Allergic reactions to foods by inhalation

Allergic Reactions to Foods by Inhalation John M. James, MD, and Jesús Fernández Crespo, MD Corresponding author John M. James, MD Colorado Allergy and Asthma Centers, 1136 East Stuart Street, Suite 3200, Fort Collins, CO 80524, USA. E-mail: [email protected] Current Allergy and Asthma Reports 2007, 7:167–174 Current Medicine Group LLC ISSN 1529-7322 Copyright © 2007 by Current Medicine Group LLC Although allergic reactions to foods occur most commonly after ingestion, inhalation of foods can also be an underlying cause of these reactions. For example, published reports have highlighted the inhalation of allergens from fish, shellfish, seeds, soybeans, cereal grains, hen’s egg, cow’s milk, and many other foods in allergic reactions. Symptoms have typically included respiratory manifestations such as rhinoconjunctivitis, coughing, wheezing, dyspnea, and asthma. In some cases, anaphylaxis has been observed. In addition, there have been many investigations of occupational asthma following the inhalation of relevant food allergens. This report reviews the current literature focusing on allergic reactions to foods by inhalation. observed, and the typical clinical scenarios in which to suspect these reactions. Overview of Adverse Food Reactions “Adverse food reaction” is a useful general term to describe any abnormal reaction following the ingestion of a food or a food ingredient [2]. These reactions can be divided into toxic and nontoxic adverse reactions. Toxic reactions (eg, food poisoning) may occur in anyone if a sufficient dose of the toxin is ingested. Nontoxic reactions are more individual and may depend on immune reactions (ie, allergy/hypersensitivity) or nonimmune (intolerance) reactions (eg, carbohydrate malabsorption). The two broad groups of immune reactions are immunoglobulin (Ig) E-mediated and non–IgE-mediated. The IgE-mediated reactions are usually divided into immediate-onset reactions and immediate plus late phase reactions (ie, in which the immediate-onset symptoms are followed by symptoms that are prolonged in time or persistent). The former have been well characterized in many studies, whereas the latter are under more intense scrutiny to determine their mechanisms and to unravel the role of the immune system. Introduction Route of Exposure to Food Allergens Food hypersensitivity reactions typically include cutaneous, gastrointestinal, and respiratory symptoms such as urticaria, atopic dermatitis, nausea, vomiting, diarrhea, coughing, and asthma [1]. In addition, systemic anaphylactic reactions can be observed with food reactions. Although the vast majority of published reports have focused on specific allergic symptoms and clinical manifestations following the ingestion of food allergens, an increasing number of investigations have highlighted allergic reactions to foods that have occurred following inhalation. Therefore, the evaluation of food allergy should be considered among patients with histories of allergic reactions, not only after the ingestion of a suspected food allergen, but also following relevant inhalational exposures. This article summarizes the most recent published information highlighting allergic reactions to foods by inhalation with a specific focus on the individual foods that have been involved, the types of clinical symptoms Oral ingestion of food allergens Oral ingestion of food allergens is the primary route of exposure that can cause or exacerbate food hypersensitivity symptoms. The vast majority of published reports have focused on cutaneous, gastrointestinal, and respiratory tract symptoms following the ingestion of food allergens. Using well-controlled oral food challenges, a short list of specific foods have been implicated and confi rmed in food hypersensitivity reactions [3–6]. Typically, these foods have included peanut, hen’s egg, cow’s milk, soy, wheat, fish, shellfish, and tree nuts. More recently, sesame seeds have been reported to be a cause of serious food allergy provoking both respiratory symptoms and systemic anaphylaxis [7•]. Anaphylactic reactions to foods, including significant respiratory symptoms and, in some cases, fatal and near fatal anaphylactic reactions, have also been reported [8–10]. Respiratory reactions, including wheezing, throat tightness, and nasal congestion, were reported 168 Food Allergy in 42% and 56% of respondents as part of their initial reactions to peanuts and tree nuts, respectively [11], and the presence of asthma was a risk factor for these patients to have more severe reactions (33% vs 21%; P < 0.0001). Finally, respiratory symptoms including shortness of breath and throat tightness were reported by more than 50% of patients with fish or shellfish allergy in a recent published survey [12]. Inhalation of food allergens As opposed to the ingestion route, exposure to food allergens through inhalation can also cause food hypersensitivity reactions. Several published reports have highlighted cases of food hypersensitivity reactions that have been precipitated after inhalation of airborne food allergens. The following sections review the different foods that have been implicated and