A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents.

BACKGROUND: Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes. METHODS: Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease. RESULTS: Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found. CONCLUSION: A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.

[Situation of environmental and food area disinfectants registered in Spain under directive 98/8/CE]. / Situación de los desinfectantes de uso ambiental y en industria alimentaria registrados en España tras la publicación de la directiva 98/8/CE.

BACKGROUND: Directive 98/8/EC harmonizes and regulates in the European market authorization and registration of biocides and establishes a period of 14 years for review of active substances. This study analyzes the most significant changes produced in the registry of biocides used as disinfectants registered since the publication of the Directive. METHOD: Information was obtained from the registry of biocides published in the website of the Ministry of Health, Social Policy and Equality in May 2010. We used an Excel data base for the dump and data processing. RESULTS: There are 1575 biocides with intended use as environmental and food area disinfectants registered in Spain (1137 formulas and 438 active ingredients). Formulas are composed of 56 active sustances which are being assessed for their inclusion in the Community list of authorized substances. 54% of the formulas are registered as both bactericide and fungicide, 79% are contact disinfectants, 42% of the formulas correspond to those composed of quaternary ammonium compounds and 67.9% are made with a single active substance. Regarding hazardous properties 45.3% are corrosive, 25.7% irritant, 9.8% harmful, 1.1% toxic , and 33.1% are dangerous to the environment. CONCLUSIONS: The Spanish registry of biocides has complied with the provisions of the Directive cancelling the registrations of the formulas containing substances not included in the list. Of all the substances which are under review in Europe, 58% of environmental disinfectants and 76.4% of food area disinfectants are authorized in Spain.