Allergen Immunotherapy (AIT) is broadly used all over the world as the only available disease-modifying treatment option. The aim of this experts' perspective is to address seven important unmet needs for the further direction of AIT and to provide the readership with the authors' positions on these topics.

An international group of experts in the field of AIT have formulated seven important aspects for the future position of AIT, performed a current literature review and proposed a consented position on these topics.

The aspects discussed and consented by the authors include i) alternative routes of allergen application in AIT, ii) the potential of recombinant vaccines, iii) the role of allergy diagnosis based on component-resolved diagnosis for AIT composition, iv) the impact of COVID-19 vaccination for further innovations in AIT, v) potential of combining biologics to AIT, vi) future innovations in high-risk children/adolescents and vii) the future regulatory position on AIT.

Important unmet needs and topics for AIT have been addressed in this expert review. The authors' views and personal position on these seven aspects have also been elaborated.

The SARS-CoV-2 pandemic has brought new insights into the immunological intricacies of asthma. In this review, we discuss the epidemiology of asthma in patients infected with SARS-CoV-2 and the risk of severe infection. Type 2 inflammation had an overall protective effect against SARS-CoV-2 infection by various mechanisms summarized in this review. Asthma, intranasal, and inhaled corticosteroids decreased the ACE2 receptor, an important receptor for SARS-CoV-2 entry into host cells. We summarize the nuances of treatment of type 2 inflammation despite its underlying protective effects. Research to date has shown that patients on various allergen immunotherapies and biologics do benefit from being vaccinated.

Data are limited for clinical outcomes with house dust mite (HDM) allergen immunotherapy beyond 2 years' observation.

A post-marketing drug-use survey assessed the safety and effectiveness of the 300 index of reactivity (IR) HDM tablet during use for up to 4 years in Japan.

538 patients were evaluable for safety and 383 for effectiveness. Most adverse drug reactions (ADRs) occurred early and were local reactions; 5.6% of 249 total events were reported during years 2 to 4 as new ADRs after the interim analysis. The CAP-RAST score was identified as a potential risk factor for ADRs. The proportion of evaluable patients with severe allergic rhinitis symptoms decreased from 46.4% at baseline (n = 317) to 1.0% at 4 years (n = 104). Patients (n = 16) who discontinued 300 IR HDM tablet due to symptomatic improvement had sustained improvement relative to baseline 1 to 2 years later.

Long-term use of the 300 IR HDM tablet is safe and effective.

Allergen immunotherapy (AIT)-associated adverse events (AEs) limit its usage in the management of allergic diseases. The monoclonal anti-IgE antibody (omalizumab) and AIT have complementary actions. However, no consensus has been reached on whether their combination could exert superior efficacy and safety.

To evaluate whether the combination of AIT with omalizumab is superior to AIT alone in treating allergic diseases.

The MEDLINE/PubMed, Embase, Scopus and Cochrane Library databases were searched to identify randomized control trials (RCTs) reporting the outcomes of omalizumab combined with AIT (omalizumab + AIT) versus AIT alone. A random-effect model was established to estimate outcomes with a 95% confidence interval (CI).

A total of 11 eligible RCTs (involving 901 patients) were screened out for the meta-analysis. According to a pooled analysis, omalizumab + AIT significantly increased the number of patients achieving the target maintenance dose (TMD) and sustained unresponsiveness (SU) to allergens (odds ratio [OR] = 2.43; 95% CI: 1.33-4.44; p = 0.004; I2 = 35%, and OR = 6.77; 95% CI: 2.10-21.80; p = 0.001; I2 = 36%, respectively). Similarly, individuals receiving the combination therapy reported significantly fewer episodes of severe systemic AEs than AIT alone (OR = 0.32; 95% CI: 0.18-0.59; p = 0.0003; I2 = 0%). Meanwhile, the improvements in symptom severity score (mean difference [MD] = -0.26), rescue medication daily means score (MD = -0.14), and number of patients consuming epinephrine in AIT (OR = 0.20) were all more evident than those in AIT alone.

Omalizumab + AIT can significantly enhance the efficacy and safety of AIT by increasing TMD and SU to allergens, while decreasing severe systemic Aes.

