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Objectives:  The aim was to examine if a diagnostic intervention set up to assess current food allergy to cow’s milk, hen’s egg, fish, or wheat among teenagers had an impact on generic and disease specific health-related quality of life (HRQL). The study compared HRQL scoring before and two years after the intervention, and in relation to age matched controls without reported food allergy.

Methods: The study was performed within the Obstructive Lung Disease in Northern Sweden (OLIN) studies where a cohort study on asthma and allergic diseases among 8-year-old schoolchildren was initiated in 2006. At age 12 years, the 125/2612 (5%) children who reported allergy to cow’s milk, hen’s egg, fish, or wheat were invited to a diagnostic intervention including clinical examination, blood tests and evaluation by a pediatric allergist. Of 94 participants, 79 completed generic and disease specific HRQL questionnaires. Additionally, a random sample of 200 (62% of invited) children without food allergy from the OLIN cohort answered the generic HRQL questionnaire. The respondents of the HRQL questionnaires were reexamined two years later and 57 teenagers with and 154 without reported allergy participated.

Results: There were no significant differences in generic HRQL scores between teenagers with and without reported food allergy at study entry, or after the intervention. Among those with reported food allergy, we found a significant improvement in disease specific HRQL after the intervention (mean values: 3.41 vs 2.80, p<0.001). Teenagers with only food allergy had better disease specific HRQL compared to those with one, two or three concomitant allergic diseases, both before and after the intervention. Children with only food allergy significantly improved their HRQL after the intervention, 1.84 vs. 2.87 (p<0.001) but this association was not seen in children with one other allergic disorder (3.16 vs. 3.65, p = 0.121) or those with two or more allergic disorders (3.72 vs. 3.90, p = 0.148).

Conclusion: The diagnostic intervention showed a long-term improvement of disease specific HRQL but not generic HRQL.

Aim: To describe clinical presentation and development of tolerance among children with Food protein-induced enterocolitis syndrome (FPIES) in a population in northern Sweden.

Methods: A retrospective review of medical records of children presenting with FPIES symptoms from 1 January 2004, to 31 May 2018.

Results: Sixty children (65% boys) with FPIES were included. The estimated incidence gradually increased to 0.45% in 2016–2017. The most common food triggers were cow's milk (40%), fish (37%) and oat (23%). Symptoms presented in 31 (60%) children before 6 months and in 57 (95%) before 1 year of age. The median age for FPIES diagnosis was 7 (range 3–134) months and for fish FPIES 13 (range 7–134) months. By 3 years of age, 67% of children with FPIES to milk and oat but none of the children with fish FPIES had developed tolerance. Allergic conditions like eczema and asthma were reported in 52% of the children.

Conclusion: The cumulative FPIES incidence was 0.45% in 2016–2017. Most children presented with symptoms before 1 year of age, but the diagnosis was often delayed, especially for FPIES to fish. Tolerance development occurred at an earlier age when FPIES was triggered by milk and oat compared to fish.

Background: The prevalence of reported food hypersensitivity among children has increased in Western countries. However, the prevalence varies largely due to differences in methods used in different studies. Double-blind placebo-controlled food challenge (DBPCFC) is the most reliable method to verify or exclude food hypersensitivity. The use of double-blind food challenges is increasing in clinical praxis, but since the method is time- and resource consuming it is rarely used in population-based cohort studies. There is a lack of knowledge on how adolescents and mothers experience participation in double-blind placebocontrolled food challenges and to what extent the food is reintroduced after a negative challenge. While several studies have described the impact of IgEmediated food allergy on Health-Related Quality of Life (HRQL), few studies have described HRQL among children with other food hypersensitivity phenotypes.

Aim: The aim of this thesis was to estimate the prevalence of reported food hypersensitivity, associated risk factors, and symptom expressions among schoolchildren. We also examined HRQL among children with total elimination of cow's milk, hen’s egg, fish or wheat due to food hypersensitivity as a group compared with children with unrestricted diet, and after we categorised the children with eliminated foods into different phenotypes of FHS. Finally, adolescents' and mothers' experience of DBPCFC was examined as well if the food had been reintroduced.

Methods: Three studies were based on the Obstructive Lung Disease in Northern Sweden (OLIN) paediatric cohort II. The cohort was recruited in 2006 when all children in first and second grade (7-8 years) in three municipalities in Norrbotten were invited to a parental questionnaire study and 2,585 (96% of invited) participated. The questionnaire included questions about food hypersensitivity, asthma, rhinitis, eczema and possible risk factors. The children in two municipalities were also invited to skin prick testing with 10 airborne allergens, and 1,700 (90%) participated. Paper I is based on this initial survey of the cohort. Four years later, at age 11-12 years, the cohort was followed up using the same methods and with the same high participation rate. At the follow-up, 125 children (5% of the cohort) reported total elimination of cow's milk, hen's egg, fish or wheat due to food hypersensitivity. These children were invited to a clinical examination and to complete a generic (KIDSCREEN-52) and a diseasespecific HRQL questionnaire (FAQLQ-TF) (n=75). Based on the clinical examination the children were categorised into different phenotypes of food hypersensitivity: current food allergy, outgrown food allergy and lactose intolerance. In addition, a random sample of children with unrestricted diet from the same cohort, answered the generic questionnaire (n=209). Paper II is based on this HRQL study. Children categorised as having current food allergy were invited to a further evaluation including DBPCFC. Eighteen months after the challenges, these children were interviewed about their experiences during and after the challenge (n=17). Paper III is based on these interviews. Paper IV was based on interviews with mothers to children referred to a paediatric allergy specialist for evaluation of food allergy using DBPCFC (n=8). In the two interview studies results were analysed using qualitative content analysis.

Results: At age 7-8 years, the prevalence of reported food hypersensitivity was 21%. Food hypersensitivity to milk, egg, fish, wheat or soy was reported by 10.9% and hypersensitivity to fruits or nuts by 14.6%. The most common essential food to trigger symptoms was milk, reported by 9%. The most frequently reported food induced symptoms, were oral symptoms mainly caused by fruits, followed by gastrointestinal symptoms mainly caused by milk. The risk factor pattern was different for food hypersensitivity to milk compared to hypersensitivity to other foods. No significant difference in distribution in generic or disease-specific HRQL was found among children with reported total elimination of milk, egg, fish and/or wheat due to FHS compared to children with unrestricted diet. However, a trend indicated that the disease-specific HRQL was most impaired among children with current food allergy compared to children with outgrown food allergy and lactose intolerance. The proportion of poor HRQL defined as ≥75 percentile was significantly higher among children with current food allergy than the other phenotypes. A DBPCFC was an opportunity for the adolescents and the mothers to overcome the fear of reactions to food that had been eliminated for a long time. After the challenge, when the food was partially or fully reintroduced, socializing became easier and both adolescents and mothers experienced more freedom regarding food intake. A negative challenge was not consistently associated with reintroduction of the food. Reasons for reintroduction failure were fear of allergic reactions, that the adolescent did not like the taste of the food, or that living with an elimination diet was considered as normal. Conclusion In this population-based study, one in five of children at age 7-8 years reported food hypersensitivity to any food. The generic HRQL was similar among children with and without food hypersensitivity. However, poor disease-specific HRQL was more common among children with current food allergy compared to children with other FHS phenotypes. If the tested food was reintroduced after a DBPCFC, both adolescents and mothers described a changed life with less fear, and that life had become easier regarding meal preparations and social events. As reintroduction failure was present despite a negative food challenge, follow-ups and evaluations of food reintroduction should be performed independent of the outcome of a food challenge.

Bakgrund: Andelen barn med rapporterad födoämnesöverkänslighet har ökat. Prevalensen varierar mycket beroende på var studien genomförts och vilka metoder som använts. Dubbel-blinda placebo-kontrollerade födoämnesprovokationer (DBPCFC) är den mest tillförlitliga metoden för att utesluta eller verifiera födoämnesöverkänslighet. I klinisk praxis används DBPCFC alltmer, men eftersom metoden är resurskrävande används den sällan i populationsbaserade studier. Det saknas kunskap om mödrars och tonåringars egna upplevelser av att delta i DBPCFC och i vilken utsträckning livsmedlet återintroduceras efter en negativ provokation. Studier har beskrivit IgE-medierad födoämnesallergi och dess påverkan på hälsorelaterad livskvalitet men det saknas studier om livskvalitet bland barn med andra fenotyper av födoämnesöverkänslighet.

Syfte: Syfte med avhandlingen var att undersöka rapporterad förekomst av födoämnesöverkänslighet, riskfaktorer och symtomyttringar bland skolbarn. Vi har även studerat hälsorelaterad livskvalitet bland barn som helt eliminerat baslivsmedel, som hel grupp jämfört med barn utan eliminerad föda, samt efter att barnen kategoriserats i olika fenotyper av födoämnesöverkänslighet. Ett ytterligare syfte var att beskriva ungdomars och mödrars upplevelser, konsekvenser av DBPCFC samt i vilken omfattning livsmedlet återintroducerades.

Metod: Tre studier baseras på en barnkohort som rekryterades 2006 inom OLIN studierna (Obstruktiv Lungsjukdom i Norrbotten). Kohorten innefattade alla barn i årskurs 1 och 2 (7-8 år) i Luleå, Kiruna och Piteå där 2585 (96 % av de inbjudna) deltog i en föräldrabesvarad enkät. Enkäten innehöll frågor om födoämnesöverkänslighet, astma, rinit, eksem och möjliga riskfaktorer. Barn från Kiruna och Luleå inbjöds även till pricktest med 10 luftburna allergen och 1700 (90 %) deltog. Artikel I baseras på denna initiala enkätstudie. Fyra år senare följdes kohorten upp med samma metoder och höga deltagande. Totalt 125 barn (5 % av kohorten) uppgav total elimination av mjölk, ägg, fisk och/eller vete på grund av födoämnesöverkänslighet. Dessa barn inbjöds till en klinisk undersökning och 94 barn deltog. Sjuttiofem (80 %) av dessa barn besvarade hälsorelaterade livskvalitetsfrågor innefattande det generiska mätinstrumentet KIDSCREEN-52 samt det sjukdomsspecifika frågeformuläret FAQLQ-TF. Frågeformuläret KIDSCREEN-52 skickades även till ett slumpurval av barn utan eliminationskost från samma kohort, och 209 barn (65 %) deltog. Artikel II baseras på denna hälsorelaterade livskvalitetsstudie. Baserat på den kliniska undersökningen kategoriserades barnen med eliminerad kost i olika fenotyper av födoämnesöverkänslighet: pågående födoämnesallergi, utläkt födoämnesallergi och laktosintolerans. De barn som bedömdes ha pågående födoämnesallergi inbjöds till DBPCFC. Arton månader efter provokationen intervjuades deltagarna om sina upplevelser av provokationen och i vilken omfattning livsmedlet återintroducerades. Artikel III baseras på dessa intervjuer. Den fjärde studien baseras på intervjuer av mödrar vars barn remitterats till en pediatrisk barnallergolog för utredning av misstänkt födoämnesallergi med DBPCFC. Intervjuerna har analyserats med kvalitativ innehållsanalys.

Resultat: Vid 7-8 år var prevalensen av rapporterad födoämnesöverkänslighet 21 %. Överkänslighet mot basföda (mjölk, ägg, fisk, vete eller soja) rapporterades av 10.9% och 14.6% uppgav att de reagerade på frukt eller nötter. Klåda i munnen var det vanligaste rapporterade födoämnesutlösta symtomet som huvudsakligen orsakades av frukt. Det näst vanligaste symtomet var mag- och tarmbesvär, huvudsakligen orsakat av mjölk. Riskfaktormönstret för födoämnesöverkänslighet mot mjölk skiljde sig från överkänslighet mot andra födoämnen. Vi fann ingen statistiskt signifikant skillnad i generisk eller sjukdomsspecifik hälsorelaterad livskvalitet mellan barn som helt eliminerat mjölk, ägg, fisk eller vete på grund av födoämnesöverkänslighet jämfört med barn utan eliminerad kost. En trend indikerade att barn med pågående födoämnesallergi hade sämre sjukdomsspecifik hälsorelaterad livskvalitet jämfört med barn med utläkt födoämnesallergi eller laktosintolerans. Dålig livskvalitet, definierat som den ≥75e percentilen i det sjukdomsspecifika frågeformuläret, var vanligast hos barn med pågående födoämnesallergi. Deltagande i DBPCFC var en möjlighet för tonåringar och mödrar att övervinna rädslan för födoämnesorsakade symtom. I de fall då det testade livsmedlet helt eller delvis återintroducerades efter provokationen, upplevde både tonåringarna och mödrarna att det sociala umgänget blev lättare och att de inte längre behövde ha samma kontroll över födoämnesintaget. Ett negativt provokationsutfall resulterade inte alltid i att det testade livsmedlet återintroducerades i kosten. Orsaker till att inte återintroducera födoämnet var rädsla för allergiska reaktioner, att livsmedlet inte smakade gott och att det upplevdes som normalt att leva ett liv utan det eliminerade livsmedlet.

