Browsing by Author "Harvey O. Coxson"

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    DSP variants may be associated with longitudinal change in quantitative emphysema
    (2019-07-19) Woori Kim; Michael H. Cho; Phuwanat Sakornsakolpat; David A. Lynch; Harvey O. Coxson; Ruth Tal-Singer; Edwin K. Silverman; Terri H. Beaty; National Jewish Health; GlaxoSmithKline, USA; Brigham and Women's Hospital; Faculty of Medicine, Siriraj Hospital, Mahidol University; The University of British Columbia; Johns Hopkins Bloomberg School of Public Health
    © 2019 The Author(s). Background: Emphysema, characterized by lung destruction, is a key component of Chronic Obstructive Pulmonary Disease (COPD) and is associated with increased morbidity and mortality. Genome-wide association studies (GWAS) have identified multiple genetic factors associated with cross-sectional measures of quantitative emphysema, but the genetic determinants of longitudinal change in quantitative measures of emphysema remain largely unknown. Our study aims to identify genetic variants associated with longitudinal change in quantitative emphysema measured by computed tomography (CT) imaging. Methods: We included current and ex-smokers from two longitudinal cohorts: COPDGene, a study of Non-Hispanic Whites (NHW) and African Americans (AA), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE). We calculated annual change in two quantitative measures of emphysema based on chest CT imaging: percent low attenuation area (≤ - 950HU) (%LAA-950) and adjusted lung density (ALD). We conducted GWAS, separately in 3030 NHW and 1158 AA from COPDGene and 1397 Whites from ECLIPSE. We further explored effects of 360 previously reported variants and a lung function based polygenic risk score on annual change in quantitative emphysema. Results: In the genome-wide association analysis, no variants achieved genome-wide significance (P < 5e-08). However, in the candidate region analysis, rs2076295 in the DSP gene, previously associated with COPD, lung function and idiopathic pulmonary fibrosis, was associated with change in %LAA-950 (β (SE) = 0.09 (0.02), P = 3.79e-05) and in ALD (β (SE) = - 0.06 (0.02), P = 2.88e-03). A lung function based polygenic risk score was associated with annual change in %LAA-950 (P = 4.03e-02) and with baseline measures of quantitative emphysema (P < 1e-03) and showed a trend toward association with annual change in ALD (P = 7.31e-02). Conclusions: DSP variants may be associated with longitudinal change in quantitative emphysema. Additional investigation of the DSP gene are likely to provide further insights into the disease progression in emphysema and COPD.
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    Increased Ratio of Visceral to Subcutaneous Adipose Tissue in Septic Patients Is Associated with Adverse Outcome
    (2016-11-01) Chawika Pisitsak; Joseph G.H. Lee; John H. Boyd; Harvey O. Coxson; James A. Russell; Keith R. Walley; The University of British Columbia; Mahidol University
    Copyright © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. Objectives: Visceral and subcutaneous adipose tissue may contribute differentially to the septic inflammatory response. Accordingly, we tested the hypothesis that the ratio of visceral to subcutaneous adipose tissue is associated with altered sepsis outcome. Design: A retrospective analysis from a cohort of sepsis patients admitted between 2004 and 2009. Setting: A mixed medical-surgical ICU at St. Paul's Hospital in Vancouver, Canada. Patients: Patients older than 16 years old who had sepsis and underwent abdominal CT scan (n = 257) for clinical reasons. Interventions: None. Measurements and Main Results: We measured the visceral adipose tissue and subcutaneous adipose tissue areas and calculated the visceral adipose tissue-to-subcutaneous adipose tissue ratio. Visceral adipose tissue/subcutaneous adipose tissue was not correlated with body mass index (r2= -0.015, p = NS) and therefore provides additional unique information independent of body mass index. Sepsis patients with higher visceral adipose tissue/subcutaneous adipose tissue had greater 90-day mortality than patients with lower visceral adipose tissue/subcutaneous adipose tissue (log-rank test, linear-by linear association p < 0.005). After adjustment for significant covariates using Cox regression, increased visceral adipose tissue/subcutaneous adipose tissue quartile was significantly associated with increased 90-day mortality with hazard ratios of 2.01 (95% CI, 1.01-3.99) for the third visceral adipose tissue/subcutaneous adipose tissue quartile compared with the first quartile and 2.32 (95% CI, 1.15-4.69) for the highest visceral adipose tissue/subcutaneous adipose tissue quartile when compared with the first quartile. Increased mortality for patients with higher visceral adipose tissue/subcutaneous adipose tissue was found for both patients with body mass index less than 25 kg/m2(p = 0.004) and for body mass index greater than or equal to 25 kg/m2(p = 0.023). Furthermore, we found significantly greater need for mechanical ventilation, renal replacement therapy, and ICU stay in patients in the highest visceral adipose tissue/subcutaneous adipose tissue quartile. The ratio of proinflammatory (interleukin-8) to anti-inflammatory (interleukin-10) plasma cytokine levels was greater in patients with higher visceral adipose tissue/subcutaneous adipose tissue than in those with lower visceral adipose tissue/subcutaneous adipose tissue (p = 0.043). Conclusions: Visceral obesity, defined by a high visceral adipose tissue-to-subcutaneous adipose tissue ratio, contributes to adverse outcome in sepsis patients perhaps because of a greater pro- versus anti-inflammatory response.