Successful Desensitization to Sorafenib and Imatinib-A Report of Two Cases and a Literature Review.

BACKGROUND: Drug desensitization allows for safe administration of a drug to a patient with a previous hypersensitivity reaction. Successful desensitization protocols have been described for different medications, including protocols for oncology patients. Few cases of desensitization to sorafenib and imatinib have been described in the literature so far. OBJECTIVE: The objective of this paper is to describe the process of the sorafenib and imatinib drug hypersensitivity diagnosis and desensitization process in two patients. METHODS: Two oncology patients who experienced non-immediate hypersensitivity reactions to sorafenib and imatinib underwent desensitization to these drugs. We designed a protocol for the first patient and used a modified protocol from the literature for the second patient. RESULTS: By using a slow desensitization technique and gradual tapering of corticosteroids and antihistamines, both patients reached the target dose of the incriminated drug. CONCLUSIONS: Desensitization to sorafenib and imatinib can be an effective therapeutic option in patients with hypersensitivity to those medications, without alternative treatment options.

Asthma Inflammatory Phenotypes: How Can We Distinguish Them?

BACKGROUND AND OBJECTIVES: induced sputum is used to assess different inflammatory phenotypes in asthma, but is not used routinely. We aimed to determine the proportion of inflammatory asthma phenotypes based on induced sputum, to find biomarkers that can discriminate between phenotypes, and to evaluate biomarkers in patients with and without biological therapy in different inflammatory asthma phenotypes. MATERIALS AND METHODS: this cross-sectional study investigated clinical characteristics, asthma control tests, skin prick test, impulse oscillometry (IOS), spirometry, induced sputum, biomarkers (IgE, eosinophils, fractional exhaled nitric oxide (FeNO), serum periostin, IL-5, IL-6, IL-8, IL-17A, IL-33) in 80 asthmatics. A total of 17/80 patients were treated with biologics (10 with omalizumab, 7 with benralizumab). RESULTS: a total of 31% of patients had eosinophilic asthma (EA), 30% had mixed granulocytic asthma (MGA), 24% had paucigranulocytic asthma (PGA), and 15% had neutrophilic asthma (NA). The difference was found in blood eosinophils (p = 0.002), the highest observed in EA. The cut-off ≥ 240/µL eosinophils, with 64% sensitivity and 72.7% specificity, identified EA (AUC = 0.743, p = 0.001). A higher IL-8 level was associated with NA (p = 0.025). In 63 non-biologic asthma group, eosinophils were higher in EA than in NA, MGA, and PGA (p = 0.012, p = 0.028, and p = 0.049, respectively). A higher IL-17A was associated with EA without biologics (p = 0.004). A significantly higher IL-5 was found in EA treated with biologics, in comparison with EA without biologics (p = 0.043). The number of leucocytes and neutrophils was higher in MGA without biologics (p = 0.049, p = 0.019), while IL-5, IL-6, and IL-8 levels were higher in MGA treated with biologics (p = 0.012, p = 0.032, p = 0.038, respectively). CONCLUSIONS: EA and MGA were the most prevalent asthma phenotypes. Blood eosinophils can identify EA, both in patients with and without biologics. Apart from the clinical profile, a broad spectrum of biomarkers for assessing inflammatory phenotypes is necessary for an adequate therapy approach to patients with asthma.

Autoimmune/inflammatory syndrome induced by adjuvants in a woman with Hashimoto thyroiditis and familial autoimmunity-a case report and literature review.

Introduction: Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) consists of a wide spectrum of symptoms and immunological features that are believed to develop in predisposed individuals after exposure to an adjuvant, including a silicone breast implant (SBI). Different autoimmune diseases (AIDs) have been associated with ASIA, but ASIA development after SBI in women with Hashimoto thyroiditis (HT) and familial autoimmunity has rarely been described. Case report: A 37-year-old woman presented in 2019 with arthralgia, sicca symptoms, fatigue, + antinuclear antibody (ANA), + anti SSA, and + anticardiolipin Immunoglobulin G (IgG) antibodies. She was diagnosed with HT and vitamin D deficiency in 2012. The familial autoimmunity was present: the patient's mother had been diagnosed with systemic lupus erythematosus and secondary Sjogren's syndrome and her grandmother with cutaneous lupus and pernicious anemia. In 2017, the patient had a cosmetic SBI procedure that was complicated by repeated right breast capsulitis. After 2 years of irregular visits due to COVID-19, she presented with + ANA, + anticentromere antibodies both in sera and seroma, sicca syndrome, arthralgias, twinkling in extremities, abnormal capillaroscopic findings, and reduced diffusing capacity of the lungs for carbon monoxide. She was diagnosed with ASIA, and antimalarial and corticosteroid therapy were introduced. Conclusion: In patients with HT and familial autoimmunity, SBI should be carefully considered due to the possibility of ASIA development. Hashimoto thyroiditis, familial autoimmunity, and ASIA seem to be interconnected in the complex mosaic of autoimmunity in predisposed individuals.

