FORSKNINGENS DAG. Forskning vid Öron-, Näs- och Halskliniken Karolinska Universitetssjukhuset Välkomna till Forskningens dag den 20 december 2013

FORSKNINGENS DAG Forskning vid Öron-, Näs- och Halskliniken Karolinska Universitetssjukhuset Välkomna till Forskningens dag den 20 december 2013 Program: 08.00 Kaffe 08.30 Introduktion av dagens program. Lars-Olaf Cardell 08.35 Hard core facts about NKS. Bo Tideholm 08.50 NKS och ÖNH vilka möjligheter?!! Mats Holmström 09.20 Grupparbete I; utgående från MHs dragning. Malou Hultcrantz 09.30 Kaffe + grupparbete 10.15 Redovisning av grupparbete + röstning 11.00 Elektroniska labboken, Annika Aspnor, Lotta Tengroth 11.30 Core facilites, undersköterskor. Lars Olaf Cardell 11.40 Lunch + Grupparbete II. baserat på resultatet av gr.arb. I. Pär Stjärne 13.00 Redovisning grupparbete 2 14.10 Avslutning Lars Olaf Cardell 1

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Innehållsförteckning Registrering publikationer...4. Kontaktpersoner...5. Medlemmar FoU-rådet...5. Professorer och docenter...6. Disputationer/halvtidskontroller 2011-2013...7. Närvaro vid halvtidskontroller 2010-2012...8. Seniora forskare...9. Forskningssammanfattningar, seniora forskare...11. Enhetens doktorander...57. Projektsammanfattningar, doktorander...59. 3

Enhetens ekonomi står och faller med att vi rapporterar in våra publikationer. Detta gäller både KI-anknutna och de som har en ren SLL-anställning. Registrering av publikationer KI: https://bibliometrics.ki.se/verify/users/login Kräver KI-login SLL: http://inuti.karolinska.se/templates/divisionstart 106590.aspx Kräver Stockholms läns landstings etjänstekort Brister i adresseringen av publikationer från KI/SLL En inte försumbar andel av de publikationer som forskare vid verifiering anger har skrivits vid KI/SLL saknar en giltig KI- eller SLL-adress på själva publikationen. De genererar t.ex. inte statliga medel eller bibliometriska poäng i olika rankingar. 1. Styrelsen för forskning vid KI samt SLL:s FoUU-ledning rekommenderar: Alla som är affilierade till Karolinska Institutet bör ange universitetets adress på sina publikationer enligt mallen: Karolinska Institutet, Dept X, 171 77 Stockholm, Sweden. 2. Dessutom anger man i förekommande fall sin sjukhusadress enligt mallen: and Karolinska Univ Hosp, Department of Otorhinolaryngologi, 171 76 Stockholm 3. Anställda vid SLL som forskar helt i landstingets regi och inte är affilierade till Karolinska Institutet ska ange sitt sjukhus som sin adress enligt mallen: Karolinska Univ Hosp, Department of Otorhinolaryngologi, 171 77 Stockholm, Sweden. 4

Kontaktpersoner Enhetsledning CLINTEC ledningen Enhetschef/Professor/Stf prefekt Prefekt Lars Olaf Cardell Li Tsai lars-olaf.cardell@ki.se li.tsai@ki.se 08-5858 1453 08-585 87191 Stf enhetschef Adminstrativ chef StenHellström Elizabeth All Sten.hellfstrom@ki.se elizabeth.all@ki.se 073-626 1861 08-524 87741 Stf enhetschef Ekonomichef Malou Hultcrantz Britt-Louise Gothnier Malou.hultcrantz@karolinska.se britt-louise.gothnier@ki.se 08-517 75653 08-524 87749 Institutionssekreterare/ Studierektor forskarutbildn. LADOK-administratör Mats Blennow Agneta Wittlock mats.blennow@ki.se agneta.wittlock@ki.se 08-585 81428 08-585 87353 Medlemmar i FoU rådet Lars Olaf Cardell, ordförande Sten Hellström Malou Hultcrantz Mats Holmström Jan-Erik Juto Pia Nerfeldt Åsa Bonnard Eva Munck-Wikland Pär Stjärne Bo Tideholm Agneta Wittlock, ständig sekr. 5

Professorer och docenter Professor och senior professor Lars Olaf Cardell, professor Sten Hellström, professor emeritus Dan Bagger-Sjöbäck, professor emeritus Ulf Rosenhall, professor emeritus Adj.professorer / gästprofessorer Malou Hultcrantz Eva Munck Wikland Pär Stjärne Paolo Macchiarini Claus Bachert Wolf-Dieter Baumgartner Docenter Johan Bergenius Maoli Duan Anders Freijd Danielle Friberg Stellan Hertegård Mats Holmström Esma Idrizbegovic Jan-Erik Juto Richard Kuylenstierna Per-Åke Lindestad Riitta Möller Britt Nordlander Petri Olivius 6

Disputationer / halvtidskontroller 2012-2014 Datum Namn Titel 2012-01-20 Disputation Bengt Svensson Restoration of Scarred Vocal Folds with Stem Cell Implantation Analyses in a Xenograft Model 2012-02-03 Halvtid Marit Westman Rhinitis and rhinosinusitis in the BAMSE birth cohort, followed up to 16 years of age 2012-05-15 Halvtid Filip Asp Bilateral Cochlear Implants in Children- Clinical and Experimental Studies 2012-05-16 Disputation Per Attner Clinical Implications of Human Papilloma Virus (HPV) in oropharyngeal cancer 2012-06-11 Halvtid Eva Karltorp Cochlear implantation in early childhood 2012-09-07 Disputation Karin Lundkvist Pharyngeal surgery and epidemiology in sleep apnea 2012-09-18 Halvtid Yuan Xu Nicotine and endotoxin in asthma pathogenesis 2012-12-07 Disputation Elin Marsk Bell s palsy - study design, prognosis and quality of life 2012-12-12 Halvtid Louise Honeth Hörsel hos svenska jägare 2013-04-05 Disputation Terese Hylander Novel Potential Targets for Treatment of Airway Inflammation 2013-04-12 Halvtidskontroll Åsa Bonnard Östrogen och hörsel 2013-05-16 Halvtidskontroll Lotta Tengroth Pathogen-recognition receptors (PRRs) and inflammation in human upper airway disease 2013-06-10 Halvtidskontroll Daniel Nilsson Identification of risk factors in allergic rhinitis using association studies 2013-11-15 Halvtidskontroll Andreas Kaiser The use of organotypic culture and in vivo-studies to investigate implantation of progenitor neuronal cells to the auditory nervous system. 2013-11-22 Disputation Nanna Browaldh Upper airway surgery in obstructive sleep apnoea - descriptive, observational and randomised controlled studies 2013-12-13 Disputation Eva Karltorp Congenital cytomegalovirus infection and connexin 26 mutations in childhood deafness. Intervention with early cochlear implantation 2014 2014-01-24 Disputation Camilla Rydberg ÖNH:s föreläsningssal, Solna Pattern-Recognition Receptors and Neutrophils in Cancer Inflammation 2014-02-28 Disputation Tatjana Tomanovic ÖNH:s föreläsningssal, Solna Persistent geotropic nystagmus. A different kind of cupula pathology 7

Närvaro vid halvtidskontroll under perioden 2010-10 till 2013-11-15 8

Forskningssammanfattningar, seniora forskare Bachert, Claus... 11. Bark, Rusana... 16. Baumgartner, Wolf-Dieter... 17. Berninger, Erik... 18. Brantberg, Krister... 19. Browaldh, Nanna... 20. Cardell, Lars Olaf... 21. Duan, Maoli... 23. Ekborn, Andreas... 24. Engmér Berglin, Cecilia... 25. Friberg, Danielle... 26. Granath, Anna... 27. Hammarstedt Nordenvall, Lalle... 28. Hellström, Sten... 29. Henriksson, Gert... 30. Hertegård, Stellan... 31. Hessén Söderman, Anne-Charlotte... 32. Holmström, Mats... 33. Hultcrantz, Malou... 34. Idrizbegovic, Esma... 36. Karltorp, Eva... 37. Kumlien Georén, Susanna... 38 Larsson, Olivia... 39. Lindestad,Per-Åke... 40. Lundkvist, Karin... 41. Macchiarini, Paolo... 42. Marklund, Linda... 44. Marsk, Elin... 45. Munck-Wikland, Eva... 46. Möller, Riitta... 48. Nerfeldt, Pia... 49. Olsson, Petter... 50. Palmgren, Björn... 51. Ryott, Michael... 52. Stjärne, Pär... 53. Tideholm, Bo... 54. Uhlén, Inger... 55. 9

