FOOD ALLERGIES: CHARTING A ROADMAP TO SAFETY

Over the past 20 years, public concerns have grown in response to the apparent rising prevalence of food allergy and related atopic conditions,¹ such as eczema. Although evidence on the true prevalence of food allergy is complicated by insufficient or inconsistent data and studies with variable methodologies, many health care experts who care for patients agree that a real increase in food allergy has occurred and that it is unlikely to be due simply to an increase in awareness and better tools for diagnosis. Many stakeholders are concerned about these increases, including the general public, policy makers, regulatory agencies, the food industry, scientists, clinicians, and especially families of children and young people suffering from food allergy.

Food allergy has important implications not only for those individuals directly affected but also for their families, day care and school settings, and society (Gupta, 2014; Pawanker et al., 2011). Some children naturally grow out of a food allergy, while other children or adults develop a food allergy for the first time later in life. In either case, having a food allergy is a chronic disease that can influence a person's quality of life throughout the lifespan and, in some unfortunate individuals, lead to death. The human stories of food-related anaphylaxis and the heavy burden of protecting children from foods that might initiate such serious allergic conditions are particularly compelling. This burden includes fear of accidental consumption, difficulties with missing (or misunderstood) food labels, and bullying at school. Those not afflicted with such a disorder may have difficulty even imagining what life is like for severely food-allergic individuals, some of whom are allergic to multiple commonly encountered foods, such as milk, eggs, peanuts, tree nuts, and shellfish. To illustrate some of these issues, Box 1-1 includes real-life example statements from children, adolescents (DunnGalvin et al., 2009) and caretakers (Kahn, 2014; Monaco, 2015) as they describe quality-of-life impacts and hazards of having a severe food allergy.

BOX 1-1

Statements from Children or Their Caretakers.

Ultimately, answering questions about the actual prevalence of food allergy, the mechanisms underlying allergen sensitization and the development of food allergy, and how to estimate the severity of disease in affected individuals, among many other research questions, requires adequate support from research funding sources. Similarly, protecting those with food allergy from accidental exposure and providing appropriate treatment for those who develop reactions, demand effective governmental policy and consumer protections across multiple sectors, including agricultural production, the food industry, product labeling, regulatory authorities, and the food and entertainment industries. At the present time, however, despite a mounting body of data on the prevalence, health consequences, and associated costs of food allergy, this chronic disease has not garnered the level of societal attention that it warrants. Moreover, for patients and families at risk, recommendations and guidelines have not been clear about preventing exposure or the onset of reactions or for managing this disease.

In brief, the scientific knowledge about food allergy has significant gaps and, for those at risk, few or no reliable prevention strategies or treatments exist. How did we get to this situation? First, the accepted gold standard for identifying a food allergy—the oral food challenge (OFC)—has not been used widely due to difficulties of the procedure (e.g., risk of a severe reaction, length of procedure, the need to standardize the food), especially in research where large numbers of study participants are needed.

Second, conducting research on food allergy presents various types of practical barriers: studies are very costly due to the long duration of typical therapeutic studies (e.g., 2 to 4 years); the heterogeneity of participants; difficulty recruiting participants; and notably, too few research centers and researchers equipped to conduct high-quality studies.

Third, food allergy is a complicated, multifactorial disease and researchers do not fully understand its causes, mechanisms, and effects. Except for having atopic parents (i.e. parents with a predisposition to allergic reactions), the contributions of various factors to food allergy remain unclear and under investigation. Genetics, time, route of allergen exposure, diet, factors related to pregnancy and lactation, and the microbiome all are being studied as potential influences on the development of food allergy. The fact that food allergy develops in infants makes the research difficult, as conducting trials during pregnancy or in infants could be unethical.

Finally, few effective therapies for food allergy currently exist. The gaps in scientific understanding have impaired the development of effective therapies, although many promising ones are being investigated.

Professional medical associations continue to update their practice guidelines for food allergy despite limitations in the evidence, based on the most recent knowledge on diagnosis, prevention, treatment, and management. Yet, unlike other chronic diseases related to diet, such as diabetes or cardiovascular diseases, where specific strategies for prevention or management have been established (ADA, 2015; Goff et al., 2014), recommendations by governments or professional associations for preventing the onset of a food allergy have been hampered by limited or inconsistent data. Recent and ongoing research and clinical progress on assessment, diagnosis, and treatment of food allergy hold the promise of improving future practice and management strategies. These advances include the safe use of OFCs as the gold standard for diagnosis, emerging data on the role of early exposure to potential allergens for favoring prevention, and high-quality studies of effective therapies. Indeed, based on the latest findings in food allergy prevention science, and particularly the latest findings on the protective effects of early exposure to peanut, leading organizations are rethinking the current recommendations and considering promising new approaches. Still, new thinking and approaches can have the unintended consequence of confusing parents and all the institutions that interact with people with food allergy, including schools, airlines, and restaurants.

