Kent Lam1,2, Robert C Kern1, Amber Luong3. 1. Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL. 2. Department of Otorhinolaryngology-Head and Neck Surgery, McGovern Medical School at, The University of Texas Health Science Center at Houston, Houston, TX. 3. Department of Otorhinolaryngology-Head and Neck Surgery, McGovern Medical School at, The University of Texas Health Science Center at Houston, Houston, TX. amber.u.luong@uth.tmc.edu.
Abstract
BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory condition of the sinonasal mucosa consisting of poorly defined subtypes and characterized by variable clinical manifestations, responses to therapy, and underlying pathophysiologies. In the related disorder of asthma, progress has been made in defining disease subtypes on both clinical and pathophysiologic levels, facilitating the development of targeted biologic pharmacotherapy. The potential role of these drugs for the management of CRS will be reviewed. The objective of this work is to highlight the emerging therapeutic targets in CRS in light of evolving treatment options for asthma and enhanced understandings of the clinical manifestations and pathophysiology of CRS. METHODS: This article is a review of recent studies regarding current and future advances in biomarker-directed therapies in the medical treatment of CRS. RESULTS: Various biologic therapies used in the management of asthma have demonstrated clinical promise for CRS, particularly within the CRS with nasal polyposis (CRSwNP) phenotype. Several randomized, double-blind, placebo-controlled studies increasingly support the targeting of immunoglobulin E (IgE) and interleukin (IL)-5 pathways to improve outcome measures in CRSwNP patients. The IL-4/IL-13 pathway and other type 2 inflammatory pathways have also shown potential as targets for CRSwNP, but all pathways require further investigation. CONCLUSION: Recalcitrant CRS in the United States and Europe is most commonly associated with nasal polyposis and a type 2 cytokine skewing in the tissue, resulting in tissue infiltration of eosinophils, mast cells, and basophils. Targeting biomarkers of the associated type 2 pathways may be a practical treatment option for recalcitrant CRSwNP in the future.
BACKGROUND:Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory condition of the sinonasal mucosa consisting of poorly defined subtypes and characterized by variable clinical manifestations, responses to therapy, and underlying pathophysiologies. In the related disorder of asthma, progress has been made in defining disease subtypes on both clinical and pathophysiologic levels, facilitating the development of targeted biologic pharmacotherapy. The potential role of these drugs for the management of CRS will be reviewed. The objective of this work is to highlight the emerging therapeutic targets in CRS in light of evolving treatment options for asthma and enhanced understandings of the clinical manifestations and pathophysiology of CRS. METHODS: This article is a review of recent studies regarding current and future advances in biomarker-directed therapies in the medical treatment of CRS. RESULTS: Various biologic therapies used in the management of asthma have demonstrated clinical promise for CRS, particularly within the CRS with nasal polyposis (CRSwNP) phenotype. Several randomized, double-blind, placebo-controlled studies increasingly support the targeting of immunoglobulin E (IgE) and interleukin (IL)-5 pathways to improve outcome measures in CRSwNP patients. The IL-4/IL-13 pathway and other type 2 inflammatory pathways have also shown potential as targets for CRSwNP, but all pathways require further investigation. CONCLUSION: Recalcitrant CRS in the United States and Europe is most commonly associated with nasal polyposis and a type 2 cytokine skewing in the tissue, resulting in tissue infiltration of eosinophils, mast cells, and basophils. Targeting biomarkers of the associated type 2 pathways may be a practical treatment option for recalcitrant CRSwNP in the future.