confirmed in these reactions. Fish Highly allergic persons may react when exposed to clinically relevant levels of allergenic food in a seafood restaurant, or when fish or shellfish are cooked in a confi ned area. These allergens may become aerosolized during food preparation [13]. One report highlighted the clinical characteristics found in 21 children who experienced allergic reactions upon incidental inhalation of fish odors or fumes, from a group of 197 children diagnosed with IgE-mediated fish hypersensitivity [14]. The vast majority (19/21) of these patients showed cutaneous symptoms, either alone or, less frequently, associated with other clinical manifestations. After diagnosis, all these patients were placed on a strict fish-avoidance diet. During this period of avoidance, patients (mean age, 7 years) reported allergic reactions after incidental exposure to airborne fish odors or fumes. Clinical manifestations through inhalation were respiratory, mainly wheezing, in 12 patients, and cutaneous, mainly urticaria, in nine patients. Nineteen of 21 patients reported three or more episodes upon exposure to fish aerosols. In most cases, these episodes occurred at home when other people were eating fish. These data suggest that incidental inhalation of odors or fumes may play an important role in accidental and unknown encounters with fish in children on fish-avoidance diets for fish IgEmediated hypersensitivity. Investigators have examined the possibility of passively aerosolized fish allergen in an open-air fish market using an air sampling technique and a competitive IgE immunoassay [15]. Air samples were collected on 41 different days from both an open-air fish market and an outdoor residential area. Fish allergens were specifically quantified with a competitive IgE immunoassay using pooled sera from fish-sensitive individuals. The residential air samples contained no detectable allergen; however, fish allergen was detectable in the air samples from the open-air fish market. Therefore, avoidance of certain food allergens, such as fish, should include not only the prevention of the ingestion of the relevant fish, but also the prevention of exposure to aerosolized particles through inhalation in relevant environments. Occupational asthma due to fish inhalation, confi rmed by specific bronchial challenge (SBC), has been reported by Rodriguez et al. [16]. Two fish-processing workers with asthma experienced an exacerbation of their symptoms following occupational exposure to fish in their workplace. Positive skin tests were observed in patient 1 with raw and cooked plaice, salmon, hake, and tuna and in patient 2 with anchovy, sardine, trout, salmon, Atlantic pomfret, and sole. Specific IgE serum antibodies were found to salmon in patient 1 and to trout, anchovy, and salmon in patient 2. Peak expiratory flow rate measurements differed significantly (P < 0.001) between work and off-work periods for both patients. SBC with raw hake, salmon, plaice, and tuna extracts in patient 1 and raw salmon extract in patient 2 were all positive with an immediate response. In three asthmatic, non–fish-allergic controls, SBC with tuna, hake, salmon, and plaice were all negative. The investigators concluded that fish inhalation can elicit IgE-mediated occupational asthma. Seafood A recent investigation examined the prevalence, work-related symptoms, and possible risk factors for IgE-mediated sensitization in seafood processing workers [17 ]. Sixty-four fish and seafood processing workers were compared with 60 controls regarding sensitization to seafood allergens. Twenty-three of 64 workers (35.9%) were sensitive to at least one of the seafood allergens tested, as opposed to 10% of the controls. Presence of atopy, as well as the intensity and the duration of exposure, were found to be potential risk factors for sensitization. Four of 64 (6.25%) workers reported work-related symptoms. Therefore, occupational exposure to fish and seafood may increase the likelihood of sensitization to these foods. Occupational asthma has been shown to be a highly prevalent disease among snow crab–processing workers [18]. To investigate an immunologic mechanism for this condition, skin prick testing with snow crab meat extract and snow crab cooking water were performed on 119 workers. Crab-specific IgE was assessed by radioallergosorbent testing (RAST) in sera from 115 workers with snow crab meat and water extracts. Both skin testing and RAST were performed in 58 individuals. Diagnosis of occupational asthma had been confi rmed previously in 54 individuals. A highly significant relationship was demonstrated between the presence of immediate skin test reactivity or increased serum levels of specific IgE to crab extracts and the occurrence of occupational asthma. There was good agreement between the results of skin testing and RAST with extracts of snow crab or snow crab cooking water. The investigators concluded that occupational asthma in snow crab–processing workers is mediated through an IgE mechanism. Allergic Reactions to Foods by Inhalation Thirty-one workers with occupational asthma caused by snow crab processing were assessed by long-term