Allergen-specific Immunotherapy Treatment Research Articles

The Quality of Life of Allergic Cats, Treated with Allergen-Specific Immunotherapy – A Retrospective Study

Abstract Feline atopic skin syndrome (FASS) describes allergic skin diseases in cats associated with sensitivity to environmental allergens. Allergen-specific immunotherapy (ASIT) aims to reduce or eliminate symptoms associated with subsequent exposure to the causative allergen. The primary outcome of this study was to determine if the quality of life (QoL) of cats and owners improved as a result of ASIT. The secondary outcome was to determine whether the QoL improved in cats treated with ASIT compared with cats treated symptomatically. Eight cats were included in the ASIT group (AG) and 6 cats in the control group (CG). Validated quality of life questionnaires were retrospectively completed by cat owners for the period before and after treatment. The QoL of cats improved significantly with ASIT. Cats were significantly less lazy, nervous, aggressive, restrained, preened less while sleeping and hid less, were less disturbed by consultations, were more playful and interactive with their environment, and had better appetites than before treatment. Owners felt significantly less physically exhausted and less emotionally distressed compared to before ASIT treatment and their expenses were significantly lower. On the contrary various symptomatic treatments did not significantly improve the quality of life of the cats or their owners in any of the terms. No serious side effects were observed with ASIT. The quality of life of animals suffering from chronic diseases is important as it determines the decisions of owners and veterinarians on the modalities of lifelong treatment. Validated questionnaires are still rarely used in veterinary practice and research.

Thermosensitive PLGA-PEG-PLGA Hydrogel as Depot Matrix for Allergen-Specific Immunotherapy.

Allergen-specific immunotherapy (AIT) is the only currently available curative treatment option for allergic diseases. AIT often includes depot-forming and immunostimulatory adjuvants, to prolong allergen presentation and to improve therapeutic efficacy. The use of aluminium salts in AIT, which are commonly used as depot-forming adjuvants, is controversially discussed, due to health concerns and Th2-promoting activity. Therefore, there is the need for novel delivery systems in AIT with similar therapeutic efficacy compared to classical AIT strategies. In this study, a triblock copolymer (hydrogel) was assessed as a delivery system for AIT in a murine model of allergic asthma. We show that the hydrogel combines the advantages of both depot function and biodegradability at the same time. We further demonstrate the suitability of hydrogel to release different bioactive compounds in vitro and in vivo. AIT delivered with hydrogel reduces key parameters of allergic inflammation, such as inflammatory cell infiltration, mucus hypersecretion, and allergen-specific IgE, in a comparable manner to standard AIT treatment. Additionally, hydrogel-based AIT is superior in inducing allergen-specific IgG antibodies with potentially protective functions. Taken together, hydrogel represents a promising delivery system for AIT that is able to combine therapeutic allergen administration with the prolonged release of immunomodulators at the same time.

Paediatric Allergen-Specific Immunotherapy Studies Required by the European Medicines Agency: Is It Time for a Reassessment?

Allergen-specific immunotherapy (AIT) works well both in children and adults. An often-alleged gap between the level of evidence of AIT efficacy in adults versus children is based upon the flawed ‘children-are-not-small-adults’ and ‘children-are-therapeutic-orphans’ mantras, both of which emerged in the 1960s. These mantras led to paediatric legislation in the USA in 1997 and the European Union (EU) paediatric regulation 10 years later. Although preterm newborns and newborns are vulnerable, during the first year of life their organs mature. Young children are no longer physiologically newborns; their immune system can overreact and cause allergic reactions, and AIT works for them just like it does in adults. Young patients need dosing recommendations and safety observations, rather than repetition of proof of efficacy. Placebo-controlled efficacy studies withhold effective treatment, increase the risk of asthma in the placebo group and are, therefore, in the authors’ opinion, unethical as well as in breach of the declaration of Helsinki. Individuals under the age of 18 years are not offered AIT treatments that are available to adults that are 18 years or older, but AIT treatment would be a suitable option. Since 2007, there were >100 EMA paediatric investigation plans that demanded ‘paediatric’ AIT studies involving tens of thousands of minors. Almost none were successfully undertaken and those that were done were unnecessary. It is time for the specialty of allergy to face this challenge.

