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.
