University Clinic of Respiratory and Allergic Diseases

Golnik, Slovenia

University Clinic of Respiratory and Allergic Diseases

Golnik, Slovenia
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Rupnik H.,University of Ljubljana | Rupnik H.,Dermatology Center Arsderma | Rijavec M.,University Clinic of Respiratory and Allergic Diseases | Korosec P.,University Clinic of Respiratory and Allergic Diseases
British Journal of Dermatology | Year: 2015

Background The influence of filaggrin gene (FLG) mutations on early- vs. late-onset development of atopic dermatitis (AD), allergic contact dermatitis (ACD) and chronic irritant contact dermatitis (CICD) is not completely understood. Objectives To assess the association between FLG mutations and development of AD, ACD and CICD. Methods This study assessed 241 patients with AD. AD developed during infancy in 85 patients, during childhood in 79 patients (32 early and 47 late) and during adulthood in 77 patients. We also included 100 patients with ACD and 44 with CICD, as well as 164 healthy controls. Four prevalent FLG loss-of-function mutations were genotyped (R501X, 2282del4, R2447X and S3247X). Results The 2282del4 mutation was significantly associated with a greater risk of AD in the entire group [odds ratio (OR) 4·33, 95% confidence interval (CI) 1·26-14·96]. However, the 2282del4 mutation was associated only with AD that developed during infancy or in early childhood (≤ 8 years: OR 20·91, 95% CI 2·73-159·9), not with AD development in late childhood or adulthood (> 8 or > 18 years), or ACD or CICD. Similar associations were also observed for the combined 2282del4 or R501X genotype. Carriers of FLG mutations also experienced a longer duration of AD and required hospitalization more often. Conclusions FLG mutations are associated with only the early onset of AD, not late onset. Other factors should receive attention in patients with late-onset AD. © 2014 British Association of Dermatologists.


Dolenc-Voljc M.,University of Ljubljana | Zolnir-Dovc M.,University Clinic of Respiratory and Allergic Diseases
Acta Dermatovenerologica Alpina, Pannonica et Adriatica | Year: 2010

Mycobacterium marinum infection is the most common atypical skin mycobacterial infection of increasing importance. It results from skin injury and contact with contaminated aquarium water, fish, or shellfish; it is only rarely related to swimming pool sources nowadays. Diagnosis should be confirmed by isolation and identification of the organism; however, this gold standard is difficult to achieve in practice. Therefore, the diagnosis is primarily based on clinical examination, histopathology, and response to therapy. Awareness of this infection is still low and diagnosis often delayed, as presented in this case of a young immunocompetent patient with M. marinum infection of a chronic course. The reasons for the delay in diagnosis are discussed and current diagnostic and treatment recommendations are reviewed.


Rozman A.,University Clinic of Respiratory and Allergic Diseases Golnik | Rozman A.,University Clinic of Respiratory and Allergic Diseases | Camlek L.,University Clinic of Respiratory and Allergic Diseases | Marc-Malovrh M.,University Clinic of Respiratory and Allergic Diseases | And 2 more authors.
Respirology | Year: 2013

Background and objective Thoracoscopy with a semi-rigid instrument is a recent technique successfully used for diagnosing pleural diseases. However, there are concerns about the diagnostic adequacy of biopsy samples obtained by semi-rigid procedures when compared with rigid thoracoscopy. The purpose of this study was to compare the size, quality and diagnostic adequacy of biopsy specimens obtained at semi-rigid and rigid thoracoscopy in a prospective, randomized fashion. Methods Patients with pleural effusion of unknown origin and/or pleural irregularities suspicious for pleural malignancy were included after less invasive means of diagnosis had failed. All procedures were performed under local anaesthesia with intravenous sedation/analgesia with a single point of entry. Patients were randomly assigned to a rigid instrument procedure (Olympus EndoEYE WA50120A, forceps) or semi-rigid instrument procedure (Olympus LTF-160, FB-55CR-1 forceps). Results Eighty-four patients were randomized. Five of them were excluded because of lack of pleural space. Thirty-eight patients were assigned to a rigid and 41 to a semi-rigid procedure, with mean follow up 24.1 (±8.1) months after the procedure. The average size of the sample obtained by rigid thoracoscopy was 24.7 mm2 (±12.9), and 11.7 mm2 (±7.6) by semi-rigid thoracoscopy. There were no differences in the quality and interpretability of the specimens assessed by the pathologist. The diagnostic accuracy was 100% for the rigid procedure and 97.6% for the semi-rigid procedure. Conclusions The samples obtained by semi-rigid thoracoscopy were smaller, but of adequate quality. The diagnostic accuracy was comparable with that of rigid thoracoscopy in the evaluation of pleural disease. © 2013 Asian Pacific Society of Respirology.


