Editorial: New perspectives in the pathogenesis and management of rhinologic and allergic airway disease It is such an honor to have the opportunity to serve as Guest Editor for this edition of the American Journal of Rhinology and Allergy (AJRA), and I want to express my deepest thanks to the Editors-in-Chief Alexander Chiu, Rakesh Chandra, and Anju Peters for their continued support and outstanding leadership. The AJRA is committed to presenting the latest and highest quality clinical and translational research in the fields of rhinology, allergy, and skull base pathology. To that end, the March/April issue of the AJRA encompasses a broad spectrum of studies offering novel perspectives on a variety of allergy and rhinology related topics. Since its characterization, much knowledge has been gained regarding the multifaceted inflammaJivianne tory nature of chronic rhinosinusitis (CRS), with both host (i.e., allergy, immunodeficiency, anatomic obstruction, etc.) and environmental factors (i.e., bacterial/viral infections, biofilms, pollutants, etc.) understood to be involved in its pathogenesis.1 However, despite extensive research efforts, no clear etiology for CRS has been delineated.1 In this issue, several studies aim to deepen our understanding of the complex pathophysiology of CRS and provide further insight into new treatment alternatives for this disease entity. On a molecular level, Lawrence et al investigate the effects of superoxide dismutase (SOD) on fungal antigen induced inflammatory responses in human sinonasal epithelial cells (HSNECs).2 SOD treatment of HSNECs derived from CRS with nasal polyp patients attenuated inflammation triggered by Aspergillus and Alternaria, suggesting that SOD could be used as a potential therapeutic option for CRS in the future.2 From a clinical aspect, Stevens and Peters examine how underlying immunodeficiencies may contribute to CRS.3 In their review, multiple immune disorders (i.e., common variable immunodeficiency, selective IgA deficiency, and specific antibody deficiencies) are discussed including appropriate diagnosis, treatment, and impact on CRS.3 Timely management of such immunodeficiencies with immunoglobulin replacement, etc. may have beneficial effects on the clinical course of CRS, particularly in patients with refractory disease. Likewise, Sedaghat and colleagues explore clustering patterns of CRS symptoms to determine correlations with demographic characteristics, comorbidities, and other objective findings.4 Such unique associations indicate that distinct pathophysiologic processes may be responsible for specific CRS symptomatology. Endoscopic sinus surgery (ESS) plays an integral role in the surgical therapy of CRS, with well-documented benefits in both symptoms and quality of life (QOL).5 However, local complications such as synechiae formation, middle turbinate lateralization, and mucosal edema can impede postoperative healing and ultimately compromise long-term surgical outcomes.6,7 In their systematic review, Hobson and colleagues evaluate the utility of middle meatal packing in reducing the risk of scarring following ESS.8 A meta-analysis of pooled data from eighteen randomized controlled trials was performed, which demonstrated a nonsignificant trend toward decreased adhesions in patients in whom middle meatal packing was placed.8 Like ESS, endonasal endoscopic skull base surgery (EESBS) can also lead to significant changes in intranasal anatomy. Utilizing 3-dimensional computational fluid dynamic simulations and virtual surgery models, Frank-Ito et al illustrate the effects of EESBS on sinonasal physiology.9 Alterations in severity, direction, and allocation of airflow were reported with EESBS as well as disruption of mucosal wall interactions.9 Although smaller in scope, partial turbinectomy has also been pre-
sumed to negatively impact nasal functionality.10 In their in vivo study, Tsakiropoulou et al compare the intranasal air conditioning capacity of healthy controls to patients with partial inferior turbinate resection.10 Diminished air heating was observed in the latter group but no change in humidification was reported.10 Similar to surgery, radiation therapy can also lead to long-term adverse local effects. Riva et al evaluate nasal cytological alterations in patients who received chemoradiation for nasopharyngeal carcinoma.11 Radiated subjects exhibited a significantly higher percentage of rhinorrhea, nasal obstruction, T. Lee, M.D. and nasopharyngeal secretions than healthy controls.11 A greater proportion of treated patients also showed neutrophilic inflammation and squamous cell metaplasia on histopathology, implying that radiation induced mucosal changes can contribute to clinical rhinitis symptoms.11 