Risk factors and early origins of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease is mainly a smoking-related disorder and affects millions of people worldwide, with a large effect on individual patients and society as a whole. Although the disease becomes clinically apparent around the age of 40-50 years, its origins can begin very early in life. Different risk factors in very early life--ie, in utero and during early childhood--drive the development of clinically apparent chronic obstructive pulmonary disease in later life.

Effects of small airway dysfunction on the clinical expression of asthma: a focus on asthma symptoms and bronchial hyper-responsiveness.

Background: The small airways are an important site of inflammation in asthma. However, the relation between small airway dysfunction and clinical expression of asthma has hardly been studied.

Aim: To investigate the association of small and large airway dysfunction with asthma symptoms and bronchial hyper-responsiveness (BHR).

Susceptibility to COPD: differential proteomic profiling after acute smoking.

Cigarette smoking is the main risk factor for COPD (Chronic Obstructive Pulmonary Disease), yet only a subset of smokers develops COPD. Family members of patients with severe early-onset COPD have an increased risk to develop COPD and are therefore defined as "susceptible individuals". Here we perform unbiased analyses of proteomic profiles to assess how "susceptible individuals" differ from age-matched "non-susceptible individuals" in response to cigarette smoking.

Advanced glycation end products in the skin are enhanced in COPD.

Background: Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD) inducing oxidative stress and local tissue injury, resulting in pulmonary inflammation. Advanced glycation end products (AGEs) are produced by glycation and oxidation processes and their formation is accelerated in inflammatory conditions. In this study we assessed whether AGE accumulation in the skin is elevated in COPD and associates with disease severity.

Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis.

Asthma and chronic obstructive pulmonary disease (COPD) are thought to share a genetic background ("Dutch hypothesis"). We investigated whether asthma and COPD have common underlying genetic factors, performing genome-wide association studies for both asthma and COPD and combining the results in meta-analyses. Three loci showed potential involvement in both diseases: chr2p24.

A large lung gene expression study identifying fibulin-5 as a novel player in tissue repair in COPD.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive, incurable lung disease characterised by abnormal tissue repair causing emphysema and small airways fibrosis. Since current therapy cannot modify this abnormal repair, it is crucial to unravel its underlying molecular mechanisms. Unbiased analysis of genome-wide gene expression profiles in lung tissue provides a powerful tool to investigate this.

Effects of cigarette smoke extract on human airway smooth muscle cells in COPD.

We hypothesised that the response to cigarette smoke in airway smooth muscle (ASM) cells from smokers with chronic obstructive pulmonary disease (COPD) would be intrinsically different from smokers without COPD, producing greater pro-inflammatory mediators and factors relating to airway remodelling. ASM cells were obtained from smokers with or without COPD, and then stimulated with cigarette smoke extract (CSE) or transforming growth factor-β1. The production of chemokines and matrix metalloproteinases (MMPs) were measured by ELISA, and the deposition of collagens by extracellular matrix ELISA.

Associations between particulate matter elements and early-life pneumonia in seven birth cohorts: results from the ESCAPE and TRANSPHORM projects.

Evidence for a role of long-term particulate matter exposure on acute respiratory infections is growing. However, which components of particulate matter may be causative remains largely unknown. We assessed associations between eight particulate matter elements and early-life pneumonia in seven birth cohort studies (N total=15,980): BAMSE (Sweden), GASPII (Italy), GINIplus and LISAplus (Germany), INMA (Spain), MAAS (United Kingdom) and PIAMA (The Netherlands).

Screen time, adiposity and cardiometabolic markers: mediation by physical activity, not snacking, among 11-year-old children.

Background: There is evidence for a relation of TV viewing with adiposity and increased cardiometabolic risk factors in children and adolescents. It is unclear to what extent this relation is mediated by snacking and lack of physical activity. We determined whether associations of screen time with adiposity and cardiometabolic markers were mediated by these behaviours.

Co-morbidities are the key nominators of the health related quality of life in mild and moderate COPD.

Background: Co-morbidities are common in chronic obstructive pulmonary disease (COPD). We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients.

Methods: Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis.

Genome-wide association analysis identifies six new loci associated with forced vital capacity.

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2.

Integrated care pathways for airway diseases (AIRWAYS-ICPs).

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies.

Pharmacogenetic analysis of GLCCI1 in three north European pediatric asthma populations with a reported use of inhaled corticosteroids.

Background: GLCCI1 rs37972 has previously been associated with decreased lung function improvement upon treatment with inhaled corticosteroids (ICS) in asthmatics.

Aim: To assess whether variation in rs37972 is associated with altered ICS efficacy in north European asthmatic children and young adults with a reported use of ICS.

Patients & Methods: rs37972 was genotyped in three cohort studies of asthmatic children with a reported use of ICS.

Untargeted lipidomic analysis in chronic obstructive pulmonary disease. Uncovering sphingolipids.

Rationale: Cigarette smoke is the major risk factor in the development of chronic obstructive pulmonary disease (COPD). Lipidomics is a novel and emerging research field that may provide new insights in the origins of chronic inflammatory diseases, such as COPD.

Objectives: To investigate whether expression of the sputum lipidome is affected by COPD or cigarette smoking.

Antibiotic treatment of moderate-severe community-acquired pneumonia: design and rationale of a multicentre cluster-randomised cross-over trial.

Background: For the empirical treatment of community-acquired pneumonia requiring admission to a non-ICU ward, the Dutch guidelines recommend either beta-lactam monotherapy, beta-lactam and macrolide combination therapy, or fluoroquinolone monotherapy. The lack of convincing evidence to preferentially recommend any of the three empiric regimens results from intrinsic limitations of current studies, such as bias by indication and residual confounding in observational studies, and the unknown effects of pre-randomisation antibiotic use in randomised controlled trials. In this paper we discuss the methodological drawbacks of observational cohorts and randomised controlled trials in antibiotic therapy.

A novel 6-mercaptopurine oral liquid formulation for pediatric acute lymphoblastic leukemia patients - results of a randomized clinical trial.

Objective: Pediatric patients with acute lymphoblastic leukemia (ALL) are treated with oral 6-mercaptopurine (6MP) for nearly 2 years, but no pediatric formulation has been available. In this study, an oral 6MP liquid suitable for pediatric use was developed and tested in the target population.

Method: A randomized cross-over study was performed in 20 pediatric ALL patients (age 1.

Association of occupational pesticide exposure with accelerated longitudinal decline in lung function.

Cross-sectional studies have shown that occupational exposure to vapors, gases, dusts, and fumes (VGDF) and pesticides is associated with a lower level of lung function. These associations seem to be stronger in ever smokers. In the current study, we aimed to assess whether occupational exposure to VGDF and pesticides is associated with longitudinal decline in lung function.

Susceptibility to chronic mucus hypersecretion, a genome wide association study.

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution.

Keeping your eyes continuously on the ball while running for catchable and uncatchable fly balls.

When faced with a fly ball approaching along the sagittal plane, fielders need information for the control of their running to the interception location. This information could be available in the initial part of the ball trajectory, such that the interception location can be predicted from its initial conditions. Alternatively, such predictive information is not available, and running to the interception location involves continuous visual guidance.

Risk factors for chronic mucus hypersecretion in individuals with and without COPD: influence of smoking and job exposure on CMH.

Background: Chronic mucus hypersecretion (CMH) is highly prevalent in smokers and associated with an accelerated lung function decline and chronic obstructive pulmonary disease (COPD). Several risk factors contribute to CMH and to COPD. It is, however, unknown if risk factors for CMH are similar in persons with and without COPD.