Biologicals in der Rhinologie – Individualisierte Konzepte der Zukunft

Adam M. Chaker

doi:10.1055/s-0043-123484

Laryngo-Rhino-Otologie, Table of Contents

CC BY-NC-ND 4.0 · Laryngorhinootologie 2018; 97(S 01): S142-S184
DOI: 10.1055/s-0043-123484

Referat

Biologicals in der Rhinologie – Individualisierte Konzepte der Zukunft

Article in several languages: deutsch | English

Authors

Adam M. Chaker

¹Klinik für Hals-Nasen-Ohrenheilkunde und Zentrum für Allergie und Umwelt, Klinikum rechts der Isar, Technische Universität München

Abstract

Zusammenfassung

Sinunasale Erkrankungen zählen mit zu den häufigsten chronischen Erkrankungen und führen zu einer erheblichen Störung der Lebensqualität, ein komorbides Asthma ist häufig. Trotz leitliniengerechter Therapie ist anzunehmen, dass mind. 20% der Patienten ihre Erkrankungssymptome nicht adäquat kontrollieren können. Neben den etablierten chirurgischen und konservativen Therapieoptionen finden sich nun vielversprechende Therapieansätze, die bspw. mittels therapeutischer Antikörper mechanistisch gezielt in die Pathophysiologie der Erkrankungen eingreifen können. Die Auswahl der geeigneten Patienten durch geeignete Biomarker und die richtige Therapie zum richtigen Stadium der Erkrankung anbieten zu können, ist das Ziel stratifizierter Medizin und eine wichtige Perspektive für die HNO.

Schlüsselwörter

Rhinitis - Sinusitis - Rhinosinusitis - CRS - Biologica - Nasenpolypen - personalisierte Medizin

