Pediatric allergic rhinoconjunctivitis has become a public concern with an increasing incidence year by year. Conventional subcutaneous immunotherapy (SCIT) has long treatment time, high cost and poor compliance. The novel immunotherapy significantly shortens the course of treatment by directly injecting allergens into cervical lymph nodes, which can perform faster clinical benefits to children.

By comparing with SCIT, this study aimed to evaluate the long term efficacy and safety of intra-cervical lymphatic immunotherapy (ICLIT).

This is a prospective randomized controlled study. A total of 50 allergic rhinoconjunctivitis children with dust mite allergy was randomly divided into ICLIT group and SCIT group, receiving three cervical intralymphatic injections of dust mite allergen or three years of subcutaneous injection, separately. Primary outcomes included total nasal symptom scores (TNSS), total ocular symptom scores (TOSS), total symptom scores (TSS), total medication scores (TMS), and total quality of life score. Secondary outcomes included pain perception and adverse reactions during treatment. Other secondary outcome was change in Dermatophagoides pteronyssinus (Derp) and Dermatophagoides farina (Derf) -specific IgE level.

Both groups had significantly decreased TNSS, TOSS, TSS, TMS, and total quality of life score after 36 months of treatment (p<0.0001). Compared with SCIT, ICLIT could rapidly improve allergic symptoms (p<0.0001). The short-term efficacy was consistent between the two groups (p=0.07), while the long-term efficacy was better in SCIT group (p<0.0001). The pain perception in ICLIT group was lower than that in SCIT group (p<0.0001). ICLIT group was safer. Specifically, the children had only 3 mild local adverse reactions without systemic adverse reactions. The SCIT group had 14 systemic adverse reactions. At last, the serum Derp and Derf-specific IgE levels in ICLIT and SCIT groups decreased 3 years later (p<0.0001).

ICLIT could ameliorate significantly the allergic symptoms in pediatric patients with an advantage in effectiveness and safety, besides an improved life quality including shortened period of treatment, frequency of drug use and pain perception.

Sublingual immunotherapy (SLIT) has been widely applied to treat patients with allergic rhinitis (AR). However, meta-analyses on the efficacy of SLIT in AR patients with asthma are still limited.

Literature without language limitation published before October 28, 2022, were retrieved from PubMed, EMBASE, and Cochrane Library. STATA 16.0 software was used for the meta-analysis of the extracted data. The results reported were symptom scores, drug scores, adverse effects rates, and cost of treatment.

Ten studies involving 1722 patients met the inclusion criteria. The total rhinitis score (TRSS) (weighted mean difference [WMD] = -1.23, 95% CI: -1.39--1.06, P < .001) and total asthma symptom score (TASS) (WMD = -1.00, 95% CI: -1.12-0.89, P < .001) were significantly lower in the SLIT group than the placebo group. The SLIT group had higher rates of treatment-related adverse events (relative risk [RR] = 2.82, 95% CI: 1.77 4.48, P < .001) and total costs of treatment (standardized mean difference [SMD] = 0.71, 95% CI: 0.45-0.97, P < .001). There was no significant difference in inhaled corticosteroids (ICS) dose (P = .195), fractional exhaled nitric oxide (FeNO) (P = .158), forced expiratory volume in 1 s (FEV1) (P = .237), and direct costs of treatment (P = .630) between the SLIT and placebo groups.

SLIT may be a therapeutic method for improving rhinitis symptoms and asthma symptoms in AR patients with asthma. However, as there was significant heterogeneity in results, more high-quality and well designed studies are needed in the future to elucidate the efficacy of SLIT.

In patients suffering from allergic asthma, especially in the pediatric age-group, allergen immunotherapy (AIT) could be of benefit and has the potential of long-term disease modification.

We reviewed the evidence for a beneficial effect of AIT in allergic asthma. A correct selection of the possible candidates for AIT is crucial. We define the comprehensive allergic asthma diagnosis: confirming asthma, confirming allergic sensitization and having symptoms on exposure to the relevant allergens.We analyze why the first trials on AIT for asthma were contradictory; we consider the results of systematic reviews and discuss the high degree of heterogeneity often found in meta-analysis. We assess recent, double-blind, placebo-controlled trials in sublingual AIT that provide robust evidence for a reduction in acute asthma exacerbations and a decrease in the use of inhaled corticosteroids. Further, we demonstrate how real-world trials and large pharmacy data-based analyses confirm these findings for SLIT and SCIT. Finally, we explore the option of AIT in severe asthma patients, once well-controlled on biologic therapy.