With continual advances in endoscopic transnasal surgical approaches, indications for such procedures have broadened considerably to encompass increasingly more novel applications. In their review, Miyake and Bleier discuss the challenges of formulating drug targeting strategies to bypass the blood-brain barrier and deliver therapeutics to the central nervous system (CNS).12 The authors describe the innovative use of endoscopic grafting techniques to facilitate drug administration to the subarachnoid space via an intranasal route.12 A nasal mucosal surgical flap is created employing established skull base reconstruction methods to serve as a vehicle for pharmaceutical delivery to the CNS.12 As more advanced endoscopic skull base procedures are developed, it is important to assess the clinical outcomes of such surgeries. In their study, Deckard et al track QOL measures following endoscopic resection of sinonasal and skull base neoplasms.13 Concurrent use of multiple validated instruments elucidated significant changes in QOL metrics following surgery and enabled identification of various factors (malignant histopathology, advanced tumor staging, etc.) associated with worsened postoperative QOL.13 Recent years have also witnessed introduction of new materials and approaches in esthetic and reconstructive rhinologic surgery. In their retrospective study, Kim et al evaluated the use of tutoplast-processed fascia lata for dorsal augmentation in primary and revision rhinoplasty and reported positive surgical outcomes with minimal morbidity.14 In addition to CRS, this issue also includes studies investigating the pathogenesis and management of other allergic and non-allergic inflammatory airway diseases. As sensitization has been shown to occur early in life, Yu and colleagues analyze the impact of gestational environment on the neonatal immune response.15 Interestingly, maternal atopic status was not found to influence neonatal sensitization and maternofetal transfer of allergen specific IgE was not detected.15 Similarly, Tokunaga et al conduct an epidemiologic survey of high school students in Japan to identify factors influencing development and remission of a spectrum of allergic processes, including rhinitis and asthma.16 Their findings lend further support to the hygiene hypothesis and the potential effects of intestinal flora on the clinical course of allergic airway disease.16 In their prospective study, Yenigan et al compare plasma 24-hydroxyvitamin D levels in patients with and without allergic rhino-conjunctivitis (ARC).17 Significantly lower plasma vitamin D measurements were observed in the ARC group,
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American Journal of Rhinology & Allergy
Delivered by Ingenta to: Guest User IP: 195.34.78.87 On: Sun, 26 Jun 2016 05:28:20 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
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implying that vitamin D deficiency may contribute to development of ARC.17 With the rising use of sublingual immunotherapy (SLIT) in the United States, Lee and colleagues perform a comprehensive review of SLIT in the treatment of allergic rhinitis.18 The clinical indications, dosing protocols, efficacy, and safety of this therapeutic modality are discussed along with the relevant evidence.18 Following this tangent, Halderman and Sindwani conduct a systematic review of the literature evaluating the surgical management of vasomotor rhinitis.19 Endoscopic vidian neurectomy was found to significantly improve symptoms of rhinorrhea and nasal obstruction with no long-term adverse sequelae.19 Endoscopic posterior nasal neurectomy was also studied, although evidence to support its efficacy is still lacking.19 Finally, as olfaction may be affected by multiple rhinologic and allergic disorders, new tools for assessing smell thresholds have emerged. In their pilot study, Jiang and Liang evaluate the validity of a Self-administered Computerized Olfactory Testing System (SCOTs) and report strong test-retest reliability for this approach.20 In addition, Hsu et al describe use of the Taiwanese Smell Identification Test (TWSIT) and highlight the importance of developing culturally specific olfactory testing systems that can be easily administered in the office setting.21 Thus, the collection of articles in this edition of the AJRA utilize various methods of study to address a potpourri of allergic and rhinologic disease. We hope that our readership finds the content of this issue to be beneficial not only from a clinical practice standpoint but also as a springboard for innovative research and scholarship in the future. Jivianne T. Lee, M.D.
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REFERENCES 1.
