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.

Submental flap for reconstruction of anterior skull base, orbital, and high facial defects.

PURPOSE: Large anterior skull base, orbital, and high facial defects can present a challenging reconstructive problem. Limited data exists in the literature on the use of a submental flap for reconstructing such defects. We aimed to describe the feasibility, success, and advantages of using variations of the submental flap for reconstruction of anterior skull base, orbital, and high facial defects. MATERIALS & METHODS: Outcomes measured included flap method, flap survival, flap size, reconstructive site complications, donor site complications, and length of hospital stay. RESULTS: Nine patients were identified that underwent submental flap reconstruction of anterior skull base, orbital, or high facial soft tissue defects. There were 5 pedicled, 2 hybridized, and 2 free submental flap reconstructions. Flap survival was 100%. One flap required leech therapy for early post-operative venous congestion. Average flap skin paddle size was 63.7 cm2. Average length of hospital stay was 7.3 days. No complications from the donor site were reported. CONCLUSIONS: Different variations on the submental flap are viable options for reconstruction of high defects in the head and neck. Such flaps have a number of unique qualities that are suitable for reconstruction of anterior skull base, orbital, and high facial defects.

Management of rhinosinusitis during pregnancy: systematic review and expert panel recommendations.

BACKGROUND: Management of rhinosinusitis during pregnancy requires special considerations. OBJECTIVES: 1. Conduct a systematic literature review for acute and chronic rhinosinusitis (CRS) management during pregnancy. 2. Make evidence-based recommendations. METHODS: The systematic review was conducted using MEDLINE and EMBASE databases and relevant search terms. Title, abstract and full manuscript review were conducted by two authors independently. A multispecialty panel with expertise in management of Rhinological disorders, Allergy-Immunology, and Obstetrics-Gynecology was invited to review the systematic review. Recommendations were sought on use of following for CRS management during pregnancy: oral corticosteroids; antibiotics; leukotrienes; topical corticosteroid spray/irrigations/drops; aspirin desensitization; elective surgery for CRS with polyps prior to planned pregnancy; vaginal birth versus planned Caesarian for skull base erosions/ prior CSF rhinorrhea. RESULTS: Eighty-eight manuscripts underwent full review after screening 3052 abstracts. No relevant level 1, 2, or 3 studies were found. Expert panel recommendations for rhinosinusitis management during pregnancy included continuing nasal corticosteroid sprays for CRS maintenance, using pregnancy-safe antibiotics for acute rhinosinusitis and CRS exacerbations, and discontinuing aspirin desensitization for aspirin exacerbated respiratory disease. The manuscript presents detailed recommendations. CONCLUSIONS: The lack of evidence pertinent to managing rhinosinusitis during pregnancy warrants future trials. Expert recommendations constitute the current best available evidence.

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

KEY POINTS: 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.

Assessment of a Novel Tool for the Clinical Grading of Nasal Septal Perforation.

BACKGROUND: Nasal septal perforations (NSP) can have a heterogeneous appearance on endoscopic examination with varying degrees of crusting, inflammatory change, and associated septal deviation. The clinical applicability of these findings as contributors to patient symptoms may be enhanced by use of a standardized assessment. METHODS: Video nasal endoscopy recordings were obtained from 40 patients with NSP. Five raters with varied levels of training ranging from a senior resident to an experienced septal perforation surgeon independently reviewed the videos for the following exam findings: crusting, scarring, granulation tissue, septal deviation, and edema. Scoring for each item was reported on a 3-point (0-2) scale, and each reviewer repeated scoring at a 14-day interval. Interrater and intrarater agreement were calculated using Fleiss kappa for each item and the total scores. Additionally, endoscopy scores were correlated with patient-reported NOSE-Perf symptom scores. RESULTS: Interrater agreement for the overall instrument was in the "fair-to-moderate" range with the following interrater agreement for each item: crusting (0.458-0.575), scarring (0.286-0.308), granulation (0.403-0.406), deviation (0.487-0.494), and edema (0.253-0.406). Intrarater agreement was generally "substantial" for individual items as well as the overall instrument (0.688). The NSP endoscopy scores were moderately correlated with NOSE-Perf scores (r = 0.44, p = 0.008). CONCLUSIONS: An endoscopic evaluation of NSP comprising five exam findings has acceptable interrater and intrarater reliability and correlates with patient-reported outcomes. NSP endoscopy may be applied to future clinical studies for characterization of NSP and assessment of treatment outcomes. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3049-3053, 2024.

