Chronic Rhinosinusitis—An Update on
Epidemiology, Pathogenesis and Management
Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, 400015 Cluj-Napoca, Romania;
Received: 6 July 2020; Accepted: 9 July 2020; Published: 18 July 2020
Chronic rhinosinusitis (CRS) is one of the most common chronic medical conditions worldwide,
aﬀecting all age groups. Its estimated incidence is 12.3% in the USA, 10.9% in Europe and 13% in
]. CRS is also a condition leading to a signiﬁcant decrease in the quality of life of patients [
It has been demonstrated that CRS had a greater eﬀect on social function that ischemic heart disease or
chronic heart failure .
Furthermore, it is documented that CRS is also an economic burden for society. It is estimated
that in the USA, the direct costs associated with CRS are approximately USD 10–13 billion per year [
Moreover, indirect costs of CRS are due to missed workdays, absenteeism and productivity loss, and are
estimated to exceed USD 20 billion per year in the USA .
It is well acknowledged that the Journal of Clinical Medicine (JCM) publishes well-performed
basic research and well-conducted clinical studies. As a result of a demanding peer-review process and
careful selection process, relevant articles to an extensive readership are issued regularly in the journal.
The special issue of JCM, entitled Prevention, Diagnosis and Management of Chronic Rhinosinusitis
exempliﬁes the attempt to deliver high-quality topics relevant for both clinicians and researchers.
Staphylococcus aureus is one of the bacteria commonly found in CRS patients, and S. aureus bioﬁlms
are frequently associated with recalcitrant or recurrent disease [
]. It has been demonstrated that
S. aureus is able to penetrate the barrier of the columnar epithelium of the paranasal sinuses, thus
enhancing the inﬂammatory process [
]. In this issue of JCM, Hu et al. [
] studied the eﬀects
of sub-inhibitory clindamycin and azithromycin on the production of S. aureus exoproteins and the
ensuing eﬀect of decreasing inﬂammation, epithelial barrier disruption and invasion. The study was
performed on primary human nasal epithelial cells (HNECs) from patients undertaking endoscopic
skull base techniques without clinical or radiological evidence of CRS. This study emphasizes that
S. aureus exoproteins induce severe cytotoxicity and interrupt the mucosal barrier, upsetting its function
and decreasing inﬂammation.
The authors demonstrated that sub-inhibitory clindamycin successfully blocked S. aureus
exoprotein production, subsequently preventing toxicity, reversing the damaging eﬀects on the
mucosal barrier architecture and function and modulating its pro-inﬂammatory features. To a lesser
degree, sub-inhibitory azithromycin had comparable eﬀects on these actions. Moreover, the authors
demonstrated that subinhibitory clindamycin or azithromycin was able to considerably decrease the
S. aureus bioﬁlm protein assembly. S. aureus treated with clindamycin—but not azithromycin—no
longer display an invasive ability on HNECs. This study has important clinical consequences, as these
antibiotics might decrease inﬂammation associated with S. aureus bioﬁlm exoproteins.
Understanding the CRS pathophysiology may oﬀer better diagnostic techniques and permit the
development of new treatment strategies. The contribution of nitric oxide (NO) in CRS is discussed in
the current literature [
]. Vlad et al. [
] assessed the arginase (ARG) expression in the mucosa of
CRS patients. Increased ARG concentration can decrease NO levels by lessening the accessibility of its
J. Clin. Med. 2020,9, 2285; doi:10.3390/jcm9072285 www.mdpi.com/journal/jcm
J. Clin. Med. 2020,9, 2285 2 of 5
CRS patients expressed signiﬁcantly higher ARG2 levels as compared to controls. ARG2 levels were
signiﬁcantly increased in CRS without polyps, while in polyposis, ARG2 levels did not reach statistical
signiﬁcance despite showing an increase. CRS without allergy displayed signiﬁcantly increased levels
of ARG2. Compared to controls, ARG2 levels were also signiﬁcantly increased in non-asthmatic CRS
patients and in non-allergic, non-asthmatic CRS patients. In the univariate analysis of CRS patients
using the comparisons of allergic vs. non-allergic, asthmatic vs. non-asthmatic, non-asthmatic allergic
vs. non-asthmatic non-allergic, and non-allergic asthmatic vs. non-allergic-non-asthmatic, ARG2 levels
were statistically higher in non-allergic CRS patients and non-allergic and non-asthmatic patients.
