Plasma CAF22 Levels as a Useful Predictor of Muscle Health in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Skeletal muscle dysfunction and reduced physical capacity are characteristic features of chronic obstructive pulmonary disease (COPD). However, the search for a reliable biomarker to assess muscle health in CODP remains elusive. We analyzed the course of hand-grip strength (HGS) and appendicular skeletal mass index (ASMI) in COPD in relation to spirometry decline and plasma extracellular heat shock protein-72 (eHSP72) and c-terminal fragment of agrin-22 (CAF22) levels. We evaluated male, 62-73 years old patients of COPD (N = 265) and healthy controls (N = 252) at baseline and after 12 and 24 months for plasma biomarkers, spirometry and HGS measurements. HGS declined significantly over time and plasma CAF22, but not eHSP72 levels, had a significant negative association with HGS and ASMI in COPD. Plasma CAF22 also had an association with walking speed and daily steps count in advanced COPD. Lower ASMI was associated with reduced HGS at all time-point. Narrow age-span of the study cohort and exclusion of lower-limb muscles from the analysis are limitations of this study. Taken together, we report that the plasma CAF22 may be a useful tool to assess muscle weakness and atrophy in COPD patients.

Keywords: COPD; biomarkers; muscular atrophy; skeletal muscle; spirometry.

Figure 1

Study flow. FEV₁%: Forced expiratory volume in the first second and GOLD: global initiative for obstructive lung diseases.

Figure 2

Relationship of serum levels of eHSP72 and CAF22 with hand-grip strength (HGS; A–C) and appendicular skeletal muscle mass (ASMI; D–F) at the baseline (A,D), 12 (B,E) and 24-month (C,F) time points in healthy controls and patients with COPD GOLD stages 1 and 2 and 3 and 4 (N = 64–68 participants/group/time point for pooled data).

Figure 3

Relationship of hand-grip strength (HGS) with appendicular skeletal muscle mass (ASMI) at the baseline (A), 12 (B) and 24-month (C) time points in healthy controls and patients with COPD GOLD stages 1 and 2 and 3 and 4 (N = 64–68 participants/group/time point for pooled data).