Sinus cycle leading to RS (Adapted from Ahmad and Zacharek, 2008) Adult chronic RS was defined as a group of disorders characterized by inflammation of the mucosa of the nose and paranasal sinuses of at least 12 weeks duration. In the past, chronic RS was characterized as a disease process caused by an anatomical obstruction of the sinus ostia, specifically ostiomeatal complex occlusion. The factors leading to this obstruction included viral infection aided by anatomical factors, leading to mucosal inflammation and edema, with thickening of mucus secretions and secondary bacterial infection. It has become clear that the pathogenic mechanisms are more complex than would be explained by a simple model and that there are other chronic inflammatory processes that contribute to the development of chronic RS. However, the exact mechanism by which allergy predisposes to the development of chronic RS has not been fully elucidated. According to another model of the pathogenesis of RS, chronic RS is characterized by basement membrane thickening, subepithelial fibrosis and edema, goblet cell hyperplasia, and persistent inflammation (Christodoulopoulos et al., 2000). Like in asthma, remodeling of the mucosa occurs in response to this chronic and progressive inflammation. This model of 

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... Rhinitis and its Impact on Asthma (ARIA) guidelines recommend that asthma patients be evaluated for AR and, conversely, that AR patients be evaluated for asthma (Bousquet et al., 2001). In a prospective study evaluating 375 adults with persistent moderate to severe AR and 115 controls, the authors concluded that patients with persistent moderate to severe AR without an asthma diagnosis should be evaluated for the lower airway with pulmonary function testing (Ciprandi et al., 2008). Similarly, ARIA 2008 updates recommend that persistent AR patients should be evaluated for asthma (Bousquet et al., 2008). In our previous study, 173 AR patients were evaluated for the lower airway with the methacholine bronchoprovocation test and we recommend lower airway evaluation for the selected patients with nasal polyps, moderate to severe symptoms, and high blood eosinophil count (>320 cells/μL) instead of a routine lower airway evaluation (Ahn et al., 2010). In another study, persistent type of rhinitis and parental history of asthma were significant and independent risk factors for bronchial hyperresponsiveness in AR children (Choi et al., 2007). Early, active treatment of AR may be appropriate to decrease the incidence and morbidity associated with asthma. In a retrospective US cohort study of medical records covering 1 year for 4,944 asthmatic patients, approximately 73% were treated for AR. Asthma-related events occurred more often in untreated patients than in treated patients (6.6% vs. 1.3%) (Crystal-Peters et al., 2002). Controlling nasal symptoms with intranasal steroids improves asthma symptoms and nonspecific bronchial hyperresponsiveness (Watson et al., 1993). The authors reported that bronchial hyperresponsiveness to methacholine was significantly reduced in patients with perennial AR and asthma following treatment with intranasal steroids but not following intranasal placebo. More importantly, they also performed a radiolabeled deposition study of intranasal steroid administration and found that less than 2% was deposited in the chest area. These results suggest that treatment of inflammation in the upper airways indirectly improves asthma symptoms and decreases bronchial hyperresponsiveness, which is not a direct effect of the intranasally administered corticosteroid on the lower airways (Watson et al., 1993). A 3-year retrospective cohort study conducted in 14 US centers evaluated whether treatment with intranasal corticosteroid (INS) in patients of 5 years or older with asthma was associated with a reduced risk of emergency room visits for asthma (Adams et al., 2002). Treatment of nasal conditions, particularly with INSs, appeared to prevent asthma exacerbations leading to emergency room visits. AR and RS are increasingly being regarded as interrelated and part of a spectrum of upper airway inflammatory disease. AR also may be a contributing factor in 25% to 30% of patients with acute maxillary sinusitis and in as many as 60% to 80% of patients with chronic sinusitis (Spector, 1997). At the least, AR is associated with and probably a predisposing factor in the development of RS (Slavin, 1998). Both conditions are characterized by an inflammatory response leading to an altered milieu within the nose and paranasal sinuses, thus rendering normal host defenses weakened and susceptible to further inflammatory insult. However, the role of allergy in the pathogenesis of RS has been under debate and controversy over the past several years. RS is an inflammation of the nose and paranasal sinuses, attributed to many potential factors. The term “rhinosinusitis” rather than “sinusitis” reflects more accurately close anatomical and pathophysiological relationship between rhinitis and chronic sinusitis, which are commonly comorbid. The typical pathophysiological scheme leading to the development of RS starts with some inciting agents (viral, bacterial, fungal, allergen) or predisposing factor (anatomical, immunological) leading to generalized mucosal edema and inflammation. In the development of RS, mucosal inflammation leads to ciliary