Natural Course Of Allergic Diseases Research Articles

Association between exposure to greenness and atopic march in children and adults-A systematic review and meta-analysis.

Allergic diseases are a global public health problem. Food allergy, atopic dermatitis (AD), allergic rhinoconjunctivitis, allergic rhinitis (AR) and asthma represent the natural course of allergic diseases, also known as the "atopic march". In recent years, a large number of studies have been published on the association between greenness exposure and allergic diseases. However, systematic reviews on the association between greenness exposure and multiple allergic diseases or atopic march are lacking. In this study, PubMed, EMBASE, ISI Web of Science, and Scopus were systematically searched. Meta-analyses were performed if at least three studies reported risk estimates for the same outcome and exposure measures. Of 2355 records, 48 studies were included for qualitative review. Five birth cohort studies, five cross-sectional studies, and one case-control study were included for asthma meta-analysis, respectively. Four birth cohort studies were included for AR meta-analysis. Our results support that exposure to a greener environment at birth reduces the risk of asthma and AR in childhood. In addition, higher greenness exposure was associated with decreased odds of current asthma in children. There was a large heterogeneity among the included studies and most of them did not specify the vegetation type and causative allergens. Therefore the study results need to be further validated. In addition, a small number of studies evaluated the association between greenness and food allergy, AD and allergic rhinoconjunctivitis. More research is needed to strengthen our understanding of the association between greenness and allergic diseases.

Impact of coronavirus pandemic on safety and time of administration of subcutaneous immunotherapy among pediatric patients

Introduction: Allergen immunotherapy is the only targeted therapy that can modify the natural course of allergic diseases. In pediatric patients, SCIT with aeroallergens is an effective treatment and should be considered as a preventive strategy in the treatment of allergic diseases, even though one of the major concerns about it is its safety. The main purposes of this study were to assess the safety of SCIT ultra-rush schedules with polymerized extracts in a pediatric population and to determine the impact of the COVID-19 pandemic on the safety and time of administration of subcutaneous immunotherapy among pediatric patients. Methods: A retrospective medical records review of patients under 18 years of age undergoing SCIT was made and re-scheduling due to restrictions imposed by the COVID-19 pandemic was recorded. Results: A total of 192 pediatric patients were included. Fifty-nine (31%) had local reactions and systemic reactions were not reported. In March 2020, the first case of COVID-19 was diagnosed in Portugal and all non-urgent appointments and procedures were postponed. In our group of pediatric patients, 43 (22%) were referred to primary care, 38 (20%) stopped AIT definitively and 111 (58%) maintained administrations in the hospital. Only 2 (2%) of them had reactions upon reinitiation. Conclusion: In this study, the ultra-rush protocol using polymerized extracts was safe in pediatric patients. Although the effectiveness of AIT may be compromised due to prolonged suspension of the treatment, it is important to note that despite longer interruptions, administrations may continue without compromising safety, maintaining shorter visits and a lower number of injections.

Recent Advances in Allergen-Specific Immunotherapy in Humans: A Systematic Review.

Allergen-specific immunotherapy (AIT) is presumed to modulate the natural course of allergic disease by inducing immune tolerance. However, conventional AITs, such as subcutaneous immunotherapy and sublingual immunotherapy, require long treatment durations and often provoke local or systemic hypersensitivity reactions. Therefore, only <5% of allergy patients receive AIT as second-line therapy. Novel administration routes, such as intralymphatic, intradermal and epicutaneous immunotherapies, and synthetic recombinant allergen preparations have been evaluated to overcome these limitations. We will review the updated views of diverse AIT methods, and discuss the limitations and opportunities of the AITs for the treatment of allergic diseases in humans.

