Top

European Archives of Oto-Rhino-Laryngology

Published in:

01-06-2018 | Rhinology

Influence of MP 29-02 on ciliary beat frequency in human epithelial cells in vitro

Authors: D. Häussler, J. U. Sommer, A. Nastev, C. Aderhold, A. Wenzel, B. Kramer, B. A. Stuck, R. Birk

Published in: European Archives of Oto-Rhino-Laryngology | Issue 6/2018

Abstract

Purpose

MP 29-02, which contains fluticasone propionate and azelastine hydrochloride, is used as a topical nasal application for the treatment of seasonal and perennial allergic rhinitis. Although a multitude of data is available on the clinical symptom reduction and treatment safety of MP 29-02, the effect of MP 29-02 on ciliary beat frequency (CBF) has not been evaluated thus far.

Methods

MP 29-02-containing solution was applied at concentrations of 2.5, 5, 10, and 20% to 14 healthy subjects, and nasal ciliated epithelial cells were then visualized using a phase-contrast microscope. CBF was measured after the application of MP 29-02. For a comparison, fluticasone propionate was used. CBF measurements were then performed for 15 min at 22 °C. Ringer’s solution was applied as a negative control.

Results

MP 29-02 significantly reduced CBF at all the tested concentrations compared with that of the control group within the observation time. At a 2.5% concentration, MP 29-02 significantly reduced CBF from 6.81 Hz (SD ± 1.35 Hz) at baseline to 4.88 Hz (SD ± 1.52 Hz, p < 0.001) after 15 min. In contrast, for fluticasone propionate, a significant reduction was observed only with the 20% concentration after 5, 10, and 15 min.

Conclusions

MP 29-09 significantly reduced CB, with an almost linear relationship between the MP 29-09 concentration and reduction in CBF. For fluticasone propionate, a significant reduction of CBF was observed only at the highest analyzed concentration. The findings have implications for the long-term use of the MP 29-02. Yet, further clinical studies are needed to confirm these results in vivo, especially in patients with seasonal or perennial allergic rhinits.

Bauchau V, Durham SR (2004) Prevalence and rate of diagnosis of allergic rhinitis in Europe. Eur Respir J 24(5):758–764. https://doi.org/10.1183/09031936.04.00013904 CrossRefPubMed

Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, Zuberbier T et al (2008) Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 63(Suppl 86):8–160. https://doi.org/10.1111/j.1398-9995.2007.01620.x CrossRefPubMed

Ozdoganoglu T, Songu M, Inancli HM (2012) Quality of life in allergic rhinitis. Ther Adv Respir Dis 6(1):25–39. https://doi.org/10.1177/1753465811424425 CrossRefPubMed

Stuck BA, Czajkowski J, Hagner AE, Klimek L, Verse T, Hormann K, Maurer JT (2004) Changes in daytime sleepiness, quality of life, and objective sleep patterns in seasonal allergic rhinitis: a controlled clinical trial. J Allergy Clin Immunol 113(4):663–668. https://doi.org/10.1016/j.jaci.2003.12.589 CrossRefPubMed

BfArM BfAuM (2017) Summary of product characteristics. Deutsches Institut für Medizinische Dokumentation und Information (DIMDI). https://portal.dimdi.de/amispb/doc/2017/10/10/2185237/O6f397096b9794bf7a9d66263ffa71d24.pdf. (Accessed 11 Oct 2017)

Klimek L, Mullol J, Hellings P, Gevaert P, Mosges R, Fokkens W (2016) Recent pharmacological developments in the treatment of perennial and persistent allergic rhinitis. Expert Opin Pharmacother 17(5):657–669. https://doi.org/10.1517/14656566.2016.1145661 CrossRefPubMed

Bush RK (2004) Etiopathogenesis and management of perennial allergic rhinitis: a state-of-the-art review. Treat Respir Med 3(1):45–57CrossRefPubMed

Meltzer EO, LaForce C, Ratner P, Price D, Ginsberg D, Carr W (2012) MP29-02 (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate) in the treatment of seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled trial of efficacy and safety. Allergy Asthma Proc 33(4):324–332. https://doi.org/10.2500/aap.2012.33.3587 CrossRefPubMed

Carr W, Bernstein J, Lieberman P, Meltzer E, Bachert C, Price D, Munzel U et al (2012) A novel intranasal therapy of azelastine with fluticasone for the treatment of allergic rhinitis. J Allergy Clin Immunol 129(5):1282–1289 e1210. https://doi.org/10.1016/j.jaci.2012.01.077 CrossRefPubMed

10.

