Abatacept (Cytotoxic T Lymphocyte Antigen 4-Fragment Crystallizable) Reduces Allergic Inflammation of Ovalbumin-Sensitized Mice.

Background Abatacept (Aba) is a cytotoxic T-lymphocyte antigen-4 and fragment crystallizable fusion protein. Aba blocks B7/Cluster of differentiation 28 - cytotoxic T-lymphocyte antigen-4 costimulatory pathway, inhibits cluster of differentiation 4+ T-cell activation, and is used as an anti-inflammatory drug. Objectives We conducted this study to assess the effectiveness of Aba in the treatment of allergic rhinitis (AR) in a mouse model. Methods We divided 40 four-week-old BALB/c mice into four groups: control group ( n = 10), positive control group (AR, n = 10), Aba group (AR + Aba, n = 10), and dexamethasone group (AR + Dex, n = 10). Mice in each group were challenged intranasally with daily ovalbumin (OVA) administration. Episodes of sneezing and nose rubbing were counted. Mice were sacrificed on day 42 and cytokines were measured in nasal lavage fluid. Nasal mucosae of five mice from each group were used for reverse transcriptase-polymerase chain reaction and western blot assay. Samples were collected from five mice from each group for histological analysis. Results Symptoms of AR significantly improved in the AR + Aba and AR + Dex groups compared with the AR group. Fewer eosinophils and goblet cells were seen in the AR + Aba and AR + Dex groups compared with the AR group. Both the AR + Aba and AR + Dex groups showed a significant decrease in nasal T helper 2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13 and T cell activation related IL-17A, and interferon gamma (IFN- γ). Total immunoglobulin (Ig) E and OVA-specific IgG1 levels were also significantly lower in the AR + Aba and AR + Dex groups. OVA-specific IgE level was also significantly lower in the AR + Aba than AR group. Conclusions Aba suppresses allergic inflammation and appears to be a good treatment for AR.

Co-Expression and Localization of Angiotensin-Converting Enzyme-2 (ACE2) and the Transmembrane Serine Protease 2 (TMPRSS2) in Paranasal Ciliated Epithelium of Patients with Chronic Rhinosinusitis

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme-2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) as a primary receptor for invasion. Cell entry by the virus requires the co-expression of these molecules in the host cells. Objective We investigated ACE2 and TMPRSS2 expression and localization in paranasal epithelium of eosinophilic chronic rhinosinusitis (ECRS) patients (n = 38), non-ECRS (n = 31), and healthy controls (n = 25). CRS inflammatory patterns are characterized by the type of cytokines; we investigated whether inflammatory endotypes are associated with cell-entry molecules, as this could be linked to susceptibility to SARS-CoV-2 infection. Methods The ACE2, TMPRSS2, and other inflammatory cytokine mRNA levels were assessed by quantitative RT-PCR. The localizations of ACE2- and TMPRSS2-positive cells were examined with immunofluorescent double-staining using laser scanning confocal microscopy (LSCM). Results The non-ECRS patients showed significantly increased ACE2 and TMPRSS2 mRNA expressions compared to the ECRS patients. The CRS patients’ ACE2 and TMPRSS2 mRNA levels were positively correlated with IFN-γ ( r = 0.3227 and r = 0.3264, respectively) and TNF-α ( r = 0.4008, r = 0.3962, respectively). ACE2 and TMPRSS2 were negatively correlated with tissue eosinophils ( r = −0.3308, r = −0.3112, respectively), but not with IL-13. ACE2 mRNA levels were positively correlated with TMPRSS2 ( r = 0.7478). ACE2 and TMPRSS2 immunoreactivities were localized mainly in the epithelial ciliated cells, as confirmed by co-staining with TMPRSS2 and acetylated α-tubulin, a cilia organelle marker. Using LSCM imaging, we observed higher expressions of these molecules in the non-ECRS patients versus the ECRS patients. Conclusion ECRS patients with type 2 inflammation showed decreased ACE2 and TMPRSS2 expressions in their sinus mucosa. ACE2 and TMPRSS2 regulation seems to be positively related to IFN-γ and TNF-α production in CRS patients; ACE2 and TMPRSS2 were co-expressed in the ciliated epithelium of their paranasal mucosa, implicating the paranasal epithelium as a portal for initial infection and transmission.