Effect of Subcutaneous Immunotherapy on The Natural Course of Allergic Diseases in Pediatric Patients: A Real-Life Cohort

Effect of Subcutaneous Immunotherapy on The Natural Course of Allergic Diseases in Pediatric Patients: A Real-Life Cohort

Role of Allergen Immunotherapy in Asthma Treatment and Asthma Development

Allergen immunotherapy may modify the natural course of allergic diseases and induce remission. It includes subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). For asthma, allergen immunotherapy using house dust mite (HDM) improves clinical symptoms and airway hyperresponsiveness and decreases drug requirements. Furthermore, it has been suggested that allergen immunotherapy also has the following effects: (1) the effect can be maintained for more than a year even if the treatment is terminated, (2) the remission rate of childhood asthma can be increased, (3) new allergen sensitization can be suppressed, and (4) asthma development can be prevented if allergen immunotherapy was performed in the case of pollinosis. Allergen immunotherapy differs from conventional drug therapy, in particular the effect of modifying the natural course of allergic diseases and the effect of controlling complicated allergic diseases such as rhinoconjunctivitis. The general indication for HDM-SCIT in asthma is HDM-sensitized atopic asthma with mild-to-moderate disease and normal respiratory function. HDM allergens should be involved in the pathogenesis of asthma, and a duration of illness of less than 10 years is desirable. HDM-SLIT is available for allergic rhinitis but not for asthma in Japan. However, as the efficacy of SLIT for asthma has been fully proven internationally, SLIT is also applied in asthmatics with complicated allergic rhinitis in Japan.

Distribution of serum specific IgE in children with allergic conjunctivitis and analysis of its concomitant allergic diseases.

BackgroundAllergic conjunctivitis (AC) is predominantly caused by serum specific-IgE (sIgE)-mediated type I allergy. This study aims to analyze the distribution of sIgE in children with AC, and the concomitant allergic diseases.MethodsThe clinical data from 310 children, diagnosed with AC and admitted to our hospital from January 2017 to January 2019 were retrospectively collected. The children were divided into three groups: infant group (2 months to 1 year old, 91 cases), child group (1 to 3 years old, 112 cases), and preschool group (3 to 6 years old, 107 cases). Children in every group were analyzed for positive rates, the number of positive sIgE types, the distribution of positive inhaling and ingesting allergens and concomitant allergic diseases.ResultsThe sIgE positive rate of infant was significantly lower than that of the other two groups, and the number of 18.75% sIgE positive species was 1. The number of sIgE positive species in the child group and preschool group was more than 2 (78.30%, 71.15%). The positive rate of sIgE to dust mites, house dust, animal dander, eggs, beef, mutton and mango in the preschool group was significantly higher than the other groups (P<0.05). The positive rate of sIgE to milk in infant group was significantly higher than the other two groups (P<0.05). Children in the preschool group showed the highest incidence of AC, AC + allergic rhinitis, AC + allergic rhinitis + wheezing, while those in the infant group displayed the lowest incidence (P<0.05). AC + gastrointestinal allergy, AC + atopic dermatitis, AC + gastrointestinal allergy + atopic dermatitis in infant group was significantly higher than the other two groups (P<0.05). Patients in the child group displayed a significantly higher incidence of AC + infant wheezing than the other two groups (P<0.05).ConclusionsWe correlated children’s age with the positive rate and gradual increase in types of AC allergens. Concomitant allergic diseases of children with AC at different ages conform to the natural course of allergic diseases. In clinic, improving the diagnostic efficiency of AC in children, and early interventional treatment will positively contribute to their prognosis, and reduce the risk of other allergic diseases.

Tolerance mechanisms in allergen immunotherapy.

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. 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-β, 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. 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.

Basophil sensitivity reflects long-term clinical outcome of subcutaneous immunotherapy in grass pollen-allergic patients.