Slutsats: Vart femte barn rapporterade någon form av födoämnesöverkänslighet i denna populationsbaserade studie. Det var ingen signifikant skillnad i generisk livskvalitet mellan barn med och utan födoämnesöverkänslighet men barn med pågående födoämnesallergi tenderade att ha sämre sjukdomsspecifik livskvalitet jämfört med barn med utläkt födoämnesallergi och laktosintolerans. De deltagare som återintroducerade det testade livsmedlet efter provokationstestet upplevde att livet var mindre begränsat jämfört med innan provokationen. Alla återintroducerade inte det testade livsmedlet trots en negativ provokation, vilket styrker vikten av uppföljning och utvärdering av födoämnesprovokationer.

Background:

While Health Related Quality of Life has been investigated among children with IgE-mediated food allergy, less is known about quality of life among children with other types of hypersensitivity to food. The aim of this study was to investigate Health Related Quality of Life (HRQL) in children with and without food hypersensitivity. Further, we compared HRQL between children with different phenotypes of food hypersensitivity.  

Methods:

In a large population-based cohort of schoolchildren in Northern Sweden, the parents of 2,612 (96% of invited) completed a questionnaire. All 125 (5%) children who reported complete elimination of milk, egg, fish or wheat due to food hypersensitivity were invited to a clinical examination and 94 children participated. Of these, 75 children also completed a generic (KIDSCREEN -52) and a disease-specific HRQL questionnaire (FAQLQ-TF). Thereafter, these children were categorised into the different phenotypes: current food allergy, outgrown food allergy, and lactose intolerance. Additionally, 209 children with unrestricted diets answered the generic questionnaire.

Results:

The median score of all KIDSCREEN -52 domains were above the population norm of 50 both in children with and without food hypersensitivity. No significant differences in distribution in generic or disease-specific HRQL were found between children with or without food hypersensitivity. There were no significant differences in HRQL between children with different phenotypes of food hypersensitivity. However, children with current food allergy tended to have the lowest HRQL. Further, poor HRQL defined as ≥75th percentile for the disease specific score was significantly more common in the current food allergy phenotype in the domain Emotional impact and the total FAQLQ, compared to the other phenotypes.

Conclusions:  

In this population-based study, 12-13 year old children reported good HRQL regardless of having food hypersensitivity or not. However, the children with the current phenotype reported lower HRQL than the other phenotypes. 

AIM: There has been a lack of research on adolescents' who undergo double-blind placebo-controlled food challenges. The aim of this study was to investigate food allergic adolescents' experiences and consequences of double-blind placebo-controlled food challenges.

METHODS: This qualitative, descriptive interview study included 17 adolescents aged 14-15 years with total elimination of cows' milk, hens' eggs or cod due to food allergies. The participants, who were initially identified from a large population-based cohort study, were interviewed 18 months after completing their challenges.

RESULTS: The double-blind placebo-controlled food challenge proved to be a complex experience for the adolescents, involving fear of potential reactions and the hope that the food could be reintroduced. Experiences during the challenge were described in three themes: facing fears in a secure environment, being hesitant but curious about unknown tastes and waiting for unknown food reactions. Experiences after the challenge were desribed in two themes: gaining control and freedom and continuing old habits. A negative challenge was not consistently associated with the reintroduction of the challenged food.

CONCLUSION: This study highlighted the importance of considering the adolescents' expectations and experiences of the challenge and the reintroduction process to ensure desirable changes in their dietary habits. Follow ups should be performed regardless of the outcome of challenges.

AIM: We investigated phenotypes of milk hypersensitivity among schoolchildren aged 11-12 in Northern Sweden.

METHODS: In a population-based cohort, 1,824 (98%) children aged 11-12 participated in a questionnaire survey, skin prick testing, interviews on food hypersensitivity and assessment of body mass index (BMI). Of the 265 children reporting milk hypersensitivity, milk avoidance and no celiac disease, 236 (89%) participated in a structured interview and blood samples for analyses of milk-specific Immunoglobulin E. The children were then categorised into milk hypersensitivity phenotypes according to preset criteria.

RESULTS: In all, 14.5% reported milk hypersensitivity. Of these, 3% were categorised as current milk allergy, 23% as outgrown milk allergy, 40% as probable lactose intolerance and 11% were non-definable. Furthermore, 23% had discontinued their elimination diet. Milk allergy was associated with other atopic disorders and lower BMI, with an odds Ratio of 0.82 and 95% confidence interval of 0.80-0.98. Only 2% had previously undergone an oral challenge.