For individuals who are already diagnosed, complete avoidance is still the only established method for preventing a reaction and, as indicated in Box 1-1, it is not easy to achieve. This is particularly the case when effective policies and practices are not implemented in places where foods are purchased or consumed (e.g., the hospitality and food service industries). Likewise, policies to ensure that relevant settings are prepared to identify and treat a severe reaction are not always enacted, implemented, or enforced. For example, epinephrine may not be available in relevant places, such as early care and education centers, schools, afterschool programs, camps, or airplanes. To promote greater safety in such settings, nongovernmental organizations are creating tools and guidelines to increase awareness, help parents and children with strategies for avoiding allergens, advocate for better policies, and/or increase the effectiveness of research efforts. Likewise, professional organizations of various industry sectors (e.g., manufacturers, retailers, food service) have created guidelines and training programs for their stakeholders. Federal, state, and local governments also are beginning to include allergy management as an element of their food safety policies. However, despite all the policies and guidelines for the various settings (e.g., food industry practices, regulatory agencies, early care and education centers, schools, higher education, and public transport), their development may not be keeping pace with the science and their implementation and enforcement varies greatly across the United States.

In addition, food allergy is a major global challenge and prevention strategies are needed across the globe. Although the prevalence and implementation of policies will vary by country, similar management approaches could be adopted across countries.

For all of these reasons, it was thought to be timely and important, in the interest of public health, for the National Academies of Sciences, Engineering, and Medicine to conduct a consensus study to review the science and management practices of food allergy. The committee intends that this report will (1) clarify the nature of the disease, its causes, and its current management, (2) highlight gaps in knowledge, (3) encourage the implementation of management tools at many levels and among many stakeholders, and (4) delineate a roadmap to safety for those who have, or are at risk of developing, food allergy, as well as for others in society who are responsible for public health.

STATEMENT OF TASK

This study originated as a result of the broad public interest in the health aspects of food allergy; the relevance to public health, health care, and society; and the current lack of solutions both for the prevention of food allergy and its management. The apparent increase in food allergies, and concerns about a lack of good management strategies, prompted informal discussions that resulted in a planning meeting in Washington, DC, under the auspices of the National Academies of Sciences, Engineering, and Medicine on May 24, 2014. Various experts gave presentations on what is known about food allergy prevalence, causes, and risk determinants; perceptions regarding food labeling; and treatment approaches. Representatives from stakeholder groups with an interest in food allergy also attended. The group discussed the concerns related to those topics and provided comments about questions that would be of value to include in a consensus study from the National Academies. Following this meeting, a Statement of Task (see Box 1-2) was developed with contributions from all stakeholders.

APPROACH OF THE COMMITTEE

Expert Committee and Advisory Panel

An ad hoc committee of 15 experts was selected and nominated to respond to the statement of task. Committee members were drawn from a broad range of disciplines, including food allergens and methods of detection, pediatrics, clinical medicine, immune-related illness, genetics, epigenetics, the microbiome, epidemiology, biostatistics, nutrition/dietetics, food safety, public education, public health policy, clinical trials, prediction and prevention of food allergy, and child development. To expand the geographical context and experiences, food allergy experts from the United Kingdom and Australia were included in the committee. The committee held one public session on June 22, 2015, and one public workshop on August 31-September 1, 2015, to gather information. The committee also met on five occasions in closed sessions to discuss the findings, draw conclusions, and craft recommendations. The public session and workshop were valuable in providing the committee with the perspectives of sponsoring organizations and with information regarding diverse aspects related to the task (see Appendix A for public sessions and workshop agenda).

In order for the committee to consider the perspectives of those affected by food allergy, the study also included an advisory panel made up of nine parents of children with food allergies and one individual with food allergy. The advisory panel members were selected from a group of approximately 50 individuals recommended by the sponsor organizations. All members of the advisory panel live with the challenges of food allergy on a daily basis and some are active advocates in their communities, participants in policy work and public speaking, or mentors for families who are new to food allergy. Although their opinions may not represent those of all people with the disease, they were invaluable to the committee as good examples of the sentiments and burden of living with food allergy. Some of the concerns brought up by this panel included the need for more clarity in food labeling, appropriate training for emergency personnel, access to epinephrine, and for improvements in well-being and safety at specific settings, such as schools, camps, restaurants, and transportation.

