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11.
Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies
Jean Bousquet, Jean-Paul Cristol, Wienczyslawa Czarlewski, Josep M. Antò i Boquè, Adrian Martineau, Tari Haahtela, Susana C. Fonseca, Guido Iaccarino, Hubert Blain, Alessandro Fiocchi, Nisera Bajrović, Natalija Edelbaher, Maja Jošt, Peter Kopač, Anja Koren, Mitja Košnik, Karmen Kramer Vrščaj, Samo Kreft, Nika Lalek, Bojan Madjar, Tonka Poplas-Susič, Irma Rozman Sinur, Tanja Soklič, Katja Triller Vadnal, Nadja Triller, Jure Urbančič, Mihaela Zidarn, 2020, pregledni znanstveni članek

Povzetek: There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR[gamma]:Peroxisome proliferator-activated receptor, NF[kappa]B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2[alpha]:Elongation initiation factor 2[alpha]). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
Ključne besede: Covid-19, SARS-CoV-2, food, insulin resistance, obesity, Nrf2, nutrients, TRPA1
Objavljeno v DiRROS: 25.01.2021; Ogledov: 1589; Prenosov: 618
.pdf Celotno besedilo (1,61 MB)

12.
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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13.
Emphysema and extrapulmonary tissue loss in COPD: a multi-organ loss of tissue phenotype
Bartolome R. Celli, Nicholas Locantore, Ruth Tal-Singer, John Riley, Jørgen Vestbo, Julie C. Yates, Bruce E. Miller, Edwin K Silverman, Caroline A. Owen, Miguel Divo, 2018, izvirni znanstveni članek

Povzetek: We tested whether emphysema progression accompanies enhanced tissue loss in other body compartments in 1817 patients from the ECLIPSE chronic obstructive pulmonary disease (COPD) cohort. Clinical and selected systemic biomarker measurements were compared in subjects grouped by quantitative tomography scan emphysema quartiles using the percentage of low attenuation area (LAA%). Lowest and highest quartile patients had amino-acid metabolomic profiles. We related LAA% to 3 years decline in lung function (forced expiratory volume in 1 s (FEV1)), body mass index (BMI), fat-free mass index (FFMI) and exacerbations, hospitalisations and mortality rates. Participants with more baseline emphysema had lower FEV1, BMI and FFMI, worse functional capacity, and less cardiovascular disease but more osteoporosis. Systemic C-reactive protein and interleukin-6 levels were similar among groups, but club cell protein 16 was higher and interleukin-8, surfactant protein D and soluble receptor for advanced glycation end product were lower with more emphysema. Metabolomics differed between extreme emphysema quartiles. Patients with more emphysema had accelerated FEV1, BMI and FFMI decline and more exacerbations, hospitalisations and mortality. COPD patients with more emphysema undergo excessive loss of pulmonary and extrapulmonary tissue, which is probably related to abnormal tissue maintenance. Because of worse clinical outcomes, we propose this subgroup be named the multi-organ loss of tissue (MOLT) COPD phenotype.
Ključne besede: COPD, chronic obstructive pulmonary disease, emphysema
Objavljeno v DiRROS: 14.12.2020; Ogledov: 1143; Prenosov: 350
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14.
The global impact of the COVID-19 pandemic on the management and course of chronic urticaria
Emek Kocatürk, Andaç Salman, Ivan Cherrez-Ojeda, Paulo Ricardo Criado, Jonny Peter, Elif Comert-Ozer, Mohamed Abuzakouk, Rosana Câmara Agondi, Mona Al-Ahmad, Sabine Altrichter, Mojca Bizjak, Mitja Košnik, 2020, izvirni znanstveni članek

