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Мета роботи — визначити наявність небажаних ефектів базисної терапії у дітей, хворих на алергічну бронхіальну астму (БА).Матеріали та методи. Обстежено 224 дитини з алергічною БА віком від 6 до 17 років із визначенням вмісту гомоцистеїну та судинного ендотеліального фактора росту, проведенням ультрасонографії сон­ної та плечової артерій на апараті Philips HD11 XE у В-режимі з кольоровим допплерівським картуванням потоків.Результати. Порівнюючи показники вмісту гомоцистеїну та судинний ендотеліальний фактор росту у дітей, хворих на БА, залежно від наявності базисної протизапальної терапії (БПЗТ), нами було встановлено, що їх уміст вірогідно нижчий у дітей, які не отримували БПЗТ (р < 0,05). Лікування середніми та високими дозами інгаляційних глюкокортикоїдів є чинником ризику підвищення вмісту гомоцистеїну (ОR 1,504; 95% CI 1,141–7,519 та ОR 2,456; 95% CI 1,427–29,343 відповідно). Вміст судинного ендотеліального фактора росту вірогідно підвищується при застосуванні низьких (OR 1,385; 95% CI 1,117–4,602) та середніх (OR 2,462; 95% CI 1,200–30,275) доз інгаляційних глюкокортикоїдів. Потовщення комплексу інтими-медії понад 0,9 мм (OR 1,157; 95% CI 1,080–4,777) не мало дозозалежного ефекту.

Background Although population studies have implicated emotional burden in asthma severity, the underlying genetic risk factors are not completely understood. We aimed to evaluate the genetic influence of a functional single-nucleotide polymorphism (SNP) in the stress-related μ-opioid receptor gene (OPRM1; A118G SNP, rs1799971) on asthma severity. Methods We initially assessed disease severity in asthmatic outpatients carrying A118G. Using an ovalbumin-induced experimental asthma rodent model harboring the functionally equivalent SNP, we investigated the mechanism by which this SNP influences the allergic immune response. Results Among 292 outpatients, 168 underwent airway hyperresponsiveness (AHR) to methacholine testing. Compared with patients carrying the AA and AG genotypes, those carrying the GG genotype exhibited enhanced AHR. The stress levels were presumed to be moderate among patients and were comparable among genotypes. Compared with Oprm1 AA mice, GG mice demonstrated aggravated asthma-related features and increased pulmonary interleukin-4+CD4+ effector and effector memory T cells under everyday life stress conditions. Intraperitoneal naloxone methiodide injection reduced effector CD4+ T cell elevation associated with increased eosinophil numbers in bronchoalveolar lavage fluid of GG mice to the levels in AA mice, suggesting that elevated Th2 cell generation in the bronchial lymph node (BLN) of GG mice induces enhanced eosinophilic inflammation. Conclusions Without forced stress exposure, patients with asthma carrying the OPRM1 GG genotype exhibit enhanced AHR, attributable to enhanced Th2 cell differentiation in the regional lymph node. Further research is necessary to elucidate the role of the OPRM1 A118G genotype in the Th2 cell differentiation pathway in the BLN.

Background A subset of individuals with allergic asthma develops a late phase response (LPR) to inhaled allergens, which is characterized by a prolonged airway obstruction, airway inflammation and airway hyperresponsiveness. The aim of this study was to identify changes in the plasma proteome and circulating hematopoietic progenitor cells associated with the LPR following inhaled allergen challenge. Methods Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed by mass spectrometry and immunosorbent assays. Peripheral blood mononuclear cells were analyzed by flow cytometry. Mass spectrometry data were analyzed using a linear regression to model the relationship between airway obstruction during the LPR and plasma proteome changes. Data from immunosorbent assays were analyzed using linear mixed models. Results Out of 396 proteins quantified in plasma, 150 showed a statistically significant change 23 h post allergen challenge. Among the most upregulated proteins were three protease inhibitors: alpha-1-antitrypsin, alpha-1-antichymotrypsin and plasma serine protease inhibitor. Altered levels of 13 proteins were associated with the LPR, including increased factor XIII A and decreased von Willebrand factor. No relationship was found between the LPR and changes in the proportions of classical, intermediate, and non-classical monocytes. Conclusions Allergic reactions to inhaled allergens in asthmatic subjects were associated with changes in a large proportion of the measured plasma proteome, whereof protease inhibitors showed the largest changes, likely to influence the inflammatory response. Many of the proteins altered in relation to the LPR are associated with coagulation, highlighting potential mechanistic targets for future treatments of type-2 asthma.

Introduction: Many patients sensitized to mites remain symptomatic and uncontrolled despite traditional treatment. Sublingual immunotherapy (SLIT) has demonstrated to reduce the symptoms of allergic rhinitis, the need for additional drug treatments, and to reduce the number of moderate and severe exacerbations in patients with allergic asthma caused by mites that had not been adequately controlled. Areas covered: After reviewing the most recent literature, a scientific committee composed by five pneumologists experts in asthma proposed 41 items that addressed the diagnosis of allergic asthma caused by mites, the role of house dust mite (HDM) SLIT tablet in the therapeutic plan and in the control of the disease, and the profile of patients with asthma candidates for this therapy. Through a modified Delphi method, the items were send to 106 pneumologists involved in asthma to be agreed. Expert opinion: The high degree of consensus reached by the panel of pneumologists shows the importance of HDM SLIT tablet in the treatment of allergic asthma caused by mites, particularly taking into account that they barely use this therapy because until now they did not have a registered treatment with solid evidence of efficacy and safety.

Asthma is a chronic inflammatory disease of the respiratory tract in which the numerous immune cells, including eosinophils, neutrophils, macrophages, T-lymphocytes, mast cells and epithelial lining play key roles. The numerous anti-asthmatic drugs are available in modern medicine to treat asthma, but they have several disadvantages, including side effects and the cost variations, which compromise treatment compliance. The literature review reveals that traditional herbal medicines have good potential as alternative treatment and management for asthma. However, communities hesitated to use the traditional herbal medicines due to lack of established mechanism of action about their anti-asthmatic potential. The present review aimed to summarise the information stated in the literature about the potential effect of traditional medicinal plants (TMPs) conferring protection against ovalbumin (OVA)-induced asthma model. The literature search was conducted in database like PubMed, Scopus, Google Scholar and ScienceDirect. After screening through the literature from 2011 to date, a total of 27 medicinal plants and two polyherbal extracts have been reported to be used as traditional herbal medicines and also utilised to be tested against OVA-induced asthma, were included. We found them to be an important alternative source of treatment for asthma, since some have comparable efficacies with drugs commonly used in the modern system against asthma. All the reported medicinal plants confirmed their traditional use against asthma or its related inflammation. The present review provides faith in traditional information and also offers new insight into the potential of natural products against asthma.