dysfunction and mucus stasis, as well as edema of the sinus ostia. The stasis of secretions within the sinuses serves as a nidus for bacterial colonization and growth. These events coupled with the impairment of host defenses as a result of the inflammatory mediators released in response to the inciting agent, create a cycle of sustained inflammation that can chronically damage the nasal and paranasal sinus linings (Ahmad and Zacharek, 2008; Gwaltney et al., 1995) (Fig. 3). pathogenesis also supports the notion of a unified airway with similar histopathological changes and immunological mechanism occurring as a result of inflammatory insult. In a 1989 study, skin testing in 2 groups of young adults, one with acute maxillary sinusitis, and a matched group without sinusitis, revealed that the prevalence of positive allergen testing was greater in the group with RS (45% vs. 33%) (Savolainen, 1989). The author thus concluded that allergy did play a role in the development of acute RS, and that it was more common among atopic individuals. In another study, positive inhalant allergy testing was present in over 50% of the 120 patients undergoing endoscopic sinus surgery, which led him to conclude that allergy may be a predisposing cause of chronic sinusitis (Kennedy, 1992). The contribution of allergy in the pathophysiology of both acute and chronic RS has been supported by studies examining the role of the ethmoid sinuses in terms of immunological, histopathological and postsurgical changes. The ethmoid mucosa affected by RS demonstrates an increased CD4/CD8 ratio and increase in the number of eosinophils and mast cells as well as extracellular matrix deposition, basement membrane disruption, and denudation of the epithelium (Christodoulopoulos et al., 2000). These findings are similar to the effect of allergy on other parts of the respiratory tract. In another study attempting to correlate tissue histopathology in chronic RS with immune mechanisms in allergic disease, the conclusions were that the proposed method for quantifying tissue eosinophilia in sinus mucosa was reliable and valid and that a relatively strong correlation existed between CT scan stage and tissue eosinophilia in chronic RS (Bhattacharyya et al., 2001). Several studies examining the relationship between allergen exposure or provocation and RS exacerbation have also suggested a common mechanism in AR and RS (Pelikan and Pelikan-Filipek, 1990; Conner et al., 1989; Slavin, 1998). The investigators demonstrated an increase in metabolic activity of the maxillary sinus mucosa in chronic RS patients during ragweed season, using single-photon emission CT scanning (Slavin, 1998). Evidence of a common pathophysiological mechanism between AR and RS is convincing. Although a clear causal mechanism leading from AR to the development of RS remains to be elucidated, an increasing number of studies have found the possibility and evidence of this link. OME is one of the most commonly encountered diseases in children, affecting approximately 90% of children at some time before school age (Tos, 1984). OME is characterized by an accumulation of fluid in the middle ear behind an intact tympanic membrane in the absence of signs and symptoms of acute infection. If we look at the natural history of OME, many cases are self-limited and resolve spontaneously (Williamson et al., 1994). But, OME is the most frequent cause of hearing loss in children (Thomas et al., 2006; Shekelle et al., 2002). An epidemiologic link between OME and AR has been demonstrated in many trials (Alles et al., 2001; Tomonaga et al., 1988). Prevalence of AR among patients with chronic or recurrent OME is higher than that seen in the same age group in the general population. The etiology of OME is multifactorial. It may be related to bacterial infection, poor clearance due to Eustachian tube (E-tube) dysfunction, local inflammatory reactions and possibly atopy (Thomas et al., 2006; Luong and Roland, 2008). Data from several animal studies have suggested a link between nasal allergic inflammation and E-tube dysfunction. For example, an intranasal pollen antigen challenge significantly compromised E-tube function in 23 passively sensitized juvenile rhesus monkeys (Doyle et al., 1984). A nasal allergen challenge in rats resulted in E-tube inflammation, negative pressure and hindrance of mucociliary clearance (Ebert et al., 2007). Another previous study showed negative middle ear pressure following nasal allergen challenge in subjects with AR and hypothesized the involvement of both immunological and mechanical mechanisms (O'Connor et al., 1984). E-tube dysfunction developed during allergy season in 60% of children with seasonal AR and correlated with AR symptom severity (Osur et al., 1989). Because the E-tube lining is contiguous with the nasopharynx, allergic disorders such as AR may cause inflammation and swelling in this region resulting in E-tube obstruction in the same manner as in the nasal mucosa (Alles et al., 2001; Luong and Roland, 2008; Fireman, 1988) (Fig. 4). Furthermore, it has been found that a reduction in the size of the lumen in an inflamed E-tube could impede mucociliary function, thus delaying clearance of acute infective middle ear effusion, leading to recurrent OME (Alles et al., 2001). Several studies analyzing middle ear mucosa and effusions in atopic patients with OME have demonstrated that the composition of the inflammatory ...