Does allergen immunotherapy impact the susceptibility and severity of COVID-19?

To investigate the safety profile of subcutaneous immunotherapy (SCIT) versus sublingual immunotherapy (SLIT) in patients with allergic rhinitis (AR) caused by house dust mites. The treatment compliance and related factors were also evaluated. A total of 160 patients with AR were enrolled in this study and received either SCIT (Alutard SQ, ALK-Abelló) or SLIT (Chanllergen-Df drops, Wolwo Pharma). All subjects were divided into two groups: SCIT group consisted of 81 patients aged 7 to 62 years [(21.5 ± 14.6) years, x ± s], and SLIT group consisted of 79 patients aged 6 to 53 years [(15.1 ± 10.3) years]. The selected patients were persistent and moderate to severe AR sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Local and systemic reactions, as well as patient's adherence to the treatment, were carefully recorded and analyzed during the immunotherapy schedules (followed up for 6 months to 2 years). Statistical analysis was performed using a SPSS13.0 software. Local swelling commonly occurred following injections throughout the treatment duration (62.9% of overall injections) in the SCIT group. Oral itching associated with drop intakes was reported by 4 subjects (5.1%) in the SLIT group. All local reactions were mild, well tolerated and self-limiting in both groups. A total of 11 patients (13.6%) with 18 injections (0.9%) experienced systemic reactions in the SCIT group, involving respiratory distress, asthmatic attacks, and urticaria. These adverse effects were mostly immediate reactions, and occurred more frequently in patients during the maintenance phase of treatment. There were also 11 patients (13.9%) who experienced systemic reactions in the SLIT group, including gastrointestinal symptoms, urticaria, and rhinitis exacerbations. However, systemic reactions to SLIT were mainly observed in patients during the up-dosing phase of treatment. No significant difference in the overall incidence of systemic adverse effects was found between the SCIT and SLIT groups (13.6% and 13.9% respectively, χ(2) = 0.004, P > 0.05). There was only one case of non-life-threatening systemic reaction (severe asthma) in the SCIT group. Others were mild or moderate and no anaphylactic shock occurred in any group. No significant difference in treatment compliance was found between the SCIT and SLIT groups (86.4% and 79.7% respectively, χ(2) = 0.84, P > 0.05), with an overall rate of compliance (83.1%) among 160 patients. The most common cause for treatment withdrawal was insufficient ineffectiveness, in both groups of SCIT (6.2%) and SLIT (10.1%). The results suggest that the frequency of systemic adverse effects of SCIT is not significantly different from SLIT in mite-sensitized patients with AR, and both treatments are well tolerated and had favorable compliance during the study period.

Allergic asthma in children significantly impacts quality of life, and immunotherapy, including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), has emerged as an effective treatment. However, their comparative immunological mechanisms remain unclear. This study aimed to compare the effects of SCIT and SLIT on immune response in children with allergic asthma and to explore their underlying immunological mechanisms. A total of 86 children aged 5-12 years with allergic asthma who visited Hangzhou Children's Hospital were prospectively enrolled and randomly assigned to three groups: inhaled corticosteroids (ICS) group (n = 30), SCIT group (n = 30), and SLIT group (n = 26). Clinical and immunological parameters-including Childhood Asthma Control Test (C-ACT) scores, forced expiratory volume in the first second percentage (FEV1%), Th17, Treg cells, and serum levels of IL-17, IL-9, IL-10-were assessed before treatment and after one year. After treatment, all three groups showed significant improvements in C-ACT scores and FEV1% compared to baseline (all p < 0.05). The SCIT and SLIT groups demonstrated greater improvements than the ICS group (all p < 0.05), with no significant differences between the SCIT and SLIT groups (p > 0.05). In terms of immune markers, significant differences were observed in all parameters before and after treatment in the SCIT and SLIT groups (all p < 0.05), while Treg levels in the ICS group remained unchanged (p > 0.05). No statistically significant differences in immune markers were found among the three groups post-treatment (all p >0.05). Both SCIT and SLIT, when combined with ICS, offer superior efficacy compared to ICS monotherapy. The comparable immunological changes observed in SCIT and SLIT suggest a shared mechanism of immune tolerance, potentially mediated through Treg cell induction.