Mouse models have become an indispensable tool in translational research of human airway disease and have provided much of our understanding of the pathogenesis of airway disease such as asthma. In these models the ability to assess pulmonary function and particularly airway responsiveness is critically important. Existing methods for testing pulmonary function in mice in vivo include noninvasive and invasive technologies. Noninvasive head-out body plethysmography is a well-established and widely accepted technique which has been proven as a reliable method to measure lung function on repeated occasions in intact, conscious mice. We have performed several validation studies in allergic mice to compare the parameter midexpiratory flow (EF50) as a noninvasive marker of airflow limitation with invasively measured gold standard parameters of lung mechanics. The results of these studies showed a good agreement of EF50 with the invasive assessment of lung resistance and dynamic compliance with a somewhat lower sensitivity of EF50. The measurement of EF50 together with basic respiratory parameters is particularly appropriate for simple and repeatable screening of pulmonary function in large numbers of mice or if noninvasive measurement without use of anesthesia is required. Beyond known applications, head-out body plethysmography also provides a much-needed high-throughput screening tool to gain insights into the impact and kinetics of respiratory infections such as SARS-COV-2 on lung physiology in laboratory mice.

Background: Trigonella foenum-graecum L. (fenugreek) seeds have a long history of treating allergic asthma known as “Rabv” in Persian medicine. The protective effects of fenugreek on asthma have been noted in Persian medicine texts. Objective: The aim of the present study was to investigate the protective effects of aqueous fenugreek seed extract (AFSE) on the reduction of Th2 cytokines via decreasing the levels of mRNA expression of Th2 cytokines in bronchoalveolar lavage fluid (BALF). Methods: 28 female Balb/c mice were divided into four groups of seven animals. Negative and positive control groups received Phosphate-buffered saline and ovalbumin (OVA), respectively. The remaining two groups were firstly sensitized with OVA to induce asthma and then received Theophylline and AFSE. Thereafter, the mRNA expressions of Th2-type interleukins (IL-4, IL-5, and IL-13) and mucin5 as well as the concentrations of IL-5, IL-13, and IL-33 in BALF samples were measured and pathological alterations of lung tissues were analyzed. Results: AFSE treatment of Balb/c mice significantly decreased the number of eosinophils, the mRNA expressions of IL-4, IL-5, IL-13, and mucin5 and the concentrations of IL-5, IL-13, and IL-33 in their BALF specimens. It also considerably prevented peribronchial and perivascular inflammations, mucus hypersecretion, and goblet cell hyperplasia in lung tissues in comparison to OVA-sensitized mice. Conclusion: The present study demonstrated that the aqueous fenugreek seeds extract could be an alternative medication for the treatment of allergic asthma.

Aim:- To study the effect of exercises in childhood allergic asthma, and to reveal their optimal frequency, intensity, and duration, because of missing consensus about them. Material and Methods:- 12 children (age 11.17 ± 2.69 years) with allergic asthma were followed for one year. At the beginning and the end of the year, they were treated for 10 days with low daily doses of inhaled corticosteroids and exercises (breathing retraining, respiratory muscle training, and musculoskeletal flexibility with posture/balance training). The children and their parents were instructed to continue the same exercises at home as frequently, intensely, and prolong as possible for one year. Standard spirometry was performed four times – at the beginning and the end of the two 10-day treatment courses. The results were recorded as percentages of the actual versus the predicted spirometric parameters. MANOVA with Bonferronis multiple comparison post-hoc tests and Pearsons correlation with multiple regression post-hoc tests were used for the statistical analysis. Results:- The spirometric parameters showed a significant improvement at the end of each 10-day treatment course versus at the beginning (P0.05). The regression analysis revealed that with increasing the exercise intensity and frequency (at least once daily) the spirometric parameters are improving significantly (P

Airway inflammation in asthma is accompanied by reconstruction of the bronchial wall extracellular matrix that most likely occurs with a contribution of matrix metalloproteinases (MMPs). Recently we have reported that omalizumab may decrease reticular basement membrane (RBM) thickness together with fibronectin deposits in asthmatic airways, although mechanisms involved are unknown.In the present study, we have investigated the impact of omalizumab on MMPs concentrations in bronchoalveolar lavage fluid (BAL) of asthmatic subjects in relation to airway remodeling changes in histology.The study group consisted of 13 severe allergic asthmatics treated with omalizumab for at least 12 months. In each subject, clinical and laboratory parameters, bronchoscopy with BAL, and endobronchial biopsy were evaluated before and after the biologic therapy. RBM thickness, fibronectin, and collagen deposits in bronchial mucosa specimens were analyzed in histology. The investigations also included BAL cytology and BAL concentrations of MMP-2, -3, and -9.Omalizumab was related to a decrease in all measured MMPs in BAL (Our data suggest that omalizumab therapy is associated with decreased BAL MMPs concentration in the subgroup of asthma patients. The decline was linked with a reduction in the RBM thickness what might play a beneficial role in airway remodeling.

Allergic Asthma is one among the diseases which imposes a great burden on the subjects by hampering the quality of life of patients, reducing productivity, and causing work absence. The literary search hinted that there are no published works reporting both clinical and immunological(IgE) outcomes in Allergic Asthma. So the present study was a pre and post test clinical study to evaluate the effect of Ayurvedic line of management in inducing both immunological(IgE) and clinical outcomes in Allergic Asthma. In this study 30 patients were administered classical Virecana Karma (drug induced purgation) followed by Shamanoushadi (internal medicine) for 30 days. Statistical Analysis was done using SPSS VER. 20. Wilcoxon signed rank test was used to evaluate the Subjective parameters, in order to interpret the time of significant change. For objective parameters Paired Samples t- Test was used to evaluate the difference of significant change. The results showed improvement in the subjective criteria, objective criteria and the overall effect of the therapy with the exception of no statistically significant results in immunomodulatory (IgE) effect which proves that the particular management protocol adopted is found to be clinically efficant but not effective in inducing changes at the immune level.

In recent years, several new asthma therapeutics have been developed. Although many of these agents show promise in treating allergic asthma, they are less effective against nonallergic forms of asthma. The gut microbiome has important roles in human health and disease, and a growing body of evidence indicates a link between the gut microbiome and asthma. Here, we review those data focusing on the role of the microbiome in mouse models of nonallergic asthma including obese asthma and asthma triggered by exposure to air pollutants. We describe the impact of antibiotics, diet, and early life events on airway responses to the air pollutant ozone, including in the setting of obesity. We also review potential mechanisms responsible for gut-lung interactions focusing on bacterial-derived metabolites, the immune system, and hormones. Finally, we discuss future prospects for gut microbiome-targeted therapies such as fecal microbiome transplantation, prebiotics, probiotics, and prudent use of antibiotics. Better understanding of the role of the microbiome in airway responses may lead to exploration of new microbiome-targeted therapies to control asthma, especially nonallergic forms of asthma.

