Spirometric patterns in young and middle-aged adults: a 20-year European study.

BACKGROUND: Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset). METHODS: We used data from the population-based cohort of the European Community Respiratory Health Survey (ECRHS). Prebronchodilator forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were assessed longitudinally at baseline (ECRHS1, 1993-1994) and again 20 years later (ECRHS3, 2010-2013). Spirometry patterns were defined as: restrictive if FEV1/FVC≥LLN and FVC<10th percentile, obstructive if FEV1/FVC

Air pollution and IgE sensitization in 4 European birth cohorts-the MeDALL project.

BACKGROUND: Whether long-term exposure air to pollution has effects on allergic sensitization is controversial. OBJECTIVE: Our aim was to investigate associations of air pollution exposure at birth and at the time of later biosampling with IgE sensitization against common food and inhalant allergens, or specific allergen molecules, in children aged up to 16 years. METHODS: A total of 6163 children from 4 European birth cohorts participating in the Mechanisms of the Development of ALLergy [MeDALL] consortium were included in this meta-analysis of the following studies: Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) (Sweden), Influences of Lifestyle-Related Factors on the Human Immune System and Development of Allergies in Childhood (LISA)/German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development (GINIplus) (Germany), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA) (The Netherlands). The following indicators were modeled by land use regression: individual residential outdoor levels of particulate matter with aerodynamic diameters less than 2.5 µm, less than 10 µm, and between 2.5 and 10 µm; PM2.5 absorbance (a measurement of the blackness of PM2.5 filters); and nitrogen oxides levels. Blood samples drawn at ages 4 to 6 (n = 5989), 8 to 10 (n = 6603), and 15 to 16 (n = 5825) years were analyzed for IgE sensitization to allergen extracts by ImmunoCAP. Additionally, IgE against 132 allergen molecules was measured by using the MedALL microarray chip (n = 1021). RESULTS: Air pollution was not consistently associated with IgE sensitization to any common allergen extract up to age 16 years. However, allergen-specific analyses suggested increased risks of sensitization to birch (odds ratio [OR] = 1.12 [95% CI = 1.01-1.25] per 10-µg/m3 increase in NO2 exposure). In a subpopulation with microarray data, IgE to the major timothy grass allergen Phleum pratense 1 (Phl p 1) and the cat allergen Felis domesticus 1 (Fel d 1) greater than 3.5 Immuno Solid-phase Allergen Chip standardized units for detection of IgE antibodies were related to PM2.5 exposure at birth (OR = 3.33 [95% CI = 1.40-7.94] and OR = 4.98 [95% CI = 1.59-15.60], respectively, per 5-µg/m3 increase in exposure). CONCLUSION: Air pollution exposure does not seem to increase the overall risk of allergic sensitization; however, sensitization to birch as well as grass pollen Phl p 1 and cat Fel d 1 allergen molecules may be related to specific pollutants.

Occupational exposures and incidence of chronic bronchitis and related symptoms over two decades: the European Community Respiratory Health Survey.

OBJECTIVES: Chronic bronchitis (CB) is an important chronic obstructive pulmonary disease (COPD)-related phenotype, with distinct clinical features and prognostic implications. Occupational exposures have been previously associated with increased risk of CB but few studies have examined this association prospectively using objective exposure assessment. We examined the effect of occupational exposures on CB incidence in the European Community Respiratory Health Survey. METHODS: Population samples aged 20-44 were randomly selected in 1991-1993, and followed up twice over 20 years. Participants without chronic cough or phlegm at baseline were analysed. Coded job histories during follow-up were linked to the ALOHA Job Exposure Matrix, generating occupational exposure estimates to 12 categories of chemical agents. Their association with CB incidence over both follow-ups was examined with Poisson models using generalised estimating equations. RESULTS: 8794 participants fulfilled the inclusion criteria, contributing 13 185 observations. Only participants exposed to metals had a higher incidence of CB (relative risk (RR) 1.70, 95% CI 1.16 to 2.50) compared with non-exposed to metals. Mineral dust exposure increased the incidence of chronic phlegm (RR 1.72, 95% CI 1.43 to 2.06). Incidence of chronic phlegm was increased in men exposed to gases/fumes and to solvents and in women exposed to pesticides. CONCLUSIONS: Occupational exposures are associated with chronic phlegm and CB, and the evidence is strongest for metals and mineral dust exposure. The observed differences between men and women warrant further investigation.

