Đivo Ljubičić

Objective: Emphysema is an important chronic obstructive pulmonary disease (COPD) phenotype characterized by the destruction of air spaces distal to the terminal bronchiole. Aiming to detect potential emphysema biomarkers and to assess the systemic effects of emphysema in blood plasma, we conducted a small cross-sectional shotgun proteomics study. Methods: This study included N = 40 participants divided into four subgroups (N = 10 per group): patients with emphysema and COPD (CE), patients with COPD but without emphysema (CN), healthy smokers (HS) and healthy never-smokers (HN). The participants were sampled non-probabilistically to be similar in terms of age, sex and comorbidities. Participants’ blood plasma was analyzed using liquid chromatography–mass spectrometry. Bioinformatic analysis included detection of differentially expressed proteins (DEPs) and overrepresentation analysis (ORA). Results: Across all groups, a total of 994 proteins were identified, with NADP-dependent malic enzyme (NADP-ME; encoded by ME1) being the only DEP in the CE vs. CN contrast. Proteins such as BMP1, ADAMTSL-2, -4 and IGFBP4, -5, 6 were identified to be upregulated in CE vs. HN. Fibulin-1, -3 and several immunoglobulin components were identified to be downregulated in the CE vs. HN contrast. ORA revealed several enriched processes, including serine-type endopeptidase activity, insulin-like growth factor I and II binding, and signaling receptor binding. Conclusion: We propose NADP-ME, an important enzyme of intermediary metabolism and redox homeostasis, as a potential biomarker candidate of emphysema. Notably, NADP-ME is also implicated in anoikis resistance. Additionally, changes in the expression levels of BMP1, ADAMTSL-2 and -4, and fibulin suggest potential major systemic effects of extracellular matrix perturbation. As all data was derived from LC-MS analysis, these findings need to be further evaluated with complementary methods.

Pneumocystis jirovecii pneumonia (PCP) remains a frequent cause of intensive care unit (ICU) admission among people living with HIV (PLWH), despite widespread antiretroviral therapy (ART) use. We conducted a retrospective cohort study of 39 PLWH with PCP admitted to the ICU at the Croatian national HIV referral center between 2002 and 2023. Patients were grouped by calendar period (pre-2015 vs. post-2015, reflecting the adoption of the “test and treat” strategy in 2015). Primary outcomes included ICU, 30-day, and 1-year mortality. We also evaluated the association between in-ICU ART initiation and survival. There were 37 (94.9%) males with a median age of 49 years (Q1–Q3, 37.5–54.5). Thirty-three (84.6%) were newly diagnosed with HIV. There were no differences between the observed periods regarding demographic characteristics. ART was initiated in the ICU in 21 (53.8%) patients, more frequently after 2015 (p < 0.001). ICU, 30-day, and 1-year mortality rates were 53.9% (n = 21), 51.3% (n = 20), and 66.7% (n = 26), respectively. Survival significantly improved in the later period, with 1-year survival reaching 54.5% (12/22). In-ICU ART initiation was associated with improved survival in univariable analysis, but this effect attenuated after adjusting for APACHE II or calendar year. Early ART may offer benefit but remains confounded by disease severity and evolving care standards.

Summary Introduction The impact of asthma and chronic obstructive pulmonary disease (COPD) in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) infection is not clearly defined. Blood eosinophil count is a standard diagnostic test which, according to the previously published literature, might have a potential prognostic role on mortality in patients with SARS-CoV‑2 infection. Aim To investigate the potential prognostic value of peripheral blood eosinophil count on all-cause mortality of patients hospitalized with SARS-CoV‑2 infection, as well as to assess the impact of asthma or COPD premorbidity on all-cause mortality. Material and methods We conducted a retrospective registry-based cohort study. Survival analysis was performed by employing the Cox proportional hazards regression model at 30 days of follow-up. Prognostic value of eosinophil count on all-cause mortality was assessed using receiver-operating characteristic (ROC) curve analysis. Results A total of 5653 participants were included in the study. Our model did not reveal that pre-existing asthma or COPD is a statistically significant covariate for all-cause mortality but, indicated that higher eosinophil count at admission might have a protective effect (hazard ratio, HR 0.13 (95% confidence interval, CI 0.06–0.27), p = 0.0001). ROC curve analysis indicates cut-off value of 20 cells/mm³ (81% specificity; 30.9% sensitivity). Conclusion Our results indicate that eosinophil count at hospital admission might have a potential prognostic role for all-cause mortality at 30 days of follow-up; however this was not demonstrated for pre-existing obstructive lung diseases.

