Endotypes of Chronic Rhinosinusitis with Nasal Polyps: Pathology and Possible Therapeutic Implications

Bachert, Claus; Marple, Brad; Hosemann, Werner; Cavaliere, Carlo; Wen, Wang; Zhang, Nan

doi:10.1016/j.jaip.2020.03.007

Cited by 71 publications

(75 citation statements)

References 42 publications

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“…Blood eosinophils in this sample are relatively high (491.55±327) and 35% had >500/µL eosinophils, which means that most had a T2 phenotype [7] as previously observed.…”

supporting

confidence: 83%

Where Has All the Nasal Polyposis Gone?

Ortega-Martín¹,

Betancor²,

Barroso³

et al. 2021

J Investig Allergol Clin Immunol

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“…Blood eosinophils in this sample are relatively high (491.55±327) and 35% had >500/µL eosinophils, which means that most had a T2 phenotype [7] as previously observed.…”

supporting

confidence: 83%

Where Has All the Nasal Polyposis Gone?

Ortega-Martín¹,

Betancor²,

Barroso³

et al. 2021

J Investig Allergol Clin Immunol

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“…In addition, patients with type 2 CRSwNP and existing asthma at the time of surgery and those with newly developing asthma within the next decade after surgery both have an increased risk of disease recurrence after surgery 172 . By contrast, patients with type 1 or type 3 CRS do not have a higher prevalence of asthma than the general population 173 . In Europe and the USA, ~80% of patients with CRSwNP have a type 2 immune reaction and, interestingly, 50% of European patients with CRSsNP have increased type 2 biomarkers in sinus tissue, although the increase is modest compared with patients with CRSwNP and has limited clinical consequences 174 .…”

Section: Endotypingmentioning

confidence: 85%

“…Several clinical signs and biomarkers indicative of type 2 disease have been identified in patients with CRSwNP, of which comorbid late-onset asthma, tissue eosinophilia in the surgical specimen, blood eosinophils >300 cells per microliter, total serum IgE >150 kU/l and the presence of SE-IgE are considered strong indicators 173 . Of these, a combination of asthma comorbidity and blood eosinophil counts of >300 per microliter has a 95% specificity and 86% sensitivity for type 2 CRSwNP.…”

Section: Endotypingmentioning

confidence: 99%

Adult chronic rhinosinusitis

Bachert

Marple

Schlosser

et al. 2020

Nat Rev Dis Primers

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176

175

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Chronic rhinosinusitis (CRS), that is, inflammation of the mucosa of the nose and paranasal sinuses for at least 12 weeks, occurs in >10% of adults in Europe and the USA and poses a substantial global health and economic burden. Common symptoms include facial pain or pressure, nasal discharge, congestion, and hyposmia or anosmia (Fig. 1). Patients with CRS may also have other inflammatory airway conditions such as asthma and allergic rhinitis. CRS can be differentiated into disease without nasal polyps (CRSsNP) and disease with nasal polyps (CRSwNP) based on nasal endoscopic findings. Both CRSsNP and CRSwNP have distinct symptoms, CT findings, treatments, and risks of recurrence and comorbid asthma 1. In addition, both phenotypes are characterized by structural remodelling (with collagen and fibrin deposition) and inflammation, and have combinations of type 1, 3 and/or type 2 inflammatory signatures that vary between diseases (Table 1). The inflammatory signatures determine the CRS endotype, which affects disease severity, comorbidity, prognosis and response to treatment 2. Our understanding the pathophysiology of CRS has evolved from impaired ventilation and drainage of the sinus cavities to a mucosal concept, which focuses on the immunology of the sinus mucosa and its deviation. Indeed, non-type 2 CRSsNP and type 2 CRSwNP are the two ends of a spectrum of disease that require different pharmacological and, eventually, biologic treatments in addition to different surgical approaches from mucosa-sparing functional surgery to mucosa-removing reboot surgery. With the advent of monoclonal antibodies targeting type 2 key immune regulators and effectors, CRS, in particular uncontrolled severe CRSwNP, will likely turn into a disease often controlled by biologics, which can be combined with tailored surgery if necessary. The mucosal concept based on endotyping may allow a precision treatment approach for all patient groups with CRS. This Primer provides a classical overview on CRS, covering state-of-the art clinical topics ranging from epidemiology to prevention and from diagnosis to pharma cological and surgical management of the disease. Of note, this Primer also discusses the role of immunology of the sinus mucosa and the interaction with offenders, such as Staphylococcus aureus, that leads to severe CRSwNP. In addition, the therapeutic principles targeting immune reactions in CRSwNP are discussed. Epidemiology CRS was thought to be one of most common diseases, imparting a substantial burden on individuals and society; however, the global epidemiology has only recently been understood. Objective diagnostic tools, such as nasal endoscopy or sinus CT, are recommended to confirm the diagnosis of CRS in clinical settings but are difficult to apply in large-scale population studies. Furthermore, symptom-based diagnosis may not be highly precise, as ~40% of patients with a symptom-based diagnosis show no endoscopic or radiologic evidence for the disease 3. However, the introduction Hyposmia Reduced ability to smell. Anosmi...

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“…Other type 2 signs are the presence of comorbid late-onset asthma, the diagnosis of AERD, histopathologic findings of eosinophils in former surgery specimen, and finally elevated blood eosinophil counts and increased polyclonal serum IgE concentrations. 44 Current treatment approaches have been extensively described in national and international guidelines. Within the patients with type 2 CRSwNP, there is a group of about 25% to 30% of subjects who will relapse after oral GCSs or conventional sinus surgery, and often need several surgeries in lifetime; more than 60% of these patients also have late-onset asthma.…”

Section: Type 2 Inflammation In Crswnpmentioning

confidence: 99%

Biologics for chronic rhinosinusitis with nasal polyps

Bachert

Zhang

Cavaliere

et al. 2020

Journal of Allergy and Clinical Immunology

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124

113

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With the increasing recognition of the role of type 2 immune responses in chronic rhinosinusitis, its severity, recurrence, and comorbidities, several biologics targeting IL-4, IL-5, and IL-13 as well as IgE have been administered in small proof-of-concept studies. Recently, the first phase 3 trials have been reported with dupilumab, an IL-4 receptor antagonist, demonstrating a significant and clinically relevant reduction of the disease burden from polyp size and sinus involvement to symptoms and smell; these changes consecutively led to an important increase in quality of life. Finally, the biologic versus placebo treatment reduced the need for systemic glucocorticosteroids and sinus surgery significantly and clinically meaningfully. Dupilumab today is registered for the treatment of chronic rhinosinusitis with nasal polyps in Europe and the United States. Within a year, 2 further phase 3 trials with omalizumab and mepolizumab will be reported. With this development, without any doubt, a new era for the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps has begun. Questions on the indication of the biologics, the selection of patients, and finally criteria for monitoring the efficacy in individual patients need to be urgently answered, and care pathways need to be established integrating the current standard of care including surgery.

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Endotypes of Chronic Rhinosinusitis with Nasal Polyps: Pathology and Possible Therapeutic Implications

Cited by 71 publications

References 42 publications

Where Has All the Nasal Polyposis Gone?

Where Has All the Nasal Polyposis Gone?

Adult chronic rhinosinusitis

Biologics for chronic rhinosinusitis with nasal polyps

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