Clear indications for AIT in asthma guidelines would benefit allergic asthmatics. AIT is a therapeutic option in appropriately selected asthmatics. Three years treatment has the potential for long-term tolerance, with persisting benefits years after discontinuation.

Cow milk (CM) allergy is the most prevalent food allergy in young children in the US and Great Britain. Current diagnostic tests are either unreliable (IgE, skin prick test), or resource-intensive with risks (food challenges).

Here we set out to determine if allergen-specific T cells in cow milk allergic (CMA) patients have a distinct quality and/or quantity that could potentially be used as a diagnostic marker.

Using PBMC from 147 pediatric food allergic subjects, we mapped T cell responses to a set of reactive epitopes in cow milk that we compiled in a peptide pool. This pool induced cytokine responses in in vitro cultured cells distinguishing CMA from non-CMA subjects. We further used the pool to isolate and characterize antigen specific CD4 memory T cells using flow cytometry and scRNA/TCR-Seq assays.

We detected significant changes in the transcriptional program and clonality of cow milk antigen-specific (CM+) T cells elicited by the pool in CMA vs. non-CMA subjects ex vivo. CM+ T cells from CMA subjects had increased percentages of FOXP3+ over FOXP3- cells. FOXP3+ cells are often equated with regulatory T cells (Tregs) that have suppressive activity, but CM+ FOXP3+ cells from CMA subjects showed significant expression of interferon-responsive genes and dysregulated chemokine receptor expression compared to non-CMA subjects, suggesting that these are not conventional Tregs. The CM+ FOXP3+ cells were also more clonally expanded than the FOXP3- population. We were further able to utilize surface markers (CD25, CD127, CCR7) in combination with our peptide pool stimulation to quantify these CM+ FOXP3+ cells by a simple flow cytometry assay. We show increased percentages of CM+ CD127 CD25+ cells from CMA subjects in an independent cohort, which could be used for diagnostic purposes. Looking specifically for Th2 cells normally associated with allergic diseases, we found a small population of clonally expanded CM+ cells that were significantly increased in CMA subjects and that had high expression of Th2 cytokines and pathogenic Th2/Tfh markers.

Overall, these findings suggest that there are several differences in the phenotype of CM+ T cells with CM allergy and that the increase in CM+ FOXP3+ cells is a potential diagnostic marker of an allergic state. Such markers have promising applications in monitoring natural disease outgrowth and/or the efficacy of immunotherapy that will need to be validated in future studies.

Food allergies represent a serious health concern and, since the 1990s, they have risen gradually in high-income countries. Unfortunately, the problem is complex because genetic, epigenetic, and environmental factors may be collectively involved. Prevention and diagnoses have not yet evolved into efficacious therapies. Identification and control of allergens present in edible substances hold promise for multi-purpose biomedical approaches, including oral immunotherapy. This review highlights recent studies and methods to modify the otherwise innocuous native proteins in most subjects, and how oral treatments targeting immune responses could help cancel out the potential risks in hypersensitive individuals, especially children. We have focused on some physical methods that can easily be conducted, along with chemo-enzymatic modifications of allergens by means of peptides and phytochemicals in particular. The latter, accessible from naturally-occurring substances, provide an added value to hypoallergenic matrices employing vegetal wastes, a point where food chemistry meets sustainable goals as well.