Povzetek: Introduction: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. Aim: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19. Materials and methods: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19. Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.
Ključne besede: chronic urticaria, pandemics, omalizumab, cyclosporine, COVID-19, SARS-CoV-2, UCARE, treatment
Objavljeno v DiRROS: 14.12.2020; Ogledov: 1385; Prenosov: 350
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15.
Cold urticaria : what we know and what we do not know
Natalya Maltseva, Elena Borzova, Daria Fomina, Mojca Bizjak, Dorothea Terhorst, Mitja Košnik, Kanokvalai Kulthanan, Raisa Meshkova, Simon Francis Thomsen, Marcus Maurer, 2020, izvirni znanstveni članek

Povzetek: Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterised by the development of wheals, angioedema or both in response to cold exposure. Recent research and guideline updates have advanced our understanding and management of ColdU. Today, its pathophysiology is thought to involve the cold-induced formation of autoallergens and IgE to these autoallergens, which provoke a release of proinflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold-induced wheals usually develop on rewarming and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient's history and cold stimulation testing. Additional diagnostic work-up, including a search for underlying infections, should only be done if indicated by the patient's history. The management of ColdU includes cold avoidance, the regular use of nonsedating antihistamines, and the off-label use of omalizumab. However, many questions regarding ColdU remain unanswered. Here, we review what is known about ColdU, and we present important unanswered questions on the epidemiology, underlying pathomechanisms, clinical heterogeneity and treatment outcomes. Our aim is to guide future efforts that will close these knowledge gaps and advance the management of ColdU.
Ključne besede: urticaria, cryopyrin-associated periodic syndromes, cold-induced urticaria, familial cold autoinflammatory syndrome, cold stimulation testing, wheals, cryoglobulinemic vasculitis, cryoglobulins
Objavljeno v DiRROS: 14.12.2020; Ogledov: 1242; Prenosov: 354
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16.
Hereditary angioedema due to C1-inhibitor deficiency in Macedonia : clinical characteristics, novel SERPING1 mutations, and genetic factors modifying the clinical phenotype
Vesna Grivčeva-Panovska, Mitja Košnik, Peter Korošec, Slađana Andrejević, Ljerka Karadža-Lapić, Matija Rijavec, 2018, izvirni znanstveni članek

Povzetek: Objective: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease, characterized by swellings. We aimed to characterize on a clinical and molecular basis C1-INH-HAE patients in the Republic of Macedonia. Results: All 15 patients from six unrelated families were diagnosed with C1-INHHAE type I, with a mean age of symptom onset of 11 years and an average delay of diagnosis of 7 years. Patients reported on average 31 angioedema attacks/year, with a median clinical severity score (CSS) of 7. We identified three known mutations, and two mutations (c.813_818delCAACAA and c.1488T>G) were reported for the first time. To address the genotype-phenotype association, a pooled analysis including 78 C1-INH-HAE south-eastern European patients was performed, with additional analysis of F12-46C/T and KLKB1- 428G/A polymorphisms. We demonstrated that patients with nonsense and frameshift mutations, large deletions/insertions, splicing defects, and mutations at Arg444 exhibited an increased CSS compared with missense mutations, excluding mutations at Arg444. In addition, the CC F12-46C/T polymorphism was suggestive of earlier disease onset. Discussion: Genetic analysis helped identify the molecular basis of C1-INH-HAE given that causative mutations in SERPING1 were detected in all patients, including an infant before the appearance of clinical symptoms. We identified two novel mutations and further corroborated the genotype-phenotype relationship, wherein mutations with a clear effect on C1-INH function predispose patients to a more severe disease phenotype and CC F12-46C/T predisposes patients to earlier disease onset.
Ključne besede: hereditary angioedemas -- genetics -- Macedonia, C1 inhibitor, SERPING1 gene, C1 inhibitor, SERPING1 gene
Objavljeno v DiRROS: 30.11.2020; Ogledov: 1231; Prenosov: 269
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17.
Functional complement analysis can predict genetic testing results and long-term outcome in patients with complement deficiencies
Štefan Blazina, Maruša Debeljak, Mitja Košnik, Saša Simčič, Sanja Stopinšek, Gašper Markelj, Nataša Toplak, Peter Kopač, Breda Zakotnik, Marko Pokorn, Tadej Avčin, 2018, izvirni znanstveni članek

Povzetek: Background: Prevalence of complement deficiencies (CDs) is markedly higher in Slovenian primary immunodeficiency (PID) registry in comparison to other national and international PID registries. Objective: The purposes of our study were to confirm CD and define complete and partial CD in registered patients in Slovenia, to evaluate frequency of clinical manifestations, and to assess the risk for characteristic infections separately for subjects with complete and partial CD. Methods: CD was confirmed with genetic analyses in patients with C2 deficiency, C8 deficiency, and hereditary angioedema or with repeated functional complement studies and measurement of complement components in other CD. Results of genetic studies (homozygous subjects vs. heterozygous carriers) and complement functional studies were analyzed to define complete (complement below the level of heterozygous carriers) and partial CD (complement above the level of homozygous patients). Presence of characteristic infections was assessed separately for complete and partial CD. Results: Genetic analyses confirmed markedly higher prevalence of CD in Slovenian PID registry (26% of all PID) than in other national and international PID registries (0.5–6% of all PID). Complement functional studies and complement component concentrations reliably distinguished between homozygous and heterozygous CD carriers. Subjects with partial CD had higher risk for characteristic infections than previously reported. Conclusion: Results of our study imply under-recognition of CD worldwide. Complement functional studies and complement component concentrations reliably predicted risk for characteristic infections in patients with complete or partial CD. Vaccination against encapsulated bacteria should be advocated also for subjects with partial CD and not limited to complete CD.
Ključne besede: complement deficiency, primary immunodeficiency, laboratory analysis, genetic analysis, clinical manifestations
Objavljeno v DiRROS: 12.11.2020; Ogledov: 1344; Prenosov: 586
.pdf Celotno besedilo (1000,60 KB)

18.
Cabbage and fermented vegetables : from death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19
Jean Bousquet, Josep M. Antò i Boquè, Wienczyslawa Czarlewski, Tari Haahtela, Susana C. Fonseca, Guido Laccarino, Hubert Blain, Alain Vidal, Aziz Sheikh, Cezmi A. Akdis, Torsten Zuberbier, Samo Kreft, Klemen Jenko, Maja Jošt, Peter Kopač, Mitja Košnik, Karmen Kramer Vrščaj, Bojan Madjar, Davor Plavec, Tanja Soklič, Jure Urbančič, Mihaela Zidarn, 2020, izvirni znanstveni članek

Povzetek: Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage were associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin converting enzyme 2 (ACE2). As a result of SARS-Cov-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1R) axis associated with oxidative stress. This leads to insulin resistanceas well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block the AT1R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are given: Kimchi in Korea, westernized foods and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects helpful in mitigating COVID-19 severity.
Ključne besede: COVID-19, diet, sulforaphane, Lactobacillus, Angiotensin converting enzyme 2, kimchi, cabbage, fermented vegetable
Objavljeno v DiRROS: 07.10.2020; Ogledov: 1341; Prenosov: 315
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19.
Is diet partly responsible for differences in COVID-19 death rates between and within countries? : protocol for a systematic review
Jean Bousquet, Josep M. Antò i Boquè, Guido Laccarino, Wienczyslawa Czarlewski, Tari Haahtela, Aram Anto, Cezmi A. Akdis, Hubert Blain, Giorgio Walter Canonica, Karmen Kramer Vrščaj, Tari Haahtela, Mitja Košnik, Anja Koren, Peter Kopač, Maja Jošt, Samo Kreft, Klemen Jenko, Bojan Madjar, Davor Plavec, Tanja Soklič, Jure Urbančič, Mihaela Zidarn, 2020, pregledni znanstveni članek

Povzetek: Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.
Ključne besede: coronavirus, diet, angiotensin-converting enzyme, antioxidant, food
Objavljeno v DiRROS: 09.09.2020; Ogledov: 1458; Prenosov: 1154
.pdf Celotno besedilo (1,12 MB)
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20.
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: 1031
.pdf Celotno besedilo (679,90 KB)
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