Combination therapy of specific aeroallergens immunotherapy and omalizumab, in children with severe asthma.

In most cases, severe asthma in children has an allergic etiology, but allergen-specific immunotherapy (AIT) is contraindicated. This study aimed at analyzing the safety and efficacy of AIT in patients with severe asthma treated with omalizumab (OM). A descriptive real-life study was carried out by reviewing medical records. Effectiveness was measured by the degree of control (CAN questionnaire), number of hospitalizations per year, number of exacerbations per year, and maintenance treatment and lung function (FEV1). Some adverse reactions occurred (AAI-EAACI-WAO guidelines). The retrospective study included 29 patients up to 18 years of age with severe asthma with OM plus AIT treatment. AIT treatment was started in a cluster schedule when patients treated with OM achieved disease control. Before starting AIT, patients were treated with OM for 1 year for achieving asthmatic control. AIT to mites (51%), Alternaria (37.9%), or pollens (10.3%) was administered. After one year with OM plus AIT,statistically significant differences in CAN scores and FEV1 measures were observed (P < 0.001). No patients under treatment with OM plus AIT required hospital admission. During the clustering schedule, only 3/64 doses showed systemic adverse reactions. During the AIT maintenance treatment, 348 doses were administered, with no significant adverse reactions. In this population-based study in children with severe asthma, the combined treatment with OM plus AIT was safe and effective. This strategy allows these pediatric patients to be safely treated with AIT.

Methods for Experimental Allergen Immunotherapy: Subcutaneous and Sublingual Desensitization in Mouse Models of Allergic Asthma.

Allergic asthma is characterized by airway hyperresponsiveness, remodeling, and reversible airway obstruction. This is associated with an eosinophilic inflammation of the airways, caused by inhaled allergens such as house dust mite or grass pollen. The inhaled allergens trigger a type-2 inflammatory response with the involvement of innate lymphoid cells (ILC2) and Th2 cells, resulting in high immunoglobulin E (IgE) antibody production by B cells and mucus production by airway epithelial cells. As a consequence of the IgE production, subsequent allergen reexposure results in a classic allergic response with distinct early and late phases, both resulting in bronchoconstriction and shortness of breath. Allergen-specific immunotherapy (AIT) is the only treatment that is capable of modifying the immunological process underlying allergic responses including allergic asthma. Both subcutaneous AIT (SCIT) as well as sublingual AIT (SLIT) have shown clinical efficacy in long-term suppression of the allergic response. Although AIT treatments are very successful for rhinitis, application in asthma is hampered by variable efficacy, long duration of treatment, and risk of severe side effects. A more profound understanding of the mechanisms by which AIT induces tolerance to allergens in sensitized individuals is needed to be able to improve its efficacy. Mouse models have been very valuable in preclinical research for characterizing the mechanisms of desensitization in AIT and evaluating novel approaches to improve its efficacy. Here, we present a rapid and reproducible mouse model for allergen-specific immunotherapy. In this model, mice are sensitized with two injections of allergen adsorbed to aluminum hydroxide, followed by subcutaneous injections (SCIT) or sublingual administrations (SLIT) of allergen extracts as an immunotherapy treatment. Finally, mice are challenged by intranasal allergen administrations. We will also describe the protocols as well as the most important readout parameters for the measurements of invasive lung function, serum immunoglobulin levels, isolation of bronchoalveolar lavage fluid (BALF), and preparation of cytospin slides. Moreover, we describe how to perform ex vivo restimulation of lung single-cell suspensions with allergens, flow cytometry for identification of relevant immune cell populations, and ELISAs and Luminex assays for assessment of the cytokine concentrations in BALF and lung tissue.