Genetic regulation of IL1RL1 methylation and IL1RL1-a protein levels in asthma.

Interleukin-1 receptor-like 1 (IL1RL1) is an important asthma gene. (Epi)genetic regulation of IL1RL1 protein expression has not been established. We assessed the association between IL1RL1 single nucleotide polymorphisms (SNPs), IL1RL1 methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma.Associations of IL1RL1 SNPs with asthma were determined in the Dutch Asthma Genome-wide Association Study cohort and three European birth cohorts, BAMSE (Children/Barn, Allergy, Milieu, Stockholm, an Epidemiological survey), INMA (Infancia y Medio Ambiente) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy), participating in the Mechanisms of the Development of Allergy study. We performed blood DNA IL1RL1 methylation quantitative trait locus (QTL) analysis (n=496) and (epi)genome-wide protein QTL analysis on serum IL1RL1-a levels (n=1462). We investigated the association of IL1RL1 CpG methylation with asthma (n=632) and IL1RL1-a levels (n=548), with subsequent causal inference testing. Finally, we determined the association of IL1RL1-a levels with asthma and its clinical characteristics (n=1101).IL1RL1 asthma-risk SNPs strongly associated with IL1RL1 methylation (rs1420101; p=3.7×10-16) and serum IL1RL1-a levels (p=2.8×10-56). IL1RL1 methylation was not associated with asthma or IL1RL1-a levels. IL1RL1-a levels negatively correlated with blood eosinophil counts, whereas there was no association between IL1RL1-a levels and asthma.In conclusion, asthma-associated IL1RL1 SNPs strongly regulate IL1RL1 methylation and serum IL1RL1-a levels, yet neither these IL1RL1-methylation CpG sites nor IL1RL1-a levels are associated with asthma.

Specific IgE and IgG measured by the MeDALL allergen-chip depend on allergen and route of exposure: The EGEA study.

BACKGROUND: The nature of allergens and route and dose of exposure may affect the natural development of IgE and IgG responses. OBJECTIVE: We sought to investigate the natural IgE and IgG responses toward a large panel of respiratory and food allergens in subjects exposed to different respiratory allergen loads. METHODS: A cross-sectional analysis was conducted in 340 adults of the EGEA (Epidemiological study of the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy) (170 with and 170 without asthma) cohort. IgE and IgG responses to 47 inhalant and food allergen components were analyzed in sera using allergen microarray and compared between 5 French regions according to the route of allergen exposure (inhaled vs food allergens). RESULTS: Overall 48.8% of the population had allergen-specific IgE levels of 0.3 ISAC standardized units (ISU) or more to at least 1 of the 47 allergens with no significant differences across the regions. For ubiquitous respiratory allergens (ie, grass, olive/ash pollen, house dust mites), specific IgE did not show marked differences between regions and specific IgG (≥0.5 ISU) was present in most subjects everywhere. For regionally occurring pollen allergens (ragweed, birch, cypress), IgE sensitization was significantly associated with regional pollen exposure. For airborne allergens cross-reacting with food allergens, frequent IgG recognition was observed even in regions with low allergen prevalence (Bet v 1) or for allergens less frequently recognized by IgE (profilins). CONCLUSIONS: The variability in allergen-specific IgE and IgG frequencies depends on exposure, route of exposure, and overall immunogenicity of the allergen. Allergen contact by the oral route might preferentially induce IgG responses.

The emerging landscape of dynamic DNA methylation in early childhood.

BACKGROUND: DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood. RESULTS: By analysing 538 paired DNA blood samples from children at birth and at 4-5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of p < 1.14 × 10-7. Genes with an increase in age-differential methylation were enriched in pathways related to 'development', and were more often located in bivalent transcription start site (TSS) regions, which can silence or activate expression of developmental genes. Genes with a decrease in age-differential methylation were involved in cell signalling, and enriched on H3K27ac, which can predict developmental state. Maternal smoking tended to decrease methylation levels at the identified da-DMSs. We also found 101 a-DMSs (0.71%) that were regulated by genetic variants using cis-differential Methylation Quantitative Trait Locus (cis-dMeQTL) mapping. Moreover, a-DMS-associated genes during early development were significantly more likely to be linked with disease. CONCLUSION: Our study provides new insights into the dynamic epigenetic landscape of the first 8 years of life.