Allergic rhinoconjunctivitis is a public health problem. Allergen Immunotherapy is an effective and safe treatment, that modifies the natural course of allergic disease and induces long-term tolerance. To correlate basophil and antibody biomarkers of subcutaneous immunotherapy to clinical outcomes and cellular changes in target tissue. Adults suffering from allergic rhinoconjunctivitis due to grass pollen allergy were randomized to receive subcutaneous immunotherapy (n=18) or to an open control group (n=6). Patients reported daily symptom and medication scores and weekly rhinitis related quality of life scores during four pollen seasons. Biomarkers were measured every 3months for three years treatment and every 6months in the follow-up year. Nasal and cutaneous allergen challenge tests were performed annually. Leukocyte subsets were assessed in nasal mucosa biopsies at baseline and after treatment. Subcutaneous immunotherapy led to a 447-fold decrease in basophil sensitivity during the first treatment year. This remained 100-fold lower than baseline during the 3year-treatment period and 10-fold lower during the follow-up year (n=18, P=.03). Decrease in basophil sensitivity after three weeks of treatment predicted long-term improvement in seasonal combined symptom and medication scores (ῥ=-0.69, P=.0027) during three years of treatment. AUC of IgE-blocking factor correlated to nasal allergen challenge (ῥ=0.63, P=.0012) and SPT (ῥ=0.45, P=.03). Plasma cell numbers in the nasal mucosa increased during treatment (P=.02). Decrease in basophil sensitivity after three weeks of subcutaneous allergen immunotherapy predicted the clinical outcome of this treatment.

Advances in biomarkers related to the efficacy of specific immunotherapy

Allergy specific immunotherapy(AIT) was initiated by Leonard Noon in 1911 for the treatment of patients with hay fever.It is recognized as a therapy that changes the natural course of allergic diseases through immunoregulatory mechanisms.After more than 100 years of development, its safety and effieacy has been recognized by scholars at home and abroad.At present, AIT was used to treat the patients of AR and AS.In recent years, some scholars have used AIT as a treatment for food allergy and atopic dermatitis, but 40% of allergic rhinitis and 10%~20% children with asthma are not effective.There are no validated biomarkers to monitor or predict clinical efficacy, and further explorations are needed. Key words: Immunotherapy; Efficacy; Biomarker

Factors Associated with Adherence to Allergen Specific Subcutaneous Immunotherapy

PurposeAllergen-specific immunotherapy (AIT) is known to be the only therapeutic modality to alter the natural course of allergic diseases. However, at least 3 years of treatment is recommended for achieving long-term disease modifying effect. This study aimed to investigate factors associated with immunotherapy non-adherence in real practice.Materials and MethodsWe retrospectively reviewed medical records of patients who were diagnosed with allergic rhinitis, asthma, or atopic dermatitis, and received AIT to common allergens such as house dust mite and/or pollens from January 2007 to August 2014. In this study, non-adherence was defined as not completing 3 years of AIT.ResultsAmong 1162 patients enrolled, 228 (19.6%) failed to complete 3 years of AIT. In multivariate analysis, age less than 20 years [odds ratio (OR) 3.11, 95% confidence interval (CI) 1.70–5.69] and 20 to 40 years (OR 2.01, 95% CI 1.17–3.43), cluster build-up (OR 1.78, 95% CI 1.05–3.02) and ultra-rush build-up schedules (OR 5.46, 95% CI 2.40–12.43), and absence of visit to other departments in the same hospital (OR 1.87, 95% CI 1.05–3.32) were independently associated with immunotherapy non-adherence. Disease duration of 5–10 years was negatively associated with non-adherence compared to shorter disease duration of less than 5 years (OR 0.61, 95% CI 0.40–0.94). Although male sex and commercial product of AIT, Tyrosine S®, compared to Novo-Helisen® were non-adherent factors in univariate analysis, no statistical significances were identified in multivariate analysis.ConclusionVarious factors are associated with immunotherapy adherence affecting the utility of immunotherapy. Clinicians should be aware of factors associated with adherence to maximize the utility of allergen-specific subcutaneous immunotherapy.

Inmunoterapia alérgeno específica: Prevalencia de alérgenos en consulta privada de alergología en Cáceres.

