Respiratory manifestations of food allergy

INTRODUCTION — Respiratory tract symptoms observed with food hypersensitivity reactions include nasal congestion, rhinorrhea, sneezing, itching of the nose and throat, coughing, and wheezing [1]. Food allergen exposure is usually through ingestion, but the inhalation of food proteins in the form of dust or aerosolized particles may also trigger respiratory symptoms.

Isolated asthma or rhinitis secondary to food allergy is reported but is rare [2]. More commonly, respiratory symptoms of food allergy are accompanied by skin and/or gastrointestinal manifestations. Foods can elicit asymptomatic airway hyperreactivity or symptomatic asthmatic responses. In addition, systemic anaphylactic reactions often have a respiratory component.

This topic review covers the etiology, diagnosis, and clinical manifestations of respiratory symptoms related to food allergy. Other clinical manifestations of food allergy, oral allergy syndrome, and food-induced anaphylaxis are discussed separately. Occupational asthma and rhinitis are discussed in more detail elsewhere (See "Clinical manifestations of food allergy: An overview" and "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)" and "Food-induced anaphylaxis" and "Occupational rhinitis" and "Occupational asthma: Definitions, epidemiology, causes, and risk factors".)

EPIDEMIOLOGY — Respiratory symptoms as a component of systemic allergic reactions triggered by food occur in up to 50 percent of patients. However, isolated food-induced respiratory symptoms occur in only 2 to 8 percent of patients with food allergy.

Prevalence — While respiratory symptoms as a component of systemic allergic reactions triggered by food occur in almost one-half of patients, isolated food-induced respiratory symptoms are rare. As an example, of 314 positive food challenges in one-year-old infants, 4 percent experienced respiratory or cardiovascular compromise, and none of these symptoms occurred in isolation [2].

The prevalence of respiratory symptoms in patients with food allergies has been reported in several studies:

●In a US population-based study of 6942 people reporting a convincing allergic reaction to a major food allergen (cow's milk [hereafter referred to in this topic as "milk"], hen's egg [hereafter referred to in this topic as "egg"], wheat, soy, peanut, tree nuts, fish, shellfish), 22.6 percent reported chest tightness, 15.8 percent repetitive cough, 29 percent trouble breathing, and 21.8 percent wheezing. In comparison, the most common symptom, hives, was reported in 57.9 percent of reactions [3].

●A population study in France found that the overall prevalence of food allergy was approximately 3 percent [4]. Rhinitis and asthma were each reported as symptoms during food allergy reactions in 6 percent of cases. Asthma was the most common manifestation of food allergy in children four to six years of age.

●Another investigation summarized data from a voluntary registry of 5149 persons (median age five years) with peanut and/or tree nut allergy in the United States [5]. Respiratory reactions, including wheezing, throat tightness, and nasal congestion, were reported as part of the initial reaction in approximately one-half of respondents. Registrants with asthma were significantly more likely than those without asthma to have severe reactions (33 versus 21 percent).

●A random telephone survey estimated the prevalence of seafood allergy in the United States [6]. Fish or shellfish allergy was reported in 6 percent of households (326 of 5529) and 2 percent (344 of 11,948) of persons. Shortness of breath and throat tightness were reported by more than 50 percent of those with seafood allergy.

ASSOCIATIONS BETWEEN FOOD ALLERGY AND ASTHMA — In addition to respiratory symptoms occurring as a presentation of food allergy, patients with food allergy are at increased risk for developing asthma and often severe asthma.

Atopic march — Children with a family history of atopy and sensitization to food proteins in early infancy are at high risk of subsequent respiratory allergic disease [7].

●Egg allergy in infancy has been reported to predict respiratory allergic disease by four years of age [8]. Two percent of children in a cohort of 1218 consecutive births followed until four years of age developed egg allergy. Increased risk of respiratory allergy (rhinitis or asthma) was associated with egg allergy (odds ratio [OR] 5.0, 95% CI 1.1-22.3), with a positive predictive value of 55 percent. Furthermore, the presence of eczema in association with egg allergy increased the positive predictive value to 80 percent.

