How to manage asthma in a food-allergic patient: A practical approach

Abstract

This article examines the intricate interplay between food allergy and asthma by focusing on the challenges of managing food allergy in patients with asthma. Although asthma is a prevalent comorbidity in food allergy, often > 50% among older children, its impact on food allergy outcomes remains not fully understood. Studies indicate a higher prevalence of asthma among individuals experiencing fatal anaphylaxis, yet there is no consistent evidence that supports a direct causal link between food allergy and the development of asthma. Clinicians and patients often overestimate asthma control, which leads to underestimated risks associated with severe food allergy reactions. This article underscores the critical need for optimal asthma control before and during oral food challenges and dietary advancement therapies, highlighting the heightened risk of severe reactions in individuals with poorly controlled asthma. Whereas biologics such as omalizumab show promise in enhancing asthma control and increasing food allergy thresholds, a comprehensive, multifaceted approach that involves diligent asthma management, patient education, and appropriate treatment strategies is essential for ensuring safe and effective management of food allergy in individuals with asthma. Integrated management, which addresses both conditions concurrently, is vital for improving patient safety and quality of life.

Managing patients with food allergy requires a thorough understanding of the individual as a whole. Food allergies influence various aspects of a patient’s life, extending beyond the medical to include psychosocial, financial, and quality-of-life factors. However, the presence of other comorbid medical conditions can also directly impact the management of food allergies. Specifically, asthma is a common comorbidity that affects a substantial proportion of individuals with food allergy.¹ Asthma can lead to worsening food allergy outcomes and alterations in management strategies, often depending on asthma control. Unfortunately, both clinicians and patients frequently overestimate asthma control, which results in an underrecognized risk for these patients with food allergy and asthma. This risk becomes especially pertinent with the implementation of dietary advancement therapies (DAT), such as food ladders and oral immunotherapy (OIT).²

This article assesses the coexistence of food allergies and asthma, identifies areas in which poor control may place patients at risk, and suggests practical management strategies to enhance safety and improve outcomes.

WHAT IS THE LINK BETWEEN ASTHMA AND FOOD ALLERGY?

Asthma and food allergies frequently develop in individuals who are atopic and often progress independently along the atopic march. However, the coexistence of asthma and food allergy is well recognized. Approximately ≥ 50% of patients with food allergies may have comorbid asthma.¹ In younger patients, the presence of food allergy sensitization is identified as a risk factor for the prediction of asthma in the Modified Asthma Predictive Index.³ Just as allergic rhinitis may influence asthma and atopic dermatitis may impact food allergies, asthma may also affect outcomes in food allergy. However, there is no consistent evidence that food allergies cause asthma or vice versa, and, aside from rare occupational exposures, food allergies do not worsen asthma control.⁴

WHAT IS THE LINK BETWEEN ASTHMA AND FOOD ALLERGY SEVERITY?

Not surprisingly, because respiratory compromise is one of the most common presentations in life-threatening anaphylaxis, it has been postulated that asthma is associated with these severe reactions.⁵ Analysis of some initial data that suggests a modifying effect of asthma on more severe food allergy outcomes came from a retrospective analysis of fatal anaphylaxis. In 2007, Bock et al.⁶ reported a retrospective analysis of American patients who experienced fatal anaphylaxis. Among these 31 patients, 23 (74%) had asthma, whereas it was unclear whether the remaining 8 did or did not have asthma.⁶ Notably, at least 22 of these patients (71%) also failed to receive epinephrine in a timely manner.⁶ Similarly, Pumphrey and Gowland⁷ reported that 43 of 48 patients (90%) in the United Kingdom with fatal food allergy were treated for asthma, and 10 experienced some degree of asthma exacerbation that precedes the fatal reaction. This apparent overrepresentation of asthma in these populations raised concerns that asthma may be linked to worse outcomes. However, given the prevalence of food allergy and asthma, alongside the rarity of fatal or near-fatal anaphylaxis, it is evident that not all patients with asthma and food allergy are at risk for severe reactions simply due to the presence of asthma.

Ultimately, the severity of a food reaction is not solely determined by the presence or absence of one comorbidity, such as asthma.¹ It is related to the allergen itself, the existence of cofactors such as exercise, illness, or medication; the presence of other diseases, including cardiovascular or hematologic conditions; and access to prompt and appropriate emergency treatment epinephrine.

