Roles Played by the PI3K/Akt/HIF-1α Pathway and IL-17A in the Chinese Subtype of Chronic Sinusitis with Nasal Polyps

Background. The Chinese subtype of CRSwNP may have a unique pathogenesis. This study was designed to seek the role of the PI3K/Akt/HIF-1α pathway and IL-17A in CRSwNP. Methods. The total IgE, ECP, and IL-17A levels were determined by UniCAP100 and ELISA. The activity of MPO was detected by the biochemical techniques. The protein expressions of HIF-1α, p-Akt, and PI3K were detected by the WB method. HIF-1α and IL-17A mRNA levels were measured by RT-PCR. Results. The CRSwNP group showed significantly elevated MPO activity, PI3K, p-AKT protein, HIF-1α, and IL-17A mRNA levels in nasal polyps. Stimulated by the TNF-α, the PI3K, p-AKT, HIF-1α, and IL-17A levels significantly elevated in the fibroblasts. Inhibited by the Wortmannin, those indicators significantly declined in the fibroblasts. Conclusion. The PI3K/Akt/HIF-1α pathway played a role in the pathogenesis of CRSwNP. The elevated IL-17A level might be responsible for the neutrophilic inflammation in CRSwNP. The PI3K/Akt/HIF-1α pathway might regulate the IL-17A-related inflammation in CRSwNP.

IgE is associated with exacerbations and lung function decline in COPD

Background Both allergen-specific IgE and total IgE in serum play a major role in asthma. However, the role of IgE in chronic obstructive pulmonary disease (COPD) is poorly understood. It was the aim of this study to systematically analyze the relationship between serum IgE levels and disease characteristics in large COPD cohorts. Methods COSYCONET is a comprehensively characterized cohort of patients with COPD: total IgE and IgE specific to common aeroallergens were measured in serum of 2280 patients, and related to clinical characteristics of the patients. WISDOM is another large COPD population (2477 patients): this database contains the information whether total IgE in serum was elevated (≥ 100 IU/l) or normal in patients with COPD. Results Both in COSYCONET and WISDOM, total IgE was elevated (≥ 100 IU/l) in > 30% of the patients, higher in men than in women, and higher in currently than in not currently smoking men. In COSYCONET, total IgE was elevated in patients with a history of asthma and/or allergies. Men with at least one exacerbation in the last 12 months (50.6% of all men in COSYCONET) had higher median total IgE (71.3 IU/l) than men without exacerbations (48.3 IU/l): this difference was also observed in the subgroups of not currently smoking men and of men without a history of asthma. Surprisingly, a history of exacerbations did not impact on total IgE in women with COPD. Patients in the highest tertiles of total IgE (> 91.5 IU/ml, adjusted OR: 1.62, 95% CI 1.12–2.34) or allergen-specific IgE (> 0.19 IU/ml, adjusted OR: 2.15, 95% CI 1.32–3.51) were at risk of lung function decline (adjusted by: age, gender, body mass index, initial lung function, smoking status, history of asthma, history of allergy). Conclusion These data suggest that IgE may play a role in specific COPD subgroups. Clinical trials using antibodies targeting the IgE pathway (such as omalizumab), especially in men with recurrent exacerbations and elevated serum IgE, could elucidate potential therapeutic implications of our observations.

Atopic Status in Children with Asthma and Respiratory Allergies—Comparative Analysis of Total IgE, ImmunoCAP Phadiatop/fx5 and Euroimmun Pediatric Immunoblot

