Search

Background Circulating levels of the chitinase-like protein YKL-40 are influenced by genetic variation in its encoding gene (chitinase 3–like 1 [CHI3L1] ) and are increased in patients with several diseases, including asthma. Epigenetic regulation of circulating YKL-40 early in life is unknown. Objective We sought to determine (1) whether methylation levels at CHI3L1 CpG sites mediate the association of CHI3L1 single nucleotide polymorphisms (SNPs) with YKL-40 levels in the blood and (2) whether these biomarkers ( CHI3L1 SNPs, methylation profiles, and YKL-40 levels) are associated with asthma in early childhood. Methods We used data from up to 2405 participants from the Spanish Infancia y Medio Ambiente; the Swedish Barn/Children, Allergy, Milieu, Stockholm, Epidemiological survey; and the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohorts. Associations between 68 CHI3L1 SNPs, methylation levels at 14 CHI3L1 CpG sites in whole-blood DNA, and circulating YKL-40 levels at 4 years of age were tested by using correlation analysis, multivariable regression, and mediation analysis. Each of these biomarkers was also tested for association with asthma at 4 years of age by using multivariable logistic regression. Results YKL-40 levels were significantly associated with 7 SNPs and with methylation at 5 CpG sites. Consistent associations between these 7 SNPs (particularly rs10399931 and rs4950928) and 5 CpG sites were observed. Alleles linked to lower YKL-40 levels were associated with higher methylation levels. Participants with high YKL-40 levels (defined as the highest YKL-40 tertile) had increased odds for asthma compared with subjects with low YKL-40 levels (meta-analyzed adjusted odds ratio, 1.90 [95% CI, 1.08-3.36]). In contrast, neither SNPs nor methylation levels at CpG sites in CHI3L1 were associated with asthma. Conclusions The effects of CHI3L1 genetic variation on circulating YKL-40 levels are partly mediated by methylation profiles. In our study YKL-40 levels, but not CHI3L1 SNPs or methylation levels, were associated with childhood asthma. [ABSTRACT FROM AUTHOR]

The potential effect of gestational exposure to phthalates on the lung function levels during childhood is unclear. Therefore, we examined this association at different ages (from 4 to 11 years) and over the whole childhood. Specifically, we measured 9 phthalate metabolites (MEP, MiBP, MnBP, MCMHP, MBzP, MEHHP, MEOHP, MECPP, MEHP) in the urine of 641 gestating women from the INMA study (Spain) and the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1) and FEV 1 /FVC in their offspring at ages 4, 7, 9 and 11. We used linear regression and mixed linear regression with a random intercept for subject to assess the association between phthalates and lung function at each study visit and for the overall childhood, respectively. We also assessed the phthalate metabolites mixture effect on lung function using a Weighted Quantile Sum (WQS) regression. We observed that the phthalate metabolites gestational levels were consistently associated with lower FVC and FEV 1 at all ages, both when assessed individually and jointly as a mixture, although most associations were not statistically significant. Of note, a 10% increase in MiBP was related to lower FVC (−0.02 (−0.04, 0)) and FEV 1 z-scores (−0.02 (−0.04, −0.01) at age 4. Similar significant reductions in FVC were observed at ages 4 and 7 associated with an increase in MEP and MnBP, respectively, and for FEV 1 at age 4 associated with an increase in MBzP. WQS regression consistently identified MBzP as an important contributor to the phthalate mixture effect. We can conclude that the gestational exposure to phthalates was associated with children's lower FVC and FEV 1 , especially in early childhood, and in a statistically significant manner for MEP, MiBP, MBzP and MnBP. Given the ubiquity of phthalate exposure and its established endocrine disrupting effects in children, our findings support current regulations that limit phthalate exposure. [Display omitted] • Gestational phthalates exposure was associated with lower lung function at all ages. • The lung function decline was stronger in younger than in older children. • The reduction in lung function observed at 4 and 7 years was not persistent. • MiBP and MBzP were the key phthalate metabolites driving the lung function reduction. [ABSTRACT FROM AUTHOR]

