LONDON—Allergies can exacerbate asthma and make symptom control more difficult. Although food allergies can produce respiratory symptoms, their role in life-threatening asthma has not been examined in detail, nor has the relationship between the lungs and gut in the context of food allergy and asthma been well studied. Recently, however, researchers in the United Kingdom found that in children, a combination of poor asthma control and food allergy can greatly increase the risk of a life-threatening asthma exacerbation.[1]

They conducted a case-control study of 19 children (ages 1 to 16) who were admitted to a pediatric ICU with severe asthma that required ventilation and 38 children—two for each case patient—who were admitted to the emergency department (ED) with asthma. All of the children were asked about exposure to food allergens and symptoms of anaphylaxis within the 24 hours prior to their asthma exacerbation.

Children were assessed between 18 and 20 months after their initial hospitalization or ED admission. At this time, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were measured before and 15 minutes after administration of twice the usual dose of a bronchodilator. Skin testing was performed for grass and tree pollens, molds, dog, cat, and house dust mite. In addition, specific immunoglobulin E to common food allergies was measured.

FOOD ALLERGY A RISK FACTOR

Food allergy, which was present in 10 cases and four controls, was a significant risk factor for life-threatening asthma; it increased the risk of a severe exacerbation almost sixfold. The average number of diagnoses for other allergies was 3.58 and 2.73 among cases and controls, respectively. The presence of more than three allergies increased the risk of life-threatening asthma.

Among the cases, FEV1 (as a percentage of predicted) was 81% after treatment with oral and inhaled corticosteroids, compared with 93.4% among the control group. There was a trend toward reduced bronchodilator reversibility in the case group as well.

“It is difficult to know what caused the decline in lung function and reduced bronchodilator response,” said Gideon Lack, FRCPCH, Senior Lecturer and Consultant in Pediatric Allergy and Immunology at St. Mary’s Hospital in London. “Decreased lung function with a poor bronchodilator response in asthma despite adequate anti-inflammatory treatment is suggestive of airway remodeling.”

After logistic regression, the independent risk factors for life-threatening asthma were food allergy and frequent hospitalization for asthma, with adjusted odds ratios of 5.89 and 9.85, respectively. According to the authors, more than one third of children with food allergies have asthma, and as many as 8% of children with asthma have food allergies.

FOOD ALLERGY/ASTHMA CONNECTION?

What are some possible explanations for the apparent relationship between food allergy and life-threatening asthma? “There isn’t really a clear-cut connection between the gut and the respiratory tract as there appears to be between the upper and lower respiratory tract,” admitted John M. James, MD, an allergy and immunology specialist at the Colorado Allergy and Asthma Centers in Fort Collins. “There are allergic reactions that can be isolated to the lung or gut, and there are also systemic anaphylactic reactions, which can involve the skin, intestines, and lungs.” The type of reaction a patient will have is highly variable and, Dr. James pointed out, “It isn’t easy to predict what will happen—particularly if the patient has not had a similar reaction in the past.”

“The important point is that food allergy has been artificially separated from inhalant allergies,” said Dr. Lack. “Thus, food allergies are seen to cause gastrointestinal symptoms, and inhalant allergies, respiratory symptoms.” Instead, Dr. Lack suggested that physicians be aware that “food allergens can behave like inhalant allergens in the sense that they can become aerosolized in the environment and cause only late-phase responses.” An example of this would be vapors from boiling seafood.

Whatever the mechanism, control of asthma symptoms is critical in patients with coexistent asthma and food allergy. “If someone has poorly managed asthma, there may be a diminished bronchodilator response over time,” said Dr. James. This can be seen in people with occupational asthma, he observed. If they remain in their current jobs and are constantly exposed to asthma triggers, their lung function will decline.

Dr. Lack suggested that food allergy may be an indicator or biological marker for children who are susceptible to severe asthma. “Perhaps the most important message is that special attention should be given to children who have food allergies and asthma.”

