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