Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported

Kåre Håkansson, Claus Bachert, Lars Konge, Simon Francis Thomsen, Anders Elm Pedersen, Steen Seier Poulsen, Tomas Martin-Bertelsen, Ole Winther, Vibeke Backer, Christian von Buchwald, Kåre Håkansson, Claus Bachert, Lars Konge, Simon Francis Thomsen, Anders Elm Pedersen, Steen Seier Poulsen, Tomas Martin-Bertelsen, Ole Winther, Vibeke Backer, Christian von Buchwald

Abstract

Background: It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma.

Objective: We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii) bronchial inflammation exists in all CRSwNP patients irrespective of clinical asthma status.

Methods: We collected biopsies from nasal polyps, inferior turbinates and bronchi of 27 CRSwNP patients and 6 controls. All participants were evaluated for lower airway disease according to international guidelines. Inflammatory cytokines were investigated using a Th1/Th2 assay including 14 chemokines and cytokines; tissue concentrations were normalized according to tissue weight and total protein concentration. Individual cytokines and multivariate inflammatory profiles were compared between biopsy sites and between patients and controls.

Results: We found significantly higher concentrations of Th2 cytokines in nasal polyps compared to inferior turbinate and bronchial biopsies. In addition, we showed that the inflammatory profile of nasal polyps and bronchial biopsies correlated significantly (p<0.01). From the Th2 cytokines measured, IL-13 was significantly increased in bronchial biopsies from CRSwNP patients with, but not without asthma.

Conclusion: Our findings support the united airways concept; however, we did not find evidence for subclinical bronchial inflammation in CRSwNP patients without asthma. Finally, this study indicates for the first time that nasal polyps potentially play an important role in the airway inflammation rather than being a secondary phenomenon.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Inflammatory cytokines in bronchial biopsies…
Fig 1. Inflammatory cytokines in bronchial biopsies (MCP-4, IL-5, IL-13 and TARC) in CRSwNP patients and controls, stratified by asthma severity.
Log transformed data, concentrations in pg/mL. I = Intermittent; MiP = Mild persistent; MoP = Moderate persistent; SP = Severe persistent. P-values represent comparison by Kruskal-Wallis test. In this analysis we included biopsies from controls with asthma that were not included in the inter-group analyses. This analysis indicates that bronchial inflammation increases with increasing asthma-severity.
Fig 2. Concentration of Th1 and Th2…
Fig 2. Concentration of Th1 and Th2 cytokines in nasal polyps, ITs and bronchial biopsies in CRSwNP patients.
A: Th1 cytokines. B: Th2 cytokines. Log transformed data, concentrations in pg/mL. NP = nasal polyp, BB = bronchial biopsy, IT = inferior turbinate. P-values represent comparison by a paired Wilcoxon signed rank test. Both CRSwNP patients with and without asthma are included in this analysis. All Th2 cytokines were increased in the nasal polyps compared to the bronchii; this difference was not seen for Th1 cytokines.

