Acute Urticaria: Symptoms, Causes, and Evaluation of Phenotypes Prone to Chronicity.

INTRODUCTION: Urticaria is a condition that is characterized by the development of wheals (hives), angioedema, or both. If symptoms persist for less than 6 weeks, it is classified as acute urticaria (AU), and if they persist for longer than 6 weeks, it is classified as chronic urticaria (CU). Disease activity is evaluated using validated patient-reported outcome measures (PROMs) such as the 7-day urticaria activity score (UAS-7) and urticaria control test (UCT). In this study, we aimed to determine whether there was a difference between patients with chronic and recovered urticaria in terms of age, sex, symptoms, disease severity, disease control, and triggering factors by following patients with AU for 6 months. METHODS: The routine tests were requested at the first admission of the patients. If previously examined, anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody, etc., were recorded. After the first examination, the patients were evaluated again using a visual analog scale (VAS), UCT, UAS-7, and medication scores (MSs) in the 1st, 3rd, and 6th months. RESULTS: One hundred nine (F/M: 80/29) patients were included in the study. Twenty-seven patients had a previous history of AU, 22 of these patients were evaluated as having recurrent AU, and five became chronic during follow-up. Urticaria continued in 22 of 82 patients who presented with first-attack AU in the 3rd month and 17 in the 6th month. We had a chronicity rate of 24.7%. It was determined that having positive anti-TPO increased the risk of CU 1.69 times. A statistically significant improvement was found in the mean VAS, UCT, UAS-7, and MSs evaluated in the 1st, 3rd, and 6th months of patients with CU compared with baseline. CONCLUSION: AU is a common disease and usually heals in a short time without becoming chronic. Studies on the causes of chronicity are limited. Testing anti-TPO in patients presenting with AU may be useful in terms of disease course and risk of chronicity.

Evaluation of sinonasal involvement in patients with asthma and chronic obstructive pulmonary disease.

Background: Asthma and chronic obstructive pulmonary disease (COPD) are the most common obstructive diseases. Based on the similarities, we aimed to evaluate sinonasal symptoms in patients with asthma or COPD, and compare the two diseases with regard to upper-airway involvement. Methods: Patients with asthma or with COPD who were followed up at Ankara University Immunology and Allergy or Chest Diseases Departments were included in the study. The participants went through pulmonary function tests, skin-prick tests, and disease severity assessment of either disease. Nasal endoscopic evaluations of all the patients were performed in the Department of Otorhinolaryngology. Lund-Mackay scoring was performed on the computed tomography of the paranasal sinus. Chronic rinosinusitis (CRS) diagnosis was made as recent guidelines. Results: A total of 112 subjects (number of women/men: n = 67/45; median age, 49 years [The range for IQR was 22 years]) were included in the study. Fifty-five patients had asthma, 33 had COPD, and 24 were healthy controls. Nasal symptoms were more frequent in the patients with asthma (patients with asthma, n = 52 [98%]; patients with COPD, n = 17 [52%]; controls, n = 9 [38%]) (p < 0.001). The median (IQR) 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire score was higher in the patients with asthma (33 [20-50]) than in the patients with COPD (8 [1.5-18.7]) and the control group (3.5 [0-18.7]) (p < 0.01). Patients with asthma had significantly higher prevalence rates of rhinosinusitis than did those in the COPD and the control groups (36%, 15.6%, 8.3%, respectively; p < 0.01). The SNOT-22 optimal cutoff score was calculated as ≥11 to detect the score limit for CRS prediction with the best sensitivity and specificity. Conclusion: As a result, patients with both asthma and COPD may have upper-airway symptoms. CRS, was primarily seen in the patients with asthma. Accordingly, SNOT-22 scores were higher in the patients with asthma than in those in the COPD and the control groups. A referral to the Ear Nose Throat department for further evaluation with nasal endoscopy and computed tomography of the paranasal may be required in a subgroup of patients.

Global warming and implications for epithelial barrier disruption and respiratory and dermatologic allergic diseases.