follow-up upon three occasions after leaving work [19]. The diagnosis of work-related asthma was initially confi rmed in all of them by specific inhalation challenges at the workplace, by laboratory inhalation of snow crab boiling water (n = 24), or by serial monitoring of airway caliber and bronchial responsiveness to histamine at work and off work (n = 7). Total duration of work-related exposure was 12.8 ± 5.6 months (range, 3–21 months), and the duration of symptoms after onset was 6.8 ± 4.2 months (range, 1 – 18 months). At the time of diagnosis, all 31 subjects required medication for asthma, 11 had a forced expiratory volume in 1 second (FEV1) less than or equal to 85% predicted, and all subjects had a PC20 less than or equal to 16 mg/mL (PC20: provocative challenge dose with histamine that caused a 20% decrease in FEV1 during the histamine inhalation bronchial challenge). Twelve of 25 serum samples assessed showed high levels of specific IgE antibodies to crab meat and/or snow crab boiling water. At the fi rst follow-up, there was a reduction in the number of subjects still requiring medication and a significant reduction in the number of subjects with PC20 less than or equal to 16 mg/mL. Similarly, the mean FEV1 and FEV1/forced vital capacity (FVC) improved significantly from the time of diagnosis to the fi rst follow-up (P < 0.01), with a plateau thereafter. The length of time from leaving work to the fi rst follow-up was approximately 13 months (12.8 ± 5.4 months). Other investigators have demonstrated that snow crab antigens can cause immunological reactivity and can be found in the air upon sampling the plant’s atmosphere [20]. Area air samplers worn by workers at four different work sites of snow crab–processing plants were obtained. Snow crab was being boiled and processed during the air sampling periods. Eluate from one of the four sites (site 2) had the highest protein concentration and yielded the highest percent inhibition of RAST: 13% inhibition with snow crab meat, and 23% and 28% inhibition with snow crab water RAST in two separate assays. An eluate taken from a fi lter at another site (site 1) showed borderline reactivity (1% and 10% inhibition in two assays), whereas the two others and a control fi lter were negative. The two fi lters that contained snow crab proteins were the ones nearest the boiling process, site 2 being the nearest followed by site 1. This study suggested that airborne snow crab–derived proteins, released during the boiling process, may be the cause of occupational asthma to snow crab. Sixty-three subjects with occupational asthma caused by crab (n = 31) were studied after cessation of exposure at work for at least 6 months in every subject [21]. Nineteen of the subjects with asthma caused by crab were still symptomatic for asthma. Although 48 of 52 subjects still had significant airway hyperresponsiveness, improvement in bronchial responsiveness to histamine was significant (P < 0.01) in the group with asthma caused by crab. James and Crespo 169 Asymptomatic subjects with asthma caused by crab had worked for shorter intervals after onset of symptoms. It was concluded that subjects with occupational asthma caused by crab can remain symptomatic of asthma even after the exposure was removed and they demonstrate a persistence of bronchial hyperresponsiveness for prolonged intervals after the cessation of occupational exposure. Seeds Several recent reports have focused on the role of seeds as a cause of food allergy following relevant inhalation. For example, one investigation involved a 16-year-old boy who developed erythema, angioedema, conjunctivitis, and dyspnea following the inhalation of poppy seed [22]. Another report highlighted the possibility of sensitization to sunflower seeds through inhalation of the dust from the seeds, as may occur when the seeds are used to feed birds. Once allergic sensitization has occurred, oral allergy symptoms can occur after the ingestion of sunflower seeds [23]. Although the ingestion of lupine seed flour has been reported as a cause of allergic reactions, the allergenic potential of this seed after inhalation has also been documented. Clinical and immunologic reactivity to lupine in employees working with this seed flour at an agricultural research center has been examined [24]. Subjects reported work-related allergy symptoms immediately after being exposed to lupine. Allergic sensitization was documented by positive skin prick test results with lupine seed flour extract and the measurement of lupine-specific IgE antibodies. Double-blinded, placebo-controlled lupine seed flour oral challenge results were positive in some sensitized subjects. Thus, the inhalation of lupine flour could be an important cause of allergic sensitization in exposed workers and might give rise to occupational asthma and food allergy. Finally, lupine inhalation was reported to trigger allergic asthma in an 8-year-old asthmatic child who suffered an attack while playing with his brother, who had been eating lupine seed as a snack [25]. Skin testing showed a positive result with Lupinus albus extract, and serum-specific IgE antibodies were positive to lupine. The patient had an asthma exacerbation within 5 minutes of manipulation of lupine seeds. Soybeans Bakery workers have been reported to develop IgE-mediated occupational asthma to soybean flour. The allergens involved are predominantly high-molecular-weight proteins that are present both in soybean hull and flour [26]. Sensitization to soybean hull allergens has been reported in subjects from Argentina, a soybean-producing country. Specific IgE and IgG4 to an identified soybean hull allergen are common in serum samples from allergic individuals living in rural areas of Argentina. Sensitization to this allergen is common in subjects who are repeatedly exposed to soybean dust inhalation [27 ]. 