To evaluated the risk ratio of Allergic rhinitis (AR) people on the symptoms after COVID-19 infection, and explored the relationship between AR and the symptoms after COVID-19 infection. An observational study was performed of people from outpatient department of the Hospital of Chengdu University of Chinese Medicine. Participants completed an electronic survey and between January 10 to January 20, 2023. We divided the participants into three groups according to the disease information of the population: non-AR people group (AR-N), AR patients with sublingual immunotherapy group (AR-S), and AR patients with conventional therapy group (AR-C). A total of 1116 participants were included in the study, with an average age of 21.76 ± 8.713, women accounted for 62.5%, men accounted for 37.5%. The final results showed that the risk of most symptoms after AR-C infection was not different from that of AR-N, except for sore throat, dry and itchy, chest distress, shortness of breath, and dyspnea. AR-S could effectively reduce the risk of post-infection symptoms including: dry and itchy (OR = 0.484, 95%CI: 0.335-0.698), pain (OR = 0.513, 95%CI:0.362-0.728), cough (OR = 0.506, 95% CI:0.341-0.749), expectoration (OR = 0.349, 95% CI:0.244-0.498), fever (OR = 0.569, 95% CI:0.379- 0.853), head and body pain (OR = 0.456, 95% CI:0.323-0.644), fatigue (OR = 0.256, 95% CI:0.177-0.371), cold limbs (OR = 0.325, 95%CI:0.227-0.465), diarrhea (OR = 0.246, 95% CI:0.132-0.457), constipation (OR = 0.227, 95%CI:0.100-0.513), hyposmia (OR = 0.456, 95% CI:0.296-0.701), hypogeusia (OR = 0.397, 95% CI:0.259-0.607), chest distress (OR = 0.534, 95% CI:0.343-0.829), shortness of breath (OR = 0.622, 95% CI:0.398- 0.974), palpitations (OR = 0.355, 95% CI:0.206-0.613). The risk of symptoms after COVID-19 infection in allergic rhinitis population receiving sublingual immunotherapy is lower.

Allergic rhinitis (AR) is a chronic inflammatory disorder, and sublingual immunotherapy (SLIT) is an important therapy. However, SLIT exhibits a wide range of fluctuations and lacks objective monitoring indicators. Therefore, exploring biomarkers for early prediction of the efficacy of SLIT is urgently needed.

We recruited two independent cohorts. In the discovery cohort, house dust mite (HDM) -induced AR patients underwent SLIT for at least 1 year, and were categorized into response and no response groups based on early efficacy. Serum proteomics was conducted to detect variations in protein expression levels between the two groups. The candidate proteins were confirmed in the validation cohort with enzyme-linked immunosorbent assay (ELISA), and their predictive values and levels of change before and after treatment were evaluated.

Serum proteomics identified a total of 113 differential proteins between the two groups, including 41 proteins upregulated and 72 downregulated in the no response group than the response group. The top 5 up- and down-regulated proteins were selected for further validation, and ELISA results revealed that serum CCL14, LTA4H, S100A11 and MMP9 levels were significantly elevated, and TGFBI and MASP1 were decreased in the response group than those in the no response group(P 0.7, P < 0.05). Furthermore, these two biomarkers exhibited significant reductions 1 year after SLIT, particularly in those patients who responded positively to the treatment (P < 0.05).

Serum S100A11 and MMP9 have the potential to serve as iomarkers for early prediction of the effectiveness of SLIT and monitoring the therapeutic effects. The circulating proteomic alterations might contribute to guiding treatment and understanding the mechanism of SLIT in AR patients.

Sesame is a significant food allergen causing severe and even fatal reactions. Given its increasing prevalence in western diet, sesame is listed as an allergenic food requiring labeling in the United States and EU. However, data on the population reaction doses to sesame are limited.

All sesame oral food challenges (OFCs), performed either for diagnosis or for threshold identification before the beginning of sesame oral immunotherapy (OIT) between November 2011 and July 2021 in Shamir medical center were analyzed for reaction threshold distribution. Safe dose challenges with 90-120 min intervals were also analyzed.

Two hundred and fifty patients underwent 338 positive OFCs, and additional 158 safe-dose OFCs were performed. The discrete and cumulative protein amounts estimated to elicit an objective reaction in 1% (ED01) of the entire cohort (n = 250) were 0.8 mg (range 0.3-6.3) and 0.7mg (range 0.1-7.1), respectively, and those for 5% of the population (ED05) were 3.4 mg (range 1.2-20.6) and 4.5 mg (range 1.2-28.8), respectively. Safe-dose OFCs showed similar values of ED01 (0.8, 0.4-7.5 mg) and ED05 (3.4, 1.2-22.9 mg). While doses of ≤1 mg sesame protein elicited oral pruritus in 11.6% of the patients, no objective reaction was documented to this amount in any of the challenges, including safe dose OFCs.