Changes in Sleep Quality Following Treatment for Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis

Background Chronic rhinosinusitis (CRS) presents with broad and systemic manifestations, including impaired sleep; however, the impact of CRS treatments upon sleep is unknown. Objective To establish the effect of medical or surgical CRS treatment on subjective and objective sleep metrics for patients not previously diagnosed with sleep apnea. Methods Review of PubMed, Scopus, Web of Science, and the Cochrane Library was performed from the databases’ date of inception through August 13, 2020, for studies evaluating the effect of CRS treatment on sleep quality. All studies reporting on subjective and objective sleep parameters for patients with CRS, with completed pre- and posttreatment data were included. Studies composed of patients with diagnosed sleep apnea were excluded. Results Sixteen unique studies reporting data on a total of 1770 patients (mean age, 50.6 ± 15.6 (n = 1675) years) following treatment for CRS were included. Patient-reported outcome measures, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Fatigue Severity Scale, demonstrated mean posttreatment differences of −2.8 (95% CI: −4.9 to −0.7), −2.4 (95% CI: −3.7 to −1.2), and −1.2 (95% CI: −1.6 to −0.7), respectively. The SNOT-22 and its sleep domain demonstrated a mean posttreatment difference of −23.5 (95% CI: −31.7 to −15.3) and −5.4 (95% CI: −6.8 to −4.0), respectively. EpSS, FSS and SNOT-22 exceeded their respective reported MCID values. Objective findings did not significantly change with treatment; mean difference: AHI: 0.7 (95% CI: −1.5 to 2.9), oxygen nadir: 0.3 (95% CI: −0.4 to 0.9). Conclusions Treatment of CRS may lead to clinically meaningful reduction in disease burden and improvements in both overall sleep quality and patient-reported fatigue. Despite clinically meaningful quality of life improvements, objective sleep parameters did not demonstrate corresponding posttreatment improvements.

Trends in Academic Achievement Within Otolaryngology: Does Fellowship Training Impact Research Productivity?

Background Scholarly productivity and research output vary among different subspecialties. The h-index was developed as a more wholesome metric that measures an author's contribution to literature. Objective Through a web-based cross-sectional analysis, we investigated the differences in scholarly impact and influence of both fellowship and nonfellowship-trained academic otolaryngologists in the United States. A secondary objective was to further understand the output among the larger fellowship fields. Methods A cross-sectional analysis was performed for active faculty otolaryngologists. A total of 1704 otolaryngologists were identified as faculty in residency training programs across the United States. Their h-index and publication data were gathered using the Scopus database. The data were obtained in August 2019 and analysis occurred in January 2020. Results Head and neck surgical faculty (25.5%) had the highest representation with fellowship experience. Among all faculty, there was no statistical difference in the overall average h-index scores when comparing faculty that had fellowship training with those who did not (12.6 and 12.1, respectively, P = .498). Rhinologists had the highest publication output per year at 3.90. Among fellowship-trained faculty, the highest average h-index and total publications were seen in head & neck surgery, while facial plastics had the lowest averages ( P < .001). Conclusions In this study, fellowship-trained faculty had a greater but not significant scholarly impact than nonfellowship faculty. Furthermore, there were significant variations in output among the various subspecialties of otolaryngology. Growing fields, as academic rhinology, are continuing to flourish in robust research productivity and output. This study further demonstrates the potential, growing influence of fellowship training on research involvement and academic advancement within the otolaryngology subspecialties.