Two recent systematic reviews sought to evaluate the risk of asthma and the severity of anaphylaxis. In 2021, Tejedor-Alonso et al.⁸ conducted a meta-analysis and systematic review, which suggested that the presence of asthma resulted in an odds ratio of 1.89 (1.26, 2.83) for the severity of anaphylaxis when asthma is present. Several of these studies exhibited a moderate-to-high risk of bias, and the quality of evidence was GRADEd to be low.⁸ However, Turner et al.¹ recently suggested no conclusive association between the presence of asthma and the severity of food allergy. This study assessed the risks of more severe anaphylaxis, intubation, and intensive care unit admission from accidental reactions as well as anaphylaxis during food challenges, with no significant increase in risk. The only exception arose when retrospective observational studies were evaluated, which showed a weak association.⁹ This review also noted that retrospective data linked poor control of asthma to more severe anaphylaxis.⁹ Thus, although having asthma likely does not directly lead to severe anaphylaxis, critically assessing asthma control may be valuable for improving outcomes for these patients.

It is important to note that even though the prevalence of asthma in some clinical trials, such as the PEPITES epicutaneous immunotherapy trial, may be similar to the 50% reported in other epidemiologic studies, these studies typically exclude moderate-to-severe or uncontrolled asthma from these trials.¹⁰ This exclusion leads to an underrepresentation of patients with more severe asthma in these studies;¹⁰ however, it highlights the critical concern that significant or uncontrolled asthma has the potential to worsen outcomes in food allergy.

THE PROBLEM OF ASTHMA CONTROL

Unfortunately, clinicians and patients often overestimate the adequacy of asthma control for individual patients. Nonetheless, clinicians should ideally strive to ensure proper assessment of control and provide adequate treatment to maintain it.

A significant Canadian publication that evaluated “The Reality of Asthma Control in Canada” highlighted the disproportionate perceptions of control.¹¹ When guideline-based asthma control criteria were applied, only 47% of patients were deemed “controlled.”¹¹ In contrast, > 97% of patients reported that their asthma was under control. Physicians demonstrated slightly better accuracy in assessing these patients' control, with 88–90% of clinicians believing their patients were well controlled.

The reasons for this substantial disparity in perceptions and the worsening of the disease are numerous and may include patient unawareness, habituation, cognitive biases among physicians and patients alike, steroid phobia, previous misdiagnosis, and a fundamental lack of time for clinicians to adequately assess control (Table 1).¹¹ This is especially prevalent in patients who are atopic and with multiple allergic conditions that need assessment and management in a single visit. This critical oversight may increase the risk of accidental reactions, incidents during oral food challenges (OFC), or complications during active treatment with DATs such as food ladders and OIT.

Table 1.

Reasons for lack of asthma control

Category	Reason	Impact on Food Allergy Management
Patient factors	Lack of awareness	Underestimation of severity, poor adherence to treatment
	Habituation to symptoms	Delay in seeking medical attention, continued exposure to allergens
	Cognitive biases (e.g., steroid phobia)	Avoidance of effective treatments
	Poor medication adherence	Ineffective treatment, increased risk of exacerbations
Clinician factors	Time constraints during single visits (multiple allergic diseases)	Inadequate assessment of asthma control
	Previous misdiagnosis	Incorrect treatment, delayed diagnosis of asthma
	Overestimation of asthma control	Underestimation of risk during OFCs and DATs
Systemic factors	Lack of resources and/or support for optimal management (e.g., education, monitoring, cost of medications)	Inadequate management strategies, increased risk of severe reactions

OFC = Oral food challenge; DAT = dietary advancement therapy.

HOW SHOULD CLINICIANS APPROACH ORAL FOOD CHALLENGES WITH THOSE WITH ASTHMA?

OFCs represent the criterion standard for diagnosing food allergies and are generally regarded as safe. Despite the performance of countless OFCs, only two fatalities have been reported, one of which involved an individual with asthma.¹² Recent guidelines for conducting OFCs acknowledge that reactions during an OFC may manifest as cough, wheeze, and/or dyspnea, and indicate that reactions could be more severe if asthma is uncontrolled or untreated.¹³ Notably, certain foods may predispose patients to lower respiratory tract symptoms. A recent evaluation of OFC outcomes indicated that these lower respiratory tract symptoms were significantly more prevalent in baked milk OFCs.¹⁴ Although the systematic review by Turner et al.¹ did not establish a link between asthma and the severity of OFC reactions, this is not surprising because individuals who are symptomatic or with untreated asthma are generally not recommended for these challenges.

Practically, the recent guidelines on OFCs list the following as reasons to reschedule or delay OFC: concurrent illness or active respiratory symptoms such as wheeze or cough, use of a short-acting β-agonist in the preceding 48 hours for cough or wheeze, or poorly controlled asthma.¹³

To ensure asthma control, a thorough patient assessment, including medical history and focused asthma history, should be conducted before each food challenge. A physical examination should take place before initiating OFC, particularly if the history suggests potential asthma symptoms. Objective assessments, including vital signs, peak flow, spirometry, and pulse oximetry, should be considered, especially in patients with a history of asthma (Table 2).