Full Text

References

Literatur
1 Boyman O. et al. EAACI IG Biologicals task force paper on the use of biologic agents in allergic disorders. Allergy 2015; 70: 727-754
2 Agency EM. EMA GUIDELINE ON SIMILAR BIOLOGICAL MEDICINAL PRODUCTS. 2005 (http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003517.pdf (10th of October, 2017))
3 Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975; 256: 495-497
4 Quianzon CC, Cheikh I. History of insulin. J Community Hosp Intern Med Perspect 2012; 2
5 Suiter TM. First and next generation native rFVIII in the treatment of hemophilia A. What has been achieved? Can patients be switched safely?. Semin Thromb Hemost 2002; 28: 277-284
6 Beauvais P, Billette de Villemeur T. Prion diseases and blood transfusion. Transfus Clin Biol 1999; 6: 24-28
7 Frasier SD. The not-so-good old days: working with pituitary growth hormone in North America, 1956 to 1985. J Pediatr 1997; 131: S1-S4
8 Ayyar VS. History of growth hormone therapy. Indian J Endocrinol Metab 2011; 15 (Suppl. 03) S162-S165
9 Mosmann TR. et al. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136: 2348-2357
10 Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989; 7: 145-173
11 Bryan SA. et al. Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000; 356: 2149-2153
12 Friedrich M. et al. Immunomodulation by interleukin-10 therapy decreases the incidence of relapse and prolongs the relapse-free interval in Psoriasis. J Invest Dermatol 2002; 118: 672-677
13 Trepicchio WL. et al. Interleukin-11 therapy selectively downregulates type I cytokine proinflammatory pathways in psoriasis lesions. J Clin Invest 1999; 104: 1527-1537
14 Goel N, Chance K. Biosimilars in rheumatology: understanding the rigor of their development. Rheumatology (Oxford) 2017; 56: 187-197
15 Dorvignit D. et al. Expression and biological characterization of an anti-CD20 biosimilar candidate antibody: A case study. MAbs 2012; 4: 488-496
16 Elliott MJ. et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 1994; 344: 1105-1110
17 Taylor PC. Developing anti-TNF and biologic agents. Rheumatology (Oxford) 2011; 50: 1351-1353
18 Upchurch KS, Kay J. Evolution of treatment for rheumatoid arthritis. Rheumatology (Oxford) 2012; 51 (Suppl. 06) vi28-vi36
19 Roque-Navarro L. et al. Humanization of predicted T-cell epitopes reduces the immunogenicity of chimeric antibodies: New evidence supporting a simple method. Hybrid Hybridomics 2003; 22: 245-257
20 Croft M, Benedict CA, Ware CF. Clinical targeting of the TNF and TNFR superfamilies. Nat Rev Drug Discov 2013; 12: 147-168
21 Parren P, Carter PJ, Pluckthun A. Changes to International Nonproprietary Names for antibody therapeutics 2017 and beyond: of mice, men and more. MAbs 2017; 9: 898-906
22 Vultaggio A. et al. Manifestations of Antidrug Antibodies Response: Hypersensitivity and Infusion Reactions. J Interferon Cytokine Res 2014; 34: 946-952
23 Vultaggio A. et al. Circulating T cells to infliximab are detectable mainly in treated patients developing anti-drug antibodies and hypersensitivity reactions. Clin Exp Immunol 2016; 186: 364-372
24 Robert F. et al. Phase I study of anti-epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer. J Clin Oncol 2001; 19: 3234-3243
25 Bourhis J. et al. Phase I/II study of cetuximab in combination with cisplatin or carboplatin and fluorouracil in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol 2006; 24: 2866-2872
26 Bonner JA. et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006; 354: 567-578
27 O'Neil BH. et al. High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol 2007; 25: 3644-3648
28 Chung CH. et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 2008; 358: 1109-1117
29 Budach W, Bolke E, Homey B. Severe cutaneous reaction during radiation therapy with concurrent cetuximab. N Engl J Med 2007; 357: 514-515
30 Commins SP, Platts-Mills TA. Delayed anaphylaxis to red meat in patients with IgE specific for galactose alpha-1,3-galactose (alpha-gal). Curr Allergy Asthma Rep 2013; 13: 72-77
31 Commins SP, Platts-Mills TA. Tick bites and red meat allergy. Curr Opin Allergy Clin Immunol 2013; 13: 354-359
32 Galili U. The alpha-gal epitope and the anti-Gal antibody in xenotransplantation and in cancer immunotherapy. Immunol Cell Biol 2005; 83: 674-686
33 Fischer J. et al. Galactose-alpha-1,3-galactose sensitization is a prerequisite for pork-kidney allergy and cofactor-related mammalian meat anaphylaxis. J Allergy Clin Immunol 2014; 134: 755-759 e1
34 Kleponis J, Skelton R, Zheng L. Fueling the engine and releasing the break: combinational therapy of cancer vaccines and immune checkpoint inhibitors. Cancer Biol Med 2015; 12: 201-208
35 Perez-Alvarez R. et al. Biologics-induced autoimmune diseases. Curr Opin Rheumatol 2013; 25: 56-64
36 Weise M. et al. Biosimilars: the science of extrapolation. Blood 2014; 124: 3191-3196
37 Ledford H. First biosimilar drug set to enter US market. Nature 2015; 517: 253-254
38 Kurki P. et al. Interchangeability of Biosimilars: A European Perspective. BioDrugs 2017; 31: 83-91
39 Agency EM. Guideline on similar biological medicinal products. 2013 (http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/10/WC500176768.pdf) Accessed on 10th October 2017