Adverse events in children and adolescents undergoing allergen immunotherapy for respiratory allergies-Report from the Allergen Immunotherapy Adverse Events Registry (ADER), a European Academy of Allergy and Clinical Immunology taskforce.

BACKGROUND: Although it has been shown that allergen immunotherapy (AIT) is well-tolerated in children, systematic and prospective surveillance of AIT safety in real life settings is needed. METHODS: The multinational Allergen Immunotherapy Adverse Events Registry (ADER) was designed to address AIT safety in real life clinical practice. Data on children ≤18 years old with respiratory allergies undergoing AIT were retrieved. Patient- and AIT-related features were collected and analyzed. The characteristics of adverse events (AE) and risk factors were evaluated. RESULTS: A total of 851 patients, 11.3 ± 3.4 years old, with rhinitis only (47.6%); asthma and rhinitis (44.5%); asthma (7.9%), receiving 998 AIT courses were analyzed. Sublingual immunotherapy (SLIT) accounted for 51% of the courses. In 84.5% of patients only one AIT treatment was prescribed. Pollen was the most frequent sensitizer (57.1%), followed by mites (53.4%), molds (18.2%) and epithelia (16.7%). Local and systemic AEs were reported in 85 patients (9.9%). Most AEs (83.1%) were mild and occurred in <30 min (87%). Respiratory and cutaneous symptoms were more frequent. Only 4 patients (0.47%) had severe AE (none after 6 weeks of maintenance). The risk of AE was higher in patients undergoing SCIT. CONCLUSIONS: AIT is safe and well tolerated in children and adolescents with respiratory allergies in real-life clinical practice. Though SCIT is more prone to AE compared to SLIT, overall severe reactions are rare and occur during build-up and early maintenance.

Developing COVID-19 vaccine recommendations during the pandemic: The experience of Serbia's Expert Committee on Immunization.

A National Immunization Technical Advisory Group (NITAG) is a multi-disciplinary body of national experts that provide evidence-based recommendations to policy-makers to assist them in making informed immunization policy and programme decisions. During the COVID-19 pandemic, NITAGs faced many challenges in making evidence-based recommendations for COVID-19 vaccines due to the rapidly evolving situation with new vaccine products available in a short time period and limited data on vaccine effectiveness. The authors reviewed the process used by Serbia's NITAG, which is called the Serbian Expert Committee on Immunization, to develop COVID-19 vaccine recommendations during the pandemic. The article examines the challenges and successes faced by the committee. Serbia's expert committee used the best available evidence to develop over forty recommendations on all aspects of COVID-19 vaccination. These expert committee recommendations facilitated the early procurement and successful roll-out of COVID-19 vaccines, guidance for vaccination of individuals at the highest risk, and high COVID-19 vaccination coverage in the country. The availability of five COVID-19 vaccines in Serbia was an advantage for the successful roll-out but posed challenges for the expert committee. Serbia's expert committee plans to use the experience and best practices developed during the pandemic to improve and expand its work moving forward.

Diagnosis and treatment of adult asthma patients in Serbia: a 2022 experts group position statement.

