Proteomic Risk Score of Increased Respiratory Susceptibility: A Multicohort Study

Area of Science:

• Pulmonary Medicine
• Proteomics
• Epidemiology

Background:

• Accelerated lung function decline predicts COPD, hospitalizations, and mortality.
• Identifying this decline using spirometry is clinically challenging.

Purpose of the Study:

• To assess if a proteomic risk score, based on accelerated lung function decline, can predict future respiratory disease and mortality risk.

Main Methods:

• Longitudinal spirometry (FEV1) data from CARDIA cohort identified decline trajectories.
• Proteomic signatures associated with accelerated decline were identified using logistic and LASSO regression.
• A proteomic respiratory susceptibility score was developed and validated in UK Biobank and COPDGene cohorts.

Main Results:

• Higher susceptibility scores correlated with increased all-cause mortality (UKBB: HR 1.56; COPDGene: HR 1.75).
• Scores predicted respiratory mortality (UKBB: HR 2.39; COPDGene: HR 1.83) and incident COPD (UKBB: HR 1.84).
• The score also associated with respiratory exacerbations and hospitalizations in COPDGene.

Conclusions:

• A proteomic signature of respiratory susceptibility effectively identifies individuals at risk for respiratory death, COPD, and exacerbations.
• This score, using known and novel lung-associated proteins, shows potential for early lung disease detection.
• It offers a promising alternative to prolonged spirometry monitoring for risk assessment.