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To determine the frequency of common symptoms in long COVID and their effect on the quality of life, and to determine the factors contributing to a more severe long COVID.The study enrolled 266 patients who were either referred to long-COVID outpatient clinic or were inpatients undergoing rehabilitation. The data were collected between December 2020 and May 2021. We evaluated the symptoms experienced during acute and long COVID and comorbidities. Functional status was assessed with Post Covid Functional Status (PCFS).The final sample consisted of 261 patients. After acute COVID-19 period (4 weeks), almost 80% of patients had impaired functional status. Only 21.5% reported no functional impairment (0 on PCFS scale). A higher PCFS score was associated with female sex (P0.001) and oxygen therapy requirement during acute disease (P=0.001). However, it was not associated with having a pre-existing lung disease (P=0.749). Disease severity did not pose a risk for developing a more severe long COVID.Women were at greater risk for developing greater functional impairment in long COVID, although we have no explanation why. Malignant disease and hypertension also presented a risk factor for greater functional impairment. More studies are warranted to determine if patients with certain lung disease are more susceptible to long COVID.

To determine the effect of lockdown measures on lung transplant patients during the COVID-19 pandemic.We collected data from Croatian lung transplant patients before and after the lockdown and analyzed changes in weight, BMI, lung function and blood lipid status.An average increase of 3.74 kg (+4.92%) body weight during the 4 month lockdown period was observed. Lung function values and blood lipid status remained stable.Such weight gain could have detrimental effects on the morbidity and mortality of lung transplant patients. Further follow up is needed to determine the long term impacts of this observation.

Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation plays an important role in chronic obstructive pulmonary disease (COPD) pathogenesis and might be involved in ongoing chronic inflammation. This study aimed to determine interleukin-1beta (IL-1β) plasma concentration as well as IL1B, NLRP3 and caspase-1 (CASP1) gene expression in the Croatian COPD patients. 109 patients with stable COPD and age- and sex-matched 95 controls were included in the study. Plasma IL-1β concentration was measured by Luminex technology, and gene expression analysis was performed using TaqMan assays. It was shown that COPD patients had increased concentration of IL-1β and enhanced gene expression of IL1B, NLRP3 and CASP1 compared to controls. There was no difference in IL-1β or IL1B, NLRP3 and CASP1 in patients with COPD regarding airflow obstruction severity and smoking history. Finally, the diagnostic potential of the determined parameters was evaluated, and it was found that IL-1β correctly classified 89% of cases in the combination with common inflammatory biomarkers, white blood cell count and fibrinogen, showing a potential in COPD prediction. In conclusion, up-regulation of IL1B, NLRP3, CASP1 and increased IL-1β concentration suggest the activation of NLRP3 inflammasome in the systemic compartment of patients with stable COPD.

Background: Besides the burden of acute covid care, a fraction of patients report symptoms after the period of acute covid illness which affect quality of life and prolong recovery. Aim: To assess the profile of patients reporting to our post-covid clinic, their quality of life and frequency of persisting symptoms. Methods: Covid- 19 survivors, referred (at least a month after the acute illness) from December 2020 to January 2021 to our Centre’s post-covid clinic. Patients entered this study by filling out a questionnaire which also included current symptoms and standardised Post-Covid Functional Scale (PCFS) score. Results: 112 patients were included in the study. Males predominated (62.5% ; mean age 56) over females (37.5% ; mean age 48). In the acute phase, 72.3% were treated as outpatients, 27.6% at the ward and 7.1% in the ICU. Most common comorbidities were hypertension (21.4%), various chronic lung diseases (22.3%) and type 2 diabetes (5.4%). Corticosteroid therapy was given in 45.5% of patients, either in the acute phase, post-covid period, or both. The most frequent post- covid complaints were exhaustion (63.4%), shortness of breath (48.2%), muscle weakness (31.3%), dry cough (34.8%) and chest pain (25.0%). Of 110 patients with known PCFS value, 27 (24.5%) reported 0, while 34 (30.9%), 31 (28.2%), 17 (15.5%), and one (0.9%) patient reported scores of 1, 2, 3, and 4, respectively. Conclusion: Even though the majority of our patients were treated as outpatients in the acute phase and presumably had milder disease forms, three-quarters of them still experience impairment of life quality (PCFS >1) with pronounced respiratory symptoms months after the illness.

Chronic inflammatory lung diseases are characterized by uncontrolled immune response in the airways as their main pathophysiological manifestation. The lack of specific diagnostic and therapeutic biomarkers for many pulmonary diseases represents a major challenge for pulmonologists. The majority of the currently approved therapeutic approaches are focused on achieving disease remission, although there is no guarantee of complete recovery. It is known that angiotensin-converting enzyme 2 (ACE2), an important counter-regulatory component of the renin–angiotensin–aldosterone system (RAAS), is expressed in the airways. It has been shown that ACE2 plays a role in systemic regulation of the cardiovascular and renal systems, lungs and liver by acting on blood pressure, electrolyte balance control mechanisms and inflammation. Its protective role in the lungs has also been presented, but the exact pathophysiological mechanism of action is still elusive. The aim of this study is to review and discuss recent findings about ACE2, including its potential role in the pathophysiology of chronic inflammatory lung diseases:, i.e., chronic obstructive pulmonary disease, asthma, and pulmonary hypertension. Additionally, in the light of the coronavirus 2019 disease (COVID-19), we will discuss the role of ACE2 in the pathophysiology of this disease, mainly represented by different grades of pulmonary problems. We believe that these insights will open up new perspectives for the future use of ACE2 as a potential biomarker for early diagnosis and monitoring of chronic inflammatory lung diseases.

