Recently, a locus centred on rs9273349 in the HLA-DQ region emerged from genome-wide association studies of adult-onset asthma. We aimed to further investigate the role of human leukocyte antigen (HLA) class II in adult-onset asthma and a possible interaction with occupational exposures.We imputed classical HLA-II alleles from 7579 single-nucleotide polymorphisms in 6025 subjects (1202 with adult-onset asthma) from European cohorts: ECRHS, SAPALDIA, EGEA and B58C, and from surveys of bakers and agricultural workers. Based on an asthma-specific job-exposure matrix, 2629 subjects had ever been exposed to high molecular weight (HMW) allergens. We explored associations between 23 common HLA-II alleles and adult-onset asthma, and tested for gene-environment interaction with occupational exposure to HMW allergens. Interaction was also tested for rs9273349.Marginal associations of classical HLA-II alleles and adult-onset asthma were not statistically significant. Interaction was detected between the DPB1*03:01 allele and exposure to HMW allergens (p50.009), in particular to latex (p50.01). In the unexposed group, the DPB1*03:01 allele was associated with adult-onset asthma (OR 0.67, 95%CI 0.53-0.86). HMW allergen exposures did not modify the association of rs9273349 with adult-onset asthma.Common classical HLA-II alleles were not marginally associated with adult-onset asthma. The association of latex exposure and adult-onset asthma may be modified by DPB1*03:01.
@ERSpublicationsIn an analysis involving .6000 European adults, classical HLA-II alleles were not associated with adult-onset asthma
Young children differ from adults in their exposure and susceptibility to environmental chemicals (e.g. pesticides) because of various factors such as behavior, diet and physiology. Their heightened vulnerability to environmental stressors makes it important to obtain appropriate urine samples for exposure characterization. However, collecting urine from non-toilet-trained children has been shown to be methodologically and practically challenging. Four urine collection approaches were tested: a disposable diaper, a urine bag, a collection pad and the clean catch. The success rate and the user rating of each method was evaluated. The success rates were 67%, 21%, 17% and 4% for the disposable diaper, urine bag, collection pad and clean catch, respectively. The average user ratings on a 0-10 (0 = inconvenient, 10 = convenient) scale were 9.0, 4.7, 7.3 and 2.5, respectively. Subsequently, the best rated method, the disposable polyacrylate diaper was tested with hydroxy-tebuconazole as an exposure biomarker for the fungicide tebuconazole and creatinine for urine density adjustment. After LC-MS/MS analysis, the recoveries of hydroxy-tebuconazole in the range of 0.05-25 ng/mL were on average 106%, and for creatinine 87%. Precisions (relative standard deviation) were for both 3%. The overall procedure including collection and extraction was assessed, resulting in three out of seven positive samples. Based on this study, the disposable diaper is a suitable method for urine collection of non-toilet-trained children for biomonitoring of tebuconazole. This method can serve as a basis for extension to other substances of interest.
The implementation of One Health/EcoHealth/Planetary Health approaches has been identified as key (i) to address the strong interconnections between risk for pandemics, climate change and biodiversity loss, and (ii) to develop and implement solutions to these interlinked crises. As a response to the multiple calls of scientists in that direction, we have put forward seven long term research questions regarding COVID-19 and emerging infectious diseases (EIDs) that are based on an effective integration of environmental, ecological, evolutionary, and social sciences to better anticipate and mitigate EIDs. Research needs cover the social-ecology of infectious disease agents, their evolution, the determinants of susceptibility of humans and animals to infections, and the human and ecological factors accelerating infectious disease emergence. For comprehensive investigation, they include the development of nature-based solutions to interlinked global planetary crises, addressing ethical and philosophical questions regarding the relationship of humans to nature and regarding transformative changes to safeguard the environment and human health. In support of this research, we propose the implementation of innovative multidisciplinary facilities embedded in social-ecosystems locally: the “ecological health observatories” and the “living laboratories”. This work has been carried out in the frame of the EC project HERA (www.HERAresearchEU.eu) that aims to set the priorities for an environment, climate and health research agenda in the EU by adopting a systemic approach in the face of global environmental change.
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