Resumen: Según la Sociedad Española de Alergología e Inmunología Clínica (SEAIC), las enfermedades alérgicas afectan a un 30% de la población española. La alergia ocupa la sexta posición dentro de las diez enfermedades o problemas de salud que la población de 15 años o más refiere padecer con mayor frecuencia (13,37%), según la Encuesta Europea de Salud en España (EESE) 2014, realizada por el Instituto Nacional de Estadística (INE). Desde la primera inoculación subcutánea por Leonard Noon en el año 1911 de un extracto de Phleum pratense a pacientes polínicos, se han publicado múltiples estudios controlados que demuestran que la inmunoterapia alérgeno específica es el único tratamiento capaz de modificar el curso natural de la enfermedad alérgica, reduciendo significativamente la severidad de la enfermedad y el consumo de medicación, así como mejorar considerablemente la calidad de vida. En el presente estudio se han recogido datos de 46 pacientes mayores de 14 años que reciben inmunoterapia, con pauta rush, en una consulta de alergia privada de la ciudad de Cáceres para conocer cuál es el alérgeno frente al que más se vacunaban y su seguridad, obteniendo un mayor porcentaje en “Mezcla de gramíneas 100%”, que representa un 47,83% de los estudiados, seguida de “Mezcla gramíneas 50% Olea europaea 50%” con un 28,26% y se demuestra que la inmunoterapia subcutánea es un método seguro y adecuado para el tratamiento de la alergia.

Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy

Allergy immunotherapy targets the immunological cause of allergic rhinoconjunctivitis and allergic asthma and has the potential to alter the natural course of allergic disease. The primary objective was to investigate the effect of the SQ grass sublingual immunotherapy tablet compared with placebo on the risk of developing asthma. A total of 812 children (5-12years), with a clinically relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma, were included in the randomized, double-blind, placebo-controlled trial, comprising 3years of treatment and 2years of follow-up. There was no difference in time to onset of asthma, defined by prespecified asthma criteria relying on documented reversible impairment of lung function (primary endpoint). Treatment with the SQ grass sublingual immunotherapy tablet significantly reduced the risk of experiencing asthma symptoms or using asthma medication at the end of trial (odds ratio=0.66, P<.036), during the 2-year posttreatment follow-up, and during the entire 5-year trial period. Also, grass allergic rhinoconjunctivitis symptoms were 22% to 30% reduced (P<.005 for all 5years). At the end of the trial, the use of allergic rhinoconjunctivitis pharmacotherapy was significantly less (27% relative difference to placebo, P<.001). Total IgE, grass pollen-specific IgE, and skin prick test reactivity to grass pollen were all reduced compared to placebo. Treatment with the SQ grass sublingual immunotherapy tablet reduced the risk of experiencing asthma symptoms and using asthma medication, and had a positive, long-term clinical effect on rhinoconjunctivitis symptoms and medication use but did not show an effect on the time to onset of asthma.

Effects of specific allergen immunotherapy on biological markers and clinical parameters in asthmatic children: a controlled-real life study

BackgroundAllergen-specific immunotherapy (AIT) is the only treatment able to change the natural course of allergic diseases. We aimed at investigating the clinical efficacy of SLITOR (Serbian registered vaccine for sublingual allergen specific immunotherapy).Methods7–18 years old children with allergic asthma and rhinitis were enrolled and addressed to the active (AIT plus pharmacological treatment) or control (standard pharmacological treatment only) group. Clinical and medications scores, lung function and exhaled FeNO were measured at baseline and at every follow-up.ResultsThere was a significant improvement in both nasal and asthma symptom scores as well as in medication score in SLIT group. SLIT showed an important influence on lung function and airway inflammation.ConclusionsOur data showed that SLITOR was effective not only in terms of patient reported outcomes but an improvement of pulmonary function and decrease of lower airway inflammation were also observed.