The nutritional status in chronic obstructive pulmonary disease (COPD) patients is an important factor that influences the prognosis of the disease. The aim of this investigation was to study nutritional status in COPD patients and to investigate the association between nutritional status, disease severity and exercise capacity in four different regions of Croatia. In a multicentre study, 534 patients with COPD were recruited and their demographic characteristics were evaluated. Measurements included body composition by bioelectrical impedance analysis - fat free mass (FFM), fat free mass index (FFMI), sarcopenic index (SI), phase angle (PhA), pulmonary function tests and 6-minute walk test (6MWT). There were 325 (60, 9%) male and 209 (39, 1%) female patients with 66, 7±8, 4 years. FEV1 was 52±19, 3% (males) and 60±23, 8% (females), 6MWT was 396, 5±110, 8m. Body mass index (BMI) was 26, 3±5, 5kg/m2, FFM was 61, 8±10kg (males) and 46±8, 3kg (females), FFMI was 20, 6±2, 8kg/m2 (males) and 18, 6±3, 1kg/m2 (females), SI was 8, 2±1, 4kg/m2 (males) and 6, 9±1kg/m2 (females) with no statistical difference between centres (p=0.313 ; p=0.971 ; p=0.565 ; p=0.860 ; p=0.690 ; p=0.562). PhA was 6±1, 8° (males) and 5, 6±1, 7° (females). There were significant positive correlation of FEV1 with BMI (r=0, 148, p=0, 001), PhA (r=0, 256, p=0, 00), FFM (r=0.365, p=0, 00), SI (r=0, 238, p=0, 00), but no significant correlation of 6MWT with BMI (r=-0, 049, p=0, 254), FFM (r=0.065, p=0, 133) and SI (r=-0, 007, p=0, 867). Data showed that our patients are well-nourished and that there is no significant difference between centres in BMI, FFM, FFMI and SI. There is a significant correlation between nutritional status and disease severity.

Here we retrospectively analyzed the post-COVID-19 register of University Hospital Zagreb, Clinic for Pulmonary Diseases Jordanovac in Croatia to compare COVID-19 incidence between smokers and nonsmokers. No significant differences among smokers and non-smokers were found regarding the severity of the disease. COVID-19 should be used as a chance to educate the public about adaptive, healthy stress-release methods and the necessity for smoking cessation, to prevent and preserve overall physical and psychical health.

Background and Aims: Limited number of studies investigated lipid profile in chronic obstructive pulmonary disease (COPD) with inconsistent results. This study aimed to investigate lipid parameters in sera of patients with stable COPD and their associations with disease severity, smoking, comorbidities and therapy. Methods and Results: The study included 137 COPD patients and 95 controls. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed. Non-HDL-C (NHC), atherogenic coefficient (AC), TG/HDL-C, atherogenic index of plasma (AIP), Castelli's risk index I and II (CRI- I, CRI-II), and monocyte to HDL ratio (MHR) were calculated. HDL-C and MHR were increased, while other lipid parameters and indices were decreased in COPD patients compared to healthy individuals. Smoking did not influence lipid parameters. However, lipid profile was altered only in more severe disease stages. AC, CRI-I and CRI-II showed positive association with lung function parameters in COPD patients, and negative with COPD multicomponent indices (ADO, BODCAT, BODEx, CODEx and DOSE). Combined model that included CRI-II, C- reactive protein, fibrinogen and white blood cells showed great diagnostic performances, and correctly classified 72% of study participants with an AUC of 0.800 (0.742 - 0.849), P < 0.001. Bronchodilator monotherapy and statins have opposite impact on TC, LDL-C and NHC, while TG, TG/HDL-C and AIP were increased in COPD patients with cardiovascular diseases. Conclusion: Lipid disbalance is present in COPD, and it seems to occur later as the disease progresses. Further studies are needed to illuminate the underlying mechanism of dyslipidaemia.

