Plasma Protein Biomarkers of Spirometry Measures of Impaired Lung Function a summary of the June 2025 article published in the Chest Journal

Summary: Circulating Protein Biomarkers and Lung Function

Study Objective

This study aimed to identify circulating plasma protein biomarkers that are associated with lung function and explore their links to chronic respiratory diseases (CRDs) and comorbidities such as cardiovascular and metabolic disorders.

Key Findings

• Wide-scale Proteomic Analysis: Researchers analyzed nearly 3,000 proteins in 32,493 individuals from the UK Biobank and validated results in 740 participants from the Framingham Heart Study (FHS).

• Significant Associations:

  • Over 1,200 proteins were linked to lung function measures like FEV1, FVC, and FEV1/FVC ratio.

  • Many of these proteins are involved in inflammatory, fibrotic, and tumorigenic pathways.

• Causal Inference (Mendelian Randomization):

  • Identified >100 proteins with putative causal links to impaired lung function.

  • Some proteins (e.g., IL1RL1, TNFRSF6B) may be protective, reducing inflammation and preserving lung function.

  • Others (e.g., fibulin-like ECM proteins, scavenger receptors) may contribute to fibrosis and lung damage.

• Comorbidities: These biomarkers are also associated with cardiometabolic diseases, cancers, and obesity, highlighting shared underlying mechanisms.

Biological Insights

• Proteins were enriched in lung tissue, but also expressed in adipose tissue, coronary arteries, and gut, reflecting systemic involvement.

• Key pathways included IL-6/JAK/STAT3, TNF-α/NF-κB, interferon responses, and extracellular matrix regulation.

• Systemic inflammation, especially from adipose tissue dysfunction, plays a major role in lung disease progression.

Interpretation

• Many newly identified proteins offer novel diagnostic and therapeutic targets.

• Findings emphasize the systemic nature of lung disease, particularly the contribution of obesity and inflammation.

• Biomarkers like soluble IL1RL1 and TNFRSF6B may represent natural defenses against inflammatory damage in the lungs.

Limitations

• Mostly European participants limit generalizability.

• Lack of direct lung volume data may misclassify some patients.

• Cross-sectional design cannot separate early-life lung impairment from progressive decline.

Conclusion

This study advances our understanding of lung disease by identifying a broad array of protein biomarkers linked to lung function. It underscores the interconnectedness of lung health with systemic inflammation, obesity, and comorbid diseases, opening pathways for better diagnostics and personalized therapies.

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