Determinación de la seguridad de la inmunoterapia subcutánea con extractos polimerizados de Dermatophagoides farinae, Dermatophagoides pteronyssinus y Blomia tropicalis administrada en pacientes con enfermedad alérgica

Introducción: las enfermedades alérgicas afectan la calidad de vida de quienes las padecen y en los últimos años su prevalencia ha aumentado significativamente. La inmunoterapia con extractos alergénicos es usada para mejorar el curso de la enfermedad; no obstante, aún es necesario conocer su efectividad y seguridad. Objetivo: describir las reacciones adversas sistémicas producidas por la administración de inmunoterapia subcutánea con extractos polimerizados de ácaros. Materiales y métodos: se realizó un estudio de cohorte retrospectivo de pacientes con enfermedad alérgica mediada por IgE que recibieron inmunoterapia subcutánea con extractos polimerizados de Dermatophagoides farinae, Dermatophagoides pteronyssinus y Blomia tropicalis en el servicio de Alergología Clínica de la IPS Universitaria de la Universidad de Antioquia (Medellín, Colombia). Se realizó un análisis descriptivo de las variables demográficas y clínicas y su asociación con el riesgo de reacción adversa sistémica. Resultados: se incluyeron 622 pacientes; 92,8% con diagnóstico de rinitis, 60,3% de asma, 56,9% de conjuntivitis y 19,6% de dermatitis atópica. Un total de 73 (11,7%) pacientes experimentaron reacciones sistémicas adversas (razón de reacción/inyección = 1,06 x 100 inyecciones); de estos 47 (64,4%) recibieron adrenalina intramuscular. El 93,1% de los pacientes presentaron reacciones sistémicas grado 1 y 2. El asma fue el diagnóstico con mayor riesgo de presentar reacción sistémica (riesgo relativo = 1,96). Conclusiones: la inmunoterapia subcutánea con extractos polimerizados de ácaros administrada en pacientes con enfermedad alérgica demostró ser segura. No obstante, debe ser indicada y aplicada por personal clínico experto y advertírsele al paciente sobre los posibles riesgos y efectos adversos.

Cytokine Responses to Specific Immunotherapy in House Dust Mite-Induced Allergic Rhinitis Patients.

Allergen-specific immunotherapy is the only immunomodulatory treatment that may alter the natural course of allergic disease. However, cytokine responses accompanying sublingual immunotherapy (SLIT) responder phenotypes have not been fully understood. Herein, we examined the level of crucial plasma cytokines during SLIT and evaluated whether their changes correlated to symptom scores. We observed that the levels of interleukin (IL)-17 and complement components C3a and C5a as well as IL-4 at year 3 of SLIT were significantly decreased than those at baseline. In contrast, there was no significant difference in the levels of IL-5, IL-13, and interferon (IFN)-γ. Notably, a significant positive correlation was found between the levels of IL-17 and the symptom scores at year 3. These results suggest that IL-17 could be considered a potential biomarker for the therapeutic effect of SLIT in allergic rhinitis caused by house dust mite.

Application of allergen-specific immunotherapy in atopic dermatitis

Allergens are closely related to the occurrence of atopic dermatitis(AD). Studies have verified the effectiveness and safety of subcutaneous injection immunotherapy and sublingual immunotherapy for the treatment of AD. Allergen-specific immunotherapy has been considered to be the only etiotropic treatment that can change the natural course of allergic diseases. Moreover, there have been some new promising immune approaches, such as intralymphatic immunotherapy and epicutaneous immunotherapy, to the treatment of AD. Key words: Dermatitis, atopic; Allergens; Allergy and immunology; Therapeutic uses; Patient safety

Long-term sublingual immunotherapy for Japanese cedar pollinosis and the levels of IL-17A and complement components 3a and 5a

Allergen-specific immunotherapy is the only treatment that can alter the natural course of allergic disease. We performed long-term sublingual immunotherapy (SLIT) for patients with seasonal allergic rhinitis caused by Japanese cedar pollen (SAR-JCP), screened molecules as candidate biomarkers, and investigated serum IL-17A and complement components 3a (C3a) and C5a in order to evaluate whether these molecules show changes correlated to symptom scores. In this study, we found that the long-term SLIT reduced the serum levels of IL-17A and C3a and C5a. The levels of C3a in the patients significantly decreased from year 1 compared with those at the baseline, and their levels of IL-17A significantly decreased from year 2 compared with those at baseline. The levels of IL-17A, C3a, and C5a at year 4 of SLIT were significantly lower than not only those at baseline, but also those at year 1. A significant positive correlation was found between the symptom medication scores and the levels of IL-17A at year 4. The symptom medication scores in the group in which IL-17A levels decreased at year 4 were significantly lower than those in the group without such a decrease. The serum level of IL-17A might prove useful as a biological parameter to ascertain the effectiveness of SLIT for patients with SAR-JCP. It is necessary to produce new therapeutics for non-responders in whom serum IL-17A levels are still higher against long-term SLIT.

