9.4. Chronic rhinosinusitis with or without NP
In chronic rhinosinusitis we need:
To consider if the prevalence of and predisposing factors
for CRSsNP and CRSwNP differs in low, middle and high income
To determine the relative frequency and prognostic
significance of different symptoms and signs in CRSsNP and
CRSwNP in Primary Care.
To refine severity staging and its impact on QoL, using both
subjective and objective measures
For endotyping and phenotyping, to define the minimal
criteria for measuring sinus inflammation. eg sampling
procedures and expression of data should be unified (ng of
cytokine per ml, mg of tissue or protein content) so that a
meta-analysis may be done.
To refine the inclusion criteria of non-ENT control groups.
To consider response to standard treatments for endotyping.
- A long-term study on the natural history of osteitis.
A randomised trial comparing different treatment options for
patients with CRS with significant osteitis.
A trial to show if the purulence of nasal discharge is truly
an indicator of bacterial infection and can be used as a
clinically important response to antibiotics in CRS?
To establish what, if any, childhood events increase chances
of developing CRSwNP.
To establish how smoking increases the risk of CRS and
whether the risk is reduced by smoking cessation.
To show if recognition of and appropriate treatment of
allergic rhinitis reduce the incidence of CRSsNP and CRSwNP?
To investigate the impact of psychological problems such as
depression, stress exposure and anxiety on subjective
severity scores and to consider the impact of neurological
co-morbidities like chronic fatigue, post-traumatic stress
disorder, neurological hyposmia, and measures of other
neural-based disorders that play a role in non-allergic
rhinitis, which may have an impact on rhinosinusitis scores.
To consider neural aspects of facial pain, headache, smell
disorders and hypersecretion.
- To consider the role of gastro-oesophageal reflux.
With respect to inflammatory mechanisms in CRSwNP and CRSsNP, we
should consider if it is possible to:
Develop a classification of CRS of phenotypes/endotypes
based on "hypothesis-free" cluster analyses.
Understand the regulation of TGF-ß and related molecules in
Understand the T regulatory cell deficit and the role of T
effector cells in nasal polyp disease.
- Understand the role of dendritic cells in CRS.
Understand the links between inflammation and remodeling.
Understand the impact of the microbiome on inflammation
Understand epigenetic regulation of upper airway disease.
Understand the pathogenesis of 'allergic' fungal
rhinosinusitis and AERD.
Understand the link between CRSwNP and lower airway disease.
Nasal epithelial remodelling is a part of this natural defence
mechanism, including migration, proliferation, and
differentiation of epithelial cells, as well as the interactions
between epithelial cells and stromal cells. To date, it is not
possible to distinguish between a cause and an effect with
regard to epithelium remodelling, nor are there clear roles for
the many factors involved in nasal infectious and inflammatory
diseases, due to a lack of intrinsic information about nasal
epithelial cell responses. Most reported data are derived from
lower airway studies or animal models. Therefore, research based
on human nasal epithelial stem/progenitor cells can offer new
light on pathophysiology of nasal airway disease from a
different, more specific perspective. It will also allow
molecular studies of human nasal epithelial cell interactions,
differentiation, and repair, as well as responses to both
environmental agents and to potential anti-inflammatory
Further research is needed on the impact of bacterial,
fungal or other microbial colonization/infection, with clear
definition of such impact and we need some standardized
methodology for research. For example should measures of
minimal undetectable colonization, like PCR, or molecular
cultivating techniques or hardly detectable immune response
to colonizer be taken into account and if so, when?
If infection is characterized by invasion, as well as by
immune response to the micro-organism, we need to define how
this invasion is established at both a local and systemic
Nearly all of the currently conducted human research is
performed in patients who already have established disease
or controls who do not. While this is useful in identifying
unique contributors to the pathophysiology of CRS and
subsequent treatments, it does not identify the actual cause
of the disease. Currently available animal models are either
allergic models or genetically manipulated animals that
artificially generate an inflammatory response and again, do
not answer the cause of the disease. There is thus a need
for innovative experimental models in CRS.
We should also focus on the differences between CRSwNP in
western patients and elsewhere in the world. We need to
identify key cytokines which mediate Th2 skewing across the
epithelial barrier: TSLP vs. IL-25 vs. IL-33 vs.? The second
key issue is the identity of the key effector cell(s): mast
cells vs. esoinophils vs. neutrophils vs. ?
There are variations in local anatomic immune response that
are not related to airflow and environmental exposures.
Research is needed into variations in immune response of the
ethmoid/middle meatus for example, as this is different from
the mucosal response of the septum or inferior turbinate.
In the assessment of rhinosinusitis symptoms and examination
in chronic rhinosinusitis, we need better tools for the
diagnosis and differential diagnosis of facial pain.
We need to understand the environmental factors that alter
gene expression which may predispose to CRS. This may allow
us to begin recognizing disease-causing agents versus
disease-modifiers or exacerbating agents and in turn may
allow us to alter behavior or implement therapies that can
counteract any genetic predispositions and reverse/ moderate