Opiate Use After Endoscopic Endonasal Transsphenoidal Surgery

Background The literature on opiate use after endoscopic endonasal transsphenoidal surgery (EETS) is limited. Objective To determine the risk factors for higher opiate use following EETS and the quantity of opiates used after discharge. Methods A retrospective review of 144 patients undergoing EETS from July 2018 to July 2020 was conducted. Patient, tumor, and surgical factors were documented. Pain scores and medications used on postoperative days (POD) 0 and 1, and discharge prescriptions, were recorded. Opiate use was quantified using morphine milligram equivalents (MME) dose. Multiple linear regression determined risk factors independently associated with POD0 to 1 opiate use. Results On POD 0 to 1, mean pain score was 4.9/10 (standard deviation [SD] ± 2.0). Mean acetaminophen use was 3.4 tablets (SD ± 1.6; 650 mg per tablet). Mean opiate use was 35.6 MME (SD ± 36.3), equivalent to 4.7 tablets (SD ± 4.8) of oxycodone 5 mg. Multiple linear regression showed that current smokers required an additional 37.1 MME ( P = .011), and patients with grade 3 intraoperative cerebrospinal fluid leaks required an additional 36.7 MME ( P = .046) on POD0 to 1. On discharge, mean opiate prescription was 117.7 MME (SD ± 102.1), equivalent to 15.7 tablets (SD ± 13.6) of oxycodone 5 mg. Thirty-nine patients (27.1%) did not require prescriptions. Only 10 patients (6.9%) required opiate refill(s) within 30 days after surgery. Conclusion Patients undergoing EETS have higher opiate needs compared to those undergoing endoscopic sinus surgery, although the overall requirements are still considered low. Independent risk factors associated with higher opiate use in the immediate postoperative period included current smokers and grade 3 intraoperative cerebrospinal fluid leaks.

Airway Nitric Oxide in Children with HDM-Induced Allergic Rhinitis

Background Rhinitis is a common problem in children. Airway nitric oxide (NO) was proposed to represent eosinophilic inflammation. Objectives To evaluate airway NO level in children with house dust mite (HDM)-induced allergic rhinitis Methods Children aged 5 to 18 years old with moderate–severe persistent rhinitis and positive result for the HDM nasal provocation test (NPT) was enrolled. The nasal symptoms evaluated by total nasal symptom score (TNSS) and visual analog scale (VAS) were recorded. Skin prick test (SPT) to common aeroallergens, fractional exhaled nitric oxide (FeNO), nasal nitric oxide (nNO), and blood test for specific IgE (sIgE) to HDM was measured. Rhinitis severity was categorized as severe if the VAS score > 7. Results Forty-eight children with HDM-induced allergic rhinitis with the mean age of 9.3 ± 2.4 years were enrolled. nNO levels and VAS score were significantly correlated (R = 0.398, P = .005). Children with severe rhinitis had significantly higher nNO levels than moderate rhinitis (1652.05 vs 941.30 parts per billion [ppb], P = .002), while there was no difference in FeNO level. ROC curve analysis demonstrated the cut-off value of nNO at 1350 ppb (AUC 0.764, 95% CI: 0.616-0.911, P = .002) for detecting severe HDM-induced allergic rhinitis with the sensitivity of 78% and the specificity of 71%. The level of FeNO in children who had HDM mean wheal diameter (MWD) > 8 mm was significantly higher than those with HDM MWD of 3 to 8 mm and those with a negative test (39.7 vs 14.3 vs 14.4 ppb; P = .006, respectively). Children who had sIgE to HDM < 0.35 KUA/L had significantly lower FeNO than those with sIgE to HDM 0.35 to 50 KUA/L and >50 KUA/L (9.5 vs 19.7 vs 40.4 ppb; P = .029, respectively). Conclusions Cut-off value for the diagnosis of severe HDM-induced chronic rhinitis was proposed. Rhinitis children who had a higher degree of HDM sensitization had a higher level of FeNO.

Nasal Nitric Oxide and Nasal Cytology as Predictive Markers of Short-Term Sublingual Allergen-Specific Immunotherapy Efficacy in Children with Allergic Rhinitis

Background Few studies have been conducted on the short-term response to sublingual immunotherapy (SLIT). Objective The purpose of our experimental trial was to evaluate if two markers such as nasal nitric oxide (nNO) and nasal cytology could be useful to identify a precocious clinical efficacy of SLIT treatment. Methods We enrolled 34 children aged 6 to 14 years old with diagnosis of allergic rhinitis (AR) and documented sensitization towards house dust mites. We started allergoid-monomeric tablets immunotherapy along with any conventional therapy for AR and we evaluated at baseline (T0), after one (T1), two (T2), three (T3), and six months (T6) the effects of the treatment through the study of: i) a visual analogue scale (VAS 1-10); ii) measurement of nNO; iii) measurement of FeNO; iv) nasal cytology; v) spirometry; and vi) evaluation of any conventional therapy. Results We observed an improvement in symptoms evaluated by global VAS (T0 vs. T6: 47.13 vs. 17.57; p < .05) and a statistically significant reduction of nNO (1035.2 ± 956.08 vs. 139.2 ± 59.01; p < .05). In this case, significance was reached when the patients completed the 6 months of treatment. Cytological evaluation revealed significant reduction in nasal eosinophils (T0 vs. T6: 87% vs. 16%; p < .01). Moreover, at T0, 56% of patients had also neutrophils that were reduced up to the 8% at T6 (p < .05). Conclusions Our data confirm the effectiveness of SLIT treatment from a clinical perspective and identifies two biomarkers, such as nNO and nasal cytology, as predictive of treatment efficacy in the short term.