BOX 1-2

Statement of Task.

Boundaries and Clarifications About the Task

As mentioned above, food allergy, as a chronic disease, shares characteristics with other conditions and diseases. It is therefore necessary to be very clear about the task and its interpretation by the committee. The committee focused its efforts on the questions in the statement of task as they refer to the definition of food allergy by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). This definition states that food allergy is “an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food.” Food allergies fall into two major types—immunoglobulin E (IgE)-mediated and non-IgE-mediated—and the committee focused mostly on IgE-mediated food allergies (see Chapter 2 for definitions). Some of the discussions, where appropriate, also pertained to non-IgE-mediated food allergies, such as food protein–induced enterocolitis, particularly when discussing diagnostic methodologies that are unique for each type of food allergy. However, the literature reviews, findings, conclusions, and recommendations reviewed in this consensus study refer exclusively to IgE-mediated food allergies. Other food-related diseases, such as celiac disease, or food intolerances, such as lactose intolerance, or toxicity of food additives, are not covered in this report because they were beyond the scope of the statement of task.

Although any protein can be allergenic, certain proteins and specific foods that contain them (e.g., Ara h 2 in peanut) are characteristically allergenic and have been recognized as such because of the frequency or severity of the symptoms they cause in individuals at risk. The list of common allergenic foods varies by country. This variation is often due to the nature of diets or native foods in a given region but also to different criteria that are used to qualify a food for inclusion in the list. The committee's literature reviews were conducted from the perspective of foods that are considered allergenic in the United States. However, global evidence was considered to the extent that it informed the central issues the committee reviewed. Moreover, most recommendations also apply to any allergenic food today or those that may become clinically important allergens in the future. The committee did not review the scientific or regulatory aspects of the potential for proteins from genetically modified foods to be allergenic. The reader is referred to the 2016 National Academies of Sciences, Engineering, and Medicine report Genetically Engineered Crops: Experiences and Prospects for a review and recommendations on this topic (NASEM, 2016).

Although the study is meant to have a global perspective, it would not be feasible to answer all the questions in the statement of task from the perspective of all countries. Research data are being generated worldwide but implementation of research findings depends on contextual factors that would be different for each country or region. When it was valuable and feasible to do so, data collected about implementation in the United States, as well as in other countries, were used to guide the committee's deliberations and recommendations. It should be noted that while the recommendations are focused on the United States, many could be implemented in other regions of the world.

This report is not meant to duplicate or replace important guidelines that have been developed in the past and that will continue to provide essential information about progress in diagnosis, treatment, and management of food allergy in the United States. Instead, this report is meant to be a call for unified action among all stakeholders and the public, both to recognize the importance of this disease and to join forces in efforts to markedly improve our ability to understand, effectively manage, and ultimately, cure this disease, and to make the world safer for those afflicted with it. Rather than conducting evidence-based reviews for all topics relevant to the task, the committee offered the support of specific guidelines where appropriate. In addition, the committee has conducted selected evidence-based reviews of the scientific literature where recent developments or the need for reinforcement deemed it necessary. Moreover, the committee did not review therapeutic approaches that are currently being investigated and instead recommended more research efforts in this area. These key guidelines include the following: 2010 NIAID/NIH-sponsored Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel (Boyce et al., 2010), the European Academy of Allergy & Clinical Immunology (EAACI) Food Allergy and Anaphylaxis Guidelines (Muraro et al., 2014), two Practice Parameters (Lieberman et al., 2015; Sampson et al., 2014), and two Clinical Reports (Sicherer et al., 2007, 2010). Table 1-1 includes the guidelines (and systematic reviews on which they were based) and the names by which they are referred to in this report.

TABLE 1-1

Food Allergy Guidelines and Systematic Reviews.

A DEVELOPMENTAL AND ECOLOGICAL PERSPECTIVE ON FOOD ALLERGY

During its review and deliberations, the committee recognized that addressing the task and goals of the consensus study would benefit from taking a developmental and ecological perspective. Preventing and treating food allergy, and delineating a roadmap to safety are a multifaceted undertaking that must take into account many interacting systems that influence both risks and safety. For every individual, the risks and possible protections for food allergy vary and change over the life course, depending on individual genetic factors, biological development, exposures to allergens, and the nature of the contexts in which the individual lives. From a societal and public health perspective, the safety and well-being of many potential individuals with food allergy requires recognition that risks and protections for public safety are spread across many systems, including food production and distribution systems, health care systems, and education systems, among others. This section explains how the committee undertook a developmental and ecological approach toward the health and safety of individuals with food allergy.