40 Glue P. et al. Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group. Clin Pharmacol Ther 2000; 68: 556-567
41 Mok TS. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-957
42 Krueger J. et al. Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: A randomized phase 2 study. J Allergy Clin Immunol 2016; 137: 1079-1090
43 Aguilar-Pimentel A. et al. Improved efficacy of allergen-specific immunotherapy by JAK inhibition in a murine model of allergic asthma. PLoS One 2017; 12: e0178563
44 Boyle MP, De Boeck K. A new era in the treatment of cystic fibrosis: correction of the underlying CFTR defect. Lancet Respir Med 2013; 1: 158-163
45 Quon BS, Wilcox PG. A new era of personalized medicine for cystic fibrosis – at last!. Can Respir J 2015; 22: 257-260
46 Krug N. et al. Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme. N Engl J Med 2015; 372: 1987-1995
47 IMS Institute for Healthcare Informatics, Delivering on the Potentialof Biosimilar Medicines; The Role of Functioning Competitive Markets. 2016 (http://www.medicinesforeurope.com/wp-content/uploads/2016/03/IMS-Institute-Biosimilar-Report-March-2016-FINAL.pdf am 04.01.2018)
48 GKV Spitzenverband Deutschland. Biosimilars aus Sicht der Kostenträger. 2016 https://www.bfarm.de/SharedDocs/Downloads/DE/Service/Termine-und-Veranstaltungen/dialogveranstaltungen/dialog_2016/160627/08_Folien_Haas.pdf?__blob=publicationFile&v=2 zuletzt am 04.01.2018)
49 Health, I. Impact of Biosimilar Competion 2016. 2016 (https://www.imshealth.com/files/web/Market Insights/IMS_Health_Impact_of_Biosimilar_Competition_EU_2016.pdf online am 10.10.2017)
50 Chaker AM, Wagenmann M. Schleimhaut der Nase. Allergo J 2014; 23: 14
51 Pabst R, Chaker A. Integriertes Schleimhautimmunsystem der oberen Atemwege: Intraepitheliale Lymphozyten, NALT und der Waldeyersche Rachenring. Biedermann, Heppt, Renz, Röcken: Allergologie 2016; 1: 147-155
52 Bachert C, Holtappels G. Pathophysiology of chronic rhinosinusitis, pharmaceutical therapy options. Laryngorhinootologie 2015; 94 (Suppl. 01) S32-S63
53 Afzelius BA. Cilia-related diseases. J Pathol 2004; 204: 470-477
54 Stanke F. The Contribution of the Airway Epithelial Cell to Host Defense. Mediators Inflamm 2015; 2015: 463016
55 Sisson JH. et al. Smoke and viral infection cause cilia loss detectable by bronchoalveolar lavage cytology and dynein ELISA. Am J Respir Crit Care Med 1994; 149: 205-213
56 Ganz T, Lehrer RI. Defensins. Pharmacol Ther 1995; 66: 191-205
57 Radicioni G. et al. The innate immune properties of airway mucosal surfaces are regulated by dynamic interactions between mucins and interacting proteins: the mucin interactome. Mucosal Immunol 2016; 9: 1442-1454
58 Cobo ER. et al. Colonic MUC2 mucin regulates the expression and antimicrobial activity of beta-defensin 2. Mucosal Immunol 2015; 8: 1360-1372
59 Delacroix DL. et al. IgA subclasses in various secretions and in serum. Immunology 1982; 47: 383-385
60 Brandtzaeg P. Pillars Article: Mucosal and Glandular Distribution of Immunoglobulin Components: Differential Localization of Free and Bound SC in Secretory Epithelial Cells. J Immunol 1974; 112: 1553-1559 J Immunol 2017; 198: 1768–1774
61 Macpherson AJ. et al. The immune geography of IgA induction and function. Mucosal Immunol 2008; 1: 11-22
62 Pawankar RU. et al. Phenotypic and molecular characteristics of nasal mucosal gamma delta T cells in allergic and infectious rhinitis. Am J Respir Crit Care Med 1996; 153: 1655-1665
63 Mjosberg JM. et al. Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol 2011; 12: 1055-1062
64 Brandtzaeg P, Pabst R. Let's go mucosal: communication on slippery ground. Trends Immunol 2004; 25: 570-577
65 Chaker AM. Anatomy and Microanatomy of Tonsils. Encyclopedia of Immunobiology 2016; 3: 420-426
66 Gevaert P. et al. Organization of secondary lymphoid tissue and local IgE formation to Staphylococcus aureus enterotoxins in nasal polyp tissue. Allergy 2005; 60: 71-79
67 Fokkens WJ. et al. Langerhans cells in nasal mucosa of patients with grass pollen allergy. Immunobiology 1991; 182: 135-142
68 Fokkens WJ. et al. Characterization and quantification of cellular infiltrates in nasal mucosa of patients with grass pollen allergy, non-allergic patients with nasal polyps and controls. Int Arch Allergy Appl Immunol 1990; 93: 66-72
69 Jahnsen FL. et al. Human nasal mucosa contains antigen-presenting cells of strikingly different functional phenotypes. Am J Respir Cell Mol Biol 2004; 30: 31-37
70 Allam JP. et al. Comparative analysis of nasal and oral mucosa dendritic cells. Allergy 2006; 61: 166-172
71 Soyka MB. et al. Defective epithelial barrier in chronic rhinosinusitis: the regulation of tight junctions by IFN-gamma and IL-4. J Allergy Clin Immunol 2012; 130: 1087-1096 e10
72 Zhou B. et al. Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat Immunol 2005; 6: 1047-1053
73 Xu G. et al. Opposing roles of IL-17 A and IL-25 in the regulation of TSLP production in human nasal epithelial cells. Allergy 2010; 65: 581-589
74 Zissler UM. et al. Interleukin-4 and interferon-gamma orchestrate an epithelial polarization in the airways. Mucosal Immunol 2016; 9: 917-926
75 Soyka MB. et al. The Induction of IL-33 in the Sinus Epithelium and Its Influence on T-Helper Cell Responses. PLoS One 2015; 10: e0123163