References

    1. Larsen K. The clinical relationship of nasal polyps to asthma. Allergy Asthma Proc; 17(5):243–9.
    1. Zhang N, Van Zele T, Perez-Novo C, Van Bruaene N., Holtappels G, DeRuyck N, et al. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease. J Allergy Clin Immunol; 122(5):961–8. 10.1016/j.jaci.2008.07.008
    1. Klossek JM, Neukirch F, Pribil C, Jankowski R, Serrano E, Chanal I, et al. Prevalence of nasal polyposis in France: a cross-sectional, case-control study. Allergy; 60(2):233–7.
    1. Granstrom G, Jacobsson E, Jeppsson PH. Influence of allergy, asthma and hypertension on nasal polyposis. Acta Otolaryngol Suppl; 492:22–7.
    1. Bachert C, Zhang N. Chronic rhinosinusitis and asthma: novel understanding of the role of IgE 'above atopy'. J Intern Med; 272(2):133–43. 10.1111/j.1365-2796.2012.02559.x
    1. Ardehali MM, Amali A, Bakhshaee M, Madani Z, Amiri M. The comparison of histopathological characteristics of polyps in asthmatic and nonasthmatic patients. Otolaryngol Head Neck Surg; 140(5):748–51. 10.1016/j.otohns.2009.01.027
    1. Bateman ND, Shahi A, Feeley KM, Woolford TJ. Activated eosinophils in nasal polyps: a comparison of asthmatic and non-asthmatic patients. Clin Otolaryngol; 30(3):221–5.
    1. Dhong HJ, Kim HY, Cho DY. Histopathologic characteristics of chronic sinusitis with bronchial asthma. Acta Otolaryngol; 125(2):169–76.
    1. Haruna S, Nakanishi M, Otori N, Moriyama H. Histopathological features of nasal polyps with asthma association: an immunohistochemical study. Am J Rhinol; 18(3):165–72.
    1. Bachert C, Zhang N, Holtappels G, De Lobel L., van Cauwenberge P., Liu S, et al. Presence of IL-5 protein and IgE antibodies to staphylococcal enterotoxins in nasal polyps is associated with comorbid asthma. J Allergy Clin Immunol; 126(5):962–8, 968. 10.1016/j.jaci.2010.07.007
    1. Tsicopoulos A, Shimbara A, de Nadai P., Aldewachi O, Lamblin C, Lassalle P, et al. Involvement of IL-9 in the bronchial phenotype of patients with nasal polyposis. J Allergy Clin Immunol; 113(3):462–9.
    1. Lamblin C, Bolard F, Gosset P, Tsicopoulos A, Perez T, Darras J, et al. Bronchial interleukin-5 and eotaxin expression in nasal polyposis. Relationship with (a)symptomatic bronchial hyperresponsiveness. Am J Respir Crit Care Med; 163(5):1226–32.
    1. Lamblin C, Gosset P, Salez F, Vandezande LM, Perez T, Darras J, et al. Eosinophilic airway inflammation in nasal polyposis. J Allergy Clin Immunol; 104(1):85–92.
    1. Ragab A, Clement P, Vincken W. Correlation between the cytology of the nasal middle meatus and BAL in chronic rhinosinusitis. Rhinology; 43(1):11–7.
    1. Ediger D, Sin BA, Heper A, Anadolu Y, Misirligil Z. Airway inflammation in nasal polyposis: immunopathological aspects of relation to asthma. Clin Exp Allergy; 35(3):319–26.
    1. Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl; (23):3–298.
    1. Fabbri L, Pauwels RA, Hurd SS. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: GOLD Executive Summary updated 2003. COPD; 1(1):105–41.
    1. Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, FitzGerald M, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J; 31(1):143–78. 10.1183/09031936.00138707
    1. Håkansson K, Thomsen SF, Konge L, Mortensen J, Backer V, von Buchwald C. A comparative and descriptive study of asthma in chronic rhinosinusitis with nasal polyps. American Journal of Rhinology & Allergy; 28(5):383–7.
    1. British Thoracic Society Bronchoscopy Guidelines Committee. British Thoracic Society guidelines on diagnostic flexible bronchoscopy. Thorax; 56 Suppl 1:i1–21.
    1. Good PI. Permutation, Parametric, and Bootstrap Tests of Hypotheses (Springer Series in Statistics) Springer; 2005.
    1. Team R. R Development Core Team 2013. R: A Language and Environment for Statistical Computing.
    1. Togias A. Rhinitis and asthma: evidence for respiratory system integration. J Allergy Clin Immunol; 111(6):1171–83.
    1. Staikuniene J, Vaitkus S, Japertiene LM, Ryskiene S. Association of chronic rhinosinusitis with nasal polyps and asthma: clinical and radiological features, allergy and inflammation markers. Medicina (Kaunas); 44(4):257–65.
    1. Han DH, Kim SW, Cho SH, Kim DY, Lee CH, Kim SS, et al. Predictors of bronchial hyperresponsiveness in chronic rhinosinusitis with nasal polyp. Allergy; 64(1):118–22. 10.1111/j.1398-9995.2008.01841.x
    1. Larsen K, Tos M. A long-term follow-up study of nasal polyp patients after simple polypectomies. Eur Arch Otorhinolaryngol; 254 Suppl 1:S85–S88.
    1. Larsen K, Tos M. Clinical course of patients with primary nasal polyps. Acta Otolaryngol; 114(5):556–9.
    1. Braunstahl GJ, Fokkens W. Nasal involvement in allergic asthma. Allergy; 58(12):1235–43.
    1. Bachert C, Gevaert P, Holtappels G, Cuvelier C, van Cauwenberge P. Nasal polyposis: from cytokines to growth. Am J Rhinol; 14(5):279–90.
    1. Kanai N, Denburg J, Jordana M, Dolovich J. Nasal polyp inflammation. Effect of topical nasal steroid. Am J Respir Crit Care Med; 150(4):1094–100.
    1. Wallwork B, Coman W, Feron F, Mackay-Sim A, Cervin A. Clarithromycin and prednisolone inhibit cytokine production in chronic rhinosinusitis. Laryngoscope; 112(10):1827–30.
    1. Snijdewint FG, Kapsenberg ML, Wauben-Penris PJ, Bos JD. Corticosteroids class-dependently inhibit in vitro Th1- and Th2-type cytokine production. Immunopharmacology; 29(2):93–101.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere