Worldwide patterns of bronchodilator responsiveness: results from the Burden of Obstructive Lung Disease study.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Criteria for a clinically significant bronchodilator response (BDR) are mainly based on studies in patients with obstructive lung diseases. Little is known about the BDR in healthy general populations, and even less about the worldwide patterns. 10 360 adults aged 40 years and older from 14 countries in North America, Europe, Africa and Asia participated in the Burden of Obstructive Lung Disease study. Spirometry was used before and after an inhaled bronchodilator to determine the distribution of the BDR in population-based samples of healthy non-smokers and individuals with airflow obstruction. In 3922 healthy never smokers, the weighted pooled estimate of the 95th percentiles (95% CI) for bronchodilator response were 284 ml (263 to 305) absolute change in forced expiratory volume in 1 s from baseline (ΔFEV(1)); 12.0% (11.2% to 12.8%) change relative to initial value (%ΔFEV(1i)); and 10.0% (9.5% to 10.5%) change relative to predicted value (%ΔFEV(1p)). The corresponding mean changes in forced vital capacity (FVC) were 322 ml (271 to 373) absolute change from baseline (ΔFVC); 10.5% (8.9% to 12.0%) change relative to initial value (ΔFVC(i)); and 9.2% (7.9% to 10.5%) change relative to predicted value (ΔFVC(p)). The proportion who exceeded the above threshold values in the subgroup with spirometrically defined Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 and higher (FEV(1)/FVC <0.7 and FEV(1)% predicted <80%) were 11.1%, 30.8% and 12.9% respectively for the FEV(1)-based thresholds and 22.6%, 28.6% and 22.1% respectively for the FVC-based thresholds. The results provide reference values for bronchodilator responses worldwide that confirm guideline estimates for a clinically significant level of BDR in bronchodilator testing.ALTANA Aventis AstraZeneca Boehringer-Ingelheim Chiesi GlaxoSmithKline Merck Novartis Pfizer Schering-Plough Sepracor University of Kentucky Boehringer Ingelheim Schering Ploug

Is fruit and vegetable intake associated with asthma or chronic rhino-sinusitis in European adults? Results from the Global Allergy and Asthma Network of Excellence (GA(2)LEN) Survey

Background: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases. Objective: We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults. Methods: A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA(2)LEN) screening survey, in which 55,000 adults aged 15-75 answered a questionnaire on respiratory symptoms. Asthma score (derived from self-reported asthma symptoms) and CRS were the outcomes of interest. Dietary intake of 22 subgroups of fruits and vegetables was ascertained using the internationally validated GA(2)LEN Food Frequency Questionnaire. Adjusted associations were examined with negative binomial and multiple regressions. Simes procedure was used to control for multiple testing. Results: A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8% reported having at least 1 asthma symptom (asthma score >= 1), whilst 19.5% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (beta-coefficient -2.34;95% confidence interval [CI] -4.09,-0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and alliums vegetables (adjusted beta-coefficient 0.23; 95% CI 0.06, 0.40). None of these associations remained statistically significant after controlling for multiple testing. Conclusion and clinical relevance: There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults.Peer reviewe

Lung Development Genes and Adult Lung Function

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Dietary Intake of Flavonoids and Ventilatory Function in European Adults : A GA(2)LEN Study

Background: Flavonoids exert anti-inflammatory properties and modulate oxidative stress in vitro, suggesting a protective effect on lung function, but epidemiological studies examining this association are scarce. Methods: A stratified random sample was drawn from the GA(2)LEN screening survey, in which 55,000 adults aged 15 to 75 answered a questionnaire on respiratory symptoms. Post-bronchodilator spirometry was obtained from 2850 subjects. Forced vital capacity (FVC), the ratio between the forced exhaled volume in 1 second (FEV1) and FVC (FEV1/FVC), FVC below lower limit of normal (FVC <LLN), and FEV1/FVC <LLN were calculated. Intake of the six main subclasses of flavonoids was estimated using the GA(2)LEN Food Frequency Questionnaire. Adjusted associations between outcomes and each subclass of flavonoids were examined with multivariate regressions. Simes' procedure was used to test for multiple comparisons. Results: A total of 2599 subjects had valid lung function and dietary data. A lower prevalence of FVC <LLN (airway restriction) was observed in those with higher total flavonoid (adjusted odds ratio (aOR), higher vs. lowest quintile intake 0.58; 95% Confidence Interval (CI) 0.36, 0.94), and pro-anthocyanidin intakes (aOR 0.47; 95% CI 0.27, 0.81). A higher FEV1/FVC was associated with higher intakes of total flavonoids and pro-anthocyanidins (adjusted correlation coefficient (a -coeff 0.33; 0.10, 0.57 and a -coeff 0.44; 95% CI 0.19, 0.69, respectively). After Simes' procedure, the statistical significance of each of these associations was attenuated but remained below 0.05, with the exception of total flavonoids and airway restriction. Conclusions: This population-based study in European adults provides cross-sectional evidence of a positive association of total flavonoid intake and pro-anthocyanidins and ventilatory function, and a negative association with spirometric restriction in European adults.Peer reviewe

“It ain’t (just) what you do, it’s (also) the way that you do it”: The role of Procedural Justice in the Implementation of Anti-social Behaviour Interventions with Young People

This paper provides an analysis of the introduction and implementation of hybrid powers to regulate anti-social behaviour, during a period of regulatory ‘hyperactivity’ in the UK. It explores the role of procedural justice by drawing on findings from a study conducted in England which investigated the implementation practices and experiences of young people and parents. These are considered against seven characteristics of procedural justice: voice; voluntariness; respectful treatment; parsimony; accuracy of information; fairness; and neutrality. The paper analyses the manner in which principles of voluntary cooperation can be corrupted by threats of punitive sanctions. It questions the extent to which the use of such hybrid orders fosters perceptions of legitimacy and supports the capacity of young people to avoid criminalisation

The association between chronic airflow obstruction and poverty in 12 sites of the multinational BOLD study.

Poverty is strongly associated with mortality from COPD, but little is known of its relation to airflow obstruction.In a cross-sectional study of adults aged ≥40 years from 12 sites (N=9255), participating in the Burden of Obstructive Lung Disease (BOLD) study, poverty was evaluated using a wealth score (0-10) based on household assets. Obstruction, measured as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (%) after administration of 200 μg salbutamol, and prevalence of FEV1/FVC<lower limit of normal were tested for association with poverty for each site, and the results were combined by meta-analysis.Mean wealth scores ranged from 4 in Blantyre (Malawi) and Kashmir (India) to 10 in Riyadh (Saudi Arabia), and the prevalence of obstruction, from 16% in Kashmir to 3% in Riyadh and Penang (Malaysia). Following adjustments for age and sex, FEV1/FVC increased by 0.36% (absolute change) (95%CI: 0.22, 0.49; p<0.001) per unit increase in wealth score. Adjustments for other confounders reduced this effect to 0.23% (0.11, 0.34), but even this value remained highly significant (p<0.001). Results were consistent across sites (I(2)=1%; phet=0.44). Mean wealth scores explained 38% of the variation in mean FEV1/FVC between sites (r(2)=0.385, p=0.031).Airflow obstruction is consistently associated with poverty at individual and community levels across several countries

Chronic airflow obstruction and ambient particulate air pollution

Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised

Association of Forced Vital Capacity with the Developmental Gene <i>NCOR2</i>

Background Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. Methods Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 chi

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. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease