Oral food challenge: a Brazilian panorama

Conclusions: Although this study’s methodology involves intrinsic biases, this is the first exploration of OFC practice in Brazil. OFCs are still underperformed nationwide


Introduction
The worldwide prevalence of food allergy (FA) is estimated to range from 1% to 10%, affecting people of different ages, ethnicities, and socioeconomic conditions. 1 Approximately 30% of children with FA may experience reactions to multiple food allergens. 2ata on the prevalence of FA in the Brazilian population are scarce.A national multicenter study observed high sensitization rates, mainly to cow's milk (84.2%) and egg (70.5%), in a selected population with a medical diagnosis of FA. 3 It also showed a significant increase in sensitization to cow's milk, peanuts, and corn from 2004 to 2016. 3,4e symptoms of FA are nonspecific, and laboratory tests alone are not sufficient to confirm or exclude the diagnosis.The oral food challenge (OFC) is still considered the diagnostic gold standard for FA when performed in a double-blind, placebo-controlled manner. 5The OFC is also used to investigate acquisition of tolerance to food allergens, which can happen spontaneously or be induced (immunotherapy). 57][8] Elimination diet remains the cornerstone of FA management, which may imply nutritional risk, especially for patients with allergies to multiple food allergens. 9herefore, a thorough investigation is essential to avoid misdiagnosis and thereby prevent the implementation of unnecessary diets, which reduce quality of life. 10The OFC is associated with better QoL independent of challenge outcome because it elucidates some aspects of the FA. 11 note, the OFC has only been covered by the Brazilian Unified Health System (Sistema Único de Saúde, SUS) and private health insurances (Brazilian Hierarchic Code of Medical Procedures/TUSS code 2.01.01.36-8) since 2022, and only for children aged up to 24 months in need of diagnosis and/or monitoring of allergy to cow's milk. 12,13nsidering the increase in the prevalence of FA in recent decades, as well as the incipient inclusion of the OFC in private and public health systems and its complexity, it is likely that the test is insufficiently performed in Brazil.With the objective of describing the profile of OFC performance in Brazil, including barriers, the Scientific Department of Food Allergy of the Brazilian Association of Allergy and Immunology 2021-2022 (ASBAI) conducted a survey on the topic to be answered by ASBAI members.

Methods
This was a cross-sectional study that assessed OFC performance by allergists and immunologists.Participants answered an on-line questionnaire on Google Forms ® (Annex 1).All 2,500 ASBAI members received an institutional e-mail between June and December 2022 inviting them to participate in the survey, with a link to the questionnaire and the informed consent form.The 15 members of ASBAI's Scientific Department of Food Allergy were excluded from the survey to avoid bias.
Oral food challenge: a Brazilian panorama -Camargo-Lopes-de-Oliveira L et al.
The study was approved by the research ethics committee of Universidade Federal de São Paulo under no.5.421.086(0241/2022).
Categorical variables were expressed as frequencies and proportions and compared using Fisher's exact test.Statistical analyses were performed using Epi Info 7.2.5.0.

Results
One of the respondents did not provide informed consent and was excluded from the study.A total of 290 respondents (11.6%) were included, of whom 96.9% had completed medical residency or a fellowship program in Allergy and Immunology, and 45.5% of them had finished their residency/fellowship at least 10 years ago.Education-related characteristics, such as time since residency/fellowship completion and OFC training during residency/fellowship, are presented in Table 1 in relation to whether or not OFC is offered in clinical practice.In our sample, 106 physicians (36.5%) did not perform OFC during residency/fellowship, of whom 40 (37.7%) had completed their education in the last 19 years.
Not offering OFC in clinical practice was statistically higher in the group of physicians who completed their residency/fellowship between 20 and 29 years ago.Those who performed OFC during their medical education were more likely to offer OFC in current clinical practice (p < 0.01), especially if 6 or more OFCs were performed (Table 1).
Figure 1 shows the distribution of respondents according to the state where they work.Three physicians reported working in more than 1 state.Most respondents (n = 158 [54.5%]) reported offering OFC in current clinical practice, especially in the private sector (Figure 2).Just over 62% of these professionals perform up to five OFC with food monthly, and almost 16% perform 11 or more tests/month.As for the environment in which OFC is commonly performed, most respondents (38%) answered the hospital environment, followed by out-of-hospital/ outpatient (28.5%), both (25.3%), and the rest, level III centers.Most physicians obtain informed consent from patients/guardians (89.9%).Cow's milk (83.5%) and egg (11.4%) are the most tested foods, followed by seafood (3.2%).
Figure 3 shows the types of OFC most commonly performed (open, single-blind, or double-blind and placebo-controlled).The single-blind method is the most performed, and 74% of respondents reported only performing this method.The food is most often provided by the family (67.1%),followed by the doctor (20.3%) and nutritionist/medical staff member (12%).The food is more commonly administered to the patient by the doctor (82.3%) or a nurse/practical nurse (13.3%), and a nutritionist is only involved in 1.9% of cases.A hundred and fifty-two physicians (45.5%) reported not offering OFC due to the following barriers: lack of appropriate resources and space (46%), lack of technical capacity (21%), inadequate reimbursement (12%), lack of health insurance (11%), and patient or family refusal (2%).Among suggested solutions (1 possible answer in the multiple-choice test), the availability of standardized national protocols for performing OFC was selected as the best one (Figure 4).