Introduction: Omalizumab is used to treat severe uncontrolled allergic asthma and chronic spontaneous urticaria (CSU), and is approved for self-administration in prefilled syringes. It is thus important to understand the advantages, critical issues, and indications for home administration.Areas covered: The present review summarizes the available evidence on home administration of omalizumab in asthma and CSU to illustrate the advantages derived from self-administration of patients in this setting.Expert opinion: The available data suggest that patients can safely administer biologics at home with suitable training, and that home administration is time saving and cost-effective. The majority of patients with severe asthma or CSU treated with omalizumab are likely to be suitable candidates for self-administration, which can be proposed to anyone that the clinician deems suitable. In addition to clinicians, pharmacists can also play a key role in managing patients who are prescribed home administration. A practical flow chart is proposed on selection of patients and their management during home administration. Self-administration of biologics can be considered as a valid alternative to traditional injections in a clinical setting, and the evidence has shown that no major issues need to be overcome in terms of safety or efficacy.

Background Polyvalent Mechanical Bacterial Lysate (PMBL®) contains antigens of bacteria responsible for respiratory infections. PMBL® has been proven to reduce the number of respiratory infections, and in its use, immunological benefits have been seen in allergic patients. PMBL® activates both innate and specific immune responses. The lysate induces dendritic cells, T and B lymphocytes and IgA secretion, as well as the production of antibodies directed against administered bacterial antigens. Moreover, it increases the response against other bacteria and viruses. The immunologic mechanism of lysate’s action is not yet clearly determined. The objective of this study was to assess the effect of PMBL® on T cells in children with allergic asthma. Methods This study was a part of the EOLIA study. Herein, 49 children with allergic asthma and house dust mites allergy were included: 21 in PMBL® and 28 in the Placebo group, both, drug and placebo were administered sublingually. The tests were done at baseline and 12 weeks after the last tablet intake. The lymphocytes CD45+, lymphocytes T CD3+, CD3+CD25+, CD3+CD69+, Th CD3+CD4+, CD4+CD25+, CD4+CD25+ high, CD4+CD69+, Treg CD4+CD25+FOXP3, Tc CD3+CD8+, CD8+CD25+, CD8+CD69+, NK-like T CD3+CD16+CD56+ and NK cells CD3−CD16+CD56+ were described. Results At baseline, no significant differences between groups relative to blood count cells were observed, except for eosinophils. After 12 weeks, we observed an increase of T lymphocytes count. In addition, CD4+CD25+FOXP3+, CD8+ and CD3−CD16+CD56+ and (insignificantly) Th count increased. However, CD69+ and CD25+ subset of CD3+ significantly decreased. Conclusions The EOLIA study demonstrated that PMBL® administration 10 days per month for 3 months changed the panel of T lymphocytes. Trial registration Clinical Trial Registration: This study was a part of the EOLIA (Efficacy Of mechanical bacterial Lysate In Allergic children), a clinical study NCT02541331. Frederic Durmont, MD Lallemand Pharma International AG. Date of registration 09/08/2013. URL of trial registry record: https://clinicaltrials.gov/ct2/show/study/NCT02541331.

Context Modified BuShenYiQi formula (M-BYF) is derived from BuShenYiQi formula, used for the treatment of allergic asthma. The exact effect and mechanism of M-BYF on the improvement of asthma remain unclear. Objective We investigated the mechanism underlying the therapeutic effect of M-BYF on allergic asthma. Materials and methods The asthma model was established in female BALB/c mice that were sensitized and challenged with ovalbumin (OVA). Mice in the treated groups were orally treated once a day with M-BYF (7, 14 and 28 g/kg/d) or dexamethasone before OVA challenge. Control and Model group received saline. Pathophysiological abnormalities and percentages of lung type 2 innate lymphoid cells (ILC2s) and Th9 cells were measured. Expression levels of type 2 cytokines and transcription factors required for these cells function and differentiation were analysed. Expression of vasoactive intestinal polypeptide (VIP)–VPAC2 signalling pathway-related proteins, and percentages of VIP expressing (VIP+) cells and VPAC2, CD90 co-expressing (VPAC2+CD90+) cells were detected. Results M-BYF alleviated airway hyperresponsiveness, inflammation, mucus hypersecretion and collagen deposition in asthmatic mice. M-BYF down-regulated percentages of ILC2s and Th9 cells with lower expression of GATA3, PU.1 and IRF4, reduced IL-5, IL-13, IL-9 and VIP production. The decrease in the expression of VIP–VPAC2 signalling pathway and percentages of VIP+ cells, VPAC2+CD90+ cells were observed after M-BYF treatment. The LD50 value of M-BYF was higher than 90 g/kg. Discussion and conclusions M-BYF alleviated experimental asthma by negatively regulating ILC2s and Th9 cells and the VIP–VPAC2 signalling pathway. These findings provide the theoretical basis for future research of M-BYF in asthma patient population.

To describle how respiratory tract infections (RTIs) that occurred in children with allergic asthma (AA) on allergen immunotherapy (AIT) during an influenza season. Data including clinical symptoms and treatment history of children (those with AA on AIT and their siblings under 14 years old), who suffered from RTIs during an influenza season (Dec 1st, 2019–Dec 31st, 2019), were collected (by face to face interview and medical records) and analyzed. Children on AIT were divided into 2 groups: stage 1 (dose increasing stage) and stage 2 (dose maintenance stage). Their siblings were enrolled as control. During the study period, 49 children with AA on AIT (33 patients in stage 1 and 16 patients in stage 2) as well as 49 children without AA ( their siblings ) were included. There were no significant differences in occurrences of RTIs among the three groups (p > 0.05). Compared with children in the other two groups, patients with RTIs in stage 2 had less duration of coughing and needed less medicine. Children on AIT with maintenance doses had fewer symptoms and recovered quickly when they were attacked by RTIs, which suggested that AIT with dose maintenance may enhance disease resistance of the body.