Eosinophil Peroxidase: A Biomarker for Eosinophilic Chronic Rhinosinusitis Agnostic of Polyp Status.

OBJECTIVE: To evaluate eosinophil peroxidase (EPX) as a biomarker for tissue levels of eosinophilia, cytokines, and chemokines within chronic rhinosinusitis (CRS). METHODS: Twenty-eight subjects undergoing sinonasal surgery were prospectively enrolled. Ethmoid tissue was analyzed with an in-house EPX immunoassay and a 48-plex cytokine-chemokine array. Clinical severity was assessed using SNOT-22 and Lund-Mackay scores. Subjects were grouped as follows: controls, polyp status (CRS with [CRSwNP] and without nasal polyps [CRSsNP]), tissue eosinophilia (eosinophilic CRS [eCRS], non-eosinophilic CRS [neCRS]), or combinations thereof (eCRSwNP, eCRSsNP, neCRSsNP). eCRS was defined as >10 eosinophils per high power field (HPF). Subjects without CRS or asthma were enrolled as controls. RESULTS: EPX was elevated in CRSwNP compared to control (p = 0.007), in eCRS compared to neCRS (p = 0.002), and in eCRSwNP along with eCRSsNP compared to neCRSsNP (p = 0.023, p = 0.015, respectively). eCRS displayed elevated IL-5 compared to neCRS (p = 0.005). No significant differences in EPX or IL-5 were observed between eCRSwNP and eCRSsNP. IL-5 was elevated in eCRSwNP (p = 0.019) compared neCRSsNP. Area under the receiver operator characteristic curve was 0.938 (95% CI, 0.835-1.00) for EPX and tissue eosinophilia, with an optimal cut-point of 470 ng/mL being 100% specific and 81.25% sensitive for tissue eosinophilia. Linear regression revealed a strong correlation between EPX and IL-5 (R2 = 0.64, p < 0.001). Comparing EPX and IL-5, only EPX displayed significant correlation with SNOT-22 (p = 0.04) and Lund-Mackay score (p = 0.004). CONCLUSION: EPX is associated with tissue eosinophilia in CRS patients regardless of polyp status. EPX correlates with IL-5 and could be potentially considered a biomarker for anti-IL-5 therapies. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:69-78, 2024.

Oral steroid therapy in chronic rhinosinusitis with and without nasal polyposis.

Chronic rhinosinusitis (CRS) is a heterogeneous group of disorders characterized by inflammation of the sinonasal mucosa. CRS can be divided into two subtypes: CRS without polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). Corticosteroids are frequently employed to treat CRS due to their potent anti-inflammatory effects. Treatment of CRS with oral steroids must be carefully balanced against potential adverse effects. This article reviews the current literature on management of CRS with systemic corticosteroids. We discuss the available evidence in CRSsNP, CRSwNP, and allergic fungal sinusitis (AFS). Studies are evaluated for level of evidence and graded to provide evidence-based recommendations. Our review finds a lack of high-quality evidence supporting oral corticosteroid therapy in CRSsNP. In comparison, randomized controlled trails support the use of oral corticosteroids for CRSwNP. Similarly, systemic steroids for AFS treatment are supported by quality studies demonstrating efficacy. Utilization of steroids is also recommended in the perioperative setting for CRSwNP.

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.

Unified Airway Disease: Diagnosis and Subtyping.

The concept of a unified airway posits that pathology affects the respiratory tract in a continuum and that disease in one part of the respiratory tract may be associated with or directly or indirectly affect the function of a different part. Transcriptomic analysis has shown 91% homology between the genes expressed in the upper and the lower airway. Approaching inflammatory airway disorders using the unified airway hypothesis allows for a better clarification of disease process and provides a detailed and a high-level overview of dysfunction. There are several tools available to the clinician to use to subtype and diagnose accurately the abnormal pathways operating in inflammatory airway disorders. These tools include clinical history, physical examination findings, imaging (computed tomography and MRI), allergy and laboratory testing, pulmonary function testing (PFT), and tissue histopathology. Tests can be categorized based on platform, by specimen, or the marker being studied.

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.

Sex Differences in Airway Diseases.