Background and Aims: COPD is progressive lung disease with known higher cardiovascular (CV) risk, mainly attributed to smoking of cigarettes as the main etiological factor of disease. The aim of this study was to compare CV risk in patients with COPD to control groups of smokers and non‐COPD and to investigate the relation of lung function variables, COPD severity, and smoking with Systemic Coronary Risk Estimation (SCORE) risk calculation, arterial stiffness (AS) values, and biological systemic inflammatory markers.Methods: A total of 208 subjects were included in this study: 61 subjects diagnosed with COPD, 83 smokers without COPD, and 64 nonsmokers without COPD. Medical history and clinical data were recorded, including assessment of pulmonary function and AS, calculation of ankle‐brachial index, blood analysis, and CV risk assessment by SCORE risk calculation.Results: Subjects with COPD had significantly higher values of SCORE calculation of risk, central aortic pressure, AS, and markers of systemic inflammation compared to control groups of smokers and nonsmokers without COPD (p < 0.001). Furthermore, statistically significant increase in hs‐CRP concentration was found between the COPD group and the control group of non‐COPD smokers (p < 0.001), and a statistically significantly higher SCORE calculation was found in the COPD group compared to control groups of smokers and nonsmokers without COPD (p < 0.001).Conclusion: The results of the research support further identification and research of biological markers and simple specific tests such as arteriography that will enable progress in personalized treatment of patients with COPD and better primary and secondary prevention of comorbidities with the aim of improved treatment outcome.

SARS-CoV-2 has been circulating in population worldwide for the past year and a half, and thus a vast amount of scientific literature has been produced in order to study the biology of the virus and the pathophysiology of COVID-19, as well as to determine the best way to prevent infection, treat the patients and eliminate the virus. SARS-CoV-2 binding to the ACE2 receptor is the key initiator of COVID-19. The ability of SARS-CoV-2 to infect various types of cells requires special attention to be given to the cardiovascular system, as it is commonly affected. Thorough diagnostics and patient monitoring are beneficial in reducing the risk of cardiovascular morbidity and to ensure the most favorable outcomes for the infected patients, even after they are cured of the acute disease. The multidisciplinary nature of the fight against the COVID-19 pandemic requires careful consideration from the attending clinicians, in order to provide fast and reliable treatment to their patients in accordance with evidence-based medicine principles. In this narrative review, we reviewed the available literature on cardiovascular implications of COVID-19; both the acute and the chronic.

Chronic obstructive pulmonary disease (COPD) is a complex condition, whose diagnosis requires spirometric assessment. However, considering its heterogeneity, subjects with similar spirometric parameters do not necessarily have the same functional status. To overcome this limitation novel biomarkers for COPD have been investigated. Therefore, we aimed to explore the potential value of N-glycans as COPD biomarkers and to examine the individual variation of plasma protein and immunoglobulin G (IgG) glycosylation profiles in subjects with COPD and healthy controls. Both the total plasma protein and IgG N-glycome have been profiled in the total of 137 patients with COPD and 95 matching controls from Croatia. Replication cohort consisted of 61 subjects with COPD and 148 controls recruited at another Croatian medical centre. Plasma protein N-glycome in COPD subjects exhibited significant decrease in low branched and conversely, an increase in more complex glycan structures (tetragalactosylated, trisialylated, tetrasialylated and antennary fucosylated glycoforms). We also observed a significant decline in plasma monogalactosylated species, and the same change replicated in IgG glycome. N-glycans also showed value in distinguishing subjects in different COPD GOLD stages, where the relative abundance of more complex glycan structures increased as the disease progressed. Glycans also showed statistically significant associations with the frequency of exacerbations and demonstrated to be affected by smoking, which is the major risk factor for COPD development. This study showed that complexity of glycans associates with COPD, mirroring also the disease severity. Moreover, changes in N-glycome associate with exacerbation frequency and are affected by smoking. In general, this study provided new insights into plasma protein and IgG N-glycome changes occurring in COPD and pointed out potential novel markers of the disease progression and severity.

Introduction: Due to direct impact on survival, cardiovascular (CV) diseases are the most important comorbidities in COPD. Immediate assessment of arterial properties has been widely researched in last decade, as traditional risk factors for CV disease only indirectly suggest the atherosclerotic processes that herald future CV events. Arterial stiffness (AS) is generally accepted as a predictive factor for cardiovascular morbidity and mortality. Aims and objectives: To determine if patients with COPD, without documented comorbidities, have different determinants of AS compared to control groups of apparently healthy smokers and nonsmokers. Methods: Cross-sectional study in 2017 included 61 COPD patients, 83 non-COPD smokers and 65 non-COPD nonsmokers, without comorbidities. After medical history and physical examination, oscillometric device and software were used to assess aortic pulse wave velocity (PWVao) noninvasively. COPD was evaluated by GOLD guidelines. Statistical analysis used Kolmogorov-Smirnov Test and One way ANOVA. Results: Patients with COPD achieved significantly (P<0.001) higher PWVao values (A=11.67 m/s, SD 2.72, 95%CI 10.97–12.36) than control group of non-COPD smokers (A=9.58 m/s, SD 1.61, 95%CI 9.23-9.93) and group of non-COPD nonsmokers (A=9.09 m/s, SD 1.61, 95%CI 8.68-9.49). No difference in AS parameters was observed between two control groups of smokers and non-smokers (P=0.424). Conclusions: Patients with COPD have higher AS and ultimately elevated cardiovascular risk compared to non-COPD controls of smokers and nonsmokers. These results add to the pool of evidence that COPD, independently of smoking, contributes to pathogenesis of atherosclerosis.