76 Bachert C. et al. IL-5 synthesis is upregulated in human nasal polyp tissue. J Allergy Clin Immunol 1997; 99: 837-842
77 Van Zele T. et al. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy 2006; 61: 1280-1289
78 Bachert C. et al. Total and specific IgE in nasal polyps is related to local eosinophilic inflammation. J Allergy Clin Immunol 2001; 107: 607-614
79 Linneberg A. et al. The link between allergic rhinitis and allergic asthma: a prospective population-based study. The Copenhagen Allergy Study. Allergy 2002; 57: 1048-1052
80 Anderson HR, Bland JM, Peckham CS. Risk factors for asthma up to 16 years of age. Evidence from a national cohort study. Chest 1987; 91 6 Suppl 127S-130S
81 Shaaban R. et al. Rhinitis and onset of asthma: A longitudinal population-based study. Lancet 2008; 372: 1049-1057
82 Jarvis D. et al. Asthma in adults and its association with chronic rhinosinusitis: the GA2LEN survey in Europe. Allergy 2012; 67: 91-98
83 Settipane GA, Chafee FH. Nasal polyps in asthma and rhinitis. A review of 6,037 patients. J Allergy Clin Immunol 1977; 59: 17-21
84 Bachert C, Zhang L, Gevaert P. Current and future treatment options for adult chronic rhinosinusitis: Focus on nasal polyposis. J Allergy Clin Immunol 2015; 136: 1431-1440
85 Williamson PA. et al. Airway dysfunction in nasal polyposis: A spectrum of asthmatic disease?. Clin Exp Allergy 2011; 41: 1379-1385
86 Hens G. et al. Sinonasal pathology in nonallergic asthma and COPD: ‘united airway diseaseʼ beyond the scope of allergy. Allergy 2008; 63: 261-267
87 Spergel JM, Paller AS. Atopic dermatitis and the atopic march. J Allergy Clin Immunol 2003; 112 6 Suppl S118-S127
88 Braunstahl GJ. et al. Segmental bronchial provocation induces nasal inflammation in allergic rhinitis patients. Am J Respir Crit Care Med 2000; 161: 2051-2057
89 Braunstahl GJ. et al. Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways. J Allergy Clin Immunol 2001; 107: 469-476
90 Braunstahl GJ. et al. Segmental bronchoprovocation in allergic rhinitis patients affects mast cell and basophil numbers in nasal and bronchial mucosa. Am J Respir Crit Care Med 2001; 164: 858-865
91 Assanasen P. et al. The nasal passage of subjects with asthma has a decreased ability to warm and humidify inspired air. Am J Respir Crit Care Med 2001; 164: 1640-1646
92 Naclerio RM. et al. Observations on the ability of the nose to warm and humidify inspired air. Rhinology 2007; 45: 102-111
93 Eccles R. Is the common cold a clinical entity or a cultural concept?. Rhinology 2013; 51: 3-8
94 Lewis-Rogers N, Bendall ML, Crandall KA. Phylogenetic relationships and molecular adaptation dynamics of human rhinoviruses. Mol Biol Evol 2009; 26: 969-981
95 Palmenberg AC. et al. Sequencing and analyses of all known human rhinovirus genomes reveal structure and evolution. Science 2009; 324: 55-59
96 Caliskan M. et al. Rhinovirus wheezing illness and genetic risk of childhood-onset asthma. N Engl J Med 2013; 368: 1398-1407
97 Bianco A. et al. Th2 cytokines exert a dominant influence on epithelial cell expression of the major group human rhinovirus receptor, ICAM-1. Eur Respir J 1998; 12: 619-626
98 Xepapadaki P. et al. Duration of postviral airway hyperresponsiveness in children with asthma: effect of atopy. J Allergy Clin Immunol 2005; 116: 299-304
99 Toussaint M. et al. Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation. Nat Med 2017; 23: 681-691
100 Bartlett NW. et al. Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Nat Med 2008; 14: 199-204
101 Institut, R.K. Influenza. Robert Koch Website, online am 10.10.2017: p. http://www.rki.de/DE/Content/InfAZ/I/Influenza/IPV/IPV_Node.html
102 Zomer-Kooijker K. et al. Increased risk of wheeze and decreased lung function after respiratory syncytial virus infection. PLoS One 2014; 9: e87162
103 Sigurs N. et al. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med 2000; 161: 1501-1507
104 American Academy of Pediatrics Committee on Infectious, D. and C. American Academy of Pediatrics Bronchiolitis Guidelines, Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 2014; 134: e620-e638
105 Heinecke L. et al. Induction of B7-H1 and B7-DC expression on airway epithelial cells by the Toll-like receptor 3 agonist double-stranded RNA and human rhinovirus infection: In vivo and in vitro studies. J Allergy Clin Immunol 2008; 121: 1155-1160
106 Seshadri S. et al. Increased expression of the epithelial anion transporter pendrin/SLC26A4 in nasal polyps of patients with chronic rhinosinusitis. J Allergy Clin Immunol 2015; 136: 1548-1558 e7
107 Fokkens WJ. et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. Rhinology 2012; 50 (Suppl. 23) 1-305
108 Wang DY. et al. A survey on the management of acute rhinosinusitis among Asian physicians. Rhinology 2011; 49: 264-271
109 Revai K. et al. Incidence of acute otitis media and sinusitis complicating upper respiratory tract infection: the effect of age. Pediatrics 2007; 119: e1408-e1412
110 Wang JH, Kwon HJ, Jang YJ. Rhinovirus enhances various bacterial adhesions to nasal epithelial cells simultaneously. Laryngoscope 2009; 119: 1406-1411
111 Woytschak J. et al. Type 2 Interleukin-4 Receptor Signaling in Neutrophils Antagonizes Their Expansion and Migration during Infection and Inflammation. Immunity 2016; 45: 172-184