Global warming has direct and indirect effects, as well as short- and long-term impacts on the respiratory and skin barriers. Extreme temperature directly affects the airway epithelial barrier by disrupting the structural proteins and by triggering airway inflammation and hyperreactivity. It enhances tidal volume and respiratory rate by affecting the thermoregulatory system, causing specific airway resistance and reflex bronchoconstriction via activation of bronchopulmonary vagal C fibers and upregulation of transient receptor potential vanilloid (TRPV) 1 and TRPV4. Heat shock proteins are activated under heat stress and contribute to both epithelial barrier dysfunction and airway inflammation. Accordingly, the frequency and severity of allergic rhinitis and asthma have been increasing. Heat activates TRPV3 in keratinocytes, causing the secretion of inflammatory mediators and eventually pruritus. Exposure to air pollutants alters the expression of genes that control skin barrier integrity and triggers an immune response, increasing the incidence and prevalence of atopic dermatitis. There is evidence that extreme temperature, heavy rains and floods, air pollution, and wildfires increase atopic dermatitis flares. In this narrative review, focused on the last 3 years of literature, we explore the effects of global warming on respiratory and skin barrier and their clinical consequences.

[The profile of severe asthmatics: Results from a specialized asthma clinic]. / Özellesmis bir astim polikliniginin agir astim verileri.

Introduction: In patients with severe asthma, individualized treatment, and appropriate phenotyping are required to achieve control. In our study, our aim was to examine the characteristics of a specific patient group in a specialized tertiary asthma outpatient clinic, which is the primary setting for evaluating severe asthma patients, with the intention of obtaining national data. Materials and Methods: In this cross-sectional observational study, sociodemographic, clinical presentations, laboratory results, and spirometry measurements of patients with severe asthma who were followed up in our specialized asthma outpatient clinic for at least one year were recorded. Patients were defined as eosinophilic if they had a blood eosinophil count of 300/µL or higher at least twice during the oral corticosteroid free-period or 150/µL or higher under oral corticosteroids as allergic if they had sensitization to at least one inhalant allergen consistent with their history. Result: Overall, 201 severe asthma patients (74.1% female) with a median disease duration of 15 (min-max= 1-49) years and a median follow-up duration of 7 (min-max= 1-40) years were analyzed. Most of the patients (56.7%) had adult-onset asthma [median age of onset was 32 (min-max= 10-62) years]. Overweight and obese patients were in the majority (31.8%, and 41.8%, respectively) and the median body mass index was 29 (min-max= 17.5-49.5). More than half of the patients (55.2%) had controlled asthma and the median Asthma Control Test score at the last visit was 23. Biologic therapies were applied to 73.1% (n= 147) of the patients [60.5% (n= 89) omalizumab, 39.5% (n= 58) mepolizumab]. Half of the group was allergic (49.3%) and three-quarters of them were eosinophilic (72.1%). Allergic patients had earlier asthma onset and had more controlled disease than nonallergic ones. Eosinophilic patients were younger and less obese than noneosinophilic patients. Obese and late-onset asthmatics had more uncontrolled disease than normal weight subjects and early onset patients. Conclusions: The high rate of disease control in the patients with severe asthma in the current study demonstrated the importance of targeted individualized therapy with accurate phenotyping in specialized asthma outpatient clinics.

[Biologics for the treatment of severe asthma: Current status report 2023]. / Agir astim tedavisinde biyolojikler: Güncel durum raporu 2023.

Severe asthma is associated with increased use of healthcare services, significant deterioration in the quality of life, and high disease and economic burden on patients and societies. Additional treatments are required for severe forms of asthma. Biological agents are recommended for the treatment of severe asthma. In this current status report, we aimed to evaluate the efficacy, effectiveness, and safety data of approved biologics; omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, in the treatment of severe asthma and appropriate patient profiles for these biologics. Pubmed and Cochrane databases based on randomized controlled trials, posthoc analyses, meta-analyses, and real-life studies examining the efficacy and effectiveness of biologics in severe asthma were searched, and the results of these studies on important asthma outcomes were reviewed. Existing studies have shown that all the approved biologic agents targeting cells, receptors, and mediators involved in type 2 inflammation in the bronchial wall in severe asthma significantly reduce asthma exacerbations, reduce the need for oral corticosteroids, and improve asthma control, quality of life, and pulmonary functions. Characterizing the asthma endotype and phenotype in patients with severe asthma and determining which treatment would be more appropriate for a particular patient is an essential step in personalized treatment.