Kosnik M.,University Clinic of Respiratory and Allergic Diseases | Subic T.,University Clinic of Respiratory and Allergic Diseases
Respiratory Medicine | Year: 2011

Antihistamines (AH) alleviate pruritus and decrease the incidence of hives in patients with chronic idiopathic urticaria (CU). However, some patients do not respond completely to this therapy. We hypothesized that some of them might benefit from the addition of leukotriene receptor antagonists (LA). We screened patients diagnosed and treated for CU and selected those that had symptoms despite antihistamine treatment. In a double-blind crossover study, patients took the leukotriene antagonist montelukast (10 mg per day) of placebo. Efficacy was assessed by a symptom score. In a group of 22 patients, the symptom score was not significantly different between periods using montelukast (48.8; 0-214) of placebo (68.5; 0-230). However in the subgroup of five patients with the most severe urticaria, defined as patients with symptom scores in the upper quartile at inclusion in the study, montelukast (41; 11 214) was superior to placebo (95.5; 48 230; p < 0.05), but only when using an in-house symptom score questionnaire and not when using a validated urticaria activity score questionnaire. We showed that in patients with antihistamine-resistant CU the addition of montelukast significantly diminished symptoms in only a small minority of patients. However, response to add-on montelukast was seen in the subgroup of patients with particularly severe disease. To confirm this observation, a study with a larger group of patients is warranted. © 2011 Elsevier Ltd. All rights reserved.


Kristan S.S.,University Clinic of Respiratory and Allergic Diseases
Archivum Immunologiae et Therapiae Experimentalis | Year: 2013

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is not fully reversible; this airflow limitation is both progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gasses. COPD is undoubtedly an umbrella term, and it seems unlikely that all patients with COPD have the same underlying disease processes; thus, there is a need for differential treatment of different subgroups. A potential solution is to find modifiable biomarkers that can assist in drug development and distinguish subgroups of COPD. With the exception of lung function tests, there are currently no well-validated biomarkers or surrogate endpoints that can be used to establish the efficacy of a drug for COPD. This article discusses biomarkers of inflammation (fibrinogen, C-reactive protein, pulmonary and activation-regulated chemokine/CC-chemokine ligand-18, serum surfactant protein D, interleukin (IL)-6, IL-8 and tumor necrosis factor α, complement factor C5a), angiogenesis factors as a part of the pathogenetic aspect in this disease (vascular endothelial growth factor, angiogenin, and IL-8), and matrix degradation biomarkers. Troponin and natriuretic peptides are presented as biomarkers of cardiac involvement in the light of COPD comorbidities. Trials based on research on known clinical variables such as FEV1, BODE, and 6MWT in combination with biomarkers from lung and blood specimens will probably clarify part of the prognosis and natural history of the disease. This will also represent an additional step in COPD phenotyping and new treatment possibilities. © 2013 L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.


Background: We report here on 14438 Streptococcus pneumoniae and 14770 Haemophilus influenzae isolates collected from 560 centres globally between 2004 and 2012 as a part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.). Methods: MIC testing was performed using broth microdilution methods as described by the Clinical and Laboratory Standards Institute (CLSI) using CLSI-approved breakpoints; US Food and Drug Administration breakpoints were used for tigecycline as CLSI breakpoints are not available. Results: At least 99% of S. pneumoniae isolates globally were susceptible to levofloxacin, linezolid, tigecycline or vancomycin. Penicillin resistance was observed among 14.8% of S. pneumoniae and was highest in Asia/Pacific Rim (30.1%) and Africa (27.6%); 23.4% of S. pneumoniae isolates were penicillin-intermediate, which were most common in Africa (37.6%). Minocycline susceptibility among S. pneumoniae decreased by 20% between 2004-2008 and 2009-2012. High (>98.5%) susceptibility was reported among H. influenzae to all antimicrobial agents on the T.E.S.T. panel excluding ampicillin, to which only 78.3% were susceptible. β-lactamase production was observed among 20.2% of H. influenzae isolates; 1.5% of isolates were β-lactamase negative, ampicillin-resistant. Conclusions: S. pneumoniae remained highly susceptible to levofloxacin, linezolid, tigecycline and vancomycin while H. influenzae was susceptible to most antimicrobial agents in the testing panel (excluding ampicillin). © 2014 Tomic and Dowzicky.


