Type 2-high airway inflammation in childhood asthma distinguishes a more severe phenotype

Skov FR, Sultan T, Fischer-Rasmussen K, et al. Pediatr Allergy Immunol. 2025; 36:e70032. doi:10.1111/pai.70032

Abstract

Background

It remains unclear whether phenotyping of type 2-high (T2-high) asthma can distinguish clinical characteristics and lung function trajectories in childhood.

Objective

To explore differences between T2-high and T2-low asthma from birth to age 18 years.

Methods

We included 47 children with asthma and 165 as a control group from the Copenhagen Prospective Studies on Asthma in Childhood₂₀₀₀ mother–child cohort. T2-high and T2-low asthma was defined at age 7 by sensitization to aeroallergens, elevated eosinophilic blood count, and/or elevated fractional nitric oxide. Lung function measurements included whole-body plethysmography, spirometry, exercise test, cold air provocation, and methacholine challenge.

Differences in lung function trajectories and traits were analyzed using linear mixed models, Wilcoxon rank-sum test, Fisher's exact test, and Quasi-Poisson regression.

Results

Z-scores for log-transformed specific airway resistance (sRaw)
across age in T2-high versus T2-low asthma.

At age 7 years, 47 had asthma (26 T2-high, 21 T2-low). By age 18, 12 (46.2%) with T2-high had persistent asthma whereas 2 (9.2%) with T2-low; OR 8.14 [1.57–42.34]. Specific airway resistance (sRaw) was 12.5% higher through childhood in children with T2-high asthma (estimate 0.53 [0.06; 1.01]); lung function was more reversible (OR 3.37 [1.03–11.00] for spirometry and OR 2.60 [1.17; 5.75] for sRaw), and they had increased airway hyperresponsiveness (AHR) to methacholine (as shown by 41% lower dose required to cause a 20% drop in lung function (estimate −0.70 [−1.18; −0.23])). There was no significant difference in exacerbation rate and other lung function measurements.

Conclusion

Childhood T2-high asthma differs from T2-low asthma in terms of onset, duration, airway resistance, and airway responsiveness.

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