Chronic rhinosinusitis (CRS) is an inflammation of the nose and paranasal sinuses and is
characterized by two or more symptoms, one of which should be either nasal
blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip),
lasting for 12 weeks or longer. In addition, facial pain or pressure and a reduction in
the sense of smell can occur. The condition can occur with or without nasal polyps.
Chronic rhinosinusitis (CRS) is a significant health problem and affects 5-12% of the
general population.
The physiopathology of CRS is poorly understood with multiple environmental, host and
microbial factors being implicated. Putative pathological factors include changes in the
microbiota, imbalance of the local or systemic immune system, allergens, toxins and
genetic predisposition.
A dysbiosis mechanism has been proposed as modulating inflammation in diseased sinuses.
This hypothesis suggests that externally influenced changes in the nasal microbiome can
result in dysbiosis, i.e. a shift from a "normal" or "healthy" microbial community
structure and that this shift may be responsible for the initiation or maintenance of
CRS. For example, the disruption of the commensal biofilm during a viral upper
respiratory tract infection can create a niche for pathogenic species to grow. Despite
many contradictory statements in the different studies some common trends emerge. Less
diversity in the microbial community rather than an increased overall bacterial load
seems to characterize CRS compared to the healthy state with no consensus about specific
genera indicative of disease. However, anaerobes and S. aureus are found to be
significantly more prevalent and abundant in CRS versus healthy controls. Bacterial
biofilm is detected on the sinus mucosa in up to 80% of CRS patients and its presence
does not imply that it is causing mucosal inflammation. However, in the context of CRS,
there are several possible mechanisms by which biofilms may be pro-inflammatory including
the release of planktonic organisms and the release of superantigens, which can cause
ciliary dysfunction and inhibition of ciliary clearance. Bacterial biofilms are likely a
key modulator of the refractory nature of CRS.
Although clinical evidence from well-designed trials is scarce, European Guidelines for
chronic rhinosinusitis recommend daily nasal saline irrigation for reduction of the
severity of symptoms of CRS. A recent Cochrane analysis has concluded that daily nasal
irrigation with hypertonic saline solution is more effective than placebo to improve
patient symptoms. The exact mechanisms by which nasal irrigation works are not known.
However, most of the experts agree that it is primarily a mechanical intervention leading
to direct cleansing of the nasal mucosa. Nevertheless, the efficacy of such solution
remains moderate.
Healsea® Chronic is a CE marked medical device indicated in adults for the treatment of
nasal symptoms of chronic rhinosinusitis. This is a seawater-based nasal spray
supplemented with a natural Symbiofilm® extract (0.02%) isolated from marine bacteria.
The nasal solution is hypertonic (NaCl 2.2%). Symbiofilm® is a marine postbiotic
comprising active exopolysaccharides with emulsifying properties and in vitro antibiofilm
activity. Antibiofilm properties have been demonstrated with the colorimetric microtiter
plate assay. In this model, a significant inhibition of biofilm formation by
Staphylococcus aureus and Haemophilus influenzae are observed. Detachment properties from
human nasal epithelial cells of Staphylococcus aureus and Pseudomonas aeruginosa has also
been demonstrated in vitro, suggesting an inhibition of biofilm formation at early stage
in this model. Symbiofilm® has no bacteriostatic nor bactericidal activities.
To date, properly designed studies to evaluate the effect of topical therapies on
microbiome are scarce so no definite conclusion can be made. In one study, use of saline
irrigation with or without budesonideDCI used was not associated with significantly
distinct microbiota composition among either controls or post-operative CRS patients with
polyp.
This exploratory study is designed with aim to determine if the antibiofilm properties of
Symbiofilm® may modify sino-nasal microbiota, impacting α and/ or β diversities. To this
end middle meatus swab specimen will be taken from CRS patients before and after
treatment with Healsea® Chronic. Bacteria colonization will be assessed using
quantitative PCR and 16S rRNA gene sequencing.
Improvement of nasal symptoms and quality of life will be assessed with the Sino-Nasal
Outcome Test score-22 (SNOT-22). Post-market vigilance of Healsea® Chronic and vigilance
of study procedures will be assessed throughout the study.