Table 2.

Asthma control checklist before food challenge or OIT^*

Patient history:

□ Asthma Diagnosis and History: Confirmed diagnosis? Duration of asthma? Frequency of exacerbations?

□ Current Asthma Symptoms: Presence of cough, nocturnal cough, wheeze, shortness of breath, or chest tightness in the past few weeks?

□ Asthma Medications: List all current asthma medications (inhalers, controllers, etc.) and frequency of use. Are they being used correctly?

□ Recent Medication Changes: Any recent changes to asthma medication regimen?

□ Recent Illness: Any recent infections (colds, flu, etc.)?

□ Other Relevant History: Atopy (eczema, allergic rhinitis), other comorbidities? History of anaphylaxis?

□ OIT/DAT therapy: Active immunotherapy treatment? Details of any symptoms or issues during therapy.

□ Use of Short-Acting β-Agonists: Use of a short-acting β-agonist (e.g., albuterol) in the past 48 hours? If so, how frequently and for what reason? How well do they respond?

Physical examination:

□ Respiratory Assessment: Auscultation of lungs; listen for wheezes, rales, or rhonchi.

□ Vital Signs: Measurement of heart rate, respiratory rate, oxygen saturation. Note any abnormalities.

□ Peak Expiratory Flow: Measurement of peak expiratory flow (if applicable); compare with personal best.

□ Spirometry: If clinically indicated, spirometry should be performed to assess lung function.

Objective measures:

□ Pulse Oximetry: Measurement of oxygen saturation

□ Asthma Control Assessment Tool: Use of a validated asthma control questionnaire. (e.g., Asthma Control Test, Trudy B. Pendergraft, MSPH, GlaxoSmithKline, Research Triangle Park, North Carolina)

Clinical decision:

□ Asthma Control Assessment: Based on the above, is the patient's asthma considered well controlled? (Consider severity, frequency, and response to treatment.)

□ Food Challenge and/or OIT Decision: Is the patient suitable for the food challenge based on his or her asthma control? If not, what are the appropriate next steps?

□ Documentation: Thorough documentation of all assessments and clinical decisions.

OIT = Oral immunotherapy; DAT = dietary advancement therapy.

^*This checklist is for informational purposes only and should not replace the judgment of a qualified health-care professional. The decision to proceed with food challenge and/or OIT should be made by a physician or allergist experienced in managing food allergies in patients with asthma.

Finally, it is important to note that epinephrine and albuterol are structurally quite similar. Epinephrine effectively treats respiratory symptoms as well as other allergic reactions, including hypotension, whereas albuterol primarily results in bronchodilation.¹⁵ Thus, as per guidelines, the primary treatment for a patient with asthma who presents with respiratory symptoms should be epinephrine, with albuterol used as an adjunct if necessary.¹⁶

HOW SHOULD CLINICIANS APPROACH DATs IN INDIVIDUALS WITH ASTHMA?

Whereas OFCs are conducted in the office under clinician supervision, the active treatment of food allergies requires a high level of asthma control because most of the treatment occurs at home.¹⁷ DATs, such as food ladders and immunotherapies, are being used more frequently to modify food allergies in select individuals.¹⁸

Food ladders are increasingly used among patients allergic to eggs and milk as a way to enhance dietary options and potentially expedite the resolution of these allergies. Initially designed for low-risk, non–immunoglobin E (IgE) mediated patients, food ladders have also gained traction with patients facing higher-risk, IgE-mediated conditions.¹⁷ Discussions around standardizing these ladders for individuals with IgE-mediated food allergies have raised cautions for patients with asthma. A recent review by Venter et al.¹⁹ indicated that patients without asthma are preferable candidates for food ladders, whereas patients who are stable and actively treated may also be suitable.

Unfortunately, both fatal and near-fatal anaphylaxis have been reported among patients managed with DATs. Similar to earlier data on fatal accidental anaphylaxis, a recent 2023 review by Mack et al.¹² highlighted that all these patients were asthmatic, with 63% either uncontrolled or experiencing an exacerbation. Whereas a more recent systematic review suggested reasonable safety for most patients undergoing DATs, it was limited by highly biased, poorly controlled, often retrospective data.²⁰

Regardless, several groups have attempted to provide guidance to enhance safety for patients by incorporating DATs, e.g., food ladders, at home.^19,21 A checklist-based approach underscores the critical importance of asthma control by outlining the symptoms parents should monitor.²¹ This group also emphasized the “red-flag” warnings when a new diagnosis of asthma is made in these patients or if asthma becomes uncontrolled.

