Associations of oxygenated hemoglobin with disease burden and prognosis in stable COPD: Results from COSYCONET

Abstract

We studied whether in patients with stable COPD blood gases (BG), especially oxygenated hemoglobin (OxyHem) as a novel biomarker confer information on disease burden and prognosis and how this adds to the information provided by the comorbidity pattern and systemic inflammation. Data from 2137 patients (GOLD grades 1-4) of the baseline dataset of the COSYCONET COPD cohort were used. The associations with dyspnea, exacerbation history, BODE-Index (cut-off ≤2) and all-cause mortality over 3 years of follow-up were determined by logistic and Cox regression analyses, with sex, age, BMI and pack years as covariates. Predictive values were evaluated by ROC curves. Capillary blood gases included SaO₂, PaO₂, PaCO₂, pH, BE and the concentration of OxyHem [haemoglobin (Hb) x fractional SaO₂, g/dL] as a simple-to-measure correlate of oxygen content. Inflammatory markers were WBC, CRP, IL-6 and -8, TNF-alpha and fibrinogen, and comorbidities comprised a broad panel including cardiac and metabolic disorders. Among BG, OxyHem was associated with dyspnoea, exacerbation history, BODE-Index and mortality. Among inflammatory markers and comorbidities, only WBC and heart failure were consistently related to all outcomes. ROC analyses indicated that OxyHem provided information of a magnitude comparable to that of WBC, with optimal cut-off values of 12.5 g/dL and 8000/µL, respectively. Regarding mortality, OxyHem also carried independent, additional information, showing a hazard ratio of 2.77 (95% CI: 1.85-4.15, p < 0.0001) for values <12.5 g/dL. For comparison, the hazard ratio for WBC > 8000/µL was 2.33 (95% CI: 1.60-3.39, p < 0.0001). In stable COPD, the concentration of oxygenated hemoglobin provided additional information on disease state, especially mortality risk. OxyHem can be calculated from hemoglobin concentration and oxygen saturation without the need for the measurement of PaO₂. It thus appears well suited for clinical use with minimal equipment, especially for GPs.

Figure 1

Heatmap of associations between comorbidities, blood gases and systemic inflammation with symptom burden (GOLD mMRC)), exacerbation history (GOLD), BODE Index (cut-off value 2) and mortality analyzed by logistic regression analyses. The figure shows p values as derived from multiple regression analyses. The p values for the anthropometric characteristics refer to those obtained from the blood gas analyses. Colors indicate the strength of the associations (from green, p ≥ 0.05, to dark red, strongly significant, p ≤ 0.0001).

Figure 2

The figure shows the absolute change of BODE-Index as derived from multiple linear regression analysis adjusting for sex, age, BMI and pack years for defined changes in four selected predictors. The change is given for a change in OxyHem by −2 g/dL, in WBC count by +2000/µL, or the presence of coronary artery disease (CAD) or heart failure (HF). Additionally, the numerical values of the changes in the BODE-Index, their 95% confidence intervals and the corresponding p values are shown.

Figure 3

Cox proportional hazards cumulative survival curves stratified for either OxyHem <12.5 g/dL, or WBC count >8000/µL. The corresponding hazard ratios for the binary OxyHem were 2.77 (95% CI: 1.85–4.15, p < 0.0001), and for the binary WBC count 2.33 (95% CI: 1.60–3.39, p < 0.0001 s), respectively. We additionally show the combined value in the sense, that either both measures were on the side of elevated risk, or both not, in order to demonstrate their combined value.