Papers by Mirjana Turkalj

Medicina, Jan 6, 2024
Allergic diseases are one of the most common chronic conditions and their prevalence is on the ri... more Allergic diseases are one of the most common chronic conditions and their prevalence is on the rise. Environmental exposure, primarily prenatal and early life influences, affect the risk for the development and specific phenotypes of allergic diseases via epigenetic mechanisms. Exposure to pollutants, microorganisms and parasites, tobacco smoke and certain aspects of diet are known to drive epigenetic changes that are essential for immune regulation (e.g., the shift toward T helper 2-Th2 cell polarization and decrease in regulatory T-cell (Treg) differentiation). DNA methylation and histone modifications can modify immune programming related to either pro-allergic interleukin 4 (IL-4), interleukin 13 (IL-13) or counter-regulatory interferon γ (IFN-γ) production. Differential expression of small non-coding RNAs has also been linked to the risk for allergic diseases and associated with air pollution. Certain exposures and associated epigenetic mechanisms play a role in the susceptibility to allergic conditions and specific clinical manifestations of the disease, while others are thought to have a protective role against the development of allergic diseases, such as maternal and early postnatal microbial diversity, maternal helminth infections and dietary supplementation with polyunsaturated fatty acids and vitamin D. Epigenetic mechanisms are also known to be involved in mediating the response to common treatment in allergic diseases, for example, changes in histone acetylation of proinflammatory genes and in the expression of certain microRNAs are associated with the response to inhaled corticosteroids in asthma. Gaining better insight into the epigenetic regulation of allergic diseases may ultimately lead to significant improvements in the management of these conditions, earlier and more precise diagnostics, optimization of current treatment regimes, and the implementation of novel therapeutic options and prevention strategies in the near future.

The Central European Journal of Paediatrics, Nov 4, 2022
Objective -The aim of study was to evaluate the effects of parental smoking and tobacco smoke exp... more Objective -The aim of study was to evaluate the effects of parental smoking and tobacco smoke exposure (TSE) on asthma symptoms in children, and to raise awareness of the detrimental effects of TSE for asthmatic children. Methods -A modified and validated questionnaire on TSE was completed by 76 parents and their children who were being treated at Srebrnjak Children's Hospital for asthma. Patients filled in a standardized ACT questionnaire about their asthma symptoms, whereas parental smoking data were derived from a questionnaire filled in by the parents. The answers were structured as ordinal and categorical variables. The non-parametric Mann-Whitney U test and Kruskal-Wallis test were performed. Results -There are statistically significant differences in the frequency of asthma symptoms in children depending on whether household members smoked cigarettes, with statistically significant differences in the frequency of asthma symptoms in children depending on whether their parents smoked cigarettes outside the house, only in one/certain room or everywhere in the house. 34.1% of smoking parents vs 9.4% of nonsmoking parents allow smoking in a car while the child is riding in it. 40.9% of parents who smoke vs 21.9% of non-smoking parents believe that their child is exposed to tobacco smoke somewhere other than in their household or car. Conclusion -TSE is associated with more symptoms and worse asthma control in asthmatic children.

Pediatric Pulmonology, Jul 1, 2009
BackgroundIt is speculated that the exposure to Mycobacterium tuberculosis, either by infection o... more BackgroundIt is speculated that the exposure to Mycobacterium tuberculosis, either by infection or by Bacillus Calmette‐Guérin vaccination, may inhibit the onset of atopy by the modification of immune profiles leading to a shift of TH1/TH2 balance to the TH1 side.ObjectiveOne hundred eighty‐six patients hyperreactive at tuberculin skin test (TST) were examined in order to investigate the prevalence of atopic disorder, particularly referring to the association between the size of the TST induration and the prevalence of sensitization and manifest atopic disorder.MethodsThe study consisted of a family history record, patients' medical history assessment and clinical examination, skin prick test (SPT), serum total and allergen‐specific IgE (sIgE) measurement and eosinophil count.ResultsAtopic disorder was present in 49 (26.3%) patients tested. No significant difference between the groups based on the TST induration size (15–24 mm vs. ≥25 mm) was found for gender distribution, family atopy history, total IgE measurement, eosinophil count, positive SPT, and the presence of sIgE. A significant difference was found for the age median (14.0 years vs. 13.0 years), childhood atopy record, and manifest atopic disorder. No association between the size of the TST induration and the incidence of allergic sensitization was demonstrated. However, a significant inverse association between the size of the TST induration and manifest atopic disorder was demonstrated.ConclusionIn patients highly hyperreactive at TST, the size of the induration is inversely associated with manifest atopic disorder. Pediatr Pulmonol. 2009; 44:701–705. © 2009 Wiley‐Liss, Inc.

