Impaired health-related quality of life in adolescents with allergy to staple foods

Background Cow’s milk, hen’s egg and wheat are staple foods in a typical western diet. Despite the ubiquity of these foods, the impact of staple food allergy on health-related quality of life (HRQL) amongst adolescents is incompletely understood. The aims of this study were to make use of the Swedish version of EuroPrevall’s disease-specific food allergy quality of life questionnaire-teenager form (FAQLQ-TF) and to investigate the association between objectively-diagnosed staple food allergy and HRQL amongst adolescents. Methods In this cross-sectional study, 58 adolescents aged 13–17 years [n = 40 (69 %) boys] with objectively-diagnosed allergy to the staple foods cow’s milk, hen’s egg and/or wheat and living in Stockholm, Sweden were included. Adolescents completed the FAQLQ-TF, which has a corresponding scale of 1 = best HRQL, and 7 = worst HRQL. Overall HRQL and domain-specific HRQL were established. Adolescents also reported symptoms, adrenaline auto injector (AAI) prescription and presence of other food allergies. A history of anaphylaxis was defined among those reporting difficulty breathing, inability to stand/collapse, and/or loss of consciousness. Clinically different HRQL was set at a mean difference of ≥0.5. Results Overall mean HRQL was poorer than average [mean: 4.70/7.00 (95 % CI 4.30–5.01)]. The domain risk of accidental exposure was significantly associated with clinically better HRQL than the domain allergen avoidance and dietary restrictions (mean difference = 0.76; p < 0.001). Girls had clinically worse, but not statistically significantly different mean HRQL than boys (mean difference = 0.71; p < 0.07). HRQL tended to be worse amongst those with allergies to more than three foods or an AAI prescription. The number and types of symptoms, including a history of anaphylaxis were not associated with worse HRQL. Conclusions As ascertained via a food allergy-specific questionnaire, adolescents with staple food allergy report poorer than average HRQL, specifically in relation to emerging independence and the need for support. Girls have clinically worse HRQL than boys. The number and type of previous symptoms and history of anaphylaxis were not associated with worse HRQL. Electronic supplementary material The online version of this article (doi:10.1186/s13601-016-0128-5) contains supplementary material, which is available to authorized users.


Background
Food allergy affects 2-8 % of adolescents [1,2]. In this group, health-related quality of life (HRQL) or 'the effects of an illness and its consequent therapy upon a patient, as perceived by the patient [3], may be impacted [4][5][6], particularly in relation to social well-being and independence [7]. Further, adolescents with food allergy report worse overall HRQL compared to matched non-food allergic controls [4,5], or to adolescents with other chronic conditions [4,8]. Notably, these studies involved the use of generic HRQL questionnaires [4,5,8], which may not identify the subtleties of food allergy or issues specific to the disease [9]. To address this limitation, EuroPrevall's

Open Access
Clinical and Translational Allergy *Correspondence: staffan.ahlstedt@ki.se 1 The Centre for Allergy Research, Karolinska Institutet, P.O. Box 287, 17177 Stockholm, Sweden Full list of author information is available at the end of the article food allergy-specific HRQL questionnaires were specifically developed and validated to glean insights into food allergy that cannot be ascertained by generic questionnaires [9,10]. The self-reported adolescent version of this questionnaire, the food allergy quality of life questionnaire-teenager form (FAQLQ-TF), presents a unique means by which to capture perceptions of HRQL of adolescents with food allergy. Self-reported data for this age group is important given the disagreement between adolescent-and parent-reported HRQL [6].
Previous studies on HRQL amongst adolescents with food allergy have focused on a wide range [4,6] or unspecified [5] foods, as well as reported, rather than objectively diagnosed food allergies [5]. However, we believe that objectively diagnosed allergies to certain foods warrant particular attention. For example, allergies to the staple foods cow's milk, hen's egg [11] and wheat [12], typically present in infancy and often exist concomitantly [12]. Although these allergies often resolve by school age [11,12], those with more severe symptoms or multiple food allergies may experience persistence of staple food allergy through later ages [11,12]. As staple foods are ubiquitous in a typical western diet and are consequently difficult to avoid, the HRQL of adolescents experiencing disease persistence is likely to be impacted. Thus, we hypothesised that adolescents with staple food allergies would have poor HRQL, and that adolescents with a history of severe symptoms would have the worst HRQL. To this end, the aims of this study were to make use of the Swedish version of EuroPrevall's FAQLQ-TF and to investigate the association between objectively-diagnosed staple food allergy and HRQL amongst adolescents.

