Viruses in chronic rhinosinusitis: a systematic review.

Background: Unlike acute rhinosinusitis (ARS) which is mostly viral in etiology, the role of viruses in chronic rhinosinusitis (CRS) remains unclear. Viruses may play a role in initiation, exacerbations or perpetuate chronic inflammatory responses in the sinonasal mucosa. Research needs to characterize whether viruses are part of the normal sinonasal microbiome, colonizers or pathogenic. Methods: Systematic review of the English literature was conducted. Following databases were searched with an initial search conducted in November 2021 and then updated through June 2023: Ovid Medline (1946 to present), Ovid Embase (1988 to present), Scopus (2004 to present) and Web of Science (1975 to present). MeSH (Medical Subject Headings) terms included: viruses, virus diseases, sinusitis, and rhinovirus. Keywords: virus, viral infection*, sinusitis, rhinovirus, chronic rhinosinusitis, CRS, respiratory virus, respiratory infection*, and exacerbat*. A supplementary search was conducted through September 2023: Ovid Medline (1946 to present), Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Daily. Keywords used were: virus, viral infection*, sinusitis, chronic rhinosinusitis, CRS, respiratory virus, respiratory infection*, and exacerbat*. Results: Thirty studies on viruses in CRS met inclusion criteria for full review. These included 17 studies on prevalence of virus in CRS, 5 examining probable causes of host susceptibility to viral infections in CRS, and 8 studies examining pathological pathways in viral association of CRS. The prevalence of viruses in nasal specimens of CRS subjects was higher as compared to controls in most studies, though a few studies showed otherwise. Rhinovirus was the most common virus detected. Studies showed that viruses may be associated with persistent hyper-responsiveness in the sinonasal mucosa, susceptibility to bacterial infections, upregulation of genes involved in the immune response and airway remodeling as well as CRS exacerbations. Presence of viruses was also associated with worse symptom severity scores in CRS subjects. Conclusion: Most data show higher presence of viruses in nasal and serum samples of CRS subjects as compared to controls but their exact role in CRS pathophysiology in unclear. Large studies with longitudinal sampling at all disease phases (i.e., prior to disease initiation, during disease initiation, during disease persistence, and during exacerbations) using standardized sampling techniques are needed to definitively elucidate the role of virus in CRS.

Combined endoscopic sinus surgery and endonasal septal perforation repair: Symptom outcomes and perforation closure rates.

KEYPOINTS: Combined endoscopic sinus surgery and nasal septal perforation repair is technically feasible. NOSE-Perf is a recently developed patient-reported outcome measure for nasal septal perforation. The decision to perform combined ESS and NSP repair should be made on a case-by-case basis.

Genome-wide Epigenetic Study of Chronic Rhinosinusitis Tissues Reveals Dysregulated Inflammatory, Immunologic and Remodeling Pathways.

BACKGROUND: Epigenetics studies mechanisms such as DNA methylation, histone modifications, non-coding RNAs, and alternative polyadenylation that can modify gene activity without changing the underlying DNA nucleotide base-pair structure. Because these changes are reversible, they have potential in developing novel therapeutics. Currently, seven pharmaceutical agents targeting epigenetic changes are FDA approved and commercially available for treatment of certain cancers. However, studies investigating epigenetics in chronic rhinosinusitis (CRS) have not been undertaken previously in the United States. OBJECTIVES: The goal of this study was to investigate sinonasal DNA methylation patterns in CRS versus controls, to discern environmentally-induced epigenetic changes impacting CRS subjects. METHODS AND RESULTS: Ethmoidal samples from CRS and inferior turbinate mucosal tissue samples from controls without CRS were studied. DNA methylation was studied by Reduced Representation Bisulfite Sequencing. RADMeth® biostatistical package was used to identify differentially methylated regions (DMRs) between CRS and controls. Ingenuity Pathway analysis of DMRs was performed to identify top upstream regulators and canonical pathways. Ninety-three samples from 64 CRS subjects (36 CRSwNP; 28 CRSsNP) and 29 controls were studied. CRS and control samples differed in 13 662 CpGs sites and 1381 DMRs. Top upstream regulators identified included: 1. CRS versus controls: TGFB1, TNF, TP53, DGCR8, and beta-estradiol. 2. CRSwNP versus controls: TGFB1, CTNNB1, lipopolysaccharide, ID2, and TCF7L2. 3. CRSsNP versus controls: MYOD1, acetone, ID2, ST8SIA4, and LEPR. CONCLUSIONS: Differential patterns of methylation were identified between controls and CRS, CRSwNP, and CRSsNP. Epigenetic, environmentally-induced changes related to novel, inflammatory, immunologic, and remodeling pathways appear to affect epithelial integrity, cell proliferation, homeostasis, vascular permeability, and other yet uncharacterized pathways and genes.