Objectives: Cystic fibrosis (CF) is a chronic, life-shortening disease with a significant treatment burden. Today, managing CF is an ongoing challenge - from adhering to treatment plans to managing symptoms to optimize quality of life. The aim of this study is to show if nurse-provided education can improve adherance and quality of life in patients with CF. Methods: 28 CF patients (12 male, 14 female), aged 18 to 36, were recruited from adult CF centre in Zagreb, Croatia. Nurse educated each patient on the importance of respiratory clearance and nutrition, taking medication and inhaler therapy use. Forced expiratory volume in 1 second (FEV 1 ) and BMI were measured prior to education and again 4 months later. Patients completed Short form 36 Health Survey Questionnaire (SF-36), Morisky, Green and Levine scale (MGL) and the Culig Scale before and 4 months after education. Results: After education, FEV1 value increased by 5, 27% and BMI increased 2, 31%. Difference was not statistically significant but correlation shows statistically significant positive connection. Results obtained at the beginning using MGL scale show that 65% of patients (17 out of 26) occasionally forgot to take prescribed treatment. 4 months later, results show 16, 9% improvement. Čulig scale indicates forgetfulness as main reason for non-adherence and 18% improvement after 4 months. Both results are not statistically significant. SF-36 indicate a positive trend in improving perception of one’s health and quality of life since 7% of patients responded their overall health improved. Conclusion: This study suggests a significant role of the nurse in patient care and importance of nurse-provided education.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide, with 5-year overall survival less than 15%. Therefore, it is essential to find biomarkers for early detection and prognosis. Aberrant DNA methylation is a common feature of human cancers and its utility is already recognized in cancer management. The aim of this study was to explore the diagnostic and prognostic value of the promoter methylation status of the ASC/TMS1/PYCARD and MyD88 genes, key adaptor molecules in the activation of the innate immune response and apoptosis pathways. METHODS: A total of 50 non-small cell lung cancer (NSCLC) patients were enrolled in the study. Methylation of bisulphite converted DNA was quantified by pyrosequencing in fresh frozen malignant tissues and adjacent non-malignant tissues. Associations between methylation and lung function, tumor grade and overall survival were evaluated using receiver-operating characteristics (ROC) analysis and statistical tests of hypothesis. RESULTS: Methylation level of tested genes is generally low but significantly decreased in tumor tissues (ASC/TMS1/PYCARD, P

AimsChronic obstructive pulmonary disease (COPD) is characterised with oxidative stress. Paraoxonase 1 (PON1) is an enzyme, coded by PON1 gene, with distinctive antiatherogenic and antioxidative roles. We aimed to investigate the frequencies of Q192R, L55M and −108C>T polymorphisms and association of those polymorphisms with paraoxonase and arylesterase activities in patients with COPD.MethodsPON1 genotype was determined by PCR–restriction fragment length polymorphism method. PON1 activity was measured by paraoxon and phenylacetate.ResultsOnly −108C>T polymorphism resulted in significantly different distribution of genotypes and alleles, with higher frequency of TT genotype and T allele in patients compared with control subjects. Moreover, T allele (OR 2.29 (95% CI 1.54 to 3.41); pT polymorphism was suggested as a significant diagnostic predictor for the disease (OR (95% CI) 2.65 (1.53 to 4.59), p=0.001), with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.84 to 0.93) and with 83.90% of correctly classified cases.ConclusionsHigher frequency of TT genotype and T allele could contribute to the observed reduction of PON1 activity in patients with COPD. T allele and TT genotype are associated with COPD, and the PON1−108C>T polymorphism could be a potential predictor of the disease.

Chronic obstructive pulmonary disease (COPD) is a complex inflammatory condition that can affect haemostasis. This study aimed to determine differences in platelet-related parameters between controls and COPD subjects. The hypothesis was that platelet indices are disturbed in COPD patients, and this would be accompanied by increased C-reactive protein (CRP), fibrinogen (Fbg) and white blood cells (WBC). Therefore, platelet count (Plt), platelet-related parameters – mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (Pct), their ratios (MPV/Plt, MPV/Pct, PDW/Plt, PDW/Pct), platelet to lymphocyte ratio (PLR), Plt index as well as CRP, Fbg and WBC were assessed. Materials and methods: Study included 109 patients with stable COPD and 95 control subjects, recruited at Clinical Department for Lung Diseases Jordanovac, University Hospital Centre Zagreb (Zagreb, Croatia). Complete blood count was performed on Sysmex XN-1000, CRP on Cobas c501, and Fbg on BCS XP analyser. Data were analysed with MedCalc statistical software. Results: Platelet (P = 0.007) and PLR (P = 0.006) were increased, while other platelet indices were decreased in COPD patients compared to controls. Combined model that included PLR, PDW and WBC showed great diagnostic performances, and correctly classified 75% of cases with an AUC of 0.845 (0.788 – 0.892), P < 0.001. Comorbidities (cardiovascular or metabolic diseases) had no effect on investigated parameters, while inhaled corticosteroids/long-acting β2-agonists (ICS/LABA) therapy increased MPV and PDW values in COPD patients. Conclusion: Platelet indices were altered in COPD patients and they could be valuable as diagnostic markers of COPD development, especially if combined with already known inflammatory markers.