Study design and participants
In this cross-sectional study, adolescents aged 13-17 years with paediatric allergist-diagnosed allergy to one or more staple foods (cow's milk, hen's egg and/ or wheat) were identified from medical records and recruited in 2010-2012 by a paediatric nurse from the outpatient allergy clinic at Sachs' Children and Youth Hospital, Södersjukhuset, in Stockholm, Sweden.
Inclusion criteria were a convincing history of allergy to one or more of the above-mentioned staple foods ascertained either by a positive food challenge with evident symptoms, or by levels of food specific Immunoglobulin E (IgE) antibodies levels associated with a 95 % probability of a positive result in a double-blind placebo controlled food challenge [13]. Exclusion criteria were an unclear allergy diagnosis to staple food(s), poor understanding of the Swedish language, or presence of coeliac disease, diabetes and/or a malignancy. Information on concomitant allergic disease (asthma, allergic rhinitis, allergic conjunctivitis, eczema) was also obtained. A total of 87 adolescents were eligible and invited to participate. These adolescents were mailed the FAQLQ-TF (described below, English version available as an Additional file 1), as well as an information letter and a postage-paid return envelope. Parents were mailed an information letter and consent form. Completed FAQLQ-TF and signed parental consent forms were received from 58 adolescents (67 % of those eligible; Fig. 1). Adolescents received two movie tickets following receipt of completed questionnaires. This study was approved by the Regional Ethical Review Board in Stockholm, Sweden (Dnr 2009/84-31/5). Personal data were treated according to the Swedish Personal Data Act.

Exposures
Both the number of staple food allergies, as well as the number of offending foods (at least one staple food allergy and, participant-reported allergies to other foods) were considered as exposures.
Adolescents responded to 36 closed-ended questions on food allergy symptoms, from which we generated specific symptoms: Gastrointestinal: stomach upset; vomiting; diarrhoea. Oral: itchy tongue, mouth or lips; swollen tongue or lips.
The most severe symptoms, including difficulty breathing, inability to stand/collapse, and/or loss of consciousness, involved the respiratory-and/or cardiovascular/ neurological systems. In keeping with our previous publications on children [27] and adults [26], and approximating as best as possible the criteria outlined by Sampson et al. [14], such symptoms are collectively referred to as anaphylaxis. Adolescents were asked if they had been prescribed an adrenaline auto injector (AAI).

Food allergy quality of life questionnaire-teenager form (FAQLQ-TF)
The FAQLQ-TF [9] was translated into Swedish as per World Health Organization guidelines [15], and was piloted in 10 Swedish-speaking adolescents to ascertain comprehension. Following minor linguistic adjustments, the translation was deemed adequate. The FAQLQ-TF contains 28 questions on HRQL, each of which has corresponding closed-ended answers on a 7-point scale where 1 is best HRQL and 7 is worst HRQL [9]. Overall HRQL established by taking the mean of the 28 questions. These questions were also designed to address three domains: allergen avoidance and dietary restrictions (AADR), emotional impact (EI) and risk of accidental exposure (RAE). The first domain, AADR, describes adolescents' perceptions of limitations, hesitations and refusals of foods that they purchase or are offered in social situations. The second domain, EI, reflects adolescents' fears of an allergic reaction or accidental consumption of the food(s) to which they are allergic and their disappointment when others do not take their food allergy seriously. The third domain, RAE, captures adolescents' assessments of needing to be cautious about purchasing food or eating out in relation to changes in ingredients, incorrect disclosure of ingredients and touching certain foods.

Statistics
Floor and ceiling effects (percentages of patients with minimal and maximum scores, respectively) of the FAQLQ-TF were calculated to verify discriminative capacity. These effects were considered present if >15 % of a sample of a minimum of 50 individuals achieved the lowest or highest possible scores, respectively. Absence of these effects demonstrates the efficacy of the questionnaire.
Descriptive statistics included sample sizes (n), percentages, means, parametric two-sample t-tests and 95 % CI. Statistical significance was set at p < 0.05. Overall and domain-specific HRQL scores were calculated for the entire study population and stratified by gender. To permit statistical comparisons, the number of staple food allergies was classified into 2 dichotomous groups: 1 vs. 2-3. The number of offending foods was classified into 4 groups: 1, 2, 3 or >3. As described above, adolescents reported on symptoms. Adolescents may forget or inaccurately report their symptoms. Thus, we performed intraclass correlations of adolescent-reported symptoms with those reported by their parents as part of a parallel study [32] to measure reliability. These analyses showed modest correlations between adolescent-and parent-reported symptoms, with increasing reliability with increasingly severe symptoms (results not shown). As such, we present the results herein based on adolescent-reported symptoms.
Univariable and multivariable linear regression analyses were performed to identify predictors of HRQL. Potential covariates were identified based on prior knowledge of the exposures and outcome. The covariates gender, number of symptoms, history of anaphylaxis, AAI prescription and concomitant allergic disease were included in the final model as they statistically and independently altered the prediction model. The same models were used for overall and domain-specific HRQL. In keeping with previous publications on HRQL assessed via the FAQLQ, a score of ≥ ±0.5 was considered to be clinically relevant [9,16]. Analysis was performed with STATA Statistical Software (release 13.1; StataCorp, College Station, Texas, USA).

