From Mouse to Man: Translational Value of Animal Models of Allergic Rhinitis

Allergic rhinitis (AR) is the most prevalent atopic disease in the world, affecting 10-20% of the population or up to 600 million people (Asher et al. 2006; Meltzer and Bukstein 2011). Data from multi-year international studies show that the incidence of upper airway allergy is greater than that for asthma, and since 1994 the prevalence of AR has increased more rapidly than allergic asthma (Asher et al. 2006; Weinmayr et al. 2008). The common clinical definition of AR is nasal obstruction, sneezing, rhinorrhea, and pruritus associated with known or suspected allergens. Comorbidity with asthma is common, with 50% to 100% of allergic asthma patients in the United States and Europe reporting AR symptoms (Gaugris et al. 2006). Furthermore, as much as 30% of individuals with AR have lower airway symptoms, such as bronchial hyperreactivity, and AR has emerged as a risk factor for eventually developing asthma (Ciprandi and Cirillo 2006; Ponikau et al. 2003). Because of the frequency of AR coexisting with allergic asthma, a role for common pathophysiologic linkages between asthma and AR has been a focus of discussion among clinical scientists. Comparison of the nasal and bronchial mucosa from allergic airways reveal similar inflammatory and epithelial cell alterations in both tissues, suggesting that common mechanisms of pathogenesis may contribute to each condition (Chanez et al. 1999). Given the clinical and pathologic commonalities of AR and asthma, recent efforts of physicians worldwide has led to Allergic Rhinitis and its Impact on Asthma (ARIA), a collaborative development of diagnostic and therapeutic strategies to treat AR as an asthma risk (Bousquet et al. 2001). A central tenet of ARIA is that AR and asthma represent a “united airway disease” and should be viewed as an interrelated disease with common etiology, features and treatments (Compalati et al. 2010; Marple 2010). However the inherent differences in the anatomic, morphologic, and functional aspects of nasal versus pulmonary airways result in unique inflammatory and allergic responses in each site. For example, airway obstruction in upper and lower airways occurs by very different mechanisms. Smooth muscle contraction narrows conducting airways in lung, whereas acute vasodilation of vascular tissue limits airflow through nasal airways. Mucus overproduction and hypersecretion may also contribute to airway occlusion and obstruction in both nasal and bronchial airways. Excess mucus such as during rhinorrhea might be more easily cleared from the nose, but mucus plugging in pulmonary airways is a prominent feature associated with mortality in status asthmaticus. While the “one-airway” concept may be an attractive paradigm to describe relationships in allergic airways in support of the ARIA framework, differences in clinical opinions for treatment remain (Chipps et al. 2010).