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Claus Bachert Forskare, professor Tel. 0032 473310902 claus.bachert@ki.se Chronic rhinosinusitis: Endotypes and genetic determinants Chronic rhinosinusitis (CRS) is an inflammatory disorder ofthe sinuses with a large phenotypic variability. The mechanisms of the disease are largely unknown, but are believed to result from a combination of environmental factors and the genetic background of affected individuals. CRS is subclassified into CRS with and without nasal polyposis (CRSwNP, CRSsNP), but recent work identified about 4 different endotypes (based on single major patho-mechanisms). Such pathomechanisms include IL-5 as a major Th2- cytokine, polyclonal IgE based on the impact of Staphylococcal superantigens, TNF-alpha and IL-22 related to bacterial stimuli, and others. Those endotypes may not only guide us to a new understanding of CRS, but also guides the selection of therapeutic targets such as anti-ige, anti-il5 etc for individual patients. Furthermore, those endotypes should help to sharpen genetic studies on CRS. Previous studies of CRS have defined 53 single nucleotide polymorphisms (SNPs) as associated with the CRSwNP or CRSsNP phenotypes. In a first step, we have investigated the reproducibility of previous SNP associations with CRS with and without NP. The study population consisted of 613 patients (248 females and 365 males), with 275 patients having CRS with NP and 338 patients having CRS without NP, and a set of 1588 background population controls (1042 females and 546 males) from the publicly available Illumina icontrol database. In this study, we replicated associations between genetic variants in 7 genes and the CRS phenotype. With P values of less than.01 and Q values of less than 0.1, the SNPs in PARS2, TGF-beta1, and NOS1 are all good candidates for further analysis, in particular because they are also plausible candidates from a functional biological perspective. These studies will be continued using the endotypes defined by tissue markers, and finally pooled genome-wide association study (pgwas) approaches based on endotypes. Publikationer 2011, 2012, 2013 1. J Patou, G Holtappels, K Affleck, P Van Cauwenberge, C Bachert. Syk-kinase inhibition prevents mast cell activation in human nasal tissue. Rhinology 2011;49:100-106 2. 276 IF 6.271. Kowalski ML, Cieślak M, Pérez-Novo CA, Makowska J, Bachert C. Clinical and immunological determinants of severe/ refractory asthma (SRA): association with Staphylococcal superantigen specific IgE antibodies. Allergy 2011;66:32-8 3. Meng J, Xuan J, Qiao X, Li X, Liu F, Liu S, Zhang N, Bachert C. Assessment of sleep disturbance in persistent allergic rhinitis patients using polysomnography. Int Arch Allergy Immunol 2011;155:57-62 4. PJ. Bousquet, G Passalacqua, M Calderon, P Demoly, J Brozek, D Larenas, C Bachert, GW Canonica, T Casale, J Fonceca, R Dahl, SR Durham, H Merk, M Worms, U Wahn, T Zuberbier, HJ Schünemann, J Bousquet.The CONSORT statement applied to sublingual immunotherapy with inhalant allergens. A GA2LEN Paper. JACI 2011;127:49-56 5. Zhang N, G Holtappels, P Gevaert, J Patou, B Dhaliwal, H Gould, C Bachert. Mucosal tissue polyclonal IgE is functional in response to allergen and SEB. Allergy 2011;66:141-8 epub 2010 6. Bachert C. Evidence-based management of nasal polyposis by intranasal corticosteroids: from the cause to the clinic Int Arch Allergy Immunol 2011;155:309-321 7. Krysko O, G Holtappels, N Zhang, M Kubica, K Deswarte, L Derycke, S Claeys, H Hammad, GG Brusselle, P Vandenabeele, DV Krysko, C Bachert. Alternatively activated macrophages and impaired phagocytosis of S. aureus in chronic rhinosinusitis. Allergy 2011;66:396-403 8. Bousquet PJ, Calderon MA, Demoly P, Larenas D, Passalacqua G, Bachert C, Brozek J, Walter Canonica G, Casale T, Fonseca J, Dahl R, Durham SR, Merk H, Worm M, Wahn U, Zuberbier T, Schünemann HJ, Bousquet J. The Consolidated Standards of Reporting Trials (CONSORT) Statement applied to allergen-specific immunotherapy with inhalant allergens: A Global Allergy and Asthma European Network (GA(2) LEN) article. J Allergy Clin Immunol. 2011;127:49-56 epub Nov 2010 9. J Bousquet, J Anto, C Auffray, M Akdis, A Cambon-Thomsen, T Keil, T Haahtela, BN Lambrecht, DS Postma, J Sunyer, R Valenta, CA Akdis, I Annesi-Maesano, A Arno, C Bachert, F Ballester, X Basagana, U Baumgartner, C Bindslev-Jensen, B Brunekreef, KH Carlsen, L Chatzi, R Crameri, E Eveno,F Forastiere, J Garcia-Aymerich, S Guerra, H Hammad, J Heinrich, D Hirsch, F Kauffmann, B Jacquemin, M Kerkhof, M Kogevinas, GH Koppelman, ML Kowalski, S Lau, KC Lodrup-Carlsen, M Lopez-Botet, J Lotvall, C Lupinek, D Maier, MJ Makela, F Martinez, J Mestres, I Momas, MC Nawijn, A Neubauer, S Oddie, S Palkonen, I Pin, C Pison, F Rancé, S Reitamo, E Rial-Sebbag, M Salapatas, V Siroux, D Smagghe, M Torrent, E Toskala, P van Cauwenberge, AJM van Oosterhout, R Varaso, L von Hertzen, M Wickman, C Wijmenga, M 11