Introduction: An atopic status assessment (skin prick test or specific immunoglobulin (sIgE)) in asthmatic children is considered a milestone in identifying potential risk factors and triggers provoking loss of asthma control and asthma exacerbation. Objective: The study aims to perform a comparative analysis of different laboratory methods for a serological assessment of an atopic status in asthma and respiratory allergies in children. Material and methods: A total of 86 children were included, all of whom were diagnosed with bronchial asthma, aged from 5 to 17 years and screened for total IgE level using enzyme-linked immunosorbent assay (ELISA). In 48 randomly selected children, we performed a semi-quantitative serological in vitro assessment of the specific IgE antibodies against food and aeroallergen, using two different laboratory methods—Euroimmun Immunoblot and ImmunoCAP (Phadiatop/fx5). Results: In 70% of the children with a history of allergies, and 65.3% without clinically manifested allergies, multiscreen test ImmunoCAP Phadiatop/fx5 showed positivity and confirmed atopy. Our results showed a significant moderate to strong correlation between multiscreen ImmunoCAP Phadiatop/fx5, and Euroimmun specific IgE titers against aero-allergens—cats, mites, tree mix and food allergens—soy, wheat (р = 0.006), rice, р = 0.090), apple р = 0.007) and peanut. A sensitivity of 63% and specificity of 73.5% was observed for EUROIMMUN Pediatric (food allergens, IgE titer > 1) compared with the gold standard ImmunoCap/fx5. The mean value of total IgE is significantly higher in children with asthma and concomitant with allergic rhinitis compared to those without allergic rhinitis (mean 202.52 U/mL, IQR 102.50 (24.20–363.95) vs. 316.68, IQR 261.00 (109.20–552.50), p = 0.005). Conclusion: Establishing the spectrum of the most common respiratory and food allergens is an essential factor for maintaining asthma control, both through a strategy to avoid allergen exposure and by developing a recommendation plan. The immunoblotting technique is easily applicable in daily clinical and laboratory practice. It is also a cost-effective and reliable alternative to the “gold standard” ImmunoCAP Phadiatop/fx5 in diagnosing atopy in children.

Are Markers of Allergic Inflammation in Grass Pollen Allergy Influenced by H1 Antihistamines?

Soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular adhesion molecule-1 (VCAM-1) play important roles in allergic rhinitis (AR). Treatment with H1 antihistamines improves AR symptoms and in vitro reduces the levels of adhesion molecules. The aim of the study was to evaluate serum levels of ICAM-1 and VCAM-1 in patients with AR to grass pollen and their response to different H1 antihistamines. Material and methods: A total of 50 patients with grass pollen AR were clinically and biologically evaluated. ICAM-1 and VCAM-1 serum levels were evaluated during pollen season before and after treatment with levocetirizine and desloratadine through the ELISA method. Results: ICAM-1, VCAM-1, eosinophils, and total IgE were elevated in patients with AR, compared with healthy subjects. Both antihistamines improved specific symptoms of AR and increased patients’ quality of life during pollen season after one month of treatment. H1 antihistamines reduced VCAM-1, ICAM-1, and total IgE after one-month treatment but not significantly. Patients with increased baseline values tend to remain with increased values after one-month AH1 treatment. Conclusions: ICAM-1 and sVCAM-1 levels are higher in patients with grass pollen-induced AR than healthy controls during pollen exposure. Their serum levels tend to remain at high values during pollen season despite antihistaminic therapy.

Atopy and Allergic Diseases Have No Impact on the Severity of COVID-19

Objective: The clinical features of COVID-19 range from asymptomatic disease to severe pneumonia or even death. Therefore, many researchers have investigated the factors that could affect the severity of COVID-19. We aimed to assess the impact of aero-allergen sensitization and allergic diseases on the severity of COVID-19. Materials and Methods: We included 60 adult patients with symptomatic COVID-19 and allocated them into two groups equal in number as having severe and non-severe COVID-19. We evaluated the demographic features and allergic diseases in addition to clinical, laboratory and radiological findings of COVID-19. Skin prick tests (SPTs) with common aero-allergens, serum total IgE levels and blood eosinophil counts were evaluated 3 months after the patient’s recovery from COVID-19.Results: The mean age of the patients was 52 ± 11 years and 73.3% of the patients were male. There was no significant difference between the two groups in terms of age, gender, smoking habits, obesity and comorbidities. Although the frequency of sensitization to aero-allergens and the allergic diseases were similar, the history of allergic diseases in the family was higher in the severe group (p<0.001). The polysensitization in SPTs was associated with the presence of a cytokine storm during the infection (p=0.02). Total IgE levels and blood eosinophil counts were not significantly different between the two groups.Conclusion: The presence of atopy or allergic diseases does not seem to be related to the severity of COVID-19. However, polysensitization and a family history of allergic diseases are more prominent in those having a cytokine storm and severe COVID-19, respectively. Keywords: COVID-19, atopy, allergic disease, aero-allergen sensitization, cytokine storm

