Abstract

BackgroundAsthma 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.ObjectiveOur aim was to further characterize this subgroup of non-type 2 asthmatics, including the use of a broad panel of inflammation-related proteins.MethodsSex- 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 kUA/L (NAA; n = 24), non-atopic controls with IgE < 0.35 kUA/L (NAC; n = 24), and atopic asthmatics with IgE ≥ 0.35 kUA/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.ResultsNAA 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).ConclusionIn 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.

Highlights

  • Asthma associated with elevated type 2 immune responses is termed type 2 asthma, and is often related to atopy, especially in young subjects [1]

  • matrix metalloproteinase (MMP)-1 was elevated in this group, which deserves further studies

  • We have recently reported the persistence of clinically relevant type 2 inflammatory signals in young asthmatics with immunoglobulin E (IgE) antibody concentrations below 0.35 kUA/L, and we have suggested a cut-off of 0.10 kUA/L for ruling out type 2 inflammation [4]

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Summary

Introduction

Asthma associated with elevated type 2 immune responses is termed type 2 asthma, and is often related to atopy, especially in young subjects [1]. We have recruited a large sample of young (10– 35 years) patients with asthma, from both primary and secondary care: the MIDAS cohort [2, 9] Within this cohort, we have identified a non-atopic subgroup with perceived food hypersensitivity that showed lower asthma-related quality of life and poorer asthma control compared with both atopic asthmatics and non-atopic asthmatics without reported food hypersensitivity [6]. We have identified a non-atopic subgroup with perceived food hypersensitivity that showed lower asthma-related quality of life and poorer asthma control compared with both atopic asthmatics and non-atopic asthmatics without reported food hypersensitivity [6] These subjects were characterized by low FeNO, suggesting non-type 2 asthma. We have previously identified a subgroup of young non-atopic asthmatics with perceived food hypersensitivity and poor asthma control

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