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1.
International consensus on lung function testing during COVID-19 pandemic and beyond
Aisling McGowan, Pierantonio Laveneziana, Sam Bayat, Nicole Beydon, Piotr Boros, Felip Burgos, Matjaž Fležar, Monika Franczuk, Maria-Alejandra Galarza, Adrian H. Kendrick, Frans de Jongh, 2021, izvirni znanstveni članek

Povzetek: COVID-19 has negatively affected the delivery of respiratory diagnostic services across the world due to the potential risk of disease transmission during lung function testing. Community prevalence, reoccurrence of COVID-19 surges, and the emergence of different variants of the SARS-CoV-2 virus have impeded attempts to restore services. Finding consensus on how to deliver safe lung function services for both patients attending and for staff performing the tests are of paramount importance. This international statement presents the consensus opinion of 23 experts in the field of lung function and respiratory physiology balanced with evidence from the reviewed literature. It describes a robust roadmap for restoration and continuity of lung function testing services during the COVID-19 pandemic and beyond. Important strategies presented in this consensus statement relate to the patient journey when attending for lung function tests. We discuss appointment preparation, operational and environmental issues, testing room requirements including mitigation strategies for transmission risk, requirement for improved ventilation, maintaining physical distance, and use of personal protection equipment. We also provide consensus opinion on precautions relating to specific tests, filters, management of special patient groups, and alternative options to testing in hospitals. The pandemic has highlighted how vulnerable lung function services are and forces us to re-think how long term mitigation strategies can protect our services during this and any possible future pandemic. This statement aspires to address the safety concerns that exist and provide strategies to make lung function tests and the testing environment safer when tests are required.
Ključne besede: Covid-19, testi pljučne funkcije - organizacija in vodenje, zagotavljanje varnosti -metode, soglasje
Objavljeno v DiRROS: 10.01.2022; Ogledov: 841; Prenosov: 564
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2.
Mnenje za spremljanje bolnikov po preboleli covidni pljučnici
Matjaž Turel, Natalija Edelbaher, Matjaž Fležar, Matevž Harlander, Peter Kecelj, Izidor Kern, Majda Kočar, Peter Kopač, Mitja Košnik, Robert Marčun, Igor Požek, Mirjana Rajer, Irena Šarc, Jurij Šorli, Dušanka Vidovič, Katarina Osolnik, 2021, izvirni znanstveni članek

Povzetek: Pljučnica je najpogostejši vzrok za težji potek okužbe z virusom SARS-CoV-2 in s hospitalizacijo. Potek covidne pljučnice je lahko različen; infiltrati, vidni na rentgenski sliki, se lahko resorbirajo spontano, včasih pa je potrebno zdravljenje s sistem-skimi glukokortikoidi. Ob odpustu iz bolnišnice zdravljenje običajno še ni končano, zato je Združenje pulmologov Slovenije v želji po enotnem obravnavanju bolnikov s covidno pljučnico izdelalo mnenje za obravnavo in sledenje bolnikov po od-pustu iz bolnišnice. Zavedamo se, da ob novi bolezni ne gre za dokončno priporočilo, saj bodo nova spoznanja o covidni pljučnici zanesljivo zahtevala obnavljanje priporočil.
Ključne besede: covid-19, mnenja, pljučnica, pulmologija, sistemski glukokortikoidi, covidna pljučnica
Objavljeno v DiRROS: 15.12.2021; Ogledov: 1059; Prenosov: 188
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3.
Fractional heat shock protein 27 urine excretion as a short-term predictor in acute exacerbation of chronic obstructive pulmonary disease
Denise Traxler, Matthias Zimmermann, Elisabeth Simader, Elisa Einwallner, Dragan Copic, Alexandra Graf, Thomas Mueller, Cecilia Veraar, Mitja Lainščak, Robert Marčun, Mitja Košnik, Matjaž Fležar, Aleš Rozman, Peter Korošec, 2020, izvirni znanstveni članek