Hampel FC, Ratner PH, Van Bavel J, Amar NJ, Daftary P, Wheeler W, Sacks H (2010) Double-blind, placebo-controlled study of azelastine and fluticasone in a single nasal spray delivery device. Ann Allergy Asthma Immunol 105(2):168–173. https://doi.org/10.1016/j.anai.2010.06.008 CrossRefPubMed

11.

Price D, Shah S, Bhatia S, Bachert C, Berger W, Bousquet J, Carr W et al (2013) A new therapy (MP29-02) is effective for the long-term treatment of chronic rhinitis. J Investig Allergol Clin Immunol 23(7):495–503PubMed

12.

Berger WE, Shah S, Lieberman P, Hadley J, Price D, Munzel U, Bhatia S (2014) Long-term, randomized safety study of MP29-02 (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in an advanced delivery system) in subjects with chronic rhinitis. J Allergy Clin Immunol Pract 2(2):179–185. https://doi.org/10.1016/j.jaip.2013.09.019 CrossRefPubMed

13.

Klimek L, Bousquet J, Price D (2016) Safety evaluation of MP29-02 (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate) for allergic rhinitis. Expert Opin Drug Saf 15(1):117–129. https://doi.org/10.1517/14740338.2016.1122755 CrossRefPubMed

14.

Cohen NA (2006) Sinonasal mucociliary clearance in health and disease. Ann Otol Rhinol Laryngol Suppl 196:20–26CrossRefPubMed

15.

Inoue D, Furubayashi T, Ogawara K, Kimura T, Higaki K, Shingaki T, Kimura S et al (2013) In vitro evaluation of the ciliary beat frequency of the rat nasal epithelium using a high-speed digital imaging system. Biol Pharm Bull 36(6):966–973CrossRefPubMed

16.

Mirra V, Werner C, Santamaria F (2017) Primary ciliary dyskinesia: an update on clinical aspects, genetics, diagnosis, and future treatment strategies. Front Pediatr 5:135. https://doi.org/10.3389/fped.2017.00135 CrossRefPubMedPubMedCentral

17.

Stannard W, O’Callaghan C (2006) Ciliary function and the role of cilia in clearance. J Aerosol Med 19(1):110–115. https://doi.org/10.1089/jam.2006.19.110 CrossRefPubMed

18.

Antunes MB, Gudis DA, Cohen NA (2009) Epithelium, cilia, and mucus: their importance in chronic rhinosinusitis. Immunol Allergy Clin North Am 29(4):631–643. https://doi.org/10.1016/j.iac.2009.07.004 CrossRefPubMed

19.

Duchateau GS, Graamans K, Zuidema J, Merkus FW (1985) Correlation between nasal ciliary beat frequency and mucus transport rate in volunteers. Laryngoscope 95(7 Pt 1):854–859PubMed

20.

Sun SS, Hsieh JF, Tsai SC, Ho YJ, Kao CH (2002) Evaluation of nasal mucociliary clearance function in allergic rhinitis patients with technetium 99 m-labeled macroaggregated albumin rhinoscintigraphy. Ann Otol Rhinol Laryngol 111(1):77–79. https://doi.org/10.1177/000348940211100112 CrossRefPubMed

21.

Hee J, Guillerm R (1977) [Mucociliary function and its alteration by certain irritants (author’s transl)]. Bull Eur Physiopathol Respir 13(1):11–25PubMed

22.

