Childhood Asthma Trajectories Across Eleven Danish Birth Cohorts: Predictors of Asthma Remission and Persistence – A Nationwide DAIRE Study
Abstract
INTRODUCTION Asthma is the most common chronic childhood disease. However, predictors of asthma remission and persistence are sparsely investigated. In line with this, nationwide studies are rare and few birth cohort studies with a follow-up until age 18 years have been reported. METHODS All Danish children born between 1995-2005 were included in the study and were followed from birth until their 18th birthday. Pharmacotherapy, blood eosinophil count, atopy (elevated Total-IgE, antiallergic treatment or >1 positive specific-IgE) and birth data was sourced from national databases. Children had individual-level treatment trajectories created based on treatment intensity according to age-specific GINA 2023 guidelines and were clustered using unsupervised trajectory clustering. The clusters were named based on age of onset, disease severity, and treatment persistence or remission at the age of 18 years. RESULTS A total of 236,272 children and adolescents were included (51% girls). Cluster analyses found eight clusters, of which seven (9.8% of children) included children treated with inhaled pharmacotherapy. Of treated children, 49% belonged to clusters with transient symptoms, where treatment ceased after infancy (Clusters B & C, Figure 1). Early onset, remitting asthma was seen in 32% of treated children (Clusters D & E), early onset, persistent asthma was seen in 5% of treated children (Cluster F), whereas school-age onset, persistent asthma was seen in 8% (Cluster G) and adolescent onset, persistent asthma was seen in 7% of treated children (Cluster H). Compared to those with transient or no asthma treatment, children with persistent asthma had higher blood eosinophil counts (0.26 vs 0.20 cells/uL; 42 vs 29% >0.3 cells/uL) and a higher prevalence of atopy (37 vs 8.1%) was seen. Low birthweight (6.7 vs 3.9%) and prematurity (9.1 vs 6.5%) was more common amongst children with asthma. Metropolitan residence was lower in children with asthma (20 vs 37%). Children with remitting asthma, compared to persistent asthma, had higher blood eosinophil counts (0.32 vs 0.22 cells/uL; 35 vs 52% >0.30 cells/uL) and a higher prevalence of atopy (61 vs 22%). Differences in low birthweight (7.2% vs 5.8%), prematurity (9.8% vs 7.9%) and metropolitan residence (19 vs 22%) for remitting versus persistent childhood asthma were smaller compared to asthma/no asthma clusters. CONCLUSIONS Across eleven Danish nationwide birth cohorts, 9.8% of children were treated with inhaled pharmacotherapy. Remission of childhood asthma was seen in two-thirds of treated children. Type 2 inflammatory markers and atopy predicted both childhood asthma and its persistence into adulthood.
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