Povzetek: Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is characterized by episodes of acute exacerbations. Finding a systemic biomarker that reliably predicts outcome after an acute exacerbation remains a major challenge. Heat shock protein 27 (HSP27) has been previously studied in COPD, however, urine excretion trajectory and prognostic value after an exacerbation is unknown. Methods: In this retrospective post hoc analysis of a prospective study that included 253 COPD patients who were hospitalized for acute exacerbation, 207 patients were analyzed. Urine and serum were sampled at admission, discharge, and 180 days after discharge; urine excretion trajectory was analyzed and correlated with clinicopathological and survival data. Results: HSP27 urine excretion increased after an exacerbation episode [1.8% admission, 1.8% discharge, 2.3% 180 days after discharge (P=0.091)]. In severely ill patients (GOLD IV) this course was even more distinct [1.6% admission, 2.1% discharge, 2.8% 180 days after discharge (P=0.007)]. Furthermore, fractional HSP27 urine excretion at discharge was increased in GOLD IV patients (P=0.031). In Kaplan-Meier and univariable Cox proportional hazard models patients with HSP27 urine excretion below 0.845% showed significantly worse survival at 30, 90 and 180 days after discharge. In a multivariable Cox proportional hazard model including established COPD outcome parameters fractional HSP27 urine excretion remained a significant predictor of survival at 30 and 90 days after discharge. Comparing this model to our already published model that includes HSP27 serum concentration we could show that fractional HSP27 urine excretion performs better in short-term survival. Conclusions: Our findings provide novel information about fractional HSP27 urine excretion trajectory in acute exacerbation of COPD. Fractional HSP27 urine excretion may be significantly reduced during an episode of acute exacerbation in COPD patients and may be used as a predictor of short-term all-cause mortality.
Ključne besede: biomarkers, heat-shock proteins, chronic obstructive pulmonary disease, urine, heat shock protein 27
Objavljeno v DiRROS: 25.01.2021; Ogledov: 1401; Prenosov: 988
.pdf Celotno besedilo (691,92 KB)
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4.
Inhaled therapies in patients with moderate COPD in clinical practice : current thinking
Ariel Amnon, Matjaž Fležar, 2018, pregledni znanstveni članek

Povzetek: COPD is a complex, heterogeneous condition. Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality. Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations. However, current clinical practice frequently differs from published guidelines on the management of COPD. This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease. We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups.
Ključne besede: dual bronchodilation, inhaled corticosteroid, LAMA, LABA, tiotropium, anticholinergic
Objavljeno v DiRROS: 17.12.2020; Ogledov: 1272; Prenosov: 839
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5.
GLCCI1 polymorphism rs37973 and asthma treatment response to inhaled corticosteroids
Matija Rijavec, Mateja Žavbi, Anton Lopert, Matjaž Fležar, Peter Korošec, 2018, izvirni znanstveni članek

Povzetek: Background. Asthma treatment response is highly variable and pharmacogenetic markers that predict treatment response would be one step closer to personalized treatment. GWAS studies have shown that polymorphisms GLCCI1 could be associated with asthma treatment response to inhaled corticosteroids (ICS). Materials and methods. We genotyped rs37973 of GLCCI1 in 208 adult asthma patients treated with ICS. Change in % predicted FEV1 was analysed after short-term (3 months) and after long-term (at least 3 years) treatment. Treatment success was defined as good when FEV1 decreased less than 30 ml/year. Results. After 3 months of treatment, change of % predicted FEV1 was higher in patients with GG genotype than in patients with AG+AA genotype, and this genotype dependent difference was only evident in non-smokers. Similar results were found after at least 3 years of treatment when all patients were analysed, in non-smokers and patients with atopy. Even though, no differences in treatment success (good vs. poor response) were observed when analysing the entire group of patients, genotype dependent treatment success was highly influenced by smoking and atopy. GG genotype was overrepresented in non-smokers and patients with atopy with good response. Conclusions. Rs37973 was associated with short- and long-term treatment response; however, there was a great influence of smoking and atopy on pharmacogenetic association. Furthermore, we found GG genotype to be associated with better treatment response, what is contrary to results found in GWAS.
Ključne besede: asthma -- diagnosis -- therapy, pharmacogenetics, genetic polymorphism, smoking, inhaled corticosteroids, atopy, GLCCI1, FEV1, rs37973
Objavljeno v DiRROS: 16.12.2020; Ogledov: 1356; Prenosov: 377
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6.
Systemic and airway oxidative stress in competitive swimmers
Sabina Škrgat, Peter Korošec, Izidor Kern, Mira Šilar, Julij Šelb, Matjaž Fležar, Robert Marčun, 2018, izvirni znanstveni članek

