International Journal of Chronic Obstructive Pulmonary Disease · Oct 30, 2026

L-Shaped Association of C-Reactive Protein-Albumin-Lymphocyte Index and COPD Incidence: A Nationwide Cohort Study in the UK Biobank

By Shi Y, Jiang H, Pu S et al.

BACKGROUND: The C-reactive protein-albumin-lymphocyte (CALLY) index has shown prognostic value in various chronic conditions, but its prospective association with incident chronic obstructive pulmonary disease (COPD) and potential non-linear dose-response patterns remain unexplored. METHODS: This prospective cohort study included 292,945 UK Biobank participants. Multivariable Cox proportional hazards regression was used to estimate the association between the natural-log-transformed CALLY (ln-CALLY) index and incident COPD. Restricted cubic spline (RCS) curves and two-segment Cox regression were applied to characterize non-linear associations and identify inflection points. Subgroup and sensitivity analyses were conducted to assess robustness. RESULTS: During a mean follow-up of 13.6 years, 6618 incident COPD events occurred. Each one-unit increment in ln-CALLY was associated with a 17% lower risk of COPD in the fully adjusted model (HR = 0.83, 95% CI: 0.81-0.85, P < 0.001). The highest quartile exhibiting a 41% risk reduction versus the lowest (HR = 0.59, 95% CI: 0.54-0.64, P < 0.001). RCS analysis revealed a significant L-shaped relationship. Threshold effect analysis identified an inflection point at ln-CALLY = 7.00; below this threshold, each one-unit increase was associated with a 19% risk reduction (HR = 0.81, 95% CI: 0.78-0.83, P < 0.001), whereas above the threshold the association was non-significant. The inverse association was more pronounced in participants aged <65 years. Sensitivity analyses yielded consistent results. CONCLUSION: The CALLY index exhibits a significant L-shaped association with incident COPD risk, characterized by a pronounced protective effect below ln-CALLY = 7.00 and a risk plateau above this threshold. These findings support the broader concept that immuno-nutritional status is a determinant of respiratory health.

doi.org/10.2147/copd.s640670Open accessPubMed 42979126Biomarkers