“Today,” said Dr. James, “one question that clinicians should ask if they have a chronic asthma patient who is not responding to appropriate treatment is, ‘Is there a food allergy exposure?’ Features that may indicate the need for evaluation of food allergy include recalcitrant or otherwise unexplained acute, severe asthma, asthma triggered after ingestion of a specific food, and asthma that is accompanied by other manifestations of food allergy (eg, moderate to severe atopic dermatitis or anaphylaxis).”

It is important to keep in mind that patients can have severe anaphylaxis without asthma, and vice versa. However, Dr. James added, “Patients with asthma are a higher-risk group for anaphylaxis than those without asthma.”

Pollen Allergy Causes GI Symptoms

Göteborg, Sweden—In some patients with food allergies, challenge with the trigger food produces a gastrointestinal (GI) reaction that is similar to the reaction seen in the respiratory mucosa of patients with seasonal allergies. The converse has now also been demonstrated: Researchers in Sweden observed an inflammatory response in the GI tracts of atopic individuals during birch pollen season—but not in healthy nonallergic controls.[1] Nine patients with birch pollen allergy and nine controls were recruited. All subjects had their atopic status confirmed by skin tests and serum immunoglobulin E (IgE) measurements. They also completed a questionnaire about their reactions to birch- associated foods, if and when they had GI symptoms, and if they fulfilled the criteria for irritable bowel syndrome. The subjects underwent gastroscopy at the end of two different birch pollen seasons, when maximum exposure was most likely. Duodenal biopsy was performed and serum samples obtained after a seven-day period during which all birch-associated foods were avoided. The second biopsy specimens were taken after the birch pollen season, when patients were free of symptoms. Allergy symptoms were recorded on diary cards for two weeks, beginning with the seven-day period when all birch-associated foods were withdrawn. The atopic patients were then asked to stop using all allergy medications. SYMPTOMS DURING ALLERGY SEASON After ingesting birch-associated foods, the nine atopic patients all had oral symptoms (itchy throat, hoarseness, sensation of swollen throat, or pain and redness in the throat). Six of the patients also had oral allergy symptoms during birch pollen season, and seven reported GI symptoms, such as abdominal pain, nausea, diarrhea, flatulence, abdominal pain, and constipation. GI symptoms were present in three patients year-round and in four during the birch pollen season only. In three patients, these symptoms varied with the severity of the birch pollen season. Five patients with GI symptoms fulfilled the criteria for irritable bowel syndrome. The nine control patients, by definition, had neither oral nor GI symptoms following birch pollen exposure. During the birch pollen season, the number of IgE cells and major basic protein (MBP) eosinophils was elevated in the duodenal mucosa of atopic patients but not in controls. Off-season, MBP eosinophil and IgE cell counts in the villi did not differ between groups. A SYSTEMIC REACTION? According to the authors, this study suggests the presence of allergic inflammation in the duodenal mucosa in atopic patients during the birch pollen season. Theoretically, GI reactions could be caused by dissolved inhalants in the oropharynx passing into the digestive tract. However, an in vitro experiment showed that after 30 minutes in duodenal juices, birch pollen retains only 10% of its original allergenic activity. Eosinophilic inflammation has been observed in the duodenal mucosa of atopic, nonatopic, and asthmatic patients, suggesting the involvement of the mucosal immune system. This view has been supported by studies in nonasthmatic patients with food allergies, who have increased levels of eosinophils, neutrophils, and interleukin 8 in sputum—pointing to the presence of airway inflammation. The authors argue that their results provide evidence of a relationship between the allergic response in the respiratory tract and the gut, and that a systemic inflammatory response occurred in the patients with birch pollen allergy. —Gale Jurasek

Reference 1. Magnusson J, Lin XP, Dahlman-Höglund A, et al. Seasonal intestinal inflammation in patients with birch pollen allergy. J Allergy Clin Immunol. 2003;112:45-51.

—Gale Jurasek