Background:House-dust mites (HDM) allergen is one of the most important allergens in southern China; however, studies on the Dermatophagoides pteronyssinus components are relatively lacking.Objective:This study analyzed the molecular components of D. pteronyssinus in patients with allergic asthma (AS) and/or allergic rhinitis (AR) sensitized to D. pteronyssinus, and aimed to improve HDM immunotherapy in southern China.Methods:Allergen component-resolved diagnosis detection technology was used to detect the serum levels of specific immunoglobulin E (sIgE) to D. pteronyssinus allergen components (Der p 1, 2, 3, 5, 7, 10, and 23) in patients who were sensitized to D. pteronyssinus and with AR (n = 106), AS (n = 144), or AR combined with AS (n = 134).Results:The highest positive rates ofD. pteronyssinuscomponents were Der p 1 (94.8%), followed by Der p 2 (77.6%), Der p 23 (62.5%), Der p 7 (34.6%), Der p 5 (17.7%), Der p 10 (12.2%), and Der p 3 (2.6%). Patients with AR+AS had the highest positive rates to Der p 2 (85.8%), Der p 23 (62.7%), Der p 7 (40.3%), Der p 5 (25.0%), and Der p 10 (16.4%). Der p 1 had the highest positive rate in patients with AR (95.3%). The Der p 3 positive rate in patients with AS (6.0%) was higher than that in patients with AR (0.0%, χ2= 6.872, p < 0.05) and patients with AR+AS (0.7%, χ2= 6.063, p < 0.05) Among the patients with AR+AS, 19.1% were co-sensitized to Der p 1, Der p 2, Der p 23, and Der p 7. Interestingly, only one patient with AR was exclusively sensitized to Der p 23. An optimal scale analysis showed that Der p 5, Der p 23, and Der p 7 had strong connection (Cronbach α = 93.7%).Conclusion:Der p 1 and Der p 2 were the main sensitization components of D. pteronyssinus, and patients with AS+AR had the highest positive rate for five of seven D. pteronyssinus allergen components. This research can provide suggestions for personalized HDM-specific immunotherapy in southern China.

Funder: ALK-Abello A/S, BACKGROUND: This paper reports the duration of moderate and severe exacerbations in patients with house dust mite induced allergic asthma and the impact on patients' quality of life. METHODS: Post-hoc analyses were conducted using data collected during a phase III multi-national trial (MT-04) that investigated time to moderate or severe asthma exacerbation among 485 patients during withdrawal from inhaled corticosteroids. Patient diaries were analysed to ascertain duration of exacerbations. The impact on patients' quality of life was measured by calculating utilities for five health states using the EuroQol-5 Dimension (EQ-5D-3L) and Asthma Quality of Life Questionnaire (AQL-5D). A regression analysis predicted the disutility of moving from 'well controlled asthma' to the other four health states: 'partially controlled asthma', 'uncontrolled asthma', 'moderate exacerbation' and 'severe exacerbation'. RESULTS: Two hundred four patients experienced exacerbations. Moderate and severe exacerbations involved statistically significant reductions in lung function compared to the constant peak expiratory flow observed for patients without exacerbations. Lung function decline occurred for 28 days, decreasing approximately 14 days before an exacerbation followed by a return to baseline over 14 days. Asthma symptoms, the use of short-acting β2-agonists, and frequency of nocturnal awakening all increased, starting 10-14 days before an exacerbation, and returned to baseline within 10-28 days following exacerbations. Compared to 'well controlled asthma', the disutility of having a 'moderate exacerbation' ranged from - 0.0834 to - 0.0921 (EQ-5D-3L) and from - 0.114 to - 0.121 (AQL-5D); and of having a 'severe exacerbation' from - 0.115 to - 0.163 (EQ-5D-3L) and from - 0.153 to - 0.217 (AQL-5D), depending on the length of the observation period. CONCLUSIONS: The impact of moderate and severe exacerbations in house dust mite induced allergic asthma extends 14 days before and 28 days after the peak exacerbation event. The impact of exacerbations on patients' health-related quality of life (HRQoL) continues long after their occurrence.

BACKGROUND: Severe asthma is a major burden on health-economic resources; hence, knowing the epidemiology of these patients is important in planning and provision of asthma care. In addition, identifying and managing the comorbidities helps improve symptoms and reduce associated morbidity and mortality. OBJECTIVES: Epidemiology of difficult asthma has not been well studied in the Middle East, so in this study, we present the demographic and clinical characteristics of severe asthma in the United Arab Emirates (UAE). METHODS: We retrospectively reviewed the notes of severe asthma patients attending three tertiary care hospitals between May 2015 and December 2019. Data on baseline demographics, asthma characteristics, treatment, and comorbidities were collected. RESULTS: We reviewed the notes of 458 patients (271 females and 187 males) that fulfilled the 2019 Global Initiative for Asthma guidelines for the diagnosis of severe asthma. The mean age was 47.7 (standard deviation 17.2) years. Males had significantly higher asthma control test scores (17.9 vs. 16, P = 0.01) and mean blood eosinophils (0.401 vs. 0.294, P

Allergic asthma is a type of asthma that provokes symptoms when an individual is exposed to certain triggers, such as pollen, animal sources of allergens, and other various types of allergens. These allergens cause an immune response that influences lungs and leads to difficulties in breathing. The current study is performed to estimate the concentrations of immunoglobulin E (IgE) and interleukin-13 (IL-13), tested by using the enzyme-linked immunosorbent assay (ELISA) and the numbers of eosinophils, calculated by using hematological analyzers, in the blood of patients with allergic asthma. A total of 150 patients and 50 healthy individuals were randomly selected for the study. The results revealed that IgE and IL-13 levels as well as eosinophil percentage were significantly increased (p

Background Allergic bronchopulmonary aspergillosis (ABPA) has been reported in various degrees among patients with persistent allergic asthma (PAA). Currently, there is no gold standard approach for diagnosis of ABPA. Objectives In the current study, we aimed the evaluation of three different mainly used algorithms as Rosenberg & Patterson (A), ISHAM Working Group (B) and Greenberger (C) for diagnosis of ABPA in 200 patients with underlying PAA. Methods All patients were evaluated using Aspergillus skin prick test (SPTAf), Aspergillus-specific IgE (sIgEAf) and IgG (sIgGAf), total IgE (tIgE), pulmonary function tests, radiological findings and peripheral blood eosinophil count. The prevalence rate of ABPA in PAA patients was estimated by three diagnostic criteria. We used Latent Class Analysis for the evaluation of different diagnostic parameters in different applied ABPA diagnostic algorithms. Results Aspergillus sensitisation was observed in 30 (15.0%) patients. According to algorithms A, B and C, nine (4.5%), six (3.0%) and 11 (5.5%) of patients were diagnosed with ABPA, respectively. The sensitivity and specificity of criteria B and C were (55.6% and 99.5%) and (100.0% and 98.9%) respectively. sIgEAf and sIgGAf showed the high significant sensitivity. The performance of algorithm A, in terms of sensitivity and specificity, was somewhat better than algorithm B. Conclusion Our study demonstrated that the sensitivity of different diagnostic algorithms could change the prevalence rate of ABPA. We also found that all of three criteria resulted an adequate specificity for ABPA diagnosis. A consensus patterns combining elements of all three criteria may warrant a better diagnostic algorithm.

