Background Previously identified asthma-susceptibility genes account for a small part of asthma heritability and their role in asthma pathogenesis is unclear. We explored associations between genetic variants in the 17q21 locus, CDHR3 (cadherin-related family member 3) , coding a receptor for Rhinovirus-C, preschool wheeze and asthma at 7 years. Methods Four genetic variants in the 17q21 locus (rs8076131, rs12603332, rs8079416, rs3859192) and rs6967330 in CDHR3 were studied regarding associations with preschool wheeze and asthma at 7 years. We compared 125 cases, enrolled during an acute wheezing episode, with 96 healthy controls at preschool age (6-45 months). At 7 years cases with asthma (N=68) and without asthma (N=31) were compared regarding genetic variants and other clinical parameters. Results Rs8076131 (AA vs GG) was associated with preschool wheeze (OR 3.50, p=0.001), and asthma at 7 years (OR 8.55, p=0.002). Rs12603332 (CC vs TT) was related to asthma at 7 years irrespective of rhinovirus infection at inclusion or current signs of airborne allergy (aOR 7.17, p=0.016). The association of rs6967330 with asthma was restricted to children with specific genotypes in the 17q21 locus; rs8076131-AA (p=0.028) , rs8079416-CC (p=0.006), and rs3859192-TT (p=0.042). Rhinovirus infection at inclusion was significantly related to asthma exclusively in homozygotes rs8079416-CC (p=0.032) and rs3859192-TT (p=0.027). Conclusion Our results highlight the impact of asthma heritability by reporting strong associations between 17q21 locus and asthma in a high-risk cohort. The association of rs6967330 in CDHR3 and early-life rhinovirus infection with asthma at school age might be dependent on specific genotypes in the 17q21 locus.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization and natural history review. Numerous factors that may affect disease activity and patient wellbeing need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even ‘real-time’, monitoring between visits. Following an approach that included needs assessment, evidence appraisal and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

Background: This initiative aimed to elucidate the clinical relevance of type 2 (T2) inflammation as a driver of asthma, atopic dermatitis, chronic rhinitis, chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic esophagitis. Methods: A steering committee (SC) conducted a non-systematic literature search to inform the design of a Delphi questionnaire including 23 consensus statements, which was circulated to 30 experts including the SC. Experts rated their agreement with each statement on a 9-point Likert scale and provided optional feedback that was used to develop a second Delphi questionnaire. On 22 October 2020, a meeting was held to discuss the conclusions from the questionnaires and explore how this initiative may impact the management of patients with T2 inflammation-driven disease. Post meeting, a consensus statement on the role of T2 inflammation in eosinophilic esophagitis was circulated to the experts. Results: It was agreed that T2 inflammation may be an underlying driver of asthma, atopic dermatitis, chronic rhinitis, CRSwNP and eosinophilic esophagitis, and that the published evidence suggests that these diseases overlap. Some of this overlap may include related multimorbid conditions driven by T2 inflammation. Thus, in patients with multiple T2 inflammation-driven diseases, a cross-speciality approach is warranted to provide effective care. A question guide with input from relevant experts was proposed, to identify comorbidities and facilitate appropriate holistic patient management. Conclusions: These consensus recommendations should be used as a framework to further understand the extent of T2 inflammation-driven multi-organ disease and to improve the holistic management and care of these patients.