Worm, J Wright, T Zuberbier. MeDALL (Mechanisms of the Development of ALLergy): An integrated approach from phenotypes to system medicine. Allergy 2011;66:596-604 10. Van Bruaene N, Bachert C. Tissue remodeling in chronic rhinosinusitis. Curr Opin Allergy Clin Immunol. 2011;11:811 11. Tomassen P, Newson RB, Hoffmans Ruth, Fokkens W, Bachert C, Burney P, Jarvis D, on behalf of the GA2LEN Survey. Reliability of symptom criteria and nasal endoscopy in the assessment of chronic rhinosinusitis based on EP3OS-guidelines - a GA²LEN study. Allergy 2011; 66:556-61epub Nov 2010 12. Krysko DV, A Kaczmarek, O Krysko, L Heyndrickx, J Woznicki, P Bogaert, A Cauwels, N Takahashi, S Magez, C Bachert, P Vandenabeele. TLR-2 and TLR-9 are sensors of apoptosis in a mouse model of doxorubicin-induced acute inflammation. Cell Death Differ 2011;18:1316-25 Feb 11 13. Sejima T, G Holtappels, C Bachert. The expression of fibrinolytic components in chronic paranasal sinus disease. Am J Rhinol Allergy 2011; 25:1-6 14. Krysko DV, P Agostinis, O Krysko, AD Garg, C Bachert, B Lambrecht, P Vandenabeele. Emerging role of DAMPs derived from mitochondria in inflammation. Trends in Immunology 2011;32:157-164 15. Bachert C, Zhang N, Holtappels G, Tomassen P, Liu S, Lin P, Bousquet J. Nasal polyp endotypes: IL-5 and asthma co-morbidity. J Allergy Clin Immunol. 2011 Mar 10 16. Schäfer T, Schnoor M, Wagenmann M, Klimek L, Bachert C. Therapeutic Index (TIX) for intranasal corticosteroids in the treatment of allergic rhinitis. Rhinology 2011;49:272-280 17. Mösges R, Bachert C, Rudack C, Hauswald B, Klimek L, Spaeth J, Rasp G, Vent J, Hörmann K. Efficacy and safety of mometasone furoate nasal spray in the treatment of chronic rhinosinusitis. Adv Ther. 2011;28:238-49 18. Ba L, N Zhang, Lin P, Liu S, Bachert C. Bacterial colonization is associated with different inflammatory pattern in rhinosinusitis with nasal polyps. Allergy 2011;66:1296-1303 epub 19. Bachert C. Evidence-Based Management of Nasal Polyposis by Intranasal Corticosteroids: From the Cause to the Clinic. Int Arch Allergy Immunol 2011;155:309 321 20. Tomassen P, Zele TV, Zhang N, Perez-Novo C, Bruaene NV, Gevaert P, Bachert C. Pathophysiology of chronic rhinosinusitis. Proc Am Thorac Soc. 2011;8:115-20. 21. Van Crombruggen K, L Van Nassauw, L Derycke, J-P Timmermans, G Holtappels, D Hall, C Bachert. Capsaicin-induced vasodilatation in human nasal vasculature is mediated by modulation of cyclooxygenase-2 activity and abrogated by sulprostone. Naunyn-Schmiedeberg s Archives of Pharmacology 2011;383:613-626 22. Bousquet J, Schünemann HJ, Bousquet PJ, Bachert C, Canonica GW, Casale TB, Demoly P, Durham S, Carlsen K-H, Malling H-J, Passalacqua G, Simons FER, Anto J, Baena-Cagnani CE, Bergmann K-C, Bieber T, Briggs AH, Brozek J, Calderon MA, Dahl R, Devillier P, Gerth van Wijk R, Howarth P, Larenas D, Papadopoulos NG, Schmid-Grendelmeier P, Zuberbier T. How to design and evaluate randomized controlled trials in immunotherapy for allergic rhinitis: an ARIA-GA(2) LEN statement. Allergy 2011; 66:1398-9995 23. Huvenne W, E Lanckacker, O Krysko, KR Bracke, T Demoor, PW Hellings, G Brusselle, G Joos, C Bachert, T Maes. Exacerbation of cigarette smoke-induced pulmonary inflammation by Staphylococcus aureus Enterotoxin B in mice. Respir Research 2011;12:69 24. Hastan D, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, Bousquet PJ, Brozek G, Bruno A, Dahlén SE, Forsberg B, Gunnbjörnsdóttir M, Kasper L, Kramer U, Kowalski ML, Lange B, Lundbäck B, Salagean E, Todo-Bom A, Tomassen P, Toskala E, Bousquet J, Zuberbier T, Jarvis D, Burney P. Chronic rhinosinusitis in Europe - an underestimated disease. A GA2LEN in study. Allergy 2011;66:1216-23 25. Glorieux S, C Bachert, HW Favoreel, A Vandekerckhove, L Steukers, A Rekecki, W Van den Broeck, RF Clayton, HJ Nauwynck. Herpes Simplex Virus Type 1 Penetrates the Basement Membrane in Human Nasal Respiratory Mucosa. PlosOne 2011;6(7):e22160. 26. Bachert C. Treatment of respiratory allergy with allergy immunotherapy tablets. Allergy 2011;66 Suppl 95:57-9 27. A Foreman, G Holtappels, AJ Psaltis, J Jervis-Bardy, J Field, PJ Wormald, C Bachert. Adaptive immune responses in Staphylococcus aureus biofilm associated chronic rhinosinusitis. Allergy 2011;66:1449-56 28. Van Crombruggen K, Zhang N, Gevaert P, Tomassen P, Bachert C. Pathogenesis of chronic rhinosinusitis: Inflammation. CURRENT PER- SPECTIVES. J Allergy Clin Immunol. 2011;128:728-32. 29. Scadding G, Hellings P, Alobid I, Bachert C, Fokkens W, G van Wijk R, Gevaert P, Guilemany J, Kalogjera L, Lund V, Mullol J, Passalacqua G, Toskala E, van Drunen C. Diagnostic tools in Rhinology EAACI position paper. Clinical and Translational Allergy 2011, 1:2 30. Gevaert P, N van Bruaene, T Cattaert, K van Steen, T Van Zele, F Acke, N De Ruyck, K Blomme, A Sousa, R Marshall, C Bachert. Mepolizumab, a humanised anti-il-5 monoclonal antibody, as treatment option for severe nasal polyposis. JACI 2011;128:989-995 31. Mechtcheriakova D, Sobanov J, Knittelfelder R, Bachert C, Jensen-Jarolim E. Gene expression pattern associated with activation-induced cytidine deaminase, AID, in chronic paranasal disorders. PlosOne 2011; 6:e25611 32. Bachert C, Maspero G. Efficacy of Second-Generation Antihistamines in Patients with Allergic Rhinitis and Comorbid Asthma. J Asthma 2011;48:965-73 33. Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, Canonica GW, Carlsen KH, Cox L, Haahtela T, Lodrup Carlsen KC, Price D, Samolinski B, Simons FE, Wickman M, Annesi-Maesano I, Baena-Cagnani CE, Bergmann KC, Bindslev-Jensen C, Casale TB, Chiriac A, Cruz AA, Dubakiene R, Durham SR, Fokkens WJ, Gerth-van-Wijk R, Kalayci O, Kowalski ML, Mari A, Mullol J, Nazamova- Baranova L, O Hehir RE, Ohta K, Panzner P, Passalacqua G, Ring J, Rogala B, Romano A, Ryan D, Schmid-Grendelmeier P, Todo-Bom A, Valenta R, Woehrl S, Yusuf OM, Zuberbier T, Demoly P. Practical guide to skin prick tests in allergy to aeroallergens. Allergy 2012;67:18-24 34. Jarvis D, Newson R, Lotval J, Hastan D, Tomassen P, Bousquet PJ, Bousquet J, Zuberbier T, Bachert C, Fokkens W, Burney P. Asthma in adults and its association with chronic rhinosinusitis: The GA2LEN survey in Europe. Allergy 2012;67:91-98 35. Zhang N, Van Crombruggen K, Holtappels G, Bachert C. A Herbal Composition of Scutellaria baicalensis and Eleutherococcus senticosus Shows Potent Anti-Inflammatory Effects in an Ex Vivo Human Mucosal Tissue Model. Evid Based Complement Alternat Med. 2012;2012:673145 36. Bousquet J, Ansótegui I, Canonica GW, Zuberbier T, -Cagnani B, Bachert C, Alez G, Kuna P, Morais-Almeida M, Mullol J, Sánchez-Borges M, An Valiente R. Establishing the place in therapy of bilastine in the treatment of allergic rhinitis according to ARIA: evidence review. 37. Curr Med Res Opin. 2012;28:131-139 38. Baumann D, Bachert C, Högger P. Development of a novel model for comparative evaluation of intranasal pharmacokinetics and effects of anti-allergic nasal sprays European Journal of Pharmaceutics and Biopharmaceutics 2012;80:156-163 39. Bachert C, Walter Canonica G, Bufe A. SIT: efficacy depends on product, not on route of application. Pediatr Allergy Immunol. 2012;23:401 40. Pilan RR, Pinna FR, Bezerra TF, Mori RL, Padua FG, Bento RF, Perez-Novo C, Bachert C, Voegels RL. Prevalence of chronic rhinosinusitis in Sao Paulo. Rhinology 2012;50:129-38 12

