Potential asthma biomarkers identified by nontargeted proteomics of extracellular vesicles in exhaled breath condensate

The journal of allergy and clinical immunology. Global Pub Date : 2025-01-30 DOI:10.1016/j.jacig.2025.100432

Reina Hara MD , Yoshito Takeda MD, PhD , Takatoshi Enomoto MD , Hanako Yoshimura MD, PhD , Makoto Yamamoto MD , Satoshi Tanizaki MD , Yuya Shirai MD, PhD , Takahiro Kawasaki MD, PhD , Mana Nakayama , Saori Amiya MD , Yuichi Adachi MD , Yoshimi Noda MD , Takayuki Niitsu MD , Ryuya Edahiro MD, PhD , Moto Yaga MD, PhD , Yuki Hosono MD, PhD , Maiko Naito MD, PhD , Kentaro Masuhiro MD, PhD , Yujiro Naito MD, PhD , Takayuki Shiroyama MD, PhD , Atsushi Kumanogoh MD, PhD

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Abstract

Background

Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are often misdiagnosed or undiagnosed, highlighting the need for more noninvasive and accessible diagnostic tools. Although exhaled breath condensate (EBC) is recognized as a biomarker resource for respiratory diseases, nontargeted proteomics of extracellular vesicles (EVs) in EBC has not been explored.

Objective

Our aim was to identify protein signatures in EBC-derived EVs (EBC-EVs) and potential biomarkers for BA and COPD.

Methods

EBC-EVs were isolated from 8 patients with BA, 5 patients with COPD, and 9 healthy controls by using the phosphatidylserine affinity method. The isolated EBC-EVs were analyzed by using data-independent acquisition proteomics to identify differentially expressed proteins (DEPs) and their associations with clinical parameters.

Results

Overall, 2524 proteins were identified. In the patients with BA, 20 proteins were upregulated, and 34 were downregulated. In the patients with COPD, 46 proteins were upregulated and 67 were downregulated. Although the enriched pathways and protein networks showed similarities between BA and COPD, they also indicated distinct pathophysiologic differences. In all, 5 BA-DEPs and 2 COPD-DEPs correlated with clinical parameters. For BA, S100 calcium-binding protein P levels were inversely correlated with FEV₁ value, and ribosomal protein S10 levels were inversely correlated with blood eosinophil count. Clathrin heavy chain 2 correlated with serum IgE levels. For COPD, 14-3-3 protein theta and galectin-related protein showed positive and negative correlations with FEV₁ value, respectively.

Conclusions

Proteomics of EBC-EVs has enabled the identification of potential diagnostic biomarkers for BA and COPD. “Breathomics” of EBC-EVs offers a promising noninvasive approach for diagnosis and phenotyping of respiratory diseases.

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