Introduction Omalizumab is a high-cost therapy recommended for the treatment of severe allergic asthma. Objective To find clinical parameters that are related to the sustained response to omalizumab. Patients and methods This retrospective, real-life, 4-year follow-up was provided in Poland between March 2013 and May 2019. The success of omalizumab was assessed based on composed subjective and objective criteria. Simple/multiple regression analyses were performed to search for predictors of the response to omalizumab. Results A total of 989 severe allergic asthma patients were referred for omalizumab therapy, of whom 854 patients were considered eligible for treatment. At weeks 16 and 52, omalizumab was successful in 84% and 91% of patients, respectively. Treatment effectiveness was maintained up to the 4-year follow-up. Four predictors of the response to omalizumab were found at week 16 and two at week 52. The results at week 16 may be used as predictors of success at week 52 based on the model including baseline FEV1% and change in ACQ-7 and miniAQLQ score at week 16: the area under the ROC curve equals 0.746 [95% CI: 0.672-0.820]. Conclusion Omalizumab therapy is very effective, with this efficacy sustained after 4 years of treatment. Success of the therapy can be predicted from the baseline FEV1% and clinical improvement (based on ACQ-7 and miniAQLQ scores) at week 16.

Background: international guidelines in asthma and allergy has been updated for COVID-19 pandemic and pandemic has caused dramatic changes in allergy and immunology services. However, it is not known whether specialty-specific recommendations for COVID-19 are followed by allergists. Objectives: by conducting this study, we aimed to determine the attitudes and experiences of adult/pediatric allergists on allergy management during COVID-19. Method: We used a 20-question survey to elicit data from allergists (residents and pediatric and adult allergists registered to the Turkish National Society of Allergy and Clinical Immunology) across Turkey via e-mail. We analyzed the data statistically for frequency distributions and descriptive analysis. Results: a total of 183 allergists participated in the survey. Telemedicine was used for management of asthma (73%), allergic rhinitis (53%), atopic dermatitis (51%), chronic urticaria/angioedema (59%), drug hypersensitivity (45%), food allergy (48%), venom allergy (30%), anaphylaxis (22%), and hereditary angioedema (28%). Thirty-one percent of the respondents discontinued subcutaneous immunotherapy (SCIT) during the COVID-19 pandemic. Thirty-four percent of the physicians reported interruption of systemic steroid use in asthma patients, and 25% of the respondents discontinued biological therapy. Conclusions: allergists in Turkey have been using telemedicine at a high rate during the COVID-19 pandemic for asthma and rhinitis. The continuation rate of SCIT was low while the discontinuation rate of biologicals and systemic steroid use in asthma was high in Turkey.Our study results and learning from the experiences of other countries and specialties may help to optimize allergy practice and compatibility with international guidelines., NA

Epidemic thunderstorm asthma (ETSA) is due to a complex interaction of environmental and individual susceptibility factors, with outbreaks reported globally over the last four decades. Australia has been particularly susceptible with nearly half of episodes reported internationally, culminating in the catastrophic Melbourne 2016 event.Reported ETSA episodes are reviewed for common environmental and meteorological risk factors. Allergen aerobiology interaction with thunderstorm activity and rapid weather condition changes is examined. Assessment of the clinical and immunological data highlights risk factors for ETSA presentation, hospital admission, and intensive care admission. Risk factors associated with ETSA deaths are evaluated. Public health strategies, as well as pharmacological and immunological management approaches to reduce individual susceptibility and prevent ETSA are discussed.Improved understanding of the specific meteorological factors predisposing to the greatest risk of ETSA to improve forecasting is required. Better monitoring of aeroallergen levels in areas of greatest geographic risk, with further research into allergen aerobiology underpinning mechanisms of allergen exposure is needed. The role of climate change in increasing the risk of ETSA outbreaks requires further research. Public awareness and education are required to reduce exposure, and to improve uptake of pharmacological and immunological risk reduction and preventive strategies.

Purpose of review Allergen immunotherapy (AIT) is a well-known disease-modifying intervention for allergic diseases. Its benefit in allergic asthma, ranging from prevention to facilitating asthma control, is yet to be clarified. Recent findings In 2017, following several well-designed randomised controlled trials (RCTs) with house-dust mites (HDM) sublingual (SLIT) tablets in asthma, global initiative for asthma (GINA) guidelines highlighted the need to treat the allergic component of asthma. In 2019, the European Academy of Allergy and Clinical Immunology published the first comprehensive guidelines for HDM AIT in allergic asthma, formulating separate recommendations for subcutaneous, SLIT drops, and SLIT tablets. Significant steps were undertaken in understanding the mechanisms of allergic asthma, facilitating the stratified approach for selecting responders and in translating the immune-modulation effect in achieving long-term control of the chronic inflammation in asthma. Summary Currently existing guidelines recommend AIT as a therapeutic option in controlled or partially controlled HDM allergic asthma. Limited data are available for pollen, molds and pets, as well as for the severe allergic asthma population. The challenge for the future research will be to clarify the subendotypes of allergic asthma responding to AIT, the mechanisms facilitating its' preventive and disease-modifying effect, the optimal duration of the treatment, and route of administration.

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 Užice region, Serbia. Material and methods A time-stratified case-crossover design was applied to 424 ED visits for asthma exacerbation that occurred in the Užice region, Serbia, in 2012-2014. Data about ED visits were routinely collected in the Užice 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 Užice region increases the risk of ED visits for asthma, particularly during the heating season.

Aim/Purpose: Exposure to various allergens has been shown to increase expression of ORMDL3 in the lung in models of allergic asthma. Studies using genetically modified (transgenic or knock out) mic...

Uncontrolled asthma continues to be a problem for many patients with moderate-to-severe allergic asthma. Dupilumab, which blocks the receptors for interleukin-4 and interleukin-13, has been effective in reducing asthma exacerbations, improving forced expiratory volume in one second (FEV1), and reducing oral corticosteroid use. When selecting patients for dupilumab, it is important to consider entry criteria for the original studies, subgroups that have responded best, and the presence of comorbid diseases that may also respond to dupilumab. Factors that were considered when selecting patients likely to respond to dupilumab in asthma studies include: failure of moderate or high dose inhaled steroids in combination with an additional controller medication, baseline FEV1 reversibility of 12% or greater, and Asthma Control Questionnaire > 1.5. The baseline characteristics that predicted a better response to dupilumab included blood eosinophils > 150 cells/mm3 and fractional exhaled nitric oxide > 25 parts per billion. Comorbidities that may also respond to treatment with dupilumab include atopic dermatitis, chronic rhinosinusitis, and allergic rhinitis. A combination of these factors should be considered when selecting the patients most likely to benefit from dupilumab.