41. Carr W, Bernstein J, Lieberman P, Meltzer E, Bachert C, Price D, Munzel U, Bousquet J. A novel intranasal therapy of azelastine with fluticasone for the treatment of allergic rhinitis. J Allergy Clin Immunol. 2012;129:1282-1289 42. Stuck BA, Bachert C, Federspil P, Hosemann W, Klimek L, Mösges R, Pfaar O, Rudack C, Sitter H, Wagenmann M, Weber R, Hörmann K. Rhinosinusitis guidelines-unabridged version: S2 guidelines from the German Society of Otorhinolaryngology, Head and Neck Surgery. HNO 2012;60:141-62 43. Derycke L, Zhang N, Holtappels G, Dutré T, Bachert C. IL-17A as a regulator of neutrophil survival in nasal polyp disease of patients with and without cystic fibrosis. J Cyst Fibros. 2012;11:193-200 44. Merkonidis C, Gudziol V, Cecchini M, Gerber J, Seo H, Bachert C, Hummel T. Improvement of chronic rhinitis under Aspirin; case report. Respiratory Care 2012;57:460-3 45. Sejima T, Holtappels G, Kikuchi H, Imayoshi S, Ichimura K, Bachert C. Cytokine profiles in Japanese patients with chronic rhinosinusitis. Allergol Int. 2012;61:115-22. 46. Meltzer EO, Gates D, Bachert C. Mometasone furoate nasal spray increases the number of minimal-symptom days in patients with acute rhinosinusitis. Ann Allergy Asthma Immunol 2012;108:275-9 47. Bousquet J, JM Anto, P Demoly, HJ Schünemann, A Togias, M Akdis, C Auffray, C Bachert et al. Severe chronic allergic (and related) diseases: a uniform approach a MeDALL-GA2LEN-ARIA Position Paper. In collaboration with the WHO Collaborating Center for Asthma and Rhinitis. Int Arch Allergy Immunol 2012;158:216-231 48. Van Crombruggen K, Holtappels G, De Ruyck N, Derycke L, Tomassen P, Bachert C. RAGE- processing in chronic airway conditions: involvement of Staphylococcus aureus and ECP. J Allergy Clin Immunol 2012;129:1515-1521 49. Antó JM, Pinart M, Akdis M, Auffray C, Bachert C, Basagaña X, Carlsen KH, Guerra S, von Hertzen L, Illi S, Kauffmann F, Keil T, Kiley JP, Koppelman GH, Lupinek C, Martinez FD, Nawijn MC, Postma DS, Siroux V, Smit HA, Sterk PJ, Sunyer J, Valenta R, Valverde S, Akdis CA, Annesi-Maesano I, Ballester F, Benet M, Cambon-Thomsen A, Chatzi L, Coquet J, Demoly P, Gan W, Garcia-Aymerich J, Gimeno-Santos E, Guihenneuc-Jouyaux C, Haahtela T, Heinrich J, Herr M, Hohmann C, Jacquemin B, Just J, Kerkhof M, Kogevinas M, Kowalski ML, Lambrecht BN, Lau S, Lødrup Carlsen KC, Maier D, Momas I, Noel P, Oddie S, Palkonen S, Pin I, Porta D, Punturieri A, Rancière F, Smith RA, Stanic B, Stein RT, van de Veen W, van Oosterhout AJ, Varraso R, Wickman M, Wijmenga C, Wright J, Yaman G, Zuberbier T, Bousquet J. Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: A Mechanisms of the Development of Allergy (MeDALL) Seminar. J Allergy Clin Immunol. 2012;129:943-54 50. Calus L, Zele TV, Derycke L, Krysko O, Dutre T, Tomassen P, Dullaers M, Bachert C, Gevaert P. Local Inflammation in Chronic Upper Airway Disease. Curr Pharm Des 2012;18:2336-46 51. Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaerts P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang DY, Wormald PJ. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology 2012;50:1-12 52. Pace E, Scafidi V, Di Bona D, Siena L, Chiappara G, Ferraro M, La Grutta S, Gallina S, Speciale R, Ballacchino A, Bachert C, Bousquet J, Gjomarkaj M. Increased expression of IL-19 in the epithelium of patients with chronic rhinosinusitis and nasal polyps. Allergy 2012;67:878-86 53. Bachert C, K van Steen, N Zhang, G Holtappels, T Cattaert, B Maus, R Buhl, C Taube, S Korn, M Kowalski, J Bousquet, P Howarth. Specific IgE against Staphylococcus aureus enterotoxins: an independent risk factor for asthma. J Allergy Clin Immunol. 2012 Aug;130(2):376-381. e8. Epub 2012 Jun 26. 54. Bachert C, Zhang N, van Zele T, Gevaert P. From one disease to different phenotypes. Pediatric Allergy Immunol 2012;23:S22, 2-4 55. Van Bruaene N, C Perez Novo, N Deruyck, G Holtappels, P Van Cauwenberge, C Bachert. Inflammation and remodeling patterns in earlystage chronic rhinosinusitis. Clin Exp Allergy 2012;42:883-90 56. Wang XD, N Zhang, S Glorieux, G Holtappels, M Vaneechoutte, O Krysko, L Zhang, DM Han, HJ Nauwynck, C Bachert. Herpes simplex virus type 1 infection facilitates invasion of Staphylococcus aureus into the nasal mucosa and nasal polyp tissues. PLoS One 2012;7(6):e39875. Epub 2012 Jun 29. 57. Bachert C, Zhang N. Chronic rhinosinusitis and asthma: novel understanding of the role of IgE above atopy. J Intern Med. 2012;272:133-43 58. Groot Kormelink T, Lien Calus, Natalie de Ruyck, Gabriele Holtappels, C Bachert, FA Redegeld, P Gevaert. Local free light chain expression is increased in chronic rhinosinusitis with nasal polyps. Allergy 2012;67:1165-72 59. Yang YC, Zhang N, Van Crombruggen K, Hu GU, Hong SL, Bachert C. Transforming growth factor beta1 in inflammatory airway disease: A key for understanding inflammation and remodeling. Allergy 2012;67:1193-202 60. Jund R, Mondigler M, Steindl H, Stammer H, Stierna P and Bachert C. Clinical efficacy of a dry extract of five herbal drugs in acute viral rhinosinusitis. Rhinology 2012:50:417-426 61. Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl. 2012;23:3, 1-298 62. Pezato R, Świerczyńska M, Nizankowska-Mogilnicka E, Derycke L Bachert C, Pérez-Novo CA. Role of imbalance of eicosanoids pathways and staphylococcal superantigens in chronic rhinosinusitis. Allergy 2012;67:1347-56 63. Zhang Y, Song X, Zhao Y, Zhang L, Bachert C. Single nucleotide polymorphisms in thymic stromal lymphopoietin gene are not associated with allergic rhinitis susceptibility in Chinese subjects. BMC Medical Genetics 2012;13;79 64. Blomme K, Tomassen P, Lapeere H, Huvenne W, Bonny M, Acke F, Bachert C, Gevaert P. Prevalence of Allergic Sensitization versus Allergic Rhinitis Symptoms in an Unselected Population. Int Arch Allergy Immunol. 2012;160:200-207 65. Bousquet J, Schünemann HJ, Samolinski B, Demoly P, Baena-Cagnani CE, Bachert C, Bonini S, Boulet LP, Bousquet PJ, Brozek JL, Canonica GW, Casale TB, Cruz AA, Fokkens WJ, Fonseca JA, Gerth van Wijk R, Grouse L, Haahtela T, Khaltaev N, Kuna P, Lockey RF, Lodrup Carlsen KC, Mullol J, Naclerio R, O Hehir RE, Ohta K, Palkonen S, Papadopoulos NG, Passalacqua G, Pawankar R, Price D, Ryan D, Simons FE, Togias A, Williams D, Yorgancioglu A, Yusuf OM, Aberer W, Adachi M, Agache I, Aït-Khaled N, Akdis CA, Andrianarisoa A, Annesi-Maesano I, Ansotegui IJ, Baiardini I, Bateman ED, Bedbrook A, Beghé B, Beji M, Bel EH, Ben Kheder A, Bennoor KS, Bergmann KC, Berrissoul F, Bieber T, Bindslev Jensen C, Blaiss MS, Boner AL, Bouchard J, Braido F, Brightling CE, Bush A, Caballero F, Calderon MA, Calvo MA, Camargos PA, Caraballo LR, Carlsen KH, Carr W, Cepeda AM, Cesario A, Chavannes NH, Chen YZ, Chiriac AM, Chivato Pérez T, Chkhartishvili E, Ciprandi G, Costa DJ, Cox L, Custovic A, Dahl R, Darsow U, De Blay F, Deleanu D, Denburg JA, Devillier P, Didi T, Dokic D, Dolen WK, Douagui H, Dubakiene R, Durham SR, Dykewicz MS, El-Gamal Y, El-Meziane A, Emuzyte R, Fiocchi A, Fletcher M, Fukuda T, Gamkrelidze A, Gereda JE, Diaz SG, Gotua M, Guzmán MA, Hellings PW, Hellquist-Dahl B, Horak F, O B Hourihane J, Howarth P, Humbert M, Ivancevich JC, Jack- 13