Mickenhagen A, Siefer O, Neugebauer P, Stennert E (2008) [The influence of different alpha-sympathomimetic drugs and benzalkoniumchlorid on the ciliary beat frequency of in vitro cultured human nasal mucosa cells]. Laryngorhinootologie 87(1):30–38. https://doi.org/10.1055/s-2007-966891 CrossRefPubMed

23.

Hofmann T, Gugatschga M, Koidl B, Wolf G (2004) Influence of preservatives and topical steroids on ciliary beat frequency in vitro. Arch Otolaryngol Head Neck Surg 130(4):440–445. https://doi.org/10.1001/archotol.130.4.440 CrossRefPubMed

24.

Jiao J, Meng N, Zhang L (2014) The effect of topical corticosteroids, topical antihistamines, and preservatives on human ciliary beat frequency. ORL J Otorhinolaryngol Relat Spec 76(3):127–136. https://doi.org/10.1159/000363575 CrossRefPubMed

25.

Klossek JM, Laliberte F, Laliberte MF, Mounedji N, Bousquet J (2001) Local safety of intranasal triamcinolone acetonide: clinical and histological aspects of nasal mucosa in the long-term treatment of perennial allergic rhinitis. Rhinology 39(1):17–22PubMed

26.

Naclerio RM, Baroody FM, Bidani N, De Tineo M, Penney BC (2003) A comparison of nasal clearance after treatment of perennial allergic rhinitis with budesonide and mometasone. Otolaryngol Head Neck Surg 128(2):220–227. https://doi.org/10.1067/mhn.2003.70 CrossRefPubMed

27.

Achterrath-Tuckermann U, Saano V, Minker E, Stroman F, Arny I, Joki S, Nuutinen J et al (1992) Influence of azelastine and some selected drugs on mucociliary clearance. Lung 170(4):201–209CrossRefPubMed

28.

Tamaoki J, Chiyotani A, Sakai N, Takeyama K, Konno K (1993) Effect of azelastine on sulphur dioxide induced impairment of ciliary motility in airway epithelium. Thorax 48(5):542–546CrossRefPubMedPubMedCentral

29.

Sommer JU, Gross S, Hormann K, Stuck BA (2010) Time-dependent changes in nasal ciliary beat frequency. Eur Arch Otorhinolaryngol 267(9):1383–1387. https://doi.org/10.1007/s00405-010-1211-5 CrossRefPubMed

30.

Thomas B, Rutman A, O’Callaghan C (2009) Disrupted ciliated epithelium shows slower ciliary beat frequency and increased dyskinesia. Eur Respir J 34(2):401–404. https://doi.org/10.1183/09031936.00153308 CrossRefPubMed

31.

Sisson JH, Stoner JA, Ammons BA, Wyatt TA (2003) All-digital image capture and whole-field analysis of ciliary beat frequency. J Microsc 211(Pt 2):103–111CrossRefPubMed

32.

Team RC (2013) R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing

33.

Bjorksten B, Clayton T, Ellwood P, Stewart A, Strachan D, Group IPIS. (2008) Worldwide time trends for symptoms of rhinitis and conjunctivitis: phase III of the International Study of Asthma and Allergies in Childhood. Pediatr Allergy Immunol 19(2):110–124. https://doi.org/10.1111/j.1399-3038.2007.00601.x CrossRefPubMed

34.

Sheth K (2008) Evaluating the safety of intranasal steroids in the treatment of allergic rhinitis. Allergy Asthma Clin Immunol 4(3):125–129. https://doi.org/10.1186/1710-1492-4-3-125 CrossRefPubMedPubMedCentral

35.

Weiner JM, Abramson MJ, Puy RM (1998) Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ 317(7173):1624–1629CrossRefPubMedPubMedCentral

36.

Yanez A, Rodrigo GJ (2002) Intranasal corticosteroids versus topical H1 receptor antagonists for the treatment of allergic rhinitis: a systematic review with meta-analysis. Ann Allergy Asthma Immunol 89(5):479–484. https://doi.org/10.1016/S1081-1206(10)62085-6 CrossRefPubMed

37.

