Publications by authors named "Don D Sin"

Introduction: The rapid growth in popularity of e-cigarettes over the past decade has prompted concerns about their impact on long-term respiratory health. Small airway injury is suspected to be a direct consequence of e-cigarette use and may be quantifiable by novel structural and functional diagnostic modalities.

Methods And Analysis: In a multicentre observational longitudinal study, participants will be enrolled in either an adolescent (ages ≥12 and <19 years) or an adult arm (≥19 years old) and followed over 3 years across three time points (baseline, 18 months and 36 months).

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Background: Little is known about the association between chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) in people with established CVD. Knowing if COPD is associated with a higher risk of cardiovascular events would guide appropriate secondary prevention.

Objective: To examine the risk of COPD on major adverse cardiac events (MACEs, acute myocardial infarction, stroke and cardiovascular death) in a complete real-world population of a large province, with known CVD.

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Background: A subset of COPD patients have high levels of eosinophils in the distal airways ("airway eosinophilia").

Objectives: To compare the gene expression of type 2 inflammation in airway epithelial brushings of COPD patients with and without airway eosinophilia and to investigate the changes after inhaled corticosteroids (ICS).

Methods: Post-hoc analyses of the DISARM randomised controlled trial investigated the expression of airway inflammation (type 1, 2, and 17), IL-13, and mast cell gene signatures at baseline and after 12-week ICS treatment.

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Most genetic variants identified through genome-wide association studies (GWASs) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis.

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The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report states that the diagnosis of COPD should be considered in individuals with chronic respiratory symptoms and/or exposure to risk factors. Forced spirometry demonstrating airflow obstruction after bronchodilation is required to confirm the diagnosis using a threshold of forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC) ratio <0.7.

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While spatial transcriptomics offer valuable insights into gene expression patterns within the spatial context of tissue, many technologies do not have a single-cell resolution. Here, we present SMART, a marker gene-assisted deconvolution method that simultaneously infers the cell type-specific gene expression profile and the cellular composition at each spot. Using multiple datasets, we show that SMART outperforms the existing methods in realistic settings.

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Purpose Of Review: Nutritional intake plays a major role in the management of lung health. This review provides the latest perspective on how dietary choices can modulate lung function in patients with chronic obstructive pulmonary disease (COPD) and asthma.

Recent Findings: The pathophysiology of COPD and asthma is driven by oxidative stress and inflammation of the airways, which is exacerbated by modifiable risk factors such as cigarette smoking and diet.

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Background: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.

Methods: We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets.

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Article Synopsis
  • The study hypothesizes that better cardiorespiratory fitness (CRF) can slow down aging, especially in people with chronic airflow limitation (CAL).
  • Researchers analyzed DNA methylation and conducted exercise tests on 78 participants aged 40 and older to see how CRF impacts biological aging.
  • Findings showed that higher initial CRF was linked to slower aging according to various epigenetic markers, suggesting that improving CRF could benefit health in those with chronic respiratory issues.
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Lung cancer remains the leading cause of cancer mortality, despite declining smoking rates. Previous lung cancer GWAS have identified numerous loci, but separating the genetic risks of lung cancer and smoking behavioral susceptibility remains challenging. Here, we perform multi-ancestry GWAS meta-analyses of lung cancer using the Million Veteran Program cohort (approximately 95% male cases) and a previous study of European-ancestry individuals, jointly comprising 42,102 cases and 181,270 controls, followed by replication in an independent cohort of 19,404 cases and 17,378 controls.

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Article Synopsis
  • - A study created a detailed map of the airway cells in patients with pulmonary long COVID, focusing on those who have persistent respiratory symptoms after a COVID-19 infection.
  • - Participants with long COVID were compared to those whose symptoms had resolved or who had never been infected, with analysis revealing unique neutrophil clusters in the long COVID group.
  • - The findings suggest that increased inflammation and changes in airway cell function, particularly involving neutrophils, may be responsible for the lingering respiratory issues seen in long COVID patients.
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  • COPD usually doesn't show symptoms until it's really bad, making it tough to treat.
  • In this study, scientists looked at early signs of COPD, especially how a specific protein called HIF-3α is affected by smoking and low oxygen levels.
  • They found that helping HIF-3α could be a good way to prevent lung damage and slow down the disease before symptoms appear.
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Background: Lung fibroblasts play a central role in maintaining lung homeostasis and facilitating repair through the synthesis and organization of the extracellular matrix (ECM). This study investigated the cross-talk between interleukin-1 alpha (IL-1α) and transforming growth factor-β (TGF-β) signaling, two key regulators in tissue repair and fibrosis, in the context of lung fibroblast repair in the healthy lung.

Results: Stimulation of lung fibroblasts with TGF-β1 and TGF-β2 induced collagen-I and fibronectin protein expression (p < 0.

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Most genetic variants identified through genome-wide association studies (GWAS) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis.

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Background: DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. We investigated whether bronchoalveolar lavage (BAL) cells of people living with HIV (PLWH) demonstrate epigenetic disruptions and advanced epigenetic aging.

Methods: BAL cell DNA methylation from 25 PLWH and 16 HIV-uninfected individuals were tested for differential methylation of Alu and LINE-1 sites, markers of aging.

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Rationale: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear.

Objectives: Define high-risk COPD subtypes using both genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.

Methods: We defined high-risk groups based on PRS and TRS quantiles by maximizing differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets.

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Article Synopsis
  • - Hyperpolarized Xe gas MRI is a new method for assessing lung function, focusing on gas distribution and exchange, and it complements traditional chest CT imaging which is the current standard due to its speed and accessibility.
  • - CT scans allow for detailed structural measurements of the lungs, while Xe MRI helps evaluate functional aspects, together providing better insights into lung health and diseases.
  • - The text outlines a method for registering Xe MRI and CT images, discusses current applications and challenges in the field, and suggests future directions for research to improve the integration of these imaging techniques.
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