Die Anzahl der von Allergien betroffenen Patienten nimmt weltweit zu. Hiermit gehen erhebliche Kosten fur die Gesundheits- und Sozialsysteme durch allergische Erkrankungen einher. Integrierte Versorgungskonzepte sind erforderlich, die innerhalb der nationalen Gesundheitssysteme eine umfassende Versorgung ermoglichen. Die ARIA-Initiative entwickelt international gultige Leitlinien fur allergische Atemwegserkrankungen. ARIA dient der verbesserten Versorgung von Patienten mit Allergien und chronischen Atemwegserkrankungen. In Zusammenarbeit mit anderen internationalen Initiativen, nationalen Fachgesellschaften und Patientenorganisationen im Bereich Allergien und Atemwegserkrankungen wurde eine realitatsnahe, integrative Versorgungsleitlinie („integrated care pathways“, ICPs) fur eine digital unterstutzte, integrative, individualisierte Behandlung von allergischer Rhinitis (AR) mit komorbidem Asthma entwickelt, die in der vorliegenden Arbeit auf das deutsche Gesundheitssystem ubertragen wird. Die vorliegende ICP-Versorgungsleitlinie umfasst wesentliche Bereiche der Versorgung von Patienten mit AR mit und ohne Asthma einschlieslich der Sicht von Patienten und weiterer versorgungsnaher Gesundheitsdienstleister. Eine umfassende ICP-Leitlinie kann die Versorgungsrealitat wesentlich besser abbilden als herkommliche Leitlinienmodelle.

With asthma affecting over 300 million individuals world-wide and estimated to affect 400 million by 2025, developing effective, long-lasting therapeutics is essential. Allergic asthma, where Th2-type immunity plays a central role, represents 90% of child and 50% of adult asthma cases. Research based largely on animal models of allergic disease have led to the generation of a novel class of drugs, so-called biologicals, that target essential components of Th2-type inflammation. Although highly efficient in subclasses of patients, these biologicals and other existing medication only target the symptomatic stage of asthma and when therapy is ceased, a flare-up of the disease is often observed. Therefore, it is suggested to target earlier stages in the inflammatory cascade underlying allergic airway inflammation and to focus on changing and redirecting the initiation of type 2 inflammatory responses against allergens and certain viral agents. This focus on upstream aspects of innate immunity that drive development of Th2-type immunity is expected to have longer-lasting and disease-modifying effects, and may potentially lead to a cure for asthma. This review highlights the current understanding of the contribution of local innate immune elements in the development and maintenance of inflammatory airway responses and discusses available leads for successful targeting of those pathways for future therapeutics.

Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic rhinitis (AR). Multiple modalities of AIT dosed via sublingual or oral routes are becoming available. This review discusses current evidence and practicalities of aqueous and tablet sublingual immunotherapy (SLIT) and oral mucosal immunotherapy (OMIT) in the treatment of AR and allergic asthma. Several large-scale studies demonstrate the efficacy and safety of SLIT. These studies have led to the United States Food and Drug Administration (USFDA) approval of tablet SLIT against grass, ragweed, and house dust mites (HDM). However, off-label use of aqueous SLIT is still practiced as a safe and effective alternative in polysensitized patients. Growing evidence suggests a role for SLIT in patients with allergic asthma. The literature supports the efficacy and safety of aqueous and tablet SLIT for AR, while some controversy remains over the utility of SLIT for allergic asthma. OMIT is currently in the early stages of development.

Asthma is a cause of substantial burden of disease in the world, including both premature deaths and reduced quality of life. A leading hypothesis to explain the worldwide increase of asthma is the “hygiene hypothesis,” which suggests that the increase in the prevalence of asthma is due to the reduction in exposure to infections/microbial antigens. In allergic asthma, the most common type of asthma, antigen-specific T helper (Th)2 and Th17 cells and their cytokines are primary mediators of the pathological consequences. In contrast, Th1 and T regulatory (Treg) cells and their cytokines play a protective role. This article aims to review the information on the effect of mycobacteria and their antigens in modulating Th2/Th17 responses towards Th1/Treg responses and protection against asthma in humans and animal models.

Introduction Inadequately controlled severe asthma patients require additional therapy accounting for significant clinical and economic burden. Our analysis aims to determine the cost-effectiveness of omalizumab in the management of severe allergic asthma in Italy based on observational data from the PROXIMA study. Methods Observational data on efficacy, healthcare resource utilization and changes in quality of life at 12 months after the initiation of omalizumab were examined to estimate the cost-effectiveness compared to pre-omalizumab period and results were expressed with Incremental Cost-Effectiveness Ratio (ICER). The cost-utility analysis estimated the cost per quality-adjusted life-year (QALY) gained. Direct health costs were assessed from the perspective of the Italian National Health Service (NHS). Results Omalizumab reduced the incidence of exacerbations, number of hospitalizations, physician visits, and improved quality of life after 12 months of treatment. Omalizumab had a greater effectiveness than pre-omalizumab treatment involving 0.132 QALYs gained and led to a €3729 per patient reduction in direct healthcare costs, excluding the add-on treatment cost. Nevertheless, the addition of omalizumab cost led to €7478 increase in total direct costs with respect to pre-omalizumab period. Based on difference in total direct cost and difference in QALY between post and pre-omalizumab period, the ICER was €56,847. According to sensitivity analysis, omalizumab provided a cost-effective use of NHS resources, already at 20% discounted price. Conclusion This study offers a real-world evidence of omalizumab effectiveness in Italy. Despite the high acquisition cost of the innovative drug, omalizumab is a sustainable treatment option for patients with uncontrolled severe allergic asthma.

Introduction/Objective. Interleukin 33 (IL-33) has a very significant function in inflammatory and autoimmune mechanisms, but its significance in immunopathogenic mechanisms of different allergic diseases, including allergic asthma (AA), is becoming increasingly emphasized. The objective of the study was to investigate serum levels of IL-33 in children with AA before applying inhalation corticosteroid therapy (ICS Th) and six months after it, correlating the gathered values of IL-33 with some clinical traits of the patient. Methods. The serum value of IL-33 has been determined in 61 children with AA before starting treatment and six months after treatment with ICS Th, and this was repeated in 30 healthy children. Results. Values of IL-33 in serum are significantly higher in children with AA that have not been treated with ICS Th during six months (p = 0.00; p < 0.05), which is also the case when comparing with healthy children (p = 0.00; p < 0.05). Serum values of IL-33 in children with AA after six months of ICS Th and in healthy children do not show significant difference (p = 0.88; p > 0.05). The correlation between serum values of IL-33 before applying ICS Th and the severity, degree of AA control, and the applied dose of ICS Th is statistically significant and positive. Conclusion. IL-33 values in the serum are significantly higher in children with untreated AA in those with poorly controlled AA. Six-month treatment with ICS Th leads to significant reduction of IL-33 serum levels, whose values are in positive correlation with the severity and control of AA.

