Faculty of Medicine

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EVALUATING CHRONIC RHINOSINUSITIS AS A COMORBID DRIVER IN COPD
(Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 2025-07-18)
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Debreshlioska, Angjela
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Introduction: Chronic rhinosinusitis (CRS) is increasingly recognized as a significant comorbidity in patients with chronic obstructive pulmonary disease (COPD), particularly under the framework of the “united airways” model, which emphasizes shared inflammatory mechanisms across the upper and lower respiratory tract. Aim: To evaluate inflammatory biomarker profiles among COPD patients with and without CRS, and to assess differences across distinct COPD phenotypes—non-exacerbators (NE), frequent exacerbators (E), and asthma-COPD overlap (ACO). Material and methods: A cross-sectional study was conducted on 36 COPD patients at a university clinic in Skopje, including 21 with CRS and 15 patients without CRS. All participants underwent clinical phenotyping, nasal endoscopy, sinus CT, and serum biomarker analysis (IL-4, IL-5, IL-6, IL-8, CRP, leukocytes). Statistical comparisons were made using Mann–Whitney U and Kruskal–Wallis tests. Results: CRS was predominantly found in patients with the ACO phenotype (71.4%, p = 0.0006). No statistically significant differences were observed in systemic biomarkers (IL‑4, IL‑5, IL‑6, IL‑8, CRP, leukocytes) between COPD patients with and without CRS. IL‑5 and IL‑6 were undetectable. Similarly, inflammatory profiles did not significantly differ among COPD phenotypes. Conclusion: CRS appears disproportionately represented in the ACO phenotype, likely due to shared type‑2 inflammatory pathways. However, conventional systemic biomarkers lack the sensitivity to detect upper airway involvement or differentiate COPD phenotypes. These findings highlight the need for comprehensive airway assessment and more specific biomarkers in future studies to better understand the interplay between CRS and COPD.
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COPD prevalence and characteristics among sample of working population
(Frontiers Media SA, 2025-05-27)
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Brborović, Hana
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Milošević, Milan
Introduction: COPD is a global public health problem, causing a very high rates of morbidity, mortality, and work disability in the last decades worldwide. Objective: To determine the prevalence and characteristics COPD in a random sample of workers form the city of Skopje, and its relation to occupational exposures. Methods: A cross-sectional study was conducted including 1,867 workers (959 males and 908 females) from the city of Skopje. Afterwards, the study subjects were divided into exposed (1.287/68.9%) and unexposed (580/31.1%) groups based on their current job exposure to noxious particles and gasses. All study participants completed a questionnaire and underwent pre-and post-bronchodilator spirometry. Results: COPD prevalence was 3.9% among all workers. COPD prevalence in exposed workers was significantly higher compared to unexposed (4.7% vs. 2.4%). Significant difference was found in exposed workers with exposure duration longer than 20 years as compared to those with shorter duration of exposure (6.0 vs. 3.2%). COPD prevalence in workers who smoked was significantly higher than in non-smoking workers in both exposed (6.0% vs. 3.9%, p = 0.037) and unexposed (3.9% vs. 1.8%, p = 0.000) groups. The difference between workers with COPD in terms of use of solid and liquid bio fossil fuels at home and central heating/electricity is not significant (5.0% vs. 3.6%), both in exposed (5.4% vs. 4.3%), as well as non-exposed workers (3.8% vs. 1.9%). Conclusion: Our findings confirmed the role of occupational exposures in COPD prevalence indicating a need of more effective preventive activities in order to reduce the overall disease burden.