Picturing asthma in Turkey: results from the Turkish adult asthma registry.

INTRODUCTION: National data on asthma characteristics and the factors associated with uncontrolled asthma seem to be necessary for every country. For this purpose, we developed the Turkish Adult Asthma Registry for patients with asthma aiming to take a snapshot of our patients, thereby assigning the unmet needs and niche areas of intervention. METHODS: Case entries were performed between March 2018 and March 2022. A web-based application was used to record data. Study outcomes were demographic features, disease characteristics, asthma control levels, and phenotypes. RESULTS: The registry included 2053 patients from 36 study centers in Turkey. Female subjects dominated the group (n = 1535, 74.8%). The majority of the patients had allergic (n = 1158, 65.3%) and eosinophilic (n = 1174, 57.2%) asthma. Six hundred nineteen (32.2%) of the patients had obese asthma. Severe asthma existed in 670 (32.6%) patients. Majority of cases were on step 3-5 treatment (n: 1525; 88.1%). Uncontrolled asthma was associated with low educational level, severe asthma attacks in the last year, low FEV1, existence of chronic rhinosinusitis and living in particular regions. CONCLUSION: The picture of this registry showed a dominancy of middle-aged obese women with moderate-to-severe asthma. We also determined particular strategic targets such as low educational level, severe asthma attacks, low FEV1, and chronic rhinosinusitis to decrease uncontrolled asthma in our country. Moreover, some regional strategies may also be needed as uncontrolled asthma is higher in certain regions. We believe that these data will guide authorities to reestablish national asthma programs to improve asthma service delivery.

Comparison of 300 mg versus 600 mg daily maintenance doses of aspirin treatment after desensitization in N-ERD: A three-year multicentre experience.

Background: Aspirin treatment after desensitization (ATAD) is effective in preventing nasal polyps recurrence as well as respiratory symptoms in patients with nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory diseases (N-ERD). However, there is no consensus on effective daily maintenance doses in ATAD. Therefore, we aimed to compare the effects of two different maintenance doses of aspirin on clinical outcomes for 1-3 years of ATAD. Methods: This was a retrospective, multicenter study that involved four tertiary centers. The maintenance doses of daily aspirin were 300 mg in one center and 600 mg in the remaining three. The data of patients who were on ATAD for 1-3 years were included. Study outcomes (nasal surgeries, sinusitis, asthma attacks, hospitalization, oral corticosteroid use, and medication uses) were assessed in a standardized way and recorded from case files. Results: The study initially included 125 subjects, 38 and 87 were receiving 300 and 600 mg daily aspirin for ATAD, respectively. Number of nasal polyp surgeries decreased after 1 -3 years compared with before ATAD in both groups (group 1, baseline: 0.44 ± 0.07 versus first year: 0.08 ± 0.05; p < 0.001 and baseline: 0.44 ± 0.07 versus 3rd year: 0.01 ± 0.01; p < 0.001; and group 2, baseline 0.42 ± 0.03 versus first year: 0.02 ± 0.02; p < 0.001 and baseline: 0.42 ± 0.03 versus 3rd year: 0.07 ± 0.03; p < 0.001). Conclusion: Given the comparable effects of 300 mg and 600 mg aspirin daily as maintenance treatment of ATAD on both asthma and sinonasal outcomes in N-ERD, our results suggest using 300 mg of aspirin daily in ATAD owing to its better safety profile.

Field sting reactions in patients receiving Hymenoptera venom immunotherapy: real-life experience.