Folate is implicated in carcinogenesis via effects on DNA synthesis, repair, and methylation. Efficient folate metabolism requires other B vitamins and is adversely affected by smoking and alcohol. Esophageal adenocarcinoma (EAC) may develop through a process involving inflammation [reflux esophagitis (RE)] leading to metaplasia [Barrett's esophagus (BE)] and carcinoma. Within a population-based, case-control study, we investigated associations between dietary folate and related factors and risks of EAC, BE, and RE. EAC and BE cases had histologically confirmed disease; RE cases had endoscopically visible inflammation. Controls, age-sex frequency matched to EAC cases, were selected through population and general practice registers. Participants underwent structured interviews and completed food-frequency questionnaires. Multivariate ORs and 95% CIs were computed using logistic regression. A total of 256 controls and 223 EAC, 220 BE, and 219 RE cases participated. EAC risk decreased with increasing folate intake (OR highest vs. lowest = 0.56; 95% CI: 0.31, 1.00; P-trend < 0.01). Similar trends were found for BE (P-trend < 0.01) and RE (P-trend = 0.01). Vitamin B-6 intake was significantly inversely related to risks of all 3 lesions. Riboflavin intake was inversely associated with RE. Vitamin B-12 intake was positively associated with EAC. For EAC, there was a borderline significant interaction between folate intake and smoking (P-interaction = 0.053); compared with nonsmokers with high (≥ median) folate intake, current smokers with low intakes (

Background: YKL-40 is a chitinase-like protein that, in cross-sectional clinical studies, has been associated with severe asthma and COPD in smokers. Aim: To determine the longitudinal relation of circulating YKL-40 to levels and decline of lung function in the general population. Methods: We used longitudinal data from up to 13 surveys from the population-based TESAOD study which was conducted in Tucson, Arizona between 1972 and 1996. In cross-sectional analyses, we also used data from 3 Spanish centers of the multicenter ECRHS study (ECRHS-Sp). Serum YKL-40 was measured at baseline in TESAOD and in survey 2 in ECRHS-Sp using ELISAs. Multivariate linear regression was used to test associations of serum YKL-40 to concomitant lung function. In TESAOD, random coefficients models were used to test associations of serum YKL-40 to subsequent decline of lung function. Results: Data on YKL-40 and lung function were available from 1088 TESAOD and 854 ECRHS-Sp adult participants (59% and 51% females; respectively). In adjusted multivariate meta-analyses, being in the highest YKL-40 quartile was associated cross-sectionally with significant deficits in FEV1 and FVC %predicted. In adjusted longitudinal analyses, TESAOD participants in the top YKL-40 quartile had an FEV1 decline that was 5 ml/yr (p = 0.05) faster than subjects in the third quartile, 5 ml/yr (p = 0.02) faster than subjects in the second quartile, and 10 ml/yr (p < 0.001) faster than subjects in the lowest YKL-40 quartile. These longitudinal effects were particularly strong in smokers and absent in never smokers. After adjusting for covariates, as compared with the other three quartiles combined, the top YKL-40 quartile was associated with a 9 ml/yr (p = 0.001) faster FEV1 decline among smokers, while no significant effects were found among never smokers (2 ml/yr, p = 0.35). Conclusions: Circulating YKL-40 is associated with levels and decline of lung function in the general population and may be a biomarker of susceptibility to the long-term effects of cigarette smoking. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Our objective was to describe the geographical variation in cancer incidence using gastro-intestinal and non-melanoma skin cancer incidence data in Ireland using two different Bayesian spatial models and to compare the performance of these models. Methods: Cases diagnosed between 1994 and 2003 were extracted from the National Cancer Registry of Ireland. Population data were estimated from census data. For each of 3401 electoral divisions (EDs), relative risk (RR) estimates were calculated and smoothed using a conditional autoregressive model (CAR) and a spatial partition model introduced by Hegarty and Barry using a product partition model (PPM). The results were compared by mapping the ratio of the two RR estimates and other mainly descriptive statistics. Results: The two methods gave broadly similar results. For gastro-intestinal cancers the RRs were lower in a northwest/southeast band across the country with greater RRs around Dublin, Cork and in Donegal. Greater RR of non-melanoma skin cancer was observed in coastal areas. Median differences between the RR estimates were small (=0.01). The range of RRs was wider when estimated by the CAR model illustrating that the PPM smoothed the data to a greater extent than the CAR model. Conclusions: The two approaches gave similar results providing stronger evidence for the resulting geographical patterns. PPMs give a more global picture of the risk distribution whereas CAR models provide more local estimates. The observed patterns may reflect socio-demographic or geographic variations in risk factors or access to cancer services. By helping to identify those risks, these maps may help in the optimal allocation of scarce health resources. [Copyright &y& Elsevier]