Síndrome LTP: Caraterização do perfil clínico e molecular de sensibilização – Método Alex® Macroarray

Introdução: A alergia alimentar afeta milhões de pessoas globalmente. As proteínas de transferência lipídica (LTP) são panalergénios presentes em alimentos vegetais cujos sintomas de sensibilização variam de síndrome de alergia oral (SAO) a anafilaxia. Objetivo: Caraterização do perfil de sensibilização clínica e molecular de doentes com história de reação prévia a alimentos contendo LTP. Material e métodos: Estudo retrospetivo incluindo 15 doentes com história de reação sistémica a alimentos contendo LTP. Os doentes foram caracterizados quanto a sintomas e sensibilização em testes cutâneos por picada (TCP) com extrato comercial e alimentos em natureza (TC PP). Foi realizado Macroarray Allergy Explorer-ALEX® para avaliação de valores de IgE total, IgE específica para componentes moleculares (IgEcm) e extratos totais (IgEet). Resultados: Quinze doentes, 73% mulheres, média de idades 30,7±13,7 anos. Média de idades no primeiro episódio foi 21,8±10,5 anos, manifestando-se como anafilaxia n=8 (maçã, pêssego, frutos secos), urticária/angioedema n=4 (maçã, pêssego, amendoim) e SAO n=3 (maçã, pêssego, amendoim). IgE total média: 430,5kU/L. Identificaram-se as seguintes LTP (N; IgEcm média±desvio padrão-kU/L): Pru p 3 (15; 15,7±21,5), Ara h 9 (10; 2,9±4), Mal d 3 (9; 1,5±1,7), Act d 10 (6; 0,6±1), Vit v 1 (6; 1,8±2,5), Cor a 8 (4; 0,1±0,2), Sola l 6 (1; 0,88). Com pêssego todas as associações entre clínica, testes cutâneos e valores de IgE tiveram concordância k=1; concordância da clínica com TCP e TC PP foi superior para maçã (k=0,44; p=0,03); concordância da clínica com IgEet foi superior para amendoim (k=0,87; p<0,01); concordância da clínica com IgEcm foi superior para avelã (k=0,70; p<0,01) e uva (k=0,55; p=0,02). Conclusões: A técnica ALEX® permitiu identificar simultaneamente a IgE total, IgEet e IgEcm, simplificando a interpretação e correlação clínica dos resultados. Neste estudo demonstramos que, para diferentes alimentos, o método diagnóstico com maior concordância com a clínica é variável e dependente do alimento. Será necessário um estudo prospetivo mais alargado para aferir a sensibilidade e especificidade deste teste.

Clinical and immunological changes in patients with chronic inflammatory diseases of the upper respiratory tract at different periods after administration of influenza vaccine. Message 1. The influence of parenteral influenza vaccination on the clinical condition and indicators of systemic humoral immunity in patients with chronic inflammatory diseases of the upper respiratory tract