Authors: Eli O Meltzer; Daniel L Hamilos; James A Hadley; Donald C Lanza; Bradley F Marple; Richard A Nicklas; Allen D Adinoff; Claus Bachert; Larry Borish; Vernon M Chinchilli; Melvyn R Danzig; Berrylin J Ferguson; Wytske J Fokkens; Stephen G Jenkins; Valerie J Lund; Mahmood F Mafee; Robert M Naclerio; Ruby Pawankar; Jens U Ponikau; Mark S Schubert; Raymond G Slavin; Michael G Stewart; Alkis Togias; Ellen R Wald; Birgit Winther Journal: J Allergy Clin Immunol Date: 2006-11 Impact factor: 10.793
Authors: Prescott G Woodruff; Barmak Modrek; David F Choy; Guiquan Jia; Alexander R Abbas; Almut Ellwanger; Laura L Koth; Joseph R Arron; John V Fahy Journal: Am J Respir Crit Care Med Date: 2009-05-29 Impact factor: 21.405
Authors: Gail M Gauvreau; Paul M O'Byrne; Louis-Philippe Boulet; Ying Wang; Donald Cockcroft; Jeannette Bigler; J Mark FitzGerald; Michael Boedigheimer; Beth E Davis; Clapton Dias; Kevin S Gorski; Lynn Smith; Edgar Bautista; Michael R Comeau; Richard Leigh; Jane R Parnes Journal: N Engl J Med Date: 2014-05-20 Impact factor: 91.245
Authors: D Jarvis; R Newson; J Lotvall; D Hastan; P Tomassen; T Keil; M Gjomarkaj; B Forsberg; M Gunnbjornsdottir; J Minov; G Brozek; S E Dahlen; E Toskala; M L Kowalski; H Olze; P Howarth; U Krämer; J Baelum; C Loureiro; L Kasper; P J Bousquet; J Bousquet; C Bachert; W Fokkens; P Burney Journal: Allergy Date: 2011-11-04 Impact factor: 13.146
Authors: Wytske J Fokkens; Valerie J Lund; Joachim Mullol; Claus Bachert; Isam Alobid; Fuad Baroody; Noam Cohen; Anders Cervin; Richard Douglas; Philippe Gevaert; Christos Georgalas; Herman Goossens; Richard Harvey; Peter Hellings; Claire Hopkins; Nick Jones; Guy Joos; Livije Kalogjera; Bob Kern; Marek Kowalski; David Price; Herbert Riechelmann; Rodney Schlosser; Brent Senior; Mike Thomas; Elina Toskala; Richard Voegels; De Yun Wang; Peter John Wormald Journal: Rhinol Suppl Date: 2012-03
Authors: Nicholas Van Bruaene; Claudina Angela Pérez-Novo; Tomasz M Basinski; Thibaut Van Zele; Gabriele Holtappels; Natalie De Ruyck; Carsten Schmidt-Weber; Cezmi Akdis; Paul Van Cauwenberge; Claus Bachert; Philippe Gevaert Journal: J Allergy Clin Immunol Date: 2008-06 Impact factor: 10.793
Authors: Michael Noonan; Phillip Korenblat; Sofia Mosesova; Heleen Scheerens; Joseph R Arron; Yanan Zheng; Wendy S Putnam; Merdad V Parsey; Sean P Bohen; John G Matthews Journal: J Allergy Clin Immunol Date: 2013-05-29 Impact factor: 10.793
Authors: Sarah Tait; Dorina Kallogjeri; Jasmina Suko; Sara Kukuljan; John Schneider; Jay F Piccirillo Journal: JAMA Otolaryngol Head Neck Surg Date: 2018-07-01 Impact factor: 6.223
Authors: M Gelardi; L Iannuzzi; M De Giosa; S Taliente; N De Candia; N Quaranta; E De Corso; V Seccia; G Ciprandi Journal: Acta Otorhinolaryngol Ital Date: 2017-02 Impact factor: 2.124
Authors: Robert C Kern; J Pablo Stolovitzky; Stacey L Silvers; Ameet Singh; Jivianne T Lee; David M Yen; Alfred M C Iloreta; Francis P J Langford; Boris Karanfilov; Keith E Matheny; James W Stambaugh; Anna K Gawlicka Journal: Int Forum Allergy Rhinol Date: 2018-01-19 Impact factor: 3.858
Authors: J Pablo Stolovitzky; Robert C Kern; Joseph K Han; Keith D Forwith; Randall A Ow; Simon K Wright; Andrew Gould; Keith E Matheny; Boris Karanfilov; Saling Huang; James W Stambaugh; Anna K Gawlicka Journal: Am J Rhinol Allergy Date: 2019-05-23 Impact factor: 2.467