Changes in forced expiratory volume in 1 second over time in COPD.

Background: A key feature of chronic obstructive pulmonary disease (COPD) is an accelerated rate of decline in forced expiratory volume in 1 second (FEV(1)), but data on the variability and determinants of this change in patients who have established disease are scarce.

Methods: We analyzed the changes in FEV(1) after administration of a bronchodilator over a 3-year period in 2163 patients. A random-coefficient model was used to evaluate possible predictors of both FEV(1) levels and their changes over time.

The influence of obesity and obstructive sleep apnea on metabolic hormones.

Background: Obstructive sleep apnea syndrome (OSAS) is a common disorder characterized by excessive daytime sleepiness and repetitive upper airway obstruction episodes during sleep. Clinically, obesity is a major risk factor for developing OSAS. However, OSAS has been associated with hormonal and metabolic alterations that could predispose patients to obesity.

Night-time symptoms: a forgotten dimension of COPD.

Sleep quality is often poor in patients with chronic obstructive pulmonary disease (COPD), but these night-time symptoms are frequently unnoticed by physicians and/or not reported by patients themselves. Therefore, the prevalence and clinical impact of sleep disturbances and night-time symptoms in COPD is not well understood and has not been a clinical focus to date. To address this gap, an expert panel meeting was convened in Barcelona, Spain, in March 2011 to discuss the aetiology, evolution, burden, long-term clinical consequences and optimal management of night-time symptoms in COPD.

Day-night variations in endothelial dysfunction markers and haemostatic factors in sleep apnoea.

Patients with sleep apnoea have a significant alteration in the day-night pattern of myocardial infarction and sudden cardiac death observed in the general population. The aim of this study was to investigate the influence of sleep apnoea on the diurnal variations in various haemostatic parameters (factor VII, von Willebrand factor and plasminogen activator inhibitor (PAI)-1) and markers of endothelial dysfunction (asymmetric dimethylarginine (ADMA) and soluble CD40 ligand (sCD40L)). We studied 26 male patients with obstructive sleep apnoea syndrome (OSAS; 13 patients with severe OSAS (apnoea/hypopnoea index (AHI) >30 events · h(-1)) and 13 patients with mild-to-moderate OSAS (AHI <30 events · h(-1))) and 12 controls of similar body mass index (BMI) and waist circumference.

Predicting outcomes from 6-minute walk distance in chronic obstructive pulmonary disease.

Background: Exercise tolerance is an important clinical aspect of chronic obstructive pulmonary disease that can be easily and reliably measured with the 6-minute walking test (6MWT). To improve the utility of the 6MWT for patient and health care system management, the interpretation of the functional status measure in relation to death and hospitalization should be elucidated.

Methods: Three-year, prospective, multicenter observational study to evaluate the predictive power of 6MWD for death or exacerbation-related hospitalization and to evaluate the factors that help determine 6MWD.

Systems medicine and integrated care to combat chronic noncommunicable diseases.

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes.

Differential modulation of the glutamate-nitric oxide-cyclic GMP pathway by distinct neurosteroids in cerebellum in vivo.

The glutamate-nitric oxide (NO)-cGMP pathway mediates many responses to activation of N-methyl-d-aspartate (NMDA) receptors, including modulation of some types of learning and memory. The glutamate-NO-cGMP pathway is modulated by GABAergic neurotransmission. Activation of GABA(A) receptors reduces the function of the pathway.

Current controversies and future perspectives in chronic obstructive pulmonary disease.

Over the past decade there has been much research and interest in COPD. As a result, the understanding and management of the disease has improved significantly. Yet, there are many uncertainties and controversies that require further work.

p38 MAP kinase is a therapeutic target for hepatic encephalopathy in rats with portacaval shunts.

Objective: Inflammation plays a role in neurological alterations in patients with hepatic encephalopathy (HE). Animal models of HE show neuroinflammation. Treatment with ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), reduces neuroinflammation and restores cognitive and motor function in rats with HE due to portacaval shunts (PCS).

Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease.

Background: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Methods: In two double-blind, 52-week studies, ACCLAIM/COPD I (n=843) and II (n=804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1<80% of the predicted value.

Molecular mechanisms of inflammation during exacerbations of chronic obstructive pulmonary disease.

Introduction: Exacerbations of chronic obstructive pulmonary disease (COPD) are characterised by an inflammatory and systemic response that persists for some time after their clinical resolution. The mechanisms of this inflammatory process are not well known.

Objectives: To explore the inflammatory changes and possible mechanisms during COPD exacerbation.

Impaired circadian variation of platelet activity in patients with sleep apnea.

Background: Cardiovascular diseases are frequent in patients with obstructive sleep apnea (OSAS). There is evidence that the day-night pattern of myocardial infarction and sudden cardiac death observed in the general population is altered in patients with OSAS. This study investigates potential abnormalities in the circadian profiles of platelet activity in OSAS.

[Clinical phenotypes of COPD].

Chronic obstructive pulmonary disease (COPD) is a complex, multifaceted disease. The clinical presentation is highly heterogeneous and consequently, within what is known today as COPD, there may be some groups (phenotypes) of patients who share clinical and/or biological characteristics but who have distinct prognoses and/or who require different therapeutic approaches. In its broadest sense, phenotype is defined as any observable characteristic in the body, but "clinical phenotype" is defined as a characteristic or set of characteristics of a disease that can be used to distinguish individuals with COPD and are related to significant clinical outcomes, such as symptoms, exacerbations, treatment response, disease progression or death.

P4 medicine: the future around the corner.

Traditional medical practice has been "reactive" (doctor takes part when disease appears). The theoretical (scale free networks and complex systems), technological (high efficiency "omic" technologies) and conceptual (biology systems) advances throughout the last decade, allow us to anticipate the transition to an "anticipatory" medicine, based on health (not on disease). This review establishes the conceptual bases and discusses the principal aspects of this new medicine, known as "P4 Medicine" standing for personalized, predictive, preventive and participatory.

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

Background: Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes.

Methods: To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited.

Addressing the complexity of chronic obstructive pulmonary disease: from phenotypes and biomarkers to scale-free networks, systems biology, and P4 medicine.

Chronic obstructive pulmonary disease (COPD) is a complex disease at the clinical, cellular, and molecular levels. However, its diagnosis, assessment, and therapeutic management are based almost exclusively on the severity of airflow limitation. A better understanding of the multiple dimensions of COPD and its relationship to other diseases is very relevant and of high current interest.

Effects of exercise on mitochondrial DNA content in skeletal muscle of patients with COPD.

Background: Exhausting exercise reduces the mitochondrial DNA (mtDNA) content in the skeletal muscle of healthy subjects due to oxidative damage. Since patients with chronic obstructive pulmonary disease (COPD) suffer enhanced oxidative stress during exercise, it was hypothesised that the mtDNA content will be further reduced.

Objective: To investigate the effects of exercise above and below the lactate threshold (LT) on the mtDNA content of skeletal muscle of patients with COPD.

Anti-tissue antibodies are related to lung function in chronic obstructive pulmonary disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is a multicomponent disease. Autoimmunity can contribute to the pathogenesis of COPD.

Objectives: This study investigates the prevalence of circulating antinuclear antibodies (ANA) and anti-tissue (AT) antibodies, two common markers of autoimmunity, in COPD and their relationship with several components of the disease.

Educational sessions in pharmacovigilance: What do the doctors think?

Background: The aim of this study was to determine physicians' opinion regarding pharmacovigilance feedback sessions. A survey was conducted in a teaching hospital, and the physicians who attended the sessions were invited to participate by filling out a structured questionnaire. All sessions included a review of adverse drug reactions identified at the hospital and information on pharmacovigilance issues (news on warnings released by regulatory agencies or drug toxicity problems identified by recently published studies in medical journals).