●A cohort study of over 333,000 children found that food allergy was associated with the development of asthma (OR 2.16, 95% CI 1.94-2.40) and rhinitis (OR 2.72, 95% CI 2.45-3.03) [9].

●In a 10-year follow-up of the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort that included 565 children of mothers with allergies, egg sensitization at one year of age was a better predictor of developing asthma in later years than sensitization to milk [10].

●Investigators followed 271 children over six years of age and 296 children less than six years from a family-based food allergy cohort in Chicago, Illinois [11]. Food allergy status was determined based upon the type and timing of clinical symptoms after ingestion of a specific food and results of specific immunoglobulin E (IgE) to foods using skin prick testing and allergen-specific IgE. Symptomatic food allergy was associated with asthma in both older (OR 4.9, 95% CI 2.5-9.5) and younger children (OR 5.3, 95% CI 1.7-16.2). The association was stronger among children with multiple or severe food allergies, especially in older children. Children with food allergy developed asthma earlier and at a higher prevalence than children without food allergy. There was a significant association between food allergy and asthma.

●A case-control study was conducted with 69 children (ages 7.2 to 13.3 years) with allergy to egg (n = 60) and/or fish (n = 29) in the first three years of life [12]. Asthma symptoms were reported more frequently in the study group than in control subjects (154 children, 70 of whom had aeroallergen sensitization but no food allergy). In addition, study patients showed a significantly increased frequency of positive responses to methacholine challenge compared with controls.

●Based upon a sample of 8203 participants in the National Health and Nutrition Examination survey 2005 to 2006, where serologic tests were used to estimate food allergy prevalence, having a likely food allergy was associated with an adjusted OR of 3.8 (95% CI 1.5-10.7) for having current asthma and 6.9 (95% CI 2.4-19.7) for having had an emergency department visit for asthma in the preceding year [13].

●A cluster analysis of 398 children with atopic risk factors failed to show an association of food sensitization with asthma outcomes [14]. This finding was verified in an additional cohort of 3051 children. However, eczema and rhinitis did cluster with food sensitization.

●In a UK birth cohort study of 1456 children followed into adulthood, food allergy at age four years was significantly associated with asthma at age 26 years (adjusted OR 2.62, 95% CI 1.32-5.20) [15].

Marker for asthma severity — Food allergen sensitivity and food allergy may also be a marker for increased asthma severity.

●Food allergen sensitization was examined in children with asthma living in an urban environment in the United States [16]. In vitro specific IgE testing to six common food allergens (egg, milk, soy, peanut, wheat, and fish) was performed. Forty-five percent of the children were sensitized to at least one food. Children sensitized to foods had higher rates of hospitalization for asthma exacerbations and required more treatment with glucocorticoids.

●Nineteen children with severe exacerbations of asthma requiring mechanical ventilation were investigated [17]. These patients had an increased risk of food allergy (OR 8.6, 95% CI 1.8-39.7) and frequent asthma admissions (OR 14.2, CI 1.8-113.6) compared with controls. Fifty percent of the cases had food allergy versus 10 percent of the controls.

●Another group studied a cohort of 203 urban adults (mean age 48 years) with persistent asthma. Patients with self-reported allergies to more than one food had increased asthma hospitalizations, emergency department visits for asthma, and use of oral glucocorticoids [18].

●The International Study of Asthma and Allergies in Childhood (ISAAC) self-report questionnaire was administered to 13- to 14-year-old students from randomly selected junior high schools in Israel. Students with asthma and food allergy had significantly more markers of severe asthma than those without food allergy [19].

●In a questionnaire study of Jewish and Arab adolescents with over 11,000 responses, children with asthma who also had food allergy had significantly more signs of severe asthma than those without food allergy [19].

Marker for fatal anaphylaxis — Food-induced respiratory symptoms, especially asthma, are a risk factor for fatal and near-fatal anaphylactic reactions. (See "Fatal anaphylaxis".)

ETIOLOGY — A number of different food allergens can induce respiratory symptoms via ingestion and/or inhalation routes of exposure. In children, sensitization may occur through the gastrointestinal tract or possibly the skin. Factors favoring the acquisition of food allergy with respiratory manifestations in adulthood include sensitization to pollens and occupational exposure by inhalation [20,21]. (See "Pathogenesis of food allergy".)

