Are peanut oral food challenges still useful? An evaluation of children with suspected peanut allergy, sensitization to Ara h 2 and controlled asthma.

BACKGROUND: Sensitization to Ara h 2 has been proposed as a promising biological marker for the severity of peanut allergy and may reduce the need for oral food challenges. This study aimed to evaluate whether peanut oral food challenge is still a useful diagnostic tool for children with suspected peanut allergy and an elevated level of Ara h 2-specific IgE. Additionally, we assessed whether well-controlled asthma is an additional risk for severe reactions. METHODS: A retrospective analysis of 107 children with sensitization to Ara h 2-specific IgE (> 0.35 kU/l) undergoing open peanut challenges during 2012-2018 in the Tampere University Hospital Allergy Centre, Finland. RESULTS: Of the 107 challenges, 82 (77%) were positive. Serum levels of Ara h 2 -sIgE were higher in subjects with a positive challenge than in those who remained negative (median 32.9 (IQR 6.7-99.8) vs. 2.1 (IQR 1.0-4.9) kU/l), p < 0.001) but were not significantly different between subjects with and without anaphylaxis. No correlation was observed between the serum level of Ara h 2-sIgE and reaction severity grading. Well-controlled asthma did not affect the challenge outcome. CONCLUSIONS: Elevated levels of Ara h 2-specific IgE are associated with a positive outcome in peanut challenges but not a reliable predictor of reaction severity. Additionally, well-controlled asthma is not a risk factor for severe reactions in peanut challenges in children with sensitization to Ara h 2.

Elevated serum adipsin may predict unsuccessful treatment for cows' milk allergy but other biomarkers do not.

AIM: This study evaluated whether 15 allergy, immunology or inflammatory markers predicted the long-term use of cows' milk or milk products seven years after the start of oral immunotherapy (OIT) for cows' milk allergy in children. METHODS: The following laboratory parameters were measured before the OIT at Tampere University Hospital, Finland, and after the six-month escalation phase: serum total immunoglobulin (Ig) E, milk-specific IgG and IgG4, eosinophil cationic protein, eosinophil-derived neurotoxin, interleukins 4, 5, 6, 10 and 12p70 and serum adipokines adiponectin, adipsin, leptin and resistin. Follow-up data from a seven-year phone questionnaire in 2015 were available for 24 children: 14 successful and 10 unsuccessful milk users. RESULTS: There were no significant differences in any of the 15 markers measured at the start of the study between the subjects who later formed the successful and unsuccessful groups. At the end of the six-month escalation phase of OIT, serum adipsin was higher in the group who were unsuccessful milk users at the seven-year follow-up study. CONCLUSION: None of the 15 allergy, immunology or inflammatory markers were useful in predicting the outcome of OIT. Preliminary evidence was found that high serum adipsin after the six-month escalation phase of OIT might predict unsuccessful outcome.

Changes in biomarkers during a six-month oral immunotherapy intervention for cow's milk allergy.

AIM: Oral immunotherapy (OIT) is a promising but still experimental method to treat children with cow's milk (CM) allergy (CMA). We evaluated changes in allergic, immunological and inflammatory parameters, which happened during the six-month OIT for CMA. METHODS: We treated 28 school-aged children with CMA using OIT with a double-blind placebo-controlled design. After the controlled study finished, the placebo group was treated with the same but open-label OIT protocol. Sixteen immune variables were tested before and after the six-month OIT. RESULTS: Before OIT, the median serum CM-specific immunoglobulin (Ig) E was 18.0kIU/L in the intervention group and 9.4kIU/L in the placebo group (p = 0.46). At six months, interleukin (IL)-6 and IL-10 were significantly higher in the intervention group. When the changes during the blinded and open OIT were analysed together for both groups, blood eosinophils and serum total IgE decreased and milk-specific IgG and IgG4, serum IL-4 and IL-6, and serum leptin and resistin increased significantly. CONCLUSION: Preliminary evidence was found that markers of allergy such as blood eosinophils and serum IgE decreased and milk-specific IgG and IgG4 increased during OIT. Adipokines, leptin and resistin, which functionally are cytokines linked to Th1-type response, increased during OIT.

Children who were treated with oral immunotherapy for cows' milk allergy showed long-term desensitisation seven years later.

AIM: This was a follow-up of 28 schoolchildren with cows' milk allergy (CMA) who attended a randomised double-blind placebo-controlled oral immunotherapy (OIT) study. In the original study, 26 (92.9%) completed the six-month escalation phase, and 25 (89.3%) used milk daily at 12 months and 24 (85.7%) at 36 months. This study evaluated the outcome seven years later, with special attention paid to milk consumption and symptoms. METHODS: Outcome data were collected through a postal questionnaire completed three, four and five years after enrolment and by a phone questionnaire after seven years. We asked about the daily dose of milk products, any adverse reactions, any medication needed and possible discontinuation of daily milk consumption. RESULTS: Data were available at the seven-year point for 24 children and 14 (58.3%) of these continued to use milk (≥200 mL) or milk products (protein ≥6400 mg) daily for seven years. However, three (21.4%) of these still reported symptoms associated with milk consumption. Of the 10 remaining children, two children used milk products daily but consumed less due to symptoms and eight (33.3%) had discontinued milk consumption. CONCLUSION: Oral immunotherapy was an effective and safe way of desensitising schoolchildren with persistent CMA.

Stability of parent-reported food allergy in six and 7-year-old children: the first 5 years of the Finnish allergy programme.

AIM: The Finnish national allergy programme was introduced in 2008 to decrease the burden of allergy in the population. This study, carried out in 2013, evaluated the prevalence of parent-reported food allergies, treated with an avoidance diet until early school age, and discussed the rates in relation to those found in an identical study in 2009. METHODS: School health nurses used a structured questionnaire to interview the parents of 1653 children aged of six or seven in the first year of elementary school. The criterion for a parent-reported food allergy was that the parents considered it necessary for their child to follow an avoidance diet at school. RESULTS: In 2013, 6.1% of the children were allergic to at least one food and 2.5% of the children were allergic to basic foods, such as cows' milk, eggs and wheat, compared with 2.7% in 2009. A significant decrease was seen in allergies to nuts, fruits and vegetables. CONCLUSION: Parent-reported allergies to basic foods, such as cow's milk, eggs and wheat, remained rather stable in first graders of elementary schools during the first 5 years of the Finnish national allergy programme, but allergies to nuts, fruits and vegetables decreased.

Milk oral immunotherapy is effective in school-aged children.

AIMS: To study the efficacy of oral immunotherapy (OIT) in schoolchildren with cow's milk (CM) allergy (CMA). METHODS: Twenty-eight children aged 6-14 years with CMA documented by oral challenge were enrolled into a randomized, double-blind, placebo-controlled OIT study. In the active treatment, CM protein amount was increased during 23 weeks from 0.06 mg to a maximum of 6400 mg (200 mL of milk). RESULTS: Twenty-four (86%) patients completed the protocol: 16/18 in active and 8/10 in placebo groups. All children in the active and 2/3 in the placebo group suffered from symptoms considered by the parents as induced by milk. The children were contacted by phone 12 months later, and 13 (81%) used daily CM or milk products corresponding 6400 mg of CM protein. After double-blind OIT, all 10 children in the placebo group completed successfully an open-label OIT by an identical protocol, and all used daily CM or milk products 6 months later. Three to 3.5 years later, one child more had discontinued daily milk use. Thus, the long-term success rate was 22/28 (79%). CONCLUSIONS: This placebo-controlled, double-blind study confirmed that OIT was effective in desensitizing schoolchildren with CMA. With occasional exceptions, the reached desensitization sustained for more than 3 years.

Enrolment of 22,000 adolescent women to cancer registry follow-up for long-term human papillomavirus vaccine efficacy: guarding against guessing.

Human papillomaviruses (HPVs, most notably types 16 and 18) cause cervical carcinoma, the second most common cancer among women. Vaccination of adolescents against HPV16/18 might prevent large proportion of cervical and other anogenital cancers. However, because of ethical reasons this cannot be proven by clinical studies. To determine the long-term vaccine efficacy (VE) of HPV16/18 virus-like-particle (VLP) vaccine against cervical carcinoma in situ (CIS+) and invasive cervical carcinoma, the following three population-based cohorts of adolescent women have been enrolled: (1) women vaccinated with the HPV vaccine; (2) women vaccinated with hepatitis A control vaccine; and (3) unvaccinated control women. These cohorts will be passively followed for cumulative incidence of CIS+ endpoints by population-based cancer registry. Overall 24,046 16- to 17-year-old adolescent women from 18 cities in Finland were invited between May 2004 and June 2005 to participate in a phase III trial with bivalent HPV16/18 VLP vaccine. A total of 58,996 18- to 19-year-old women were invited in May 2005 to participate as unvaccinated controls. Women who reported their willingness to participate in an HPV vaccination trial had they been 1-2 years younger were eligible. Cumulative incidence (CI) of CIS+ in our cohorts over 15 years is approximately 0.45%. VE of 70% against CIS+ with 80% power requires 3357-3189 HPV16/18 vaccine recipients, 3357-3189 other vaccine recipients, and 6714-9567 unvaccinated controls. We have now enrolled 2404 HPV16/18 vaccine recipients, 2404 hepatitis A-vaccine recipients, and 5130 unvaccinated controls. This enrolment in addition to our earlier enrolment in another phase III trial guarantees enough power so that by 2020 we can ultimately provide data on the efficacy of HPV16/18 vaccination against CIS+.