CONCLUSION: The most common symptom phenotypes among Swedish children aged 11-12 with self-reported milk hypersensitivity and milk avoidance, were lactose intolerance and outgrown milk allergy while current milk allergy was uncommon. Children with milk allergy had a lower BMI and most lacked a challenge proven diagnosis. 

Objectives Knowledge about the prevalence of allergies to foods in childhood and adolescence is incomplete. The purpose of this study was to investigate the prevalence of allergies to milk, egg, cod, and wheat using reported data, clinical examinations, and double-blind placebo-controlled food challenges, and to describe the phenotypes of reported food hypersensitivity in a cohort of Swedish schoolchildren. Methods In a population-based cohort of 12-year-old children, the parents of 2612 (96% of invited) completed a questionnaire. Specific IgE antibodies to foods were analyzed in a random sample (n=695). Children reporting complete avoidance of milk, egg, cod, or wheat due to perceived hypersensitivity and without physician-diagnosed celiac disease were invited to undergo clinical examination that included specific IgE testing, a celiac screening test, and categorization into phenotypes of food hypersensitivity according to preset criteria. Children with possible food allergy were further evaluated with double-blind challenges. Results In this cohort, the prevalence of reported food allergy to milk, egg, cod, or wheat was 4.8%. Food allergy was diagnosed in 1.4% of the children after clinical evaluation and in 0.6% following double-blind placebo-controlled food challenge. After clinical examination, children who completely avoided one or more essential foods due to perceived food hypersensitivity were categorized with the following phenotypes: allergy (29%), outgrown allergy (19%), lactose intolerance (40%), and unclear (12%). Conclusions There was a high discrepancy in the prevalence of allergy to milk, egg, cod and wheat as assessed by reported data, clinical evaluation, and double-blind food challenges. Food hypersensitivity phenotyping according to preset criteria was helpful for identifying children with food allergy.

Background: Double-blind, placebo-controlled food challenges are the gold standard for diagnosing the clinical relevance of a suspected food allergy. Hitherto there are no descriptions on how adolescents' experience this procedure. The aim of this study was to describe adolescents' experiences of double-blind, placebo-controlled food challenges and to what extent the provoked food was reintroduced following the challenge. Method: Seventeen adolescents were interviewed after participating in double-blind, placebo-controlled food challenges. The interview data was analyzed using qualitative content analysis.Results: Experiences during the challenge were: challenging fears in a secure environment, being curious but also hesitant to unknown tastes and waiting for unknown food reactions. Experiences after the challenge were: gaining control and freedom or to stay in old habits. Out of 20 challenges the outcome was negative in 11 cases and positive in 9. Five adolescents with a negative outcome and 4 with mild reactions reintroduced the provoked food. Conclusions: During the challenge the adolescents received knowledge about whether and how they reacted to the provoked food. Reintroduction of the food was not always consistent with the challenge outcome. Independent of the outcome of the challenge and the choices made based on the challenge result, all the adolescents strived for what they felt was a normal life. This study provides a better understanding of young people's experience of double-blind, placebo-controlled food challenge and their motivations to introduce -or not- the previously eliminated food. The result indicate that follow ups are important since the adolescents need support in their striving to manage new food-related situations after the challenge, independent of the outcome.

AIM: This study examined the prevalence, symptom expression and risk factors for food hypersensitivity among Swedish schoolchildren.

METHODS: Parents of 2585 (96% of invited) children aged 7-8 years completed a questionnaire regarding food hypersensitivity and allergic diseases. A random sample of 1700 children (90% of invited) also participated in skin prick testing with ten airborne allergens.

RESULTS: The overall prevalence of reported food hypersensitivity to milk, egg, fish, wheat, soya, fruits and, or, nuts was 21%, with symptoms caused by milk (9%) being the most common. The most frequently reported symptoms were oral symptoms (47.4%), mainly caused by fruit, and gastrointestinal symptoms (45.7%), mainly caused by milk. Factors associated with any food hypersensitivity were female sex, allergic heredity and a positive skin prick test. Eczema was consistently associated with symptoms caused by milk, egg, fish, wheat, soya, fruits and nuts. Rhinitis was associated to the same foods, except milk.

CONCLUSION: Reported food hypersensitivity was common among Swedish schoolchildren. The most frequent symptom expressions were oral symptoms triggered by fruits and gastrointestinal symptoms triggered by milk. The high prevalence of reported symptoms should be validated by clinical examinations to provide a diagnosis.