Erzen R.,University Clinic of Respiratory and Allergic Diseases | Kosnik M.,University Clinic of Respiratory and Allergic Diseases | Silar M.,University Clinic of Respiratory and Allergic Diseases | Korosec P.,University Clinic of Respiratory and Allergic Diseases
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2012

Background There is no in vitro test to predict the induction of long-term tolerance in patients treated with venom immunotherapy (VIT). The aim of this study was to investigate whether immunotherapy-induced changes in basophil responsiveness reflect a state of protection and the induction of a tolerance. Methods Twenty-three patients with allergic reaction after Hymenoptera sting (11 wasp and 12 honeybee) were treated with VIT. In all patients, a CD63 basophil activation test was performed before the beginning of immunotherapy, after 1 year and after completing 4-6.5 years of immunotherapy (approximately 1 year after stopping). The tolerance was then evaluated by a sting challenge test. The basophil activation test was repeated 3-6 months after the challenge. Results Twenty-two subjects showed a negative sting challenge, and one subject, a positive sting challenge. Allergen-specific basophil response remained unchanged after 1 year of immunotherapy. However, after immunotherapy, a significant and approximately fourfold decrease was demonstrated in all tolerant subjects mainly in response to submaximal 0.1 μg/ml allergen concentration. This depression was sustained and did not change with the sting challenge test. In a nontolerant patient with a positive sting challenge, basophil response did not change. Conclusions Our results suggest that the depression of allergen-specific basophil response seems to be associated with the induction of a tolerance after completing a course of VIT. © 2012 John Wiley & Sons A/S.


Rijavec M.,University Clinic of Respiratory and Allergic Diseases | Volarevic S.,University of Rijeka | Osolnik K.,University Clinic of Respiratory and Allergic Diseases | Kosnik M.,University Clinic of Respiratory and Allergic Diseases | Korosec P.,University Clinic of Respiratory and Allergic Diseases
Respiratory Medicine | Year: 2011

Natural killer T (NKT) cells, a unique subgroup of lymphocytes with features of both T and natural killer (NK) cells, represent a bridge between innate and adaptive immunity. They have the ability to either promote of suppress immune responses. With these immunoregulatory functions, NKT cells have emerged as an important subset of lymphocytes with a protective role in some disorders, such as infections, cancer, and possibly sarcoidosis, and a pathogenic role in others, such as asthma, chronic obstructive pulmonary disease and hypersensitivity pneumonitis. Immunotherapeutic interventions to modulate the immune response by targeting iNKT cell functions has become a challenging field and has shown promising results for the development of new therapies. © 2011 Elsevier Ltd. All rights reserved.


Kosnik M.,University Clinic of Respiratory and Allergic Diseases | Korosec P.,University Clinic of Respiratory and Allergic Diseases
Expert Review of Clinical Immunology | Year: 2015

Venom-specific immunotherapy (VIT) is considered for the treatment of patients with IgE-mediated systemic allergic reactions (SARs) after developing a Hymenoptera venom allergy. Tolerance is achieved in a majority of patients after only a few days or even hours of rush immunotherapy. After VIT discontinuation, the allergy returns in up to 15% of patients. During VIT, the majority of patients have local reactions at the site of venom injections. SARs to VIT are much more frequent in honeybee-treated patients than in wasp-treated patients. Increased baseline serum tryptase and increased allergen-specific sensitivity of basophils are other factors that might be associated with systemic reactions (SRs) during VIT. Severe SRs occur mainly during the build-up phase but can also occur in the maintenance phase of the VIT, even in patients with a well-tolerated dose-increase phase. Pre-treatment with humanized anti-IgE antibodies (omalizumab) is effective in patients with repeated SARs; however, this use of omalizumab is off-label. In highly exposed patients with a history of very severe reactions, there are virtually no absolute contraindications for VIT. © 2015 Informa UK, Ltd.


Lalek N.,University Clinic of Respiratory and Allergic Diseases | Kosnik M.,University Clinic of Respiratory and Allergic Diseases | Silar M.,University Clinic of Respiratory and Allergic Diseases | Korosec P.,University Clinic of Respiratory and Allergic Diseases
Clinical and Experimental Allergy | Year: 2010

Background The effects of pollen immunotherapy on effector cells of allergic inflammation, such as mast cells and basophils, are poorly understood. Objective For this reason, we conducted an open study on basophil allergen threshold sensitivity during birch pollen immunotherapy. Methods Basophil sensitivity was measured by CD63 flow cytometry in 14 patients with moderate-severe intermittent birch pollen rhinitis using four log allergen concentrations. In nine patients, we analysed the basophil sensitivity before and during treatment with subcutaneous birch immunotherapy (perennial scheme with allergoid). We also included eight birch-allergic donor subjects for IgG inhibition experiments and eight control subjects. Results There was a decrease in basophil allergen threshold sensitivity after 2, 3, and 5 months of immunotherapy. This decrease was correlated with an improvement in patients' symptoms measured on a visual analogue scale. The serum obtained after immunotherapy induced a significant decrease in allergen threshold sensitivity in donor birch-allergic basophils. This inhibition was not observed after IgG depletion from the serum. Conclusions In this study, we showed that birch immunotherapy-induced IgG antibodies are associated with a reduction in basophil allergen threshold sensitivity. Further studies are needed to show whether the changes in basophil sensitivity are of clinical relevance in pollen immunotherapy. © 2010 Blackwell Publishing Ltd.

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