Respiratory Food Allergy

Elham Hossny, MD, PhD, FAAAAI

Head, Pediatric Allergy and Immunology Unit, Children’s Hospital, Ain Shams University Conflicts of Interest

Nothing to disclose • There is clinical evidence that food allergy plays a role in the pathogenesis of respiratory disorders • This seems to be more common in infants and young children than adults CONTENT

• Causative food allergens

• Respiratory manifestations of food allergy

• Indications of screening for food allergy

• Key notes and unmet needs Causative Food Allergens

Class I food allergens: Milk, egg, seafood, peanut, tree nuts, wheat, and soy (most common)

Class II food allergens: Fruits and vegetables (food-pollen syndrome) • Cow's milk is one of the first foreign proteins ingested by infants and is one of the most common and potent food allergens.

• Contamination of probiotic preparations with milk allergens can cause anaphylaxis in children with cow's milk allergy. Causative food allergens (Cont’d)

The presence of egg allergy in infancy especially when coexisting with eczema increases the likelihood of respiratory allergy and aeroallergen sensitization in early childhood.

Tariq SM, et al. Pediatr Allergy Immunol 2000;11:162-7. Food Pollen Syndrome = Oral Allergy Syndrome • Cross-reactive allergens between certain foods and airborne pollens • The most famous cross reacting allergen is profillin Birch pollen – almonds – apples – apricots – carrots – celery – cherries – kiwifruit – parsley – peaches – pears – peppers – plums – potatoes – prunes Food Pollen Syndrome (Cont’d)

Grass pollen – Melons – Tomatoes – Oranges Ragweed pollen – Banana – Cantaloupe – Watermelon – Cucumber – Zucchini 0-5 6-10 11-15

Pollen food syndrome amongst children with seasonal allergic rhinitis attending allergy clinic Ludman S, et al. Pediatr Allergy Immunol 2016:27:134-140.

Pediatric Allergy and Immunology Volume 27, Issue 2, pages 134-140, 9 DEC 2015 DOI: 10.1111/pai.12504 http://onlinelibrary.wiley.com/doi/10.1111/pai.12504/full#pai12504-fig-0001 Pollen allergens and cross-reactive foods in pollen-food syndrome

Plant Allergen Cross-reacting protein Fruits and vegetables Birch Bet v 1 PR-10 Apple, apricot, carrot, celery, cherry, hazelnut, peanut, pear, soy, strawberry

Bet v 2 Profilin Ragweed Amb a 8 Profilin Almond, apple, banana, carrot, celery, Timothy grass Phl p 12 Profilin hazelnut, kiwi, melon, peach, pineapple, soy, strawberry, tomato Mugwort Art v 4 Profilin

Art v 3 Lipid transfer protein Asparagus, apple, apricot, cherry, grape, hazelnut, lettuce, corn, peach, strawberry, tomato, walnut Latex Hev b 2 PR-2 (β-1,3-glucanase) Banana Hev b 8 Profilin Almond, apple, banana, carrot, celery, hazelnut, kiwi, melon, peach, pineapple, soy, strawberry, tomato

Hev b 11 PR-3 (class I chitinases) Avocado, banana, chestnut, kiwi, mango, papaya, passion fruit, tomato

Adapted from Bird JA, Lack G, Perry TT. J Allergy Clin Immunol Pract 2015;3:1-11. Pollen allergens and cross-reactive foods in pollen-food syndrome

Plant Allergen Cross-reacting protein Fruits and vegetables Birch Bet v 1 PR-10 Apple, apricot, carrot, celery, cherry, hazelnut, peanut, pear, soy, strawberry

Hev b 11 PR-3 (class I chitinases) Avocado, banana, chestnut, kiwi, mango, papaya, passion fruit, tomato

Adapted from Bird JA, Lack G, Perry TT. J Allergy Clin Immunol Pract 2015;3:1-11. Natural rubber latex (NRL) • It is widely used in infants and children. • Infant pacifiers, balloons, toys, sport equipment .. etc. • Medical procedures, e.g., surgery (gloves), and catheterization. Reactions to food additives: • Symptoms to multiple unrelated foods. • Allergy to a food when commercially prepared but not when home-made. • When SPT excludes a role for food protein.

