The Utility of Nasal Challenges to Phenotype Asthma Patients

Abstract

Asthma is a heterogeneous disease in terms of both phenotype and response to therapy. Therefore, there is a great need for clinically applicable tools allowing for improved patient classification, and selection for specific management approaches. Some interventions are highly helpful in selected patients (e.g., allergen immunotherapy or aspirin desensitization), but they are costly and/or difficult to implement. Currently available biomarkers measurable in peripheral blood or exhaled air display many limitations for asthma phenotyping and cannot identify properly the specific triggers of the disease (e.g., aeroallergens or NSAID). The united airway concept illustrates the relevant epidemiological and pathophysiological links between the upper and lower airways. This concept has been largely applied to patient management and treatment, but its diagnostic implications have been less often explored. Of note, a recent document by the European Academy of Allergy and Clinical Immunology proposes the use of nasal allergen challenge to confirm the diagnosis of allergic asthma. Similarly, the nasal challenge with lysine acetylsalicylate (L-ASA) can be used to identify aspirin-sensitive asthma patients. In this review, we will summarize the main features of allergic asthma and aspirin-exacerbated respiratory disease and will discuss the methodology of nasal allergen and L-ASA challenges with a focus on their capacity to phenotype the inflammatory disease affecting both the upper and lower airways.

The causality between C-reactive protein and asthma: a two-sample Mendelian randomization analysis

“…Asthma is a complex syndrome involving many phenotypes and subphenotypes (5). According to different classi cation criteria, asthma can be divided into different subtypes, including etiology, pathophysiology, clinical manifestations, treatment response.…”

Organ‐specific allergen challenges in airway allergy: Current utilities and future directions

“…[9][10][11][12] Nevertheless, the success of these interventions largely depends on the correct identification of the allergic triggers affecting each patient, 13 and organ-specific allergen challenges may be used for this purpose. 14 The aim of this review is to summarize novel data regarding the methodology of NAC, CAC, and BAC, and to address these aspects in the context of existing clinical protocols. Moreover, the potential of organ-specific allergen challenges for precision medicine in respiratory conditions will be emphasized.…”

“…Finally, some therapeutic interventions (e.g., allergen immunotherapy (AIT) or anti‐IgE treatment) are recommended by the clinical guidelines only for allergic individuals 9–12 . Nevertheless, the success of these interventions largely depends on the correct identification of the allergic triggers affecting each patient, 13 and organ‐specific allergen challenges may be used for this purpose 14 …”

Nasal challenge with ketorolac: utility and safety in clinical practice

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To de Editor, Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs)-exacerbated respiratory disease (AERD -NERD) is characterized by an underlying Th2 airway disease exacerbated by the intake of this type of medication. The nasal challenge test with NSAIDs, specifically with lysine acetylsalicylic acid (NLC) or ketorolac (NKC), is indicated for its diagnosis as an alternative to oral/bronchial challenges when FEV1<70% or with uncontrolled asthma [1][2][3]. NKC is also used as a first step in aspirin desensitization protocols for AERD-NERD patients [4,5].NKC has lower sensitivity, specificity, positive predictive value, and negative predictive value compared to OAC (gold standard) [6].

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“…Inflammatory mediators migrate from the nasal mucosa to the lower airways after nasal challenge, causing bronchial inflammation [3]. NKC has been proposed as a safer diagnosis challenge for patients contraindicated to bronchial or oral challenges.…”