Document Type

Article

Publication Date

2024

DOI

10.1111/all.16000

Publication Title

Allergy

Volume

79

Issue

3

Pages

643-655

Abstract

Background: Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma.

Methods: Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with atopy (n = 207), asthma without atopy (n = 554), atopy without asthma (n = 147), compared to neither (n = 948)).

Results: Meta-analysis of 4860 proteins identified 115 significantly (FDR<0.05) associated with asthma. Multiple signaling pathways related to airway inflammation and pulmonary injury were enriched (FDR<0.05) among these proteins. A proteomic score generated using machine learning provided predictive value for asthma (AUC = 0.77, 95% CI = 0.75-0.79 in training set; AUC = 0.72, 95% CI = 0.69-0.75 in validation set). Twenty proteins are targeted by approved or investigational drugs for asthma or other conditions, suggesting potential drug repurposing. The combined asthma-atopy phenotype showed significant associations with 20 proteins, including five not identified in the overall asthma analysis.

Conclusion: This first large-scale proteomics study identified over 100 plasma proteins associated with current asthma in adults. In addition to validating previous associations, we identified many novel proteins that could inform development of diagnostic biomarkers and therapeutic targets in asthma management.

Rights

© 2024 The Authors.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. Foreign copyright may apply.

Data Availability

Article states: "Complete summary statistics and association results are available in the supplementary material. For ALHS, requests for the underlying data should be submitted to the executive committee of the parent cohort Agricultural Health Study by emailing Dr. Mikyeong Lee. Data requests will be evaluated based on pre-existing data sharing policies (https://aghealth.nih.gov/collaboration/process.html). For ARIC, proteome and phenotypic data will be available via application through the ARIC Data Coordinating Center (https://sites.cscc.unc.edu/aric/distribution-agreements)."

Original Publication Citation

Smilnak, G. J., Lee, Y., Chattopadhyay, A., Wyss, A. B., White, J. D., Sikdar, S., Jin, J., Grant, A. J., Motsinger-Reif, A. A., Li, J. L., Lee, M., Yu, B., & London, S. J. (2024). Plasma protein signatures of adult asthma. Allergy, 79(3), 643-655. https://doi.org/10.1111/all.16000

ORCID

0000-0003-1230-5162 (Sikdar)

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