Novel hematological parameters such as immature granulocytes (IG), activated neutrophils (NEUT-GI, NEUT-RI) and lymphocytes (RE-LYMP, AS-LYMP) are shown to be valuable for detecting and monitoring infections and inflammations. Our aim was to assess the connection between these parameters and the severity and outcome of COPD exacerbations (AECOPD). 90 patients with AECOPD who visited our pulmonary emergency room from May to August 2018 were included in this retrospective study. Patients’ sex, age, therapy, smoking status, laboratory findings, comorbidities, spirometry results, blood gas analysis, hospitalization or discharge from the ER, duration of hospitalization and survival were evaluated. Hematological parameters were determined by flow cytometry method on a SYSMEX XN-1000 hematological analyzer. Pearson’s correlation test, Chi square and t-test were used for data analysis. 52 patients were male (58%) and 38 female (42%). There were 57 active smokers (64%), 5 former smokers (5.5%) and 28 non- smokers (31%). All patients had comorbidities, mostly hypertension (75, 5%) and diabetes (20%). 19 were admitted to the hospital (21%), and 4 died (4.4%). Correlation between CRP and IG (r=0.363) and NEUT-GI (r=0.230) was low positive, and between CRP and AS-LYMP (r=-0.068), RE-LYMP (r=-0.039) and NEUT-RI (r=-0.251) was low negative. There was no significant difference in these parameters between patients who were discharged from the ER and those who were hospitalized, as well as between patients who died and those who survived. In conclusion, further research on a larger number of patients is required, given these parameters could be promising new biomarkers of inflammation.

Introduction: Chronic obstructive pulmonary disease (COPD) is a condition with underlying systemic inflammation and haemostatic changes. Aims and objectives: Assessment of the platelet indices - platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) and platelet to lymphocyte ratio (PLR), evaluation of their diagnostic value and association with well-known inflammatory markers. Methods: 109 patients with stable COPD and 95 healthy controls were included. Blood samples were collected in different tubes depending on the analysis. The results were analyzed by Mann-Whitney Rank Sum test performed by MedCalc statistical software. Results: Among platelet indices, PLT (P=0.007) and PLR (P=0.005) were significantly increased, while MPV (P

Introduction: guidelines for nontuberculous mycobacterial pulmonary disease (NTMPD) treatment are mainly based on cohort studies and data on M. avium complex (MAC). Methods: retrospective analysis of all Croatian residents with respiratory NTM isolate from 2006 to 2016. ATS/IDSA guidelines were used for NTMPD definition. Cure was defined as multiple negative cultures at the end of treatment or at 12 months follow-up in case of shorter regimens. Regimens were grouped as: tuberculosis (TB), adequate NTM (NTM)

Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive decline in lung function due to airflow limitation, mainly related to IL-1β-induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in NLRP genes, coding for key regulators of IL-1β, are associated with pathogenesis and clinical phenotypes of COPD. We recruited 704 COPD individuals and 1238 healthy controls for this study. Twenty non-synonymous SNPs in 10 different NLRP genes were genotyped. Genetic associations were estimated using logistic regression, adjusting for age, gender, and smoking history. The impact of genotypes on patients’ overall survival was analyzed with the Kaplan–Meier method with the log-rank test. Serum IL-1β concentration was determined by high sensitivity assay and expression analysis was done by RT-PCR. Decreased lung function, measured by a forced expiratory volume in 1 s (FEV1% predicted), was significantly associated with the minor allele genotypes (AT + TT) of NLRP1 rs12150220 (p = 0.0002). The same rs12150220 genotypes exhibited a higher level of serum IL-1β compared to the AA genotype (p = 0.027) in COPD patients. NLRP8 rs306481 minor allele genotypes (AG + AA) were more common in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of group A (p = 0.0083). Polymorphisms in NLRP1 (rs12150220; OR = 0.55, p = 0.03) and NLRP4 (rs12462372; OR = 0.36, p = 0.03) were only nominally associated with COPD risk. In conclusion, coding polymorphisms in NLRP1 rs12150220 show an association with COPD disease severity, indicating that the fine-tuning of the NLRP1 inflammasome could be important in maintaining lung tissue integrity and treating the chronic inflammation of airways.

Interstitial lung diseases (ILD) are a heterogeneous group of diseases and one of the differential diagnosis which have to be excluded during diagnostic procedures are malignancies. We will present four patients who were referred to our Department because of suspicion of interstitial lung diseases according to radiology finding. In one case only, one of the radiologist’s differential diagnosis was pulmonary lymphangitic carcinomatosis. All four patients had exertional dyspnea and dry cough which are nonspecific and can be first manifestation of ILD or obstructive lung diseases. After diagnostic evaluation in three cases, diagnosis was pulmonary lymphangitic carcinomatosis due to metastatic lung adenocarcinoma and in one due to metastatic adenocarcinoma of unknown primary origin. Patients with lymphangitic carcinomatosis have poor prognosis without treatment and usually die because of respiratory failure. With these four cases we want to highlight importance of thinking about malignancies when we have patients with suspicion of interstitial lung disease especially when reticular pattern is present on chest X ray. We also wanted to show how important is radiology finding and multidisciplinary approach, and how radiologist’s differential diagnosis can be very helpful in making decisions in further investigations and way of clinicians thinking.