INTRODUCTION: Asthma is the most common non-communicable chronic lung condition across all ages. Epidemiological data indicate that many asthma patients in Serbia remain undiagnosed and untreated. The implementation of recent global advances in asthma management is limited due to the lack of a systematic approach, drug availability and regulatory affairs. In addition, the global coronavirus disease pandemic has posed a significant challenge, particularly in resource-limited settings. AREAS COVERED: In this paper, we propose an algorithm for treating adult asthma patients in Serbia. We performed PubMed database search on published asthma clinical trials and guidelines from 1 January 2015 to 10 March 2020. The consensus process incorporated a modified Delphi method that included two rounds of e-mail questionnaires and three rounds of national asthma expert meetings. We focus on 1) objective diagnosis of asthma, 2) the implementation of up-to-date therapeutic options, and 3) the identification and referral of severe asthma patients to newly established severe asthma centers. EXPERT OPINION: Regional specificities and variations in healthcare systems require the adaptation of evidence-based knowledge. Practical, clinically oriented algorithms designed to overcome local barriers in healthcare delivery may facilitate timely and adequate asthma diagnosis and the local implementation of current advances in asthma management.

'CT and CT image-based texture image analysis in radiological diagnostics of allergic fungal rhinosinusitis'.

BACKGROUND: This prospective study is focused on evaluating radiological properties of AFRS. We analysed specific CT features related to the presence of AFRS, as well as explored the possible usefulness of the texture image analysis (TIA) as an additional diagnostical parameter. METHODS: The CT images of maxillary sinuses of 37 adult patients diagnosed with chronic rhinosinusitis were analysed for homogeneity, high-attenuation areas, density of the soft tissue mass, bony wall thickness and density. TIA included assessment of uniformity, contrast, homogeneity and entropy of sinus content. RESULTS: In the F+ group, soft tissue mass was significantly more non-homogeneous, high-attenuation areas were more prevalent, while soft tissue densities were higher. The sinus wall showed a tendency towards decreased thickness and significantly higher density in the F+ group. Among TIA parameters only homogeneity was significantly lower in the F+ group. CONCLUSIONS: Presence of fungi should be suspected when the sinus is filled with a non-homogenous soft tissue content of a high CT density not necessarily presented as clearly visible hyperattenuation material. Additional criteria in radiological diagnostics of AFRS should encompass assessment of sinus bony wall density. TIA may serve as a tool for quantitative assessment of subjective CT features such as homogeneity of the soft tissue mass for investigative purposes. However, other TIA parameters showed limited potential.

Allergic patients during the COVID-19 pandemic-Clinical practical considerations: An European Academy of Allergy and Clinical Immunology survey.

BACKGROUND: The COVID-19 pandemic has affected health care systems unexpectedly. However, data focusing on practical considerations experienced by health care professionals (HCPs) providing care to allergic patients is scarce. METHODS: Under the framework of the European Academy of Allergy and Clinical Immunology (EAACI), a panel of experts in the field of immunotherapy developed a 42-question online survey, to evaluate real-life consequences of the COVID-19 pandemic in allergy practice. RESULTS: The respondents in the survey were 618. About 80% of HCPs indicated being significantly affected in their allergy practice. A face-to-face visit reduction was reported by 93% of HCPs and about a quarter completely interrupted diagnostic challenges. Patients with severe uncontrolled asthma (59%) and anaphylaxis (47%) were prioritized for in-person care. About 81% maintained an unaltered prescription of inhaled corticosteroids (ICS) in asthmatics. About 90% did not modify intranasal corticosteroids (INCS) in patients with allergic rhinitis. Nearly half of respondents kept biological prescriptions unmodified for asthma. About 50% of respondents kept their allergen immunotherapy (AIT) prescription patterns unchanged for respiratory allergies; 60% for insect venom allergies. Oral immunotherapy (OIT) for food allergies was initiated by 27%. About 20% kept carrying out up-dosing without modifications and 14% changed to more prolonged intervals. Telemedicine practice was increased. CONCLUSIONS: HCPs providing care to allergic patients were affected during the pandemic in diagnostic, management, and therapeutic approaches, including AIT for respiratory, insect-venom, and food allergies. Most HCPs maintained controller treatments for both asthma, and allergic rhinitis consistent with international recommendations, as well as biological agents in asthma. Remote tools are valuable in delivering allergy care.

