Editorial: Insights into disease pathogenesis and novel therapeutics

As we strive to advance our understanding and management of sinonasal disorders, the March issue of American Journal of Rhinology and Allergy continues to offer useful information to clinicians and researchers, with an eye towards the future. In general, most patients with sinonasal disorders do fairly well utilizing current practice paradigms. However, as practitioners, it is clear to us that there are populations of allergy and sinus sufferers who do not respond to our current treatments, and unfortunately do not spontaneously improve simply with the passage of time. It seems that those are the very patients that frequent our offices the most, and those are the ones we most often ponder. Why are they different? What else can we offer them? Is there anything new coming along? Isn’t someone looking into this?! In this issue, the AJRA editors have assembled an array of articles that address these very questions. Although clinicians may find it a challenge to get excited about basic science study, it is clear that further insight into disease pathogenesis underlies the consequent development of novel therapeutics. In the current issue, several papers examine disease pathogenesis in chronic rhinosinusitis (CRS) and nasal polyps, in particular with the role of the eosinophil. Eosinophils have a clear role in allergic inflammation, nasal polyp formation, steroid-responsiveness, Staphylococcus aureus pathogenicity, and clinical outcomes. The eosinophil is inextricably linked to sinonasal inflammation, and therefore we all should have some interest in it! Shin and colleagues show a trend towards more eosinophils and atopy in Korean polyp patients, and suggest that Asian polyp patients are apparently becoming more like their counterparts in the Western world.1 Eosinophilic CRS appears to be an emerging phenomenon, and as such, a better understanding of eosinophil-mediated disease is imperative. A separate study in this issue shows that eosinophil-epithelial cell interactions result in proinflammatory cytokine release and tissue remodeling that may contribute to ongoing disease.2 In addition, Gunel et al.3 have shown that P-glycoprotein is upregulated in eosinophilic CRS, and now they are able to link this to osteitis.2 Aside from eosinophilic inflammation, further study into T-cells and their function in sinus inflammation continues. T lymphocytes have a known function in the inflammatory process in allergic rhinitis and asthma, and their role in particular CRS subtypes has been a hot topic for recent study. Pant and colleagues examine regulatory T-cell phenotypes in the context of inflammation, allergy, and infection.4 Finally, hypoxia in airway epithelium is known to result in many major downstream effects mediated through HIF1, and Mo et al.5 offers the first investigation into the potential roles of HIF1in allergic rhinitis. This is truly an exciting finding, given that lower airway researchers have demonstrated hypoxia to be a key initiator of inflammation, coupled with the known potential for hypoxic microenvironments within the upper airway. The majority of this March issue focuses on novel therapeutics. This begins with further inquiry into currently available medical therapies, such as the potential for improved topical distribution and local absorption with the use of HFA aerosol corticosteroid compounds over traditional aqueous sprays.6 Prior work published in AJRA has shown that delivery method influences the efficacy of topical intranasal corticosteroids in CRS, and therefore we really should be looking for methods to increase local drug delivery, retention, and efficacy for our current topical steroid formulations.7 Data regarding the role of immunotherapy in atopic CRS patients was also reviewed systematically by DeYoung et al.8 These authors elucidated some improvements in both subjective and objective measures of CRS, but also cite the lack of high level evidence, opening the door for prospective study of this question. Much attention has been paid to sublingual immunotherapy (SLIT) in recent years, but SLIT in the pediatric population is an area in need of further evidence. Here Shao et al.9 provide sorely needed data to indicate that even in children as young as 3 years of age, SLIT can be both safe and efficacious. New uses for currently available medical therapies are also explored in this issue. For instance, Ogawa et al.10 demonstrate the potential for valproic acid to facilitate olfactory regeneration in a mouse model of olfactory insult, an area where we have relatively few successful options aside from corticosteroid therapy. Indeed, corticosteroids are first-line therapies in many inflammatory disorders, but what can we offer to the subset of patients who do not benefit from them? In steroid-unresponsive CRS patients, postoperative medical therapies are certainly in need of development. Macrolide therapy has been tried in such patients with modest success in the past, possibly due to anti-inflammatory properties beyond the known anti-microbial effects. Maniakis et al.11 show that the addition of azithromycin to the postoperative medical regimen may result in additional benefits for those patients not satisfactorily managed with topical steroids. Montelukast and the herbal remedy, thymoquine, increase ciliary beat frequency in vitro, offering a potential explanation for symptom benefits with montelukast and an alternative medical therapy that may be used to address particular symptoms such as the sensation of thick nasal mucus drainage.12 Finally, in regards to novel therapies, Fu et al demonstrate that the administration of bacterial lysate decreases allergy symptoms, histologic changes, and inflammatory parameters in a mouse model of allergic rhinitis.13 Recent NIH interest in the bacterial microbiome has spurred interest into the potential proand anti-inflammatory role of bacterial colonizers and their by-products. Bacterial lysates have been explored in the management of allergic asthma, and may provide a novel medication for upper airway inflammation in the future. New surgical techniques and innovative instrumentation are continually being explored, and here, Di Rienzo Businco et al.14 demonstrate that inferior turbinoplasty using quantic molecular resonance yields greater symptom improvement than medication alone in allergic rhinitis patients. New methods of evaluation and study are also presented in this issue. Meric et al.15 describe the relationship between pemphigus vulgaris and nasal inflammatory disease, demonstrating that these patients are more likely to exhibit nasal lesions and dysfunction of both odor threshold and identification. These findings underscore roles for nasal examination and olfactory evaluation in patients with this autoimmune disease. Jia et al.16 describe a simple small animal model for Staphylococcus aureus sinus biofilm formation. The establishment of this model is the requisite first step in testing interventions to prevent or treat sinus biofilms, a recurring theme in chronic rhinosinusits study for the past decade. From a clinical perspective, nasal peak inspiratory and expiratory flow measurements are known simple tests of nasal patency, however it is somewhat unclear how clinicians and researchers can best utilize this test. Kirtsreesakul et al.17 examine this in detail, and determine that the peak expiratory flow index is the most appropriate tool to assess nasal patency in Vijay R. Ramakrishnan, M.D.