Kennedy DW. Pathogenesis of chronic rhinosinusitis. Ann Otol Rhinol Laryngol 113:6–9, 2004. 2. Lawrence L, Mulligan J, Roach C, et al. Superoxide dismutase reduces the inflammatory response to Aspergillus and Alternaria in human sinonasal epithelial cells derived from patients with chronic rhinosinusitis. Am J Rhinol Allergy 29:89–93, 2015. 3. Stevens W and Peters A. Immunodeficiency in Chronic Sinusitis: Recognition and Treatment. Am J Rhinol Allergy 29:115–118, 2015. 4. Sedaghat A, Caradonna SD, Caradonna DS, et al. Clustering of chronic rhinosinusitis symptomatology reveals novel associations with objective clinical and demographic characteristics. Am J Rhinol Allergy 29:100–105, 2015. 5. Lee JT and Kennedy DW. Endoscopic sinus surgery. In: Bailey BJ and Johnson JT, editors. Head & Neck Surgery—Otolaryngology, 4th ed. New York: Lippincott-Raven. 459–475, 2006.
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Henriquez OA, Schlosser RJ, Mace JC, et al. Impact of synechiae after endoscopic sinus surgery on long-term outcomes in chronic rhinosinusitis. Laryngoscope 123:2615–2619, 2013. Smith TL, Litvack JR, Hwang PW, et al. Determinants of outcomes of sinus surgery: a multiinstitutional prospective cohort study. Otolaryngol Head Neck Surg 142:55–63, 2010. Hobson C, Choby GW, Wang EW, et al. Systematic review and meta-analysis of middle meatal packing following endoscopic sinus surgery. Am J Rhinol Allergy 29:135–140, 2015. Frank-Ito D, Sajisevi M, Solares A, et al. Modeling alterations in sinonasal physiology following skull base surgery. Am J Rhinol Allergy 29:145–150, 2015. Tsakiropoulou E, Vital V, Kekes G, et al. Nasal air conditioning after partial turbinectomy: myths versus facts. Am J Rhinol Allergy 29: e59–e62, 2015. Riva G, Boita M, Ravera M, et al. Nasal cytological changes as late effects of radiotherapy for nasopharyngeal cancer. Am J Rhinol Allergy 29:e41–e45, 2015. Miyake MM and Bleier BS. The blood-brain barrier and nasal drug delivery to the central nervous system. Am J Rhinol Allergy 29:124– 127, 2015. Deckard NA, Harrow BR, Barnett SL, et al. Comparative analysis of quality of life metrics after endoscopic surgery for sinonasal neoplasms. Am J Rhinol Allergy 29:151–155, 2015. Kim Y, Park DY, Shin DH, et al. Surgical outcomes of primary and revision augmentation rhinoplasty using a processed fascia lata. Am J Rhinol Allergy 29:141–144, 2015. Yu Z, Chen J, Zhang Q, et al. Maternofetal transfer of antibodies and the influence of maternal atopic status on the neonate. Am J Rhinol Allergy 29:119–123, 2015. Tokunaga T, Ninomiya T, Osawa Y, et al. Factors associated with the development and remission of allergic diseases in an epidemiological survey of high school students in Japan. Am J Rhinol Allergy 29:94– 99, 2015. Yenigun A, Dadaci Z, and Oncel M. Plasma vitamin D levels of patients with allergic rhino-conjunctivitis with positive skin prick test. Am J Rhinol Allergy 29:e46–e49, 2015. Lee S, Nolte H, and Benninger MS. Clinical considerations in the use of sublingual immunotherapy for allergic rhinitis. Am J Rhinol Allergy 29:106–114, 2015. Halderman A and Sindwani R. Surgical management of vasomotor rhinitis: a systematic review. Am J Rhinol Allergy 29:128–134, 2015. Jiang R and Liang K. A pilot study of the Self-administered Computerized Olfactory Testing System. Am J Rhinol Allergy 29:e55–e58, 2015. Hsu N, Lai J, Shen P, et al. Development of Taiwan smell identification test: A quick office-based smell screening test for Taiwanese. Am J Rhinol Allergy 29:e50–e54, 2015. e
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March–April 2015, Vol. 29, No. 2
Delivered by Ingenta to: Guest User IP: 195.34.78.87 On: Sun, 26 Jun 2016 05:28:20 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
sumed to negatively impact nasal functionality.10 In their in vivo study, Tsakiropoulou et al compare the intranasal air conditioning capacity of healthy controls to patients with partial inferior turbinate resection.10 Diminished air heating was observed in the latter group but no change in humidification was reported.10 Similar to surgery, radiation therapy can also lead to long-term adverse local effects. Riva et al evaluate nasal cytological alterations in patients who received chemoradiation for nasopharyngeal carcinoma.11 Radiated subjects exhibited a significantly higher percentage of rhinorrhea, nasal obstruction, T. Lee, M.D. and nasopharyngeal secretions than healthy controls.11 A greater proportion of treated patients also showed neutrophilic inflammation and squamous cell metaplasia on histopathology, implying that radiation induced mucosal changes can contribute to clinical rhinitis symptoms.11 