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11.
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

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
DiRROS - Objavljeno: 14.12.2020; Ogledov: 194; Prenosov: 110

12.
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

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
DiRROS - Objavljeno: 14.12.2020; Ogledov: 223; Prenosov: 55

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, Bruce E. Miller, Jørgen Vestbo, Julie C. Yates, Edwin K Silverman, Caroline A. Owen, Miguel Divo, 2018

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
DiRROS - Objavljeno: 14.12.2020; Ogledov: 150; Prenosov: 53

14.
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

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
DiRROS - Objavljeno: 25.01.2021; Ogledov: 185; Prenosov: 56
.pdf Celotno besedilo (691,92 KB)

15.
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

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
DiRROS - Objavljeno: 25.01.2021; Ogledov: 225; Prenosov: 103
.pdf Celotno besedilo (1,61 MB)

16.
Routine KIT p.D816V screening identifies clonal mast cell disease in Hymenoptera allergic patients regularly missed using baseline tryptase levels alone
Peter Korošec, Jonathan J. Lyons, Mitja Košnik, Samo Zver, Vladka Čurin-Šerbec, Yihui Liu, Young Hwan Park, Ajda Demšar, Nisera Bajrović, Matevž Škerget, Peter Kopač, Mihaela Zidarn, Renato Eržen, Matija Rijavec, Julij Šelb, 2021

Povzetek: Background. Clonal mast cell disorders and elevated BST of unknown cause(s) are associated with severe Hymenoptera venom-triggered anaphylaxis (HVA). However, some individuals with clonal disease have normal BST (<11.4 ng/mL). Objective. To evaluate whether screening for KIT p.D816V in the blood is a useful clinical tool to risk-stratify patients with venom allergy. Methods. We prospectively recruited 374 patients with Hymenoptera allergy and no overt signs of mastocytosis referred to our center in the years 2018-19. KIT p.D816V was determined in the peripheral blood with qPCR and tryptase genotyping was performed by droplet-digital PCR. Results. 351 patients (93.9%) had normal levels of BST and KIT p.D816V was detected in 8% of patients (28/351), predominantly in patients with the most severe Mueller grade IV anaphylaxis (18.2%[24/132] vs 1.8%[4/88 in grade III; 0/131 in other grades] in lower grades; P<0.001). In grade IV patients with normal BST, KIT p.D816V was associated with more severe symptoms including a significantly higher frequency of loss of consciousness (58.3%[14/24] vs 34.3%[37/108]; P=0.03) and absence of skin symptoms (41.7%[10/24] vs 15.7%[17/108]; P=0.004). Among patients with normal BST, KIT p.D816V (OR [95%CI]: 10.25[3.75-36.14]; P<0.0001) was the major risk factor associated with severe HVA. Hereditary [alpha]-tryptasemia (H[alpha]T), due to increased germline copies of TPSAB1 encoding [alpha]-tryptase was the most common cause (65.2%; 15/23) of elevated BST in patients with HVA and together with KIT p.D816V accounted for 90% (20/23) of BST elevations in HVA patients. Conclusion. These results indicate that routine KIT p.D816V screening identifies clonal disease in high-risk HVA patients regularly missed using BST alone.
Ključne besede: anaphylaxis, venoms, hypersensitivity, hereditary alpha-tryptasemia
DiRROS - Objavljeno: 31.03.2021; Ogledov: 84; Prenosov: 41

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18.
Cold agglutinins and cryoglobulins associate with clinical and laboratory parameters of cold urticaria
Mojca Bizjak, Mitja Košnik, Dorothea Terhorst, Dejan Dinevski, Marcus Maurer, 2021

Povzetek: Mast cell-activating signals in cold urticaria are not yet well defined and are likely to be heterogeneous. Cold agglutinins and cryoglobulins have been described as factors possibly associated with cold urticaria, but their relevance has not been explained. We performed a single-center prospective cohort study of 35 cold urticaria patients. Cold agglutinin and cryoglobulin test results, demographics, detailed history data, cold stimulation test results, complete blood count values, C-reactive protein, total immunoglobulin E levels, and basal serum tryptase levels were analyzed. Forty six percent (n = 16) of 35 tested patients had a positive cold agglutinin test and 27% (n = 9) of 33 tested patients had a positive cryoglobulin test. Cold agglutinin positive patients, when compared to cold agglutinin negative ones, were mainly female (P = 0.030). No gender-association was found for cryoglobulins. A positive cold agglutinin test, but not a positive cryoglobulin test, was associated with a higher rate of reactions triggered by cold ambient air (P = 0.009) or immersion in cold water (P = 0.041), and aggravated by increased summer humidity (P = 0.007). Additionally, patients with a positive cold agglutinin test had a higher frequency of angioedema triggered by ingestion of cold foods or drinks (P = 0.043), and lower disease control based on Urticaria Control Test (P = 0.023). Cold agglutinin levels correlated with erythrocyte counts (r = -0.372, P = 0.028) and monocyte counts (r = -0.425, P = 0.011). Cryoglobulin concentrations correlated with basal serum tryptase levels (r = 0.733, P = 0.025) and cold urticaria duration (r = 0.683, P = 0.042). Results of our study suggest that cold agglutinins and cryoglobulins, in a subpopulation of cold urticaria patients, are linked to the course and possibly the pathogenesis of their disease.
Ključne besede: urticaria, mast cells, cold-induced urticaria, cold urticaria, cryoglobulins, cold agglutinin, degranulation, clinical parameters, laboratory parameters
DiRROS - Objavljeno: 10.05.2021; Ogledov: 5; Prenosov: 3
.pdf Celotno besedilo (1,61 MB)

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