Medical Science Monitor, 2012
Background: Recent guidelines recommend inhaled corticosteroids as the first-line treatment for p... more Background: Recent guidelines recommend inhaled corticosteroids as the first-line treatment for persistent asthma. However, long-term corticosteroid treatment in children has raised concerns about potential growth rate deceleration. We aimed to assess the association of growth velocity with the use of inhaled corticosteroids in prepubertal children with asthma in a "real-life" setting. Material/Methods: This study included 844 children aged 4-9.5 years coming to the hospital for regular checkups between October 2006 and February 2009 for asthma with/without allergic rhinitis and no other known constraints of growth. Out of the 844 children, 790 had all data needed for analysis-245 children were not treated with ICS, 545 children received ICS (fluticasone, budesonide) with/without INCS (fluticasone, mometasone or budesonide). During the study period, 48 children with/without ICS received short SCS courses. Results: Mean (SE) height at the first checkup was 123.1 (0.31) cm; range (100.0-147.8 cm). Mean (SE) linear growth velocity (LGV) of the included children was 0.185 (0.0035) mm/day between 2 checkups. No significant difference was found in LGV between the group not treated with ICS (0.180 mm/day±0.0055) and the group treated with ICS (0.187±0.0044 mm/day). Also, there was no statistical difference between subgroups according to additional therapy with INCS and SCS. No significant correlation was found for LGV and daily dose of ICS (r=0.086, p>0.05). Conclusions: In our retrospective study using electronic hospital database, ICS and combined use of corticosteroids did not show any association with LGV in prepubertal asthmatic children in a "real-life" setting.

Patient Preference and Adherence, Feb 1, 2017
Allergic rhinitis is a common health problem in both children and adults. The number of patients ... more Allergic rhinitis is a common health problem in both children and adults. The number of patients allergic to ragweed (Ambrosia artemisiifolia) is on the rise throughout Europe, having a significant negative impact on the patients' and their family's quality of life. Allergenspecific immunotherapy (AIT) has disease-modifying effects and can induce immune tolerance to allergens. Both subcutaneous immunotherapy and sublingual immunotherapy with ragweed extracts/preparations have clear positive clinical efficacy, especially over pharmacological treatment, even years after the treatment has ended. AIT also has very good safety profiles with extremely rare side effects, and the extracts/preparations used in AIT are commonly well tolerated by patients. However, patient adherence to treatment with AIT seems to be quite low, mostly due to the fact that treatment with AIT is relatively time-demanding and, moreover, due to patients not receiving adequate information and education about the treatment before it starts. AIT is undergoing innovations and improvements in clinical efficacy, safety and patient adherence, especially with new approaches using new adjuvants, recombinant or modified allergens, synthetic peptides, novel routes of administration (epidermal or intralymphatic), and new protocols, which might make AIT more acceptable for a wider range of patients and novel indications. Patient education and support (eg, recall systems) is one of the most important goals for AIT in the future, to further enhance treatment success.
Lijec̆nic̆ki vjesnik, Jun 25, 2012
Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report. ... more Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report. Allergy 2008;63:793-6. 35. Mehl A, Rolinck-Werninghaus C, Staden U i sur. The atopy patch test in diagnostic workup of specific food-related symptoms in children. J Allergy Clin Immunol 2006;118:923-9. 36. Brindslev-Jensen C, Ballmer-Weber BK, Bengtsson U i sur. Standardization of food challenges in patients with immediate reactions to foods-position paper from the European Academy of Allergy and Clinical immunology.

Asthma research and practice, Aug 3, 2021
Despite widely and regularly used therapy asthma in children is not fully controlled. Recognizing... more Despite widely and regularly used therapy asthma in children is not fully controlled. Recognizing the complexity of asthma phenotypes and endotypes imposed the concept of precision medicine in asthma treatment. By applying machine learning algorithms assessed with respect to their accuracy in predicting treatment outcome, we have successfully identified 4 distinct clusters in a pediatric asthma cohort with specific treatment outcome patterns according to changes in lung function (FEV 1 and MEF 50 ), airway inflammation (FENO) and disease control likely affected by discrete phenotypes at initial disease presentation, differing in the type and level of inflammation, age of onset, comorbidities, certain genetic and other physiologic traits. The smallest and the largest of the 4 clusters-1 (N = 58) and 3 (N = 138) had better treatment outcomes compared to clusters 2 and 4 and were characterized by more prominent atopic markers and a predominant allelic (A allele) effect for rs37973 in the GLCCI1 gene previously associated with positive treatment outcomes in asthmatics. These patients also had a relatively later onset of disease (6 + yrs). Clusters 2 (N = 87) and 4 (N = 64) had poorer treatment success, but varied in the type of inflammation (predominantly neutrophilic for cluster 4 and likely mixed-type for cluster 2), comorbidities (obesity for cluster 2), level of systemic inflammation (highest hsCRP for cluster 2) and platelet count (lowest for cluster 4). The results of this study emphasize the issues in asthma management due to the overgeneralized approach to the disease, not taking into account specific disease phenotypes.
30th Congress of the International Society for Advancement of Cytomery : abstracts, 2015
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Papers by Mirjana Turkalj