Slow low-dose oral immunotherapy: Threshold and immunological change

Sugiura, Shiro; Kitamura, Katsumasa; Makino, Atsushi; Matsui, Teruaki; Furuta, Tomoko; Takasato, Yoshihiro; Kando, Naoyuki; Ito, Komei

doi:10.1016/j.alit.2020.03.008

Cited by 36 publications

(47 citation statements)

References 38 publications

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“…Well-designed OIT clinical trials were initiated recently, making OIT a considerably novel approach in FA management; nevertheless, the first attempts of treating children by giving small and increasing amounts of the allergen, to stimulate immune tolerance, go back to the beginning of the 20 th century (133). Most OIT trials were conducted over the last decade focusing on single allergens, predominantly on cow's milk, egg, and peanut, but there is an increasing number of publications on other allergens, such as wheat (134)(135)(136) and nuts (137). Moreover, peanut OIT and EPIT were recently approved by the FDA for the treatment of peanut-allergic children (24).…”

Section: Discussionmentioning

confidence: 99%

Oral Immunotherapy for Food-Allergic Children: A Pro-Con Debate

et al. 2021

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The prevalence of food allergy has increased in recent years, especially in children. Allergen avoidance, and drugs in case of an allergic reaction, remains the standard of care in food allergy. Nevertheless, increasing attention has been given to the possibility to treat food allergy, through immunotherapy, particularly oral immunotherapy (OIT). Several OIT protocols and clinical trials have been published. Most of them focus on children allergic to milk, egg, or peanut, although recent studies developed protocols for other foods, such as wheat and different nuts. OIT efficacy in randomized controlled trials is usually evaluated as the possibility for patients to achieve desensitization through the consumption of an increasing amount of a food allergen, while the issue of a possible long-term sustained unresponsiveness has not been completely addressed. Here, we evaluated current pediatric OIT knowledge, focusing on the results of clinical trials and current guidelines. Specifically, we wanted to highlight what is known in terms of OIT efficacy and effectiveness, safety, and impact on quality of life. For each aspect, we reported the pros and the cons, inferable from published literature. In conclusion, even though many protocols, reviews and meta-analysis have been published on this topic, pediatric OIT remains a controversial therapy and no definitive generalized conclusion may be drawn so far. It should be an option provided by specialized teams, when both patients and their families are prone to adhere to the proposed protocol. Efficacy, long-term effectiveness, possible role of adjuvant therapies, risk of severe reactions including anaphylaxis or eosinophilic esophagitis, and impact on the quality of life of both children and caregivers are all aspects that should be discussed before starting OIT. Future studies are needed to provide firm clinical and scientific evidence, which should also consider patient reported outcomes.

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Section: Discussionmentioning

confidence: 99%

Oral Immunotherapy for Food-Allergic Children: A Pro-Con Debate

et al. 2021

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“…Primary Investigators Akagawa Shohei MD, PhD 1 , Anzai Kaori, MD 2 , Bandou Kenji, MD 3 , Ikeda Akiko, MD 4 , Doi Masaaki, MD, PhD 5 , Enomoto Masahiro, MD, PhD 6 , Fujikawa Shiori, MD 7 , Nagai Megumi MD, PhD 8 , Nishiyama Atsuko, MD 9 , Otsuka Keita, MD 10 , Shimizu Satoko, MD 11,12 , Sugimoto Yukiko, MD 13 , Sumimoto Shinichi, MD, PhD 2 , Tanaka Yukiko, MD 14 , Tanaka Yuko, MD 15 , Tanaka Yuya, MD 16 , Wakahara Ryohei, MD, PhD 17 , Yamasaki Koji, MD, PhD 18 Co-Investigators Arima Tomoyuki, MD 8 , Imaide Aya, MD 6 , Fukasawa Yohei, MD 21 , Hashimoto Naoki, MD 19 , Masumi Hiroki MD 8 , Matsutani Eri, MD 3 , Kim Jong Soo, MD 20 , Nakai Yoko, MD 1 , Nakamichi Erina, MD 2 , Natsuki Momo MD 16 , Onaka Masayuki, MD 9 , Shingaki Tomoya, MD 20 , Sunaga Ayana, MD 3 , Tsurinaga Yuki, MD 21 , Yamada Saki, MD 20 , Yamagishi Mitsuru, MD 1…”

Section: Discussionmentioning

confidence: 99%

“…In Japan, the number of patients receiving OIT increased approximately sixfold from 2012 to 2015 [6]. OITs are continued at home [6][7][8], despite the ingestion of food antigens posing a risk of adverse reaction. Therefore, in home-based OIT, it is essential to prescribe therapeutic drugs, including adrenaline and antihistaminic medicines and to expand safety measures such as 24-h emergency consultation and cooperation with local emergency medical institutions.…”

