Advancing the understanding of complex rhinologic problems

Each issue of the American Journal of Rhinology and Allergy presents cutting edge basic and clinical research within the fields of allergy and rhinologic diseases. The current issue is no exception, with a diverse array of innovative studies from a worldwide collection of contributors. Readers will find basic and translational studies that explore the immunologic basis of allergic rhinitis (AR) and chronic rhinosinusitis (CRS), as well as clinical and technical studies that explore issues ranging from rhinoscleroma to cerebrospinal fluid leak repair. The July/ August issue certainly highlights the mission of the AJRA, with subject matter for basic scientists and clinicians alike. Chronic rhinosinusitis and allergic rhinitis are becoming increasingly prevalent, however, our understanding of the pathophysiology and immunologic contributors to disease development and progression remain poorly understood. Leading off the current issue, Shimizu et al1 investigate the impact of tissue remodeling and the extrinsic coagulation cascade on the pathogenesis of CRS. They found that the coagulation pathway proteins, tissue factor and tissue factor pathway inhibitor, are expressed in nasal secretions and nasal epithelial cells and hypothesize that upregulation of these factors may play an important role in fibrin deposition, tissue remodeling, and nasal polyp architecture. Studies like this should ultimately lead to new and more effective therapies for CRS, but the mainstay for medical management continues to be glucocorticosteroids. In this issue, Kook et al2 assess polyp-derived epithelial cell expression of enzymes involved in glucocorticosteroid metabolism and correlate enzyme expression with cortisol levels. Their results suggest that expression of the enzyme 11 -hydroxysteroid dehydrogenase may mediate the anti-inflammatory effect of glucocorticosteroids by increasing levels of endogenous cortisol. CRS results in many symptoms that adversely affect quality of life, with olfactory dysfunction representing one of the primary complaints of many patients. As detailed by Joo et al3 in this issue, loss of the sense of smell can be associated with both depressed mood and suicidal ideation. Unfortunately, regardless of etiology, there are few proven interventions for the long-term management of olfactory dysfunction. Improvement in olfactory outcomes following endoscopic sinus surgery is reported by Gupta et al,4 however, aggressive removal of polyps from the olfactory cleft itself remains somewhat controversial. Kuperan et al5 evaluated the benefit of endoscopic olfactory cleft polyp surgery on olfaction in a randomized singleblind study. Their results showed a statistically significant improvement in objective olfactory outcomes six months postoperatively for patients receiving surgery of the olfactory cleft. Though long-term data is still lacking, the current report suggests that directly addressing olfactory cleft polyps during endoscopic sinus surgery may provide some benefits in olfactory function. Allergic fungal sinusitis (AFS) continues to be a particularly challenging form of chronic sinus disease with a high recurrence rate. In this issue of AJRA, White et al6 set out to determine whether bony erosion patterns in AFS correlate with patient characteristics and other clinical parameters. In their cohort, erosion of bone was more common in younger and African-American patients, suggesting that these populations may mount a more severe inflammatory response. With the exception of corticosteroids, few medical interventions are consistently effective for AFS. The use of oral antifungals as an adjuvant therapy has been previously proposed by Gan et al7 with conflicting results. Patro and colleagues8 present their results of a randomized prospective study that evaluated the use of itraconazole preoperatively for management of AFS. Interestingly, patients receiving oral steroids and itraconazole experienced a reduction in disease burden based on clinical, radiologic, and endoscopic parameters, compared to those receiving steroids alone. This article highlights the potential of oral antifungals as an adjunctive management for AFS, while perhaps furthering controversy regarding the putative effectiveness of this intervention. Numerous pro-inflammatory and anti-inflammatory cytokines contribute to allergic responses and symptom development in patients with AR. In this issue of AJRA, Yokota et al9 use an allergic mouse model to explore the role of interleukin 35 (IL-35) on the inflammatory response. They found that IL-35 reduces the production of proinflammatory cytokines while simultaneously increasing the expression of anti-inflammatory cytokines. Collectively, their study suggests that IL-35 inhibits allergic T cell responses, potentially distinguishing it as a therapeutic target. An equally impactful study by Mo and colleagues10 evaluates the use of mesenchymal stem cells (MSCs) for the treatment of AR {Mo et al}. Using the same allergic mouse model, they found that injection of human tonsil-derived MSCs could reduce allergic symptoms, eosinophilic infiltration and production of proallergic cytokines. This highlights the potential of regenerative medicine and stem cell therapy as potential treatment modalities for AR and other immunologic diseases. Finally, Liu et al11 explore the physiologic role of the cold receptor, TRPM8, in the nasal mucosa. Agonists of TRPM8, such as menthol-containing medications and natural remedies, are often used to address symptoms in patients with and without AR. The basic science behind nasal mucosal temperature sensation and its effect on patient symptoms remains poorly understood, but the current study highlights a possible role for cold receptors in nasal pathophysiology. Additional articles by Jang and Kim12 as well as Degirmenci13 investigate the role of nasal provocation tests in AR diagnosis and explore the relationship between AR and autoimmune thyroiditis. While continued research into the immunologic basis of AR will likely result in new and more effective therapies, current treatment continues to rely on nasal steroid sprays and other topical medications. An article by Berger et al14 in this issue of AJRA seeks to systematically review currently available intranasal sprays used for maintenance therapy. Analyzing 20 studies, the authors found that the use of MP-AzeFlu, a single formulation nasal spray of azelastine hydrochloride and fluticasone propionate, provided greater symptom relief than either azelastine or fluticasone alone, confirming the importance of both topical antihistamines and corticosteroids in the management of AR. Many patients seek alternative treatments or Justin Turner, M.D.