Neuromuscular junction biomarker CAF22 predicts functional decline in patients with chronic obstructive pulmonary...

Functional decline is common in chronic obstructive pulmonary disease (COPD) and is not fully explained by pulmonary impairment. Early biological markers capable of identifying patients at risk of accelerated physical deterioration are lacking. C-terminal agrin fragment-22 (CAF22), a circulating biomarker of neuromuscular junction (NMJ) degradation, may detect future functional decline in COPD.

In this prospective longitudinal cohort study, 292 clinically stable patients with COPD (171 men and 121 women) were followed for 12 and 24 months. Stable patients were defined as having a preserved Short Physical Performance Battery (SPPB) score ≥9. Plasma CAF22 was measured at baseline and analyzed as quartiles and as a continuous variable. Functional decline was defined as a ≥ 1-point reduction in total SPPB score.

Baseline CAF22 concentrations were higher in patients with lower baseline SPPB scores and in those who subsequently developed functional decline. The proportion of participants experiencing decline increased progressively across higher CAF22 quartiles at both 12 and 24 months (p for trend <0.001). After multivariate adjustment, participants in the highest CAF22 quartile had increased odds of functional decline compared with the lowest quartile at 12 (AOR 2.85, 95% CI 1.32-6.17; p = 0.008) and 24 (AOR 3.60, 95% CI 1.65-7.82; p = 0.001) months. When analyzed continuously, each unit increase in CAF22 independently predicted functional decline at 12 months (AOR 1.02; p = 0.022) and 24 months (AOR 1.04; p < 0.001).

Elevated baseline plasma CAF22 independently predicts subsequent functional decline in patients with stable COPD, supporting its potential utility as an early biomarker of NMJ degradation and physical deterioration.