Effects of subcutaneous and sublingual allergen immunotherapy on immune responses in children with bronchial asthma.

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.

Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy

AimTo systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR).MethodsPubMed, Embase, Cochrane Library, and Web of Science were searched from inception to March 2, 2023. Outcomes included symptom scores (SSs), medication scores (MSs), symptom and medication scores (SMSs), new sensitizations, development of asthma, improvement, and treatment-related adverse events (TRAEs). The quality of the included studies was assessed by the modified Jadad scale and Newcastle-Ottawa scale (NOS). Meta-regression was carried out to explore the source of heterogeneity. Subgroup analysis was further conducted in terms of study design [randomized controlled trials (RCTs), cohort studies], allergen [house dust mites (HDMs), grass pollen], treatment duration (≥ 24, 12-23 or < 12 months), allergen immunotherapy (AIT) modality (drops or tablets), and AIT protocol [continuous, pre-seasonal, co-seasonal, or after the grass pollen season (GPS)]. Sensitivity analysis was conducted for all outcomes. A Bayesian framework and a Monte Carlo Markov Chain (MCMC) model were developed for indirect comparison.ResultsTotally 50 studies with 10813 AR children were included, with 4122 treated with SLIT, 1852 treated with SCIT, and 4839 treated with non-SLIT or non-SCIT therapy. For direct comparison, the SLIT group had a similar SS to the SCIT group [pooled standardized mean difference (SMD): 0.41, 95% confidence interval (CI): -0.46, 1.28, P = 0.353]. Comparable MSs were observed in the SLIT and SCIT groups (pooled SMD: 0.82, 95%CI: -0.88, 2.53, P = 0.344). For indirect comparison, no significant differences were found in SSs (pooled SMD: 1.20, 95% credibility interval (CrI): -1.70, 4.10), MSs (pooled SMD: 0.57, 95%CrI: -1.20, 2.30), SMSs (pooled SMD: 1.80, 95%CrI: -0.005, 3.60), new sensitizations [pooled relative risk (RR): 0.34, 95%CrI: 0.03, 3.58], and development of asthma (pooled RR: 0.68, 95%CrI: 0.01, 26.33) between the SLIT and SCIT groups; the SLIT group illustrated a significantly lower incidence of TRAEs than the SCIT group (pooled RR: 0.17, 95%CrI: 0.11, 0.26).ConclusionConsidering both efficacy and safety, SLIT might be a more favorable AIT than SCIT in the treatment of pediatric AR, which may serve as a decision-making reference for clinicians.Systematic review registrationPROSPERO (CRD42023460693).

Background Asthma affects 300 million individuals worldwide. It is a serious global health problem affecting all age groups. The significance of eosinophilic inflammation in asthma is well established. Allergen immunotherapy (AIT) acts by increasing tolerance to specific antigens to which individuals demonstrate clinical sensitivity. Objectives Evaluate the efficacy and safety of sublingual immunotherapy (SLIT) versus subcutaneous immunotherapy (SCIT) as regards clinical response, total immunoglobulin E (IgE), and sputum eosinophil as well as adverse effects. Methods This randomized clinical trial included 100 patients with bronchial asthma who were randomly allocated into two groups: the SLIT group (n = 50) and the SCIT group (n = 50). Patients were given a full allergy history, symptoms, and medication scores; a skin prick test; total IgE for allergens, and a sputum eosinophil count. After the end of treatment, the efficacy, as well as side effects of both treatment arms, were evaluated at 6, 12, and 18 months. Results Both SLIT and SCIT were equally effective. Success rates have been demonstrated to be as high as 86–88%. There was a statistically significant decrease in symptom and medication scores, Total IgE levels, and sputum eosinophil results after treatment (P &lt; 0.001). However, no difference was found between groups regarding the efficacy of treatment. SLIT was significantly safer than SCIT (P &lt; 0.001). Conclusion Both treatment modalities were equally effective in treating asthma, but SLIT had a higher safety profile than SCIT.

Reply

Although previous studies had confirmed the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), respectively, direct head-to-head comparison of SCIT vs SLIT is sparse. We aimed to compare the efficacy, safety, and compliance of SCIT and SLIT in allergic rhinitis (AR) children. This study is a prospective, open-label, and single-center study performed between June 2017 and June 2018. A total of 325 children were grouped into SLIT, Alutard (SCIT1), and NovoHelisen Depot (NHD) (SCIT2) according to the parents' wishes. The adherence and reasons for dropout were recorded. The efficacy of SLIT and SCIT was evaluated by a combined symptom medication score. Adverse events (AEs) were recorded and graded during the whole treatment. The compliance rate was higher in the SCIT group compared with the SLIT group (P < .05). The total nasal symptom score (TNSS), rescue medication score (RMS), and symptom medication score (SMS) after 6-month, 12-month, and 2-year treatment were lower in the SCIT group compared with the SLIT group (P < .05). But the scores between the Alutard and NHD groups were not significantly different. The occurrence of AEs in the SCIT group was significantly higher compared with the SLIT group (P < .05). Our results suggested SCIT is more effective compared with SLIT to a certain degree, whereas SLIT had less AEs compared with SCIT. The AIT routes can be chosen according to personal specific conditions.