son C, Just J, Kalayci O, Kaliner MA, Kalyoncu AF, Keil T, Keith PK, Khayat G, Kim YY, Koffi N goran B, Koppelman GH, Kowalski ML, Kull I, Kvedariene V, Larenas-Linnemann D, Le LT, Lemière C, Li J, Lieberman P, Lipworth B, Mahboub B, Makela MJ, Martin F, Marshall GD, Martinez FD, Masjedi MR, Maurer M, Mavale-Manuel S, Mazon A, Melen E, Meltzer EO, Mendez NH, Merk H, Mihaltan F, Mohammad Y, Morais-Almeida M, Muraro A, Nafti S, Namazova-Baranova L, Nekam K, Neou A, Niggemann B, Nizankowska-Mogilnicka E, Nyembue TD, Okamoto Y, Okubo K, Orru MP, Ouedraogo S, Ozdemir C, Panzner P, Pali-Schöll I, Park HS, Pigearias B, Pohl W, Popov TA, Postma DS, Potter P, Rabe KF, Ratomaharo J, Reitamo S, Ring J, Roberts R, Rogala B, Romano A, Roman Rodriguez M, Rosado-Pinto J, Rosenwasser L, Rottem M, Sanchez-Borges M, Scadding GK, Schmid-Grendelmeier P, Sheikh A, Sisul JC, Solé D, Sooronbaev T, Spicak V, Spranger O, Stein RT, Stoloff SW, Sunyer J, Szczeklik A, Todo-Bom A, Toskala E, Tremblay Y, Valenta R, Valero AL, Valeyre D, Valiulis A, Valovirta E, Van Cauwenberge P, Vandenplas O, van Weel C, Vichyanond P, Viegi G, Wang DY, Wickman M, Wöhrl S, Wright J, Yawn BP, Yiallouros PK, Zar HJ, Zernotti ME, Zhong N, Zidarn M, Zuberbier T; in collaboration with the World Health Organization Collaborating Center for Asthma and Rhinitis. Allergic Rhinitis and its Impact on Asthma (ARIA): Achievements in 10 years and future needs. J Allergy Clin Immunol. 2012 Oct 4. pii: S0091-6749(12)01306-1. doi: 10.1016/j.jaci.2012.07.053 66. Carr WW, Ratner P, Munzel U, Murray R, Price D, Canonica GW, Mullol J, Virchow JC, Lieberman P, Meltzer E, Bachert C. Comparison of intranasal azelastine to intranasal fluticasone propionate for symptom control in moderate-to-severe seasonal allergic rhinitis. Allergy Asthma Proc 2012;33:1 9 67. Calderon MA, Demoly P, Gerth van Wijk R, Bousquet J, Sheikh A, Frew A, Scadding G, Bachert C, Malling HJ, Valenta R, Bilo B, Nieto A, Akdis C, Just J, Vidal C, Varga EM, Alvarez-Cuesta E, Bohle B, Bufe A, Canonica WG, Cardona V, Dahl R, Didier A, Durham SR, Eng P, Fernandez-Rivas M, Jacobsen L, Jutel M, Kleine-Tebbe J, Klimec L, Lötvall J, Moreno C, Mosges R, Muraro A, Niggemann B, Pajno G, Passalacqua G, Pfaar O, Rak S, Senna G, Senti G, Valovirta E, van Hage M, Virchow JC, Wahn U, Papadopoulos NG. EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy. Clin Transl Allergy. 2012;2:20 68. Tantilipikorn P, Bunnag C, Nan Z, Bachert C. Staphylococcus aureus superantigens and their role in eosinophilic nasal polyp disease. Asian Pac J Allergy Immunol. 2012;30:171-6. 69. Hellings PW, Scadding G, Alobid I, Bachert C, Fokkens WJ, Gerth van Wijk R, Gevaerts P, Guilemany J, Kalogjera L, Mullol J, Passalacqua G, Toskala E, van Drunen CM. Executive summary of European Task Force document on diagnostic tools in rhinology. Rhinology. 2012;50:339-52 70. Gevaert P, L Calus, T Van Zele, K Blomme, N De Ruyck, W Bauters, P Hellings, G Brusselle, D De Bacquer, P van Cauwenberge, C Bachert. Omalizumab is effective in allergic and non-allergic patients with nasal polyposis and co-morbid asthma. J Allergy Clin Immunol 2013;131:110-116 71. Krysko O, Maes T, Plantinga M, Holtappels G, Imiru R, Vandenabeele P, Joos G, Krysko DV, Bachert C.et al. The adjuvant-like activity of Staphylococcal enterotoxin B in a murine asthma model is independent of IL-1R signaling. Allergy 2013 Jan 25. doi: 10.1111/all.12102 72. Jacob F, Novo CP, Bachert C, Van Crombruggen K. Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses. Purinergic Signal. 2013 Feb 13. [Epub ahead of print] 73. Hellings PW, Fokkens WJ, Akdis C, Bachert C, Cingi C, Dietz de Loos D, Gevaert P, Hox V, Kalogjera L, Lund V, Mullol J, Papadopoulos NG, Passalacqua G, Rondón C, Scadding G, Timmermans M, Toskala E, Zhang N, Bousquet J. Uncontrolled allergic rhinitis and chronic rhinosinusitis: where do we stand today? Allergy 2013;68:1-7 74. Gevaert P, K T Nouri-Aria, H Wu, C E Harper, P Takhar, D J Fear, F Acke, N Deruyck, G Banfield, HH Kariyawasam, C Bachert, SR Durham, HJ Gould. Local Receptor Revision and Class Switching to IgE in Chronic Rhinosinusitis with Nasal Polyps. Allergy 2013; 68: 55-63 75. Declercq HA, T De Caluwé, O Krysko, C Bachert, MJ Cornelissen. Bone grafts engineered from human adipose-derived stem cells in dynamic 3D-environments. Biomaterials 2013;34: 1004-17 76. Manise M, Holtappels G, van Crombruggen K, Schleich F, Bachert C, Louis R. Sputum IgE and cytokines in asthma: relationship with sputum cellular profile. PlosOne 2013, 8(3): e58388. doi:10.1371/journal.pone.0058388 77. Zhang Y, Wang X, Zhang W, Han D, Zhang L, Bachert C. Polymorphisms in thymic stromal lymphopoietin gene demonstrate a gender and nasal polyposis-dependent association with chronic rhinosinusitis. Hum Immunol 2013;74:241-8 78. Bonini M, Bachert C, Baena-Cagnani CE, Bedbrook A, Brozek JL, Canonica GW, Cruz AA, Fokkens WJ, Wijk RG, Grouse L, Hellings PW, Howarth P, Kalayci O, Khaltaev N, Kuna P, Linnemann DL, Nekam K, Palkonen S, Papadopoulos NG, Popov TA, Price D, Pinto JR, Rasi G, Ryan D, Samolinski B, Scadding GK, Schünemann HJ, Thomas DM, Triggiani M, Yorgancioglu A, Yusuf OM, Zuberbier T, Pawankar R, Bousquet J, Bonini S; on behalf of the ARIA Initiative, in collaboration with the WHO Collaborating Center for Asthma, Rhinitis. What we should learn from the London Olympics. Curr Opin Allergy Clin Immunol 2013;13:1-3 79. Akdis CA, Bachert C, Cingi C, Dykewicz M, Hellings P, Naclerio RM, Schleimer RP, Ledfordh D. 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 Apr 12. doi:pii: S0091-6749(13)00367-9. 10.1016/j.jaci.2013.02.036 80. Huvenne W, Hellings P, Bachert C. Role of Staphylococcal superantigens in airway disease. Int Arch Allergy Immun 2013 May 14;161(4):304-314 81. Dutre T, Al Dousary S, Zhang N, Bachert C. Allergic fungal rhinosinusitis (AFRS)- a bacterial presence coexisting with fungal disease? J Allergy Clin Immunol 2013 Apr 19. doi:pii: S0091-6749(13)00417-X. 10.1016/j.jaci.2013.02.040. Letter 82. Wang M, Zhang W, Shang J, Yang J, Zhang L, Bachert C. Immunomodulatory effects of IL-23 and IL-17 in a mouse model of allergic rhinitis. Clin Exp Allergy 2013;43:956-66 83. Katotomichelakis M, Tantilipikorn P, Holtappels G, De Ruyck N, Feng L, Van Zele T, Muangsomboon P, Jareonchasri P, Bunnag C, Danielides V, Hellings PW, Bachert C, Zhang N. Inflammatory patterns in upper airway disease in the same geographical area may change over time. Rhinology 2013 84. Meltzer E, Ratner P, Bachert C, Carr W, Berger W, Canonica GW, Hadley J, Lieberman P, Hampel FC, Mullol J, Munzel U, Price D, Scadding G, Virchow JC, Wahn U, Murray R, Bousquet J. Clinically relevant effect of a new intranasal therapy (MP29-02) in allergic rhinitis assessed by responder analysis. Int Arch Allergy Immunol 2013;161:369-377 85. Tomassen P, Jarvis D, Newson R, Van Ree R, Forsberg R, Howarth P, Janson C, Kowalski ML, Krämer U, Matricardi PM, Middelveld RJM, Todo-Bom A, Toskala E, Thilsing T, Brożek G, Van Drunen C, Burney P, Bachert C. Staphylococcus aureus enterotoxin specific IgE and its association with asthma in the general population: a GA²LEN. Allergy 2013 Oct 5. doi: 10.1111/all.12230 86. Balsalobre L, Pezato R, Perez-Novo C, Alves MT, Santos RP, Bachert C, Weckx LL. Epithelium and stroma from nasal polyp mucosa exhibits inverse expression of TGF-β1 as compared with healthy nasal mucosa. J Otolaryngol Head Neck Surg. 2013;42:29 87. Van Crombruggen K, F Jackob, Nan Zhang, C Bachert. Damage Associated Molecular Patterns and their receptors in upper airway pathologies. Cell Mol Life Science 2013 May 15 14

