Abstract Rational Chronic obstructive pulmonary disease (COPD) is characterized by heterogeneous peripheral blood inflammatory responses involving neutrophilic (NEU), eosinophilic (EOS), and lymphocytic (Lymph) profiles. Previous studies have shown that these circulating biomarkers and their ratios have prognostic values. However, it remains unclear whether longitudinal trends in these biomarkers and their ratios before COPD diagnosis are associated with mortality. In this retrospective cohort study, we aimed to identify the longitudinal immunophenotypic patterns of COPD patients and evaluate their association with all-cause mortality. Methods We retrospectively analyzed complete blood count (CBC) data with differential, including total white blood cell (WBC), NEU, EOS, and Lymph counts from patients in the Veterans Affairs (VA) healthcare system. Lymph to NEU (LNR), Lymph to WBC (LWR), EOS to WBC (EWR), EOS to NEU (ENR), EOS to Lymph (ELR) were also calculated. Patients were included if they had at least three years of longitudinal data pre- and post-index date of diagnosis. We excluded the laboratory results during hospitalization and urgent care visits. We estimated the slope of changes in the laboratory results using linear regression based on pre-diagnosis. Demographic and clinical variables including age, sex, race, ethnicity, BMI, Charlson Comorbidity Index (CCI), and all-cause mortality were also extracted. We applied binary logistic regression using all-cause mortality as the dependent variable and demographics and laboratory slopes as the independent variables. We reported the odds ratios and 95% confidence intervals (OR95%CI) and β coefficients consider p-value 0.05 as significant level. Results A total of 16,593,828 CBC counts from 142,235 unique patients were analyzed (age, 66.6±9.7 years; male, 95%; White, 77.9%; mean follow-up 8.8 years; mean number of CBCs per patient, 26). CCI 2 (OR = 1.65, 95%CI 1.61-1.69), male sex (OR = 1.68, 95% CI 1.57-1.8), African-American race (OR = 1.09, 95% CI 1.05-1.13) and Hispanic ethnicity (OR = 0.73, 95% CI 0.67-0.79) were independently associated with mortality. Increase in slopes of ELR, NWR, and LNR over time were associated with increase in mortality. Increase in slope of EWR, LWR, and LYMPH before diagnosis was associated with lower mortality. Conclusions Our results suggest that cell ratio that reflects the adaptive immunity predominance is associated with lower mortality in COPD. This longitudinal immunophenotyping based on routinely collected CBC data may have prognostic value and offer a practical method for improving disease outcome prediction. This abstract is funded by: Supported by Veterans Health Administration, Clinical Science Research and Development, Gulf War Veterans’ Illnesses (VHA-CSRD-GWVI I01# I01CX002841-01 awarded to J.R.); the Airborne Hazards and Burn Pits Center of Excellence (award FY2024-002 to J.R.); the Center for Innovations in Quality, Effectiveness, and Safety (CIN 13-413), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, and Sanofi & Regeneron Pharmaceuticals Inc. The opinions expressed are those of the authors and not necessarily those of the Department of Veterans Affairs, the U.S. government, or Baylor College of Medicine, or Sanofi, or Regeneron Pharmaceuticals Inc.
Razjouyan et al. (Fri,) studied this question.