A novel approach in allergen-specific immunotherapy: Combination of sublingual and subcutaneous routes

The aim of this paper is to assess in an open prospective pilot case-control study the tolerability, safety and efficacy of an ultra-rush sublingual immunotherapy (SLIT) protocol with Vespula venom in wasp allergic patients compared to subcutaneous immunotherapy (SCIT). Forty-one wasp allergic patients were treated with sublingual (SLIT group) or subcutaneous (SCIT group) ultrarush immunotherapy with Vespula venom extract. All patients underwent skin tests and serum specific IgE and IgG4 detection before enrollment and after 6, 12 and 24 months of immunotherapy. The SLIT group consisted of 21 (6 females and 15 males) patients who received increasing doses of Vespula venom (Aquagen, ALK-Abellò) until the final dose of 30 drops of extract in 3 hours, containing 100,000 SQ-U/ml. The maintenance dose was of 10 drops of pure venom extract 3 times a week, for a total dose of 100,000 SQ-U weekly (corresponding to 100 microgram of venom extract). The SCIT group consisted of 20 patients (16 males and 4 females) who were treated with subcutaneous ultrarush immunotherapy with Vespula venom extract (Pharmalgen, Alk-Abellò). Patients received 101.1 microgram of Vespula venom in 3 hours and were treated with 100 microgram of wasp venom monthly. During the ultrarush sublingual treatment 2 patients (9.5%) experienced mild side-effects. Specific IgE and specific IgG to wasp venom did not show any significant modification. Four patients were field-stung by a wasp during the treatment (for a total of 6 stings). Two patients (3 stings), with a previous clinical history of a grade III and IV reaction, did not experience any reaction. One patient, with a previous grade II reaction, showed a large local reaction. The fourth patient, with a previous grade III reaction, was re-stung twice (after 12 and 24 months) with two systemic reactions (SR) (mild throat constriction). During the ultrarush SCIT phase, 3 (15%) patients experienced side-effects: 2 of them showed a large local reaction and 1 had headache and stomach ache. Specific IgE showed a significant (P = 0.001) increase after 6 months of treatment and then returned to baseline levels while specific IgG showed a significant (P = 0.001) increase after 6, 12 and 24 months in comparison with baseline. Nine patients were field-stung during the treatment: 8 of them experienced large local reactions; one patient (11%) experienced an SR (dizziness). Our results, even if in a small number of patients, suggest that in patients with Hymenoptera sting allergy SLIT could be efficacious with a good tolerability profile when compared to SCIT. Larger studies are needed to assess efficacy, safety and tolerability profile of wasp venom SLIT.

Purpose: There have been several studies on comparisons of efficacy between subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with house dust mite (HDM)-sensitized allergic rhinitis (AR), without consistent results. This study was conducted to compare short-term effects between SCIT and SLIT in Korean children with HDM-sensitized AR. Methods: Fifty-three children (mean age, 11.15±2.82 years) with HDM-sensitized AR and with/without asthma (SCIT group, n=33; SLIT group, n=20) were enrolled. Clinical symptom scores and skin prick test results were assessed before, and after 3, 6, and 12 months of immunotherapy. Blood tests, including eosinophils, total serum IgE, and HDM-specific IgE, and adenosine 5’-monophosphate, and methacholine bronchial challenge tests were performed before and after 12 months of immunotherapy. Results: In the SCIT group, the symptom scores improved after 3 months compared to those before immunotherapy, whereas they improved after 6 months in the SLIT group. Significant decreases in skin reactivity to HDM were observed after 3 months only in the SCIT group. Decreases in total eosinophil counts and improvements in methacholine bronchial provocation tests were observed after 12 months of immunotherapy only in the SCIT group. No difference in severe adverse reactions was noted in either group. Conclusion: The results of this study suggest that SCIT may have more rapid effects on clinical symptoms and skin reactivity in children with AR, compared to SLIT.(Allergy Asthma Respir Dis 2015;3:180-186)

Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: Looking at the published evidence