Outcomes of Frontal Sinus Stenting With Steroid Impregnated Microsponge Versus Steroid-Eluting Implant.

BACKGROUND: Mometasone-eluting poly-L-lactide-coglycolide (MPLG) is available commercially for frontal sinus ostium (FSO) stenting. An alternative chitosan polymer-based drug delivery microsponge is also available at a lower cost per unit. OBJECTIVE: To compare the outcomes of MPLG stents versus triamcinolone-impregnated chitosan polymer (TICP) microsponge in frontal sinus surgery. METHODS: Patients who underwent endoscopic sinus surgery from December 2018 to February 2022 were reviewed to identify those with the intraoperative placement of TICP microsponge or MPLG stent in the FSO. FSO patency was evaluated by endoscopy at follow-up. Twenty-two-item sinonasal outcome test (SNOT-22) was also recorded, and complications were noted. RESULTS: A total of 68 subjects and 96 FSOs were treated. TICP was first used in August 2021 and MPLG in December 2018. MPLG placement in a Draf 3 cavity was excluded since TICP had not been used during Draf 3 procedure. Both cohorts (TICP 20 subjects, 35 FSOs; MPLG 26 subjects, 39 FSOs) had similar clinical characteristics. At a mean total follow-up of 249.2 days for TICP and 490.4 days for MPLG, FSO patency was 82.9% and 87.1%, respectively (P = .265). At an equivalent follow-up of 130.6 days in TICP and 154.0 days in MPLG, patency was 94.3% and 89.7%, respectively (P = .475). Both groups showed significant reductions in SNOT-22 (P < .001). MPLG demonstrated crusting within the FSO at 1 month (none in TICP). CONCLUSION: FSO patency for both stents was similar, although TICP had significantly lower costs per unit. Additional comparative trials may be helpful for guiding clinicians on the appropriate clinical situations for the use of these devices.

Insights into the epigenetics of chronic rhinosinusitis with and without nasal polyps: a systematic review.

Background: Epigenetics facilitates insights on the impact of host environment on the genesis of chronic rhinosinusitis (CRS) through modulations of host gene expression and activity. Epigenetic mechanisms such as DNA methylation cause reversible but heritable changes in gene expression over generations of progeny, without altering the DNA base-pair sequences. These studies offer a critical understanding of the environment-induced changes that result in host predisposition to disease and may help in developing novel biomarkers and therapeutics. The goal of this systematic review is to summarize the current evidence on epigenetics of CRS with a focus on chronic rhinosinusitis with nasal polyps (CRSwNP) and highlight gaps that merit further research. Methods: A systematic review of the English language literature was performed to identify investigations related to epigenetic studies in subjects with CRS. Results: The review identified 65 studies. These have focused on DNA methylation and non-coding RNAs, with only a few on histone deacetylation, alternative polyadenylation, and chromatin accessibility. Studies include those investigating in vivo and in vitro changes or both. Studies also include animal models of CRS. Almost all have been conducted in Asia. The genome-wide studies of DNA methylation found differences in global methylation between CRSwNP and controls, while others specifically found significant differences in methylation of the CpG sites of the thymic stromal lymphopoietin (TSLP), IL-8, and PLAT. In addition, DNA methyltransferase inhibitors and histone deacetylase inhibitors were studied as potential therapeutic agents. Majority of the studies investigating non-coding RNAs focused on micro-RNAs (miRNA) and found differences in global expression of miRNA levels. These studies also revealed some previously known as well as novel targets and pathways such as tumor necrosis factor alpha, TGF beta-1, IL-10, EGR2, aryl hydrocarbon receptor, PI3K/AKT pathway, mucin secretion, and vascular permeability. Overall, the studies have found a dysregulation in pathways/genes involving inflammation, immune regulation, tissue remodeling, structural proteins, mucin secretion, arachidonic acid metabolism, and transcription. Conclusions: Epigenetic studies in CRS subjects suggest that there is likely a major impact of the environment. However, these are association studies and do not directly imply pathogenesis. Longitudinal studies in geographically and racially diverse population cohorts are necessary to quantify genetic vs. environmental risks for CRSwNP and CRS without nasal polyps and assess heritability risk, as well as develop novel biomarkers and therapeutic agents.

