TY  - JOUR
AB  - BACKGROUND: Allergen-specific immunotherapy (AIT) is a disease-modifying therapy and is effective to reduce the symptoms of grass pollen-allergy. The airway epithelium of these patients releases inflammatory mediators including type-2 cytokines, which are associated with cellular processes involved in the symptomatic response of the affected tissue. Aim of the study was to identify epithelial biomarkers indicating AIT progress. METHODS: In an exploratory, observational allergy cohort, we longitudinally phenotyped 56 grass pollen-allergic patients undergoing AIT for over three years and 18 controls using nasal secretions at critical time windows during therapy to assess peak-season responses along the course of therapy. Type-2 cytokine protein levels were analyzed using the high-sensitivity multiplex electrochemiluminescence mesoscale technique. RESULTS: The type-2 cytokines CCL26 and POSTN oscillated seasonally, in contrast to TSLP and IL-33. However, only POSTN was reduced over the three-year AIT progression. In addition to POSTN, IL-24 and IL-37 levels were continuously reduced during AIT, while IFN-g and CCL27 were increased. Compared to healthy individuals, AIT did not restore healthy secretion levels but rather induced a novel homeostasis CONCLUSION: Nasal secretions trace the epithelial response during different phases of AIT. We demonstrate that AIT only partially controls the epithelial type 2 cytokine CCL26, which also adapts to seasonal changes, while POSTN and IL-24 are potential indicators of therapy success. Therefore, nasal secretions represent a promising, non-invasive tool for monitoring seasonal progress of AIT.
AU  - Jakwerth, C.A.
AU  - Zissler, U.M.
AU  - Oelsner, M.
AU  - Pechtold, L.
AU  - zur Bonsen, L.S.
AU  - Plaschke, M.
AU  - Kau, J.
AU  - Davidovic, M.
AU  - Mootz, M.
AU  - Haller, B.*
AU  - Chaker, A.
AU  - Schmidt-Weber, C.B.
C1  - 72726
C2  - 56714
CY  - Univ Medical Center Utrecht, Rm G05 127, Dept Otorhinol, Heidelberglaan 100, 3584 Cx Utrecht, Netherlands
SP  - 43-53
TI  - Nasal secretions trace epithelial type 2 response to allergen-specific immunotherapy.
JO  - Rhinology
VL  - 63
IS  - 1
PB  - Int Rhinologic Soc
PY  - 2024
SN  - 0300-0729
ER  - 

TY  - JOUR
AB  - The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.
AU  - Hellings, P.W.*
AU  - Akdis, C.A.*
AU  - Bachert, C.*
AU  - Bousquet, J.*
AU  - Pugin, B.*
AU  - Adriaensen, G.*
AU  - Advani, R.*
AU  - Agache, I.*
AU  - Anjo, C.*
AU  - Anmolsingh, R.*
AU  - Annoni, E.*
AU  - Bieber, T.*
AU  - Bizaki, A.*
AU  - Braverman, I.*
AU  - Callebaut, I.*
AU  - Castillo Vizuete, J.A.*
AU  - Chalermwatanachai, T.*
AU  - Chmielewski, R.*
AU  - Cingi, C.*
AU  - Cools, L.*
AU  - Coppije, C.*
AU  - Cornet, M.E.*
AU  - De Boeck, I.*
AU  - De Corso, E.*
AU  - De Greve, G.*
AU  - Doulaptsi, M.*
AU  - Edmiston, R.*
AU  - Erskine, S.*
AU  - Gevaert, E.*
AU  - Gevaert, P.*
AU  - Golebski, K.*
AU  - Hopkins, C.*
AU  - Hox, V.*
AU  - Jaeggi, C.*
AU  - Joos, G.*
AU  - Khwaja, S.*
AU  - Kjeldsen, A.*
AU  - Klimek, L.*
AU  - Koennecke, M.*
AU  - Kortekaas Krohn, I.*
AU  - Krysko, O.*
AU  - Kumar, B.N.*
AU  - Langdon, C.*
AU  - Lange, B.M.*
AU  - Lekakis, G.*
AU  - Levie, P.*
AU  - Lourijsen, E.*
AU  - Lund, V.J.*
AU  - Martens, K.*
AU  - Mösges, R.*
AU  - Mullol, J.*
AU  - Nyembue, T.D.*
AU  - Palkonen, S.*
AU  - Philpott, C.*
AU  - Pimentel, J.*
AU  - Poirrier, A.*
AU  - Pratas, A.C.*
AU  - Prokopakis, E.*
AU  - Pujols, L.*
AU  - Rombaux, P.*
AU  - Schmidt-Weber, C.B.
AU  - Segboer, C.*
AU  - Spacova, I.*
AU  - Staikuniene, J.*
AU  - Steelant, B.*
AU  - Steinsvik, E.A.*
AU  - Teufelberger, A.*
AU  - Van Gerven, L.*
AU  - Van Gool, K.*
AU  - Verbrugge, R.*
AU  - Verhaeghe, B.*
AU  - Virkkula, P.*
AU  - Vlaminck, S.*
AU  - Vries-Uss, E.*
AU  - Wagenmann, M.*
AU  - Zuberbier, T.*
AU  - Seys, S.F.*
AU  - Fokkens, W.J.*
C1  - 51120
C2  - 43068
SP  - 202-210
TI  - EUFOREA Rhinology Research Forum 2016: Report of the brainstorming sessions on needs and priorities in rhinitis and rhinosinusitis.
JO  - Rhinology
VL  - 55
IS  - 3
PY  - 2017
SN  - 0300-0729
ER  - 

