Opportunities and Challenges in the Genetics of COPD 2010: An International COPD Genetics Conference Report

Silverman, Edwin K.; Vestbo, Jørgen; Agustí, Àlvar; Anderson, Wayne H.; Bakke, Per; Barnes, Kathleen C.; Barr, R. Graham; Bleecker, Eugene R.; Boezen, H. Marike; Burkart, Kristin M.; Celli, Bartolomé R.; Cho, Michael H.; Cookson, William; Croxton, Thomas L.; Daley, Denise; DeMeo, Dawn L.; Gan, Weiniu; Garcia‐Aymerich, Judith; Hall, Ian P.; Hansel, Nadia N.; Hersh, Craig P.; Kalsheker, Noor; Kiley, James P.; Kim, Woo Jin; Lambrechts, Diether; Lee, Sang Do; Litonjua, Augusto A.; Lomas, David A.; London, Stephanie J.; Nishimura, Masaharu; Nordestgaard, Børge G.; O’Donnell, Christopher J; Postma, Dirkje S.; Puhan, Milo A.; Tesfaigzi, Yohannes; Tobin, Martin D.; Vogelmeier, Claus; Wilk, Jemma B.; Wouters, Emiel F.M.; Young, Robert P.; Ziegler-Heitbrock, Loems; MacNee, William; Crapo, James D.

doi:10.3109/15412555.2011.558864

Cited by 45 publications

(35 citation statements)

References 66 publications

(59 reference statements)

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“…To date, the most important and most studied phenotype of COPD is airflow limitation defined by pulmonary function testing (spirometry). In 2010, however, the International COPD Genetics Conference reported that additional phenotypic expressions should be considered (21). These phenotypes should include the degree, type, and distribution of emphysema; extent of thickening of airway walls; presence and degree of dyspnea; quality of gas exchange in the lungs; and presence of systemic inflammation.…”

Section: Classification Of Copd Patientsmentioning

confidence: 99%

Genetic Predisposition to Chronic Obstructive Pulmonary Disease and/or Lung Cancer: Important Considerations When Evaluating Risk

El‐Zein

Young

Hopkins

et al. 2012

Cancer Prevention Research

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Chronic obstructive pulmonary disease (COPD) is defined as a disease causing an airflow limitation that is not fully reversible. COPD is phenotypically complex and characterized by small-airway disease and/or emphysema that result from the interaction between host genetic susceptibility and environmental exposures. As in lung cancer, smoking exposure is the most important risk factor for the development of COPD, accounting for 80% to 90% of all cases. COPD affects an estimated 8% to 10% of the general adult population, 15% to 20% of the smoking population, and 50% to 80% of lung cancer patients (with substantial smoking histories). In prospective studies, COPD has been found to be an independent risk factor for lung cancer, conferring a three-to 10-fold increased risk of lung cancer when compared with smokers without COPD. These findings suggest that smokers have a host susceptibility to COPD alone, COPD and lung cancer (i.e., overlap), and lung cancer in the absence of COPD. This minireview focuses on important points that need to be addressed when studying genetic susceptibility factors for COPD and its complex relationship with susceptibility to lung cancer. Cancer Prev Res; 5(4); 522-7. Ó2012 AACR.

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Section: Classification Of Copd Patientsmentioning

confidence: 99%

Genetic Predisposition to Chronic Obstructive Pulmonary Disease and/or Lung Cancer: Important Considerations When Evaluating Risk

El‐Zein

Young

Hopkins

et al. 2012

Cancer Prevention Research

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“…Our finding does not necessarily imply that progression of COPD to GOLD IV stage results in low proportions of IFN-c or TNF-a expressing circulating CD8+ T-cells or, conversely, that patients with relatively low numbers of IFN-c or TNF-a expressing circulating CD8+ T-cells have an increased susceptibility to progress to GOLD stage IV. In any case, our findings show the importance of analysing the peripheral compartment in the context of COPD heterogeneity [31].…”

Section: Effects Of Smoking On Cytokine Expressionmentioning

confidence: 99%

Systemic CD4+ and CD8+ T-cell cytokine profiles correlate with GOLD stage in stable COPD

et al. 2011

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Chronic obstructive pulmonary disease (COPD) is associated with pulmonary and systemic inflammation. Both CD4+ and CD8+ T-lymphocytes play a key role in COPD pathogenesis, but cytokine profiles in circulating T-lymphocytes have not been well characterised.Here we report the analysis of peripheral blood T-cells from 30 stable COPD patients and 10 healthy never-smokers for interferon (IFN)-c, interleukin (IL)-4, tumour necrosis factor (TNF)-a and the T-helper 17 cytokines IL-17A, IL-17F and IL-22 by intracellular flow cytometry.We found significantly increased proportions of IFN-c+ and TNF-a+ CD8+ T-cells in COPD patients, when compared with healthy controls. This was most evident in patients with less severe disease. In contrast, expression profiles in circulating CD4+ T-cells were similar in COPD patients and healthy controls for all cytokines tested, except for IL-17F. COPD patients with more severely reduced diffusing capacity had lower proportions of IL-17A+ CD4+ T-cells. Proportions of IL-22+ cells in the CD4+ memory T-cell population were significantly increased in active smokers, when compared with past smokers.Collectively, this comprehensive cytokine analysis of circulating T-cells in COPD patients revealed a correlation for CD8+ T-cells between Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and IFN-c or TNF-a expression, but not for CD4+ T-cells.

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“…These studies have revealed association with several candidate loci such as chromosome 4q31 locus (HHIP), chromosome 4q22 locus (FAM13A) and chromosome 15q25 locus (CHRNA3/CHRNA5/IREB2), as summarised by SILVERMAN et al [12], but it remains unclear whether and how the respective genes encoded in these loci are involved in the pathophysiology of the disease.…”

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confidence: 99%

The EvA study: aims and strategy

Ziegler-Heitbrock¹,

Frankenberger²,

Heimbeck³

et al. 2012

Eur Respir J

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The EvA study is a European Union-funded project under the Seventh Framework Programme (FP7), which aims at defining new markers for chronic obstructive pulmonary disease (COPD) and its subtypes. The acronym is derived from emphysema versus airway disease, indicating that the project targets these two main phenotypes of the disease. The EvA study is based on the concept that emphysema and airway disease are governed by different pathophysiological processes, are driven by different genes and have differential gene expression in the lung. To define these genes, patients and non-COPD controls are recruited for clinical examination, lung function analysis and computed tomography (CT) of the lung. CT scans are used to define the phenotypes based on lung density and airway wall thickness. This is followed by bronchoscopy in order to obtain samples from the airways and the alveoli. These tissue samples, along with blood samples, are then subjected to genome-wide expression and association analysis and markers linked to the phenotypes are identified. The population of the EvA study is different from other COPD study populations, since patients with current oral glucocorticoids, antibiotics and exacerbations or current smokers are excluded, such that the signals detected in the molecular analysis are due to the distinct inflammatory process of emphysema and airway disease in COPD.

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Opportunities and Challenges in the Genetics of COPD 2010: An International COPD Genetics Conference Report

Cited by 45 publications

References 66 publications

Genetic Predisposition to Chronic Obstructive Pulmonary Disease and/or Lung Cancer: Important Considerations When Evaluating Risk

Genetic Predisposition to Chronic Obstructive Pulmonary Disease and/or Lung Cancer: Important Considerations When Evaluating Risk

Systemic CD4+ and CD8+ T-cell cytokine profiles correlate with GOLD stage in stable COPD

The EvA study: aims and strategy

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