| Title: | Proteomic Risk Score of Increased Respiratory Susceptibility: A Multi-Cohort Study. |
| Journal: | American Journal of Respiratory and Critical Care Medicine |
| Published: | 10 Sep 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39254293/ |
| DOI: | https://doi.org/10.1164/rccm.202403-0613oc |
Publication 13548
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Abstract
RATIONALE: Accelerated decline in lung function is associated with incident COPD, hospitalizations and death. However, identifying this trajectory with longitudinal spirometry measurements is challenging in clinical practice.</p>
OBJECTIVE: To determine whether a proteomic risk score trained on accelerated decline in lung function can assess risk of future respiratory disease and mortality.</p>
METHODS: In CARDIA, a population-based cohort starting in young adulthood, longitudinal measurements of FEV1 percent predicted (up to six timepoints over 30 years) were used to identify accelerated and normal decline trajectories. Protein aptamers associated with an accelerated decline trajectory were identified with multivariable logistic regression followed by LASSO regression. The proteomic respiratory susceptibility score was derived based on these circulating proteins and applied to the UK Biobank and COPDGene studies to examine associations with future respiratory morbidity and mortality.</p>
MEASUREMENTS AND RESULTS: Higher susceptibility score was independently associated with all-cause mortality (UKBB: HR 1.56, 95%CI 1.50-1.61; COPDGene: HR 1.75, 95%CI 1.63-1.88), respiratory mortality (UKBB: HR 2.39, 95% CI 2.16-2.64; COPDGene: HR 1.83, 95%CI 1.33-2.51), incident COPD (UKBB: HR 1.84, 95%CI 1.71-1.98), incident respiratory exacerbation (COPDGene: OR 1.11, 95%CI 1.03-1.20), and incident exacerbation requiring hospitalization (COPDGene: OR 1.18, 95%CI 1.08-1.28).</p>
CONCLUSIONS: A proteomic signature of increased respiratory susceptibility identifies people at risk of respiratory death, incident COPD, and respiratory exacerbations. This susceptibility score is comprised of proteins with well-known and novel associations with lung health and holds promise for the early detection of lung disease without requiring years of spirometry measurements.</p>
18 Authors
- Gabrielle Y Liu
- Andrew S Perry
- George R Washko
- Eric Farber-Eger
- Laura A Colangelo
- Quanhu Sheng
- Quinn Wells
- Xiaoning Huang
- Bharat Thyagarajan
- Weihua Guan
- Shaina J Alexandria
- Raúl San José Estépar
- Russell P Bowler
- Anthony J Esposito
- Sadiya S Khan
- Ravi V Shah
- Bina Choi
- Ravi Kalhan
Enabling scientific discoveries that improve human health