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Chronic Rhinosinusitis—An Update on Epidemiology, Pathogenesis and Management

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Chronic Rhinosinusitis—An Update on Epidemiology, Pathogenesis and Management

Abstract

Chronic rhinosinusitis (CRS) is one of the most common chronic medical conditions worldwide, affecting all age groups. [...]
Journal of
Clinical Medicine
Editorial
Chronic Rhinosinusitis—An Update on
Epidemiology, Pathogenesis and Management
Silviu Albu
Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, 400015 Cluj-Napoca, Romania;
silviualbu63@gmail.com
Received: 6 July 2020; Accepted: 9 July 2020; Published: 18 July 2020
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Chronic rhinosinusitis (CRS) is one of the most common chronic medical conditions worldwide,
aecting all age groups. Its estimated incidence is 12.3% in the USA, 10.9% in Europe and 13% in
China [
1
3
]. CRS is also a condition leading to a significant decrease in the quality of life of patients [
4
].
It has been demonstrated that CRS had a greater eect on social function that ischemic heart disease or
chronic heart failure [5].
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 [
6
].
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 [7].
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 [
8
]. 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 [
9
,
10
]. In this issue of JCM, Hu et al. [
11
] studied the eects
of sub-inhibitory clindamycin and azithromycin on the production of S. aureus exoproteins and the
ensuing eect 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 eects on the
mucosal barrier architecture and function and modulating its pro-inflammatory features. To a lesser
degree, sub-inhibitory azithromycin had comparable eects 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 oer 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 [
12
14
]. Vlad et al. [
15
] assessed the arginase (ARG) expression in the mucosa of
CRS patients. Increased ARG concentration can decrease NO levels by lessening the accessibility of its
precursor, L-arginine.
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. [
16
] 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. [
17
] explore the contribution of bacterial microbiota in dierent 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 dierences 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 dierences 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. [
18
] 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. [
19
] 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 eusion (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. [
20
] 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 dierent 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. [
21
] 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. [
22
] examined in an experimental study the eects
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
synechia development.
Wound healing is clinically assessed in a clinical study by Trombitas et al. [
23
] 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 eect 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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2020 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
... y Fusobacterium sp.). 51,54,55 En un modelo de infección con H. influenzae se ha encontrado que la administración de AT-RvD1 regula el transporte de leucocitos al pulmón, incrementando la fagocitosis de neutrófilos por macrófagos y reduciendo los niveles de la interleucina 6 (IL-6) y TNF-α. 56 Por otra parte, la permeabilidad del epitelio alveolar puede desencadenar una respuesta inflamatoria por la entrada de diferentes agentes exógenos y endógenos que pueden estimular de forma persistente al organismo, lo que implica un reto para el mantenimiento de la homeostasis y la resolución de la inflamación. ...
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INTRODUCTION : Topical steroids are a mainstay in the treatment of chronic rhinosinusitis (CRS). Multiple delivery methods of topical steroids following sinus surgery have been investigated. The purpose of this trial is to evaluate the effect of triamcinolone impregnated absorbable nasal packing on healing following endoscopic sinus surgery. Methods : This is a prospective, randomized, double-blind, placebo-controlled trial. A total of 22 subjects (14 without polyps and 8 with polyps) were enrolled and were randomized to receive triamcinolone impregnated packing in one sinus cavity and normal saline soaked packing in the contralateral sinus cavity. Endoscopic evaluation was completed at the first two post-operative visits, and Lund-Kennedy (LK) endoscopic scores and perioperative sinus endoscopy (POSE) scores were calculated at each visit. Results : The results of this study found no significant difference in the appearance of the sinuses at either post-operative visit. Mean LK scores for the triamcinolone and saline groups at the first and second post-op visits were 2.09 ± 1.23 v. 2.18 ± 1.01 (p=0.79) and 1.79 ± 1.08 v. 1.68 ± 1.16 (p = 0.77) respectively. POSE scores were 2.59 ± 1.71 v. 2.68 ± 1.62 (p = 0.86) and 1.74 ± 1.15 v. 1.95 ± 1.22 (p = 0.59). Conclusion : The results of this study demonstrated no significant difference in healing, crusting, polyps, edema, or secretions between the triamcinolone treated and non-triamcinolone treated sinuses. There were no adverse effects from use of triamcinolone impregnated absorbable packing. Further studies will be necessary to determine the impact of triamcinolone impregnated absorbable packing following endoscopic sinus surgery. This article is protected by copyright. All rights reserved
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. Background: Wound healing of the nasal mucosa after endoscopic sinus surgery (ESS) is frequently complicated by scaring and consequently recurrences are encountered. Methods of optimizing results have been sought. In the present study we evaluated the effects of a powerful antioxidant, astaxanthin, on nasal mucosa healing after surgery, comparing it to the extensively studied properties of dexamethasone. Materials and methods: 63 Wistar rats were used. The nasal mucosa from one side was damaged employing the brushing method. They were randomly divided into three experimental groups, one treated with astaxanthin, the second treated with dexamethasone and the third one acted as the control and was given normal saline. The rats were killed on days 5, 14 and 28 following injury. We observed the temporal evolution of the wound healing process and quantified the results by assessing four parameters: the epithelial thickness index (ETI), the subepithelial thickness index (STI), the goblet cell count and the subepithelial fibrosis index (SFI). Results: At 28 days, the ETI was significantly lower in the astaxanthin group (p < 0.05) compared to the other two groups. The STI was also lower in the astaxanthin group (p < 0.05), but comparable to the dexamethasone group at 28 days. The goblet cell count was higher in the astaxanthin group. The SFI had similar results in both dexamethasone and astaxanthin groups, with lower values compared to the control group. In the astaxanthin group there was no synechia formation. Conclusion: Astaxanthin given in the post injury period significantly decreases fibrosis, inhibits synechia development and significantly decreases subepithelial fibrosis. Moreover, it has no general or local toxic effects.
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This study aimed to identify trends in bacteria isolated from Korean adults with chronic rhinosinusitis (CRS). Enrolled were CRS patients who underwent sinus bacterial culture during endoscopic sinus surgery between 2007–2008, 2011–2012, and 2017–2018 (n = 510). Patients’ clinical characteristics, bacterial culture results, and antibiotic resistance were reviewed. The bacteria isolation rate was 76.3% (73.9% for CRS with nasal polyps and 82.8% for CRS without nasal polyps; p = 0.038). In total, 650 strains were isolated, the most common was Coagulase Negative Staphylococci (CNS) (28.0%), followed by Streptococcus species (12.2%), Propionibacterium species (8.0%), Corynebacterium species (7.5%), Staphylococcus aureus (6.2%), Haemophilus species (5.7%), Klebsiella species (5.1%), and Pseudomonas aeruginosa (4.2%). Furthermore, an analysis of the bacterial trends in the three groups showed significant increases over time for the isolation of CNS (p = 0.006), Klebsiella (p = 0.002), and P. aeruginosa (p = 0.007) and extended-spectrum beta-lactamase (ESBL) producing Klebsiella (p < 0.001) and Enterobacter (p = 0.007) species in terms of antibiotics resistance. This study demonstrates that the frequency of CNS, Klebsiella, and P. aeruginosa in CRS patients and the ESBL-producing Klebsiella and Enterobacter species has significantly increased in CRS patients over the last decade.
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Background: Chronic rhinosinusitis (CRS) is defined as a chronic inflammation of the nose and paranasal sinus mucosa associated with relapsing infections-particularly with S. aureus. Long-term treatments with protein synthesis inhibitor antibiotics have been proposed to reduce inflammation in the context chronic severe inflammatory airway pathologies, including CRS. This study assessed the effect of subinhibitory clindamycin and azithromycin on S. aureus exoprotein induced inflammation, toxicity and invasiveness. Methods: S. aureus ATCC51650 and two clinical isolates grown in planktonic and biofilm form were treated with subinhibitory clindamycin and azithromycin. Exoproteins were collected and applied to primary human nasal epithelial cells (HNECs) in monolayers and at air-liquid interface. This was followed by lactate dehydrogenase (LDH), enzyme-linked immunosorbent assay (ELISA), Transepithelial Electrical Resistance (TEER) and paracellular permeability assays to assess the effect on cell toxicity, inflammatory cytokine production and mucosal barrier structure and function, respectively. The effect of these treatments was tested as well on the S. aureus invasiveness of HNECs. Results: Subinhibitory clindamycin reduced S. aureus exoprotein production in planktonic and biofilm form, thereby blocking exoprotein-induced toxicity, reversing its detrimental effects on mucosal barrier structure and function and modulating its inflammatory properties. Sub-inhibitory azithromycin had similar effects-albeit to a lesser extent. Furthermore, clindamycin-but not azithromycin-treated S. aureus lost its invasive capacity of HNECs. Conclusion: Subinhibitory clindamycin and azithromycin reduce S. aureus exoprotein production, thereby modulating the inflammatory cascade by reducing exoprotein-induced toxicity, inflammation, mucosal barrier disruption and invasiveness.