HOW SHOULD CLINICIANS APPROACH FOOD OIT IN PATIENTS WITH ASTHMA?

Clinicians are increasingly offering OIT to patients with food allergies. A recent study indicated that > 50% of Canadian allergists are currently providing OIT.²² Reassuringly, OIT does not seem to negatively impact asthma control, with two studies showing no worsening of FEV₁, PD20, or FeNO.²³ However, this active food allergy treatment necessitates optimal asthma control to ensure safety. Real-world American data that involved 270 patients treated with peanut OIT found that intermittently treated asthma significantly increased the risk of epinephrine-treated reactions (p < 0.035).²⁴ This finding strengthened the recommendation for proper asthma treatment during OIT. Similarly, during milk OIT, asthma was identified as a risk factor for reactions by an Israeli group treating 194 patients.²⁵ Even before initiating milk OIT, the patients with asthma and milk allergy were at a significantly higher risk of anaphylaxis and hospital visits and/or admissions (all p < 0.03).²⁵ Furthermore, during milk OIT, the risk of reactions and the need for epinephrine treatment was highly significant (p < 0.0001).²⁵ These patients were also at a higher risk of OIT discontinuation or not achieving full desensitization. In addition, a recent real-world study that examined the reasons for OIT discontinuation noted that 66% of patients who stopped OIT due to uncontrolled comorbidities cited poor asthma control or inadequate medication adherence as the reasons.²⁶

As such, the PPOINT study,² an international Delphi consensus focused on adequate patient optimization and preparation before OIT, recognized the importance of asthma control. The group unanimously agreed (100%) that asthma should be well controlled before and during the OIT process.² In fact, second only to unwillingness to use epinephrine, uncontrolled asthma was one of the highest-ranked absolute contraindications to OIT. Finally, this group also endorsed that uncontrolled asthma or family refusal to treat asthma was highly concerning and justifiable to discontinue OIT if steps were not taken to improve control and adherence.²

In practice, poor treatment adherence poses a significant barrier to asthma control and OIT demands exceptional adherence to both asthma management and OIT, which requires families and clinicians to effectively manage two distinct conditions to ensure safety.²⁷ This multifaceted approach may come as a surprise to families who simply want treatment for their food allergy. Ideally, individuals with asthma should strive for optimal control by using standard methods of assessment. Most, if not all, individuals with asthma and undergoing OIT should receive active asthma treatment, and families may benefit from asthma education.²

Finally, before dosing, families need to be able to actively evaluate the safety of dosing by ensuring that asthma is under control based on symptoms and potentially home peak expiratory flow monitoring or home spirometry; similarly, before in-office dose increases, a suitable asthma history should be taken, asthma control should be verified, and objective measurements such as peak expiratory flow and FEV₁ can be undertaken.

IS THERE A ROLE FOR BIOLOGICS SUCH AS OMALIZUMAB?

Biologics such as omalizumab offer a distinctive approach to enhancing asthma control and elevating food reaction thresholds, and potentially making active treatment strategies safer. In both adult and pediatric patients, omalizumab leads to notable reductions in exacerbations, improvements in lung function, decreased reliance on relievers, and better asthma symptoms.²⁸

Due to its unique anti-IgE properties, reports of omalizumab as an adjunct to OIT have been documented for > 2 decades. More recently, a randomized controlled trial showed that omalizumab could significantly increase the threshold for patients with peanut and other food allergies, with 67% of actively treated patients versus 7% of patients on placebo achieving the primary objective of ingesting 600 mg of peanut protein.²⁹ Similar results were observed with other foods, including milk. However, this study excluded patients with severe asthma. A European study treated patients with severe asthma who also had coexisting food allergies with omalizumab and demonstrated increased threshold, reduction in food reactions, improvement in quality of life, and an impressive 61% free inclusion of the culprit food into the patient’s diet.³⁰

CONCLUSION

Managing food allergies in patients with asthma requires a comprehensive and multifaceted approach. It is crucial to maintain optimal asthma control to ensure safety for OFCs and for treatments such as OIT. Clinicians must diligently evaluate asthma control through objective measures and educate families on proper monitoring techniques. The role of biologics such as omalizumab offers promising advancements in managing both asthma and food allergies, potentially increasing treatment thresholds and enhancing quality of life. Ultimately, an integrated strategy that addresses both asthma and food allergy management is essential for achieving the best outcomes for this vulnerable population. By combining vigilant asthma control, proper education, and innovative treatments, health-care providers can offer safer and more-effective solutions for managing food allergies in patients with asthma.