Biomarkers in chronic rhinosinusitis
CRS, like asthma, can be divided into different pheno- and endotypes. The mostly used phenotype is the division into CRS with and without nasal polyps (CRSwNP and CRSsNP), although many other pheno- and endotypes are known.28,128 However, recently, the options to treat with biologicals have put more emphasis on markers of Th2 disease irrespective of the presence of nasal polyps. The first type 2 targeting biologic anti- IL4Rα (Dupilumab) has entered the market for CRSwNP patients and others like, anti-IgE, anti-IL5 and anti-IL5Rα may follow shortly.129-131Cluster analysis of CRS has shown that CRSsNP and CRSwNP are not dichotomous but instead have overlapping inflammatory signatures with type 2 inflammation as the predominant endotype mainly in CRSwNP but also CRSsNP especially in western parts of the world. Interestingly, some patients with CRS express a mixture of two or more inflammatory endotypes.22,132,133 The recently published EPOS2020 proposes a new clinical classification based on the disease being localized (often unilateral) or diffuse (always bilateral). Both these groups can be further divided into Th2 or non-Th2 disease.4
In the very near future, it may be possible to offer personalized medicine for CRS patients where treatment is based on molecular biomarkers for the endotype or sub-endotype activated in an individual patient.27,134 The major challenge is to find reliable biomarkers that define Th2 inflammation and predict reaction to treatment. Ideally, these biomarkers should be supported by a body of evidence clarifying the biological significance, be quantifiable in a cost‐efficient way and be easily measurable, preferably in blood or nasal secretion.14 Potential biomarkers could be eosinophils, neutrophils,135,136IgE,137Th2 cytokines,138 innate (epithelial) cytokines,111,137,139 but also phenotypical phenomena like smell loss,140 asthma and response to systemic corticosteroids.134 Contrary to FeNO in asthma, nasal NO has not been shown to be helpful to identify the T2 endotype because the main source of production of nasal NO are the sinuses that are closed off when CRS occurs.141The main biomarkers used at the moment to define Th2 disease are eosinophils, IgE levels, and in some more specialized centres periostin and/or IL-5. There is quite some evidence showing that tissue and blood eosinophils are a reasonable surrogate marker for Th2 disease, and that blood eosinophils are a reasonable biomarker to predict eosinophilic CRS with or without nasal polyps.133 On the other hand, low tissue and serum eosinophilia, and absence of tissue squamous metaplasia may predict a CRS phenotype suitable for a trial of long-term macrolide therapy when surgery and topical therapy has failed.142Unfortunately, recent large studies with monoclonal antibodies directed to Type 2 endotypes have not found reliable biomarkers to predict response to treatment.129,130,143-145 As in asthma,8 we need large, maybe real-life studies to find better predictors to identify responders to biological treatments. For now, our treatment decisions still heavily rely on phenotypical characteristics like smell loss, asthma, and response to surgery and systemic corticosteroids.4,27