systems modeling of severe asthma: Exploration of <span>IL</span>‐33/<span>ST2</span> antagonism Open
Asthma is a complex, heterogeneous disease with a high unmet medical need, despite therapies targeting a multitude of pathways. The ability to quantitatively integrate preclinical and clinical data on these pathways could aid in the develo…
View article: Airway remodelling rather than cellular infiltration characterizes both type2 cytokine biomarker‐high and ‐low severe asthma
Airway remodelling rather than cellular infiltration characterizes both type2 cytokine biomarker‐high and ‐low severe asthma Open
Background The most recognizable phenotype of severe asthma comprises people who are blood eosinophil and FeNO‐high, driven by type 2 (T2) cytokine biology, which responds to targeted biological therapies. However, in many people with seve…
View article: Exacerbation Profile and Risk Factors in a Type-2–Low Enriched Severe Asthma Cohort: A Clinical Trial to Assess Asthma Exacerbation Phenotypes
Exacerbation Profile and Risk Factors in a Type-2–Low Enriched Severe Asthma Cohort: A Clinical Trial to Assess Asthma Exacerbation Phenotypes Open
Rationale: The past 25 years have seen huge progress in understanding of the pathobiology of type-2 (T2) asthma, identification of measurable biomarkers, and the emergence of novel monoclonal antibody treatments. Although present in a mino…
View article: Steroid-induced fibroblast growth factors drive an epithelial-mesenchymal inflammatory axis in severe asthma
Steroid-induced fibroblast growth factors drive an epithelial-mesenchymal inflammatory axis in severe asthma Open
Asthma and inflammatory airway diseases restrict airflow in the lung, compromising gas exchange and lung function. Inhaled corticosteroids (ICSs) can reduce inflammation, control symptoms, and improve lung function; however, a growing numb…
View article: A whole genome sequencing study of moderate to severe asthma identifies a lung function locus associated with asthma risk
A whole genome sequencing study of moderate to severe asthma identifies a lung function locus associated with asthma risk Open
Genome-wide association studies (GWAS) have identified many common variant loci associated with asthma susceptibility, but few studies investigate the genetics underlying moderate-to-severe asthma risk. Here, we present a whole-genome sequ…
View article: Factors affecting adherence with treatment advice in a clinical trial of patients with severe asthma
Factors affecting adherence with treatment advice in a clinical trial of patients with severe asthma Open
Background Understanding why patients with severe asthma do not follow healthcare provider (HCP) advice to adjust treatment is critical to achieving personalised disease management. Methods We reviewed patient choice to follow HCP advice t…
View article: Lysophosphatidic acid species are associated with exacerbation in chronic obstructive pulmonary disease
Lysophosphatidic acid species are associated with exacerbation in chronic obstructive pulmonary disease Open
Background Chronic obstructive pulmonary disease (COPD) exacerbations are heterogenous and profoundly impact the disease trajectory. Bioactive lipid lysophosphatidic acid (LPA) has been implicated in airway inflammation but the significanc…
View article: Population repeated time‐to‐event analysis of exacerbations in asthma patients: A novel approach for predicting asthma exacerbations based on biomarkers, spirometry, and diaries/questionnaires
Population repeated time‐to‐event analysis of exacerbations in asthma patients: A novel approach for predicting asthma exacerbations based on biomarkers, spirometry, and diaries/questionnaires Open
Identification of covariates, including biomarkers, spirometry, and diaries/questionnaires, that predict asthma exacerbations would allow better clinical predictions, shorter phase II trials and inform decisions on phase III design, and/or…
View article: Can Social Media Data Be Utilized to Enhance Early Warning: Retrospective Analysis of the U.S. Covid-19 Pandemic
Can Social Media Data Be Utilized to Enhance Early Warning: Retrospective Analysis of the U.S. Covid-19 Pandemic Open
The U.S. needs early warning systems to help it contain the spread of infectious diseases. Conventional early warning systems use lab-test results or dynamic records to signal early warning signs. New early warning systems can supplement t…
View article: High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis
High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis Open
Introduction COPD exacerbations are heterogeneous and can be triggered by bacterial, viral, or noninfectious insults. Exacerbations are also heterogeneous in neutrophilic or eosinophilic inflammatory responses. A noninvasive peripheral bio…
View article: A randomized, placebo‐controlled trial evaluating effects of lebrikizumab on airway eosinophilic inflammation and remodelling in uncontrolled asthma (CLAVIER)
A randomized, placebo‐controlled trial evaluating effects of lebrikizumab on airway eosinophilic inflammation and remodelling in uncontrolled asthma (CLAVIER) Open
Background The anti‐interleukin 13 (IL‐13) monoclonal antibody lebrikizumab improves lung function in patients with moderate‐to‐severe uncontrolled asthma, but its effects on airway inflammation and remodelling are unknown. CLAVIER was des…