Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one‐airway‐one‐disease,” coined over 20 years ago, is a simplistic approach of the links between upper‐ and lower‐airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper‐ and lower‐airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one‐airway‐one‐disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll‐Like Receptors and IL‐17 for rhinitis alone as a local disease; IL‐33 and IL‐5 for allergic and non‐allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono‐ or pauci‐sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Precision medicine (PM) is changing the scope of allergy diagnosis and treatment. An in vitro IgE assay, a prototype PM method, was developed in the sixties and has garnered increasing interest because of the introduction of recombinant components in the test. More recently, microarrays of allergen components have significantly improved the ability to describe the IgE profile. Aim of this study was to evaluate the characteristics of the newly developed Allergy Explorer (ALEX), a macroarray containing both extracted "whole" allergens and molecular components. This method allows the acquisition of an IgE profile comprising 282 reagents (157 allergen extracts and 125 components), resulting in the widest screening of potential allergens available. Sera from 43 patients with allergies were assayed with ALEX and then with ImmunoCAP ISAC. The results of the two tests were compared, and the consistency of the molecular results with the presence of IgE in the relevant extract was also evaluated. A good correlation between ISAC and ALEX was observed. The ALEX results for second-level tests (i.e., specific IgE to complete extracted allergens) were consistent with the results obtained for the relevant components. Despite differences in the methodology, the IgE profiles detected for molecular allergens by ALEX and ISAC were very similar. The differences were mainly related to the lower dynamic range of ALEX and to the use of a CCD inhibitor in the first incubation phase, which reduced the binding of IgE to CCD, as represented in the extracted allergens and components. Based on our findings, ALEX is a novel tool for describing the IgE profile in a PM setting, where the IgE assay must be performed on many allergens and components. In particular, polysensitized patients and patients with pollen-food syndrome will have a real advantage due the combination of the second and third levels of allergy diagnostics in the same chip.

: The numerous links between allergic rhinitis and asthma have been extensively explored in the last two decades, gaining great concern within the scientific community. These two conditions frequen...