Asthma improvement and normalization of host defence: a longitudinal proteomics cluster analysis

The aim was to identify clusters in a homogenous asthma cohort based on longitudinal changes in 92 proteins and to assess the clusters’ clinical and inflammatory features. This is a secondary analysis of the NOAK study. A total of 159 non-smoking asthma patients (median age 41 years;52% males) with perennial allergy and on inhaled corticosteroid treatment, were followed for one year. Plasma proteins were measured using targeted proteomics (Olink Target 96 Inflammation) at baseline and end of the study. Unsupervised methods identified two clusters based on changes in protein levels (Figure). Proteins contributing most to cluster separation were associated with non-type-2 mechanisms, including neutrophil activation. Cluster 1 (n=80) showed higher levels at baseline and a decrease in these proteins between visits, while Cluster 2 (n=79) showed an increase resulting in no cluster difference after one year. Cluster 2 showed improved asthma control (ACQ;p=0.016) and a slight reduction in FeNO and serum ECP over the year (p<0.10 both), whereas Cluster 1 had a higher exacerbation rate (p=0.043). In a homogenous atopic asthma cohort, longitudinal proteomics data identified distinct asthma subtypes associated with divergent molecular markers. Clinical improvement was weakly associated with a reduction in type-2 inflammation but strongly associated with normalization of non-type-2 cytokines possibly involved in host defence. <fig><object-id>erj;64/suppl_68/PA838/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>