Handling of allergen immunotherapy in the COVID-19 pandemic: An ARIA-EAACI statement.

The current COVID‐19 pandemic influences many areas of social life, medical treatments and the way allergy diagnosis and treatment is performed. Allergen‐specific immunotherapy (AIT) is one of the most important treatment options for IgE‐mediated allergies and is based on immunological effects on the diseased patient. This manuscript outlines the EAACI recommendations regarding AIT during the COVID‐19 pandemic and aims at supporting allergists and all physicians performing AIT in their current daily practice with clear recommendations how to perform treatment during the pandemic and in SARS‐CoV‐2 infected patients.

Allergenicity and Safety Profile of Depigmented-Polymerized Phleum pratense Extract for Use in Allergen-Specific Immunotherapy Treatments

Allergenicity and Safety Profile of Depigmented-Polymerized Phleum pratense Extract for Use in Allergen-Specific Immunotherapy Treatments

Allergen-specific immunotherapy modulates the balance of circulating Tfh and Tfr cells

Abstract Follicular helper T cells (Tfh cells) are a CD4 T cell subset essential for germinal center formation and B cell responses, although their role in allergy and allergen-specific immunotherapy (AIT) is unclear. Here, we show that AIT-treated patients have a higher ratio of regulatory Tfh cells (Tfr) to follicular T cells (Tfh) and hypothesize an IL-2 dependent mechanism.

Allergen-specific immunotherapy prescription patterns in veterinary practice: a US population-based cohort study.

Poor adherence to continuing allergen-specific immunotherapy treatment (ASIT) may be an issue in veterinary medicine. No studies describe how allergen tests are used in general veterinary practice, including the percentage of patients that receive ASIT after allergen testing. Assess veterinary ASIT patterns in United States general practices. Dogs (n=2,557) and 121 cats allergen-tested at 177 hospitals (173 general practice and four specialty practices) in 44 states. Invoiced service descriptions of allergen tests and ASIT orders were retrieved from an aggregated database of veterinary practices. In general practice, 42% (992 of 2,360) of patients did not begin ASIT after allergen testing. ASIT was not refilled for 29% (398 of 1,368) of patients after the initial order. ASIT was initiated and refilled more often in dogs (56.6%, 71.4%, respectively) than cats (38%, 67.4%). Specialty practice patients had the highest ASIT initiation (94.4%) and refill (92.7%) percentages in comparison to general practices (P<0.001). Size, age, geographical region and type of practice were associated with whether dogs were started on ASIT. Geographical region was also associated with refilling a prescription for ASIT, which was considered to be evidence of adherence to continuing treatment. Almost one third of clients failed to continue ASIT beyond the initial order, which is a much shorter duration of therapy than the 12months recommended for determining ASIT efficacy. A large number of general practice patients did not begin ASIT after allergen testing, likely due to differences in how clinicians in general and dermatology practices use allergen tests.

The Study of Blood Vessels of Submandibular Gland and Urinary Bladder in Rats Using an Original Morphometric Analysis