Benninger MS, Ahmad N, Marple BF (2003) The safety of intranasal steroids. Otolaryngol Head Neck Surg 129(6):739–750. https://doi.org/10.1016/j.otohns.2003.10.001 CrossRefPubMed

38.

Jorissen M, Willems T, De Boeck K (2000) Diagnostic evaluation of mucociliary transport: from symptoms to coordinated ciliary activity after ciliogenesis in culture. Am J Rhinol 14(5):345–352CrossRefPubMed

39.

Merkus FW, Verhoef JC, Schipper NG, Marttin E (1998) Nasal mucociliary clearance as a factor in nasal drug delivery. Adv Drug Deliv Rev 29(1–2):13–38PubMed

40.

Minshall E, Ghaffar O, Cameron L, O’Brien F, Quinn H, Rowe-Jones J, Davies RJ et al (1998) Assessment by nasal biopsy of long-term use of mometasone furoate aqueous nasal spray (Nasonex) in the treatment of perennial rhinitis. Otolaryngol Head Neck Surg 118(5):648–654. https://doi.org/10.1177/019459989811800514 PubMedCrossRef

41.

Pipkorn U, Pukander J, Suonpaa J, Makinen J, Lindqvist N (1988) Long-term safety of budesonide nasal aerosol: a 5.5-year follow-up study. Clin Allergy 18(3):253–259CrossRefPubMed

42.

Laliberte F, Laliberte MF, Lecart S, Bousquet J, Klossec JM, Mounedji N (2000) Clinical and pathologic methods to assess the long-term safety of nasal corticosteroids. French Triamcinolone Acetonide Study Group. Allergy 55(8):718–722CrossRefPubMed

43.

Baroody FM, Cheng CC, Moylan B, deTineo M, Haney L, Reed KD, Cook CK et al (2001) Absence of nasal mucosal atrophy with fluticasone aqueous nasal spray. Arch Otolaryngol Head Neck Surg 127(2):193–199CrossRefPubMed

44.

Marple B, Roland P, Benninger M (2004) Safety review of benzalkonium chloride used as a preservative in intranasal solutions: an overview of conflicting data and opinions. Otolaryngol Head Neck Surg 130(1):131–141. https://doi.org/10.1016/j.otohns.2003.07.005 CrossRefPubMed

45.

Verret DJ, Marple BF (2005) Effect of topical nasal steroid sprays on nasal mucosa and ciliary function. Curr Opin Otolaryngol Head Neck Surg 13(1):14–18CrossRefPubMed

46.

Antunes MB, Cohen NA (2007) Mucociliary clearance—a critical upper airway host defense mechanism and methods of assessment. Curr Opin Allergy Clin Immunol 7(1):5–10. https://doi.org/10.1097/ACI.0b013e3280114eef CrossRefPubMed

Title: Influence of MP 29-02 on ciliary beat frequency in human epithelial cells in vitro
Authors: D. Häussler
J. U. Sommer
A. Nastev
C. Aderhold
A. Wenzel
B. Kramer
B. A. Stuck
R. Birk
Publication date: 01-06-2018
Publisher: Springer Berlin Heidelberg
Published in: European Archives of Oto-Rhino-Laryngology / Issue 6/2018
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI: https://doi.org/10.1007/s00405-018-4979-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Influence of MP 29-02 on ciliary beat frequency in human epithelial cells in vitro

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2018

Imaging evaluation of electrode placement and effect on electrode discrimination on different cochlear implant electrode arrays

Effect of voice therapy on vocal fold polyp treatment

Extramucosal pyriplasty without stenting for management of pyriform aperture stenosis

Systematic review of tonsil surgery quality registers and introduction of the Nordic Tonsil Surgery Register Collaboration

Cripto-1 is overexpressed in carcinoma ex pleomorphic adenoma of salivary gland

Aerodynamic findings and Voice Handicap Index in Parkinson’s disease