112 Cohen M. et al. Biofilms in chronic rhinosinusitis: a review. Am J Rhinol Allergy 2009; 23: 255-260
113 Abreu NA. et al. Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis. Sci Transl Med 2012; 4: 151ra124
114 Choi EB. et al. Decreased diversity of nasal microbiota and their secreted extracellular vesicles in patients with chronic rhinosinusitis based on a metagenomic analysis. Allergy 2014; 69: 517-526
115 Corriveau MN. et al. Detection of Staphylococcus aureus in nasal tissue with peptide nucleic acid-fluorescence in situ hybridization. Am J Rhinol Allergy 2009; 23: 461-465
116 Song WJ. et al. Staphylococcal enterotoxin sensitization in a community-based population: a potential role in adult-onset asthma. Clin Exp Allergy 2014; 44: 553-562
117 Akdis M. et al. Skin homing (cutaneous lymphocyte-associated antigen-positive) CD8 + T cells respond to superantigen and contribute to eosinophilia and IgE production in atopic dermatitis. J Immunol 1999; 163: 466-475
118 Vrieze A. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 2012; 143: 913-916 e7
119 Hastan D. et al. Chronic rhinosinusitis in Europe – an underestimated disease. A GA(2)LEN study. Allergy 2011; 66: 1216-1223
120 Beule AG. [Epidemiology of chronic rhinosinusitis, selected risk factors, comorbidities and economic burden]. Laryngorhinootologie 2015; 94 (Suppl. 01) S1-S23
121 Bousquet J. et al. Allergic Rhinitis and its Impact on Asthma (ARIA): Achievements in 10 years and future needs. J Allergy Clin Immunol 2012; 130: 1049-1062
122 Bousquet J. et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008; 63 (Suppl. 86) 8-160
123 Pearce N. et al. Self-reported prevalence of asthma symptoms in children in Australia, England, Germany and New Zealand: An international comparison using the ISAAC protocol. Eur Respir J 1993; 6: 1455-1461
124 Langen U, Schmitz R, Steppuhn H. Prevalence of allergic diseases in Germany: results of the German Health Interview and Examination Survey for Adults (DEGS1). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2013; 56: 698-706
125 Haftenberger M. et al. Prevalence of sensitisation to aeraoallergens and food allergens: Results of the German Health Interview and Examination Survey for Adults (DEGS1). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2013; 56: 687-697
126 Schmitz R, Kuhnert R, Thamm M. 12-Monats-Prävalenz von Allergien in Deutschland. Journal of Health Monitoring 2017; 2: 77-82
127 Meltzer EO. et al. Sleep, quality of life, and productivity impact of nasal symptoms in the United States: findings from the Burden of Rhinitis in America survey. Allergy Asthma Proc 2009; 30: 244-254
128 Biermann J, MHF Wehrmann W, Klimek L, Wasem J. Allergische Erkrankungen der Atemwege-Ergebnisse einer umfassenden Patientenkohorte in der deutschen gesetzlichen Krankenversicherung. Allergo Journal 2013; 22: 363-373
129 Pfaar O. et al. Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (OGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto- Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German Association of ENT Surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal Association of Pulmonologists (BDP) and the German Dermatologists Association (BVDD). Allergo J Int 2014; 23: 282-319
130 Calderon MA. et al. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev 2007; CD001936
131 Radulovic S. et al. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev 2010; CD002893
132 Radulovic S. et al. Systematic reviews of sublingual immunotherapy (SLIT). Allergy 2011; 66: 740-752
133 Nelson H. et al. Network meta-analysis shows commercialized subcutaneous and sublingual grass products have comparable efficacy. J Allergy Clin Immunol Pract 2015; 3: 256-266 e3
134 Jacobsen L. et al. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy 2007; 62: 943-948
135 Niggemann B. et al. Five-year follow-up on the PAT study: specific immunotherapy and long-term prevention of asthma in children. Allergy 2006; 61: 855-859
136 Valovirta E et al. Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy. J Allergy Clin Immunol 2017 Jul 6. pii: S0091–6749(17)31088–6
137 Kurukulaaratchy RJ. et al. Identifying the heterogeneity of young adult rhinitis through cluster analysis in the Isle of Wight birth cohort. J Allergy Clin Immunol 2015; 135: 143-150
138 Glowania A, CM Klimek L, Chaker A. Rhinitis – allergic or not?. Allergo Journal 2012; 08: 486-498
139 Hellings PW. et al. Non-allergic rhinitis: Position paper of the European Academy of Allergy and Clinical Immunology. Allergy 2017; 72: 1657-1665
140 Becker S. et al. Non-allergic rhinitis with eosinophilia syndrome is not associated with local production of specific IgE in nasal mucosa. Eur Arch Otorhinolaryngol 2016; 273: 1469-1475
141 Van Gerven L. et al. Capsaicin treatment reduces nasal hyperreactivity and transient receptor potential cation channel subfamily V, receptor 1 (TRPV1) overexpression in patients with idiopathic rhinitis. J Allergy Clin Immunol 2014; 133: 1332-1339 e1–e3
142 Wagenmann M, Scheckenbach K, Chaker AM. Endotypes in Chronic Rhinosinusitis: Biomarkers Based on a Mechanistic Insight for Targeted Treatment?. ORL J Otorhinolaryngol Relat Spec 2017; 79: 78-84
143 Hirsch AG. et al. Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample. Allergy 2017; 72: 274-281