Povzetek: Background: The environment in swimming pools, which contain chlorine, might interact with the airway epithelium, resulting in oxidative stress and/or inflammation during high intensity training periods. Methods: We evaluated pulmonary functional (metacholine challenge test, FEV1 and VC), cellular (eosinophils and neutrophils), inflammatory (FeNo, IL-5, IL-6, IL-8 and TNF-[alpha]), oxidative (8-isoprostanes) and angiogenesis factors (VEGF) in induced sputum and peripheral blood of 41 healthy non-asthmatic elite swimmers (median 16 years) during the period of high intensity training before a national championship. The second paired sampling was performed seven months later after training had been stopped for one month. Results: There was a ten-fold increase (median 82-924 pg/ml; P < 0.001) in 8-isoprostanes in induced sputum and five-fold increase (median 82-924 pg/ml; P < 0.001) in sera during training in comparison to the period of rest. However, there was no difference in FEV1 (113 vs 116%), VC (119 vs 118%), FeNo (median 34 vs 38 ppb), eosinophils (2.7 vs 2.9% in sputum; 180 vs 165 cells/[micro]l in blood), neutrophils, different cytokines or VEGF in induced sputum or sera. The only exception was TNF-[alpha], which was moderately increased in sera (median 23 vs 40 pg/ml; P=0.02) during the peak training period. Almost half (18 of 41) of swimmers showed bronchial hyperresponsiveness during the peak training period (PC20 cutoff was 4 mg/ml). There was no correlation between hyperresponsiveness and the markers of oxidative stress or inflammation. Conclusions: High intensity training in healthy, non-asthmatic competitive swimmers results in marked oxidative stress at the airway and systemic levels, but does not lead to airway inflammation. However, we could not confirm that oxidative stress is associated with bronchial hyperresponsiveness (AHR), which is often observed during the peak exercise training period.
Ključne besede: bronchial diseases, swimming, oxidative stress, bronchial hyperresponsiveness, competitive swimmers, training
Objavljeno v DiRROS: 23.11.2020; Ogledov: 1638; Prenosov: 452
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7.
Absence of adverse effects of tiotropium/ olodaterol compared with the monocomponents on long-term heart rate and blood pressure in patients with moderate-to-very-severe COPD
Stefan Andreas, Lorcan Mcgarvey, Ulrich Bothner, Matthias Trampisch, Alberto De La Hoz, Matjaž Fležar, Roland Buhl, Peter Alter, 2020, izvirni znanstveni članek

Povzetek: Introduction: Long-acting [beta]2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are established maintenance bronchodilator treatments for chronic obstructive pulmonary disease (COPD) with the potential to increase heart rate (HR) and impact blood pressure (BP). While previous studies indicate that HR and BP are not negatively influenced by tiotropium or olodaterol monotherapy, the effect of tiotropium/olodaterol has not been evaluated. We report a post hoc analysis of the effect of dual bronchodilation with tiotropium/olodaterol versus monocomponents on HR and BP in patients with moderate-to-very-severe COPD included in the large TONADO© study. Methods: The TONADO© trials (1237.5 [NCT01431274] and 1237.6 [NCT01431287]) were two replicate, randomized, double-blind, parallel-group, 52-week, Phase III trials that compared tiotropium/olodaterol (5/5 [micro]g and 2.5/5 [micro]g) with tiotropium (5 [micro]g and 2.5 [micro]g) and olodaterol (5 [micro]g) in patients with moderate-to-very-severe COPD. Patients with cardiovascular comorbidities were included. Changes in HR and systolic/diastolic BP were measured before and after dosing with the study medication at each visit (baseline, Week 12, Week 24 and Week 52). Results: Overall, 3,100 patients were included in this analysis. Over 52 weeks, small changes from baseline in mean HR (<2 beats per minute [bpm]) and small changes from pre- to post-dose (<1 bpm) were evident at different time points. There was a non-significant increase from baseline in mean diastolic and systolic BP (<2 mmHg) observed over 52 weeks of treatment. The short-term (1 hour pre- to 1 hour post-dose) mean changes in systolic and diastolic BP over 52 weeks in the tiotropium/olodaterol 5/5 [micro]g group were comparable with those observed for the monocomponents at all time points. Conclusion: There were no differences in HR or BP among patients on tiotropium/olodaterol when compared with monocomponents. This supports the already demonstrated cardiovascular safety profile of tiotropium/olodaterol as long-acting maintenance bronchodilator treatment for COPD, including patients with cardiovascular comorbidities.
Ključne besede: pulmonary disease, chronic obstructive -- drug therapy, heart rate, blood pressure, tiotropium, olodaterol
Objavljeno v DiRROS: 21.09.2020; Ogledov: 1408; Prenosov: 928
.pdf Celotno besedilo (2,84 MB)
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8.
Correlations between vitreous cytokine levels and inflammatory cells in fibrovascular membranes of patients with proliferative diabetic retinopathy
Mojca Urbančič, Danijel Petrovič, Aleksandra Milutinović Živin, Peter Korošec, Matjaž Fležar, Mojca Globočnik Petrovič, 2020, izvirni znanstveni članek

