Allergic rhinitis: the nose and beyond

Over the past 15 years, the general pathogenic interpretation of allergic rhinitis (AR) has rapidly changed and evolved. At least three main aspects of this evolution deserve special consideration: (i) the more detailed knowledge of immunological mechanisms, (ii) the pathogenic unification of the upper and lower airways and (iii) the extension of clinical investigation regarding paranasal sinuses, which has gradually introduced the term upper respiratory disease into our common language to encompass rhinitis, chronic rhinosinusitis (CRS), nasal polyposis (NP) and related disorders. In parallel, investigation has commenced in many other clinical aspects of respiratory allergy in addition to nasal symptoms. These facts have reinforced the status of allergology as a cross-sectional specialty that has increasingly more contact points with pulmonology, ENT, clinical immunology and internal medicine. The pathogenic unity of the upper and lower respiratory tract in allergy was first envisaged about 10 years ago and was gradually elucidated and confirmed. The relationship which existed between the nose and the bronchi could be hypothesized on the basis of epidemiological observations, showing the frequent co-existence of rhinitis and asthma (1, 2), and also as a consequence of the structural similarity of the nasal and bronchial mucosa. Subsequently, it was shown that allergic inflammatory responses are identical in the two compartments, that there is a bi-directional link between the nose and the bronchi, and that a systemic signalling pathway (3) is probably involved. The hypothesis of the united airways disease led to the comparative study of the inflammatory features in the nose and bronchi. In this regard, the phenomenon of remodelling (epithelial shedding, collagen deposition, basement membrane thickening, smooth muscle hyperplasia) was clearly shown to be a distinctive feature of bronchial asthma. Moreover, it was demonstrated that remodelling is, at least in part, constitutive and genetically controlled (4). Nonetheless, despite the apparent structural similarity of the nose and the bronchi, remodelling is not always clearly detectable in rhinitis and its features in the nose are somewhat less defined than in the bronchi (5). This different and peculiar behaviour of the nose can be explained either by the different embryological origin of the nasal mucosa or by the absence of smooth muscle cells (6), as a source of specific cytokines that may favour remodelling (7–9). In this issue of Allergy, these challenging aspects of remodelling in rhinitis are discussed in detail in an extensive review by Watelet et al. (10). It is important to note that the article reviews the pathogenesis of remodelling as a repairing process, not only in the nasal mucosa but also in paranasal sinuses and in nasal polyposis (11). Even though we have an impressive amount of experimental data available on nasal and bronchial mucosa in allergic diseases, little is known about the eye that, in turn, is a frequent target organ of allergy. Hughes et al. (12) used biopsies to study the structural features of conjunctiva in seasonal allergic conjunctivitis. They found that out of the pollen season, in symptom-free subjects, the expression of E-cadherin and ICAM-1 adhesion molecules as well as some keratins was significantly reduced in comparison with normal subjects. As E-cadherin and ICAM-1 are involved in the maintenance of epithelial integrity as well as in the repairing processes, the authors hypothesize that allergic conjunctiva has a constitutionally weak structure and can be easily penetrated by allergens. Over the past decade, as previously mentioned, paranasal sinuses and their diseases (nasal polyps and chronic rhinosinusitis) (13) have been extensively investigated as far as their relationships with rhinitis are concerned. Nasal G. Passalacqua Allergy and Respiratory Diseases, Department of Internal Medicine, University of Genoa, Genoa, Italy