PurposeMicroRNAs (miRs) were recently recognized to be important for immune cell differentiation and immune regulation. However, whether miRs were involved in allergen-specific immunotherapy (SIT) remains largely unknown. This study sought to examine changes in miR-146a and T regulatory cells in children with persistent allergic rhinitis (AR) after 3 months of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT).MethodsTwenty-four HDM-sensitized children with persistent AR were enrolled and treated with SCIT (n=13) or SLIT (n=11) for 3 months. Relative miR-146a and Foxp3 mRNA expression, the TRAF6 protein level, and the ratio of post-treatment to baseline IL-10+CD4+ T cells between the SCIT and SLIT groups were examined in the peripheral blood mononuclear cells (PBMCs) of AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry, and Western blot analysis, respectively. Serum levels of IL-5 and IL-10 were determined using ELISA.ResultsAfter 3 months of SIT, both the TNSS and INSS scores were significantly decreased compared to the baseline value (P<0.01). The relative expression of miR-146a and Foxp3 mRNA was significantly increased after both SCIT and SLIT (P<0.01). The ratio of post-treatment to baseline IL-10+CD4+ T cells and the serum IL-10 level were significantly increased in both the SCIT and SLIT groups (P<0.01), whereas the TRAF6 protein level and serum IL-5 level were significantly decreased (P<0.01). No significant differences in these biomarkers were observed between the SCIT and SLIT groups.ConclusionsOur findings suggest that miR-146a and its related biomarkers may be comparably modulated after both SCIT and SLIT, highlighting miR-146a as a potential therapeutic target for the improved management of AR.

Sublingual or injection immunotherapy: the final answer?

Inhaled corticosteroids (ICSs) for treating asthma are controversial because of their negative effects on the growth of asthmatic children and without clearly defined withdrawal strategy. A 2-year ICS step-down and withdrawal strategy has been developed for asthmatic children receiving 3-year subcutaneous immunotherapy (SCIT). Eleven children were included into the SCIT group and 13 children into the ICS group. ICSs were discontinued when children met the following criteria: requiring only 1 puffper day, with good control, for at least 6 months; having a forced expiratory volume in 1 second (FEV1)/forced vital capacity ≥80%; and SCIT discontinued for ≥24 months. The main endpoints were the results of both the childhood asthma control test (C-CAT) and the methacholine bronchial provocation test. In the SCIT group, all the 11 children had ICS discontinued, with one child developed asthma attack after pneumonia and received ICS again after completion of SCIT. In the ICS group, five children discontinued ICS and developed asthma attacks later and received ICS again; the other eight children developed severe symptoms during ICS step-down. Thus, the discontinuation of ICS was only achieved in the SCIT group. The dose of methacholine that caused a decrease of 20% in FEV1 continued to improve after discontinuation of ICS for the SCIT group and presented better results than the ICS group (P=0.050). After completion of SCIT, the C-CAT had improved significantly after 30 months of treatment compared with the ICS group (P<0.05). In the present study, we developed a 2-year step-down and withdrawal strategy from ICSs strategy for allergic asthma children receiving SCIT; the strategy was efficacious and safe.

To compare changes in quality of life (QOL) that resulted from sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) in a real-world clinical setting. SLIT is established as a viable alternative to SCIT for the treatment of allergic rhinitis. Although comparative trials are increasingly available, few studies have examined QOL outcomes between these two treatments. One hundred and five participants who underwent immunotherapy for airborne allergies were enrolled in this prospective, single-center study. Forty participants completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at initiation of therapy, after 6 months, and after 1 year of therapy. Only patients with complete time points were included in the ultimate analysis. Twenty-nine of these participants underwent SCIT and 11 underwent SLIT. The effects of age, sex, and asthma history were also examined. The participants in both groups demonstrated improvements in QOL regarding allergic rhinoconjunctivitis over the study period. However, the change in the RQLQ score from both baseline to 6 months and baseline to 1 year was only statistically significant in the SCIT group (p = 0.002, 6 months and 1 year). The participants in the SCIT group also demonstrated statistically significant improvement from baseline to 1 year in the specific domains of practical and emotional functioning, nasal symptoms, non-nasal/eye symptoms, and sleep. After 1 year, both SCIT and SLIT demonstrated a minimally important difference from baseline in the overall RQLQ score. Age <35 years in the SCIT group had a significant positive impact on QOL improvement (p = 0.038). Although improvements in QOL were noted in both groups, changes in overall scores and the majority of domains only achieved statistical significance in the SCIT group. A small study population and difficulties adhering to immunotherapy dosing schedules in the SLIT group may be contributing factors.

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