144 Rudmik L, Smith TL. Quality of life in patients with chronic rhinosinusitis. Curr Allergy Asthma Rep 2011; 11: 247-252
145 Rajan JP. et al. Prevalence of aspirin-exacerbated respiratory disease among asthmatic patients: A meta-analysis of the literature. J Allergy Clin Immunol 2015; 135 (676/81) e1
146 Zhang N. et al. An update on the impact of Staphylococcus aureus enterotoxins in chronic sinusitis with nasal polyposis. Rhinology 2005; 43: 162-168
147 Knopf A. et al. Rheumatic disorders affecting the head and neck: Underestimated diseases. Rheumatology (Oxford) 2011; 50: 2029-2034
148 Hofauer B. et al. Liposomal local therapy of sinunasal symptoms in ANCA associated vasculitis. Laryngorhinootologie 2014; 93: 461-466
149 Woywodt A, Matteson EL. Wegener's granulomatosis – probing the untold past of the man behind the eponym. Rheumatology (Oxford) 2006; 45: 1303-1306
150 Craven A. et al. ACR/EULAR-endorsed study to develop Diagnostic and Classification Criteria for Vasculitis (DCVAS). Clin Exp Nephrol 2013; 17: 619-621
151 Yates M. et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 2016; 75: 1583-1594
152 Wechsler ME. et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med 2017; 376: 1921-1932
153 De Gaudemar I. et al. Is nasal polyposis in cystic fibrosis a direct manifestation of genetic mutation or a complication of chronic infection?. Rhinology 1996; 34: 194-197
154 Claeys S. et al. Nasal polyps in patients with and without cystic fibrosis: a differentiation by innate markers and inflammatory mediators. Clin Exp Allergy 2005; 35: 467-472
155 Steinke JW, Borish L. Chronic rhinosinusitis phenotypes. Ann Allergy Asthma Immunol 2016; 117: 234-240
156 Kartagener M. Zur Pathogenese der Bronchektasien bei Situs viscerum inversus. Beiträge Klin. Tuberk 1933; 83: 489-511
157 Degano B. et al. Expression of nitric oxide synthases in primary ciliary dyskinesia. Hum Pathol 2011; 42: 1855-1861
158 Marthin JK, Nielsen KG. Choice of nasal nitric oxide technique as first-line test for primary ciliary dyskinesia. Eur Respir J 2011; 37: 559-565
159 Joensen O. et al. Exhaled breath analysis using electronic nose in cystic fibrosis and primary ciliary dyskinesia patients with chronic pulmonary infections. PLoS One 2014; 9: e115584
160 Soler ZM. et al. Cluster analysis and prediction of treatment outcomes for chronic rhinosinusitis. J Allergy Clin Immunol 2016; 137: 1054-1062
161 Derycke L. et al. Mixed T helper cell signatures in chronic rhinosinusitis with and without polyps. PLoS One 2014; 9: e97581
162 Zhang N. et al. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease. J Allergy Clin Immunol 2008; 122: 961-968
163 Katotomichelakis M. et al. Inflammatory patterns in upper airway disease in the same geographical area may change over time. Am J Rhinol Allergy 2013; 27: 354-360
164 Ba L. et al. The association between bacterial colonization and inflammatory pattern in Chinese chronic rhinosinusitis patients with nasal polyps. Allergy 2011; 66: 1296-1303
165 Derycke L. et al. IL-17 A as a regulator of neutrophil survival in nasal polyp disease of patients with and without cystic fibrosis. J Cyst Fibros 2012; 11: 193-200
166 Wen W. et al. Increased neutrophilia in nasal polyps reduces the response to oral corticosteroid therapy. J Allergy Clin Immunol 2012; 129: 1522-1528 e5
167 Milara J. et al. Mucin 1 downregulation associates with corticosteroid resistance in chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol 2015; 135: 470-476
168 Anderson GP. Endotyping asthma: New insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet 2008; 372: 1107-1119
169 Lotvall J. et al. Asthma endotypes: A new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 2011; 127: 355-360
170 Wenzel SE. Complex phenotypes in asthma: Current definitions. Pulm Pharmacol Ther 2013; 26: 710-715
171 Tomassen P. et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol 2016; 137: 1449-1456 e4
172 De Greve G. et al. Endotype-driven treatment in chronic upper airway diseases. Clin Transl Allergy 2017; 7: 22
173 Akdis CA. et al. Endotypes and phenotypes of chronic rhinosinusitis: A PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol 2013; 131: 1479-1490
174 Schmitt J. et al. Allergy immunotherapy for allergic rhinitis effectively prevents asthma: Results from a large retrospective cohort study. J Allergy Clin Immunol 2015; 136: 1511-1516
175 Hopkins C, Andrews P, Holy CE. Does time to endoscopic sinus surgery impact outcomes in chronic rhinosinusitis? Retrospective analysis using the UK clinical practice research data. Rhinology 2015; 53: 18-24
176 Benninger MS. et al. Impact of medically recalcitrant chronic rhinosinusitis on incidence of asthma. Int Forum Allergy Rhinol 2016; 6: 124-129
177 Hopkins C, Rimmer J, Lund VJ. Does time to endoscopic sinus surgery impact outcomes in Chronic Rhinosinusitis? Prospective findings from the National Comparative Audit of Surgery for Nasal Polyposis and Chronic Rhinosinusitis. Rhinology 2015; 53: 10-17
178 Benninger MS. et al. Early versus delayed endoscopic sinus surgery in patients with chronic rhinosinusitis: impact on health care utilization. Otolaryngol Head Neck Surg 2015; 152: 546-552
