Reviews and feature articleEndotypes 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
Section snippets
Pathophysiology of CRS
The pathophysiology of CRS is complex and includes local, systemic, microbial, environmental, genetic, and iatrogenic factors (Fig 1).
Diagnosis of rhinosinusitis
CRS endotypes depend on definition of pathophysiologic mechanisms; however, phenotypes are recognized by clinical findings. Internationally, there is consensus concerning the clinical diagnosis of rhinosinusitis.1, 75, 76 Rhinosinusitis represents a symptomatic inflammation of the paranasal sinuses involving the sinonasal tract. The diagnosis of CRS is based on the presence of at least 2 sinonasal symptoms and should be supported by objective clinical or radiologic evidence of sinonasal
Contributing factors, differential diagnosis, and comorbidities of patients with CRS
There are a variety of contributing factors and comorbid conditions that should be considered when diagnosing and managing CRS or defining endotypes. The symptoms of rhinosinusitis can be aggravated by anatomic deformities, such as nasal septal deviations, nasal valve dysfunction, concha bullosa (enlarged nasal turbinate caused by internal ethmoid air cell), adenoid hyperplasia, nasal choanal narrowing, nasal or sinus mucoceles, scarring from prior nasal or sinus surgery, and septal
Treatment of CRS
Treatment of CRS is straightforward in most cases of acute exacerbations, but a significant group of subjects have persistent or recurrent disease. This challenge is most probably due to multiple phenotypes and endotypes with different underlying mechanisms that lead to chronicity and severity. The number of different treatment options and modalities in the literature is large, but there are limited treatment options with evidence of benefit. Apart from nasal irrigation/douching, nasal and oral
Phenotypes and endotypes of CRS
CRS is a heterogeneous collection of diseases.82, 85 In clinics CRS can be phenotyped according to duration (acute vs chronic), NPs (with and without), recurrent disease, severity (mild vs moderate vs severe), conventional therapy response, mucus color, presence of peripheral specific IgE, nature of triggering events, and presence of a complication (Fig 2). However, extensive scientific evidence is accumulating that justifies a differentiation of sinus disease not only by phenotype (ie, defined
Conclusion
In this report we propose that one of the major obstacles to understanding the causes of CRS and improving treatment is the failure to understand the underlying disease mechanisms in patients with different underlying pathophysiologies (Box 2). It will be necessary to classify patients into endotypes according to the underlying disease mechanism to improve our understanding of CRS. We propose that the classification of patients with CRS according to endotype will facilitate the development of
References (111)
- et al.
Rhinosinusitis: establishing definitions for clinical research and patient care
J Allergy Clin Immunol
(2004) - et al.
The diagnosis and management of sinusitis: a practice parameter update
J Allergy Clin Immunol
(2005) Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease
Lancet
(2008)- et al.
Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome
J Allergy Clin Immunol
(2011) - et al.
Unmet needs in severe chronic upper airway disease (SCUAD)
J Allergy Clin Immunol
(2009) - et al.
Adult chronic rhinosinusitis: definitions, diagnosis, epidemiology, and pathophysiology
Otolaryngol Head Neck Surg
(2003) - et al.
Fungus and chronic rhinosinusitis: weighing the evidence
Otolaryngol Head Neck Surg
(2010) - et al.
Staphylococcus aureus enterotoxin B, protein A, and lipoteichoic acid stimulations in nasal polyps
J Allergy Clin Immunol
(2008) - et al.
Specific IgE against Staphylococcus aureus enterotoxins: an independent risk factor for asthma
J Allergy Clin Immunol
(2012) - et al.
Reduced expression of antimicrobial palate, lung and nasal epithelial clone (PLUNC) protein in polyps from patients with chronic rhinosinusitis is due to decreased number of glands [abstract]
J Allergy Clin Immunol
(2011)
Evidence for diminished levels of epithelial psoriasin and calprotectin in chronic rhinosinusitis
J Allergy Clin Immunol
Alterations in epithelial barrier function and host defense responses in chronic rhinosinusitis
J Allergy Clin Immunol
Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps
J Allergy Clin Immunol
The broad spectrum of interepithelial junctions in skin and lung
J Allergy Clin Immunol
Defective epithelial barrier in chronic rhinosinusitis: The regulation of tight junctions by IFN-gamma and IL-4
J Allergy Clin Immunol
T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma
J Allergy Clin Immunol
Allergy and hypersensitivity: mechanisms of allergic disease
Curr Opin Immunol
Localization of immunoglobulins in human nasal mucosa
Immunochemistry
Total and specific IgE in nasal polyps is related to local eosinophilic inflammation
J Allergy Clin Immunol
Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma
J Allergy Clin Immunol
Evidence for intranasal antinuclear autoantibodies in patients with chronic rhinosinusitis with nasal polyps
J Allergy Clin Immunol
Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease
J Allergy Clin Immunol
Pathogenesis of chronic rhinosinusitis: inflammation
J Allergy Clin Immunol
T(H)17 and T(H)22 cells: A confusion of antimicrobial response with tissue inflammation versus protection
J Allergy Clin Immunol
TGF-β signaling and collagen deposition in chronic rhinosinusitis
J Allergy Clin Immunol
Expression of TGF, matrix metalloproteinases, and tissue inhibitors in Chinese chronic rhinosinusitis
J Allergy Clin Immunol
Inhibition of angiogenesis by IL-32: possible role in asthma
J Allergy Clin Immunol
Clinical practice guideline: adult sinusitis
Otolaryngol Head Neck Surg
Allergic rhinitis
Lancet
Rhinosinusitis diagnosis and management for the clinician: a synopsis of recent consensus guidelines
Mayo Clin Proc
Topical steroids in chronic rhinosinusitis without polyps: a systematic review and meta-analysis
Otolaryngol Head Neck Surg
Treatment of nasal polyposis and chronic rhinosinusitis with fluticasone propionate nasal drops reduces need for sinus surgery
J Allergy Clin Immunol
Efficacy and tolerability of systemic methylprednisolone in children and adolescents with chronic rhinosinusitis: a double-blind, placebo-controlled randomized trial
J Allergy Clin Immunol
European position paper on rhinosinusitis and nasal polyps 2012
Rhinol Suppl
Chronic rhinosinusitis in Europe—an underestimated disease. A GA(2)LEN study
Allergy
Reliability of EP3OS symptom criteria and nasal endoscopy in the assessment of chronic rhinosinusitis—a GA(2) LEN study
Allergy
Untangling asthma phenotypes and endotypes
Allergy
Therapies for allergic inflammation: refining strategies to induce tolerance
Nat Med
Disordered microbial communities in asthmatic airways
PLoS One
The role of bacterial biofilms and the pathophysiology of chronic rhinosinusitis
Curr Allergy Asthma Rep
Biofilms in chronic rhinosinusitis
Curr Opin Otolaryngol Head Neck Surg
Biofilms in chronic rhinosinusitis: systematic review and suggestions for future research
J Laryngol Otol
The role of ubiquitous airborne fungi in chronic rhinosinusitis
Clin Allergy Immunol
Perspectives on the etiology of chronic rhinosinusitis: an immune barrier hypothesis
Am J Rhinol
Characterization of bacterial community diversity in chronic rhinosinusitis infections using novel culture-independent techniques
Am J Rhinol Allergy
The association between bacterial colonization and inflammatory pattern in Chinese chronic rhinosinusitis patients with nasal polyps
Allergy
Detection of Staphylococcus aureus in nasal tissue with peptide nucleic acid-fluorescence in situ hybridization
Am J Rhinol Allergy
Atopic dermatitis: a disease of altered skin barrier and immune dysregulation
Immunol Rev
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
Local immunoglobulin production in nasal polyposis is modulated by superantigens
Clin Exp Allergy
Cited by (472)
Current and Novel Biologic Therapies for Patients with Asthma and Nasal Polyps
2024, Otolaryngologic Clinics of North AmericaExploring the impact of inflammatory endotypes on olfactory function and quality of life in chronic rhinosinusitis patients
2024, Brazilian Journal of OtorhinolaryngologyAberrant follicular regulatory T cells associate with immunoglobulin hyperproduction in nasal polyps with ectopic lymphoid tissues
2024, Journal of Allergy and Clinical ImmunologyManagement of nasal polyposis in adults : A paradigm shift
2023, Revue Francaise d'AllergologieInhibition of IL-4/STAT6/IRF4 signaling reduces the epithelial-mesenchymal transition in eosinophilic chronic rhinosinusitis with nasal polyps
2023, International ImmunopharmacologyEvidence that oncostatin M synergizes with IL-4 signaling to induce TSLP expression in chronic rhinosinusitis with nasal polyps
2023, Journal of Allergy and Clinical Immunology
Disclosure of potential conflict of interest: C. A. Akdis receives research support from Novartis, PREDICTA, the Swiss National Science Foundation, MeDALL, the Global Allergy and Asthma European Network, and the Christine Kühne-Center for Allergy Research and Education; has consulted for Actellion, Aventis, Stallergenes, and Allergopharma; is president of the European Academy of Allergy and Clinical Immunology; is a fellow and interest group member of the American Academy of Allergy, Asthma & Immunology (AAAAI); is a former committee member of the Global Allergy and Asthma European Network; and is the director of the Christine Kühne-Center for Allergy Research and Education. C. Bachert has received research support from Novartis and GlaxoSmithKline. M. S. Dykewicz has consultant arrangements with Boehringer Ingelheim, Ista, and Merck. R. M. Naclerio has received travel support from AAAAI; has board memberships with Merck, TEVA, and Sunovion; has received grants from TEVA, Johnson & Johnson, and Kalypsis; and has received payment for lectures from TEVA and Sunovion. R. P. Schleimer has consultant arrangements with Intersect ENT, GlaxoSmithKline, Allakos, and Aurasense; has received research support from the National Institutes of Health; and has received stock/stock options from Allakos. D. Ledford has received travel support from AAAAI; has consultant arrangements with Genentech; and has received payment for lectures from Meda and Genentech. The rest of the authors declare that they have no relevant conflicts of interest.