ORGANIZATION OF THE REPORT

This introductory chapter describes how and why the study originated, the charge to the committee, and the developmental and ecological context. Chapter 2 is a background chapter that describes the definition of food allergy that the committee adopted, explains common food allergy signs and symptoms, summarizes common allergenic foods, and explains the mechanism of food allergy. It also comments on the misinformation among the many stakeholders in regard to what a food allergy is and how to prevent and manage it. Chapter 3 summarizes what is known about the prevalence of food allergy in the United States and abroad, highlighting the limitations in methods, especially in regard to prevalence trends. Chapter 4 includes the current diagnostic and prognostic methods used and others that are under investigation. Chapter 5 presents current knowledge about prenatal and early life determinants of food allergies, including genetic and environmental factors. Chapters 6, 7, and 8 contextualize the ways in which food allergy is currently managed in the health care system (Chapter 6), the food manufacturing industry (Chapter 7), and other settings such as schools and restaurants (Chapter 8). Chapter 9 includes all the committee's recommendations for research. Finally, Chapter 10 culminates with the committee's vision of a roadmap to safety, discussing how food allergy can be prevented and managed based on evolving knowledge, taking into consideration the roles and responsibilities of the many actors and settings that an individual interacts with throughout the life course.

The committee envisions that this report will reach the many stakeholders, including the general consumer, patients, health care providers, school leaders, food manufacturers and establishment managers, and serve as guidance for future understanding and management of food allergies. The committee also has confidence that the recommendations in this report, if implemented, will stimulate progress in the understanding of food allergies, reduce further uptakes in prevalence, and improve the quality of life of those with this chronic disease and their caregivers.