The authors suggest that an improved knowledge of ARG functions in CRS will allow the development
of personalized treatments.
Kim et al. [
] assessed in their study trends in micro-organisms isolated form CRS patients from
Korea, undergoing endoscopic sinus surgery (ESS) in the following periods: 2007–2008, 2011–2012,
and 2017–2018. During this time period, the authors undertook endoscopically guided bacterial
cultures from the sinus. A total of 510 adult patients were retrospectively reviewed. The bacteria
recovery rate was 73.9% for polyposis and 82.8% for CRS without polyps. The analysis demonstrated a
signiﬁcant increase over time in the presence of coagulase negative Staphylococci (CNS), Klebsiella and
Pseudomonas aeruginosa. The authors emphasized the signiﬁcant increasing trend of Gram-negative
bacteria isolation in CRS patients. Moreover, extended-spectrum beta-lactamase (ESBL) Klebsiella and
Enterobacter displayed an increasing trend over time. The authors underline the importance of current
recommendations of endoscopically guided cultures during ESS. Thus, pathogenic bacteria should be
isolated and targeted antibiotics should be prescribed.
Fungal rhinosinusitis is a unique type of CRS with special clinical and pathologic features. In their
paper, Lu et al. [
] explore the contribution of bacterial microbiota in diﬀerent types of CRS. It is well
known that conventional culture techniques provide limited evidence regarding bacterial pathogens.
On the contrary, next-generation sequencing (NGS), a culture-independent technique, provides a
superior illustration of microbiota. The authors undertook 16S rRNA ampliﬁcation sequencing to
discover diﬀerences between fungal and non-fungal CRS and between the middle meatus and the
nasopharynx. The authors enrolled 7 consecutive fungal and 18 consecutive non-fungal CRS patients
in the study. Extracted DNA was analyzed through 16S rRNA ampliﬁcation. The authors demonstrate
that bacterial community diversity was signiﬁcantly lower in the middle meatus of fungal CRS.
Nevertheless, no signiﬁcant diﬀerences were observed between the diversity samples collected from
the nasopharynx. Corynebacterium and Fusobacterium were detected in only non-fungal CRS patients.
On the contrary, Haemophilus and Pseudomonas were both highly prevalent and abundant in fungal
CRS. This feature could be associated with bacterial–fungal interaction. The study emphasized that
bacterial dysbiosis is more common in fungal CRS and limited to the middle meatus.
This Special Issue of JCM includes two papers on disease-speciﬁc form of CRS. The study of
Chang et al. [
] examined the occurrence of CRS among patients with Sjögren’s syndrome (SS). A huge
database was analyzed: 18,723 SS patients diagnosed between 1997 and 2011 were retrospectively
reviewed. A control group of 59,568 patients without SS were matched at the 1:4 ratio to SS patients.
Patients were matched by gender, age, income, urban and comorbidities. Comorbidities retrieved
included: rhinitis, septal deviation, gastroesophageal reﬂux disease (GERD) chronic obstructive
pulmonary disease (COPD), asthma, diabetes mellitus (DM), and hypertension (HT). The main
outcome was CRS occurrence. The authors demonstrated that the cumulative incidence of CRS
was statistically increased in the SS group as compared to controls. The Cox proportional model
demonstrated that patients with SS have a signiﬁcant increased CRS incidence (adjusted HR, 2.51;
95% CI, 2.22–2.84; p<0.001). Subgroup analyses of GERD, COPD, asthma, DM, HT, and RA showed
that SS is an independent risk factor in the occurrence of CRS. The percentage of patients undergoing
surgery in the SS group was signiﬁcantly lower. Further research is undeniably needed to highlight
the features of CRS among SS patients.