Coronavirus disease 2019 (COVID-19) is a highly contagious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has various effects on asthma, allergic rhinitis, atopic dermatitis, and urticaria and may change the course of the disease depending on the severity of the infection and control status of the disease. Conversely, these diseases may also impact the course of COVID-19. Patients with chronic urticaria and atopic dermatitis may have COVID-19-induced disease exacerbations and biological treatments reduce the risk of exacerbations. Poor asthma control is linked to severe COVID-19 while allergic asthma is associated with lower risk of death and a lower rate of hospitalization due to COVID-19 compared with nonallergic asthma. The use of intranasal corticosteroids is associated with lower rates of hospitalization due to COVID-19 in patients with allergic rhinitis, whereas the effect of inhaled corticosteroids is confounded by asthma severity. These observations reinforce the importance of keeping allergic diseases under control during pandemics. The use of biologicals during COVID-19 is generally regarded as safe, but more evidence is needed. The pandemic substantially changed the management of allergic disorders such as home implementation of various biologicals, allergen immunotherapy, food introduction, and increased use of telemedicine and even home management of anaphylaxis to reduce emergency department burden and reduce risk of infection. Physicians need to be aware of the potential impact of COVID-19 on allergic diseases and educate their patients on the importance of continuing prescribed medications and adhering to their treatment plans to maintain optimal control of their disease.

Novel diagnostic tests may help diagnose patients with local allergic rhinitis (AR) when systemic testing is negative or inconclusive. Surgical approaches including septoplasty, inferior turbinate reduction, nasal swell body reduction, and posterior nasal nerve ablation may improve symptoms in patients whose symptoms are refractory to medical therapy, though high-quality evidence is lacking in the AR population. Intralymphatic and epicutaneous immunotherapy have the potential to improve adherence to allergen immunotherapy, though comparisons with current gold standard treatments are lacking and studies reporting long-term outcomes are needed. Immunomodulatory agents in combination with subcutaneous immunotherapy (SCIT) may improve tolerance of SCIT but reports to date do not demonstrate a clear benefit in symptom alleviation. Future work in these areas may support these options as beneficial for testing and treatment of AR.

The burden of food allergy is multifaceted, including dietary, social limitations, financial burden and a significant psychological impact resulting in decreased quality of life for food-allergic Individuals. Patients and families live in fear of accidental exposures resulting in severe allergic reactions and negative outcomes, including fatalities. The perception of this last risk is often overinflated compared with the actual risk, but since it is difficult to identify with certainty patients who are most at risk, families often live in constant fear. A variety of severity scores exists for allergic reaction grading. Multiple studies have attempted to pinpoint risk factors for severe allergic reactions that are food-induced, with sometimes controversial results, and the search is ongoing.

Subcutaneous immunotherapy (SCIT) is a potential disease-modifying therapy effective for treatment of various allergic disorders. Pain and fear are common concerns of children, which can pose stress and result in negative experiences. The purpose of this study was to evaluate and compare the effectiveness of three marketed distraction devices and ethyl chloride spray (a routinely used topical anesthetic agent for painful procedures), the current clinical standard of care in reducing the perception of needle pain during SCIT administration in children.

40 children, aged 4-17 years, receiving SCIT with use of one of three alternative pain therapies or with standard practice were enrolled. Participants were randomly assigned to one of the pain modifying interventions. The three interventional groups were ShotBlocker® (Bionix, Toledo, OH, USA), Buzzy® I (Pain Care Labs, Atlanta, GA, USA) (vibration only), and Buzzy® II (vibration with ice). Control group was ethyl chloride spray. The study consisted of two visits during SCIT administration process.

Of these 40 children, 12 received the ShotBlocker, 8 received the Buzzy I, 11 received the Buzzy II, and 9 received ethyl chloride spray (control group).

There were no significant differences found between each of the distraction devices and between the control group. Type II error/false negative finding cannot be ruled out because of a small sample. Therefore, we cannot conclude that no true difference exists between each distraction device and the control group simply because of occurrence of a non-significant P-value in our study.

To investigate the effect of response intensity of allergen skin prick test (SPT) on symptom severity and long-term efficacy of dust mite subcutaneous immunotherapy (SCIT) in allergic rhinitis (AR).

AR Patients diagnosed with dust mite allergy and completed 3 years of SCIT were collected and classified into three groups: grade 2 (SPT of + +), grade 3 (SPT of + + +) and grade 4 (SPT of + + + +). Comparisons between groups were performed to examine the associations of SPT categories and symptom severity and the long-term efficacy of SCIT in AR.

181 AR patients were included. There was no significant difference in the baseline TNSS, SMS, RQLQ and VAS, and particularly to symptom severity grading among three SPT grade groups (P > 0.05). The moderate-severe AR was more likely to be smoking and accompany with asthma and had higher prevalence of sensitization to cockroach, mixed grass and tree pollen than mild AR (P < 0.05). Prevalence of sensitization to cockroach, mixed grass, ragweed and animal dander was increased in AR patients with asthma and allergic conjunctivitis (P 0.05). Similarly, long-term outcomes of patients with different SPT grades did not differ among different clinical characteristics and different efficacy determination criteria (P > 0.05).

The SPT response intensity cannot be used as an objective evaluation index for symptom severity and the long-term efficacy of SCIT in AR patients.