REFERENCES

• ADA (American Diabetes Association). Clinical practice recommendations. 2015. [April 29, 2016]. http://www​.diabetes.org​/research-and-practice​/we-support-your-doctor​/clinical-practice-recommendations.html.
• Boyce JA, Assa'ad A, Burks AW, Jones SM, Sampson HA, Wood RA, Plaut M, Cooper SF, Fenton MJ, Arshad SH, Bahna SL, Beck LA, Byrd-Bredbenner C, Camargo CA Jr., Eichenfield L, Furuta GT, Hanifin JM, Jones C, Kraft M, Levy BD, Lieberman P, Luccioli S, McCall KM, Schneider LC, Simon RA, Simons FE, Teach SJ, Yawn BP, Schwaninger JM. Guidelines for the diagnosis and management of food allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report. J Allergy Clin Immunol. 2010;126(6):1105–1118. [PMC free article: PMC4241958] [PubMed: 21134568]
• Boyce WT, Kobor MS. Development and the epigenome: The “synapse” of gene-environment interplay. Devel Sci. 2015;18(1):1–23. [PubMed: 25546559]
• Bronfenbrenner U. The ecology of human development: Experiments by nature and design. Cambridge, MA: Harvard University Press; 1979.
• Bronfenbrenner U, Morris PA. Damon W, Lerner RM. Handbook of Child Psychology. 6th ed. 4 vols. Hoboken, NJ: John Wiley & Sons; 2006. The ecology of developmental processes.
• Chafen JJ, Newberry SJ, Riedl MA, Bravata DM, Maglione M, Suttorp MJ, Sundaram V, Paige NM, Towfigh A, Hulley BJ, Shekelle PG. Diagnosing and managing common food allergies: A systematic review. JAMA. 2010;303(18):1848–1856. [PubMed: 20460624]
• de Silva D, Geromi M, Panesar SS, Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Cardona V, Dubois AE, Halken S, Host A, Poulsen LK, Van Ree R, Vlieg-Boerstra BJ, Agache I, Sheikh A. Acute and long-term management of food allergy: Systematic review. Allergy. 2014;69(2):159–167. [PubMed: 24215577]
• Del Giudice M, Ellis BJ, Shirtcliff EA. The Adaptive Calibration Model of stress responsivity. Neurosci Biobehav Rev. 2011;35(7):1562–1592. [PMC free article: PMC3068241] [PubMed: 21145350]
• Dhami S, Panesar SS, Roberts G, Muraro A, Worm M, Bilo MB, Cardona V, Dubois AE, DunnGalvin A, Eigenmann P, Fernandez-Rivas M, Halken S, Lack G, Niggemann B, Rueff F, Santos AF, Vlieg-Boerstra B, Zolkipli ZQ, Sheikh A. Management of anaphylaxis: A systematic review. Allergy. 2014;69(2):168–175. [PubMed: 24251536]
• DunnGalvin A, Gaffney A, Hourihane JO. Developmental pathways in food allergy: A new theoretical framework. Allergy. 2009;64(4):560–568. [PubMed: 19154549]
• Figueiredo CA, Amorim LD, Alcantara-Neves NM, Matos SMA, Cooper PJ, Rodrigues LC, Barreto ML. Environmental conditions, immunologic phenotypes, atopy, and asthma: New evidence of how the hygiene hypothesis operates in Latin America. J Allergy Clin Immunol. 2013;131(4):1064–1068. [PMC free article: PMC5027909] [PubMed: 23414599]
• Goff DC Jr., Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R, Greenland P, Lackland DT, Levy D, O'Donnell CJ, Robinson JG, Schwartz JS, Shero ST, Smith SC Jr., Sorlie P, Stone NJ, Wilson PW, Jordan HS, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr., Tomaselli GF., American College of Cardiology/American Heart Association Task Force on Practice 2014. ACC/AHA guideline on the assessment of cardiovascular risk: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;129(25 Suppl 2):S49–S73. [PubMed: 24222018]
• Gottlieb G. Probabilistic epigenesis. Devel Sci. 2007;10(1):1–11. [PubMed: 17181692]
• Guerra S, Martinez FD. Asthma genetics: From linear to multifactorial approaches. Ann Rev Medicine. 2008;59:327–341. [PubMed: 17845134]
• Gupta RS. Anaphylaxis in the young adult population. Am J Medicine. 2014;127(1 Suppl):S17–S24. [PubMed: 24384134]
• Halfon N, Larson K, Lu M, Tullis E, Russ S. Lifecourse health development: Past, present and future. Matern Child Health J. 2014;18(2):344–365. [PMC free article: PMC3890560] [PubMed: 23975451]
• Hammond RA. Complex systems modeling for obesity research. Prev Chronic Dis. 2009;6(3):A97. [PMC free article: PMC2722404] [PubMed: 19527598]
• Hochberg Z, Feil R, Constancia M, Fraga M, Junien C, Carel JC, Boileau P, Le Bouc Y, Deal CL, Lillycrop K, Scharfmann R, Sheppard A, Skinner M, Szyf M, Waterland RA, Waxman DJ, Whitelaw E, Ong K, Albertsson-Wikland K. Child health, developmental plasticity, and epigenetic programming. Endocr Rev. 2011;32(2):159–224. [PMC free article: PMC3365792] [PubMed: 20971919]
• IOM (Institute of Medicine). Preventing childhood obesity: Health in the balance. Washington, DC: The National Academies Press; 2005. [PubMed: 22379642]
• IOM and NRC (National Research Council). A framework for assessing effects of the food system. Washington, DC: The National Academies Press; 2015. [PubMed: 26203480]