Very few studies have examined the association between long-term outdoor air pollution and rhinitis severity in adults. We sought to assess the cross-sectional association between individual long-term exposure to air pollution and severity of rhinitis. Participants with rhinitis from 2 multicenter European cohorts (Epidemiological Study on the Genetics and Environment on Asthma and the European Community Respiratory Health Survey) were included. Annual exposure to NO 2 , PM 10 , PM 2.5 , and PM coarse (calculated by subtracting PM 2.5 from PM 10) was estimated using land-use regression models derived from the European Study of Cohorts for Air Pollution Effects project, at the participants' residential address. The score of rhinitis severity (range, 0-12), based on intensity of disturbance due to symptoms reported by questionnaire, was categorized into low (reference), mild, moderate, and high severity. Polytomous logistic regression models with a random intercept for city were used. A total of 1408 adults with rhinitis (mean age, 52 years; 46% men, 81% from the European Community Respiratory Health Survey) were included. The median (1st quartile-3rd quartile) score of rhinitis severity was 4 (2-6). Higher exposure to PM 10 was associated with higher rhinitis severity (adjusted odds ratio [95% CI] for a 10 μg/m3 increase in PM 10 : for mild: 1.20 [0.88-1.64], moderate: 1.53 [1.07-2.19], and high severity: 1.72 [1.23-2.41]). Similar results were found for PM 2.5. Higher exposure to NO 2 was associated with an increased severity of rhinitis, with similar adjusted odds ratios whatever the level of severity. Adjusted odds ratios were higher among participants without allergic sensitization than among those with, but interaction was found only for NO 2. People with rhinitis who live in areas with higher levels of pollution are more likely to report more severe nasal symptoms. Further work is required to elucidate the mechanisms of this association. [ABSTRACT FROM AUTHOR]

Objective: Living in an area with a high density of livestock farms has been associated with adverse respiratory health effects in some studies. As patients with COPD and asthma already have a compromised respiratory function and chronic airway inflammation, they are expected to be at increased risk for adverse respiratory health effects. The objective of this study was to assess the association between livestock exposure and exacerbations in COPD and asthma. Methods: 899 COPD and 2546 asthma patients from 15 general practices in a rural area with a high livestock density and 933 COPD and 2310 asthma patients from 15 practices in a control area in the Netherlands were included. Occurrence of exacerbations was based on the pharmaceutical treatment of exacerbations in COPD and asthma patients using 2006-2012 prescription data of electronic medical records. Farm exposure was assessed by comparing the study area with the control area, and with individual exposure estimates in the study area using Geographic Information System data. Results: The exacerbation rate was higher in the study area compared with the control area in COPD (IRR: 1.28; 95%CI: 1.06-1.55), but not in asthma patients (IRR: 0.87; 95%CI: 0.72-1.05). In general, individual exposure estimates in the study area were not associated with exacerbations. COPD patients living within a 500m radius of up to12,499 chickens had a 36% higher exacerbation rate (IRR: 1.36; 95%CI: 1.03-1.79). Conclusions: Living in an area with a high livestock density is a risk factor for exacerbations in COPD patients. The environmental exposure responsible for this increased risk remains to be elucidated. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Primary care physicians are increasingly being asked to participate in postal surveys. Difficulties in achieving adequate response rates among physicians have been reported. We investigated the effect of two low-cost interventions on response to a primary care physician postal questionnaire. Study Design and Setting: A 2×2 factorial trial was developed within the context of a national survey assessing views and practices of physicians regarding prostate-specific antigen testing. We evaluated questionnaire order (version 1: demographics first, version 2: topic-specific questions first) and written precontact. A national database of primary care physicians was compiled. One thousand five hundred ninety-nine physicians were randomly selected, stratified by health board, and randomized. Results: 47.9% of eligible physicians completed a questionnaire. There was a statistically significant 5.1% higher response rate among physicians receiving version 1 of the questionnaire than those receiving version 2 (50.6% vs. 45.4%, P =0.05); the adjusted odds of response were significantly raised (odds ratio=1.24; 95% confidence interval=1.01–1.54). Precontact resulted in a nonsignificant 3.6% increase in response (49.8% vs. 46.2%; P =0.16). The interventions did not interact. Conclusion: Ordering questionnaires with general questions first can significantly increase response rates, whereas precontact can achieve a modest increase. These strategies may enhance response while adding little to the cost of a physician survey. [Copyright &y& Elsevier]