J. Clin. Med. 2020,9, 2285 3 of 5
The naso-sinusal disease of 64 adult patients with primary ciliary dyskinesia (PCD) is deeply
analyzed in the study of Bequignon et al. [
] Among patients included, hearing loss and rhinorrhea
were most commonly encountered. Symptom burden was increased in older patients. Abnormal nasal
endoscopy was recorded in every case: polyps were present in 33% of patients and sticky, thick, immobile
mucus in 87.5% of cases. On the CT scan, sinuses displayed partial opacities, and hypoplasia/agenesis
was present in one third of patients. Culture-guided cultures grew Haemophilus inﬂuenzae,Streptococcus
pneumoniae and Pseudomonas aeruginosa. Otitis media with eﬀusion (OME) was frequently encountered
during childhood, but less common in adults. Half of the patients presented sensorineural hearing loss.
Ciliary function and ultrastructure were not associated with disease seriousness in the otolaryngology
ﬁeld. The OME occurrence was statistically associated with a forced expiratory volume (FEV1) <70%.
Thus, the existence of OME in adults with PCD could be a marker of severe lung disease.
In the same issue of JCM, Bequignon et al. [
] published another interesting study on the
management of CRS in adult patients with PCD. A retrospective review of 41 adult patients with PCD
is presented. On the CT scan, partial opacities were described, mainly positioned in the ethmoids and
maxillary sinuses. Positive bacteriological cultures were obtained in 83.9% of patients with purulent
mucus. Positive cultures for Pseudomonas aeruginosa were not signiﬁcantly diﬀerent between patients
bellow and above 40 years. Surgery was employed in only 19% of patients to improve sinus drainage.
The authors emphasize that in PCD patients, sinuses should be considered a bacterial pool. The paper
suggests that bacteriology and sinus symptoms rather than CT scans should guide medical and surgical
management in this group of patients.
Practical approaches to common problems are also discussed in this issue of JCM. Inverted
papilloma (IP) of the maxillary sinus is still considered a challenge for the endoscopic surgeon. In a
beautifully illustrated paper, Hildebrand et al. [
] retrospectively review 17 patients with primary
or recurrent IP of the maxillary sinus. The prelacrimal endoscopic approach has been used in all
patients. No recurrences were described after a median follow-up of 3.8 years. The surgical technique
is extensively described and relevant literature on the outcomes of IP surgery is presented to the reader.
Wound healing following ESS remains a signiﬁcant element for the particular patient. Prolonged
inﬂammation, scarring and synechiae can adversely inﬂuence the postoperative outcome. This is
the reason why researchers are strongly interested in the generation of materials that may improve
postoperative wound healing. Manciula et al. [
] examined in an experimental study the eﬀects
of astaxanthin—a powerful antioxidant—on nasal mucosa healing following surgery. The temporal
evolution of wound healing was assessed through several parameters evaluating epithelial thickness,
subepithelial thickness, goblet cells, and subepithelial ﬁbrosis. The authors clearly demonstrate
that astaxanthin given in the postoperative period signiﬁcantly decreases ﬁbrosis and prevents
Wound healing is clinically assessed in a clinical study by Trombitas et al. [
] Middle meatus
antrostomy (MMA) stenosis is still reported as an unfavorable outcome in patients undergoing surgery.
The authors present a prospective within-subject, randomized, controlled trial assessing the eﬀect of
spray cryotherapy on wound healing. Included were 26 patients with bilateral CRS without polyps.
The outcomes were represented by MMA diameter and area, histology, and symptoms. The MMA
diameter and area were signiﬁcantly increased in the cryotherapy group. Nasal obstruction and
discharge were signiﬁcantly improved following cryotherapy. Moreover, cryotherapy signiﬁcantly
decreases inﬂammation, edema and goblet cell hyperplasia.
As demonstrated by the diversity of papers selected in this Special Issue of JCM, there is something
interesting for all readers of the journal. Clinicians interested in rhinology, endoscopic surgeons,
basic science researchers, public health providers, and internal medicine physicians will ﬁnd something
of interest in this issue. The cautious selection of such articles speaks for the ongoing success of JCM as
a leading reference among open access publications.
J. Clin. Med. 2020,9, 2285 4 of 5
Funding: This research received no external funding.
Conﬂicts of Interest: The authors declare no conﬂict of interest.
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