Background: Management of hundreds of analytes obtained from the molecular multiplex techniques currently available may represent a challenge for clinicians in daily clinical practice. Objectives: The aim of the study was to describe a comprehensive and simple approach to assess such complex molecular results, to display relevant disease-specific signatures at a glance, and to facilitate their interpretation. Method: A total of 6,332 consecutive allergic patients, categorized based on clinical symptoms reported at the time of the first visit before IgE testing, were evaluated through ImmunoCAP ISAC112®. Results and Conclusions: The occurrence of bronchial asthma is associated with polcalcin, serum albumin, or lipocalin reactivity. Higher risk of severe reaction to food is linked to tropomyosin or nonspecific lipid transfer protein reactivity (in the absence of plant pathogenesis-related proteins [PR-10] or profilin sensitization). We used radar graphic display to highlight, at a glance, the molecular reactivity profiles associated with relevant disease-specific patterns.

Allergen immunotherapy (AIT) has gained a permanent place in the therapeutic arsenal for the patient with allergy. Particularly, substantial evidence has been established for the efficacy of AIT in allergic rhinitis. A hallmark of AIT is it disease modifying effect resulting in persistent benefit after the treatment has been terminated. Both the subcutaneous and sublingual mode of administration appear to be safe. It is, however, a matter of debate whether AIT can be implemented for patients with asthma. EAACI and GINA guidelines recommend sublingual AIT in house dust mite driven asthma. The question however remains whether the different available forms of AIT should be used for allergic asthma in general.

Background: This study aimed to investigate whether the choroidal vascularity index (CVI), choroidal thickness (ChT), and retinal nerve fiber thickness (RNFL) of patients with allergic asthma change compared to the healthy control group. Methods: This cross-sectional, observational study comprised 59 eyes of 59 patients with allergic asthma (Group 1) and 50 eyes of 50 age and sex-matched healthy volunteers as a control group (Group 2). CVI was measured by binarization of images obtained from choroidal enhanced depth imaging (EDI) mode optic coherence tomography. CVI was defined as the ratio of the choroidal luminal area to the total circumscribed choroidal area. ChT was measured manually at 3 points, subfoveal and 1000 microns nasal and temporal to the fovea (SFCT, N1000, and T1000 respectively). RNFL measurements were subdivided as global, nasal, temporal, superonasal, superotemporal, inferonasal, and inferotemporal quadrants. Results: Subfoveal CVI and ChT were significantly lower in asthma patients (p:0,043 and p: 0.034, respectively). N1000 and T1000 ChT and RNFL thicknesses were lower in asthma patients compared to the control group, though no significant difference was found between them (p> 0.05). Conclusion: Our findings suggest that asthma patients have choroidal structural changes. In the literature, there are not enough studies regarding the effects of asthma on ocular parameters. © 2021 Elsevier B.V.

Background Allergic asthma is a chronic airway inflammatory disease with a number of cytokines participating in its pathogenesis and progress. Interleukin (IL)-22, which is derived from lymphocytes, acts on epithelial cells and play a role in the chronic airway inflammation. However, the actual role of IL-22 in allergic asthma is still unclear. Therefore, we explored the effect of IL-22 on allergic airway inflammation and airway hyperresponsiveness (AHR) in an ovalbumin (OVA)-induced asthma mouse model. Methods To evaluate the effect of IL-22 in an allergic asthma model, BALB/c mice were sensitized and challenged with OVA; then the recombinant mouse IL-22 was administered intranasally 24 h prior to each challenge. The IL-22 levels in lung homogenates and bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay, respectively. AHR was evaluated through indicators including airways resistance (Rrs), elastance (Ers) and compliance (Crs); the inflammatory cell infiltration was assessed by quantification of differential cells counts in BALF and lung tissues stained by hematoxylin and eosin (H&E); IL-22 specific receptors were determined by immunohistochemistry staining. Results The concentration of IL-22 was significantly elevated in the OVA-induced mice compared with the control mice in lung homogenates and BALF. In the OVA-induced mouse model, IL-22 administration could significantly attenuate AHR, including Rrs, Ers and Crs, decrease the proportion of eosinophils in BALF and reduce inflammatory cell infiltration around bronchi and their concomitant vessels, compared with the OVA-induced group. In addition, the expression of IL-22RA1 and IL-10RB in the lung tissues of OVA-induced mice was significantly increased compared with the control mice, while it was dramatically decreased after the treatment with IL-22, but not completely attenuated in the IL-22-treated mice when compared with the control mice. Conclusion Interleukin-22 could play a protective role in an OVA-induced asthma model, by suppressing the inflammatory cell infiltration around bronchi and their concomitant vessels and airway hyperresponsiveness, which might associate with the expression of its heterodimer receptors. Thus, IL-22 administration might be an effective strategy to attenuate allergic airway inflammation.

BackgroundAlternaria is a major source of asthma-inducing allergens. Allergen-specific immunotherapy improves the progression of allergic asthma. The current treatment is based on crude Alternaria extracts. Alt a 1 is the predominant allergen in Alternaria. However, the treatment efficacy of recombinant Alt a 1 (rAlt a 1) in an asthmatic animal model and its influence on Tfh and Breg cells are unknown.ObjectiveTo explore the therapeutic treatment effects of rAlt a 1 on the progress of an asthmatic mouse model and its effect on Tfh and Breg cells.MethodsWe synthesized and purified rAlt a 1. Alternaria-sensitized and challenged mice received subcutaneous immunotherapy (SCIT) with four different rAlt a 1 dosages (5, 50, 100, and 150 µg) or PBS only. Finally, lung and airway inflammation, mouse mast cell protease 1 (MMCP-1), serum immunoglobulin responses, Tfh and Breg cell levels, and the correlation between asthmatic features (inflammation grades and IL-4 and IL-10 levels) and these two cell types were measured after Alternaria rechallenge.ResultsHigh purity and allergenic potency of rAlt a 1 protein were obtained. Following treatment with four different rAlt a 1 dosages, both lung and airway inflammation ameliorated, including lung pathology, serum MMCP-1 levels, inflammatory cell numbers, and cytokine levels in bronchoalveolar lavage fluid (BALF). Additionally, rAlt a 1-SCIT increased the expression of Alternaria-sIgG1, rAlt a 1-sIgG1, rAlt a 1-sIgG2a, and rAlt a 1-sIgG2b in serum. Moreover, the number and percentage of CXCR5+PD-1+Tfh cells were increased in the PC control, while they decreased in the rAlt a 1-SCIT groups. Meanwhile, the absolute numbers and proportions of Breg cells were evaluated after administration of rAlt a 1. A positive correlation was observed between CXCR5+PD-1+Tfh cells and inflammation grades (r = 0.50, p = 0.01), as well as a slightly strong positive relationship with IL-4 (r = 0.55, p = 0.005) and IL-10 (r = 0.58, p = 0.003) levels; Breg cells showed an opposite correlation with the grades of inflammation (r = -0.68, p = 0.0003), along with a negative correlation to IL-4 (r = -0.61, p = 0.001) and IL-10 (r = -0.53, p = 0.008) levels.ConclusionsWe verified that treatment with rAlt a 1 can alleviate asthma progression and further have a regulatory effect on Tfh and Breg cells in an Alternaria-induced asthmatic mouse model.

