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Review
. 2020 Apr;124(4):318-325.
doi: 10.1016/j.anai.2020.01.013. Epub 2020 Jan 30.

Use of endotypes, phenotypes, and inflammatory markers to guide treatment decisions in chronic rhinosinusitis

Anna G Staudacher  1 , Anju T Peters  2 , Atsushi Kato  1 , Whitney W Stevens  3
Affiliations
Review

Use of endotypes, phenotypes, and inflammatory markers to guide treatment decisions in chronic rhinosinusitis

Anna G Staudacher et al. Ann Allergy Asthma Immunol. 2020 Apr.

Abstract

Objective: With the advent of new treatment options for Chronic Rhinosinusitis (CRS) comes the ability for physicians to provide more individualized patient care. Physicians are now tasked with identifying who may be the best candidate for a particular therapy. In this review, existing biomarkers and potentially new methods that could guide treatment choices in CRS patients will be discussed.

Data sources: Published literature obtained through PubMed searches.

Study selection: Studies relevant to inflammatory endotypes, phenotypes, and biomarkers in CRS were included.

Results: Currently, there are no clinically validated tools that determine the best therapeutic modality for CRS patients with or without nasal polyps (CRSwNP or CRSsNP). Patients with CRS can be classified into three endotypes based on the presence of type 1, type 2, or type 3 inflammation. CRS endotypes can be influenced by age and geographic location. Clinical application however may be limited since endotyping current requires basic research laboratory support. Clinical symptoms may also predict inflammatory endotypes with smell loss being indicative of type 2 inflammation. Numbers of tissue and/or peripheral eosinophils as well as levels of IgE may predict disease severity in CRSwNP but not necessarily treatment responses. Unique clinical phenotypes or biomarkers are especially lacking that predict type 1 or type 3 inflammation in CRSwNP or type 1, type 2, or type 3 inflammation in CRSsNP.

Conclusion: While significant progress has been made in characterizing endotypes, phenotypes, and biomarkers in CRS, additional studies are needed to determine if and how these factors could assist physicians in providing more individualized clinical care.

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Figures

Figure 1.
Figure 1.. Associations between Inflammatory Endotypes and Clinical Phenotypes in Chronic Rhinosinusitis.
Immune responses can be broadly classified into 3 inflammatory endotypes (type 1, type 2, or type 3) based upon a unique signature profile comprised of specific immune cells, inflammatory mediators, and physiological functions. Several associations between inflammatory endotypes and clinical features in patients with CRS have been identified . For example, smell loss strongly associated with type 2 inflammation in all patients with CRS. In contrast, the presence of purulent nasal discharge was associated with a type 1 endotype in CRSsNP but type 1 and type 3 endotypes in CRSwNP.
Figure 2.
Figure 2.. Geographical Diversity of Inflammatory Endotypes in Chronic Rhinosinusitis.
There is a marked global heterogeneity in inflammatory endotypes among patients with CRSsNP or CRSwNP. In a study from the United States, type 1, type 2, and type 3 endotypes were determined by expression levels of IFNγ, Eosinophil Cationic Protein/Charcot Leiden Crystal, and IL-17A being above the 90% of expression in control ethmoid tissues respectively . In a separate study from Europe, Australia, and China, type 1, type 2, and type 3 endotypes were determined if levels of IFNγ, IL-5, and IL-17A respectively were detected in nasal polyps of patients with CRSwNP and in ethmoid tissue of patients with CRSsNP . Among patients living in the US, Europe, and Australia, the type 2 endotype was the predominant endotype observed in patients with CRSwNP. Type 2 inflammation was also the predominant endotype in patients with CRSsNP living in the US. Meanwhile in China, a larger percentage of patients were characterized by a type 1 inflammatory endotype, especially those patients with CRSsNP living in Beijing.
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