Comprehensive Analysis of the HLA Class I and the HLA Class II Alleles in Patients with Takayasu Arteritis: Relationship with Clinical Patterns and Prognosis

BACKGROUND: Takayasu arteritis (TA) is a systemic vasculitis, affecting mainly the aorta and its branches. OBJECTIVE: To analyze the HLA class I and class II alleles in patients with TA and explore their relationship with clinical and demographic characteristics, and potential significance in prognosis. METHODS: Twenty-five, unrelated TA patients were genotyped for HLA-A, HLA-B, HLA-C, HLA-DRB1, and the HLA-DQB1 loci. The frequencies of the HLA-A, HLA-B, and the HLA-DRB1 were compared with a control group of 1992, while the HLA-C and the HLA-DQB1 were compared with a group of 159 healthy, unrelated individuals. RESULTS: Among TA patients, 5/25 (20%) were identified as the HLA-B*52 carriers. There was a significant difference in the HLA-B*52 allele frequency in the TA patients (10%) compared with the healthy controls (1.2%). Moreover, presence of the HLA-B*52 was associated with significantly earlier disease onset, more severe clinical presentations, and a poorer response to treatment. The HLA-C*03 was detected in 32% of patients and was present exclusively in those with a clinically mild form of the TA, indicating a putative protective effect. CONCLUSION: These findings indicate that the HLA-B*52 allele contributes to a higher susceptibility to the TA whereas the HLA-C*03, can be a protective factor in the TA.

COVID-19 pandemic and allergen immunotherapy-an EAACI survey.

BACKGROUND: As in many fields of medical care, the coronavirus disease 2019 (COVID-19) resulted in an increased uncertainty regarding the safety of allergen immunotherapy (AIT). Therefore, the European Academy of Allergy and Clinical Immunology (EAACI) aimed to analyze the situation in different countries and to systematically collect all information available regarding tolerability and possible amendments in daily practice of sublingual AIT (SLIT), subcutaneous AIT (SCIT) for inhalant allergies and venom AIT. METHODS: Under the framework of the EAACI, a panel of experts in the field of AIT coordinated by the Immunotherapy Interest Group set-up a web-based retrospective survey (SurveyMonkey® ) including 27 standardized questions on practical and safety aspects on AIT in worldwide clinical routine. RESULTS: 417 respondents providing AIT to their patients in daily routine answered the survey. For patients (without any current symptoms to suspect COVID-19), 60% of the respondents informed of not having initiated SCIT (40% venom AIT, 35% SLIT) whereas for the maintenance phase of AIT, SCIT was performed by 75% of the respondents (74% venom AIT, 89% SLIT). No tolerability concern arises from this preliminary analysis. 16 physicians reported having performed AIT despite (early) symptoms of COVID-19 and/or a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSIONS: This first international retrospective survey in atopic diseases investigated practical aspects and tolerability of AIT during the COVID-19 pandemic and gave no concerns regarding reduced tolerability under real-life circumstances. However, the data indicate an undertreatment of AIT, which may be temporary, but could have a long-lasting negative impact on the clinical care of allergic patients.

Biomarkers of disease activity in patients with chronic spontaneous urticaria.

INTRODUCTION: Previous studies have examined biomarkers of coagulation, inflammation and immunity in chronic spontaneous urticaria (CSU), but no recommended biomarkers for disease activity have been established yet. AIM: To find the relationship between certain laboratory parameters and disease activity in patients with CSU. MATERIAL AND METHODS: Serum concentrations of D-dimer, C-reactive protein (CRP), C3, C4, and prothrombin time (PT), activated partial thromboplastin time (aPTT) values were measured in 44 CSU patients and compared with 33 healthy controls. Correlation between biomarkers and urticaria activity score during 7 consecutive days (UAS7) was calculated. RESULTS: Our study included 44 CSU patients (38 females and 6 males), mean age of 50.4 years and the average disease duration of 3.1 years. Based on UAS7, 23 (52.3%) CSU patients had mild urticaria, 8 (18.2%) well-controlled, 7 (15.9%) moderate and 6 (13.6%) severe urticaria. Fourteen (31.8%) patients had elevated CRP, 21 (47.7%) had elevated D-dimer and 14 (13.6%) CSU patients had elevated C4 levels. Patients with CSU had statistically significant elevated D-dimer, CRP and PT as compared with controls (p = 0.007, p = 0.005 and p = 0.029, respectively). There was no correlation between PT, aPTT, D-dimer, CRP, C3 and disease activity. Statistically significant differences in C4 levels between patients with severe and well-controlled, mild, moderate urticaria were determined (p = 0.003). CONCLUSIONS: CRP, D-dimer, and PT may be considered as biomarkers for distinguishing patients with CSU from controls. The C4 levels correlate with disease activity and may be useful as a potential biomarker of disease activity.