Wilson BG, Bahna SL. Ann Allergy Asthma Immunol 2005;95:499-507. Food sensitivity can cause reactions via routes other than ingestion e.g. • Inhalation: odors of cooked fish or opening of a package of peanuts • Contact with food e.g. workers • Perinatal exposure leading to reactions on the first exposure • Breast feeding: reactions in exclusively breast-fed infants CONTENT

• Causative food allergens

• Respiratory manifestations of food allergy

• Indications of screening for food allergy

• Key notes and unmet needs Classification of Respiratory Food Allergy

IgE-mediated reactions: • Respiratory symptoms of anaphylaxis • Bronchial asthma • Allergic rhinitis (?) • Recurrent secretory otitis media (?) Non IgE-mediated reactions: • Milk-induced chronic pulmonary disease (Heiner syndrome) • Food-induced hypersensitivity pneumonitis

El-Gamal Y, Hossny E. Pediatr Ann 2006;35:733-42. Respiratory symptoms of food-induced anaphylaxis • Respiratory manifestations are important indicators of severe anaphylaxis • Peanut, tree nuts, egg and cow milk were the most common foods associated with respiratory symptoms in fatal and near- fatal anaphylactic reactions in children.

Sampson HA, et al. N Engl J Med 1992;327:380-4. However, the causal foods may differ by the geographical region and local cuisine e.g.

In Italy, seafood was the most frequent cause.

Cianferoni A, et al. Ann Allergy Asthma Immunol 2001;87:27-32.

In France, food-induced anaphylactic reactions correlated with the co-intake of alcohol or NSAIDs

Kanny G, et al. J Allergy Clin Immunol 2001;108: 133-40. In Singapore and Far East, the most common cause of food-induced anaphylaxis and food- induced asthma in children is the bird’s nest

Thong BYH, et al. Singapore Med J 2007;48:236-40. Respiratory clinical manifestations of anaphylaxis • Bronchospasm: expiratory wheeze • Stridor due to laryngeal spasm or edema: inspiratory difficulty • Dysphonia • Oropharyngeal pruritus • Nasal congestion and rhinorrhea • Tongue or palate edema Food allergy and asthma

The incidence of FA in asthmatic children (6-8%) is lower than that in atopic eczema (35%) but when a child has asthma and atopic eczema, the likelihood of FA rises.

Sampson HA. J Allergy Clin Immunol 2004;113:805-19. Prevalence and clinical impact of IgE-mediated food allergy in school children with asthma: a DBPC food challenge study

Krogulska A, et al. Allergy Asthma Immunol Res 2015;7:547-56.

Although food-induced asthma in children is rare, it is classified as severe and associated with worse morbidity, greater severity, and poorer control

Allergy Asthma Immunol Res 2015;7:547-56. http://dx.doi.org/10.4168/aair.2015.7.6.547 Food allergy and asthma (Cont’d)

• In some patients, the manifestations of FA can be limited to subclinical bronchial hyper-reactivity (BHR) • In other words, the chronic ingestion of a food to which one is allergic may result in increased BHR despite the absence of acute symptoms on ingestion.

Krogulska A, et al. Pediatr Pulmonol 2016;51:787-95. Food Allergy and Increased Asthma Morbidity in a School-Based Inner-City Asthma Study

The percentage prevalence of symptoms experienced within one hour of food ingestion

Friedlander JL, et sl. J Allergy Clin Immunol Pract 2013;1:479-84.

The Journal of Allergy and Clinical Immunology: In Practice 2013 1, 479-484DOI: (10.1016/j.jaip.2013.06.007) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions A cross-sectional prevalence study from New Zealand on 1321 children revealed that frequent fast food and “takeaway” consumption showed a dose-dependent association with asthma symptoms and bronchial hyperresponsiveness.

Wickens K, et al. Allergy 2005;60:1537-41. Food Allergy and the Upper Airway

Allergic rhinitis typically occurs in association with other clinical manifestations e.g. cutaneous and/or gastrointestinal and rarely occurs alone

James JM, et al. Am J Respir Crit Care Med 1994;149:59-64.

Food allergy and otitis media (Cont’d)

However, due to the paucity of available data, the routine testing for food allergy in otitis media is not recommended.