Results
The discriminant capacity of the FAQLQ-TF was confirmed as domain-specific floor and ceiling effects were below 15 % (results not shown).
Our study population included 58 adolescents, of whom 40 (69 %) were boys (Table 1). Most (62 %) of participants were allergic to only one staple food, although 7 % were allergic to all three staple foods. The most common staple food allergy was to hen's egg (79 %). Other participant-reported allergies to other foods, particularly to tree nuts (60 %) and peanuts (53 %), were also common. Nearly all adolescents reported lower respiratory (95 %) and dermatological (90 %) symptoms. Gastrointestinal symptoms were also common (68 %). Although symptoms involving the cardiovascular/neurological system were the least common, they were nonetheless reported by 27 % of adolescents.
With consideration to the different domains, the mean scores for AADR and EI were comparable (Fig. 2) Investigation to the individual questions of each domain revealed further insights into the fine tuning of the HRQL of the different domains. For example, in the domain AADR, compared to the question with the highest mean score (i.e. worst HRQL), 'How troublesome  Table 2). In linear regression analyses adjusted for sex, number of symptoms, history of anaphylaxis, AAI prescription and concomitant allergic disease (excluding the predictor), girls had clinically worse and but not statistically significant HRQL than boys (B = −0.58; 95 % CI −1.34; 0.19; p = 0.13; Table 3). Similarly, allergies to >3 staple food allergies and AAI prescription reached the threshold of ≥0.5 for clinical relevance but only trended towards significance (p = 0.13 and p = 0.06, respectively).
Consideration to the presence vs. absence of specific symptoms including anaphylaxis attributable to staple foods yielded no statistically significant associations. Only previous lower respiratory symptoms reached the threshold for clinically better HRQL (B = 0.67; 95 % CI −1.37; 2.70, p = 0.51; Table 4).