Sulfur dioxide and exacerbation of allergic respiratory diseases: A time-stratified case-crossover study.

BACKGROUND: Strong epidemiological evidence suggests that air pollution plays a significant role in the exacerbation of allergic respiratory diseases. This study aimed to assess the potential relationship between daily levels of sulfur dioxide (SO2) and emergency department (ED) visits for allergic diseases. MATERIALS AND METHODS: Data regarding ED visits for allergic respiratory diseases were routinely collected from the EDs in the Zlatibor district, and the General Hospital, Uzice. The daily average concentrations of SO2 were obtained from the regional automatic air quality monitoring stations. All data were collected from June 2012 to July 2014. A time-stratified case-crossover design was used. Crude odds ratios (ORs) and ORs adjusted for weather conditions were calculated using conditional logistic regression. RESULTS: Statistically significant associations were seen between 0-day lagged exposure to SO2 and ED visits for all allergic diseases (OR = 1.62; 95% confidence interval [CI]: 1.05-2.48; P = 0.028) and between 2-day lagged exposure to SO2 and ED visits for asthma with allergic rhinitis (OR = 2.00; 95% CI: 1.03-3.88; P = 0.042). These results were adjusted for temperature, temperature2, and humidity. CONCLUSION: Our results suggest that short-term exposure to SO2 conferred an increased risk of ED visits for allergic respiratory diseases, particularly for asthma with concomitant allergic rhinitis.

Impact of atopic dermatitis on the quality of life of children and their families.

BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, with a significant effect on the quality of life (QoL). This study aims to evaluate the impact of AD on the QoL of children and their parents and to identify predictors affecting their QoL. METHODS: The cross-sectional study was conducted in Montenegro. It included 200 children with AD aged 5-16 years and their parents. The severity of disease was measured by the Three Item Severity (TIS) score, while QoL was assessed with the Children's Dermatology Life Quality Index (CDLQI) and the Dermatitis Family Impact (DFI) questionnaire. RESULTS: The mean CDLQI score of the children affected by AD was 17.11 and the mean DFI score of their parents 19.86. There was a significant correlation between AD severity score assessed by a doctor (TIS) and both CDLQI and DFI scores (r=0.53 and r=0.27, respectively). A moderate positive correlation was observed between the QoL of children with AD and QoL of their parents (r=0.53). According to multiple linear regression, more impaired QoL of affected children was associated with more severe AD, younger parent's age and their lower educational level. Poorer QoL of parents was associated with female sex, younger age of children, more severe AD, lower educational level of parents and absence of a family history of atopic disease. CONCLUSIONS: The present study confirmed that AD has a large negative impact on QoL of both patients with AD and their families. More impaired QoL was associated with more severe AD.

Short-term effects of air pollution on exacerbations of allergic asthma in Uzice region, Serbia.

INTRODUCTION: Many time-series studies have shown a positive association between air pollution and asthma exacerbation. However, till now only one study in Serbia has examined this relationship. AIM: To examine the associations between air pollution and asthma emergency department (ED) visits in the Uzice region, Serbia. MATERIAL AND METHODS: A time-stratified case-crossover design was applied to 424 ED visits for asthma exacerbation that occurred in the Uzice region, Serbia, in 2012-2014. Data about ED visits were routinely collected in the Uzice Health Centre. The daily average concentrations of particulate matter (PM2.5 and PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2), and black carbon (BC) were measured by automatic ambient air quality monitoring stations. Odds ratios and their corresponding 95% confidence intervals were estimated using conditional logistic regression adjusted for the potential confounding influence of weather variables (temperature, humidity and air pressure). RESULTS: Statistically significant associations were observed between ED visits for asthma and 3-day lagged exposure to BC (OR = 3.23; 95% CI: 1.05-9.95), and between ED visits for asthma with coexisting allergic rhinitis and 0-day lag exposure to NO2 (OR = 1.57; 95% CI: 0.94-2.65), 2-day lag exposure to SO2 (OR = 1.97; 95% CI: 1.02-3.80), and 3-day lag exposure to PM10 (OR = 2.38; 95% CI: 1.17-4.84). CONCLUSIONS: Exposure to ambient air pollution in the Uzice region increases the risk of ED visits for asthma, particularly during the heating season.

