Lal, Devyani

AbstractBackgroundBiological 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.MethodsA 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.ResultsSeventy‐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.ConclusionsAlthough 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.

ObjectiveRNA 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.MethodsRNA 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.ResultsCRS 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.ConclusionTissue 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 Evidence3 Laryngoscope, 133:2480–2489, 2023

Abstract Introduction Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and positive sinonasal bacterial cultures may be recalcitrant to topical therapy alone due to the additional local inflammatory burden associated with bacterial infection/colonization. Objective To evaluate sinonasal outcomes in CRSwNP patients with a positive perioperative bacterial culture, who were treated with postoperative intranasal corticosteroids (INCS) alone versus INCS in combination with a short-term course of oral corticosteroids (OCS). Methods This is a retrospective chart review of CRSwNP patients. A total of 59 patients met inclusion criteria, including positive perioperative bacterial culture and treatment with INCS with or without concomitant use of OCS. Two cohorts were formed based on the chosen postoperative medical treatment; 32 patients underwent postoperative INCS alone, while 27 underwent INCS plus a ≤ 2-week course of OCS. The 22-item sinonasal outcome test (SNOT-22) scores and Lund-Kennedy scores (LKS) were assessed preoperatively, and at 2-week, 4-week, and 4 to 6 months after endoscopic sinus surgery (ESS). Results There were no statistically significant differences in postoperative sinonasal symptoms or endoscopic scores between the cohorts treated with INCS plus OCS versus those prescribed INCS alone (p > 0.05). Our regression model failed to demonstrate a relationship between the use of OCS and better sinonasal outcomes at 2-week, 4-week, and 4 to 6 months after ESS (p > 0.05). Conclusion Our study suggests that in a cohort of CRSwNP patients with recent bacterial infections, the postoperative use of combined OCS and INCS did not result in a statistical improvement of endoscopic and symptomatic outcomes over INCS irrigation alone. However, both treatment groups had a clinically significant improvement based on the Minimal Clinically Important Difference.

AbstractBackgroundThe 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.MethodsWe 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.ResultsChronic 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.ConclusionsCompared 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.

Rationale: Immunoglobulin (Ig) G4–related disease (IgG4-RD) reportedly has a strong relationship with adult-onset asthma and periocular xanthogranuloma (AAPOX) and may be linked to sclerosing mucoepidermoid carcinoma (MEC). We present a rare case of IgG4-RD and AAPOX occurring in a patient with resected eosinophilic or oncocytic MEC. Patient concerns: A 52-year-old woman was referred to our rheumatology clinic in 2020 to be evaluated for suspected IgG4-RD. Diagnoses: The patient had diagnoses of periorbital xanthelasmas, worsening glucocorticoid-dependent chronic rhinosinusitis and adult-onset asthma, and cervical lymphadenopathy persisting 2 years after resection of a low-grade MEC of a minor salivary gland. Interventions: Because the patient’s symptomatic relief was glucocorticoid dependent, IgG4-RD was suspected, and she was referred to our medical center. Her amylase and lipase levels were elevated. Serum IgG4 levels were initially within normal limits, but IgG4-RD was diagnosed because of the presence of lymphadenopathy and evidence of pancreatitis, which was shown on positron emission tomography/computed tomography. Furthermore, the IgG4 levels later increased without explanation. After the patient began combination therapy with a glucocorticoid (prednisone) and methotrexate, her symptoms improved but recurred when the daily oral glucocorticoid dosage decreased below 10 mg. An excisional biopsy of her right submandibular gland in 2021 yielded results consistent with IgG4-RD. In addition, AAPOX was diagnosed, given the presence of periocular edema and plaques, adult-onset asthma, and rhinosinusitis. Outcome: The patient was carcinoma free at last follow-up and was receiving medication to treat the other conditions. Lessons: The diagnosis of these 3 concomitant, uncommon entities required approximately 7 years of medical investigations. Clinicians should know that IgG4-RD, AAPOX, and MEC may occur together.

AbstractObjectiveInvasive fungal sinusitis (IFS) in patients with active or recent COVID‐19 have been reported throughout the world. The primary purpose of the systematic review is to describe factors associated with IFS in patients with COVID‐19. The goal of the case series was to also characterize these factors in addition to evaluating the incidence of IFS at our institution after the onset of the pandemic.MethodsA systematic review using the preferred reporting in systematic reviews and meta‐analyses (PRISMA) framework identified publications of IFS cases associated with COVID‐19 (IFSAC). Search terms were “COVID‐19,” “invasive,” “fungal,” and “sinusitis.” IFS cases were evaluated for COVID‐19 status, fungal etiology, comorbidities, treatment, and outcome. A case series of patients at our center with IFS between December 1, 2018 to March 31, 2020 (“pre‐covid”) and April 1, 2020 to August 1, 2021 (“post‐covid”) was also performed with the above parameters.ResultsFourteen studies totaling 206 cases of IFSAC were identified. Most cases came from India (140/206, 68.0%), followed by Egypt (62/206, 30.1%), and North America (4/206, 1.9%). Diabetes was the most common comorbidity (151/206, 73.3%). Recent or prolonged steroid use was noted in 65.0% of cases (134/206). In our series, five pre‐covid and four post‐covid cases were identified. One had recent COVID‐19 infection. Acute myeloid leukemia was the most common pre‐covid comorbidity (3/5, 60.0%). Diabetes was the most frequent post‐covid comorbidity (2/4, 50.0%). Chronic steroid usage was noted in two pre‐covid and one post‐covid cases.ConclusionDiabetes and steroid use are common factors in reported cases of IFSAC. IFS incidence in our case series did not change appreciably after the onset of the pandemic.Level of Evidence: 4.

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.