Discussion
In this cross-sectional study of adolescents with objectively-diagnosed staple food allergies to cow's milk, hen's egg and/or wheat, overall HRQL, as ascertained by a food allergy specific questionnaire, was poorer than average. The domain risk of accidental exposure was significantly associated with clinically better HRQL than the domain allergen avoidance and dietary restrictions. Girls had clinically worse, but not statistically significantly different HRQL than boys. HRQL tended to be worse amongst adolescents with allergies to more than three foods or those who had been prescribed an AAI. In contrast, the number and type of previous symptoms and history of anaphylaxis were not associated with worse HRQL.
We highlight the key strengths of this study we used a food allergy-specific questionnaire that is robust for adolescents with food allergies [9,17] that provided insights into associations between food allergy and HRQL that could not have been gleaned via a generic questionnaire [9]. Similarly, this work presents the first results of the Swedish version of the FAQLQ-TF. In our study, participants had objectively-diagnosed allergies, thus providing insight into the impact of true, rather than perceived, food allergy on HRQL. Amongst children, HRQL does not differ between these two phenotypes [18]. However, consideration of the association between objectivelydiagnosed allergy and adolescent-reported HRQL warrants consideration as this age group is increasingly responsible for their own food choices, and thus the potential consequences of inappropriate food choices. Although adolescents' food choices are influenced by their allergies, they also make choices based on peers and sensory preferences [19]. We believe that we are the first group to report on HRQL amongst adolescents with allergies to foods that are ubiquitous in a typical western diet, but which also receive less attention in relation to HRQL than other common food allergens, such as peanuts or tree nuts.
We also acknowledge the limitations of our study. Our study was cross-sectional in design, thereby precluding establishment of a causal relationship between staple food allergy and HRQL. As well, our study population included more boys than girls. As evidenced in the general adolescent population [20], and amongst food hypersensitive adolescents for whom HRQL was established using a generic questionnaire [5], boys generally have better HRQL than girls. Thus, we surmise that, had adolescent boys and girls been equally represented, overall HRQL may have been even worse.
The FAQLQ-TF is specifically designed to capture adolescents' perceptions of HRQL [9]. Elsewhere, responses from Dutch adolescent-parent pairs to the FAQLQ have been compared [6]. In that study, adolescents were  Fig. 2 Overall-and domain-specific HRQL mean scores and 95 % CI for adolescents with objectively-diagnosed staple food allergy. Asterisk FAQLQ-TF on a scale of 1-7, where 1 corresponds to best HRQL and 7 corresponds to worst HRQL; based on self-report. † Compared to AADR (p < 0.001). HRQL health-related quality of life, AADR allergen avoidance and dietary restrictions, EI emotional impact, RAE risk of accidental exposure allergic to a wide range of common food allergens, but staple food allergy did not predominate. Amongst these adolescent-parent pairs, adolescents reported clinically worse, but not statistically significant differences in HRQL. This finding underscores the need to specifically query adolescents' perceptions of HRQL and address not only statistical differences but consideration to the magnitude of the differences. Interestingly, our domainspecific scores exceeded the clinically relevant difference of ≥0.5 compared to the Dutch study [6], as well as other studies in which the FAQLQ-TF was used [6,9,17,21]. Collectively, these studies suggest that staple food allergy is associated with worse HRQL than allergies to other foods. One can speculate that this may be due to the ubiquity of staple foods in a typical western diet, making them challenging to avoid. This challenge may be compounded by the fact that, although many countries have regulatory frameworks for allergens contained in processed foods [22], such labelling most commonly identifies non-staple foods [23] and may contribute to confusion and complacency amongst food allergic individuals [24,25].
We identified that staple food allergy impacted on adolescents' lifestyles, as underscored by poorer than average overall HRQL mean score [i.e. better HRQL], as well as within the domain, AADR. Others have reported similar findings on the impact of food allergy on adolescents' lifestyles [6]. The similarities between these findings are not surprising, as adolescents spend increasing amounts of time in social settings away from home. However, our findings extend those of previous studies, as we were able to disentangle the specific factors that contributed most to worse HRQL. In the present study, adolescents reported worse HRQL related to emerging independence and the need for support, as evidenced by domain-specific mean scores which were highest for the questions relating to needing to check for themselves if they can eat a food whilst dining out, expressing disappointment when their food allergies are not taken into account, or explaining to others about their food allergy. Previously, we reported that differences between the domains were present amongst adults [26], but not children [27] with staple food allergy. As with adults [26] and children [27], adolescents with staple food allergy reported significantly worse HRQL if they had multiple food allergies or possessed an AAI. Likewise, both adolescents and adults [26] reported worse HRQL within the domain AADR. As different domains were defined for children, a comparison of the domains between children and adolescents is not possible. In contrast to both adults [26] or children [27], adolescents did not report worse HRQL in association with a history of anaphylaxis or the number and type of symptoms. Taken together, it could be speculated that children may not feel burdened by the dietary restrictions imposed by staple food allergy, likely as the responsibility for safe food choices is assumed by their parents/guardians, whereas adolescents and adults do have to assume this responsibility. The burden of dietary restrictions and safe food choices has also been qualitatively explored amongst adolescents. Unlike nonfood allergic adolescents, those with food allergies feel safe under parental control and thus do not necessarily want to make food-related decisions independently [19]. Adolescents with food allergy describe themselves as being very mature for their age, yet dependent on others in the event of a reaction [28]. One can speculate that these opposing characteristics may result in worse food allergy-specific HRQL.
Unlike other chronic conditions which adolescents may neglect or be non-compliant [29], food allergy cannot be ignored for longer than an interval between meals or snacks. But given that food is an integral part of social events, feelings of exclusion and 'being different' may   [7]. This may begin to explain why food allergy is strongly associated with worse HRQL. This may also explain why neither the number of allergies or symptoms, nor AAI prescription is a predictor of clinically worse HRQL. Further, adolescents often base their food choices primarily on enjoyment and secondarily on content [19], thereby engaging in risk taking behaviours [30] that may potentially lead to severe reactions. Yet, like others [9], we found no difference in HRQL between those with vs. without a history of anaphylaxis. The financial burden of food allergy on healthcare systems [31] and on households [32] is high, and allergyrelated hospitalisations are increasing [33]. Worse HRQL also predicts greater healthcare costs [34]. Thus, addressing HRQL amongst adolescents, as well as children [27] and adults [26] with staple food allergy warrants considerable attention.

Conclusions
As ascertained via a food allergy-specific questionnaire, adolescents with staple food allergy report poorer than average HRQL, specifically in relation to emerging independence and the need for support. Girls have clinically worse HRQL than boys. The number and type of previous symptoms and history of anaphylaxis were not associated with worse HRQL (Additional file 1.).