The objective of the study is to elucidate the factors influencing treatment compliance of asthmatic patients and to introduce the measures which will facilitate rise of the compliance indices.Materials and methods. There were examined 104 patients from 18-50 years old. For the study management there were formed two groups with main one comprising 51 patients undergoing combined basic medication and allergen specific immunotherapy. The second, control group, included 53 patients who refused to undergo allergen specific immunotherapy and they received only basic medication-assisted treatment. The follow-up of the patients was conducted during a year. To determinate treatment compliance there was used own questionnaire and the control of treatment efficacy was done on the grounds of Asthma Control Test and Patient Quality of Life Questionnaire.Findings of the study and their discussion. At the beginning of the study the medium index of the patients’ treatment compliance was low in both groups. During each doctor’s visiting there were checked and worked out patients’ practical skills on accurate drug administration and control over treatment handling as well as conducting of monitoring and modification of triggers (the need in smoking cessation, active motion and bodily exercises performance, hypoallergic diet abiding, etc. was explained) and comorbidity treatment. Within three months the indices increased in both groups and some increase remained six and even twelve months after. Improvement in patients’ indices of treatment compliance was accompanied by the better performance of treatment control and quality of life. During the study the majority of patients of the main group managed to reduce a daily dose of inhaled corticosteroids and long-acting b2-agonists.Conclusion. The conducted study shows that after 12 months the indices of patients’ treatment compliance, ability to control asthma and quality of life increased in both groups while the triggers were decreased (by means of smoking cessation, comorbidity management and accommodation ecological factors control). At the same time, better results (bronchial asthma manageability, basic treatment volume decrease) were received in the group of patients with allergen-specific immunotherapy treatment application.

Validation of the first treatment-specific questionnaire for the assessment of patient satisfaction with allergen-specific immunotherapy in allergic patients: The ESPIA questionnaire

Satisfaction with treatment is a patient-reported outcome shown to be associated with the patient's health-related decisions and treatment-related behavior, thereby influencing the chances of successful treatment, and is especially relevant in long-term treatment, such as allergen-specific immunotherapy (AIT). We sought to assess the psychometric properties of the Satisfaction Scale for Patients Receiving Allergen Immunotherapy (ESPIA) questionnaire so as to determine the satisfaction of patients receiving AIT treatment. An observational, longitudinal, multicenter study was performed on patients with allergic rhinitis (AR) undergoing AIT treatment. Sociodemographic, clinical, and patient-centered health outcomes data were gathered at the study visits. Feasibility, reliability, validity, and sensitivity to change of the prevalidated version of the ESPIA questionnaire were assessed. Four hundred twenty-nine patients were included (52.2% women, 33.6 years of age, 54.5% of the cases with intermittent AR and 62.5% with moderate AR). Low levels of missing items and ceiling/floor effects were found for the overall score of the ESPIA questionnaire. The overall Cronbach α value and intraclass correlation coefficient were 0.90 and 0.92, respectively. The overall score for the ESPIA questionnaire was strongly associated with months receiving AIT, AR type and intensity, presence of conjunctivitis, self-perceived health status, effect of AR on daily life, and expectations about the AIT treatment. The pattern of correlations obtained with other patient-centered health outcomes was consistent with expectations. The ESPIA questionnaire also showed good sensitivity to change for improved health status. The ESPIA questionnaire to assess patient satisfaction with respect to AIT treatment presented satisfactory psychometric properties for its use in clinical practice.

Comparative Analysis of Allergic Rhinitis in Children and Adults

Allergic rhinitis (AR) is a worldwide health problem that generates a significant healthcare burden in adults, adolescents, and children. Epidemiological studies have indicated that the prevalence of AR has progressively increased over the last three decades in developed and industrialized countries. AR currently affects up to 40% of the worldwide population, with differences between adults and children and different countries of the World. Although not life-threatening, AR symptoms are frequently bothersome, adversely affecting work and quality of life of the affected patients, and causing a significant burden on both the individual and society. The symptoms have the potential to lead to both physical and mental complications, with sleep-disordered breathing in childhood and adolescence being associated with disorders in learning performance, behavior, and attention. Clinical features and comorbidities are very important for the "allergic march", and in both adults and children there is some evidence of association between AR and asthma. ARIA classifications of both symptom duration (intermittent, persistent) and severity (mild, moderate, severe) have been validated in both adult and pediatric populations. Based on the duration and severity of patient's disease, an appropriate treatment strategy has been issued for both adults and children, which consists of patient's education, allergen avoidance, and pharmacological as well as allergen-specific immunotherapy treatment. The present review will attempt to compare the characteristics of AR between children and adults, either in the epidemiology, clinical features, impact on QOL, and management of the disease.