Elevated levels of CO₂ (hypercapnia) are often observed in patients with chronic obstructive pulmonary disease (COPD). Recently it has been shown that increased CO₂, by activating intracellular calcium signalling pathways, might lead to airway obstruction in a preclinical setting. Here, we investigate whether hypercapnia influences airway resistance in patients with COPD.

We retrospectively analysed clinical characteristics, blood gases and lung function parameters of 84 patients with COPD GOLD stage 2 ? 4, who were recruited in a local registry at the University of Giessen Lung Center between 2014 and 2022. Data were obtained during routine outpatient visits. Partial pressure of oxygen (pO₂), carbon dioxide (pCO₂) in capillary blood samples and lung function obtained via plethysmography were analysed. Patients were categorised as normocapnic (<45 mmHg) or hypercapnic (>45 mmHg) based on pCO2 levels. Our results revealed that specific total airway resistance (sRtot) was markedly increased in the group of hypercapnic COPD patients. Moreover, increased sRtot was associated with GOLD stage and was strongly correlated with pCO₂ levels. Furthermore, receiver operating characteristic (ROC) analysis showed that even very moderately increased concentrations of pCO2 had high specificity and sensitivity in predicting airway obstruction in patients with COPD.

Our data suggest that pCO₂ levels are directly associated with airway obstruction in patients with COPD. As already moderate hypercapnia lead to a marked increase in airway resistance, timely correction of elevated pCO₂ levels may result in a clinical benefit in this patient group.