BACKGROUND: Hymenoptera stings can cause systemic allergic reactions (SARs) that are prevented by venom immunotherapy (VIT). Sting challenge tests or field stings are used to evaluate the outcome of VIT. OBJECTIVE: The aim of the study was to investigate the consequences of field stings in patients during or after completion of VIT, and to identify patients at higher risk. METHODS: Patients treated with VIT between 1995 and 2018 were retrospectively evaluated. Contacted patients were invited to the clinic and a questionnaire was conducted regarding the history of field stings. RESULTS: A total of 115 patients (F/M: 45/70, mean age: 38.5 ± 12 years) treated with VIT were included; 74/115 were contacted and asked about field stings after VIT cessation. A history of 73 field stings was reported in 38 patients, 25 of whom were treated with honeybee venom and 13 with common wasp venom. Eighteen of the reactions were SARs [8 with honeybees (1 grade-I, 6 grade-II, 1 grade-III) and 10 with common wasps (1 grade-I, 5 grade-II, 4 grade-III)]. There was no association between the severity of index reactions and field stings with either the honeybee or common wasp. The median duration of VIT was longer in patients showing no reaction than in patients with an SAR. Of the 7 patients on ACE inhibitors or beta-blockers, 1 asthmatic patient developed grade-II SAR due to field stings in the first year of VIT. CONCLUSIONS: This study confirms that VIT lasting at least 3 years is effective in preventing SARs after field stings.

Comparison of perennial and preseasonal allergoid immunotherapy in grass pollen allergic patients.

BACKGROUND: The clinical and immunological efficacy of preseasonal allergoid immunotherapy has been previously investigated, however, studies comparing the effectiveness of the two protocols are limited in the literature. OBJECTIVE: The aim of this study is to compare the clinical and immunological efficacy of pre-seasonal and perennial allergoid immunotherapy. METHODS: This is a prospective cross sectional two-arm study. During the season; symptom and medication scores were filled. Before and at the end of the season; RQLQ was applied, Phl p sIgE, sIgG4 and IL-10 levels were measured. RESULTS: In preseasonal group patients had better symptom control for most of the weeks, particularly during the peak pollen period (April: w-2 & w-4, p = 0.04; May: w-2, p = 0.02; June: w-1, w-2, p = 0.02; w-3, w-5, p = 0.03; July: w-2, p = 0.01; w-3, p = 0.02; w-4, p = 0.04). In the perennial group, sIgG4 [1st time point: preseasonal 0.02 mgA/L vs perennial 0.13 mgA/L (p < 0.0001); 2nd time point: preseasonal 0.52 mgA/L vs perennial 0.33 mgA/L; 3rd time point: preseasonal 0.04 mgA/L vs perennial 0.12 mgA/L (p < 0.0001)] and IL-10 (1st time point: preseasonal 1.45 pg/ml vs perennial 2.03 pg/ml; 2nd time point: preseasonal 2.29 pg/ml vs perennial 2.19 pg/ml; 3rd time point: preseasonal 2.32 pg/ml vs perennial 2.16 pg/ml) levels were higher and more stable. CONCLUSIONS: Preseasonal immunotherapy provided better control of symptoms throughout the pollen season. However, the blocking antibody response was stronger and more permanent in the perennial immunotherapy group.

Characteristics of the patients with asthmarhinitis multimorbidity.

Introduction: Asthma and allergic rhinitis frequently coexist and have been regarded as a single airway disease. Clinical features of patients with asthmarhinitis multimorbidity may change depending on the allergic sensitization pattern. The aim of our study is to determine the frequency, type, and characteristics of the patients with asthma-rhinitis multimorbidity. Materials and Methods: Patients who were followed up with a diagnosis of asthma between 2015 and 2020 in our clinic were included in our crosssectional study. Sociodemographic and clinical characteristics of the patients, rhinitis symptoms, and atopy status according to the results of the skin prick test, and sp IgE were recorded from the patient files. Result: Asthma-rhinitis multimorbidity was seen in 138 (113 F/25 M) out of 405 asthmatics and the mean age was 45.51 ± 13.56 years. They were younger and the age of onset of asthma was earlier than asthma patients without rhinitis. The rate of concomitant allergic rhinitis (AR) was 25.9%, and the rate of non-allergic rhinitis (NAR) was 8.1% in the entire group. There was no difference between patients with AR and NAR in terms of comorbidities such as NSAID sensitivity, nasal polyps, chronic rhinosinusitis, and bronchiectasis but, gastroesophageal reflux disease was more common in those with NAR than in those with AR (39.4%, 18.1%, respectively, p= 0.01). Of 105 asthmatic patients accompanied by allergic rhinitis, 41 (39.09%) were monosensitized, and 64 (60.95%) were polysensitized. House dust mites were found to be the most common responsible allergen in monosensitized patients. Sensitization to two allergens was the most common pattern among polysensitized patients, and mites and mold association was the most frequent. Patients with monosensitized allergic rhinitis had more severe asthma and a higher rate of NSAID sensitivity than polysensitized patients (p= 0.03, p= 0.04, respectively). There was no difference in the control level, frequency of eosinophilia, and other comorbidities. Conclusions: Our patients with asthma-rhinitis multimorbidity were mostly polysensitized. The most responsible allergen for the sensitization was house dust mites, regardless of whether the patient was monosensitized or polysensitized.