88. Krysko O, Løve Aaes T, Bachert C, Vandenabeele P, Krysko DV. Many faces of DAMPs in cancer therapy. Cell Death Dis. 2013 May 16;4:e631. doi: 10.1038/cddis.2013.156. 89. Bousquet J, Anto J, Sunyer J, Nieuwenhuijsen M, Vrijheid M, Keil T; MeDALL Study Group; CHICOS Study Group; ENRIECO Study Group; GA²LEN Study Group. Pooling birth cohorts in allergy and asthma: European Union-funded initiatives - a MeDALL, CHICOS, ENRIECO, and GA²LEN joint paper. Int Arch Allergy Immunol. 2013;161(1):1-10 90. Feng L, Zhang N, Zhang J, Krysko O, Zhang Q, Xian J, Derycke L, Qi Y, Li K, Liu S, Lin P, Bachert C. Forkhead box protein 3 in human nasal polyp regulatory T cells is regulated by the protein suppressor of cytokine signaling 3. J Allergy Clin Immunol. 2013 Jul 30. doi:pii: S0091-6749(13)00972-X 91. Lenoir J, Bachert C, Remon JP, Adriaens E. The Slug Mucosal Irritation (SMI) Assay: A tool for the Evaluation of Nasal Discomfort. Toxicol In Vitro. 2013;27:1954-1961 92. Katotomichelakis M, Simopoulos E, Zhang N, Tripsianis G, Danielides G, Livaditis M, Bachert C, Danielides V. Olfactory dysfunction and asthma as risk factors for poor quality of life in upper airway diseases. Am J Rhinol Allergy. 2013;27:293-8 93. Henmyr V, G Vandeplas, C Halldén, T Säll, H Olze, C Bachert, LO Cardell. Replication study of genetic variants associated with chronic rhinosinusitis and nasal polyposis. J Allergy Clin Immunol 2013 Sep 26. doi:pii: S0091-6749(13)01293-1. 10.1016/j.jaci.2013.08.011, Letter 94. Newson R, Jones M, Forsberg B, Janson C, Dahlén SE, Bossios A, Toskala E, Al-Kalemji A, Kowalski M, Rymarczyk B, Salagean E, van Drunen C, Bachert C, Wehrend T, Krämer U, Mota-Pinto A, Burney P, Leynaert B, Jarvis D. The association of asthma, nasal allergies and positive skin prick tests with obesity, leptin and adiponectin. Clin Exp Allergy. 2013 Oct 21. doi: 10.1111/cea.12221 95. Bobic S, Hox V, Callebaut I, Vinckier S, Jonckx B, Stassen JM, Jorissen M, Gevaert P, Carmeliet P, Bachert C, Ceuppens J, Helings P. Vascular Endothelial Growth Factor Receptor 1 Expression in Nasal Polyp Tissue. Allergy 2013 Oct 15. doi: 10.1111/all.12277 96. Luo B, Feng L, Jintao D, Yafeng L, Shixi L, Nan Z, Bachert C. Immunopathology features of chronic rhinosinusitis in high-altitude dwelling Tibetans. Allergy Rhinol (Providence). 2013 Summer;4(2):e69-e76. 97. Song WJ, Chang YS, Lim MK, Yun EH, Kim SH, Kang HR, Park HW, Tomassen P, Choi MH, Min KU, Cho SH, Bachert, C. Staphylococcal enterotoxin sensitization in a community-based population: a potential role in adult-onset asthma. CEA 2013 98. Meng J, Zhou P, Liu Y, Liu F, Yi X, Liu S, Holtappels G, Bachert C, Zhang N. The development of nasal polyp disease involves early nasal mucosal inflammation and remodeling. PLOS ONE 2013 99. Lupinek C, Wollmann E, Baar A, Banerjee S, Breiteneder H, Bublin M, Curin M, Flicker S, Garmatiuk T, Hochwallner H, Mittermann I, Pahr S, Resch Y, Roux KH, Srinivasan B, Vrtala S, Willison LN, Wickman M, Lodrup-Carlsen K, Antó JM, Bousquet J, Bachert C, Ebner D, Schlederer T, Harwanegg C, Valenta R. Advances in allergen-microarray technology for diagnosis and monitoring of allergy: The MeDALL allergen-chip. Methods. 2013 Oct 22. doi:pii: S1046-2023(13)00404-0. 10.1016/j.ymeth.2013.10.008 100. Krysko D, Kaczmarek A, Krysko O, Heyndrickx L, Løve Aaes T, Delvaeye T, Bachert C, Leybaert L, Vandenabeele P.TNF/TNF-R1 pathway is involved in doxorubicin-induced acute sterile inflammation. Cell death and disease 2013 101. Haahtela T, Burbach J, Bachert C, Bindslev-Jensen C, Bonini S, Bousquet J, Bousquet-Rouanet L, Bousquet PJ, Bresciani M, Bruno A, Canonica GW, Darsow U, Demoly P, Durham S, Fokkens WJ, Giavi S, Gjomarkaj M, Gramiccioni C, Kowalski ML, Losonczy G, Orosz M, Papadopoulos NG, Stingl G, Todo-Bom A, von Mutius E, Koehli-Wiesner A, Wöhrl S, Järvenpää S, Kautiainen H, Petman L, Selroos O, Zuberbier T, Heinzerling LM. Clinical relevance is associated with allergen specific wheal size in skin prick testing. Clinical implications from the GA²LEN Pan European SPT study. Clin Exp Allergy. 2013 Nov 27. doi: 10.1111/cea.12240 15