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COPD PREVALENCE AND CHARACTERISTICS AMONG RETIRED WORKERS
(Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 2025-04)
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Atanasovska, Aneta
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Bislimovska, Dragana
Introduction:Age and exposure to noxious particles and gases are considered as important risk factors for the development of COPD. Aim of the study:To assess the prevalence of COPD in a sample of retired persons from the Skopje region.Material and methods:We performed a cross-sectional study (prevalence study) in a sample of 392 randomly selected retired persons, 207 males and 185 females, aged 56 to 84 years. Study protocol included completion of a questionnaire and pre-and post-bronchodilator spirometry.Results:The prevalence of COPD in the whole sample was 8.7% (34/392),being non-significantly higher in men (9.1%) than in women (8.1%). The difference in COPD prevalence between smoking and non-smoking retired persons was within the borders of statistical significance (10.7% vs.7.5; P=0.084). The difference in COPD prevalence between retired persons exposed to vapors, gases, dusts, and fumes (VGDF) at their workplace during their active period and retired persons with no such exposure just missed statistical significance (9.5% vs.7.4%; P=0.073). COPD prevalence in the smoking retired persons occupationally exposed to VGDF during their active period was significantly higher than its prevalence in the smoking retired persons occupationally unexposed to VGDF during their active period (12.6% vs.8.2%; P=0.036). Conclusion: Our results confirm the role of age and exposure to noxious particles and gases in the COPD development.
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Correlation of Clinical and Inflammatory Parameters in Chronic Obstructive Pulmonary Disease
(SHMSHM - AAMD, 2023-04)
Angjela, Debreshlioska
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Vuinov, Venco
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Karakostova, Marija
Aim: The aim of this study was to determine the values of systemic inflammatory parameters in patients with COPD and to determine their correlation with selected clinical parameters. Material and methods. We conducted a cross-sectional analytical study at PHI University Clinic for Pulmonology and Allergy, on 59 patients diagnosed with COPD. All patients underwent anamnesis with review of medical records for demographic and clinical data, history of allergies, cigarette smoking, and history of exacerbations. Patients completed a COPD assessment questionnaire (CAT) and a modified dyspnea scale (mMRC) and the BODE (Body mass index, Obstruction, Dyspnea, Exercise capacity) index was calculated. Spirometry and lung X-ray were performed. Peripheral blood was taken for analysis of inflammatory parameters. Results: A total of 59 patients were included, of which 14 (23.72%) were women and 45 (76.27%) were men. The mean age was 65.23 years. Statistical analysis showed a significant positive correlation between CRP and GOLD, CAT, mMRC and the existence of chronic bronchitis, as well as a significant linear moderate negative correlation between CRP and CAT. A significant linear positive correlation between Le and GOLD, CAT, mMRC and BODE, a significant linear positive correlation between Ne and GOLD, mMRC and BODE, as well as a significant linear moderate negative correlation between Ne and FEV1 were also determined. Of the cytokines Il-4 showed a significant linear moderate positive correlation with chronic bronchitis, and Il-18 a significant linear strong positive correlation with the presence of emphysema. Conclusion: The existence of a correlation between selected inflammatory and clinical parameters provides additional data that may help elucidate pathogenetic mechanisms and determine potential therapeutic targets that would personalize the approach to the patient with COPD.
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Engaging stakeholders to level up COPD care in LMICs: lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia
(Springer Science and Business Media LLC, 2024-01)
Fernandes, Genevie
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Williams, Siân
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Adab, Peymané
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Gale, Nicola
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de Jong, Corina
Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned.
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METABOLIC SYNDROME (METS) AS ONE OF THE MAJOR COMORBIDITIES OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
(Association of pulmologists from Republika Srpska, 2023-05)
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Baloski, Marjan
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Bushev, Jane
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Mickovski, Ivana
Aim: We aimed to investigate the association between COPD and MetS, the relation to the severity of airflow limitation. Methods: This is a cross-sectional study including 220 patients with initially diagnosed COPD (IG), aged 40 to 75 years and 58 non-COPD subjects matched by age, smoking status, body mass index, as controls (CG). All study participants underwent anthropometric measurements, fasting blood sugar (FBS), lipid profile, pulmonary evaluation (dyspnea severity assessment, baseline and postbronchodilator spirometry, gas analyses, chest X-ray). Results: Results presented statistically significant difference in presence of MetS in COPD patients compared to controls (32.27% vs 10.34%; P=0.0009). According to the GOLD classification, the frequencies of MetS in COPD patients were categorized in stages I, II, III, IV (17.54%, 37.10%, 34.62%, 40.82%, respectively). The proportion of patients with increased glycemic values was: a) GOLD1 - 18 (31.58%); b) GOLD 2 - 32 (51.61%); c) GOLD3 - 29 (55.77%); and d) GOLD4 - 31 (63.27%). There was no significant difference between IG and CG patients regarding HDL level. According to arterial hypertension the highest proportion was observed in GOLD3 - 22 (42.31%) followed by GOLD4 - 20 (40.82%), and GOLD3 - 22 (35.48 %), smallest in GOLD1 - 17 (29.82%). Conclusion: We found higher prevalence of MetS in patients with COPD even in early COPD stages compared to non-COPD. Our findings suggest an urgent need to develop comprehensive strategies for prevention, screening and start of treatment in early stage.
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COVID-19 and chronic respiratory diseases
(Serbian Association of Allergology and Clinical Immunology, 2021)
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The burden of chronic respiratory diseases in Macedonia
(2018)
Aim: Chronic respiratory diseases involve a heterogeneous group of disease, including, COPD, asthma, sleep apnea syndrome, pulmonary hypertension and many occupational diseases. This study aims to estimate the burden of chronic respiratory diseases (CRDs) and 10-year mortality trend compared to other non-communicable diseases in Macedonia. Material and Methods: Data was retrieved from official reports by State Statistical Office, annual reports of the Health Insurance Fund, the burden of disease estimates by WHO Global Health Observatory data as well as the Institute for Health Metrics and Evaluation (IHME). Analytical and descriptive methods were used to present the results. Results: A total of 4 886 deaths due to chronic respiratory diseases were recorded in a 10-year period from 2007 to 2017 or 3% of total deaths in Macedonia, making it the 5th leading cause of death. The mortality rate increased from 18, 35 deaths per 100.000 population in 2007 to 30, 64 in 2017. Chronic respiratory diseases related Disability Adjusted Life-Year (DALYs) burden of approximately of 728.72 per 100.000 or rank 9 at the leading causes for disability and premature mortality. In Macedonia COPD is in the top 15 leading causes due to premature mortality, with an estimated burden of 504.84 DALYs per 100.000. Highest risk factors related burden was attributed to the environment and smoking. Conclusion: Although they are preventable, chronic respiratory diseases are in the top 10 leading causes for mortality and disability in Macedonia, with a projection to increase as air-pollution and smoking rates are still high and the population ages. The lack of epidemiological data, national guidelines for treatment and management allows these diseases to be on the rise, as effective policy and strategy is very much needed.
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LUNG CANCER AS A COMORBIDITY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
(2023-01)
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Buklioska Adriana
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Mickovski Ivana
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Trajkova Vesna
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COPD is a risk factor for lung cancer development independent of smoking status, with three to six times more likely to develop lung cancer at a rate of 0.8–1.7%/year. This may be associated with genetic susceptibility to cigarettes, chronic inflammation caused by toxic gases. Inflammatory mediators may promote the growth of bronchioalveolar stem cells, and activation of nuclear factor-κB and signal transducer and activator of transcription 3 play crucial roles in the development of lung cancer from COPD. The aim of the study is to evaluate the prevalence of lung cancer in patients with COPD. We performed a retrospective study, from 2012 to 2022, among patients with pathologically confirmed diagnosis of lung cancer, aged 40-75 years. Patients with lung cancer that had COPD diagnosed >= 10 years before lung cancer diagnosis, were investigated group. Histological subtypes of lung cancer were determined based on histopathology reports and were categorized as squamous carcinoma, adenocarcinoma, small cell lung cancer (SCLC), large cell lung cancer (LCLC; including large cell neuroendocrine carcinoma), and other histological types according to 2015 WHO classification of lung tumors. At the time of registration, sex, age, BMI, smoking status, treatment history, and symptoms, including the CAT score, were recorded. In addition, at the time of registration, spirometry was performed both before and after inhalation of a bronchodilator, and a blood test and chest CT were also performed. The GOLD criteria was used to diagnose and assign severity of COPD: patients with a postbronchodilator FEV1/FVC <0.70 were classified as having COPD; FEV1 ≥0.8 was defined as mild, 0.5≤ FEV1 <0.8 as moderate, 0.3≤ FEV1 <0.5 as severe, and FEV1 ≤0.3 as extremely severe. Patients were excluded if they presented with simultaneous or sequential second primary cancers or had a history of asthma, bronchiectasis, tuberculosis, pulmonary fibrosis, or other confounding diseases. The middle age of lung cancer diagnosis was 61.1±8.5 years. Of the total number of patients with COPD and lung cancer (260), 195 (75.0%) were male and 65 (25.0%) female. 