Personalized respiratory medicine: exploring the horizon, addressing the issues. Summary of a BRN-AJRCCM workshop held in Barcelona on June 12, 2014.

This Pulmonary Perspective summarizes the content and main conclusions of an international workshop on personalized respiratory medicine coorganized by the Barcelona Respiratory Network ( www.brn.cat ) and the AJRCCM in June 2014. It discusses (1) its definition and historical, social, legal, and ethical aspects; (2) the view from different disciplines, including basic science, epidemiology, bioinformatics, and network/systems medicine; (3) the bottlenecks and opportunities identified by some currently ongoing projects; and (4) the implications for the individual, the healthcare system and the pharmaceutical industry. The authors hope that, although it is not a systematic review on the subject, this document can be a useful reference for researchers, clinicians, healthcare managers, policy-makers, and industry parties interested in personalized respiratory medicine.

A systematic review of socioeconomic position in relation to asthma and allergic diseases.

The role of socioeconomic position (SEP) in the development of asthma and allergies is unclear, with some pointing to the risks of low SEP and other research pointing in the direction of higher SEP being associated with higher prevalence rates. The aim of this systematic review is to clarify associations between SEP and the prevalence of asthma and allergies. Out of 4407 records identified, 183 were included in the analysis. Low SEP was associated with a higher prevalence of asthma in 63% of the studies. Research on allergies, however, showed a positive association between higher SEP and illness in 66% of studies. Pooled estimates for the odds ratio of disease for the highest compared with the lowest SEP confirmed these results for asthma (unadjusted OR 1.38, 95% CI 1.37-1.39), allergies in general (OR 0.67, 95% CI 0.62-0.72), atopic dermatitis (unadjusted OR 0.72, 95% CI 0.61-0.83) and allergic rhinoconjunctivitis (unadjusted OR 0.52, 95% CI 0.46-0.59). Sensitivity analyses with a subsample of high-quality studies led to the same conclusion. Evidence from this systematic review suggests that asthma is associated with lower SEP, whereas the prevalence of allergies is associated with higher SEP.

Advances in allergen-microarray technology for diagnosis and monitoring of allergy: the MeDALL allergen-chip.

Allergy diagnosis based on purified allergen molecules provides detailed information regarding the individual sensitization profile of allergic patients, allows monitoring of the development of allergic disease and of the effect of therapies on the immune response to individual allergen molecules. Allergen microarrays contain a large variety of allergen molecules and thus allow the simultaneous detection of allergic patients' antibody reactivity profiles towards each of the allergen molecules with only minute amounts of serum. In this article we summarize recent progress in the field of allergen microarray technology and introduce the MeDALL allergen-chip which has been developed for the specific and sensitive monitoring of IgE and IgG reactivity profiles towards more than 170 allergen molecules in sera collected in European birth cohorts. MeDALL is a European research program in which allergen microarray technology is used for the monitoring of the development of allergic disease in childhood, to draw a geographic map of the recognition of clinically relevant allergens in different populations and to establish reactivity profiles which are associated with and predict certain disease manifestations. We describe technical advances of the MeDALL allergen-chip regarding specificity, sensitivity and its ability to deliver test results which are close to in vivo reactivity. In addition, the usefulness and numerous advantages of allergen microarrays for allergy research, refined allergy diagnosis, monitoring of disease, of the effects of therapies, for improving the prescription of specific immunotherapy and for prevention are discussed.

Cleaning products and short-term respiratory effects among female cleaners with asthma.

