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Yoon H.I.,Providence Heart and Lung Institute | Yoon H.I.,Seoul National University | Sin D.D.,Providence Heart and Lung Institute | Sin D.D.,University of British Columbia
Drugs | Year: 2011

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality across the world. Unfortunately, none of the current therapies, except for smoking cessation and supplemental domiciliary oxygen for hypoxaemic patients, can modify its natural course or alter survival. The pipeline for new compounds is not very promising owing to repeated failures, and many large pharmaceutical companies have abandoned COPD drug discovery altogether. One major barrier to new drug discovery is the lack of modifiable biomarkers that can be used as surrogates of clinical outcomes such as exacerbation and mortality. The only accepted marker in COPD is forced expiratory volume in 1 second (FEV 1). However, by definition, COPD is a non-reversible or poorly reversible condition with respect to FEV 1. Thus, very few drugs except for bronchodilators have been able to address this endpoint. Of many candidate molecules, sputum neutrophil counts, exhaled corrected alveolar nitric oxide and proline-glycine-proline (PGP) and N-α-PGP, which are breakdown products of collagen, are promising lung-based biomarkers. However, their clinical utility has not been validated in large clinical trials. Promising blood biomarkers include surfactant protein D, and pulmonary-and activation-regulated chemokine (PARCCCL-18). However, the clinical data have been inconsistent. Non-specific inflammatory biomarkers such as C-reactive protein and interleukin-6 lack specificity for COPD and thus are of limited clinical usefulness. © 2011 Adis Data Information BV. All rights reserved.

Wu J.,University of British Columbia | Sin D.D.,Providence Heart and Lung Institute
International Journal of COPD | Year: 2011

Smoking is the leading modifiable risk factor for chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD), and lung cancer. Smoking cessation is the only proven way of modifying the natural course of COPD. It is also the most effective way of reducing the risk for myocardial infarction and lung cancer. However, the full benefits of tobacco treatment may not be realized until many years of abstinence. All patients with COPD, regardless of severity, appear to benefit from tobacco treatment. Similarly, patients with recent CVD events also benefit from tobacco treatment. The risk of total mortality and rate of recurrence of lung cancer is substantially lower in smokers who manage to quit smoking following the diagnosis of early stage lung cancer or small cell lung cancer. Together, these data suggest that tobacco treatment is effective both as a primary and a secondary intervention in reducing total morbidity and mortality related to COPD, CVD, and lung cancer. In this paper, we summarize the evidence for tobacco treatment and the methods by which smoking cessation can be promoted in smokers with lung disease. © 2011 Wu and Sin, publisher and licensee Dove Medical Press Ltd.

Francis G.A.,Providence Heart and Lung Institute
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2010

Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely associated with coronary artery disease risk in large epidemiologic studies. This rule, however, has many exceptions in individual patients, and evidence suggests that other facets of high-density lipoprotein particle biology not captured by measuring HDL-C levels are responsible for HDL's effects in vivo. This article reviews the evidence for the protective nature of HDL, current evidence from animal and human studies regarding HDL-based therapies, the major steps in HDL particle formation and metabolism, alterations leading to dysfunctional HDL in diabetes and inflammatory states, and potential alternatives to HDL-C to measure HDL function and predict its protective value clinically. © 2010 Elsevier B.V.

Querido J.S.,University of British Columbia | Sheel A.W.,University of British Columbia | Cheema R.,University of British Columbia | Eeden S.V.,University of British Columbia | And 3 more authors.
Sleep and Breathing | Year: 2012

Purpose Obstructive sleep apnea (OSA) is a common disease which is associated with elevated inflammatory markers and adhesion molecules, possibly due to nightly intermittent hypoxia (IH). The purpose of this study was to test the hypothesis that IH would increase systemic inflammatory markers in healthy human males. Methods Healthy, young male subjects (n=9; 24±2 years) were exposed to a single daily isocapnic hypoxia exposure (oxyhemoglobin saturation=80%, 1 h/day) for 10 consecutive days. Serum granulocyte macrophage colonystimulating factor, interferon-γ, interleukin-1β, interleukin- 6, interleukin-8, leptin, monocyte chemotactic protein-1, vascular endothelial growth factor, intracellular adhesion molecule-1, and vascular cell adhesion molecule-1 were measured before and following the 10 days of IH using Luminex. Results Nine subjects completed the study (24±2 years; 24 ±2 kg/m2). The mean oxyhemoglobin saturation was 80.8± 1.6% during the hypoxia exposures. There was no significant change in any of the markers of inflammation (paired t test, P>0.2 all cytokines). Conclusions These findings suggest that (1) a more substantial or a different pattern of hypoxemia might be necessary to activate systemic inflammation, (2) the system may need to be primed before hypoxic exposure, or (3) increases in inflammatory markers in patients with OSA may be more related to other factors such as obesity or nocturnal arousal. © Springer-Verlag 2011.

Giles L.V.,University of British Columbia | Brauer M.,University of British Columbia | Barn P.,British Columbia Center for Disease Control | Kunzli N.,Swiss Tropical and Public Health Institute | And 15 more authors.
Environmental Health Perspectives | Year: 2011

Background: Associations between air pollution and a multitude of health effects are now well established. Given ubiquitous exposure to some level of air pollution, the attributable health burden can be high, particularly for susceptible populations. Objectives: An international multidisciplinary workshop was convened to discuss evidence of the effectiveness of actions to reduce health impacts of air pollution at both the community and individual level. Te overall aim was to summarize current knowledge regarding air pollution exposure and health impacts leading to public health recommendations. Discussion: During the workshop, experts reviewed the biological mechanisms of action of air pollution in the initiation and progression of disease, as well as the state of the science regarding community and individual-level interventions. Te workshop highlighted strategies to reduce individual baseline risk of conditions associated with increased susceptibility to the effects of air pollution and the need to better understand the role of exposure duration in disease progression, reversal, and adaptation. Conclussion: We have identified two promising and largely unexplored strategies to address and mitigate air pollution-related health impacts: reducing individual baseline risk of cardiovascular disease and incorporating air pollution-related health impacts into land-use decisions.

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