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Wise et al.

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Allergic rhinitis and acute rhinosinusitis— In addition to these more general studies, evidence exists to support the concept of an increased risk of ARS with AR. There is a significantly higher incidence of ARS in both children and adult patients with a history of AR. 1847,1848 Children with AR are also more likely to experience orbital complications of ARS compared to those without AR, especially in pollinating seasons. 1849 A mouse model has also shown that ongoing nasal allergy is associated with worsened episodes of ARS. 1850,1851 Available data supports an association between AR and ARS. However, AR is thought to be a disease-modifying or risk-modifying factor rather than a causative one. There are no studies examining the effects of treating AR on the risk of developing an episode of ARS. For example, it is unclear whether treating AR decreases the incidence of ARS. Future study may help clarify the interaction between AR and ARS (Table X.B-1). • Aggregate Grade of Evidence: C (Level 2a: 2 studies; Level 2b: 1 study; Level 3a: 1 study; Level 3b: 1 study; Table X.B-1). Allergic rhinitis and recurrent acute rhinosinusitis— The potential link between AR and RARS is an extension of the link between AR and ARS. The increase in sinonasal inflammation associated with AR is proposed to increase mucosal edema, sinus ostium obstruction, and the retention of sinus secretions. 1 This environment may support secondary bacterial overgrowth and subsequent ARS or RARS. 1 Two studies have specifically examined the association between RARS and AR, with a focus on potentially altered innate immunity. The results of these 2 studies are conflicting. One study suggests there is a decrease in the antimicrobial properties of sinonasal secretions in patients with RARS and AR compared to AR only patients as well as control patients. 1852 The second study identified an upregulation in toll-like receptor 9 expression, suggesting increased resistance to bacterial infection rather than susceptibility. 1853 Further study is required to define the association between AR and RARS (Table X.B-2). • Aggregate Grade of Evidence: D (Level 2b: 2 studies; conflicting evidence; Table X.B-2). Allergic rhinitis and chronic rhinosinusitis without nasal polyposis— CRS is a condition of the sinonasal cavity characterized by persistent inflammation. The cause of the inflammation varies from patient to patient. As AR is a cause of sinonasal inflammation, many have suspected there may be an association with the pathogenesis of CRS. However, there are no controlled studies examining the role of AR in the development of CRSsNP. Additionally, there are no studies showing that the treatment or control of allergic disease alters the progression of CRSsNP, or vice versa. 1 Given the varied pathophysiology of CRSsNP, it is challenging to determine the association between allergy and CRSsNP. Wilson et al. 1854 performed a systematic review of allergy and CRS, excluding studies that did not differentiate between CRSsNP and CRSwNP. Their review found 4 studies that supported an association between allergy and CRSsNP and 5 that did not. 1854 Because the relationship remains unclear, allergy testing is listed as an option in CRSsNP patients based on the theoretical benefit of identifying and treating comorbid allergic disease 1,1854 (Table X.B-3). • Aggregate Grade of Evidence: D (Level 1b: 1 study; Level 3a: 1 study; Level 3b: 8 studies; conflicting evidence; Table X.B-3). Adapted from Wilson et al. 1854

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Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.