Zernotti ME, Pawankar R, Ansotegui I, Badellino H, Croce JS, Hossny E, et al. World Allergy Organ J 2017;10:37. Milk-Induced Chronic Pulmonary Disease (Heiner Syndrome) • It is certainly a non-IgE mediated reaction • The significance of peripheral blood eosinophilia and elevated serum total IgE is probably limited to the associated atopy

Bahna SL, Mayer CW. Expert Rev Clin Immunol 2005;1:133-43. Heiner’s syndrome (Cont’d)

• Type III hypersensitivity (Arthus reaction) may play a role leading to the formation of immune complexes that cause inflammation in the alveolar capillaries • When such vasculitis is severe, bleeding occurs causing pulmonary hemosiderosis (PH)

Moissidis I, et al. Pediatr Allergy Immunol 2005;16:545-52. In patients who develop pulmonary hemosiderosis (PH), there are iron laden macrophages (ILM) in smears of tracheal aspirates or morning gastric washing fluid

Quoted from: Moissidis L, et al. Pediatr Allergy Immunol 2005;16: 545-52. Quoted from: Moissidis L, et al. Pediatr Allergy Immunol 2005;16: 545-52. Heiner’s syndrome (Cont’d)

• The most allergenic milk components are -lactoglobulin and casein which are heat stable followed by -lactalbumin and - globulin which are heat labile. • Although CM is the most common cause, some other foods have been incriminated in older children e.g. soy, egg and pork.

Moissidis I, et al. Pediatr Allergy Immunol 2005;16:545-52 Treatment of Heiner’s syndrome

• Strict avoidance • Milk substitutes • Food labels should be carefully inspected • In pulmonary hemosiderosis, corticosteroids and immunosuppressive drugs are sometimes indicated • Medical identification means are also advisable Medical identification means • At-risk infants should wear accurate medical identification such as a T-shirt or Velcro patch on clothes with a specific alert message, for example, ‘‘Do not give cow’s milk to this baby’’ • Medical identification bracelets made of cloth for older infants

Simons FER. J Allergy Clin Immunol 2006;117:367-77. Heiner’s syndrome (Cont’d)

• The prognosis is generally good if a milk-free diet is begun early. • Many patients would tolerate cow’s milk within a few years. • The diagnosis is based on elimination Challenge test Food-induced Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis)

• Intense or repeated exposure to organic antigens, which can be food particles (e.g. Baker’s Asthma) • More common in adults because of occupational exposure but can occur in children and often goes unrecognized Wheat allergy: diagnosis and management Cianferoni A. J Asthma Allergy 2016;9:13-25. CONTENT

• Causative food allergens

• Respiratory manifestations of food allergy

• Indications of screening for food allergy

• Key notes and unmet needs Indications of screening for food allergy in patients with respiratory disorders

1. History of wheezing triggered by food 2. Asthma associated with history of atopic dermatitis or food-induced anaphylaxis. 3. Recalcitrant bronchial asthma especially in infants. Indications of screening for food allergy in patients with respiratory disorders

4. Chronic or recurrent pulmonary infiltrates in a cow’s milk-fed infant. 5. Pulmonary hemosiderosis in infants if otherwise unexplained. 6. Chronic respiratory symptoms in subjects occupationally exposed to food dust or fumes. CONTENT

• Causative food allergens

• Respiratory manifestations of food allergy

• Indications of screening for food allergy

• Key notes and unmet needs • Food-induced asthma, although rare, is classified as severe and associated with poor control • A high index of suspicion is needed to detect cases of Heiner’s syndrome in cow’s milk fed infants • Cutting edge research in food induced respiratory allergy will help indeed combat some recalcitrant cases and improve the quality of life of this sector of children MEMBER SOCIETY OF MEMBER SOCIETY OF

The 15th International Congress of the Egyptian Society of Pediatric Allergy and Immunology (ESPAI 2019) Cairo Sheraton Hotel, September 25-26, 2019

ESPAI 2019 is accredited by the European Accreditation Council for Continuing Medical Education (EACCME): 12 CME hours

Stanley Fineman Kathleen May Allen Meadows USA USA USA ACKNOWLEDGEMENTS PAI Team

Yehia El-Gamal Khaled Awwad Zeinab Awad Elham Hossny Shereen Reda Ashraf Abd El-Baky Mohammad Hesham Gehan Mostafa Shereen Saad Dalia El-Ghoneimy Rasha El-Owaidy Hanan Abdel Lateef Nesrine Radwan Nevine Aly Amr El-Mekkawy Ghada Shousha Amira Foad Sally Gouda Mariam Abdel Naby Roba Maher Rana Zakaria PAI Lab Team Eman Ibraheim Eman Ghanem Marwa Mohammad