Routes of exposure

Ingestion — Oral ingestion is the primary route of exposure to foods that can cause or exacerbate respiratory symptoms. An internet-based survey of 51 anaphylactic reactions to foods showed that, while most of these reactions (78 percent) occurred after ingestion, 16 percent occurred following exclusive skin contact, and 6 percent occurred after inhalation of the food allergen [22]. These reactions will be discussed in more detail below. (See 'Respiratory manifestations' below.)

Inhalation — Several investigations have highlighted cases of respiratory allergic disease precipitated by inhalation of airborne food allergens [23-32]. These exposures occur in both occupational and nonoccupational settings. Prolonged exposure to high levels of food allergens, such as occurs in occupational settings, increases the risk of sensitization [33]. Occupational exposures to airborne food allergens can also result in chronic asthma.

●Highly allergic persons may react when exposed to aerosolized allergen in a seafood restaurant [23]. Exposure to airborne fish allergens can also occur at open-air fish markets [31,32].

●Asthma symptoms can occur in sensitized children when food allergens such as fish, shellfish, eggs, chickpeas, or buckwheat are cooked in a confined area [24,25]. Both acute and late-phase respiratory symptoms were demonstrated in one of these studies [25]. Peanut butter is an oily substance, and the aroma does not appear to contain sufficient protein to induce respiratory reactions [34].

●Several cases were reported of patients who developed asthma and rhinitis when exposed to raw, but not cooked, green beans and chard while preparing these vegetables for cooking in a nonoccupational environment [31,32].

●Chronic respiratory symptoms occurring only at work were reported in a restaurant cook whose job consisted solely of preparing and cutting raw meat [26]. Another patient had recurrent episodes of anaphylaxis with severe respiratory symptoms that occurred when cutting raw meat at home.

●Baker's asthma is caused by occupational exposure to airborne cereal grain or soybean dust [27,35].

●Bakery workers may also develop IgE-mediated respiratory symptoms to liquid and aerosolized egg proteins that are commonly used in the baking and confectionery industries [28].

●Occupational asthma is reported in people exposed to a variety of food proteins including egg, fish, and shellfish [36].

These data highlight the importance of considering foods as aeroallergens in patients with coexistent food allergy and allergic asthma. Dietary avoidance alone may not be sufficient for these patients. Further environmental measures may be required to limit exposure to aerosolized food. Additional information about the risks and avoidance strategies regarding inhalational exposure are discussed separately. (See "Management of food allergy: Avoidance".)

Allergens — A short list of specific foods trigger most food hypersensitivity reactions involving the respiratory tract [37-39]. These foods include peanut, tree nuts, fish, shellfish, egg, milk, and seeds. Reactions to these foods usually occur after ingestion but can also occur after inhalation.

Anaphylactic reactions to foods, including significant respiratory symptoms, are most often caused by peanut, tree nuts, or seafood [40]. Respiratory reactions, including wheezing, throat tightness, and nasal congestion, occur in approximately 50 percent of initial reactions to peanut or tree nuts [5]. A similar percentage of patients with fish or shellfish allergy report respiratory symptoms with exposure [6]. The presence of asthma is a risk factor for more severe reactions [5]. (See "Food-induced anaphylaxis".)

Other food allergens have been implicated as a cause for upper and lower respiratory tract symptoms secondary to food hypersensitivity by the inhalation route as opposed to the ingestion route [41]. The most common example is baker's asthma triggered by occupational exposure to wheat [42]. Additional foods include carrot [43], lupine [44,45], asparagus [46], and soybean [47].

A high percentage of patients with asthma perceive that food additives worsen their respiratory symptoms. However, blinded challenges often do not confirm these triggers. Several different food additives, including sulfites and sodium benzoate, have been implicated in adverse respiratory reactions. (See "Allergic and asthmatic reactions to food additives".)

DIAGNOSIS — The medical history supplemented with appropriate laboratory testing and food challenges can provide useful information in evaluating patients with respiratory symptoms that may be induced by food allergy. Further workup for IgE-mediated allergy is not generally indicated if no specific foods are implicated in the history and if skin tests or in vitro measurements of specific IgE to foods are negative.