Background The association between air pollution and rhinitis is not well established. Aim The aim of this longitudinal analysis was to study the association between modeled air pollution at the subjects' home addresses and self-reported incidence of rhinitis. Methods We used data from 1533 adults from two multicentre cohorts' studies (EGEA and ECRHS). Rhinitis incidence was defined as reporting rhinitis at the second follow-up (2011 to 2013) but not at the first follow-up (2000 to 2007). Annual exposure to NO 2 , PM 10 and PM 2.5 at the participants' home addresses was estimated using land-use regression models developed by the ESCAPE project for the 2009–2010 period. Incidence rate ratios (IRR) were computed using Poisson regression. Pooled analysis, analyses by city and meta-regression testing for heterogeneity were carried out. Results No association between long-term air pollution exposure and incidence of rhinitis was found (adjusted IRR (aIRR) for an increase of 10 μg·m −3 of NO 2: 1.00 [0.91–1.09], for an increase of 5 μg·m −3 of PM 2.5 : 0.88 [0.73–1.04]). Similar results were found in the two-pollutant model (aIRR for an increase of 10 μg·m −3 of NO 2: 1.01 [0.87–1.17], for an increase of 5 μg·m −3 of PM 2.5 : 0.87 [0.68–1.08]). Results differed depending on the city, but no regional pattern emerged for any of the pollutants. Conclusions This study did not find any consistent evidence of an association between long-term air pollution and incident rhinitis. [ABSTRACT FROM AUTHOR]

Background Inconsistent associations between socioeconomic position (SEP) and outdoor air pollution have been reported in Europe, but methodological differences prevent any direct between-study comparison. Objectives Assess and compare the association between SEP and outdoor nitrogen dioxide (NO 2 ) exposure as a marker of traffic exhaust, in 16 cities from eight Western European countries. Methods Three SEP indicators, two defined at individual-level (education and occupation) and one at neighborhood-level (unemployment rate) were assessed in three European multicenter cohorts. NO 2 annual concentration exposure was estimated at participants' addresses with land use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE; http://www.escapeproject.eu /). Pooled and city-specific linear regressions were used to analyze associations between each SEP indicator and NO 2 . Heterogeneity across cities was assessed using the Higgins' I-squared test (I 2 ). Results The study population included 5692 participants. Pooled analysis showed that participants with lower individual-SEP were less exposed to NO 2 . Conversely, participants living in neighborhoods with higher unemployment rate were more exposed. City-specific results exhibited strong heterogeneity (I 2 > 76% for the three SEP indicators) resulting in variation of the individual- and neighborhood-SEP patterns of NO 2 exposure across cities. The coefficients from a model that included both individual- and neighborhood-SEP indicators were similar to the unadjusted coefficients, suggesting independent associations. Conclusions Our study showed for the first time using homogenized measures of outcome and exposure across 16 cities the important heterogeneity regarding the association between SEP and NO 2 in Western Europe. Importantly, our results showed that individual- and neighborhood-SEP indicators capture different aspects of the association between SEP and exposure to air pollution, stressing the importance of considering both in air pollution health effects studies. [ABSTRACT FROM AUTHOR]

Abstract: Bisphenol A (BPA) exposure during early life may have endocrine-disrupting effects, but the dietary and sociodemographic predictors of BPA exposure during pregnancy and childhood remain unclear. Our aim was to evaluate the correlations between, and sociodemographic and dietary predictors of, serial urinary BPA concentrations measured during pregnancy and childhood in a Spanish birth cohort study. BPA was measured in two spot urine samples collected from 479 women during the first and third trimester of pregnancy and in one urine sample from their 4-year old children (n=130). Average dietary intakes were reported in food frequency questionnaires during the first and third pregnancy trimester and at age 4years. Multivariate mixed models and linear regression models were used to estimate associations between sociodemographic and dietary factors and BPA concentrations. A small, but statistically significant correlation was found between serial maternal BPA concentrations measured during pregnancy (r=0.17). Pregnant women who were younger, less-educated, smoked, and who were exposed to second-hand tobacco smoke (SHS) had higher BPA concentrations than others. BPA concentrations were also higher in children exposed to SHS. High consumption of canned fish during pregnancy was associated with 21% [GM ratio=1.21; 95%CI 1.02, 1.44] and 25% [GM ratio=1.25; 95%CI 1.05, 1.49] higher urinary BPA concentrations in the first and third pregnancy trimester, respectively, compared to the lowest consumption group. This study suggests that canned fish may be a major source of BPA during pregnancy in Spain, a country of high canned fish consumption. Further evaluation of specific BPA exposure sources in the sociodemographic group of younger women who smoke, are exposed to SHS, and have a low educational level is needed. Studies identifying sources of exposure would benefit from repeat BPA measurements and questionnaires specifically focused on dietary and packaging sources. [Copyright &y& Elsevier]