OBJECTIVE: We evaluated the short-term effects of exposure to cleaning products on lung function and respiratory symptoms among professional cleaning women. METHODS: Twenty-one women with current asthma and employed as professional cleaners participated in a 15-day panel study. During 312 person-days of data collection, participants self-reported their use of cleaning products and respiratory symptoms in daily diaries and recorded their forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF) three times per day using a handheld spirometer. We evaluated associations of cleaning product use with upper and lower respiratory tract symptoms using Poisson mixed regression models and with changes in FEV1 and PEF using linear mixed regression analyses. RESULTS: Participants reported using an average of 2.4 cleaning products per day, with exposure to at least one strong irritant (eg, ammonia, bleach, hydrochloric acid) on 56% of person-days. Among participants without atopy, lower respiratory tract symptoms were associated with the use of hydrochloric acid and detergents. Measurements of FEV1 and PEF taken in the evening were 174 mL (95% CI 34 to 314) and 37 L/min (CI 4 to 70), respectively, lower on days when three or more sprays were used. Evening and next morning FEV1 were both lower following the use of hydrochloric acid (-616 and -526 mL, respectively) and solvents (-751 and -1059 mL, respectively). Diurnal variation in FEV1 and PEF increased on days when ammonia and lime-scale removers were used. CONCLUSIONS: The use of specific cleaning products at work, mainly irritants and sprays, may exacerbate asthma.

Genetic heterogeneity of asthma phenotypes identified by a clustering approach.

The aim of the study was to identify genetic variants associated with refined asthma phenotypes enabling multiple features of the disease to be taken into account. Latent class analysis (LCA) was applied in 3001 adults ever having asthma recruited in the frame of three epidemiological surveys (the European Community Respiratory Health Survey (ECRHS), the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) and the Epidemiological Study on the Genetics and Environment of Asthma (EGEA)). 14 personal and phenotypic characteristics, gathered from questionnaires and clinical examination, were used. A genome-wide association study was conducted for each LCA-derived asthma phenotype, compared to subjects without asthma (n=3474). The LCA identified four adult asthma phenotypes, mainly characterised by disease activity, age of asthma onset and atopic status. Associations of genome-wide significance (p<1.25 × 10(-7)) were observed between "active adult-onset nonallergic asthma" and rs9851461 flanking CD200 (3q13.2) and between "inactive/mild nonallergic asthma" and rs2579931 flanking GRIK2 (6q16.3). Borderline significant results (2.5 × 10(-7) < p <8.2 × 10(-7)) were observed between three single nucleotide polymorphisms (SNPs) in the ALCAM region (3q13.11) and "active adult-onset nonallergic asthma". These results were consistent across studies. 15 SNPs identified in previous genome-wide association studies of asthma have been replicated with at least one asthma phenotype, most of them with the "active allergic asthma" phenotype. Our results provide evidence that a better understanding of asthma phenotypic heterogeneity helps to disentangle the genetic heterogeneity of asthma.

The influence of sensitisation to pollens and moulds on seasonal variations in asthma attacks.

No large study has described the seasonal variation in asthma attacks in population-based asthmatics in whom sensitisation to allergen has been measured. 2,637 young adults with asthma living in 15 countries reported the months in which they usually had attacks of asthma and had skin-prick tests performed. Differences in seasonal patterns by sensitisation status were assessed using generalised estimating equations. Most young adults with asthma reported periods of the year when their asthma attacks were more common (range: 47% in Sweden to 86% in Spain). Seasonal variation in asthma was not modified by sensitisation to house dust mite or cat allergens. Asthmatics sensitised to grass, birch and Alternaria allergens had different seasonal patterns to those not sensitised to each allergen, with some geographical variation. In southern Europe, those sensitised to grass allergens were more likely to report attacks occurred in spring or summer than in winter (OR March/April 2.60, 95% CI 1.70-3.97; OR May/June 4.43, 95% CI 2.34-8.39) and smaller later peaks were observed in northern Europe (OR May/June 1.25, 95% CI 0.60-2.64; OR July/August 1.66, 95% CI 0.89-3.10). Asthmatics reporting hay fever but who were not sensitised to grass showed no seasonal variations. Seasonal variations in asthma attacks in young adults are common and are different depending on sensitisation to outdoor, but not indoor, allergens.

Serum total immunoglobulin E is a surrogate of atopy in adult-onset asthma: a longitudinal study.