Impact of Tree Pollen Distribution on Allergic Diseases in Serbia: Evidence of Implementation of Allergen Immunotherapy to Betula verrucosa.

Background and objectives: The relationship between air pollen quantity and the sensitization of allergic patients is crucial for both the diagnosis and treatment of allergic diseases. Weather conditions influence the distribution of allergenic pollen and increases in pollen concentration may negatively affect the health of allergic patients. The aim of this study was to analyze the implementation of allergen immunotherapy with regard to air pollen concentration. Material and Methods: Here we examined the relationship between Betula air pollen concentration and the usage of Betula verrucosa allergen immunotherapy in Serbia. Examination covered the period from 2015 to 2018. Measurement of airborne pollen concentration was performed with Lanzoni volumetric pollen traps. The evidence of the usage of sublingual allergen immunotherapy (SLIT) was gathered from patients with documented sensitization to specific pollen. Results: During this period tree pollens were represented with 58% ± 21% of all measured air pollen species, while Betula pollen represented 15% ± 8% of all tree pollens. Betula pollination peaked in April. Allergen immunotherapy to Betula verrucosa in Serbia is entirely conducted as sublingual immunotherapy and represents 47.1% ± 1.4% of issued tree pollen SLIT. The use of pollen SLIT increased by 68% from 2015 to 2018, with an even greater increase in usage recorded for Betula SLIT-80%. Conclusions: This analysis shows a clear causative relationship between pollination and the type/prevalence of applied allergen immunotherapy. Information about the flowering seasons of allergenic plants is very important for people who suffer from allergy, for clinical allergologists, as well as for governing authorities. The presented data is of practical importance to the proper timing of immunotherapy initiation and of importance for urban landscaping. The obtained data can be the starting point for the instatement of a thorough epidemiological study and the inclusion of Serbia on the pollen map of Europe.

Does age influence the quality of life in children with atopic dermatitis?

BACKGROUND: Atopic dermatitis (AD) is one of the most common childhood skin diseases that can affect the quality of life (QoL) of children. The QoL of Montenegrin children with AD has not been sufficiently explored. The aim of this study was to assess their QoL with special emphasize on age differences. METHODS: This cross-sectional study included children with AD seen at the Clinic of Dermatology and Venereology, Clinical Center of Montenegro (CCM) in Podgorica between August 2017 and July 2018. The QoL was assessed with the Infants' Dermatitis Quality of Life Index (IDQOL) and the Children's Dermatology Life Quality Index (CDLQI). Disease severity was measured by the Three Item Severity (TIS) score. RESULTS: A total of 386 children with AD aged from newborn to 16 years took part in this study. The mean total score of the QoL was 14.7 in infants (0-4 years old), 19.4 in younger children (5-9 years old), and 16.6 in older children (10-16 years old). Age was in negative correlation with the CDLQI score, leisure domain of the CDLQI and CDLQI sleep, and in positive correlation with the IDQOL child mood. TIS score was in positive correlation with both the IDQOL and CDLQI score. CONCLUSIONS: The QoL measured by CDLQI was more impaired in younger children, whilst IDQOL child mood was more impaired in older infants. The most impaired QoL was seen in children in the age group 5-9 years. Regardless of disease severity, treatment and counseling of children suffering from AD should be tailored specifically to their age.

Evaluation of the Impact of Black Carbon on the Worsening of Allergic Respiratory Diseases in the Region of Western Serbia: A Time-Stratified Case-Crossover Study.

Background and Objectives: Many epidemiological studies have shown a positive association between black carbon (BC) and the exacerbation of allergic rhinitis and allergic asthma. However, none of the studies in Serbia examined this relationship yet. The aim of this study was to examine the associations between BC and emergency department (ED) visits for allergic rhinitis and allergic asthma in the Uzice region of Serbia. Materials and Methods: A time-stratified case-crossover design was applied to 523 ED visits for allergic rhinitis and asthma exacerbation that occurred in the Uzice region of Serbia between 2012-2014. Data regarding ED visits were routinely collected in the Health Center of Uzice. The daily average concentrations of BC were measured by automatic ambient air quality monitoring stations. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression adjusted for the potential confounding influence of weather variables (temperature, humidity, and air pressure). Results: Statistically significant associations were observed between ED visits for allergic rhinitis and 2-day lagged exposure to BC (OR = 3.20; CI = 1.00-10.18; p = 0.049) and allergic asthma and 3-day lagged exposure to BC (OR = 3.23; CI = 1.05-9.95; p = 0.041). Conclusion: Exposure to BC in the Uzice region increases the risk of ED visits for allergic rhinitis and asthma, particularly during the heating season.