With continual advances in endoscopic transnasal surgical approaches, indications for such procedures have broadened considerably to encompass increasingly more novel applications. In their review, Miyake and Bleier discuss the challenges of formulating drug targeting strategies to bypass the blood-brain barrier and deliver therapeutics to the central nervous system (CNS).12 The authors describe the innovative use of endoscopic grafting techniques to facilitate drug administration to the subarachnoid space via an intranasal route.12 A nasal mucosal surgical flap is created employing established skull base reconstruction methods to serve as a vehicle for pharmaceutical delivery to the CNS.12 As more advanced endoscopic skull base procedures are developed, it is important to assess the clinical outcomes of such surgeries. In their study, Deckard et al track QOL measures following endoscopic resection of sinonasal and skull base neoplasms.13 Concurrent use of multiple validated instruments elucidated significant changes in QOL metrics following surgery and enabled identification of various factors (malignant histopathology, advanced tumor staging, etc.) associated with worsened postoperative QOL.13 Recent years have also witnessed introduction of new materials and approaches in esthetic and reconstructive rhinologic surgery. In their retrospective study, Kim et al evaluated the use of tutoplast-processed fascia lata for dorsal augmentation in primary and revision rhinoplasty and reported positive surgical outcomes with minimal morbidity.14 In addition to CRS, this issue also includes studies investigating the pathogenesis and management of other allergic and non-allergic inflammatory airway diseases. As sensitization has been shown to occur early in life, Yu and colleagues analyze the impact of gestational environment on the neonatal immune response.15 Interestingly, maternal atopic status was not found to influence neonatal sensitization and maternofetal transfer of allergen specific IgE was not detected.15 Similarly, Tokunaga et al conduct an epidemiologic survey of high school students in Japan to identify factors influencing development and remission of a spectrum of allergic processes, including rhinitis and asthma.16 Their findings lend further support to the hygiene hypothesis and the potential effects of intestinal flora on the clinical course of allergic airway disease.16 In their prospective study, Yenigan et al compare plasma 24-hydroxyvitamin D levels in patients with and without allergic rhino-conjunctivitis (ARC).17 Significantly lower plasma vitamin D measurements were observed in the ARC group,
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American Journal of Rhinology & Allergy
Delivered by Ingenta to: Guest User IP: 195.34.78.87 On: Sun, 26 Jun 2016 05:28:20 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
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implying that vitamin D deficiency may contribute to development of ARC.17 With the rising use of sublingual immunotherapy (SLIT) in the United States, Lee and colleagues perform a comprehensive review of SLIT in the treatment of allergic rhinitis.18 The clinical indications, dosing protocols, efficacy, and safety of this therapeutic modality are discussed along with the relevant evidence.18 Following this tangent, Halderman and Sindwani conduct a systematic review of the literature evaluating the surgical management of vasomotor rhinitis.19 Endoscopic vidian neurectomy was found to significantly improve symptoms of rhinorrhea and nasal obstruction with no long-term adverse sequelae.19 Endoscopic posterior nasal neurectomy was also studied, although evidence to support its efficacy is still lacking.19 Finally, as olfaction may be affected by multiple rhinologic and allergic disorders, new tools for assessing smell thresholds have emerged. In their pilot study, Jiang and Liang evaluate the validity of a Self-administered Computerized Olfactory Testing System (SCOTs) and report strong test-retest reliability for this approach.20 In addition, Hsu et al describe use of the Taiwanese Smell Identification Test (TWSIT) and highlight the importance of developing culturally specific olfactory testing systems that can be easily administered in the office setting.21 Thus, the collection of articles in this edition of the AJRA utilize various methods of study to address a potpourri of allergic and rhinologic disease. We hope that our readership finds the content of this issue to be beneficial not only from a clinical practice standpoint but also as a springboard for innovative research and scholarship in the future. Jivianne T. Lee, M.D.
