Background: Asthma is a heterogeneous disease of phenotypes that differ by age at onset. At the same time, there is no consensus on the correct cut-off to determine late-onset asthma. This study aimed to characterize phenotypes of late-onset asthma in the general population using different minimum onset ages. Methods: We used survey and clinical data from two population-based studies. Cluster analysis with a novel deep clustering algorithm was performed in subjects with reported asthma onset at age ≥12 years ( n=3,103), ≥20 years ( n=2,431), and ≥40 years ( n=1,269) including data on anthropometrics/demographics, risk factors, asthma triggers, respiratory symptoms, asthma control, lung function, allergy, inflammation, and comorbidities. The clustering models were interpreted with decision trees, random forests, and a large language model. Potential risk factors, comorbidities, and clinical outcomes were evaluated descriptively. Results: Four clusters were identified in the ≥12 years group and three in the ≥20 years and ≥40 years groups. A partly/uncontrolled asthma cluster with dyspnea, cough, and cardiovascular comorbidity as well as an asthma cluster with broadly environmentally-triggered symptoms were identified in all age groups. A mild/moderate asthma cluster with allergic components was identified in the two younger onset age groups, while a mild asthma cluster was identified within the ≥12 years and ≥40 years groups. The clusters differed substantially by risk factors/exposures, comorbidity patterns, and clinical outcomes. Conclusions: Similar sets of asthma phenotypes arise across the course of adulthood, which are relatively easily identified. However, they are characterized by notable differences in clinical presentation, inflammation, comorbidities, and prognosis.

Introduction: Following the “hygiene hypothesis” and the increase in prevalence of atopic diseases such as allergic rhinitis, a plethora of studies have investigated the role of sibship composition as a protective factor, but findings are conflicting. Aim: To synthesize the global literature linking birth order and sibship size (number of siblings) to the risk of allergic rhinitis. Methods: Fifteen databases were systematically searched, with no restrictions on publication date or language. Observational studies with defined sibship composition (birth order or sibship size) as exposure and allergic rhinitis or allergic rhinoconjunctivitis (self-reported or clinically diagnosed) as outcome were eligible. Study selection, data extraction, and quality assessment was performed independently in pairs. Relevant data were summarized in tables. Comparable numerical data were analyzed using meta-analysis with robust variance estimation (RVE). Results: Seventy-six reports with >2 million subjects were identified. Being second- or later-born child was associated with protection against both current (pooled risk ratio [RR] 0.79, 95%CI 0.73-0.86) and ever (RR 0.77, 95%CI 0.68-0.88) allergic rhinitis. Having siblings, regardless of birth order, was associated with a decreased risk of current allergic rhinitis (RR 0.89, 95% CI 0.83-0.95) and allergic rhinoconjunctivitis (RR 0.92, 95%CI 0.86-0.98). These effects were unchanged across age, time period, and geographical regions. Conclusion: Our findings indicate that primarily, a higher birth order, and to a lesser extent the number of siblings, is associated with a lower risk of developing allergic rhinitis.

Recent reports indiciate that the prevelance of food allergy is increasing, but accurate estimates remain a challenge due to cross-reactivity and limited use of precise diagnostic methods. Component-resolved diagnostics (CRD), in which sensitization to individual molecular components of whole food allergen extracts is measured, is emerging as a promising tool for evaluation of sensitization profiles. In this systematic review, we summarized estimates of prevalence of sensitization to food allergen components in the general population in Europe. We searched seven databases with no restrictions on publication date or language. Two reviewers independently screened the literature and appraised the risk of bias in the included studies. From 4,776 de-duplicated records, five studies, with low to moderate overall risk of bias, were included and narratively synthesized. Forty-six components from 18 foods were investigated. Overall, the prevalence of sensitization was low, particularly for major allergens, and non-existent for 10 components (0% [95% CI 0-0.8]). The highest prevalence was seen for PR-10 proteins, such as Cor a 1.04 (13.6% [95% CI 10.9-16.9]). There were not enough studies to discern regional differences or perfom meta-analysis, highlighting the need for more population-representative studies in order to elucidate patterns of sensitization to food allergen components in Europe.