Food is unlikely to be the problem if respiratory symptoms persist after food elimination diets are implemented. Respiratory symptoms that recur after a regular diet has been resumed should be evaluated with a food challenge. (See "History and physical examination in the patient with possible food allergy" and "Diagnostic evaluation of IgE-mediated food allergy" and "Oral food challenges for diagnosis and management of food allergies".)

Studies have demonstrated that foods can elicit airway hyperreactivity and asthmatic responses. Thus, evaluation for food allergy should be considered in patients with:

●Recalcitrant or otherwise unexplained acute, severe asthma exacerbations

●Asthma exacerbations following ingestion or inhalation of particular foods

●Asthma and other manifestations of food allergy (eg, anaphylaxis, moderate-to-severe atopic dermatitis)

RESPIRATORY MANIFESTATIONS — Respiratory symptoms of food allergy are usually accompanied by skin and/or gastrointestinal manifestations. Isolated asthma or rhinitis caused by an allergic reaction to a food is uncommon. In adults, isolated asthma or rhinitis is most often seen in the setting of an occupational exposure. Asthma symptoms triggered by food allergy are primarily seen in children, particularly those with atopic dermatitis. (See "Anaphylaxis: Emergency treatment".)

Upper respiratory symptoms — Nasal symptoms are commonly seen as part of systemic food-triggered allergic reactions [48]. However, isolated rhinitis in response to foods is rare. An exception is occupational rhinitis in food industry workers. (See "Occupational rhinitis".)

Many patients associate the ingestion of milk and other dairy products with an increase in the production and thickness of nasal secretions. However, objective studies do not support these complaints, and they are unlikely to be due to a specific allergic reaction [49].

The role of food allergy or any allergy in recurrent serious otitis media (otitis media with effusion) has been proposed, but this association is unproven, and allergy evaluation is not specifically recommended in guidelines [50,51].

Asthma — Most studies regarding food allergy and respiratory tract symptoms have focused on patients with an underlying history of asthma. The association between food allergy and asthmatic symptoms is seen mainly in children, especially those with atopic dermatitis, and occurs primarily after ingestion of the food allergen (see 'Epidemiology' above). In adults, isolated asthma as a manifestation of food allergy is most commonly related to inhalation exposure and is seen primarily in food industry workers [52,53]. Patients with both asthma and food allergies are at increased risk for morbidity and possibly mortality from these conditions. Thus, close follow-up of these patients is advised. (See "Occupational asthma: Definitions, epidemiology, causes, and risk factors" and "Occupational asthma: Clinical features, evaluation, and diagnosis".)

Bronchospastic respiratory symptoms are also seen in children with atopic dermatitis and food allergy when they undergo food challenges. Respiratory symptoms are less commonly seen in children with non-IgE-mediated food allergy with primarily gastrointestinal manifestations.

●In a previously cited United States study, children with atopic dermatitis undergoing blinded food challenges were monitored for respiratory reactions [48]. Seventeen percent of children developed wheezing during positive food challenges. Eighty-eight patients were monitored with pulmonary function testing during food challenges. Fifteen percent (13 of 88) developed lower respiratory symptoms, including wheezing. However, only six patients had a >20 percent decrease in forced expiratory volume in one second (FEV₁). Wheezing as the only manifestation of the respiratory reaction was a rare observation. (See 'Upper respiratory symptoms' above.)

●In a review of 313 oral food challenges in children at one center, reactions on challenge were more likely if the children had asthma [54].

●In a prospective survey of 300 school-aged children living in an urban environment, 24 percent had clinician-diagnosed food allergies. Those with food allergies had an increased risk of hospitalization, worse lung function, and more use of asthma controller medications than those without food allergies [55].

Baker's asthma — Adults more commonly have food allergy-induced respiratory symptoms from inhalation exposure. These exposures typically occur in occupational settings. (See "Occupational asthma: Definitions, epidemiology, causes, and risk factors" and "Occupational asthma: Clinical features, evaluation, and diagnosis".)