This study provides data on sesame reaction threshold distribution in the largest population of allergic patients studied, with no right or left censored data, and with validation using a safe-dose OFC. It further supports the current methods for ED determination as appropriate for establishing safety precautions for the food industry.

Allergen immunotherapy (AIT) is the only treatment which acts on the causes of allergic diseases by modifying their natural history. In the eighties subcutaneous immunotherapy (SCIT) with high biological power allergen extracts caused a number of severe systemic reactions and also fatalities in the UK and the US, resulting in its limitation and in the introduction of other routes of administration. A decisive advance for SCIT safety was understanding that the major cause of mortality was injecting the allergen extract to patients with uncontrolled asthma at the time of injection.

This awareness resulted in a significant decrease in fatalities, but not in their abolition. In 2019, an increase in SCIT-related mortality was observed, suggesting to continue the research for still unidentified factors favoring severe reactions, such as the administration of a wrong extract or of allergen doses higher than listed, unintentional intravenous administration, and missed dose reduction after protracted interruption. Moreover, in the context of the improving of the safety, the role played in tolerance-promoting by adjuvants such as CpG oligodeoxynucleotides has to be taken into account, as well as the potential preventive effect performed by the monoclonal anti-IgE antibody omalizumab against the exacerbation of severe reactions during SCIT.

The safety of SCIT is good, but the research to improve it further must continue. In particular, the pathophysiological mechanisms related to AIT for inhalants and for Hymenoptera venom should be studied, based on the evident diversity demonstrated by the complete absence of fatal reactions to Hymenoptera venom immunotherapy from its introduction in comparison with the history of serious and fatal offenses examined in this review.

Oral immunotherapy (OIT) imposes a burden on parents and their children with food allergies (FAs). We already developed a questionnaire for OIT-related Parental Burden (OIT-PB) scale. However, the previous questionnaire had some problems. This study modified OIT PB and verified its reliability and validity.

A 20-item draft covering the physical and mental burdens caused by OIT was prepared jointly with multiple allergists. The Food Allergy Quality of Life Questionnaire-Parental Burden (FAQLQ-PB) and Stress Response Scale-18 (SRS-18) were used to verify concurrent validity. A questionnaire survey was administered during treatment to parents of FA children who had started OIT for the first time. An additional OIT-PB survey was performed at one specific institution 1 week after the posttreatment survey.

The responses of 64 of the 76 recruited parents were analyzed. Of the 20 questions, 1 item was excluded owing to the floor effect, 1 was excluded because its commonality was less than 0.2, and 2 were excluded because their factor loading values were less than 0.4. Factor analysis was used to classify the OIT-PB into the following 4 subscales: "burden caused by adherence to treatment plan," "anxiety about symptom induced risk," "burden due to patient's eating behavior," and "anxiety about treatment effect." The Cronbach's α for all 16 items of the OIT-PB was 0.893; Cronbach's α for each subscale was 0.876, 0.898, 0.874, and 0.717. The re-test reliability coefficient was 0.864 (95% confidence interval [CI]: 0.720- 0.937, p < 0.001). A significant positive correlation was found between the OIT-PB and FAQLQ-PB (R = 0.610 [95% CI: 0.422-0.747], p < 0.001) and the SRS-18 (R = 0.522 [95% CI: 0.306-0.687], p < 0.001). A significant negative correlation was found between the rate of increase in OIT food intake and the "anxiety about treatment effect" score (R = -0.355 [95% CI: -0.558-0.112], p < 0.001). Parents of children on the hen's egg OIT treatment scored higher on the "burden due to patient's eating behavior" subscale than did parents of children on the milk and wheat OIT treatment.

The burden of OIT experienced by parents can be broadly classified into four categories. The modified OIT-PB was able to evaluate them individually and was shown to have reliability and validity. This scale is expected to be useful in the development of OIT that considers not only therapeutic effect but also the burden experienced by FA children and their parents.