170 Food Allergy Asthma attacks and mortality due to inhalation of soybean antigens in Barcelona have also been documented [28]. Strict protective measures in the unloading process were established in 1998 to avoid the release of soybean dust into the atmosphere. Levels of soybean aeroallergen were analyzed daily during a period of 5 years. In addition, the investigators recorded the number of asthma admissions to emergency rooms, asthma patients attended at home by the public home emergency service, and judicial autopsies registering asthma deaths. The mean concentration of soybean aeroallergen in the post-intervention period compared to the pre-intervention period was significantly decreased (P < 0.0001). Moreover, significant differences in post-intervention aeroallergen concentrations were found between days of soybean unloading and days of no unloading (P < 0.0001). Implementation of stricter protective measures in silos for the soybean unloading process has reduced the concentration of soybean dust in the atmosphere, demonstrating the effectiveness of these measures. Cereal grain Occupational exposures to airborne food allergens can result in chronic asthma. For example, baker’s asthma is caused by occupational exposure to airborne cereal grain dust [29]. A significant percentage of bakers develop occupational asthma and chronic obstructive bronchitis. There was a positive methacholine test in 33% of bakers with atopic status, compared to 6.1% (P < 0.01) of nonatopic bakers. In another investigation involving bakers who displayed a positive skin test to wheat flour, specific bronchial challenge test with flour was positive in two (13.3%) bakers versus none in the bakers with a negative skin test to wheat [30]. Inhalation of dust from different enzymes can be the cause of occupational asthma in exposed workers. One study characterized exposure to inhalation dust, wheat flour, and alpha-amylase allergens in industrial and traditional bakeries [31]. Furthermore, occupational allergens (including wheat and fungal alphaamylase) can be found in house dust from the homes of bakers, and levels are associated with hygienic behavior and distance to the bakery [32]. Egg Specific proteins from egg have been described as a cause of inhalant allergy, and sometimes inhalation type I hypersensitivity to these proteins may be associated with food allergy to egg [33]. Two patients who experienced respiratory and food allergic symptoms upon exposure to egg or avian antigens following inhalation or ingestion were studied. Clinical and immunological studies were carried out to identify individual allergens from these sources that could be responsible for cross-reactivity reactions. One patient showed IgE sensitization to egg yolk livetins, feathers, and chicken serum. Specific bronchial challenge with chicken albumin and livetin extracts elic- ited a positive early asthmatic response and an increase in serum eosinophil cationic protein. Immunoblot and CAPinhibition studies (a type of immunoassay that measures specific IgE to allergens) in this patient supported that chicken albumin (alpha-livetin) was the cross-reactive antigen present in egg yolk and chicken serum and feathers. Another patient showed sensitization to egg white, ovomucoid, and lysozyme. Specific IgE-binding studies demonstrated that lysozyme was the main allergen causing egg sensitization in this patient. Conjunctival challenge test confi rmed allergy to lysozyme. Therefore, egg yolk and egg white proteins may act not only as ingested allergens, but also aeroallergens. Twenty-five workers in an egg-producing factory were evaluated for respiratory sensitization to inhaled egg proteins by a physician evaluation, serial peak expiratory flow rate (PEFR) measurements for a 1-week period, and immunologic tests [34]. The immunologic studies included skin prick tests and serum-specific IgE (RAST) to solutions prepared from commercial food allergens: factory-powdered egg white and yolk products and purified egg white fractions, including ovalbumin, ovomucoid, lysozyme, and conalbumin. Six workers had significant daily PEFR lability (> 20%), of whom five had associated cutaneous reactivity to at least one egg allergen. A diagnosis of “defi nite asthma” was established in five workers suspected by the physician as having asthma. These five workers exhibited significant decrements in daily PEFR that were accompanied by bronchial symptoms. Occupational asthma was diagnosed by the