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Chronic rhinosinusitis is the foremost manifestation in adult patients with primary ciliary dyskinesia (PCD). We present a retrospective series of 41 adult patients with a confirmed diagnosis of PCD followed in our reference centers. As part of the diagnostic work up in our centers, sinus computed tomography scans (CTs) are systematically performed. All patients also undergo a sampling of purulent secretions sampled from the middle meatus under endoscopic view for bacteriological analysis. In our series, CT opacities were consistent in all the patients, as well as mainly partial and located in ethmoid cells (100% of patients) and in maxillary sinuses (85.4% of patients), and stayed stable over time. In the 31 patients who had purulent secretions, bacteriological culture showed at least one bacterium in 83.9% (n = 26). There was no significant difference in positive cultures for Pseudomonas aeruginosa in patients >40 years old versus those <40 (p = 0.17; Fisher). Surgical management was performed in only 19% of patients in order to improve sinonasal mechanical drainage. Our data support the hypothesis that the sinuses can be considered as a bacterial reservoir. From this retrospective study, we have introduced several changes into our routine clinical practice in our reference centers. Based on our analyses, medical and surgical treatments benefit from incorporating bacteriological information and sinonasal symptoms much more than CT scan evaluation alone. All patients now undergo systematically an annual simultaneous bacteriological sampling of the middle meatus and sputum to follow the relationship between ENT and lung disease and to help to antibiotic therapy strategy.
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To date, no study precisely described ear, nose and throat (ENT) disease in adults with primary ciliary dyskinesia (PCD) and its relationship with ciliary function/ultrastructure. A retrospective study of standardized ENT data (exam, audiogram, sinus Computed tomography (CT), and bacteriology) was conducted in 64 adults with confirmed PCD who were followed in two ENT reference centers. Rhinorrhoea and hearing loss were the main symptoms. Symptom scores were higher in older patients. Nasal endoscopy was abnormal in all patients except one, showing nasal polyps in one-third of the patients and stagnant nasal mucus secretions in 87.5% of the patients. Sinus CT opacities were mainly incomplete and showed one-third of the patients with sinus hypoplasia and/or agenesis. Middle meatus mainly grew Haemophilus influenzae, Streptoccocus pneumoniae and Pseudomonas aeruginosa. Otitis media with effusion (OME), which is constant in childhood, was diagnosed in less than one-quarter of the patients. In two-thirds of the patients, audiogram showed hearing loss that was sensorineural in half of the patients. ENT disease severity was not correlated with ciliary function and ultrastructure, but the presence of OME was significantly associated with a forced expiratory volume (FEV1) < 70%. Rhinosinusitis is the most common clinical feature of PCD in adults, while OME is less frequent. The presence of active OME in adults with PCD could be a severity marker of lung function and lead to closer monitoring.
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Objective: To investigate the risk of chronic rhinosinusitis (CRS) among patients with Sjögren’s syndrome (SS). Method: A total of 18,723 patients diagnosed with SS between 1997 and 2011 were retrospectively analyzed. Moreover, 59,568 patients without SS were matched to patients with SS at a 1:4 ratio on the basis of sex, age, urbanization level, income level, and the comorbidities of rhinitis and nasal sepal deviation. Patients were followed up until death or the end of the study period (31 December, 2013). The primary outcome was the occurrence of CRS. Results: The cumulative incidence of CRS was significantly higher in patients with SS than in those without SS (p < 0.001). The adjusted Cox proportional hazard model showed that patients with SS had a significantly higher incidence of CRS (hazard ratio, 2.51; 95% confidence interval, 2.22–2.84; p < 0.001). Sensitivity and subgroup analyses demonstrated SS was an independent risk factor for CRS. The dosage of intranasal corticosteroid spray used was not different between the SS and non-SS groups. Fewer patients with CRS in the SS group underwent sinus surgery (82/407 (20.2%)) than those in the non-SS group (179/667 (26.8%)) and this finding was statistically significant (p = 0.013). The number of operations did not differ significantly between patients with CRS in the SS and non-SS groups. Conclusions: SS is an independent risk factor for CRS. Our study extends the disease spectrum and prompts physicians to be aware of potential CRS occurrence after SS.