Shortened Telomeres in Circulating Leukocytes of Patients with Chronic Obstructive Pulmonary Disease

Savale, Laurent; Chaouat, Ari; Bastuji‐Garin, Sylvie; Marcos, Élisabeth; Boyer, Laurent; Maître, Bernard; Sarni, Mourad; Housset, B.; Weitzenblum, E; Matrat, M.; Corvoisier, Philippe Le; Rideau, Dominique; Boczkowski, Jorge; Dubois‐Randé, Jean‐Luc; Chouaïd, C.; Adnot, Serge

doi:10.1164/rccm.200809-1398oc

Cited by 271 publications

(165 citation statements)

References 31 publications

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“…In our cohort of 6770 individuals with COPD we found a 1.15-fold increased risk of COPD for individuals with the shortest telomere lengths compared with those with the longest telomere lengths. To contrast this with previous findings, Savale et al 25 compared 50 COPD patients with 50 matched control subjects and found a 28-fold increased risk of COPD for individuals with short telomere length compared with individuals with long telomere length. Two other small case–control studies were unable to show an association between telomere length and lung function but found an association between smoking exposure and telomere length 26 27.…”

Section: Discussionmentioning

confidence: 58%

Short telomere length, lung function and chronic obstructive pulmonary disease in 46 396 individuals

Rode

Bojesen

Weischer

et al. 2012

Thorax

138

106

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Section: Discussionmentioning

confidence: 58%

Short telomere length, lung function and chronic obstructive pulmonary disease in 46 396 individuals

Rode

Bojesen

Weischer

et al. 2012

Thorax

138

106

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“…This relationship has not been previously reported in HIV-associated COPD. In the HIV-uninfected population, PBMC telomere shortening has been independently associated with COPD presence and severity in multiple studies[58–61]. Telomere shortening is also a well-described feature of HIV infection[62–64], independent of the degree of immune suppression[63].…”

Section: Discussionmentioning

confidence: 99%

Relationships of pulmonary function, inflammation, and T-cell activation and senescence in an HIV-infected cohort

Fitzpatrick¹,

Singh²,

Bertolet

et al. 2014

Aids

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Objective To determine associations between circulating markers of immune activation, immune cell senescence, and inflammation with HIV-associated abnormalities of pulmonary function. Design HIV infection is an independent risk factor for abnormal pulmonary function. Immune activation, immune senescence, and chronic inflammation are characteristics of chronic HIV infection that have been associated with other HIV-associated comorbidities and may be related to pulmonary disease in this population. Methods Participants from an HIV-infected cohort (n=147) completed pulmonary function testing (PFT). Markers of T-cell activation and senescence were determined by flow cytometry, and plasma levels of interleukin (IL)-6, IL-8, and C-reactive protein (CRP) were measured, as was telomere length of peripheral blood mononuclear cells (PBMC). Regression models adjusting for clinical risk factors were constructed to examine relationships between biomarkers and PFT outcomes. Results Activated CD25+ T-cells and activated/senescent CD69+/CD57+/CD28null CD4+ T-cells, IL-6, and CRP were associated with PFT abnormalities. Shortening of PBMC telomere length correlated with airflow obstruction and diffusing impairment. Paradoxically, circulating senescent CD57+/CD28null CD8+ T-cells were associated with better PFT outcomes. Conclusions Circulating T-cells expressing markers of activation and inflammatory cytokine levels are independently correlated with PFT abnormalities in HIV-infected persons. Overall telomere shortening was also associated with pulmonary dysfunction. The paradoxical association of senescent CD8+ T-cells and better PFT outcomes could suggest an unrecognized beneficial compensatory function of such cells or a redistribution of these cells from the circulation to local compartments. Further studies are needed to differentiate and characterize functional subsets of local pulmonary and circulating T-cell populations in HIV-associated pulmonary dysfunction.

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“…Telomere shortening accelerates end-stage heart failure135 and several studies in diverse populations have shown an association, which exists before the development of clinical disease, between shorter telomeres in circulating leucocytes and both CAD and coronary artery calcification 136 137. The oxidative damage and chronic inflammation in COPD, originating from environmental irritants such as cigarette smoking and air pollution, may reduce telomere length in circulating cells138 139 with important downstream effects on auto-immunity,140 potentially explaining the persistence of lung inflammation in COPD despite many years of smoking cessation, driving telomere attrition and increasing cardiac risk over and above the risk associated with smoking. Inflammation and oxidative stress are involved in virtually all cardiovascular and associated diseases which may explain the wide number of conditions associated with telomere length141 and the emerging evidence points towards the potential use of telomere length as a marker of both cardiovascular and obstructive airways disease or as a therapeutic target 142…”

Section: Models Explaining the Interaction Between Copd And Cvdmentioning

confidence: 99%

Chronic obstructive pulmonary disease: a modifiable risk factor for cardiovascular disease?

Stone

Barnes

Petersen

2012

Heart

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Significant cardiac morbidity and mortality exists in patients with COPD. Shared risk factors include age, smoking history and exposure to air pollution and passive smoke. Although the inappropriate under-prescribing of β-blockers contributes, it is now appreciated that the observed cardiac risk is not only due to smoking and conventional cardiovascular risk factors, but also other independent factors. A number of hypotheses exist for the increased cardiovascular morbidity and mortality seen in COPD including inflammation, pulmonary hypertension, lung hyperinflation and shared genetics models. Mounting evidence from large randomised controlled trials suggests that COPD treatment may be cardio-protective. We review the current evidence supporting the aforementioned hypotheses and how their modulation may prevent cardiovascular morbidity and mortality in COPD. The persisting underdiagnosis of COPD may have significant consequences. Further mechanistic studies identifying the onset and impact of individual interventions will develop our understanding of this emerging and highly relevant clinical field.

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Shortened Telomeres in Circulating Leukocytes of Patients with Chronic Obstructive Pulmonary Disease

Abstract: Given that in vivo telomere length reflects cellular turnover and exposure to oxidative and inflammatory damage, our data support accelerated aging in COPD.

Cited by 271 publications

References 31 publications

Short telomere length, lung function and chronic obstructive pulmonary disease in 46 396 individuals

Short telomere length, lung function and chronic obstructive pulmonary disease in 46 396 individuals

Relationships of pulmonary function, inflammation, and T-cell activation and senescence in an HIV-infected cohort

Chronic obstructive pulmonary disease: a modifiable risk factor for cardiovascular disease?

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