Topicality: Today, as an assessment of the effectiveness of vaccination against influenza infection is to determine the level of antibodies against influenza virus hemagglutinin, which is determined by the reaction of inhibition of hemagglutination. It is known that the effect of vaccination with modern drugs is short-lived, compared with what remains after the disease. Therefore, there is a need for further vaccinations, which are carried out without taking into account the state of immunity in those who will be vaccinated. This raises the question of the appropriateness of this approach in individuals who, according to this indicator, can already be considered protected from influenza infection and how often such patients occur in clinical practice. Material and methods: From the autumn-winter period of 2019 to November 2020, 32 donors and 32 patients with chronic inflammatory diseases of the upper respiratory tract chronic inflammatory diseases of the upper respiratory tract of both sexes who were not vaccinated for 1 year before the study were examined. Among these patients, 11 were diagnosed with chronic rhinosinusitis, 9 with chronic tonsillitis, and 12 with chronic pharyngitis. All patients with chronic inflammatory diseases of the upper respiratory tract underwent a complete otolaryngological examination prior to influenza vaccination and were monitored for another 36 weeks thereafter. Attention was paid to their general clinical condition, cases of exacerbations of chronic inflammatory diseases of the upper respiratory tract and the number of episodes of acute respiratory viral infections during the year before vaccination according to the anamnesis and for the observation period during the post-vaccination period. Samples of serum venous blood of donors, as well as persons with chronic inflammatory diseases of the upper respiratory tract were obtained at the initial examination, and in vaccinated patients 3, 12 and 36 weeks after vaccination and stored at -20°C (Ardo, Italy) until the simultaneous detection of antibodies (Ab) to influenza A and B viruses by hemagglutination inhibition reaction with human erythrocytes 0 group. Trivalent influenza inactivated split vaccine Vaxigrip (France) was used both for vaccination and in the determination of Ab in the blood for influenza viruses. In all examinations, the titer of anti-influenza Ab and the content of immune complexes were determined in the sera of patients, and the content of total IgE was measured in patients with chronic inflammatory diseases of the upper respiratory tract before and after 12 and 36 weeks. Statistical processing of the obtained results was performed in accordance with the recommendations of Glantz. Results: In 41% of those examined protectively significant titers of antibodies to hemagglutinins of vaccine strains of influenza virus vaccine Vaxigrip were detected in the blood. Parenteral vaccination of patients with chronic inflammatory diseases of the upper respiratory tract against influenza helped to improve the course of their underlying clinical disease and reduce their incidence of acute respiratory viral infections within 36 weeks after vaccination. The effect of increasing the level of antibodies to hemagglutinins of influenza virus remained at the limit of 3 months and decreased. Influenza vaccination in patients with chronic inflammatory diseases of the upper respiratory tract with the presence of most of them at the time of vaccination of clinically significant protective titers of antibodies to hemagglutinins vaccine strains of viruses led to an increase in blood in the long term of the vaccination process levels of immune complex and total IgE relative to their initial level, while these indicators did not exceed the limits of their physiological values. Conclusion: Single parenteral influenza vaccination leads to a short-term increase in the blood of specific projective antibodies, improving the clinical condition of patients with inflammatory diseases of the upper respiratory tract, increasing the level of immune complexes and total IgE.

Identifying the Clinical Pattern of Eosinophilic and Non-Eosinophilic Asthma subtype in adult patients with Bronchial Asthma

Background Context:- Asthma is a heterogenous disease with various phenotypes, it is the most common chronic disease characterized by airway limitation due to bronchospasm and airway inflammation associated with excessive mucus secretion from agitated mucus gland that occur due to air way hyper responiveness. Purpose of the study Comparison between eosinophilic and non-eosinophilic asthma patients. Patients and Methods 100 bronchial asthma patients of age ≥ 18 years old divided into2 groups according to blood eosinophilia. All patients were subjected to: history. Total Asthma Control Test. Spirometry. Sputum eosinophil count. IgE levels 6-Skin prick testing (SPT). Nasal endoscopy. Results the mean age of all patients was (35.4 ± 12.8) years, majority (61%) of patients were males,; the mean ACT score was (18.7 ± 2); 39% of cases have obstructive pattern by spirometry, 39% of cases had abnormal nasal endoscopy, SPT had significant relation with asthma, there is significant correlation between total IGE,sputum eosinophilia with eosinophilic asthma. Conclusion Blood eosinophils had the highest accuracy in the identification of sputum eosinophilia in asthma. Total IgE values and sutum eosinophilia were markedly increased in patients with eosinophilic asthma more than patients with non-eosinophilic asthma.