Discussion
Brazil is estimated to have a rate of 0.94 allergists/ immunologists per 100,000 inhabitants under the age of 18 -more than Canada (0.67) and Australia (0.87) but much less than Germany (6.50) and Japan (3.34).
Data from this survey were obtained from all Brazilian states, except Roraima (Figure 1).The questionnaire was answered only by a small number of ASBAI members (11.6%) who voluntarily agreed The rate of respondents was low but close to that observed in a similar US survey (10%). 15owever, 95% of respondents in the US survey reported offering OFC. 15 A similar survey conducted in Canada obtained a response rate of 30.2%, and 80.6% of respondents reported offering OFC. 16In our Brazilian survey, a little over half of respondents reported offering the test, although most of them work in teaching hospitals (n = 62/158, 39%).This suggests that, despite a selection bias in favor of offering the test, OFC training is not a part of medical education in many teaching hospitals, meaning that misdiagnosis may be common.Of note, it is likely that those who do not offer this type of intervention tend to not participate in this type of survey.
Specialists who completed their residency/ fellowship between 20 and 29 years ago offer less OFC in current clinical practice, probably because during their education the prevalence of FA was lower and medical residency programs did not provide OFC training.Although the rate of FA has significantly increased worldwide in the last 30 years and in Brazil in the past 2 decades, we still cannot quantify the real problem at the national level due to the scarcity of prevalence studies.No statistically significant difference was observed in those who completed their residency/fellowship > 30 years ago, probably due to the small number of respondents that constituted this group.
The performance of ≥ 5 OFCs during medical education was associated with OFC performance in current practice, showing the importance of including the procedure in medical education.More than a third (106/290) of respondents said they did not perform OFC during their residency/fellowship, higher than the rate of 29% observed in the US survey. 15most all of the allergists/immunologists who perform OFC work in more than one sector, including the private sector (148/158), and very few work exclusively in SUS (4/158) (Figure 2), meaning that most of the Brazilian population is likely to not have access to this test.Most physicians who offer OFC live in the Federal District and the Southeast Region of Brazil, possibly as a result of higher medical density in these regions, or selection bias. 17It was recently estimated that 63.1% of ASBAI's members live in the Southeast Region of Brazil, followed by the Northeast (15.0%),South (9.7%), Midwest (7.7%), and North (4.4%) regions. 18Canadian study reported a median of 12 OFCs per month per physician. 16In our survey, 62% of physicians performed up to 5 OFCs per month, and 16% performed ≥ 11 OFCs per month.
The most tested foods are cow's milk and egg, followed by seafood, peanuts, and chestnuts.As in other countries, the open challenge is the most offered, 14,15 supposedly because it is less complex.It should be noted that the rate of Brazilian physicians who obtain informed consent was similar to that of US physicians (89.9% vs. 82%) 15 but higher than that of Canadians (40%). 16Although the food to be tested is often provided by family members, the doctor is the one to administer it to the patient, similarly to what happens in the USA, where the food is administered by a nurse in 73% of cases. 15like in the US and Canadian surveys, inadequate reimbursement was not mentioned among the main barriers 15,16,19 by those who do not offer the test, but rather lack of appropriate resources and space (46%) and lack of technical capacity (21%).However, in Canada, dedicated reimbursement fee codes were suggested by 66.1% of respondents. 16Lack of support staff and office space was identified as a limitation by 72.6% and 64.5% of Canadian respondents, respectively. 16