To evaluate the effect of subcutaneous immunotherapy (SCIT) on asthma in inner-city children <4 years of age.Children between the ages of 18 to 47 months were recruited when seen in the asthma or allergy clinic at Jacobi Medical Center in Bronx, New York, which cares for a mostly low-income, inner-city population. Participants were required to have physician-diagnosed asthma or at least 2 lifetime episodes of wheezing and be at high risk of persistent asthma on the basis of an Asthma Predictive Index. Patients with any other chronic medical condition, history of severe prematurity, or a sustained oxygen requirement at birth were excluded. Although all patients had at least 1 common environmental allergen positive on skin-prick testing, most had multiple and mainly indoor allergen sensitizations. The majority of patients were male and used an asthma controller medication, with an average asthma symptom score indicating mild persistent asthma.Participants were randomly assigned to the SCIT (n = 27) or control group (n = 23). SCIT was administered per published guidelines, with biweekly maintenance injections. Asthma, nasal-ocular, and skin symptom scores and medication use were monitored by a phone call every 2 weeks. In interim power analysis, it was indicated there was an insufficient sample size to reach the planned power of 80%, so the study was terminated early before some participants had completed SCIT for 3 years.On the basis of intention-to-treat analysis, there was no statically significant difference in asthma, nasal-ocular, or skin symptom scores in the SCIT and control groups. Quality of life, as assessed by the parent, showed significant improvement in the SCIT group (β coefficient: 0.32; SE: 0.09; P ≤ .01), particularly related to interference of child’s asthma on family or work plans and nighttime symptoms. Allergen specific serum immunoglobulin G4 levels increased in the SCIT group only (P ≤ .04). New allergen sensitization or loss of sensitization rates at the end of the study were not significantly different between the SCIT and control groups. Systemic reactions occurred in in 22% of children and 1.8% of injections, all of which were mild and resolved with antihistamine administration. Children in the SCIT group missed 28% of injection visits.Apart from improved quality of life, allergen immunotherapy in inner-city children with asthma <4 years of age did not show significant improvement in asthma, allergy, or eczema clinical outcomes.Although perhaps limited by small sample size and a high rate of missed appointments, with the results, the authors support the common practice of waiting until near 5 years of age to start SCIT. Factors unique to an inner-city, younger pediatric population may warrant larger studies to determine the efficacy of early immunotherapy in improving asthma.

Immunization Update 2021

Subcutaneous immunotherapy (SCIT) is a safe, effective immunotherapy method. However, it has several limitations, most notably the prolonged build-up phase. Metformin regulates Th17/regulatory T-cell (Treg) homeostasis by increasing Tregs and anti-inflammatory cytokines. To overcome the limitation of the long build-up phase of SCIT, we propose combining SCIT with metformin. Sensitized BALB/c mice received intraperitoneal metformin (100 mg/kg or 300 mg/kg) for 9 days, except for the negative, positive, and SCIT groups. The SCIT, SCIT combined with 100 mg/kg metformin (SCIT-Met(100)), and SCIT combined with 300 mg/kg metformin (SCIT-Met(300)) groups received 3 subcutaneous injections of house dust mite (HDM) extract at 2-day intervals for immunotherapy. All groups except the negative control were given intranasal HDM extract for 5 days. Nasal symptoms, ear swelling, eosinophil count in nasopharyngeal wash-out lavage, antibody levels, and nasal mucosa histopathology were analyzed. All immunotherapy groups exhibited reduced nasal symptoms, ear swelling, eosinophil counts in nasopharyngeal lavage, eosinophils, mast cells, and goblet cells in the nasal mucosa compared to the positive and metformin-injected (Met) groups. HDM-specific immunoglobulin G1 levels increased in all immunotherapy groups. The SCIT-Met groups induced more Treg than the Met(100), Met(300) and SCIT groups. Interleukin (IL)-4, IL-5 and IL-13 mRNA levels were lower in the Met groups and SCIT-Met(300) group than in the SCIT and SCIT-Met(100) groups. Foxp3 mRNA level was significantly higher in the Met groups and SCIT-Met groups than in the SCIT group. Overall, the SCIT-Met(300) group showed relatively favorable outcomes compared with the other groups. Combining immunotherapy with metformin may alleviate allergy symptoms and enhance immune tolerance in a murine model of allergic rhinitis. Further studies are needed to confirm these findings.