TY  - JOUR
AB  - OBJECTIVES: Topical delivery of drugs to the sinuses is challenging and requires also particular administration manoeuvres from the patient. This study was conducted to investigate 1) the delivery efficiency of a pulsating aerosol (Vibrent prototype device) to the sinuses and the nose, 2) the aerosol fraction that will deposit in the lungs and 3) potential differences regarding sinus and nasal deposition ratio when comparing aerosol administration during two different administration routes. METHODS: An open label deposition study in healthy volunteers was conducted using 99mTc-DTPA radiolabeled pulsating aerosols in comparison to nasal pump sprays. Deposition and retention of pulsating aerosols was assessed by gamma camera imaging during spontaneous nasal breathing and during closed soft palate administration. RESULTS: Aerosol administration during nasal breathing vs. application with closed soft plate results in significant lung, nasal and sinus deposition. No significant differences were observed for nasal clearance. In comparison, drug delivery using nasal pump sprays resulted in non-significant sinus, 100 % nasal and non-significant lung deposition. The clearance kinetics after nasal pump spray delivery was significantly accelerated. DISCUSSION: The standard application mode of pulsation aerosols with closed soft palate results in negligible lung deposition and therefore limits drug delivery to the nasal cavity only, minimizing unwanted side effects. Administration during spontaneous nasal breathing shows only 10% lung deposition, which is tolerable during drug administration. Relevant paranasal sinus deposition is noted during both application modes and clearance kinetics remains essentially unchanged. In contrast, nasal pump sprays do not show sinus drug delivery and nasal drug residence time is shortened.
AU  - Möller, W.
AU  - Saba, G.K.
AU  - Häussinger, K.*
AU  - Becker, S.*
AU  - Keller, M.*
AU  - Schuschnig, U.*
C1  - 6634
C2  - 29013
SP  - 286-291
TI  - Nasally inhaled pulsating aerosols: Lung, sinus and nose deposition.
JO  - Rhinology
VL  - 49
IS  - 3
PB  - Int. Rhinologic Soc.
PY  - 2011
SN  - 0300-0729
ER  - 

TY  - JOUR
AB  - Although there is a high incidence of nasal disorders including chronic sinusitis, there is limited success in the topical drug delivery to the nose and the paranasal sinuses. This is caused by the nose being an efficient filter for inhaled aerosol particles and the paranasal sinuses being virtually non-ventilated. Method: The objective of this study was to visualize the efficiency of sinus ventilation in healthy volunteers using dynamic 81mKr-gas imaging in combination with pulsating airflows. Furthermore, the deposition and retention of 99mTc-DTPA aerosol particles was assessed. Results: The ventilation of the maxillary and frontal sinuses could be visualized by gamma camera imaging during pulsating airflow. In addition, using pulsating airflow, between 3% and 5% of nasally deposited aerosols penetrated into the paranasal sinuses while during application without pulsation aerosol deposition was below 1%. Furthermore pulsation increased aerosol deposition in the nasal airways by a factor of three. Conclusions: The study demonstrates the high efficiency of a pulsating airflow in paranasal sinus ventilation and aerosolized drug delivery. This proves that topical drug delivery to the paranasal sinuses in relevant quantities is possible and indicates further clinical studies are necesarry.
AU  - Möller, W.
AU  - Schuschnig, U.*
AU  - Meyer, G.*
AU  - Häussinger, K.*
AU  - Keller, M.*
AU  - Junge-Hülsing, B.*
AU  - Mentzel, H.*
C1  - 1019
C2  - 26496
CY  - Amersfoort; Netherlands
SP  - 405-412
TI  - Ventilation and aerosolized drug delivery to the paranasal sinuses using pulsating airflow: A preliminary study.
JO  - Rhinology
VL  - 47
IS  - 4
PB  - International Rhinologic Society
PY  - 2009
SN  - 0300-0729
ER  - 

TY  - JOUR
AB  - Although there is a high incidence of nasal disorders including chronic sinusitis, there is limited success in the topical drug delivery to the nose and the paranasal sinuses. This is caused by the nose being an efficient filter for inhaled aerosol particles and the paranasal sinuses being virtually non ventilated. Method: The objective of this study was to visualize the efficiency of sinus ventilation in a nasal cast using dynamic 81mKr-gas imaging in combination with pulsating airflows. Furthermore, the efficiency of the deposition of radiolabelled aerosol was assessed. Results: Pulsation increased ventilation efficiency of the sinuses more than fivefold and aerosol deposition efficiency more than twentyfold, compared to delivery without pulsation. Furthermore pulsation increased aerosol deposition in the nasal airways by a factor of three. Using pulsating airflow Kr-gas ventilation and aerosol deposition efficiencies increased with increasing sinus volume. Pulsating airflow resulted in a deposition of up to 8% of the nebulized drug within the sinuses compared to 0.2% without pulsation. Conclusions: The study demonstrates the high efficiency of a pulsating airflow in paranasal sinus ventilation and aerosolized drug delivery. This proves that topical drug delivery to the paranasal sinuses in relevant quantities is possible.
AU  - Möller, W.
AU  - Schuschnig, U.*
AU  - Meyer, G.*
AU  - Mentzel, H.*
AU  - Keller, M.*
C1  - 3260
C2  - 25579
SP  - 213-220
TI  - Ventilation and drug delivery to the paranasal sinuses: Studies in a nasal cast using pulsating airflow.
JO  - Rhinology
VL  - 46
IS  - 3
PY  - 2008
SN  - 0300-0729
ER  -