physician in four of the five workers. Defi nite asthma was significantly associated with both cutaneous reactivity to egg allergens (P < 0.01) and RAST binding (P < 0.01). The highest levels of RAST binding were detected in four workers, and the most significant binding activity was to ovomucoid and to ovalbumin fractions. Bakery workers may develop IgE-mediated allergy to liquid and aerosolized hen’s egg proteins that are commonly used in the baking and confectionery industries [35]. Four bakery workers were studied who had workrelated allergic respiratory symptoms upon exposure to hen’s egg aerosols. Specific IgE determinations to egg proteins were positive in all patients and methacholine inhalation challenges revealed bronchial hyperresponsiveness in all workers. Specific inhalation challenges elicited early asthmatic reactions in all subjects and double-blind, placebo-controlled food challenges with raw egg white were positive in three subjects. Similarly, a case report highlighted a patient with asthma induced by occupational exposure to egg used to spray cakes before baking [36]. A type I hypersensitivity to egg white was demonstrated by means of skin test, immunoassay for specific IgE, and immediate bronchial provocation test response to an egg white extract. Another group of investigators reported IgE-mediated occupational asthma among workers exposed to Allergic Reactions to Foods by Inhalation airborne egg protein at a plant that produces liquid and dried powdered egg products [37 ]. To estimate the prevalence of IgE-mediated occupational asthma among egg-exposed workers, the investigators administered a questionnaire to 188 employees to identify workers with symptoms suggestive of occupational asthma. They further evaluated 88 workers with and without symptoms by means of a clinical examination by a physician blinded to results of other tests, serial PEFR determinations every 3 hours while awake for 1 week, and skin prick tests and serum-specifi c IgE levels to extracts of factory egg products, commercial egg test reagents, and egg white protein fractions. Fourteen workers had work-related symptoms consistent with asthma by questionnaire, a physician diagnosis of occupational asthma, and evidence of IgE-mediated sensitization to one or more egg proteins. Workers exposed exclusively to liquid egg aerosol, as well as workers exposed primarily to dried airborne egg protein, developed occupational asthma. These data replicated previous observations by this group and demonstrated that workers in all areas of liquid and powdered egg production are at risk of developing occupational asthma from exposure to airborne egg proteins. Finally, a 26-year-old man employed in a company that manufactured hen egg white–derived lysozyme for use in the pharmaceutical industry was evaluated for occupational asthma [38]. The worker began to experience immediate-onset asthmatic symptoms 2 months after starting to work with egg lysozyme powder. Skin prick testing was positive to egg lysozyme and other egg protein components, but negative to whole egg white and egg yolk reagents. Serum-specific IgE to egg lysozyme was documented. Decrements in serial PEFR were associated with lysozyme exposure at work. A specific bronchoprovocation challenge to lysozyme powder was positive, demonstrating an isolated immediate asthmatic response (48% decrease from baseline FEV1). This is the fi rst reported case of lysozyme-induced asthma specifically caused by inhalation exposure to egg lysozyme. Cow milk Solutions of casein, a common cow milk protein, are typically sprayed over leather in the fi nal stage of tanning. One report focuses on an atopic tannery worker with occupational asthma that most likely was the result of the inhalation of casein [39]. Data from the clinical record support the occupational source of the patient’s symptoms, and a positive bronchial challenge with casein clearly defi ned it as the specific etiological agent. The presence of specific IgE suggests a hypersensitivity type I mechanism. In the tanning process, chromium salts, paraphenylenediamine, and formaldehyde have all been included as specific etiological agents of asthma, but occupational asthma induced by inhalation of casein had not previously been reported. Moreover, a chocolate James and Crespo 171 candy worker was diagnosed as having occupational asthma and rhinoconjunctivitis on the basis of clinical record and methacholine challenge [40]. Positive conjunctival and bronchial challenge tests with lactalbumin, another common cow milk protein, demonstrated that this protein was the pathogenic agent and a type I hypersensitivity mechanism was demonstrated by means of skin prick test and RAST. Other foods implicated in inhalation reactions Other foods have been confi rmed in allergic reactions following inhalation. Airborne carrot allergens have been reported to sensitize individuals without the implication of a previous pollen allergy [41]. Three patients had asthma when handling raw carrots. IgE immunoblot analysis determined that Dau c 1 from carrot extract and recombinant (rDau c 1) were recognized by IgE from two of these patients. Specific IgE enzyme-linked