Section: Introductionmentioning

confidence: 99%

Progress of Home-Based Food Allergy Treatment during the Coronavirus Disease Pandemic in Japan: A Cross-Sectional Multicenter Survey

Maeta

Takaoka

Nakano³

et al. 2021

Children

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The coronavirus disease 2019 (COVID-19) pandemic’s impact on food allergy treatment such as home-based oral immunotherapy (OIT) is not known. This cross-sectional, questionnaire-based anonymized survey screened 2500 parents of children with allergic diseases and was conducted in the pediatric outpatient clinics of 24 hospitals. Basic clinical data of the children were collected along with the degree of allergy control, parental anxiety about emergency visits, and the risk of COVID-19 in the first state of emergency. A total of 2439 (97.6%) questionnaires were collected, and 1315 parents who were instructed to initiate home-based OIT for their children were enrolled (OIT group). Subjective OIT progress compared to before the COVID-19 pandemic was ascertained as “Full”, “Middle”, “Low”, “Little”, and “Stop” in 264 (20.1%), 408 (31.0%), 384 (29.2%), 203 (15.4%), and 56 (4.3%) participants, respectively. Anxiety about emergency visits and the risk of COVID-19 were negatively associated with the subjective OIT progress. In Japan, approximately half of the children continued smoothly the home-based OIT during the COVID-19 pandemic. Parents with high levels of anxiety about the disruption of the medical care system due to COVID-19 and the risk of COVID-19 did not experience a smooth continuation of home-based OIT.

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“…The initial dose was based on the total doses and severity of allergic symptoms in oral food challenges. 18,19 For patients whose symptom‐provoked threshold dose was high (>66 mg CM protein or 52 mg wheat protein), the dose was increased by 10%‐20% after every 5th–10th asymptomatic ingestion. The dose was increased more slowly for the patients whose threshold was low (<66 mg CM protein or 52 mg wheat protein), as previously reported 18 .…”

Section: Methodsmentioning

confidence: 99%

“… 18,19 For patients whose symptom‐provoked threshold dose was high (>66 mg CM protein or 52 mg wheat protein), the dose was increased by 10%‐20% after every 5th–10th asymptomatic ingestion. The dose was increased more slowly for the patients whose threshold was low (<66 mg CM protein or 52 mg wheat protein), as previously reported 18 . All patients were instructed to avoid exercising and bathing one hour before and two hours after taking the dose to minimize the risk of exercise‐induced symptoms.…”

Section: Methodsmentioning

confidence: 99%

Exercise‐induced allergic reactions after achievement of desensitization to cow's milk and wheat

Kubota¹,

Kitamura²,

Matsui³

et al. 2021

Pediatric Allergy Immunology

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Background We have previously reported that more than half of the patients who achieved desensitization after wheat rush oral immunotherapy (OIT) developed exercise‐induced allergic reaction on desensitization (EIARD). However, data on EIARDs after slow OIT are lacking. Therefore, this study aimed to investigate the results of exercise provocation tests (EPTs) in patients after slow OIT for cow's milk and wheat allergies. Methods This was a retrospective chart review of 87 EPTs in 74 patients. The EPTs were performed in patients who were desensitized to at least 6,600 mg cow's milk protein or 5,200 mg wheat protein with slow OIT and were identified to be at a high risk of EIARDs. EPTs were performed after ingestion of the maximum desensitization dose. The patients’ clinical characteristics and symptoms were analyzed. Results The EPT results were positive for cow's milk in 49% (21/43) of the patients and for wheat in 48% (15/31) of the patients. There was no significant difference in the clinical characteristics between the EIARD‐positive and EIARD‐negative groups. The specific IgE (sIgE) levels before OIT and the reduction rates of sIgE before and after OIT did not correlate with the outcomes of the EPTs. Among the EIARD‐positive patients, 13 patients (cow's milk, n = 7; wheat, n = 6) underwent a second EPT, and the EIARD disappeared in 8 patients (cow's milk, n = 4; wheat, n = 4). Conclusion EIARDs were observed after slow OIT for cow's milk and wheat. Further research into the predictive factors of EIARDs in these patients is needed to understand its clinical manifestations.

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Slow low-dose oral immunotherapy: Threshold and immunological change

Cited by 36 publications

References 38 publications

Oral Immunotherapy for Food-Allergic Children: A Pro-Con Debate

Oral Immunotherapy for Food-Allergic Children: A Pro-Con Debate

Progress of Home-Based Food Allergy Treatment during the Coronavirus Disease Pandemic in Japan: A Cross-Sectional Multicenter Survey

Exercise‐induced allergic reactions after achievement of desensitization to cow's milk and wheat

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