Genetics and epigenetics of chronic rhinosinusitis.

Discerning the genetics and epigenetics of chronic rhinosinusitis (CRS) may optimize outcomes through early diagnostics, personalized and novel therapeutics, and early prognostication. CRS associated with cystic fibrosis and primary ciliary dyskinesia has well-characterized genetic mutations. Most CRS subjects, however, do not exhibit identifiable monogenic alterations. Clustering in related individuals is seen in CRS with nasal polyps. Spouses of subjects with CRS without nasal polyps also may be at increased risk of the same disease. These observations generate questions on genetic and environmental influences in CRS. Genome-wide association studies have identified variations and polymorphisms between CRS and control subjects in genes related to innate and adaptive immunity. Candidate gene and transcriptomics studies have investigated and identified genetic variations related to immunity, inflammation, epithelial barrier function, stress-response, antigen processing, T-cell regulation, and cytokines in CRS. Epigenetic studies have identified mechanisms through which environmental factors may affect these gene functions. However, causality is not determined for most variations. Inferences drawn from these data must be measured because most investigations report unreplicated results from small study populations. Large, replicated studies in tight cohorts across diverse populations remain a pressing need in studying CRS genetics.

Biological sex as a modulator in rhinologic anatomy, physiology, and pathology: A scoping review.

BACKGROUND: Biological sex is increasingly recognized as a critical variable in health care. The authors reviewed the current literature regarding sex-based differences in rhinology to summarize the data and identify critical knowledge gaps. METHODS: A scoping review was conducted. Publications reporting sex-based differences in anatomy, physiology, and pathology focusing on disease prevalence, disease burden, and outcomes in rhinology were identified. RESULTS: Seventy-five relevant manuscripts were identified. While paranasal sinuses are of similar size at birth, they become larger in males leading to differences in ostium location. Females outperform males in olfactory identification but only in the 18- to 50-year age group. Estrogen and progesterone administration can impact muscarinic and α1 -adrenergic nasal mucosa receptor density. Chronic rhinosinusitis (CRS) and CRS without nasal polyps are more prevalent in females while CRS with nasal polyps is more prevalent in males. CRS symptom burden is higher in females before and after endoscopic sinus surgery; however, no difference in endoscopic sinus surgery utilization was found based on sex. Allergic rhinitis is more common in males before puberty and in females after puberty. Epistaxis is more prevalent in males and postmenopausal females compared with premenopausal females, perhaps from differences in sex-hormonal and hypertension status. In nasopharyngeal carcinoma, the incidence of sinus abnormalities was higher in males than females. CONCLUSIONS: Although many sex-based differences exist in rhinology, further research is necessary to offer evidence-based treatment guidelines. Gonadal hormones should be studied as a therapeutic in rhinologic pathology as baseline physiologic differences exist such as those found in nasal mucosa receptor density.

Tissue Eosinophilia is Superior to an Analysis by Polyp Status for the Chronic Rhinosinusitis Transcriptome: An RNA Study.

OBJECTIVE: RNA sequencing (transcriptomics) is used to study biological pathways. However, the yield of data depends on comparing well-characterized cohorts. We compared tissue eosinophilia versus nasal polyp (NP) status as the metric to characterize transcriptomic mechanisms at play in eosinophilic and non-eosinophilic chronic rhinosinusitis (CRS) versus controls. METHODS: RNA sequencing was conducted on sinonasal tissue samples of CRS and controls. Analyses were conducted based on polyp status [with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP)] as well as tissue eosinophil levels per high power field (eos/hpf)[non-eosinophilic (<10 eos/hpf, neCRS) or eosinophilic (≥10 eos/hpf, eCRS)]. The yield of differentially expressed genes (DEGs) and biological pathways through Ingenuity Pathway Analysis (IPA) were compared. RESULTS: CRS tissue differed from controls by 736 statistically significant DEGs. Both NP status and tissue eosinophilia were effective in differentiating CRS from controls and into two distinct subgroups. Statistically significant DEGs identified when comparing CRS by NP status were 60, whereas 110 DEGs were identified using eosinophil cutoff ≥10 and <10 eos/hpf. Additionally, heatmaps showed greater homogeneity within each CRS subgroup when analyzed by tissue eosinophilia versus NP status. On IPA, the IL-17 signaling pathway was significantly different only by tissue eosinophilia status, not NP status, being higher in CRS <10 eos/hpf. CONCLUSION: Tissue eosinophilia is superior to an analysis by NP status for the study of CRS transcriptome by RNA sequencing in identifying DEGs. Classification of CRS samples by eosinophil counts agnostic of NP status may offer advantageous insights into CRS pathogenetic mechanisms. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2480-2489, 2023.