Conclusion
Only a little over 50% of respondents reported offering OFC in the setting of FA, which is concerning, as the absence of testing may lead to misdiagnosis and generate unnecessary diet restrictions with nutritional risks for patients.Furthermore, we suggest that OFC should be included in medical education and complemented by refresher courses.
After the incorporation of OFC in the SUS and private health insurances, together with the increase in FA prevalence in Brazil, we expect that the demand for OFC will increase similarly to that observed in other studies.Only a little over half of the allergists/ immunologists who participated in this survey claimed to offer OFC.However, we cannot rule out selection bias, as it is likely that those who do not perform OFC have chosen not to participate in this survey, which means that the frequency of OFC may be overestimated.
This study showed that access to this important diagnostic tool is very limited in Brazil, which is concerning for a country of continental dimensions.
Oral food challenge: a Brazilian panorama -Camargo-Lopes-de-Oliveira L et al.
The technical training of more professionals, either by including OFC training in residency/fellowship programs or by promoting refresher courses, is necessary.The lack of appropriate resources and spaces is also a concern that hinders the implementation and dissemination of the OFC.
Despite the selection bias inherent to the methodology used in this study, this pioneering Brazilian survey is important to understand and discuss the performance of this type of procedure in Brazil.

Oral food challenge: Brazilian panorama
The oral food challenge (OFC) is still considered the diagnostic gold standard for food allergies (FAs) and is also used to investigate the acquisition of tolerance in patients with a previous diagnosis of FA.However, the test is not easy to perform, and it is different from food reintroduction at home.We developed this short questionnaire (approximate duration: 7 minutes) to better understand the barriers to OFC performance by ASBAI members, and we count on your valuable contribution!

Thank you for your valuable contribution!
Oral food challenge: a Brazilian panorama -Camargo-Lopes-de-Oliveira L et al.

Annex 1 (continuation)
On-line questionnaire on performing oral food challenge (OFC) aimed at specialists in allergy/immunology

Figure 1
Figure 1 Distribution of physicians according to state (n = 293).In parentheses = percentage of physicians who offer the oral food challenge FD = Federal District.

Figure 2 1
Figure 2 Distribution of physicians (n = 158) who offer the oral food challenge according to each sector

Figure 3 Figure 4
Figure 3 Number of physicians who perform each type of oral food challenge (n = 158) did you complete your residency/fellowship training in Allergy and Immunology? o Between 1 and 5 years o Between 6 and 10 years o Between 11 and 19 years o Between 20 and 29 years o 30 years ago or more o I did not undergo residency/fellowship training in Allergy and Immunology How many OFCs did you perform during the entire period of your residency/fellowship program?o Up to 5 o Between 6 and 10 o More than 10 In which Brazilian state (or the Federal District) do you currently work?You may select more than one option.

Table 1 Education
-related characteristics of physicians who offer vs do not offer OFC (presented in absolute numbers and percentages) OFC = oral food challenge.

you taken any of the following courses? You may select more than one option.
On-line questionnaire on performing oral food challenge (OFC) aimed at specialists in allergy/immunologyOral food challenge: a Brazilian panorama -Camargo-Lopes-de-Oliveira L et al.

OFC do you offer in your clinical practice? You may select more than one option
. o Open (patient, family, and doctor know which food is being administered) o Single-blind (2-stage procedure with the food and a placebo; only the doctor knows which food is being administered) o Double-blind and placebo-controlled (2-stage procedure with the food and a placebo, but not even the doctor knows which food is being administered)

Among the options below, what would you say is the best solution to overcome these barriers
? o Well-defined criteria for when to perform OFC in a medical office or hospital environment o Standardized national protocols for performing OFC o Adequate reimbursement by health insurances o In-service OFC training during residency/fellowship training o Periodic practical courses on OFC provided by the society of which I am a member o Hospital support close to my office to guarantee OFC safety o Creation of reference centers for OFC in my city Please feel free to write further considerations on the topic below.