179 Stuck BA et al. Guideline for “rhinosinusitis”-long version: S2k guideline of the German College of General Practitioners and Family Physicians and the German Society for Oto-Rhino-Laryngology, Head and Neck Surgery. HNO 2017
180 Messerklinger W. The ethmoidal infundibulum and its inflammatory illnesses (author's transl). Arch Otorhinolaryngol 1979; 222: 11-22
181 Stammberger H, Posawetz W. Functional endoscopic sinus surgery. Concept, indications and results of the Messerklinger technique. Eur Arch Otorhinolaryngol 1990; 247: 63-76
182 Rimmer J. et al. Surgical versus medical interventions for chronic rhinosinusitis with nasal polyps. Cochrane Database Syst Rev 2014; CD006991
183 Sharma R. et al. Surgical interventions for chronic rhinosinusitis with nasal polyps. Cochrane Database Syst Rev 2014; CD006990
184 Rudmik L. et al. Topical therapies in the management of chronic rhinosinusitis: an evidence-based review with recommendations. Int Forum Allergy Rhinol 2013; 3: 281-298
185 Kalish L. et al. WITHDRAWN: Topical steroids for nasal polyps. Cochrane Database Syst Rev 2016; 4: CD006549
186 Chong LY. et al. Intranasal steroids versus placebo or no intervention for chronic rhinosinusitis. Cochrane Database Syst Rev 2016; 4: CD011996
187 Chong LY. et al. Different types of intranasal steroids for chronic rhinosinusitis. Cochrane Database Syst Rev 2016; 4: CD011993
188 Tokunaga T. et al. Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study. Allergy 2015; 70: 995-1003
189 Hellings PW. et al. Uncontrolled allergic rhinitis and chronic rhinosinusitis: where do we stand today?. Allergy 2013; 68: 1-7
190 Philpott C. et al. The burden of revision sinonasal surgery in the UK-data from the Chronic Rhinosinusitis Epidemiology Study (CRES): A cross-sectional study. BMJ Open 2015; 5: e006680
191 Nabi S. et al. Nasal spray adherence after sinus surgery: Problems and predictors. J Otolaryngol Head Neck Surg 2012; 41 (Suppl. 01) S49-S55
192 Bousquet J. et al. Unmet needs in severe chronic upper airway disease (SCUAD). J Allergy Clin Immunol 2009; 124: 428-433
193 Ishizaka K, Ishizaka T, Hornbrook MM. Allergen-binding activity of gamma-E, gamma-G and gamma-A antibodies in sera from atopic patients. In vitro measurements of reaginic antibody. J Immunol 1967; 98: 490-501
194 Johansson SG, Bennich H. Immunological studies of an atypical (myeloma) immunoglobulin. Immunology 1967; 13: 381-394
195 Johansson SG. Raised levels of a new immunoglobulin class (IgND) in asthma. Lancet 1967; 2: 951-953
196 Ring J, Bergmann C. Geschichte der Allergologie. Biedermann, Heppt, Renz, Röcken: Allergologie 2016; 1: 3-9
197 Casale TB. et al. Effect of omalizumab on symptoms of seasonal allergic rhinitis: A randomized controlled trial. JAMA 2001; 286: 2956-2967
198 Chervinsky P. et al. Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol 2003; 91: 160-167
199 Kopp MV. et al. The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis. J Allergy Clin Immunol 2002; 110: 728-735
200 Klunker S. et al. Combination treatment with omalizumab and rush immunotherapy for ragweed-induced allergic rhinitis: Inhibition of IgE-facilitated allergen binding. J Allergy Clin Immunol 2007; 120: 688-695
201 Kopp MV. et al. Combination of omalizumab and specific immunotherapy is superior to immunotherapy in patients with seasonal allergic rhinoconjunctivitis and co-morbid seasonal allergic asthma. Clin Exp Allergy 2009; 39: 271-279
202 MacGinnitie AJ. et al. Omalizumab facilitates rapid oral desensitization for peanut allergy. J Allergy Clin Immunol 2017; 139: 873-881 e8
203 Kopp MV. Role of immunmodulators in allergen-specific immunotherapy. Allergy 2011; 66: 792-797
204 Akdis CA, Akdis M. Mechanisms and treatment of allergic disease in the big picture of regulatory T cells. J Allergy Clin Immunol 2009; 123: 735-746 quiz 747-748
205 Mobs C. et al. Birch pollen immunotherapy results in long-term loss of Bet v 1-specific TH2 responses, transient TR1 activation, and synthesis of IgE-blocking antibodies. J Allergy Clin Immunol 2012; 130: 1108-1116 e6
206 Wambre E. et al. Differentiation stage determines pathologic and protective allergen-specific CD4 + T-cell outcomes during specific immunotherapy. J Allergy Clin Immunol 2012; 129: 544-551 551 e1–e7
207 Gabrielsson S. et al. Specific immunotherapy prevents increased levels of allergen-specific IL-4- and IL-13-producing cells during pollen season. Allergy 2001; 56: 293-300
208 Michaud B. et al. Quantification of circulating house dust mite-specific IL-4- and IL-13-secreting T cells correlates with rhinitis severity in asthmatic children and varies with the seasons. Clin Exp Allergy 2014; 44: 222-230
209 Francis JN, Till SJ, Durham SR. Induction of IL-10 + CD4 + CD25 + T cells by grass pollen immunotherapy. J Allergy Clin Immunol 2003; 111: 1255-1261
210 Radulovic S. et al. Grass pollen immunotherapy induces Foxp3-expressing CD4 + CD25 + cells in the nasal mucosa. J Allergy Clin Immunol 2008; 121: 1467-1472 1472 e1
211 Robinson DS, Larche M, Durham SR. Tregs and allergic disease. J Clin Invest 2004; 114: 1389-1397
212 Till S. et al. IL-5 production by allergen-stimulated T cells following grass pollen immunotherapy for seasonal allergic rhinitis. Clin Exp Immunol 1997; 110: 114-121