Fungi-Induced Upper and Lower Respiratory Tract Allergic Diseases: One Entity.

Introduction:Aspergillus can cause different allergic diseases including allergic bronchopulmonary aspergillosis (ABPA) and allergic fungal rhinosinusitis (AFRS). ABPA is allergic pulmonary disease against Aspergillus antigens. AFRS is a type of chronic rhinosinusitis (CRS) presented as hypersensitivity reactions to the fungal presence in sinuses. The aim of the present study was to clarify if ABPA and AFRS could be considered as a common disease entity. Methodology: The prospective cohort study included 75 patients with ABPA. Patients were divided into two groups and compared with each other: (i) patients with CT confirmation of rhinosinusitis and presence of fungi in sinuses (ABPA+AFRS group) and (ii) patients without CT or without mycological evidence of AFRS (ABPA group). Results: Findings of this study were: (i) AFRS was confirmed in 80% of patients with ABPA; (ii) all ABPA+AFRS patients had allergic mucin while fungal hyphae were present in 60% sinonasal aspirate; (iii) ABPA+AFRS patients had more often complicated CRS with (nasal polyps) NP (p < 0.001) and more severe forms of CRS; (iv) culture of sinonasal aspirate revealed fungal presence in 97% patients with ABPA+AFRS; (v) patients with ABPA+AFRS had more common positive skin prick test (SPT) for A. fumigatus (p = 0.037), while patients without AFRS had more common positive SPT for Alternaria alternata and Penicillium notatum (p = 0.04 and p = 0.03, respectively); (vi) 67% of ABPA patients had Aspergillus induced AFRS; (vii) larger number of fungi was isolated from the air-samples obtained from homes of patients with ABPA+AFRS than from the homes of patients without AFRS, while the most predominant species were A. fumigatus and A. niger isolated from almost 50% of the air-samples. Conclusion: The pathogenesis of ABPA and AFRS is similar, and AFRS can be considered as the upper airway counterpart of ABPA. Fungi-induced upper and lower respiratory tract allergic diseases present common entity. Next studies should clarify the mechanism by which fungi turn from "normal flora" into trigger of immunological reactions, resulting in ABPA or AFRS as well as to find new approaches for its' diagnosis and treatment.

Study toward resolving the controversy over the definition of allergic fungal rhinosinusitis.

Dysbiosis of the microbiome on the airway mucosa leads to the development of chronic inflammatory and allergic disorders. The aim of this study was to consider the potential diagnostic criteria for allergic fungal rhinosinusitis (AFRS) and nonallergic fungal rhinosinusitis (FRS), and the role of fungal presence in an environment for the development of AFRS. In this study, 136 patients were divided into two groups: patients with positive specific immunoglobulin E (sIgE) and fungal finding (AFRS group), and patients with negative sIgE and positive fungal finding (FRS group). The study design included: anamnesis data, sIgE, eosinophil count and skin-prick test, rhinology and computerized tomography (CT) observation and mycological finding. Our results showed: (i) the prevalence in Serbia is: AFRS 1.3%, FRS 2.8%; (ii) 30.4% patients with sIgE+ had more often severe and recurrent chronic rhinosinusitis (CRS) (P = .005) and the presence of polyps (P = .025); (iii) 46.4% patients with sIgE+ had positive fungi on the sinonasal mucosa and were considered as AFRS; (iv) patients with AFRS had more frequent asthma (P = .024) and chronicity of CRS >10 years (P = .000). The persistent fungal presence and prolonged duration of CRS could be a silent threat for the progression of inflammation and development of FRS. Lavage with hypertonic-NaCl should be included in the everyday hygiene routine in an effort to decrease fungal load and antigenic exposure. The presence of allergological parameters and better response to corticosteroid therapy in AFRS patients should be considered as crucial diagnostic criteria for AFRS.