Lung cancer incidence in heart transplant patients is higher than in general population and correlates with smoking history. EGFR-mutations are more frequent in adenocarcinoma and among non-smoking women but incidence in solid organ transplanted patients is still not known. We present case of a 65-year-old ex-smoker male with history of heart transplantation and EGFR positive metastatic lung adenocarcinoma. At admission he was in a severe clinical condition and treatment with erlotinib was started. Initially he had good clinical and radiologic response to treatment with only grade 1 side effects. Data about drug interactions between cyclosporine and erlotinib are insufficient but we have to take this interaction into consideration during treatment because both drugs are substrates and inhibitors of CYP34A. In our case erlotinib was safe and well tolerated drug, there were no relevant toxicity, but close monitoring and dose reduction of cyclosporine was needed.

Extracellular heat shock protein 70 (eHsp70) might modulate immune responses in chronic obstructive pulmonary disease (COPD). The aim of the study was to explore eHsp70 concentration in stable COPD, its association with disease severity and smoking status as well as its diagnostic performance in COPD assessment. Plasma samples were collected from 137 COPD patients and 95 healthy individuals, and concentration of eHsp70 was assessed by commercially available enzyme-linked immunosorbent assay (ELISA) kit (Enzo Life Science, Farmingdale, NY, USA). COPD patients were subdivided regarding airflow obstruction severity and symptoms severity according to the Global Initiative for COPD (GOLD) guidelines. eHsp70 concentration increased in COPD patients when compared to controls and increased with the severity of airflow limitation as well as symptoms burden and exacerbation history. eHsp70 concentration did not differ among COPD patients based on smoking status, yet it increased in healthy smokers compared to healthy nonsmokers. In addition, eHsp70 negatively correlated with lung function parameters forced expiratory volume in one second (FEV1) and FEV1/ forced vital capacity (FVC), and positively with COPD multicomponent indices BODCAT (BMI, airflow obstruction, dyspnea, CAT score), BODEx (BMI, airflow obstruction, dyspnea, previous exacerbations), CODEx (Charlson&rsquo, s comorbidity index, airflow obstruction, dyspnea, previous exacerbations) and DOSE (dyspnea, airflow obstruction, smoking status, previous exacerbations) With great predictive value (OR = 7.63) obtained from univariate logistic regression, eHsp70 correctly classified 76% of cases. eHsp70 is associated with COPD prediction and disease severity and might have the potential for becoming an additional biomarker in COPD assessment.

Background: Lung cancer is the leading cause of cancer-related death worldwide, with 5-year overall survival less than 15%. Therefore, it is essential to find biomarkers for early detection and prognosis. Aberrant DNA methylation is a common feature of human cancers and its utility is already recognized in cancer management. The aim of this study was to explore the diagnostic and prognostic value of the promoter methylation status of the ASC/TMS1/PYCARD and MyD88 genes, key adaptor molecules in the activation of the innate immune response and apoptosis pathways. Methods: A total of 50 non-small cell lung cancer (NSCLC) patients were enrolled in the study. Methylation of bisulphite converted DNA was quantified by pyrosequencing in fresh frozen malignant tissues and adjacent non- malignant tissues. Associations between methylation and lung function, tumor grade and overall survival were evaluated using receiver- operating characteristics (ROC) analysis and statistical tests of hypothesis. Results: Methylation level of tested genes is generally low but significantly decreased in tumor tissues (ASC/TMS1/PYCARD, P

Extracellular adenosine triphosphate (eATP)-driven inflammation was observed in chronic obstructive pulmonary disease (COPD) but was not investigated in patients’ blood. Therefore, this study aimed to investigate eATP concentration in plasma of COPD patients and its association with disease severity and smoking. Study included 137 patients with stable COPD and 95 control subjects. eATP concentration was determined in EDTA plasma by luminometric method, and mRNA expression of eATP receptors P2X7R and P2Y2R was analysed by quantitative polymerase chain reaction (qPCR). eATP concentration was increased in COPD patients compared to controls (P 1 and multicomponent indices (ADO, BODEx, BODCAT, CODEx, DOSE). Regarding gene expression, P2Y2R was increased in the blood of COPD patients. Plasma eATP could become a diagnostic and/or prognostic biomarker in COPD, as it seems to be associated with patients’ condition, quality of life and disease progression.

SUMMARY Pulmonary hypertension (PH) is a chronic disease which severely impairs quality of life (QoL). The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first disease-specific tool to assess patient-reported symptoms, functioning and QoL in PH patients. The aim of this study was to adapt and validate the CAMPHOR for use in Croatia. The adaptation process involved three stages: translation (bilingual and lay panel), cognitive debriefing interviews with patients and psychometric validation. For the latter stage, a postal survey was conducted with 50 patients to examine the reliability and validity of the adapted scale. All three scales of the Croatian CAMPHOR demonstrated excellent internal consistency (Symptoms = 0.93; Activity limitations = 0.94; QoL = 0.92) and test-retest reliability correlations (Symptoms = 0.90; Activity limitations = 0.95; QoL = 0.90). Predicted correlations with the SF-36 scales provided evidence for construct validity of the CAMPHOR scales. Evidence for known group validity was shown by the ability of the scales to distinguish between participants based on patient-perceived general health and disease severity. The Croatian version of the CAMPHOR is a valid and reliable tool for use in clinical routine and clinical research.

Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive decline in lung function due to airflow limitation, mainly related to IL-1&beta, induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in NLRP genes, coding for key regulators of IL-1&beta, are associated with pathogenesis and clinical phenotypes of COPD. We recruited 704 COPD individuals and 1238 healthy controls for this study. Twenty non-synonymous SNPs in 10 different NLRP genes were genotyped. Genetic associations were estimated using logistic regression, adjusting for age, gender, and smoking history. The impact of genotypes on patients&rsquo, overall survival was analyzed with the Kaplan&ndash, Meier method with the log-rank test. Serum IL-1&beta, concentration was determined by high sensitivity assay and expression analysis was done by RT-PCR. Decreased lung function, measured by a forced expiratory volume in 1 s (FEV1% predicted), was significantly associated with the minor allele genotypes (AT + TT) of NLRP1 rs12150220 (p = 0.0002). The same rs12150220 genotypes exhibited a higher level of serum IL-1&beta, compared to the AA genotype (p = 0.027) in COPD patients. NLRP8 rs306481 minor allele genotypes (AG + AA) were more common in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of group A (p = 0.0083). Polymorphisms in NLRP1 (rs12150220, OR = 0.55, p = 0.03) and NLRP4 (rs12462372, OR = 0.36, p = 0.03) were only nominally associated with COPD risk. In conclusion, coding polymorphisms in NLRP1 rs12150220 show an association with COPD disease severity, indicating that the fine-tuning of the NLRP1 inflammasome could be important in maintaining lung tissue integrity and treating the chronic inflammation of airways.

Introduction: COPD is characterized by airway remodeling and loss of pulmonary parenchymal elasticity. Spirometry is not enough to differentiate the contribution of each. Emphysema and bronchial wall thickness are better assessed by quantitative analysis of MSCT image data. MSCT achievements have enabled to assess the bronchial wall thickness and to quantify the extent of emphysema. Aim: to evaluate functional tests in comparison with bronchial wall thickness (Lumen/Bronchus diameter ratio) and amount of emphysema Methods: We observed 15 COPD pts with emphysema. All pts performed lung function tests and MSCT analyzed in Myrian program, module to quantify the extent of emphysema. In order to quantify bronchial wall thickness, we wanted to test lumen/whole bronchus diameter ratio (L/B ratio) as a simple indirect measure of bronchial wall thickness compared to lung function tests, therefore avoiding the need for additional calculating or computing bronchial wall area. Results: Linear regression test showed significant negative correlation of the right pulmonary emphysema with FEV1(p 0.037) and L/B ratio(p 0.035), what can not be elicited for left pulmonary emphysema and FEV1 nor L/B ratio(p 0.08, p 0.23). Positive significant correlation was established between L/B ratio and FEV1(p0.008 ; R248%), as well as among the L/B ratio and DLCO values (p0.02, R240%) Conclusion: Allowing for limited data, there is good correlation between functional tests and L/B ratio. At this point, there is only limited correlation for amount of emphysema with functional tests and L/B ratio. However, the project is in progress.

Introduction: Cigarette smoke is one of the major risk factors for development of chronic obstructive pulmonary disease (COPD), which is characterized by chronic inflammation. Extracellular Hsp70 is increased in sera of COPD patients, and can act as damage-associated molecular pattern. Aims and objectives: We explored the pro-inflammatory effects of cigarette smoke extract (CSE) alone and in combination with recombinant human Hsp70 (rhHsp70) on bronchial-epithelial NCI-H292 cell line. Methods: NCI-H292 cells were treated with 2.5% or 15% CSE alone or in combination with 0.3, 1.0 or 3.0 µg/mL rhHsp70 for 24 h. IL-1α, IL-6 and IL-8 were determined in cell supernatants by ELISA method. Results: Compared to the non-treated cell, secretion of IL-1α, IL-6 and IL-8 was significantly increased after treatment with 2.5% CSE, but not in combination with rhHsp70. Combination of rhHsp70 and CSE resulted in different secretion of IL-1α, IL-6 and IL-8 compared to the cells treated with CSE alone, and theirinteractions were antagonistic. Concentrations of IL-1α, IL-6 and IL-8 were different after treatment of cells with 15% CSE or combination of CSE and rhHsp70 compared to the non-treated cells, but their concentrations did not differ after combined treatment compared to CSE alone.