213 Yang M. et al. Interleukin-13 mediates airways hyperreactivity through the IL-4 receptor-alpha chain and STAT-6 independently of IL-5 and eotaxin. Am J Respir Cell Mol Biol 2001; 25: 522-530
214 Mantel PY et al. GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells. PLoS Biol 2007; 5 (e329)
215 Chaker AM. et al. Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti-IL-4: A randomized controlled trial. J Allergy Clin Immunol 2016; 137: 452-461 e9
216 Johansson SG. IgE in allergic diseases. Proc R Soc Med 1969; 62: 975-976
217 Donovan R. et al. Immunoglobulins in nasal polyp fluid. Int Arch Allergy Appl Immunol 1970; 37: 154-166
218 Whiteside TL. et al. The presence of IgE on the surface of lymphocytes in nasal polyps. J Allergy Clin Immunol 1975; 55: 186-194
219 Van Zele T. et al. Staphylococcus aureus colonization and IgE antibody formation to enterotoxins is increased in nasal polyposis. J Allergy Clin Immunol 2004; 114: 981-983
220 Penn R, Mikula S. The role of anti-IgE immunoglobulin therapy in nasal polyposis: A pilot study. Am J Rhinol 2007; 21: 428-432
221 Guglielmo M. et al. Recalcitrant nasal polyposis: achievement of total remission following treatment with omalizumab. J Investig Allergol Clin Immunol 2009; 19: 158-159
222 Vennera Mdel C. et al. Efficacy of omalizumab in the treatment of nasal polyps. Thorax 2011; 66: 824-825
223 Pinto JM. et al. A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis. Rhinology 2010; 48: 318-324
224 Gevaert P. et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol 2013; 131: 110-116 e1
225 Lowe PJ, Renard D. Omalizumab decreases IgE production in patients with allergic (IgE-mediated) asthma; PKPD analysis of a biomarker, total IgE. Br J Clin Pharmacol 2011; 72: 306-320
226 Castro M. et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med 2011; 184: 1125-1132
227 Haldar P. et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009; 360: 973-984
228 Nair P. et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009; 360: 985-993
229 Gevaert P. et al. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. J Allergy Clin Immunol 2011; 128: 989-995 e1–e8
230 Bachert C. et al. Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial. J Allergy Clin Immunol 2017; 140: 1024-1031 e14
231 Casale TB. Biologics and biomarkers for asthma, urticaria, and nasal polyposis. J Allergy Clin Immunol 2017; 139: 1411-1421
232 Wenzel S. et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med 2013; 368: 2455-2466
233 Beck LA. et al. Dupilumab treatment in adults with moderate-to severe atopic dermatitis. N Engl J Med 2014; 371: 130-139
234 Simpson EL. et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med 2016; 375: 2335-2348
235 Jung YG. et al. Predictive capabilities of serum eosinophil cationic protein, percentage of eosinophils and total immunoglobulin E in allergic rhinitis without bronchial asthma. J Int Med Res 2011; 39: 2209-2216
236 Shamji MH. et al. Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper. Allergy 2017; 72: 1156-1173
237 Kim SH. et al. Dipeptidyl-peptidase 10 as a genetic biomarker for the aspirin-exacerbated respiratory disease phenotype. Ann Allergy Asthma Immunol 2015; 114: 208-213
238 Dietz K. et al. Age dictates a steroid-resistant cascade of Wnt5a, transglutaminase 2, and leukotrienes in inflamed airways. J Allergy Clin Immunol 2017; 139: 1343-1354.e6
239 Boscke R. et al. Wnt Signaling in Chronic Rhinosinusitis with Nasal Polyps. Am J Respir Cell Mol Biol 2017; 56: 575-584
240 Zissler UM. et al. Current and future biomarkers in allergic asthma. Allergy 2016; 71: 475-494
241 Corren J. et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011; 365: 1088-1098
242 Bujarski S, Parulekar AD, Hanania NA. Lebrikizumab in the treatment of asthma. Expert Opin Biol Ther 2016
243 Hanania NA. et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): Replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med 2016; 4: 781-796
244 De Schryver E. et al. The effect of systemic treatments on periostin expression reflects their interference with the eosinophilic inflammation in chronic rhinosinusitis with nasal polyps. Rhinology 2017; 55: 152-160
245 Gevaert P. et al. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J Allergy Clin Immunol 2006; 118: 1133-1141
246 Matricardi PM. et al. EAACI Molecular Allergology User's Guide. Pediatr Allergy Immunol 2016; 27 (Suppl. 23) 1-250
247 Klimek L, Becker S. Molecular component-resolved allergy diagnostics in ENT. HNO 2017; 65: 818-825
248 Chaker AM, Klimek L. Individualized, personalized and stratified medicine: a challenge for allergology in ENT?. HNO 2015; 63: 334-342
249 Ethikrat Deutschland, Forum Bioethik: Die Medizin nimmt’s persönlich. 2009 (http://www.ethikrat.org/dateien/pdf/fb_2009-06-24_simultanmitschrift.pdf am 04.01.2018)
250 Muller-Berghaus J. et al. Special considerations for the regulation of biological medicinal products in individualised medicine. More than stratified medicine. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2013; 56: 1538-1544
251 Green RC, Lautenbach D, McGuire AL. GINA, genetic discrimination, and genomic medicine. N Engl J Med 2015; 372: 397-399
252 Siest G. Systems medicine, stratified medicine, personalized medicine but not precision medicine. Drug Metabol Drug Interact 2014; 29: 1-2