ASTHMA–CHRONIC OBSTRUCTIVE PULMONARY DISEASE OVERLAP: IMMUNOBIOCHEMICAL MARKERS, OXIDATIVE STRESS, KLOTHO PROTEIN AND THEIR ROLE IN OPTIMIZING PULMONARY HYPERTENSION DIAGNOSTICS

The overlap of bronchial asthma and Chronic obstructive pulmonary disease (COPD) is associated with more severe disease progression and earlier onset of pulmonary hypertension (PH), necessitating novel diagnostic approaches. Objective. To optimize the diagnosis of pulmonary hypertension in patients with asthma–COPD overlap (ACO) using immunobiochemical markers, oxidative stress parameters, and Klotho protein measurement. Materials and Methods. A total of 120 patients were examined (asthma, n = 45, COPD, n = 50, ACO, n = 25) using clinical, instrumental, and immunobiochemical assessment (IL-4, IL-18, TNFα, VEGF-A, Klotho, SOD). Compliance with ethical standards. Written informed consent was obtained from all patients prior to their participation in the study. All procedures were approved by the Ethics Committee of the Institute of Immunology and Human Genomics of the Academy of Sciences of the Republic of Uzbekistan (Protocol №. 2025-0003) and were conducted in accordance with the principles of the Declaration of Helsinki adopted in October 2024 at the 75th General Assembly of the World Medical Association. Statistical analyses were performed using SPSS 26.0. Data are presented as arithmetic mean (M) ± standard deviation (SD) or standard error of the mean (m). Differences were evaluated using Student's t-test and the Mann–Whitney U-test. A p-value < 0.05 was considered statistically significant. Funding: This work was carried out within the framework of the research plan of the Bukhara State Medical Institute (05.2022 DSc.135) entitled “Development of new approaches to early diagnosis, treatment, and prevention of pathological conditions affecting the health of the population of the Bukhara region after COVID-19 (2022–2026)”, as well as on the basis of baseline funding of the research project of the Institute of Immunology and Human Genomics of the Academy of Sciences of the Republic of Uzbekistan “Immunobiochemical and molecular-genetic diagnostics of the cardiorespiratory system in patients with overlapping bronchial asthma and chronic obstructive pulmonary disease in the experimental setting” (Protocol No. 2, 2024). Results. In ACO patients, mean pulmonary artery pressure was 1.8-fold higher compared with asthma patients (24.0 ± 2.1 vs 13.3 ± 1.7 mmHg, p<0.01). IL-18 levels were 3.4-fold higher than in controls (252.6 ± 12.3 vs 73.8 ± 6.4 pg/mL, p<0.001). Klotho protein concentration in ACO with PH exceeded control values by 6.4-fold (42.3 ± 3.1 vs 6.54 ± 0.72 pg/mL, p<0.001), indicating a compensatory response. Conclusion. The combined clinical and immunobiochemical data confirm the hypothesis that the overlap of bronchial asthma and COPD is associated with the most severe course and rapid development of pulmonary hypertension. Immunobiochemical markers, including cytokine profiles, oxidative stress indicators, and Klotho levels, provide valuable tools for improving the accuracy of diagnosis and prognosis in asthma–COPD overlap patients.