The External Exposome and Allergies: From the Perspective of the Epithelial Barrier Hypothesis.

Introduction: In the last decades, we have seen a rapid increase in the prevalence of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergies. The environmental changes caused by industrialization, urbanization and modernization, including dramatic increases in air pollutants such as particulate matter (PM), diesel exhaust, nitrogen dioxide (NO2), ozone (O3), alarming effects of global warming, change and loss of biodiversity, affect both human health and the entire ecosystem. Objective: In this review, we aimed to discuss the effects of the external exposome on epithelial barriers and its relationship with the development of allergic diseases by considering the changes in all stakeholders of the outer exposome together, in the light of the recently proposed epithelial barrier hypothesis. Method: To reach current, prominent, and comprehensive studies on the subject, PubMed databases were searched. We included the more resounding articles with reliable and strong results. Results: Exposure to altered environmental factors such as increased pollution, microplastics, nanoparticles, tobacco smoke, food emulsifiers, detergents, and household cleaners, and climate change, loss and change in microbial biodiversity, modifications in the consumption of dietary fatty acids, the use of emulsifiers, preservatives and the decrease in the antioxidant content of the widely consumed western diet may disrupt the epithelial barriers of the skin, respiratory and gastrointestinal tracts, making us more vulnerable to exogeneous allergens and microbes. Epithelial cell activation, microbial dysbiosis and bacterial translocation disrupt the immune balance and a chronic Th2 inflammation ensues. Conclusion: Dramatic increases in air pollution, worrisome effects of global warming, dysbiosis, changing dietary habits and the complex interactions of all these factors affect the epithelial barriers and local and systemic inflammation. We want to draw attention to the emerging health effects of environmental changes and to motivate the public to influence government policies for the well-being of humans and the nature of the earth and the well-being of future generations.

Eosinophilic granulomatosis with polyangitis: A new target for biologicals.

Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) is a rare systemic necrotizing granulomatous vasculitis in the spectrum of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Nevertheless, EGPA has specific clinical, biological and histological properties different from other AAVs [microscopic polyangiitis (MPA) and granulomatous polyangiitis (GPA)]. Recently, thanks to the studies conducted to understand the pathophysiology of EGPA, unlike neutrophils in other AAVs, the main cells involved in EGPA have been observed to be eosinophils. The key role of eosinophils in EGPA and recent development of targeted agents to treat other eosinophil-related diseases have created new therapeutic opportunities for EGPA. Conventional treatment of EGPA relies mainly on agents that decrease inflammation. Cornerstone therapy is systemic glucocorticoids, used as monotherapy or in combination with immunosuppressive agents. However, new therapeutic approaches are needed especially for persistent asthma symptoms, refractory disease, relapses and problems associated with corticosteroid dependence. Recently, the first large-scale randomized controlled clinical trial on polyangiitis and eosinophilic granulomatosis has demonstrated the efficacy of eosinophil-targeted biotherapy anti-interleukin-5 (IL-5) mepolizumab, and is approved for the management of EGPA. This finding opens a new era for EGPA management. This review provides an overview of eosinophilic granulomatosis with polyangiitis in the light of new targeted biological therapies.

Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease.