Könshormoner & Hörsel Rusana Bark Specialist läkare Ph.D. Tel. 08-517 76020 rusana.bark@karolinska.se Både män och kvinnor lider av åldersrelaterad hörselnedsättning, men hos män är denna mer uttalad och startar tidigare. Studier har visat könsskillnader vid hjärnstamsaudiometri (ABR), där kvinnor har kortare latenser än män. Efter menopaus blir dessa skillnader allt mindre till nackdel för kvinnorna. Kvinnor med Turner syndrom (45,X), där frånvaro/låg halt av östrogen är kardinalsymtomet, har tidig åldersrelaterad hörselnedsättning och längre ABRlatenser i de centrala nervbanorna. Östrogenets inverkan i olika vävnader har varit omdebatterad, men på senare år har dess positiva effekter övervägt, så även i örat, där både ERa och ERb finns. Negativa effekter har tillskrivits det andra kvinnliga könshormonet, progesteron. Det finns även studier där behandling med testosteron i vissa doser visat sig ge bättre hörsel. Det finns två progesteronreceptorer (PR-A och PR-B), samt en androgen receptor (AR). Pågående studier som del av mina två doktoranders avhandlinsprojekt: - Kartläggning av PR- & AR receptorer i innerörat hos råtta, gris och människa. - Longitudinell prospektiv studie av hörseln hos kvinnor med bröstcancer som behandladas med antiöstrogener. - Uppföljning av hörselutvecklingen hos kvinnor med Turner syndrom som fått östrogen substitution under uppväxten. - Effekten av östrogen substitution på hörseln hos Turnermöss. - Studier på ERb-knock-out möss och förekomsten/avsaknaden av Megalin (ligand för östrogen i innerörat) och korrelation till hörseln. ÖNH-cancer Pågående: - Risken för regional metastas hos patienter (n=162) med gingivalcancer i förhålande till tumörstorlek-, lokalisation(överkäke/underkäke), T-klass och histopatologi. - Retrospektiv studie där det studeras förekomst av cystisk metastas i patientmaterial från 2003-2013 opererade för lateral halscysta på Karolinska. Planerade: - Prospektiv studie: Är HPV en användbar markör för att skilja cystisk metastas från lateral halscysta? Handledare följande doktorander: Johan Svedbrant Huvudhandledare Åsa Bonnard Bihandledare Publikationer 2011, 2012, 2013 1. Bark R, Hammarstedt-Nordenvall L. Risk of cervical metastasis in N0 gingival cancer. In manuscript 2013. 2. Bark R, Mercke C, Munck-Wikland E, Wisniewski NA, Hammarstedt-Nordenvall L. Cancer of the Gingiva. Oral Oncology. Submitted nov 2013. 3. Bonnard Å, Sahlin L, Hultcrantz M, Simonoska R. No direct nuclear effect of Progesterone in the inner ear: other possible pathways. Acta OtoLaryngol. In press 2013. 4. Simonoska R, Stenberg A.E, Duan M, Yakimchuk K, Fridberger A, Sahlin L, J-Å Gustafsson, Hultcrantz M. Inner ear pathology and loss of hearing in estrogen receptor beta deficient mice. Journal of Endocrinology, 2009, 201:397 5. Simonoska R, Stenberg A.E, Masironi B, Sahlin L, Hultcrantz M. Estrogen receptors in the inner ear during different stages of pregnancy and development in the rat. Acta OtoLaryngol. 2009 Feb. 13: 1-7. 16

Wolf-Dieter Baumgartner Gästprofessor Tel. 0043 664 302 36 88 wolf-dieter.baumgartner@ki.se Cochlear Implants and implantable hearing aids Pediatric Cochlear Implant surgery is standard since many years. Based on neonatal hearing screening and genetic analysis of new born cochlear implant candidates a very early implantation is useful and possible. Bilateral cochlear implantation in children six months old is safe and successful. In children an adults suffering from partial deafness, so called Electric Acoustic Stimulation Cochlear Implantation is needed. This is a combination of natural acoustic hearing together with electric stimulation via cochlear implant on the same ear. Pediatric and adult patients profit from the synergy of two simultaneus stimulation modes. Cochlear implantation in single sided deafness in children and adults has shown to be successful to reestablish directional hearing and enhanced speech undesrstanding in noise. Since 1996 fully and semiimplantable hearing aids are available. Classic Vibrant Soundbridge Surgery (crimping onto the long process of incus) is helpful in sensorineural hearing loss. In mixed hearing loss and malformations Vibroplasty surgery with fixation onto the round window, oval window, ossicular remnants, stapes-suprastructure or fenestration is indicated. These surgical procedure is possible in children and adults. This year a new device, Vibrant Bonebridge, came up. This is an implantable boneconduction stimulator. Like a BAHA, bone conduction is used, but there is no screw through the skin. So far the very first implants have be performed very successfully in adults. The international pediatric study is right now in conduction and coordinated by myself. Keywords: Cochlear Implantation, children, bilateral, Electric Acoustic Stimulation, Vibrant Soundbridge, Vibroplasty, Vibrant Bonebridge Publikationer 2011, 2012, 2013 1. Laback B, Zimmermann I, Majdak P, Baumgartner WD, Pok SM. Effects of envelope shape on interaural envelope delay sensitivity in acoustic and electric hearing. J Acoust Soc Am. 2011 Sep;130(3):1515-29. 2. Arnoldner C, Gstoettner W, Riss D, Wagenblast J, Honeder C, Blineder M, Hamzavi JS, Jappel A,Baumgartner WD.Residual hearing preservation using the suprameatal approach for cochlear implantation. Wien Klin Wochenschr. 2011 Oct;123(19-20):599-602. Epub 2011 Aug 25. 3. Mueller J, Baumgartner WD, Godey B, Freijd A, Harris S, Helbig S, Quevedo MS, Mann W, Anderson I, Gstoettner W. The MED-EL SONATATI 100 cochlear implant: an evaluation of its safety in adults and children. Acta Otolaryngol. 2011 May;131(5):504-11. Epub 2011 Mar 23. 4. Riss D, Hamzavi JS, Katzinger M, Baumgartner WD, Kaider A, Gstoettner W, Arnoldner C. Effects of fine structure and extended low frequencies in pediatric cochlear implant recipients. Int J Pediatr Otorhinolaryngol. 2011 Apr;75(4):573-8. Epub 2011 Feb 15. 17