International audience; Gain-of-function mutations in NLRP3 are responsible for a spectrum of autoinflammatory diseases collectively referred to as “cryopyrin-associated periodic syndromes” (CAPS). Treatment of CAPS patients with IL-1–targeted therapies is effective, confirming a central pathogenic role for IL-1β. However, the specific myeloid cell population(s) exhibiting inflammasome activity and sustained IL-1β production in CAPS remains elusive. Previous reports suggested an important role for mast cells (MCs) in this process. Here, we report that, in mice, gain-of-function mutations in Nlrp3 restricted to neutrophils, and to a lesser extent macrophages/dendritic cells, but not MCs, are sufficient to trigger severe CAPS. Furthermore, in patients with clinically established CAPS, we show that skin-infiltrating neutrophils represent a substantial biological source of IL-1β. Together, our data indicate that neutrophils, rather than MCs, can represent the main cellular drivers of CAPS pathology.

The incidence of allergic diseases is increasing, and research on their epidemiology, pathophysiology, and the prevention of onset is urgently needed. The onset of allergic disease begins in infancy with atopic dermatitis and food allergy and develops into allergic asthma and allergic rhinitis in childhood; the process is defined as “atopic march”. Atopic march is caused by multiple immunological pathways, including allergen exposure, environmental pollutants, skin barrier dysfunction, type 2 inflammation, and oxidative stress, which promote the progression of atopic march. Using recent evidence, herein, we explain the involvement of allergic inflammatory conditions and oxidative stress in the process of atopic march, its epidemiology, and methods for prevention of onset.

BACKGROUND Alexithymia is among psychological factors reported to interfere with asthma management. Severe allergic asthma (SAA) is characterized by uncontrolled asthma despite maximal standard pharmacological treatment which can benefit from an add-on treatment with Omalizumab, an anti-IgE monoclonal antibody. OBJECTIVE To evaluate if alexithymia influences the efficacy of omalizumab in SAA. METHODS The total alexithymia score 20 (TAS 20) questionnaire allowed to detect alexithymia. SAA was monitored recording number of exacerbations, asthma control test (ACT) and asthma quality of life questionnaire (AQLQ) scores, as well as forced expiratory volumes in 1 second % (FEV1%) levels before starting omalizumab, 1 and 2 years after. RESULTS The study was conducted on 18 patients; Group 1, TAS 20 ≥ 61, was of 2 males and 4 females with SAA and alexithymia, while Group 2 , TAS 20 ≤ 51, was of 8 males and 4 females, without alexithymia. Group 1 had a statistically significant decrease in asthma exacerbations "p = 0.004", while ACT "p = 0.008" and AQLQ scores statistically increased. FEV1 values increased but not statistically significantly. Group 2 had a highly statistically significant decrease in the number of exacerbations and a highly statistically significant increase of ACT "p < 0.0001", FEV1 "p = 0.008" and AQLQ scores. CONCLUSIONS Regardless the presence or not of alexithymia, all patients with SAA obtained a marked improvement after starting treatment with omalizumab. Therefore alexithymia does not seem to influence the treatment outcome of omalizumab.

Background: Asthma is the most common chronic disease affecting children and altering their quality of life. The severity of asthma is often modulated by immunoglobulin E (IgE)-mediated allergen sensitization and is associated with comorbid allergic dis-eases. Omalizumab is a humanized monoclonal antibody anti-IgE, the first biological therapy approved to treat patients aged ≥6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omali-zumab in Romanian paediatric patients with severe allergic asthma. Methods: In this observational real-life study, 12 children aged 6 to 18 years, (mean age 12.4 years ) with severe allergic asthma received Omalizumab as an add-on treatment. The levels of asthma control, exacerbations, lung function and adverse events were evaluated at baseline and after the first year of treatment. Results: We noticed general improvements in total asthma symptom scores and the rate of exacerbation of severe asthma. Omalizumab increased the initial variables of lung function, and no serious adverse reactions were reported. FEV1 improved statistically significant after one year of treatment with Omalizumab, [ΔFEV1 (% pred.) =18.3, and similarly, ΔMEF50 (%) = 25.8]. The mean severe exacerbation rates due to asthma decreased from 4.1 (2.8 SD) to 1.15 (0.78 SD) during the treatment year (p

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates the metabolism of xenobiotics. There is growing evidence that the AhR is implicated in physiological processes such proliferation, differentiation, and immune responses. Recently, a role of the AhR in regulating allergic asthma has been suggested, but whether the AhR also regulates other type of asthma, particularly occupational/irritant-induced asthma, remains unknown. Using AhR-deficient (Ahr−/−) mice, we compared the function of the AhR in the response to ovalbumin (OVA; allergic asthma) vs. chlorine (Cl2; irritant-induced asthma) exposure. Lung inflammation and airway hyperresponsiveness were assessed 24h after exposure to Cl2 or OVA challenge in Ahr−/− and heterozygous (Ahr+/−) mice. After OVA challenge, absence of AhR was associated with significantly enhanced eosinophilia and lymphocyte influx into the airways of Ahr−/− mice. There were also increased levels of interleukin-4 (IL-4) and IL-5 in the airways. However, OVA-induced airway hyperresponsiveness was not affected. In the irritant-induced asthma model caused by exposure to Cl2, the AhR did not regulate the inflammatory response. However, absence of AhR reduced Cl2-induced airway hyperresponsiveness. Collectively, these results support a differential role for the AhR in regulating asthma outcomes in response to diverse etiological agents.

Propolis is a natural product produced by bees that is primarily used in complementary and alternative medicine and has anti-inflammatory, antibacterial, antiviral, and antitumoral biological properties. Some studies have reported the beneficial effects of propolis in models of allergic asthma. In a previous study, our group showed that green propolis treatment reduced airway inflammation and mucus secretion in an ovalbumin (OVA)-induced asthma model and resulted in increased regulatory T cells (Treg) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) frequencies in the lungs, two leukocyte populations that have immunosuppressive functions. In this study, we evaluated the anti-inflammatory effects of artepillin C (ArtC), the major compound of green propolis, in the context of allergic airway inflammation. Our results show that ArtC induces in vitro differentiation of Treg cells and monocytic MDSC (M-MDSC). Furthermore, in an OVA-induced asthma model, ArtC treatment reduced pulmonary inflammation, eosinophil influx to the airways, mucus and IL-5 secretion along with increased frequency of M-MDSC, but not Treg cells, in the lungs. Using an adoptive transfer model, we confirmed that the effect of ArtC in the reduction in airway inflammation was dependent on M-MDSC. Altogether, our data show that ArtC exhibits an anti-inflammatory effect and might be an adjuvant therapy for allergic asthma.