immunosorbent assay (ELISA)-inhibition with carrot as solid phase showed an intermediate inhibition (30%) between carrot and rDau c 1 in one patient and a considerable inhibition (nearly 100%) between carrot and rDau c 1 in the other patient. These two patients were sensitized directly from carrot allergens. Another group of investigators retrospectively analyzed 27 patients diagnosed with asparagus allergy, who reported adverse symptoms after either ingesting or handling asparagus [42]. Of the 27 subjects, eight had allergic contact dermatitis, 17 had IgE-mediated allergy, and two had both. Of 19 patients with IgE-mediated disease, 10 subjects demonstrated respiratory symptoms. Eight were diagnosed with occupational asthma confi rmed by positive asparagus inhalation challenge, whereas the remaining two had isolated rhinitis. Positive IgE immunoblotting (bands of 15 and 45 to 70 kDA) was observed in 10 subjects. They concluded that asparagus is a relevant source of occupational allergy-inducing allergic contact dermatitis and also IgE-mediated reactions. Similarly, another report highlighted the role of asparagus as a cause of asthma in a patient with respiratory symptoms occurring at work (ie, horticulture) [43]. A 28-year-old man complained of rhinoconjunctivitis and asthma when harvesting asparagus at work. Eating cooked asparagus did not provoke symptoms. A positive skin test reaction was observed with raw asparagus and a methacholine challenge test demonstrated mild bronchial hyperresponsiveness. The patient had an immediate asthmatic response after challenge with raw asparagus extract. Two unexposed subjects with seasonal allergic asthma did not react to the raw asparagus extract. The double-blind, placebo-controlled food challenge with raw asparagus was negative. IgE immunoblotting analyses identified at least six IgE-binding components, ranging from 22 to 73 kDa, only in raw asparagus. Roberts et al. [44] recently reported that a group of children with food allergies also developed asthma when exposed to the aerosolized form of the food. Children 172 Food Allergy with IgE-mediated food allergy developed asthma on inhalational exposure to the relevant food allergen while it was being cooked. Subjects were exposed for 20 minutes to the aerosolized form of the allergen and adverse clinical symptoms and lung functions were monitored. Twelve children with food allergy developed asthma on inhalational exposure to relevant food allergens. The implicated foods were fish, chickpea, milk, egg, or buckwheat. Nine of the 12 children consented to undergo a bronchial food challenge. Five challenges were positive with objective clinical features of asthma. In addition, two children developed late-phase symptoms with a decrease in lung function. Positive reactions were seen with fish, chickpea, and buckwheat; there were no reactions in the seven placebo challenges. These data demonstrate that, as in the case of other aeroallergens, inhaled food allergens can produce both early- and late-phase asthmatic responses. The investigators highlighted the importance of considering foods as aeroallergens in children with coexistent food allergy and allergic asthma. For these children, dietary avoidance alone may not be sufficient and further environmental measures may be required to limit exposure to aerosolized food. Another report focused on three patients who developed asthma and rhinitis caused by exposure to raw, but not cooked, green beans and chards in a nonoccupational environment [45]. Three women developed bronchial asthma and rhinitis after exposure to raw green beans, and one of them also when exposed to raw chards. All of them tolerated ingestion of green beans. Patients reported multiple episodes while handling these vegetables for cooking activities. Allergy to green beans and chards was demonstrated by skin testing and serum-specific IgE. Bronchial challenge test with these allergens showed positive responses to raw, but not cooked green beans and chards. Oral food challenges with green beans (raw and cooked) and chards were negative in all patients. IgE immunoblots of raw and cooked green bean extract revealed two IgEbinding bands with apparent molecular weights of 41.1 and 70.6 kD. Interestingly, a 47-kD IgE-binding protein was detected only in raw green bean extract. Rhinitis symptoms among bell pepper greenhouse employees can be caused by an allergy to occupational allergens, such as green pepper pollen [46]. This investigation was performed to estimate the effect of sensitization to these allergens on rhinitis-specific quality of life (QOL) during and outside the flowering period to evaluate whether the QOL of sensitized employees was comparable with that of chrysanthemum greenhouse employees with rhinitis and an average population sample with perennial rhinitis. Allergic sensitization to bell pepper pollen had a significant negative effective on all the domain and mean QOL scores. The other allergens had no effect on QOL. A significant decrease in all the rhinitis scores was found outside the flowering period. There were no relevant differences in the mean scores of the different domains for both