ICON: chronic rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is a public health problem that has a significant socio-economic impact. Moreover, the complexity of this disease due to its heterogeneous nature based on the underlying pathophysiology - leading to different disease variants - further complicates our understanding and directions for the most appropriate targeted treatment strategies. Several International/national guidelines/position papers and/or consensus documents are available that present the current knowledge and treatment strategies for CRS. Yet there are many challenges to the management of CRS especially in the case of the more severe and refractory forms of disease. Therefore, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), a collaboration between EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus (ICON) on Chronic Rhinosinusitis. The purpose of this ICON on CRS is to highlight the key common messages from the existing guidelines, the differences in recommendations as well as the gaps in our current knowledge of CRS, thus providing a concise reference. In this document we discuss the definition of the disease, its relevance, pharmacoeconomics, pathophysiology, phenotypes and endotypes, genetics and risk factors, natural history and co-morbidities as well as clinical manifestations and treatment options in both adults and children comprising pharmacotherapy, surgical interventions and more recent biological approaches. Finally, we have also highlighted the unmet needs that wait to be addressed through future research.

Keywords: Biologicals; Chronic rhinosinusitis; Co-morbidities; Genetics; Pathophysiology; Pharmacoeconomics; Phenotypes; Treatment; Unmet needs.

Figure 1

Prevalence of CRS. The GA2LEN study. Reported prevalence of CRS throughout Europe [9]).

Figure 2

Pathomechanisms of CRS. A. CRSwNP. In a TH2-type microenvironment with general lack of regulatory T (Treg) cell function, IL-5 induces eosinophilia, and IL-4 and IL-13 induce local IgE production. An alternatively activated macrophage subset contributes to the inflammation. The activation of epithelium colonized by bacteria and fungi leads to release of proinflammatory chemokines and cytokines with increased thymic stromal lymphopoietin (TSLP) and IL-32 levels. Activated epithelial cells die, with apoptosis resulting in a compromised epithelial barrier. B. CRSsNP. Instead of a TH2-skewed T-cell response, a TH1 or a mixed TH0 response predominates, neutrophilia is often associated, and expression of TGF-β and its receptors is increased. DC, Dendritic cell. This figure is reused with permission from the Journal of Allergy and Clinical Immunology [198].

Figure 3

"Pheno- and endotype" CRS. Pheno- and endotyping of CRS based on the recently published findings on asthma comorbidity and recurrence after surgery (Ghent classification of CRS).