Unified Airway Disease: Surgical Management.

Support for the unified airway hypothesis is embedded in similarities in upper and lower airway structure, function, and cellular/extracellular compositions. The impact of endoscopic sinus surgery (ESS) on the unified airway is influenced by multiple factors including the underlying upper and lower airway condition(s) present and severity of pathology. Beyond improvements in subjective and objective CRS outcomes, ESS also improves clinical asthma outcomes and measures of asthma control. Emerging evidence suggests that early ESS may mitigate the risk of developing asthma in CRS patients without asthma. Comprehensive management of upper and lower airways is paramount to optimize patient outcomes.

Unified Airway Disease: Genetics and Epigenetics.

Although unified airway disease (UAD) may have heritable components, genetic changes involving coexistent chronic rhinosinusitis (CRS) are not well understood. Genetic predisposition is stronger in patients with CRS with nasal polyps compared with those without nasal polyps (CRSsNP). Genetic factors account for 25% to 80% of asthma risk and 90% of allergic rhinitis risk but risk contributions are not well described for CRS. Susceptibility genes identified in coexistent CRS-asthma relate to innate and adaptive immunity, cytokine signaling, tissue remodeling, arachidonic acid metabolism, and other proinflammatory pathways. Non-type 2 UAD such as CRS-bronchitis/bronchiectasis and CRSsNP are currently inadequately characterized.

Antibody responses to the host microbiome in chronic rhinosinusitis.

BACKGROUND: The role of microbes in chronic rhinosinusitis (CRS) is poorly understood. We hypothesize that analyzing prior microbial exposures via assessing microbial protein serological reactivity in CRS versus controls may offer insights for CRS etiopathogenesis. METHODS: We profiled IgG and IgA antibodies to individual microbial proteins in serum samples of CRS patients and controls using a novel high-throughput microarray protein technology, Nucleic Acid Programmable Protein Array (NAPPA). The study was conducted on 118 subjects (39 CRS, 79 controls). A CRS-focused NAPPA array, with 1557 potentially sero-reactive microbial proteins elected from a pre-screening of 6500 genes of interest was constructed. It included membrane-associated proteins from 47 bacterial species and all proteins from 43 viral strains. Differences between CRS and controls were compared across individual antimicrobial antibodies and the species. RESULTS: Chronic rhinosinusitis patients had significantly elevated antimicrobial antibodies compared with controls. One bacterium (Staphylococcus aureus) and three viral strains (human metapneumovirus, human herpesvirus 5, and human herpesvirus 4) were identified as sources of the proteins that showed significantly elevated sero-reactivity in CRS patients. Within CRS, patients with polyps had elevated antibodies against S. aureus, influenza A virus (H1N1, H3N2), and rhinovirus B14. CRS patients without polyps showed more antibodies against human herpesvirus 1 and vaccinia virus WR. CONCLUSIONS: Compared with healthy controls, CRS patients' serum samples showed significantly increased sero-reactivity to both bacterial and viral proteins, reflecting recent or current infection or active colonization. Significantly higher antibodies against S. aureus, human metapneumovirus, human herpesvirus 5, and human herpesvirus 4 in CRS need further study.

