2.1. Study Individuals

Patients diagnosed with a severe acute exacerbation of COPD (AE-COPD), defined as those requiring hospitalization according to the Global Initiative for COPD consensus document (GOLD 2022) [16], and patients diagnosed as having stable COPD of all categories and degrees of severity according to the GOLD 2022 [16] were included in this study. Patients were consecutively gathered in real-life scenarios, without bias toward age, gender, BMI, or stage of the disease. All patients with COPD had their post-bronchodilator FEV₁/forced vital capacity (FVC) ratio below 0.7, were managed according to the refined symptom- and exacerbation-based ABCD assessment tool, and were followed up in accordance with the GOLD 2022 consensus report [16]. The exclusion criteria for patients with both stable COPD and AE-COPD included mechanical ventilation, hospitalization into an intensive care unit, unstable coronary artery disease, and the presence of active cancer. Healthy non-smokers and smokers with their lung function within a normal range were incorporated for reference. Current smokers were defined as persons who currently smoked ≥1 cigarette per day and non-smokers were defined as those who had never smoked or who had quit smoking for at least 6 months prior to this study. All study individuals were required to be without upper and lower respiratory tract infections (including acute bronchitis, bronchiolitis, and pneumonia) during this study and for at least 4 weeks before this study with the exception of patients with AE-COPD in whom acute respiratory infections other than pneumonia were allowed, provided that these infections had a causative relation to the current COPD exacerbation as judged by the treating physician. Spirometry [17] and lung diffusing capacity [18] measurements were performed in accordance with the American Thoracic Society/European Respiratory Society standards, whereas multi-ethnic and Finnish reference values were used for spirometry [19] and diffusing capacity [20] indices, respectively.