Objectives: Lung transplantation is a complex, high- risk, potentially life-saving therapy for the patient with the end-stage of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing and transplantation on the patient's quality of life. The aim of this study was to examine is there a difference in psychological status between CF patients who have not been transplanted and CF lung transplant recipients. Methods: Two patient groups, adult CF patients (N=22) and adult CF lung transplant recipients (N=6), participated in our study. The patients completed Patient Health Questionnaire-9 (PHQ 9) and the Generalized Anxiety Disorder 7-item scale (GAD 7). These data were compared to health status data, including pulmonary function testing and nutritional status measures. Results: In adult CF group, 52% of patients had mild to moderate anxiety and 95% mild to moderate depression. In adult CF lung transplant recipients group, 17% of subjects had minimal anxiety and 83% had minimal depression. Conclusion: In this study we find significant difference in the level of anxiety and depression between CF patients who have not been transplanted and CF lung transplant recipients. Lung transplantation in CF patient significantly contributed to the improvement of the psychological condition and quality of life.

Background: Asthma patients, due to their symptoms, often experience fear and anxiety when faced with daily activities. Such functional impairment over time causes lowered quality of life (QoL) and additional psychological distress expressed with depression, anxiety and stress symptoms. Objective: To evaluate the role of aerobic treadmill training among asthma patients attending pulmonary rehabilitation (PR) in their walking capacity (6 minute walking test - 6MWT), in improving QoL and reducing psychological distress. Method: We analyzed the results from 77 patients with persistent asthma divided in two groups. Patients in both groups had the same level of obstruction. They attended standard PR program five days weekly, during four weeks. In one group aerobic treadmill exercise training was added three times a week. Intensity was set at 60% of maximal work rate. Baseline and post PR status were evaluated by 6MWT in both groups, QoL, Depression (D), Anxiety (A) and Stress (S) symptoms. Results: All patients had a significant increase in 6MWT after PR (p

Objectives: Living with chronic illness such as cystic fibrosis (CF) is accompanied by medical and psychological difficulties. To identify and treat depression and anxiety in CF, the CF Foundation and the European CF Society invited a panel of experts, including physicians, psychologists, psychiatrists, nurses, social workers, a pharmacist, parents and an individual with CF, to develop consensus recommendations for clinical care. The aim of this study was to assess anxiety and depression by using validated mental health survey data. Methods: CF patients were recruited from adult CF centre in Zagreb, Croatia from October 2016 to December 2017. 22 patients (13 female, 9 male, mean age 24, 18-33 years) completed the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder 7-item scale (GAD-7). Results: 82% and 59% of our patients had a normal anxiety and depression score (0-4), 41% of patients have symptoms of anxiety, and 18% of the patients have symptoms of depression (score between 5 and 9). No one had any serious anxiety and/or depression present. Conclusions: Anxiety and depression are serious complication of chronic illnesses such as cystic fibrosis. Our results highlight the need for improved early identification and management strategies for psychological illnesses in adult CF patients. Research efforts are needed to identify effective strategies for delivering anxiety and depression treatment in CF patients and to assess their risks and benefits. Furthermore, strategies that help patients maintain or even improve lung function may be an interesting topic for further studies to learn more about resources and successful coping strategies.

Kronična opstruktivna plućna bolest karakterizirana je trajnom, progresivnom opstrukcijom dišnih putova uzrokovanom upalnom reakcijom u tim putovima i plućnom parenhimu na inhalacijske toksične čestice ili dim. Osnovni su ciljevi farmakološkog liječenja KOPB-a smanjenje simptoma, učestalosti i težine egzacerbacija te poboljšanje podnošenja fizičkog napora i zdravstvenog statusa. Osnova farmakološkog liječenja stabilnoga simptomatskog KOPB-a jesu bronhodilatatori (beta-agonisti i antikolinergici) sami ili u kombinaciji s inhalacijskim kortikosteroidima (ICS). Za pacijente koji imaju trajne simptome preporučuje se redovita primjena dugodjelujućih bronhodilatatora. Oni znatno poboljšavaju plućnu funkciju, kvalitetu života vezanu uza zdravlje i smanjuju učestalost egzacerbacija u usporedbi s placebom. Ukupno gledajući, dugodjelujući muskarinski antagonisti (LAMA) dovode do većeg poboljšanja parametara plućne funkcije, smanjenja učestalosti akutnih egzacerbacija uz manje neželjenih događaja u odnosu prema dugodjelujućim beta2-agonistima (LABA). U pacijenata čija bolest nije dobro kontrolirana primjenom monoterapije preporučuje se kombinacijska terapija koja se sastoji od dva dugodjelujuća bronhodilatatora različita mehanizma djelovanja. Kombinacijska terapija LABA-LAMA znatno poboljšava plućnu funkciju, simptome i zdravstveni status s obzirom na monoterapiju. Sigurnosni profil kombinacije LAMA-LABA usporediv je s LABA-om i LAMA-om kada se daje kao monoterapija. U pacijenata koji su skloni egzacerbacijama kombinacija ICS-a s LABA-om učinkovitija je nego bilo koja od ovih komponenata samostalno u poboljšanju plućne funkcije, zdravstvenog statusa i smanjenja učestalosti egzacerbacija. U bolesnika s teškim i jako teškim stupnjem KOPB-a i povišenim rizikom od egzacerbacija trojna terapija koja se sastoji od ICS-a, LABA-e i LAMA-e dodatno poboljšava plućnu funkciju, reducira učestalost egzacerbacija i smanjuje zaduhu u odnosu prema kombinaciji ICS-LABA., Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow obstruction caused by chronic inflammatory response of the airways and the lung parenchyma to noxious particles or gases. The main goals of pharmacologic therapy are to reduce symptoms and the frequency and severity of exacerbations as well as to improve exercise tolerance and health status. The mainstays of drug therapy of stable symptomatic COPD are inhaled bronchodilators (beta-agonists and anticholinergics) alone or in combination with inhaled corticosteroids (ICS). Regular use of long-acting bronchodilators is recommended for the management of patients with persistent symptoms. Compared to placebo, long-acting bronchodilators significantly improve lung function and health-related quality of life while reducing exacerbation rates. Overall, long-acting muscarinic antagonists (LAMAs) lead to greater improvement in lung function parameters, reduction in acute exacerbation rates and fewer adverse effects compared with long-acting beta-2 agonists (LABAs). In patients whose disease is not sufficiently controlled with monotherapy, guidelines recommended combination therapy involving two long-acting bronchodilators with differing modes of action. Compared with monotherapy, LAMA/LABA combination therapy significantly improves lung function, symptoms and health status. The safety profile of the LAMA/LABA combination therapy is similar to the safety profiles of LABAs and LAMAs when administered as monotherapy. In patients prone to exacerbations, an ICS combined with LABA is more effective than either component alone in improving lung function, health status and reducing exacerbations. In patients with severe to very severe COPD and increased exacerbation risk, triple therapy consisting of ICS, LABAs and LAMAs additionally improves lung function, reduces exacerbation rates and dyspnea compared to ICS/LABA combination therapy.

