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Accelerated ageing is implicated in the pathogenesis of respiratory diseases as chronic obstructive pulmonary disease (COPD), but recent evidence indicates that the COPD can have roots early in life. Here we hypothesise that the accelerated ageing markers might have a role in the pathobiology of young COPD. The objective of this study was to compare two hallmarks of ageing, telomere length (TL), and mitochondrial DNA copy number (mtDNA-CN, as a surrogate marker of mitochondrial dysfunction) in young (≤ 50 years) and old (>50 years) smokers, with and without COPD. Both, TL and mtDNA-CN were measured in whole blood DNA by quantitative PCR [qPCR] in: (1) young ever smokers with (n = 81) or without (n = 166) COPD; and (2) old ever smokers with (n = 159) or without (n = 29) COPD. A multivariable linear regression was used to assess the association of TL and mtDNA-CN with lung function. We observed that in the entire study population, TL and mtDNA-CN decreased with age, and the former but not the latter related to FEV1/FVC (%), FEV1 (% ref.), and DLCO (% ref.). The short telomeres were found both in the young and old patients with severe COPD (FEV1

Background: The Lung, hEart, sociAl, boDy (LEAD) Study (ClinicalTrials.gov; NCT01727518; http://clinicaltrials.gov) is a longitudinal, observational, population-based Austrian cohort that aims to investigate the relationship between genetic, environmental, social, developmental and ageing factors influencing respiratory health and comorbidities through life. The general working hypothesis of LEAD is the interaction of these genetic, environmental and socioeconomic factors influences lung development and ageing, the risk of occurrence of several non-communicable diseases (respiratory, cardiovascular, metabolic and neurologic), as well as their phenotypic (ie, clinical) presentation. Methods: LEAD invited from 2011–2016 a random sample (stratified by age, gender, residential area) of Vienna inhabitants (urban cohort) and all the inhabitants of six villages from Lower Austria (rural cohort). Participants will be followed-up every four years. A number of investigations and measurements were obtained in each of the four domains of the study (Lung, hEart, sociAl, boDy) including data to screen for lung, cardiovascular and metabolic diseases, osteoporosis, and cognitive function. Blood and urine samples are stored in a biobank for future investigations. Results: A total of 11.423 males (47.6%) and females (52.4%), aged 6–80 years have been included in the cohort. Compared to governmental statistics, the external validity of LEAD with respect to age, gender, citizenship, and smoking status was high. Conclusions: In conclusion, the LEAD cohort has been established following high quality standards; it is representative of the Austrian population and offers a platform to understand lung development and ageing as a key mechanism of human health both in early and late adulthood.

Introduction: Statins may have pleiotropic effects in COPD, but mechanisms remain unclear. Objectives: To assess the pleiotropic effect of statins in patients with stable COPD on (1): lung function (2); pulmonary and systemic inflammation (3); endothelial function (vascular stiffness) and circulating vascular growth factors; and (4), serum uric acid levels. Method: Pilot, double-blind, randomized, placebo-controlled clinical trial in 24 patients with stable COPD, all statin-naïve, who were randomized (1:1) to receive simvastatin 40 mg/24 h during 12 weeks (n = 12; 69.0 ± 7.3 years; post-bd FEV1 53.4 ± 10.0% pred.) or placebo (n = 12; 66.4 ± 4.6 years; post-bd FEV1 48.2 ± 12.6% pred.). Nine patients per group (total n = 18) completed the study. Results: Lung function, pulmonary and systemic inflammatory markers and the degree of vascular stiffness did not change significantly in any group. However, treatment with simvastatin increased the plasma levels of erythropoietin (Epo) (4.2 ± 2.2 mIU/mL to 6.8 ± 3.2 mlU/mL, p

Este artículo presenta una visión personal sobre la investigación clínica. La información presentada no está basada en la evidencia. Por tanto, todas las opiniones vertidas son discutibles y, probablemente, erróneas. En primer lugar discute qué debe entenderse por investigación clínica y el porque de su relevancia, no sólo intrínseca (per se) sino también aquella derivada de una serie de "efectos colaterales" que, a juicio del autor son importantes en el ámbito del sistema nacional de salud y no son siempre apreciados o valorados. En la segunda parte del artículo se proponen una serie de "requisitos" para poder realizar investigación clínica y se anticipa (si es que ello es posible) cual será el futuro (posiblemente ya el presente) de la investigación clínica que, de nuevo a juicio del autor, pasa ineludiblemente por la multi-disciplinariedad y la multi-centricidad. De ahí, la importancia estratégica de los diversos proyectos de investigación "en red" propuestos tanto a nivel nacional (www.retics.net) como europeo (VI Programa Marco) o norte-americano (National Institutes of Health).This article presents a very personal view of clinical research. It is not evidence based. Thus, all the opinions included are arguable and even likely to be incorrect. It first discusses what is clinical research. Then, it highlights the reasons underlying the key importance of clinical research within the broader field of biomedical research. Some of these reasons are self-evident whereas others are often missed or ignored in the context of the public health systems. In the last part of the paper, the type and extent of knowledge required by someone interested in developing a career in clinical research is also discussed. Finally, the "future" of clinical research is anticipated, although it is recognized that this future is already here (at least its beginning). It is the opinion of the author that future clinical research will be based upon two fundamental aspects: the collaboration between different scientific disciplines and the need of having different groups of investigators participating in the research project. It is in this context where the strategic importance of the new "research networks" promoted by both the European Union (VI Framework Programme) and the USA (National Institutes of Health) can be fully appreciated. In our country, this vision has been promoted by the Instituto de Salud Carlos III (specific information can be found at www.retics.net).

Este artículo presenta una visión personal sobre la investigación clínica. La información presentada no está basada en la evidencia. Por tanto, todas las opiniones vertidas son discutibles y, probablemente, erróneas. En primer lugar discute qué debe entenderse por investigación clínica y el porque de su relevancia, no sólo intrínseca (per se) sino también aquella derivada de una serie de "efectos colaterales" que, a juicio del autor son importantes en el ámbito del sistema nacional de salud y no son siempre apreciados o valorados. En la segunda parte del artículo se proponen una serie de "requisitos" para poder realizar investigación clínica y se anticipa (si es que ello es posible) cual será el futuro (posiblemente ya el presente) de la investigación clínica que, de nuevo a juicio del autor, pasa ineludiblemente por la multi-disciplinariedad y la multi-centricidad. De ahí, la importancia estratégica de los diversos proyectos de investigación "en red" propuestos tanto a nivel nacional (www.retics.net) como europeo (VI Programa Marco) o norte-americano (National Institutes of Health).