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REFERENCES 1.
Kennedy DW. Pathogenesis of chronic rhinosinusitis. Ann Otol Rhinol Laryngol 113:6–9, 2004. 2. Lawrence L, Mulligan J, Roach C, et al. Superoxide dismutase reduces the inflammatory response to Aspergillus and Alternaria in human sinonasal epithelial cells derived from patients with chronic rhinosinusitis. Am J Rhinol Allergy 29:89–93, 2015. 3. Stevens W and Peters A. Immunodeficiency in Chronic Sinusitis: Recognition and Treatment. Am J Rhinol Allergy 29:115–118, 2015. 4. Sedaghat A, Caradonna SD, Caradonna DS, et al. Clustering of chronic rhinosinusitis symptomatology reveals novel associations with objective clinical and demographic characteristics. Am J Rhinol Allergy 29:100–105, 2015. 5. Lee JT and Kennedy DW. Endoscopic sinus surgery. In: Bailey BJ and Johnson JT, editors. Head & Neck Surgery—Otolaryngology, 4th ed. New York: Lippincott-Raven. 459–475, 2006.
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Henriquez OA, Schlosser RJ, Mace JC, et al. Impact of synechiae after endoscopic sinus surgery on long-term outcomes in chronic rhinosinusitis. Laryngoscope 123:2615–2619, 2013. Smith TL, Litvack JR, Hwang PW, et al. Determinants of outcomes of sinus surgery: a multiinstitutional prospective cohort study. Otolaryngol Head Neck Surg 142:55–63, 2010. Hobson C, Choby GW, Wang EW, et al. Systematic review and meta-analysis of middle meatal packing following endoscopic sinus surgery. Am J Rhinol Allergy 29:135–140, 2015. Frank-Ito D, Sajisevi M, Solares A, et al. Modeling alterations in sinonasal physiology following skull base surgery. Am J Rhinol Allergy 29:145–150, 2015. Tsakiropoulou E, Vital V, Kekes G, et al. Nasal air conditioning after partial turbinectomy: myths versus facts. Am J Rhinol Allergy 29: e59–e62, 2015. Riva G, Boita M, Ravera M, et al. Nasal cytological changes as late effects of radiotherapy for nasopharyngeal cancer. Am J Rhinol Allergy 29:e41–e45, 2015. Miyake MM and Bleier BS. The blood-brain barrier and nasal drug delivery to the central nervous system. Am J Rhinol Allergy 29:124– 127, 2015. Deckard NA, Harrow BR, Barnett SL, et al. Comparative analysis of quality of life metrics after endoscopic surgery for sinonasal neoplasms. Am J Rhinol Allergy 29:151–155, 2015. Kim Y, Park DY, Shin DH, et al. Surgical outcomes of primary and revision augmentation rhinoplasty using a processed fascia lata. Am J Rhinol Allergy 29:141–144, 2015. Yu Z, Chen J, Zhang Q, et al. Maternofetal transfer of antibodies and the influence of maternal atopic status on the neonate. Am J Rhinol Allergy 29:119–123, 2015. Tokunaga T, Ninomiya T, Osawa Y, et al. Factors associated with the development and remission of allergic diseases in an epidemiological survey of high school students in Japan. Am J Rhinol Allergy 29:94– 99, 2015. Yenigun A, Dadaci Z, and Oncel M. Plasma vitamin D levels of patients with allergic rhino-conjunctivitis with positive skin prick test. Am J Rhinol Allergy 29:e46–e49, 2015. Lee S, Nolte H, and Benninger MS. Clinical considerations in the use of sublingual immunotherapy for allergic rhinitis. Am J Rhinol Allergy 29:106–114, 2015. Halderman A and Sindwani R. Surgical management of vasomotor rhinitis: a systematic review. Am J Rhinol Allergy 29:128–134, 2015. Jiang R and Liang K. A pilot study of the Self-administered Computerized Olfactory Testing System. Am J Rhinol Allergy 29:e55–e58, 2015. Hsu N, Lai J, Shen P, et al. Development of Taiwan smell identification test: A quick office-based smell screening test for Taiwanese. Am J Rhinol Allergy 29:e50–e54, 2015. e
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March–April 2015, Vol. 29, No. 2
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