Background 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. Methods 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. Results 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. Conclusions 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. Electronic supplementary material The online version of this article (10.1186/s12967-018-1695-0) contains supplementary material, which is available to authorized users.

Background: There are some evidence concerning Fractional exhaled Nitric Oxide (FeNO) in relation to COPD that highlights the potential role of FeNO as biomarker in monitoring the stability of COPD. It is known that patients with frequent exacerbations (FE) phenotype have more rapid decline of lung function, worse quality of life and higher mortality rates compared to patients with infrequent exacerbations (IFE). Given the importance of these events, it is important to identify patients at risk for exacerbations. Objective: To investigate if there is a difference in FeNO values between COPD patients stratified into FE and IFE phenotype. Methods: A total of 39 patients with COPD were divided into two groups, patients with FE and IFE. Both groups were subjected to FeNO measurement, pulmonary function tests and routine blood test. Results: FE group consisted of 21 patients, 85.7% male with mean age 66.52 (51±83) years. 33.3% were current smokers (CS) and mean pack-years (P-Y) was 42.14 (12±100). In IFE group were 18 patients, 72.2% male, mean age 67.67 (53±88) years. 27.8% were CS and mean P- Y was 27.44 (11±46). There was no significant difference in FeNO values between FE and IFE group (U=129.5, p

Background: It is well known that acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with increased morbidity, readmission rates and mortality, but few studies report rehospitalization and mortality rate after severe AECOPD treated in intensive care unit (ICU). The aim of our study was to assess two year readmission rates and mortality in AECOPD patients treated in ICU and to identify determinants of these outcomes. Methods: 55 patients (35 men) mean age 68.1 (±10.5) years successfully treated in respiratory ICU due to AECOPD and discharged from hospital were included in the study. Patients demographics, hematology, biochemistry and arterial blood gases on the first treating day were recorded. Results: During the median follow-up of 2.4 years, 29 (46.8%) patients had one or more readmissions due to AECOPD. The average number of readmissions was 1.2. Significant predictors for the time to next hospitalization were initial PaCO2, fibrinogen, proteins and alpha 2 globulins (p=0.001 for the overall model fit). Significant predictors for the number of readmissions were: age at admission, neutrophil count, serum sodium, bilirubin, coronary artery disease (p=0.001 for the overall model fit). During the follow-up, 21 (38.2%) patients died. Significant predictors for survival time after incident hospitalization were: BMI, monocyte count, serum LDH, cancer and hypertension (p

Background: clinical relevance of M. xenopi in Croatia seems to differ to other countries. Aims and objectives: to assess clinical relevance of M. xenopi, and differences between patients colonized with M. xenopi and those with M. xenopi pulmonary disease (PD) and identify factors that may favor the disease. Methods: Retrospective analysis of all Croatian residents with pulmonary M. xenopi isolated in the period from 2006 to 2016. American Thoracic Society guidelines were used to establish the definition of M. xenopi PD or colonization. Results: medical records were available for 188/326 (57.7%) patients with M. xenopi isolate. Of those 188, 48 had certain PD, and 117 had no disease. Out of 117 classified as no disease, 20 cases of active tuberculosis (TB) co-infection were excluded from further risk analysis. Overall median follow up was 47 month. Patients with low body mass index (BMI), bronchiectasies, or inhalation corticosteroid (ICS) therapy had 6 (p