Characterization of a subgroup of non-type 2 asthma with cow's milk hypersensitivity in young subjects

Asthma with atopy is often characterized by type 2 inflammation but less progress has been made in defining non-type 2 asthma. We have previously identified a subgroup of young non-atopic asthmatics with perceived food hypersensitivity and poor asthma control.

Our aim was to further characterize this subgroup of non-type 2 asthmatics, including the use of a broad panel of inflammation-related proteins.

Sex- and age-matched subjects (10-35 years old) were divided into three groups with regard to history of asthma and atopy: non-atopic asthmatics with perceived cow's milk hypersensitivity but with IgE antibodies < 0.35 kU_A/L (NAA; n = 24), non-atopic controls with IgE < 0.35 kU_A/L (NAC; n = 24), and atopic asthmatics with IgE ≥ 0.35 kU_A/L (AA; n = 29). Serum or plasma were analysed using the multi-allergen tests Phadiatop and fx5 (ImmunoCAP), a multiplex immunoassay comprising 92 inflammation-related proteins (Proseek Inflammation), and an ELISA for human neutrophil lipocalin (S-HNL). Fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, C-reactive protein (CRP), airway responsiveness to methacholine (PD₂₀), and asthma-related quality of life (mAQLQ) were also measured.

NAA had lower FeNO (p < 0.001) and B-Eos count (p < 0.001), but scored worse on mAQLQ (p = 0.045) compared with AA. NAA displayed higher levels of matrix metalloproteinase-1 (MMP-1) compared with both NAC (p = 0.011) and AA (p = 0.001), and lower PD₂₀ compared with NAC (p < 0.001). In NAA, S-HNL correlated negatively with PD₂₀ (rho = - 0.048, p < 0.05) and CRP correlated negatively with mAQLQ (rho = - 0.439, p < 0.05).

In a subgroup of non-atopic young asthmatics with perceived cow's milk hypersensitivity we observed poor asthma-related quality of life, airway hyperresponsiveness, and clinically relevant non-type 2 inflammation. MMP-1 was elevated in this group, which deserves further studies.