Present and future of allergen immunotherapy for allergic diseases

Current pharmacological therapies for allergic diseases can improve clinical symptoms but cannot change their long-term clinical course. There is an unmet need for a curative treatment for allergic diseases. Allergen immunotherapy (AIT) is the practice of administering increasing doses of clinically relevant allergens to an allergic subject to reduce the clinical symptoms associated with subsequent exposure to the allergen. AIT is clinically effective for allergic asthma, allergic rhinitis, venom-induced anaphylaxis, and atopic dermatitis. AIT can change the natural course of allergic diseases and induce allergen-specific immune tolerance. In current clinical practice, AIT is delivered either subcutaneously or sublingually. Both subcutaneous and sublingual AIT have long-term therapeutic efficacy after of 3-5 years of treatment. The development of safer and more effective AIT strategies is needed. Conclusion: AIT is a disease-modifying therapy for allergic diseases. Future development of AIT should be directed toward achieving long-term clinical remission in patients with allergic diseases by the safe and effective induction of immune tolerance.

Inmunoterapia con alérgenos, ¿cuándo y por qué?

La inmunoterapia específica con alérgenos es el único tratamiento que modifica el curso natural de algunas enfermedades alérgicas como asma, rinitis, conjuntivitis, dermatitis atópica y alergia al veneno de himenópteros. Sin embargo, aún existe cierta controversia respecto a su seguridad y su utilidad clínica. En el presente artículo se presenta una revisión de los mecanismos moleculares, las indicaciones y contraindicaciones de dicha inmunoterapia, y se evalúan su seguridad y eficacia en cada una de estas enfermedades mediante casos ilustrativos y una breve revisión del tema.

Patients' compliance with different administration routes for allergen immunotherapy in Germany.

BackgroundAllergen immunotherapy (AIT) is the practice of administering gradually increasing quantities of an allergen extract to an allergic subject to ameliorate the symptoms associated with the subsequent exposure to the causative allergen. It is the only treatment that may alter the natural course of allergic diseases. According to AIT guidelines and summary of product characteristics (SmPCs), the treatment should be carried out for at least 3 years. It is controversially discussed whether subcutaneous or sublingual administration routes cause higher patients’ compliance.MethodsGerman sales data for different preparations of the allergen manufacturer Allergopharma GmbH & Co. KG were retrospectively evaluated for 5 consecutive years, based on prescriptions per patient: pollen sublingual immunotherapy (SLIT) and high-dose hypoallergenic (allergoid) or unmodified depot pollen and mite preparations for subcutaneous immunotherapy (SCIT). To identify patients’ compliance, “completed treatment years” were determined. A completed treatment year was defined by the required number of prescribed allergen preparations according to the recommended dosage scheme given in the respective SmPCs.ResultsPrescription data of 85,241 patients receiving pollen or mite SCIT and 706 patients receiving pollen SLIT were included in this analysis. Patients’ compliance for at least 3 treatment years with high-dose hypoallergenic pollen SCIT was higher when administered perennially (60%) compared to preseasonally (27%). Prescriptions for at least 3 years were received from 42% of patients with pollen SCIT and from 45% of patients with mite SCIT. Compliance with SLIT was lowest with only 16% of patients receiving prescriptions for at least 3 treatment years. Children and adolescents were more compliant than adults, independent of whether they received SLIT or SCIT.ConclusionIn general, patients’ compliance with SCIT using high-dose hypoallergenic or unmodified depot preparations was higher than with pollen SLIT. Perennial application of SCIT seems to increase compliance in comparison to the preseasonal application. Children and adolescents were most compliant, independent of the preparation applied.