BACKGROUND: Studies have shown that serum total immunoglobulin E (IgE) levels are higher in asthmatics. However, the role of the serum total IgE level, independently from atopy, in adult asthma is not understood. We studied the associations between serum total IgE, the number of sensitizations and the sum of specific IgEs and new-onset asthma using longitudinal data from the European Community Respiratory Health Survey. METHODS: Serum total and specific IgE to 4 common inhalant allergens were measured at baseline in 9,175 participants, with a follow-up of 9 years. Individuals with asthma history and/or asthma symptoms were excluded. Atopy was defined as the presence of at least one specific IgE ≥0.35 kU/l. Total and specific IgEs were regressed against new-onset asthma using multivariate logistic regression with a random intercept for the study centre. RESULTS: Two hundred and ninety-seven participants had developed asthma during follow-up (incidence rate 5.7 per 1,000 person-years). A 10% higher level of total IgE was associated with a 12% increased risk of new-onset asthma (p = 0.005). However, after adjustment for the number of positive specific IgEs [odds ratio (OR) for multiple sensitization 1.74, 95% confidence interval (CI) 1.05­2.88] and the sum of allergenspecific IgEs (OR 1.18, 95% CI 1.00­1.40), the association between total IgE and asthma disappeared (OR 1.00, 95% CI 0.91­1.10). Seventeen percent of new-onset asthma cases could be attributed to atopy, and this estimate was not largely modified when the total IgE level was simultaneously taken into account. CONCLUSIONS: After taking into account the number and intensity of 4 specific IgEs, the serum total IgE level was not associated with new-onset asthma in adults.

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. METHODS: We determined lung function, the serum titers of ANA and AT by immunofluorescence, and the serum levels of C-reactive protein (CRP) by high sensitivity nephelometry in 328 patients with clinically stable COPD and in 67 healthy controls recruited in the PAC-COPD study. Multiple linear and logistic regression analysis was used to analyze results. MEASUREMENTS AND MAIN RESULTS: The prevalence of abnormal ANA and AT titers was 34% and 26% in patients and 3% and 6% in controls, respectively. Levels of AT greater than or equal to 1:320 were seen in 21% of patients with COPD and were independently associated with the severity of airflow limitation and gas transfer impairment (P < 0.05). Neither ANA or AT titers was related to body mass index, current smoking status, use of inhaled steroids, the Charlson index, or serum C-reactive protein values. CONCLUSIONS: Between a quarter and a third of patients with clinically stable COPD present abnormal titers of circulating ANA and AT. The observed relationship between AT and lung function supports a role for autoimmunity in the pathogenesis of COPD.

Occupational risk factors for hand dermatitis among professional cleaners in Spain.

BACKGROUND: Dermatitis is an important health outcome for workers whose jobs put them in contact with irritants or sensitizing agents. OBJECTIVES: We conducted an analysis of data from the Epidemiological Study on the Risk of Asthma in Cleaning Workers 2 (EPIASLI2) to assess worksites and cleaning products as risk factors for hand dermatitis among professional cleaning workers. MATERIALS/METHODS: We distributed 4993 questionnaires to employees of 37 cleaning companies, and used data from 818 (16%) respondents who provided information about skin symptoms and cleaning-related exposures. We assessed associations between the frequencies of worksite and cleaning product exposures and a symptom-based definition of hand dermatitis among current cleaning workers (n = 693) and a comparison population (n = 125). RESULTS: Hand dermatitis was reported by 28% of current cleaning workers, versus 18% of the comparison population, and was associated with cleaning outdoor areas and schools, and the use of hydrochloric acid [prevalence ratio (PR) 1.92, 95% confidence interval (CI) 1.22-3.02] and dust mop products (PR 1.75, 95% CI 1.11-2.75). CONCLUSIONS: Professional cleaning workers may not be sufficiently protected from cutaneous disease at work. Future research should further investigate the roles of multiple product exposures and personal protective equipment.

Maternal C-reactive protein levels in pregnancy are associated with wheezing and lower respiratory tract infections in the offspring.