Environmental exposure plays a major role in the development of allergic diseases. The exposome can be classified into internal (e.g., aging, hormones, and metabolic processes), specific external (e.g., chemical pollutants or lifestyle factors), and general external (e.g., broader socioeconomic and psychological contexts) domains, all of which are interrelated. All the factors we are exposed to, from the moment of conception to death, are part of the external exposome. Several hundreds of thousands of new chemicals have been introduced in modern life without our having a full understanding of their toxic health effects and ways to mitigate these effects. Climate change, air pollution, microplastics, tobacco smoke, changes and loss of biodiversity, alterations in dietary habits, and the microbiome due to modernization, urbanization, and globalization constitute our surrounding environment and external exposome. Some of these factors disrupt the epithelial barriers of the skin and mucosal surfaces, and these disruptions have been linked in the last few decades to the increasing prevalence and severity of allergic and inflammatory diseases such as atopic dermatitis, food allergy, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, and asthma. The epithelial barrier hypothesis provides a mechanistic explanation of how these factors can explain the rapid increase in allergic and autoimmune diseases. In this review, we discuss factors affecting the planet's health in the context of the 'epithelial barrier hypothesis,' including climate change, pollution, changes and loss of biodiversity, and emphasize the changes in the external exposome in the last few decades and their effects on allergic diseases. In addition, the roles of increased dietary fatty acid consumption and environmental substances (detergents, airborne pollen, ozone, microplastics, nanoparticles, and tobacco) affecting epithelial barriers are discussed. Considering the emerging data from recent studies, we suggest stringent governmental regulations, global policy adjustments, patient education, and the establishment of individualized control measures to mitigate environmental threats and decrease allergic disease.

A step-down experience in asthma treatment: a retrospective cohort study.

BACKGROUND: According to recent guidelines; patients with controlled asthma who are stable for at least three months and don't have risk factor should be considered for step down. OBJECTIVE: To evaluate our step down attempts and affecting factors. METHODS: This study was a retrospective-cohort study of patients with asthma who were followed up in our clinic for at least one year. Sociodemographic, phenotypic, clinical features and number of step-down attempts were recorded from the files. Step down was tried in well controlled patients and considered as successful whether descending step was maintained or a lower step was reached until the last visit. RESULTS: A total of 239 patients (196 F/43 M) with a mean age of 51.54 ± 15.29 years were included in the study. Step-down attempt was performed in 44.8% (n = 107) of the patients and % 74.8 (n = 80) of them were successful. Factors related to failure were lower level of education, allergic comorbidity (p = 0.04) and female gender (p = 0.04). Risk of failure was 3.45 and 1.84 times higher than university graduates in high school and primary school graduates, respectively. The probability of failure in step down was 3.38 times higher in patients with allergic comorbidity, and it was 3.92 times more likely in women than men. CONCLUSIONS: Our results showed that the step down attempt could be performed in patients receiving treatment from all steps. In addition, treatment of allergic comorbidities and increased level of education, may make a step down attempt more successful.

Coincidence of pollen season and coronavirus disease 2019 pandemic: less time outdoors - lesser allergy symptoms in 2020.

BACKGROUND: This year, pollen season coincided with the first wave of the coronavirus disease 2019 pandemic. Strict preventive measures have been implemented during April and May and then a normalization phase started in our country in June. Our aim is to evaluate the effect of preventive measures during the pandemic process on allergic airway disease symptoms. METHODS: A prospective questionnaire-based study was planned and a questionnaire form was sent to the cell-phones of the subjects with pollen allergy followed in our clinic. Number of airborne grass pollens was determined by Burkard volumetric 7-day spore trap. RESULTS: A total of 222 pollen allergic patients were included in the study. At the beginning of the pandemic, majority of the subjects were spending time mostly indoors. The rate of home-office workers gradually decreased and the rate of office workers and the number of days at work increased from April to June, significantly. Nasal and ocular symptoms of the patients, also increased in June compared to April and May and, approximately one-third of the patients had less symptoms when compared to the same period of the previous year. The rates of using a face mask and taking a shower on return home were high among the subjects during all season. CONCLUSION: Our study showed that spending less time outside during the pollen season and wearing a mask outdoors reduces exposure to pollens and causes a reduction in symptoms. Thus, strict application of measures that cannot be applied in daily practice can make a significant contribution to the management of seasonal allergic rhinitis.