A classic example is baker's asthma, which is most commonly associated with wheat allergy, although other food allergen triggers are reported:

●A small study found that bakery workers with a positive skin test to wheat may develop IgE-mediated respiratory symptoms upon bronchial challenge test with wheat flour [56].

●Bakery workers may develop IgE-mediated occupational asthma to soybean flour as well. The allergens involved are predominantly high-molecular-weight proteins that are present both in soybean hull and flour [27].

●IgE-mediated asthma can also be triggered by liquid and aerosolized egg proteins that are commonly used in the baking and confectionery industries [28].

Airway hyperresponsiveness — Ingestion of a food to which the patient is allergic may result in increased airway hyperresponsiveness (AHR) despite the absence of acute symptoms. This has been demonstrated in pediatric patients with moderate to severe asthma.

●In one investigation, 26 children with asthma and food allergy were evaluated using methacholine inhalation challenges before and after blinded food challenges [57]. Twelve of the 22 patients with positive food challenges had respiratory symptoms (cough, laryngeal reactions, and/or wheezing). The remainder of children with positive food challenges exhibited laryngeal, gastrointestinal, and/or skin symptoms without lower respiratory symptoms. Significant increases in AHR were documented in 7 of the 12 patients who experienced respiratory symptoms during these challenges. Increased AHR was also noted in one patient without respiratory symptoms during a positive challenge and one patient after a negative challenge. A similar study noted a significant increase in AHR among children with asthma without respiratory symptoms following a positive food challenge [58].

●Food allergy is less likely as a cause of increased AHR in adults than in children. As an example, in a study of 11 adults with asthma, a history of food-induced wheezing, and positive skin prick tests to the suspected foods, an equal number of patients had increased AHR by methacholine inhalation challenges after blinded food challenges to either food allergen or placebo [59].

●Three small studies indicate that 40 to 50 percent of patients with food allergy in the absence of asthma might also have increased AHR [60-62].

Anaphylaxis — Anaphylactic reactions that include respiratory symptoms can occur after the oral ingestion of a food allergen. This topic is covered in detail elsewhere. (See "Food-induced anaphylaxis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topic (see "Patient education: Food allergy symptoms and diagnosis (Beyond the Basics)")

SUMMARY

●Respiratory tract symptoms observed with food hypersensitivity reactions include nasal congestion, rhinorrhea, sneezing, itching of the nose and throat, coughing, and wheezing. (See 'Introduction' above.)

●Respiratory symptoms as a component of systemic allergic reactions triggered by food occur in up to 50 percent of patients. However, isolated food-induced respiratory symptoms occur in only 2 to 8 percent of patients with food allergy. (See 'Epidemiology' above.)

●Allergic sensitization to hen's egg and/or cow's milk in the first few years of life may be predictive of later respiratory allergic disease, including allergic rhinitis and asthma. Food allergen sensitivity may also be a marker for increased asthma severity. (See 'Associations between food allergy and asthma' above.)

●Food allergen exposure is usually through ingestion, but the inhalation of food proteins in the form of dust or aerosolized particles may also trigger respiratory symptoms. (See 'Etiology' above.)

●The most common foods that trigger food hypersensitivity reactions involving the respiratory tract are peanut, tree nuts, fish, shellfish, egg, milk, and seeds. Wheat and soybean are the most frequently implicated food allergens in inhalation-induced reactions, although egg, seafood, and other foods that are aerosolized during cooking can also cause these types of reactions. (See 'Allergens' above.)

●Respiratory symptoms of food allergy are usually accompanied by skin and/or gastrointestinal manifestations. Isolated asthma or rhinitis caused by an allergic reaction to a food is uncommon. Thus, we do not routinely test persons with asthma or rhinitis for food allergies. In adults, isolated asthma or rhinitis is most often seen in the setting of an occupational exposure. Asthma symptoms triggered by food allergy are primarily seen in children, particularly those with atopic dermatitis. (See 'Respiratory manifestations' above and 'Diagnosis' above.)

●Ingestion of a food to which the patient is allergic may result in increased airway hyperresponsiveness (AHR) despite the absence of acute symptoms. (See 'Airway hyperresponsiveness' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges John M James, MD, who contributed to earlier versions of this topic review.