| 1. |
- Mathioudakis, Alexander G., et al.
(författare)
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Research Priorities in Pediatric Asthma : Results of a Global Survey of Multiple Stakeholder Groups by the Pediatric Asthma in Real Life (PeARL) Think Tank
- 2020
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Ingår i: Journal of Allergy and Clinical Immunology: In Practice. - : Elsevier BV. - 2213-2198 .- 2213-2201. ; 8:6, s. 9-1960
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pediatric asthma remains a public health challenge with enormous impact worldwide. Objective: The aim of this study was to identify and prioritize unmet clinical needs in pediatric asthma, which could be used to guide future research and policy activities. Methods: We first identified unmet needs through an open-question survey administered to international experts in pediatric asthma who were members of the Pediatric Asthma in Real Life Think Tank. Prioritization of topics was then achieved through a second, extensive survey with global reach, of multiple stakeholders (leading experts, researchers, clinicians, patients, policy makers, and the pharmaceutical industry). Differences across responder groups were compared. Results: A total of 57 unmet clinical need topics identified by international experts were prioritized by 412 participants from 5 continents and 60 countries. Prevention of disease progression and prediction of future risk, including persistence into adulthood, emerged as the most urgent research questions. Stratified care, based on biomarkers, clinical phenotypes, the children's age, and demographics were also highly rated. The identification of minimum diagnostic criteria in different age groups, cultural perceptions of asthma, and best treatment by age group were priorities for responders from low-middle-income countries. There was good agreement across different stakeholder groups in all domains with some notable exceptions that highlight the importance of involving the whole range of stakeholders in formulation of recommendations. Conclusions: Different stakeholders agree in the majority of research and strategic (eg, prevention, personalized approach) priorities for pediatric asthma. Stakeholder diversity is crucial for highlighting divergent issues that future guidelines should consider.
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| 2. |
- Papadopoulos, Nikolaos G., et al.
(författare)
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Addressing adverse synergies between chemical and biological pollutants at schools—The ‘SynAir-G’ hypothesis
- 2024
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 79:2, s. 294-301
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Tidskriftsartikel (refereegranskat)abstract
- While the number and types of indoor air pollutants is rising, much is suspected but little is known about the impact of their potentially synergistic interactions, upon human health. Gases, particulate matter, organic compounds but also allergens and viruses, fall within the ‘pollutant’ definition. Distinct populations, such as children and allergy and asthma sufferers are highly susceptible, while a low socioeconomic background is a further susceptibility factor; however, no specific guidance is available. We spend most of our time indoors; for children, the school environment is of paramount importance and potentially amenable to intervention. The interactions between some pollutant classes have been studied. However, a lot is missing with respect to understanding interactions between specific pollutants of different classes in terms of concentrations, timing and sequence, to improve targeting and upgrade standards. SynAir-G is a European Commission-funded project aiming to reveal and quantify synergistic interactions between different pollutants affecting health, from mechanisms to real life, focusing on the school setting. It will develop a comprehensive and responsive multipollutant monitoring system, advance environmentally friendly interventions, and disseminate the generated knowledge to relevant stakeholders in accessible and actionable formats. The aim of this article it to put forward the SynAir-G hypothesis, and describe its background and objectives.
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| 3. |
- Pasanen, Anu, et al.
(författare)
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Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis.
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a genome-wide association study (GWAS) in which 5,300,000 single nucleotide polymorphisms (SNPs) were tested for association in a Finnish-Swedish population of 217 children hospitalized for bronchiolitis and 778 controls. The most promising SNPs (n=77) were genotyped in a Dutch replication population of 416 cases and 432 controls. Finally, we used a set of 202 Finnish bronchiolitis cases to further investigate candidate SNPs. We did not detect genome-wide significant associations, but several suggestive association signals (p<10(-5)) were observed in the GWAS. In the replication population, three SNPs were nominally associated (p<0.05). Of them, rs269094 was an expression quantitative trait locus (eQTL) for KCND3, previously shown to be associated with occupational asthma. In the additional set of Finnish cases, the association for another SNP (rs9591920) within a noncoding RNA locus was further strengthened. Our results provide a first genome-wide examination of the genetics underlying bronchiolitis. These preliminary findings require further validation in a larger sample size.
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| 4. |
- Pasanen, Anu, et al.
(författare)
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NKG2D gene variation and susceptibility to viral bronchiolitis in childhood.
- 2018
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Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 84, s. 451-457
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors associated with bronchiolitis are inadequately characterized. We therefore inspected a selected subpopulation of our previous genome-wide association study (GWAS) of bronchiolitis for overlap with known quantitative trait loci (QTLs) to identify susceptibility loci that potentially affect mRNA and protein levels.GWAS included a Finnish-Swedish case-control population (n=187), matched for age and site. We integrated GWAS variants (p<10-4) with QTL data. We subsequently verified allele-specific expression of identified QTLs by flow cytometry. Association of the resulting candidate loci with bronchiolitis was tested in three additional cohorts from Finland and Denmark (n=1201).Bronchiolitis-susceptibility variant rs10772271 resided within QTLs previously associated with NKG2D (NK group 2, member D) mRNA and protein levels. Flow cytometric analysis confirmed the association with protein level in NK cells. The GWAS susceptibility allele (A) of rs10772271 (odds ratio [OR]=2.34) corresponded with decreased NKG2D expression. The allele was nominally associated with bronchiolitis in one Finnish replicate (OR=1.50), and the other showed directional consistency (OR=1.43). No association was detected in Danish population CONCLUSIONS: The bronchiolitis GWAS susceptibility allele was linked to decreased NKG2D expression in the QTL data and in our expression analysis. We propose that reduced NKG2D expression predisposes infants to severe bronchiolitis.
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