190 (73.07%) were current smokers or ex-smokers. The histological subtypes identified were as follows: squamous carcinoma (96 [36.9%]), adenocarcinoma (115 [44.2%]), SCLC ( 26 [10.0%]), LCLC (13 [5.0%]), and other histologic types (including adenosquamous, carcinoma carcinoid tumors, sarcomatoid carcinoma; 16 [6.15%]). The proportion of squamous carcinoma was higher in smokers/ex smokers with COPD, while adenocarcinoma was more frequently observed in COPD non-smokers. Emphysema predominant phenotype was an independent prognostic risk factor for squamous carcinoma. The prevalence of COPD in lung cancer patients was 35.5%. Compared with lung cancer patients with non-COPD, those with COPD were older (P<0.001), had a lower BMI (P<0.001), and majority were male (P<0.001) and smokers (P<0.001). Annual low-dose computed tomography (LDCT) is an effective procedure for the early detection of lung cancer in high-risk patients like patients with COPD.
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PREVALENCE OF BRONCHIECTASIS IN COPD PATIENTS
(2023-01)
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Mickovski, Ivana
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Neshovska, Radmila
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Buklioska, Adriana
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Trajkova, Vesna
Introduction - There is increasing recognition that radiological bronchiectasis is present in many patients with COPD. Computed tomography scan images have been used to identify different radiological COPD phenotypes based on the presence and severity of emphysema, bronchial wall thickening, and bronchiectasis. Bronchiectasis is defined as an abnormal dilation of the bronchi, usually as a result of chronic airway inflammation and/or infection. The prevalence of bronchiectasis in patients with COPD is high, especially in advanced stages, estimated prevalence varies from 4% to 50%. Methods - COPD patients underwent chest CT as part of their clinical assessment. Patients were included if COPD was diagnosed based on spirometry and clinical assessment and excluded if there was clinical bronchiectasis. Scoring was by a simplified system based on Smith (Thorax, 1996) and returned a score of 0 (no bronchiectasis), 1 (0–50% of bronchi involved), or 2 (50–100% of bronchi involved) for each lobe, with a total score of 12 including the lingula; emphysema, interstitial lung disease (ILD), or other pathology was noted. A total of 220 COPD patients (77.2% ex- or current smokers, 79.5% male) were consecutively enrolled. Results - Bronchiectasis was present in 54.5% of patients (score ≥2/12) and there was significant inter-observer correlation in the scoring (r=0.63, p<0.0001). Scores were highest in the lower lobes and lowest in the middle lobes (1.66 vs 0.86, p<0.000). Patients with widespread bronchiectasis (score ≥6/12) had a trend towards reduced bronchodilator reversibility (4% vs 9%, p=0.08) than those with limited bronchiectasis. Emphysema was present in 77.2% and ILD in 11.36%. The overall prevalence of emphysema was not different between patients with and without previous pulmonary tuberculosis (PTB) n=30 (13.63%), but in those with previous PTB, a higher number of subjects with middle (p=0.002) and lower (p=0.017) lobe emphysema, higher severity score (p=0.029), higher prevalence of panlobular emphysema (p=0.015), and more extensive centrilobular emphysema (p=0.036) were observed. Conclusions - In this study, we found a higher prevalence of bronchiectasis than previously reported which may reflect the heterogeneity of COPD patients in a general respiratory clinic. Radiological features of bronchial wall thickening and mild bronchiectasis were commonly seen and when widespread this may result in reduced bronchodilator reversibility; however, the presence of radiological bronchiectasis was not related to disease severity. COPD patients with previous PTB had unique features of bronchiectasis and emphysema on HRCT, which were associated with significant dyspnea and higher frequency of severe exacerbations.

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