How should I evaluate allergic disease in patients with asthma?

TYPES OF ASTHMA

Asthma is increasingly classified by inflammatory endotype based on levels of type 2 inflammation rather than symptoms alone. Broadly, patients may exhibit a type 2-high phenotype, which is often associated with allergic sensitization, eosinophilia, and elevated fractional exhaled nitric oxide, or a type 2-low phenotype, which may be driven by obesity, smoking, irritant exposure, or non–type 2 inflammation. Allergic asthma represents a common type 2-high phenotype, particularly in childhood-onset disease, and is characterized by immunoglobulin (Ig) E–mediated sensitization with a clear correlation between symptoms and exposure.⁵

WHEN DO GUIDELINES RECOMMEND IgE AND ALLERGY TESTING?

Guidelines emphasize that IgE and allergy testing should be performed only when results are likely to influence management.^2–4 The Global Initiative for Asthma² recommends assessment of allergic sensitization using skin-prick testing or serum allergen-specific IgE as part of the structured evaluation of difficult-to-treat or severe asthma. Similarly, the National Asthma Education and Prevention Program^3,4 supports testing when allergic triggers are suspected and confirmation would guide environmental control strategies, immunotherapy eligibility, or selection of biologic therapy.

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Measurement of total serum IgE alone has limited diagnostic value. Total IgE neither confirms nor excludes allergic asthma and should not be used as a screening test. Its principal clinical role is for determining eligibility and dosing for anti-IgE biologic therapy.^2,6,7 Very high IgE levels (eg, > 1,000 IU/mL) are not specific for allergic asthma, but may warrant further evaluation for alternative diagnoses such as allergic bronchopulmonary aspergillosis or parasitic infection, depending on the clinical context.⁸

WHEN SHOULD I TEST FOR ALLERGIES IN PATIENTS WITH ASTHMA?

Allergy testing is most useful when the clinical history suggests IgE-mediated, exposure-related symptoms. Guidelines advise history-directed testing rather than indiscriminate screening, as sensitization alone does not equate to clinically relevant allergic disease.² Testing is reasonable in patients with any of the following:

• Seasonal asthma exacerbations

• Symptoms triggered by pets, dust mites, molds, or occupational exposures

• Persistent asthma with comorbid allergic rhinitis

• Childhood-onset asthma persisting into adulthood with allergic features.

In contrast, testing is typically low yield in asthma driven by exercise, irritants, obesity, or smoking unless the history suggests an allergic contribution.

SHOULD I CHOOSE BLOOD OR SKIN TESTING?

Both inhalant skin-prick testing and serum allergen-specific IgE testing are acceptable methods for evaluating allergic sensitization in asthma. Guidelines do not mandate one approach over the other; selection should be guided by clinical context and feasibility (Table 1).^2–4

For most primary care clinicians, serum allergen-specific IgE testing is the most accessible initial option. Testing should be limited to inhalant allergens relevant to the patient’s symptoms, exposures, and local environment, such as pollens, dust mites, animal dander, and molds; common inhalant panels typically include these substances. Broad screening panels are discouraged. Food allergy testing is not indicated for routine asthma evaluation unless there is a history of food-induced anaphylaxis or respiratory reactions.

Skin-prick testing offers rapid results and high sensitivity but typically requires referral to allergy and immunology specialists, temporary discontinuation of antihistamines, and absence of dermatologic conditions that limit interpretation. Serum testing is preferred when skin testing is unavailable, when antihistamines cannot be stopped, or when skin disorders such as dermatographism interfere with testing.⁹

Regardless of modality, positive results indicate sensitization, not disease. Results must be interpreted in the context of exposure history, symptom timing, and seasonality. For example, sensitization to fall pollen in a patient with exclusively spring exacerbations is unlikely to be clinically relevant. Low-level positive serum IgE results (eg, < 1.0 kU/L), although reported as positive, are frequently not clinically relevant and should not drive management decisions.²

WHAT SHOULD I DO WHEN ASTHMA IS DIFFICULT TO CONTROL?

Before escalating therapy, guidelines emphasize systematic reassessment. Clinicians should confirm the diagnosis, assess adherence and inhaler technique, identify and treat comorbidities, and optimize inhaled controller therapy. Only after these steps have been taken should asthma be classified as difficult-to-treat or severe.^2–4

Evaluation should also include assessment of which inflammatory endotype the patient’s asthma corresponds to by using targeted allergy testing and type 2 biomarkers, such as blood eosinophil count and fractional exhaled nitric oxide, to guide selection of advanced therapies.

SHOULD I USE BIOLOGICS OR ALLERGEN IMMUNOTHERAPY FIRST?

Although both target allergic mechanisms, biologic therapy and allergen immunotherapy serve distinct roles. Biologic therapies target downstream inflammatory pathways and are indicated for moderate to severe asthma that remains uncontrolled despite optimized inhaled therapy, particularly when characterized by frequent exacerbation or systemic corticosteroid dependence. Selection is guided by biomarkers, including total IgE level, blood eosinophil count, and fractional exhaled nitric oxide.⁷

Allergen immunotherapy targets upstream allergic drivers and is primarily indicated for allergic rhinitis, with asthma considered a comorbidity. It is a desensitization strategy aimed at inducing long-term immune tolerance to specific allergens and has disease-modifying potential, although clinical benefit develops gradually.^10–12

Allergen immunotherapy should be considered in patients with documented IgE-mediated sensitization, clear exposure–symptom correlation, persistent allergic rhinitis despite pharmacotherapy, and asthma that is controlled or only mildly to moderately severe.^10,12–14

Uncontrolled asthma is the strongest predictor of systemic reactions during immunotherapy and is a contraindication to starting immunotherapy. In patients with severe asthma, biologic therapy generally takes precedence. Immunotherapy may be considered only after asthma stability has been achieved and allergic rhinitis remains clinically significant.^2,11,12

DISCLOSURES

The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.

The authors disclosed use of ChatGPT 5.5 to conduct a literature search and to improve language, wording, organization, and structure in the development of the manuscript submission. The authors take full responsibility for the published content.