Erik Berninger Civ ing, Med Dr Tel. 073-699 41 01 erik.berninger@karolinska.se Spädbarns hörsel - tidig diagnostik och intervention Hörselscreening på nyfödda barn leder till tidig diagnostik och intervention. Anpassning av hörapparater på spädbarn, redan vid någon månads ålder, liksom tidig anpassning av cochleära implantat ger en tydlig förbättring av barnens kommunikativa förmåga senare i livet. Tidig anpassning av hörapparater är emellertid en komplicerad process. Kunskap om hörselns naturalförlopp under det första levnadshalvåret saknas, nuvarande objektiva mätmetoder är alltför ospecifika och tidskrävande. I kliniska och experientella studier söker vi utveckla snabba, reliabla och valida akustiska och neurofysiologiska metoder för detaljerad topisk diagnostik och beskrivning av hörseldynamiskt omfång. Identifiering av biomarkörer för tidigt debuterande hörselnedsättning samt utvärdering av förfinade algoritmer i cochleära implantat är exempel på frågeställningar med klinisk relevans. Tvillingstudier används för att studera den stora och kliniskt besvärande inter-individuella variabiliteten i innerörats mikromekaniska egenskaper vid födseln. En långsiktig målsättning är att finna orsakerna och mekanismerna bakom den vanligaste typen av medfödd hörselskada - den icke-syndromala cochleära hörselskadan - samt att identifiera eller utveckla framtida behandlingsmöjligheter. Specifikt kommer infektiösa exponeringar, genetiskt bidrag, cochleär morfologi och cochleär funktion att studeras i relation till taluppfattning i konkurrerande tal med och utan hörapparater parallellt med frågeformulär som beskriver upplevd problemförekomst i olika typer av vardagliga lyssningssituationer. Graden av progress samt nyttan av intervention under spädbarnsperioden kommer särskilt att studeras (hypotesen är att tidig intervention under spädbarnsperioden befrämjar de hörselskadade barnens kommunikativa utveckling). Handledare följande doktorander: Filip Asp Huvudhandledare Publikationer 2011, 2012, 2013 1. Asp, F., G. Eskilsson, and E. Berninger, Horizontal sound localization in children with bilateral cochlear implants: effects of auditory experience and age at implantation. Otol Neurotol, 2011. 32(4): p. 558-64. 2. Berninger, E. and B. Westling, Outcome of a universal newborn hearing-screening programme based on multiple transient-evoked otoacoustic emissions and clinical brainstem response audiometry. Acta Otolaryngol, 2011. 131(7): p. 728-39. 3. Israelsson, K.-E., R. Bogo, and E. Berninger, Reliability in hearing threshold prediction in normal hearing and hearing impaired subjects using mixed multiple ASSR, 2013, submitted. 4. Berninger, E., Å. Olofsson, A. Leijon. Analysis of click-evoked auditory brain stem responses using time domain cross-correlations between interleaved responses, Ear Hear, 2013, in press. 5. Berninger E. Report from 2012 MidWinter Research Meeting, Association for Research in Otolaryngology, San Diego, California, USA. Audio Nytt 2012;39(3):28-31. 6. Filip Asp, Gunnar Eskilsson, Erik Berninger. Early cochlear implantation promotes faster sound localization development, 2011 MidWinter Research Meeting, Association for Research in Otolaryngology, Baltimore, Maryland, USA, February 19-23, 2011. 7. Erik Berninger, Åke Olofsson, Arne Leijon. Analysis of click-evoked auditory brainstem responses using time domain crosscorrelations between interleaved responses, 2012 MidWinter Research Meeting, Association for Research in Otolaryngology, San Diego, California, USA, February 25-29, 2012. 8. Filip Asp, Åke Olofsson, Erik Berninger. Infants auditory localization accuracy measured by corneal eye-tracking: A pilot study, Modern techniques in auditory and communication sciences, Karolinska Institutet, Swedish Institute for Disability Research, Linneaeus Centre HEAD Graduate School, Lidingö, Sweden, October 16-18, 2013. 9. Filip Asp, Åke Olofsson, Erik Berninger. Infants auditory localization accuracy measured by corneal eye-tracking: A pilot study, 2014 MidWinter Research Meeting, Association for Research in Otolaryngology, San Diego, California, USA, February 22-26, 2014. 10. Anne-Marie Jakobsson, Filip Asp, Erik Berninger. Effects of induced lateral asymmetry on speech recognition and sound localization accuracy a pilot study, 2014 MidWinter Research Meeting, Association for Research in Otolaryngology, San Diego, California, USA, February 22-26, 2014. 18

Krister Brantberg Överläkare, Professor Tel. 08-51775907 krister.brantberg@karolinska.se Vibration mot skallen som test av balansorganets funktion Vetenskaplig frågeställning Kan mätning av ocular VEMP (vestibular evoked myogenic potentials från musculus obliquus inferior) detektera och kvantifiera utriculus-skador? Vilka stimulerings- och registrerings-parameter är optimala för denna mätning Områdesöversikt Örats balansorgan har fem delar, tre båggångar och två hinnsäckar (sacculus och utriculus). Båggångarna känner av huvudets vridrörelser. Hinnsäckarna känner av huvudets linjära rörelser och tyngdkraften. För båggångarna finns det såväl bra undersökningsmetoder som bra kunskap om effekten av skador (rotatorisk yrsel). Skador på hinnsäckar ger balansstörning av annan, och mindre känd, karaktär. Under de senaste 10 åren har en välfungerande klinisk test för sacculus framtagits. Vid denna test, cervical VEMP, stimuleras sacculus med ljud vilket utlöser en halsmuskelreflex som registreras med EMG. För utriculus saknas kliniskt användbar icke-perceptuell test. Baserat på såväl djurstudier som test på människa tycks det som utriculus funktion kan kvantifieras genom stimulering med vibration mot skallen och registrering av ögonmuskelsvar med hudelektroder placerade under ögonen ( ocular VEMP ). Projektbeskrivning ovemp undersöks på friska personer och på patienter med väl dokumenterade balansorgan/balansnerv sjukdomar. Stimulering med vibration med olika frekvens/duration och med olika placering på skallen provas. Betydelse En fungerande klinisk test för utriculus är av stor betydelse för att korrekt kunna skilja orsaken till, och därmed kunna förstå, en patients yrsel- och balansbesvär. Handleder följande doktorander: Luca Verrecchia Bihandledare Publikationer 2011, 2012, 2012 1. Westin M, Brantberg K. Mastoid and vertex low-frequency vibration-induced ovemp in relation to medially directed acceleration of the labyrinth. Clin Neurophysiol. 2013 Sep 26. doi:pii: S1388-2457(13)01009-2. 2. Verrecchia L, Gennser M, Tribukait A, Brantberg K. Superior vestibular dysfunction in severe decompression sickness suggests an embolic mechanism. Aviat Space Environ Med. 2012 Nov;83(11):1097-100. 3. Brantberg K, Verrecchia L. Effectiveness of different click stimuli in diagnosing superior canal dehiscence using cervical vestibular evoked myogenic potentials. Acta Otolaryngol. 2012 Oct;132(10):1077-83. 4. Brantberg K, Duan M, Falahat B. Ménière s disease in children aged 4-7 years. Acta Otolaryngol. 2012 May;132(5):505-9. 5. Brantberg K, Baloh RW. Similarity of vertigo attacks due to Meniere s disease and benign recurrent vertigo, both with and without migraine. Acta Otolaryngol. 2011 Jul;131(7):722-7. 6. Holmeslet B, Westin M, Brantberg K. Ocular vestibular evoked myogenic potentials: skull taps can cause a stimulus direction dependent double-peak. Clin Neurophysiol. 2011 Feb;122(2):391-7. 19

Nanna Browaldh Specialistläkare nanna.browaldh@karolinska.se Randomiserad studie av OSAS patienter; svalgkirurgi jämfört med ingen behandling Hypotes: Svalgkirurgi (uvulopalatofaryngoplastik, UPPP) förbättrar signifikant antal nattliga andningsstörningar, dagsömnighetssymtom och metabola parametrar jämfört med ingen behandling hos patienter med obstruktivt sömnapné syndrom (OSAS). Studiedesign: RCT med två parallella armar, där 65 patienter randomiserats till antingen UPPP direkt eller exspektans/ingen behandling i sex månader och därefter UPPP. Interventionen med UPPP har skett med konservativ teknik. Patienterna i studien har måttligt till uttalat OSAS, BMI <36, samt har slutat med eller avstått gängse behandling med CPAP och underkäksframdragande bettskena och är således utan behandling. Patienterna i studien har stora halsmandlar, eller små halsmandlar i kombination med en låg tungposition. Vid baseline samt vid uppföljning efter UPPP respektive exspektans har polysomnografi gjorts. I samband med detta har patienterna lämnat blodprov, gjort ett vigilanstest samt svarat på enkäter. Resultat: De första resultaten från RCTn visar att andningsparametrarna signifikant förbättrades i operationsgruppen jämfört med kontrollgruppen (publicerade resultat). Även dagsömnighetsvärden, livskvalitet samt vigilanstest visar på stora skillnader mellan grupperna till operationsgruppes fördel (manuskript inskickat). Frågeställning för aktuella delprojekt: 1. Förbättrar UPPP blodtryck, stress- och inflammationsparametrar, samt metabola parametrar jämfört med ingen behandling? 2. Förbättrar UPPP sömnrelaterad livskvalitet jämfört med ingen behandling (mätt med Karolinska Sleepiness Scale och Functional Outcomes of Sleep Questionnaire, FOSQ)? Publikationer 2011, 2012, 2013 1. Browaldh N, Nerfeldt P, Lysdahl M, Bring J, Friberg D. SKUP3 randomised controlled trial: polysomnographic results after uvulopalatopharyngoplasty in selected patients with obstructive sleep apnoea. Thorax 2013 Sep;68(9):846-53. doi: 10.1136/thoraxjnl-2012-202610 2. Browaldh N, Friberg D, Svanborg D, Nerfeldt P. 15-year efficacy of uvulopalatopharyngoplasty based on objective and subjective data. Acta Oto-Laryngologica, 2011; 131: 1303 1310. 20