OBJECTIVE: We assessed whether maternal C-reactive protein (CRP) levels during pregnancy and CRP gene variations are associated with wheezing and lower respiratory tract infections (LRTIs) in offspring. STUDY DESIGN: Information on wheezing and LRTIs in the offspring at 6 and 14 months of age, and maternal CRP levels and genotype was obtained from a population-based birth cohort. RESULTS: A total of 63 children (12.5%) experienced recurrent wheezing and 61 (12.4%) a recurrent diagnosis of LRTIs. Children in the highest tertile of maternal CRP levels had a higher risk of experiencing recurrent wheezing (adjusted odds ratio, 2.87; 95% confidence interval, 1.23-6.71) and being diagnosed with recurrent LRTIs (odds ratio, 2.37; 95% confidence interval, 1.01-5.55), as compared with children in the lowest tertile. The rs1205 polymorphism influenced maternal serum CRP levels but not the risk of the offspring outcomes. CONCLUSION: Higher CRP levels in pregnancy are associated with wheezing and LRTIs in offspring. However, genetic variation in CRP influencing maternal levels is not related to these phenotypes.

A workforce-based study of occupational exposures and asthma symptoms in cleaning workers.

OBJECTIVES: To study associations between use of cleaning products and asthma symptoms in cleaning workers. METHODS: Information on respiratory symptoms, history of asthma, workplaces, use of cleaning products and acute inhalation incidents were obtained through a self-administered questionnaire. 917 employees of 37 cleaning companies in Barcelona were studied. 761 (83%) were current cleaners, 86 (9%) former cleaners and 70 (8%) had never worked as cleaners. Multivariable logistic regression analyses were used to evaluate the associations between specific exposures among current cleaners and wheeze without having a cold, chronic cough and current asthma. Associations with an asthma symptom score were also studied using negative binomial regression analyses to report mean ratios. RESULTS: After adjusting for sex, age, nationality and smoking status, the prevalence of current asthma was non-significantly higher among current (OR 1.9; 95% CI 0.5 to 7.8) and former cleaners (OR 1.9; CI 0.6 to 5.5) than in never cleaners. Cleaners working in hospitals during the last year had a significantly increased prevalence of wheeze, current asthma and a 1.8 (95% CI 1.2 to 2.8) times higher mean asthma score. Use of hydrochloric acid was strongly associated with asthma score (mean ratio 1.7; 95% CI 1.1 to 2.6). Use of ammonia, degreasers, multiple purpose products and waxes was also associated with asthma score. CONCLUSIONS: Cleaning work in places with high demand for disinfection, high cleaning standards and use of cleaning products containing respiratory irritants is associated with higher risk of asthma symptoms. This suggests irritants have an important role in cleaning-related asthma.

Integration of gene expression and DNA methylation identifies epigenetically controlled modules related to PM2.5 exposure.

Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p < 0.05) associated with exposure to particulate matter < 2.5 µm in diameter (PM2.5) at birth, one of them mapping to the MIR1296 gene. Further, by integrating gene expression with DNA methylation using Functional Epigenetic Modules algorithms, we identified 9 and 6 modules in relation to PM2.5 exposure at birth and at current address, respectively (including NR1I2, MAPK6, TAF8 and SCARA3). In conclusion, PM2.5 exposure at birth was linked to differential gene expression in children and adolescents. Importantly, we identified several significant interactome hotspots of gene modules of relevance for complex diseases in relation to PM2.5 exposure.

Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts.

Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.

Environmental and nutritional impacts of dietary changes in Spain during the COVID-19 lockdown.

The COVID lockdown has affected food purchases and eating habits. In this regard, this short communication assesses the nutritional and environmental impacts of these changes during the COVID lockdown in Spain, by applying Life Cycle Assessment and an energy- and nutrient-corrected functional unit. Three environmental impacts were studied (Global Warming Potential, Blue Water Footprint and Land Use) and a total of seven weekly diet scenarios were designed: two pre-COVID diets for March and April in 2019 (MAR19, APR19), one COVID diet (COVID) and two alternative diets, one based on the National Dietary Guidelines (NDG) and another one on the Planetary Health Diet (PHD). Results show that the COVID diet had larger energy intake and lower nutritional quality, as well as higher environmental impacts (between 30 and 36%) than the pre-COVID eating patterns. Further research is needed to account for food affordability within this assessment, as well as to analyze how eating patterns will evolve after the COVID lockdown. Finally, the definition of short guidelines for sustainable food behaviors for future possible lockdowns is suggested, as well as the introduction of sustainable indicators within NDGs.