Do Otolaryngology Patients Show Gender Preference When Choosing a Surgeon? — A Quantitative and Qualitative Analysis

Abstract Introduction Otorhinolaryngology has always been considered a gender-neutral specialty, whereas in several other specialties, such as obstetrics, gynecology and urology, gender preference has been consistently shown by patients when choosing their treating surgeon. To date, no study has been performed to analyze whether this practice of gender preference is prevalent in otorhinolaryngology patients too. Objectives To identify if gender preference exists in the field of otorhinolaryngology, specifically in its four subspecialties, namely otology, pediatric otolaryngology, laryngology and head and neck surgery. Methods Patients attending our outpatient department were asked to complete a preformed proforma. The pro forma consisted of two parts, demographic details of the subjects and gender preference in the following subspecialties: otology, pediatric otolaryngology, laryngology and head and neck oncosurgery. Results A total of 1,112 subjects took part in the study, out of which 1,089 subjects were included in the final analysis. Female gender preference was highest in the field of pediatric otolaryngology, while male preference was highest for head and neck oncosurgery. Conclusion Though otorhinolaryngology and head and neck surgery has been considered a gender-neutral field, subspecialties of this field show considerable gender preference.

Do Otolaryngology Patients Show Gender Preference When Choosing a Surgeon? - A Quantitative and Qualitative Analysis.

Introduction Otorhinolaryngology has always been considered a gender-neutral specialty, whereas in several other specialties, such as obstetrics, gynecology and urology, gender preference has been consistently shown by patients when choosing their treating surgeon. To date, no study has been performed to analyze whether this practice of gender preference is prevalent in otorhinolaryngology patients too. Objectives To identify if gender preference exists in the field of otorhinolaryngology, specifically in its four subspecialties, namely otology, pediatric otolaryngology, laryngology and head and neck surgery. Methods Patients attending our outpatient department were asked to complete a preformed proforma. The pro forma consisted of two parts, demographic details of the subjects and gender preference in the following subspecialties: otology, pediatric otolaryngology, laryngology and head and neck oncosurgery. Results A total of 1,112 subjects took part in the study, out of which 1,089 subjects were included in the final analysis. Female gender preference was highest in the field of pediatric otolaryngology, while male preference was highest for head and neck oncosurgery. Conclusion Though otorhinolaryngology and head and neck surgery has been considered a gender-neutral field, subspecialties of this field show considerable gender preference.

Paediatric oral submucous fibrosis - The neglected pre-malignancy of childhood.

Oral submucous fibrosis in children is one of the devastating consequences of arecanut addiction in children. Arecanut is the fourth commonest psychoactive agents used worldwide. However, regrettably, unlike other addictions like tobacco and alcohol, its use in children has become socially acceptable atleast in a few countries. Consequently, children as young as two years have been noticed to be addicted to arecanuts. It has been a menace in most Asian countries and with increasing population migration, this has picked up even in the west. In order to understand the social factors leading to arecanut addiction in children and prognostic outcomes of paediatric oral submucous fibrosis, this review has been undertaken.

Complicated coexisting pyogenic and tuberculous otitis media affecting the temporozygomatic, infratemporal, and parotid areas: report of a rare entity.

We report an unusual case in which a 28-year-old woman presented with a long-standing history of ear discharge, hearing loss, facial weakness with ipsilateral facial swelling and cellulitis, a postauricular fistula, and an abscess of the temporozygomatic, infratemporal, and parotid areas. The pus stained positive for bacteria and acid-fast bacilli, and culture was positive for Proteus vulgaris and mycobacteria. Based on these findings, a diagnosis of tuberculous otitis media with complications was made. Computed tomography showed extensive destruction of the tympanic and mastoid part of the temporal bone, as well as lytic lesions in the skull. The patient was placed on antituberculosis drug therapy. Although her facial nerve palsy and hearing loss persisted, she otherwise responded well and did not require surgery.

Comparison of hearing outcome using a Nitinol versus Teflon prosthesis in stapedotomy.

CONCLUSION: The time-tested, readily available, and cost-effective Teflon® piston continues to have equivocal results to the newer Nitinol piston. OBJECTIVE: To compare hearing outcome using a Nitinol versus Teflon piston in stapes surgery and to ascertain the feasibility of using the Nitinol piston. METHODS: Forty patients between 18 and 45 years of age were selected and randomly allocated into two groups of 20 each and the study was conducted between September 2007 and March 2009 at Maulana Azad Medical College. RESULTS: There was no significant difference between the two groups in the postoperative air-bone gap and air-bone gap closure at 1, 2, 3, and 6 months.