Povzetek: Purpose: The purpose of this study was to investigate the levels of cytokines in the vitreous, and their correlation with the density of inflammatory cells in fibrovascular membranes (FVMs) in patients with proliferative diabetic retinopathy (PDR) to evaluate intraocular inflammatory conditions with regard to disease activity.Methods: Thirty-three patients (33 eyes) with PDR requiring vitreoretinal surgery because of FVMs and tractional detachment were enrolled in the study, and compared with 20 patients (20 eyes) with macular hole (MH; control group). All patients underwent complete ophthalmological examinations before surgery. The activity of the disease was noted in patients with PDR. Samples of vitreous and blood were taken, and cytokine (MCP-1, IL-8, IL-6, VEGF, IL-1%, TNF-%, MIP-1%, MIP-1%, IL-10, and IL-12) levels were measured using cytometric bead array (CBA). Samples of FVMs were analyzed with immunohistochemical methods for the presence of inflammatory cells (CD45+, CD14+, CD3+, CD4+, CD8+, and CD19+ cells), and the numerical areal density was calculated (NA). Spearman%s correlation was used to as-sess the association between variables. The Mann%Whitney test was used to assess the differences between independent groups. The Wilcoxon signed-rank test was used for assessing differences between two related groups. A p value of less than 0.05 was considered statistically significant.Results: Patients with active PDR had statistically significantly higher levels of MCP-1 (p = 0.003), VEGF (p = 0.009), and IL-8 (p = 0.02) in the vitreous in comparison with those with inactive PDR. CD45+, CD14+, CD3+, CD4+, CD8+, and CD19+ cells were identified in FVMs for patients with PDR. Statistically significantly higher numerical areal density of T lymphocytes (CD3+, CD4+, and CD8+) was demonstrated in patients with active PDR in comparison with patients with inactive PDR. Moderate to strong correlations were found between either MCP-1 or IL-8 in the vitreous, and the numerical areal density of cells (CD45+, CD3+, CD4+, and CD8+) in the FVMs, and weaker between either MCP-1 or IL-8 in the vitreous and the numerical areal density of CD14+ cells in the FVMs.Conclusions: The correlation of cytokine (MCP-1 and IL-8) vitreous levels with the density of inflammatory cells in FVMs, and differences in cytokine levels in the vitreous between patients with active and inactive PDR, and between the vitreous and serum in PDR indicate the importance of local intraocular inflammation in patients with PDR.
Ključne besede: diabetic retinopathy, fibrovascular membranes, inflammatory cells
Objavljeno v DiRROS: 09.09.2020; Ogledov: 1415; Prenosov: 669
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9.
Heat shock protein 27 as a predictor of prognosis in patients admitted to hospital with acute COPD exacerbation
Matthias Zimmermann, Denise Traxler, Christine Bekos, Elisabeth Simader, Thomas Mueller, Alexandra Graf, Mitja Lainščak, Robert Marčun, Mitja Košnik, Matjaž Fležar, Aleš Rozman, Peter Korošec, 2020, izvirni znanstveni članek

Povzetek: Episodes of acute exacerbations are major drivers of hospitalisation and death from COPD. To date, there are no objective biomarkers of disease activity or biomarkers to predict patient outcome. In this study, 211 patients hospitalised for an acute exacerbation of COPD have been included. At the time of admission,routine blood tests have been performed including complete blood count, C-reactive protein, cardiac troponin T and NT-proBNP. Heat shock protein 27 (HSP27) serum concentrations were determined at time of admission, discharge and 180 days after discharge by ELISA. We were able to demonstrate significantly increased HSP27 serum concentrations in COPD patients at time of admission to hospital as compared to HSP27 concentrations obtained 180 days after discharge. In univariable Cox regression analyses, a HSP27 serum concentration >/= 3098 pg/mL determined at admission was a predictor of all-cause mortality at 90 days, 180 days, 1 year and 3 years. In multivariable analyses, an increased HSP27 serum concentration at admission retained its prognostic ability with respect to all-cause mortality for up to 1year follow-up. However, an increased HSP27 serum concentration at admission was not an independent predictor of long-term all-cause mortality at 3 years. Elevated serum HSP27 concentrations significantly predicted short-term mortality in patients admitted to hospital with acute exacerbation of COPD and could help to improve outcomes by identifying high-risk patients.
Ključne besede: COPD, acute exacerbation, disease activity
Objavljeno v DiRROS: 29.07.2020; Ogledov: 1659; Prenosov: 1029
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