It is evident that sex and gender differences impact pathophysiology, disease burden, and treatment outcomes for a variety of systems and major illnesses including those affecting the unified airway. Important male-female differences in unified airway disease are driven by various intrinsic and extrinsic mechanisms including anatomic, morphometric, hormonal, genetic (and epigenetic), environmental, psycho-social, and comorbidity-related factors. This review highlights current knowledge of how patient sex influences epidemiology, diagnosis, treatment, and outcomes for diseases affecting the unified airway.

Considerations for shared decision-making in treatment of chronic rhinosinusitis with nasal polyps.

Shared decision-making is an approach where physicians and patients work together to determine a personalized treatment course. Such an approach is integral to patient-centered care in chronic rhinosinusitis with nasal polyps (CRSwNP). CRSwNP is a chronic inflammatory condition of the sinonasal cavity that can severely impact physical health, smell, and quality of life (QOL). Traditional standard-of-care treatment options include topical (i.e. sprays) and oral corticosteroids and endoscopic sinus surgery, but more recently, novel corticosteroid delivery methods (i.e. high volume irrigations, recently-approved exhalation breath-powered delivering devices, and drug-eluting steroid implants) and 3 new FDA approved biologics directed against type II immunomodulators have become available. The availability of these therapeutics offers exciting new opportunities in CRSwNP management but requires personalized and shared-decision making as each modality has variable impacts on CRSwNP and related comorbid conditions. Studies have published treatment algorithms, but the practical use of these lean guidelines is heavily influenced by the lens of the treating physician, the most common being otolaryngologists and allergy immunologists. Clinical equipoise occurs when there is no basis for one intervention to be regarded as "better" than another. While most guidelines, in general, support the use of topical corticosteroids with or without oral corticosteroids followed by ESS for the majority of unoperated CRSwNP patients, there are situations of clinical equipoise that arise particularly in CRSwNP who have failed surgery or those with severe comorbid conditions. In the shared decision-making process, clinicians and patients must consider symptomatology, goals, comfort, compliance, treatment efficacy, and treatment cost when determining the initial choice of therapy and escalation of therapy with the potential use of multiple modalities for recalcitrant CRSwNP. A summary of salient considerations that might constitute shared decision-making is presented in this summary.

Sclerotherapy for Hereditary Hemorrhagic Telangiectasia-Related Epistaxis: A Systematic Review.

OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is a common inherited condition characterized by mucosal telangiectasias, recurrent epistaxis, and arteriovenous malformations. HHT results in detriment to quality of life. Morbidity and mortality result from severe anemia. Conventional interventions for HHT-related epistaxis include nasal packing, diathermy, lasers, coblation, microdebridement, bevacizumab (topical and systemic), as well as septodermoplasty and nasal closure. Sclerotherapy has been recently described in the literature as a novel approach to HHT-related epistaxis. We hypothesize that sclerotherapy is an effective treatment for HHT-related epistaxis and improves upon the current standard of care for this disease. METHODS: A systematic review was conducted to study sclerotherapy for treating HHT-related epistaxis. Ovid MEDLINE, Ovid EMBASE, Scopus, and Web of Science were searched. Articles were evaluated and excluded according to PRISMA guidelines and reviewed by 2 authors. Reported variables included number of injections, months of follow up, changes in Epistaxis Severity Score, previous treatments used to control epistaxis, and post-injection side effects. RESULTS: Seven studies with a total of 196 patients met inclusion criteria. Three studies reported significant improvement as measured by the Epistaxis Severity Score scale. One reported improvement through subjective patient surveys and others used the Bergler-Sadick scale to measure frequency and intensity of epistaxis. All studies reported improvement in HHT-related epistaxis. The lack of uniform reporting measures however precluded formal meta-analysis. CONCLUSIONS: Based on limited data, sclerotherapy appears to be effective for treating HHT-related epistaxis and offers promise for treating this recalcitrant condition. However, larger, prospective, multi-centered studies using universally validated instruments for epistaxis are needed to definitively evaluate outcomes from sclerotherapy.

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.

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.

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.

Outcomes of limited versus extensive surgery for chronic rhinosinusitis: A systematic review and meta-analysis.

KEY POINTS: There is no consensus on the extent of appropriate surgery for chronic rhinosinusitis (CRS), particularly CRS without polyps (CRSsNP). There is wide heterogeneity in the definition of "limited" and "extensive" endoscopic sinus surgery (ESS). Studies on the appropriate extent of surgery for CRS are needed.

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.