Background The tear fluid is a valuable source of biomarkers for objective analysis of systemic diseases. 

Aim To investigate whether specific metabolites and/or proteins were differentially expressed in tears of allergic asthmatic children and controls

Method We carried out a prospective study collecting tears from prepubertal children with allergic asthma: 17 mild (Mi-A) and 14 moderate (Mo-A) compared with 44 healthy controls (HCs). We used a ?multi-omics? approach for the simultaneous evaluation of metabolic, i.e. amminoacids (AAs), free carnitine (C0) and acylcarnitines (ACs), and protein tear patterns.

Results Among the measured metabolites, C0 and acylcarnitines best drove the separation between asthmatic and HC tear samples. In particular, we found higher levels of C0 in Mi-A and Mo-A compared with HC (p<0.05) which correlated well with proteomics data. In fact, we identified 68 significant differential proteins (p<0.05 at post hoc Tukey?s HSD test) by showing that tear of asthmatic children modulated an increasing response of the energetic metabolism corroborated with an up-regulation of "glycolysis" (MiA/HC z-score = 1.89; MoA/HC z-score = 2.12) and oxidative stress related to NFE2 Like BZIP Transcription Factor-2 (NFE2L2) upstream (MiA/HC z-score = 2.168; MoA/HC z-score = 3.072).

Conclusion Our ?multi-omics? investigation unravelled metabolites and protein pathways suggesting that oxidative stress and the increase of glycolysis are factors contributing to asthma severity in children. However, further larger studies are still needed before moving to the development of treatments targeting the oxidative stress- or glycolysis related pathways.