Adenoid hypertrophy (AH) and allergic rhinitis (AR) are common pediatric diseases, seriously affecting the quality of life and growth of children. The recurrence rate of AH is higher for patients with than for those without concurrent AR. Allergen specific immunotherapy (AIT) is the only effective therapy for modifying the course of allergic diseases. This study sought to investigate the efficacy of AIT in preventing AH recurrence in patients with AR who underwent adenoidectomy. This study included 134 children aged 5-12 years with concurrent AH and AR. They were separated into the subcutaneous immunotherapy (SCIT) group treated with a double-mite allergen preparation or the non-AIT group treated symptomatically with only medications. The adenoid/nasopharyngeal ratio at one year after adenoidectomy was used to assess AH recurrence. The Obstructive Sleep Apnoea Questionnaire (OSA-18), Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), and Visual Analogue Scale (VAS) were used to assess the severity of the sleep disorders and AR. This study included 62 and 72 children with concurrent AH and AR in the SCIT and non-AIT groups, respectively. The rate of recurrence in the SCIT group was significantly lower than that in the non-AIT group (4.84% vs.16.67%; P=0.030). The OSA-18, PRQLQ, and VAS scores were significantly lower for the SCIT than (P<0.001) for the non-AIT group after one year of treatment. The findings suggest that AIT should be considered the preferred therapy for reducing postoperative recurrence of AH in children with concurrent AR following adenoidectomy, but further research is needed to confirm these findings in a larger population.

Health economics of allergen-specific immunotherapy in the United States

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Managing risk of anaphylaxis in patients receiving allergen immunotherapy: Assessing benefit versus risk

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Vaccination

Background/aimAllergic rhinitis can be associated with bronchial hyperreactivity (BHR) and create an increased risk for allergic asthma development. We aimed to investigate the effects of subcutaneous immunotherapy (SCIT) on BHR and asthma development in adult patients with allergic rhinitis.Material and methodsThe retrospective case-control study was carried out between November 2018 and May 2019 in Süreyyapaşa Chest Diseases and Thoracic Surgery Training and Research Hospital. In this study, data was recorded for patients with a mite and/or grasses/cereals pollen allergy who were tested for BHR before planned SCIT, and who had allergic rhinitis, with or without asthma. The SCIT group was selected as those who received SCIT for at least one year. The control group was selected from those who were scheduled to receive SCIT but were waived and still receiving medication. Symptom scores, prick test results, PC20 levels (methacholine challenge that is a provocative concentration causing a 20% fall in FEV1), and the presence of asthma were recorded and compared with data from at least one year after treatment.ResultsA total of sixty-eight subjects (22 males, 46 females; mean age 40.54 ± 12.27 years; SCIT: 40, Control: 28) were enrolled. Although the changes in log PC20 levels were not statistically significant in both SCIT and control groups after an average of 30–35 months of treatment, it was found to be significant in favor of the SCIT group when two groups were compared in terms of the change in log PC20 (p = 0.026). The development and improvement of asthma were not significantly different between the SCIT and control group but tended to increase in the control group. The percentage of patients with progressed/BHR was significantly higher in the controls (70.6% vs. 38.1%, p = 0.046).ConclusionIn our real life study we have demonstrated the preventative effect of SCIT on BHR, but not on asthma development.

Pediatric allergic diseases are primarily caused by an IgE-dependent immunological reaction. Despite studies reporting the involvement of T follicular Helper (TfH) cells, especially type 2 TfH cells, in class-switching to IgE production in B cells, TfH subset skewing in peripheral blood in pediatric allergy patients remains to be elucidated. This study aimed to investigate the possible involvement of type 2 TfH cells in the pathogenic mechanism underlying pediatric allergic diseases. We analyzed TfH subsets (type 1, type 2 and type 17) in peripheral blood from pediatric patients with (allergy group, 35 patients) and without (non-allergy group, 26 individuals) allergic diseases via flow cytometry to determine the percentage of each TfH subset in the total TfH cell repertoire. Furthermore, the eosinophil percentage and serum total IgE and Thymus and Activation-Regulated Chemokine (TARC) levels were measured. No significant differences were observed in sex and age between the allergy and non-allergy groups. Since IgE levels were significantly higher in the allergy group than in the non-allergy group, no significant overlap was observed in the number of patients in the allergy and non-allergy groups. Although the total IgE and TARC levels and the eosinophil percentage were significantly higher in the allergy group than in the non-allergy group, the TfH subset analysis did not display a significant skewing of specific TfH subset cells. These results suggest the occurrence of either limited changes in peripheral blood TfH cells or the involvement of the immune cell subtype TfH13 in pediatric allergic diseases.