occupational groups. Greenhouse employees scored higher on limitations in activities and much lower on emotional, sleeping, and practical problems compared with individuals with perennial rhinitis. The investigators concluded that bell pepper greenhouse employees were impaired in QOL because of their sensitization to bell pepper pollen, suggesting that bell pepper pollen is the most important occupational allergen in greenhouse workers with allergic symptoms. Sicherer et al. [47 ] have described the clinical characteristics of allergic reactions to peanuts on airplanes. Sixty-two of 3704 National Registry of Peanut and Tree Nut Allergy participants indicated an adverse reaction on an airplane; 42 of 48 patients or parental surrogates contacted confi rmed that the reaction began on the airplane (median age of affected subject, 2 years; range, 6 months to 50 years). Of these, 35 reacted to peanuts and seven to tree nuts, although three of these seven reacted to substances that may have also contained peanut. Exposures occurred by ingestion (20 subjects), skin contact (8 subjects), and inhalation (14 subjects). Reactions generally occurred within 10 minutes of exposure (32 of 42 subjects), and reaction severity correlated with exposure route (ingestion > inhalation > skin). The causal food was generally served by the airline (37 of 42 subjects). Medications were given in fl ight to 19 patients (epinephrine to five) and to an additional 14 at landing or gate return (including epinephrine to one and intravenous medication to two), totaling 79% treated. During inhalation reactions as a result of peanut allergy, more than 25 passengers were estimated to be eating peanuts at the time of the reaction. Initial symptoms generally involved the upper airway, with progression to the skin or further lower respiratory reactions (no gastrointestinal symptoms). The investigators concluded that allergic reactions to peanuts and tree nuts caused by accidental ingestion, skin contact, or inhalation occur during commercial fl ights. Reactions can be severe, requiring medications, including epinephrine. Although allergy to potato by ingestion, as well as inhalation route, is uncommon, one group of investigators was able to study cross-reactivity patterns of potato antigens in a patient with a clinical history of reacting to potato by both routes [48]. An 11-year-old girl, exclusively breast-fed for her fi rst 4 months, developed anaphylactic symptoms after ingestion of a potato at 5 months of age when she was fed potato for the fi rst time. Subsequently, she developed urticaria, angioedema, and respiratory and systemic symptoms on contact with potatoes, ingestion of potatoes, and exposure to cooking potatoes or potato pollen. Allergenic extracts from potato pulp, peel, and pollen were prepared. IgE-mediated allergy to potato extracts was demonstrated by means of immediate skin test reactivity, positive passive transfer, RAST, RAST inhibition, and leukocyte histamine release. Immunoblotting analyses demonstrated specific IgE antibodies directed against several proteins ranging from 14,000 to 40,000 d. Allergic Reactions to Foods by Inhalation Conclusions Previous investigations have clearly established the pathogenic role of food allergy in cutaneous, gastrointestinal, and respiratory tract symptoms. In addition, systemic anaphylactic reactions can occur with food allergy reactions. Oral ingestion is the primary route of exposure to food allergens that can cause or exacerbate allergic symptoms, but an increasing number of published investigations have highlighted allergic reactions to foods following inhalation. This article summarized several recent investigations documenting food allergy reactions that were precipitated by inhalation exposure to airborne food allergens, as opposed to ingestion of the implicated food allergen. For example, published reports have highlighted the inhalation of allergens from fish, shellfish, seeds, soybeans, cereal grains, chicken egg, cow milk, and many other foods in these reactions. Symptoms have typically included respiratory manifestations such as rhinoconjunctivitis, coughing, wheezing, dyspnea, asthma, and even anaphylaxis. In addition, there have been many published reports of occupational asthma following the inhalation of relevant food allergens. Therefore, the evaluation of food allergy should be considered among patients with histories of allergic reactions not only after the ingestion of suspected food allergens, but also following relevant inhalational exposures. Avoiding the ingestion of certain food allergens (eg, fish) is necessary, and preventing exposure to aerosolized particles through inhalation in relevant environments (ie, seafood restaurants, bakeries, and factories processing relevant food allergens) is also encouraged. The medical history supplemented with appropriate laboratory testing and well-designed food challenges can provide useful information in the workup of these patients. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 23. 24. 25. 1. Sampson HA: Food allergy. Part 1: Immunopathogenesis and clinical disorders. 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