Asthma-chronic obstructive pulmonary disease overlap is associated with a higher degree of neuromuscular junction degradation than either disease alone

Background

Patients with asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) exhibit an advanced form of age-related decline of skeletal muscle and physical performance, termed sarcopenia. However, the relative contribution of neuromuscular junction (NMJ) degradation to sarcopenia in these patients remains partly elusive.

Methods

We recruited older men, including controls (n=68) and patients with asthma (n=61), COPD (n=74), and ACO (n=53), to measure handgrip strength (HGS), skeletal muscle mass index (SMI), gait speed (GS), and a short physical performance battery (SPPB). We also measured plasma C-terminal agrin-fragment-22 (CAF22; a marker of NMJ degradation) and neurofilament light-chain (NfL; a marker of neurodegeneration) in the study population.

Results

Patients with asthma, COPD, and ACO had lower HGS, SMI, GS, and SPPB scores and higher CAF22 levels than controls (all p<0.05). Among individual diseases, ACO was associated with the lowest HGS and SPPB scores and highest CAF22 levels (all p<0.05). We also observed significant correlations of CAF22 with HGS, GS, and SPPB in patients with asthma, COPD, and ACO (all p<0.05). Lastly, CAF22 exhibited significant efficacy in diagnosing sarcopenia in all three diseases, with the highest AUC reported in ACO patients (all p<0.05).

Conclusion

Altogether, we report a higher degree of sarcopenia and physical compromise with elevation of NMJ degradation biomarkers in patients with ACO than those with either disease alone. Our findings suggest NMJ as a therapeutic target to restore muscle health and functional capacity in patients with chronic airway diseases.