• Kahn A. How we dialed down food allergy fears, and let son thrive. Allergic Living. 2014 [August 15, 2016]; http:​//allergicliving​.com/2014/09/11/how-we-dialed-down-food-allergy-fears-and-let-sonthrive/
• Lerner RM. Developmental science, developmental systems, and contemporary theories. In: Lerner RM, editor. Handbook of Child Psychology. Volume 1: Theoretical Models of Human Development. Hoboken, NJ: Wiley & Sons; 2006. pp. 1–17.
• Lickliter R. Biological development: Theoretical approaches, techniques, and key findings. In: Zelazo PD, editor. The Oxford Handbook of Developmental Psychology. Volume 1: Body and Mind. New York: Oxford University Press; 2013. pp. 65–90.
• Lieberman P, Nicklas RA, Randolph C, Oppenheimer J, Bernstein D, Bernstein J, Ellis A, Golden DB, Greenberger P, Kemp S, Khan D, Ledford D, Lieberman J, Metcalfe D, Nowak-Wegrzyn A, Sicherer S, Wallace D, Blessing-Moore J, Lang D, Portnoy JM, Schuller D, Spector S, Tilles SA. Anaphylaxis—A practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115(5):341–384. [PubMed: 26505932]
• Lipsitz LA. Understanding health care as a complex system: The foundation for unintended consequences. JAMA. 2012;308(3):243–244. [PMC free article: PMC3511782] [PubMed: 22797640]
• Monaco M. Little brother's fearless food allergy advocate. Allergic Living. 2015 [August 15, 2016]; http:​//allergicliving​.com/2015/06/09/little-brothers-fearless-food-allergy-advocate.
• Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, Cardona V, Dubois A, duToit G, Eigenmann P, Fernandez Rivas M, Halken S, Hickstein L, Host A, Knol E, Lack G, Marchisotto MJ, Niggemann B, Nwaru BI, Papadopoulos NG, Poulsen LK, Santos AF, Skypala I, Schoepfer A, Van Ree R, Venter C, Worm M, Vlieg-Boerstra B, Panesar S, de Silva D, Soares-Weiser K, Sheikh A, Ballmer-Weber BK, Nilsson C, de Jong NW, Akdis CA. EAACI food allergy and anaphylaxis guidelines: Diagnosis and management of food allergy. Allergy. 2014;69(8):1008–1025. [PubMed: 24909706]
• NASEM (National Academies of Sciences, Engineering, and Medicine). Genetically engineered crops: Experiences and prospects. Washington, DC: The National Academies Press; 2016. [PubMed: 28230933]
• Nwaru BI, Hickstein L, Panesar SS, Roberts G, Muraro A, Sheikh A. Prevalence of common food allergies in Europe: A systematic review and meta-analysis. Allergy. 2014;69(8):992–1007. [PubMed: 24816523]
• Overton WF. A new paradigm for developmental science: Relationism and relational-developmental systems. Applied Developmental Science. 2013;17(2):94–107.
• Panesar SS, Javad S, de Silva D, Nwaru BI, Hickstein L, Muraro A, Roberts G, Worm M, Bilo MB, Cardona V, Dubois AE, Dunn Galvin A, Eigenmann P, Fernandez-Rivas M, Halken S, Lack G, Niggemann B, Santos AF, Vlieg-Boerstra BJ, Zolkipli ZQ, Sheikh A. The epidemiology of anaphylaxis in Europe: A systematic review. Allergy. 2013;68(11):1353–1361. [PubMed: 24117770]
• Pawanker R, Canonica G, Holgate S, Lockey R. WAO White Book on Allergy 2011-2012. United Kingdom: World Allergy Organization; 2011. [August 15, 2016]. http://www​.worldallergy​.org/definingthespecialty​/2011_white_book.php.
• Reiman T, Rollenhagen C, Pietikainen E, Heikkila J. Principles of adaptive management in complex safety-critical organizations. Safety Sci. 2015;71:80–92.
• Salvilla SA, Dubois AE, Flokstra-de Blok BM, Panesar SS, Worth A, Patel S, Muraro A, Halken S, Hoffmann-Sommergruber K, DunnGalvin A, Hourihane JO, Regent L, de Jong NW, Roberts G, Sheikh A. Disease-specific health-related quality of life instruments for IgE-mediated food allergy. Allergy. 2014;69(7):834–844. [PubMed: 24836207]
• Sampson HA, Aceves S, Bock SA, James J, Jones S, Lang D, Nadeau K, Nowak-Wegrzyn A, Oppenheimer J, Perry TT, Randolph C, Sicherer SH, Simon RA, Vickery BP, Wood R. Food allergy: A practice parameter update—2014. J Allergy Clin Immunol. 2014;134(5):1016–1025. [PubMed: 25174862]
• Sicherer SH, Simons FE. Allergy and Immunology. Self-injectable epinephrine for first-aid management of anaphylaxis. Pediatrics. 2007;119(3):638–646. [PubMed: 17332221]
• Sicherer SH, Mahr T., Section on Allergy and Immunology. Management of food allergy in the school setting. Pediatrics. 2010;126(6):1232–1239. [PubMed: 21115583]
• Soares-Weiser K, Takwoingi Y, Panesar SS, Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Halken S, Poulsen L, van Ree R, Vlieg-Boerstra BJ, Sheikh A. The diagnosis of food allergy: A systematic review and meta-analysis. Allergy. 2014;69(1):76–86. [PubMed: 24329961]
• Szyf M, Bick J. DNA methylation: A mechanism for embedding early life experiences in the genome. Child Dev. 2013;84(1):49–57. [PMC free article: PMC4039199] [PubMed: 22880724]
• von Mutius E, Radon K. Living on a farm: Impact on asthma induction and clinical course. Immunol Allergy Clin North Am. 2008;28(3):631–647. [PubMed: 18572111]