Baker's asthma in bread factory workers.

Background: Baker's asthma (BA) is one of the most common causes of occupational asthma. Prevalence of BA varies from 3 to 24% in various studies; however, in our country, there are not enough data on its prevalence. Objective: The aim of this study was to evaluate wheat flour sensitivity and to determine the rate of BA in workers at a large bread factory in Ankara. Methods: All steps of the study were carried out in the workplace by the research team who made regular visits to the bread factory. A questionnaire was used to determine the presence of respiratory symptoms and its relation with the occupation. Skin-prick tests and specific immunoglobulin E measurements were performed. Pulmonary function tests and specific inhalation challenges (SIC) were performed to confirm the BA diagnosis. Results: A total of 162 workers (women/men, 3/159; mean ±standard error age, 38.25 ± 7.8 years) were included in the study. Of the 99 workers who described symptoms, 88 (88.8%) had nasal and 57 (57.5%) had lower respiratory symptoms. Sensitivity to wheat flour was present in 23 of the workers (14.2%) among all the workers. Among all the workers, seven (4.32%) were diagnosed with BA and SICs were positive in four (2.46%). Conclusion: Wheat sensitivity was high among the bakers who were exposed to wheat flour; however, the prevalence of BA was quite lower than the previous data in the literature.

Tolerance mechanisms in allergen immunotherapy.

PURPOSE OF REVIEW: Allergen immunotherapy is the only treatment modality which alters the natural course of allergic diseases by restoring immune tolerance against allergens. Deeper understanding of tolerance mechanisms will lead to the development of new vaccines, which target immune responses and promote tolerance. RECENT FINDINGS: Successful allergen immunotherapy (AIT) induces allergen-specific peripheral tolerance, characterized mainly by the generation of allergen-specific Treg cells and reduction of Th2 cells. At the early phase, AIT leads to a decrease in the activity and degranulation of mast cells and basophils and a decrease in inflammatory responses of eosinophils in inflamed tissues. Treg cells show their effects by secreting inhibitory cytokines including interleukin (IL)-10, transforming growth factor-ß, interfering with cellular metabolisms, suppressing antigen presenting cells and innate lymphoid cells (ILCs) and by cytolysis. AIT induces the development of regulatory B cells producing IL-10 and B cells expressing allergen-specific IgG4. Recent investigations have demonstrated that AIT is also associated with the formation of ILC2reg and DCreg cells which contribute to tolerance induction. SUMMARY: Research done so far, has shown that multiple molecular and cellular factors are dysregulated in allergic diseases and modified by AIT. Studies should now focus on finding the best target and ideal biomarkers to identify ideal candidates for AIT.

Environmental factors in epithelial barrier dysfunction.

The main interfaces controlling and attempting to homeostatically balance communications between the host and the environment are the epithelial barriers of the skin, gastrointestinal system, and airways. The epithelial barrier constitutes the first line of physical, chemical, and immunologic defenses and provides a protective wall against environmental factors. Following the industrial revolution in the 19th century, urbanization and socioeconomic development have led to an increase in energy consumption, and waste discharge, leading to increased exposure to air pollution and chemical hazards. Particularly after the 1960s, biological and chemical insults from the surrounding environment-the exposome-have been disrupting the physical integrity of the barrier by degrading the intercellular barrier proteins at tight and adherens junctions, triggering epithelial alarmin cytokine responses such as IL-25, IL-33, and thymic stromal lymphopoietin, and increasing the epithelial barrier permeability. A typical type 2 immune response develops in affected organs in asthma, rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, food allergy, and atopic dermatitis. The aim of this article was to discuss the effects of environmental factors such as protease enzymes of allergens, detergents, tobacco, ozone, particulate matter, diesel exhaust, nanoparticles, and microplastic on the integrity of the epithelial barriers in the context of epithelial barrier hypothesis.