Diagnosis and Localization of Cerebrospinal Fluid Rhinorrhea: A Systematic Review

Background Cerebrospinal fluid (CSF) rhinorrhea results from abnormal communications between the subarachnoid and sinonasal spaces. Accurate preoperative diagnosis and localization are vital for positive clinical outcomes. However, the diagnosis and localization of CSF rhinorrhea remain suboptimal due to a lack of accurate understanding of test characteristics. Objective This systematic review aims to assess the diagnostic accuracy of various tests and imaging modalities for diagnosing and localizing CSF rhinorrhea. Methods A systematic review of the MEDLINE and EMBASE databases was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Our search identified 4039 articles—53 cohort studies and 24 case series describing 1622 patients were included. The studies were heterogeneous and had a wide range of sensitivities and specificities. Many specificities were incalculable due to a lack of true negative and false positive results, thus precluding a meta-analysis. Median sensitivities and specificities were calculated for cohort studies of the following investigations: high-resolution computed tomography (HRCT) 0.93/0.50 (sensitivity/specificity), magnetic resonance cisternography (MRC) 0.94/0.77, computed tomography cisternography (CTC) 0.95/1.00, radionuclide cisternography (RNC) 0.90/0.50, and contrast-enhanced magnetic resonance cisternography (CEMRC) 0.99/1.00, endoscopy 0.58/1.00, topical intranasal fluorescein (TIF) 1.00/incalculable, intrathecal fluorescein (ITF) 0.96/1.00. Case series were reviewed separately. Etiology and site-specific data were also analyzed. Conclusion MR cisternography is more accurate than high-resolution CT at diagnosing and localizing CSF rhinorrhea. CT cisternography, contrast-enhanced MR cisternography, and radionuclide cisternography have good diagnostic characteristics but are invasive. Intrathecal fluorescein shows promising data but has not been widely adopted for purely diagnostic use. Office endoscopy has limited data but does not sufficiently diagnose CSF rhinorrhea independently. These findings confirm with current guidelines and evidence.

Effects of Acute Alcohol Intake on Nasal Patency

Background Acute alcohol intake may influence nasal patency; however, there is lack of objective evidence. Objective The aim of this study was to evaluate the effects of acute alcohol intake on nasal patency employing both subjective and objective measures. Methods A total of 31 participants were classified into 2 groups of non-heavy drinkers (n = 17) and heavy drinkers (n = 14). Both groups consumed wine in 1 h and were assessed for subjective nasal symptoms and objective nasal patency, using rhinomanometry and acoustic rhinometry, at baseline and at 0.5, 2, and 6 h post-alcohol consumption. Results Alcohol consumption significantly increased nasal obstruction from baseline values in both heavy and non-heavy drinking groups. Total nasal volume (TNV) and the minimal cross-sectional area (MCA) were significantly decreased and nasal airway resistance (NAR) significantly increased from baseline values by 2 h post-alcohol consumption for both heavy and non-heavy drinking groups ( P < .05). Significant differences were found in TNV, MCA, and NAR between baseline and post-drinking in allergic rhinitis subjects; with no significant differences in MCA and NAR in subjects without allergic rhinitis. Pulse rate (PR) and temperature (T) were elevated, and blood pressure (BP) was decreased after alcohol consumption ( P < .05). Blood alcohol concentration (BAC) was not significantly correlated with nasal patency with regard to any subjective or objective measurement. Conclusion Acute alcohol consumption may impair nasal patency, independent of the amount consumed. Individuals with allergic rhinitis may be more prone to nasal obstruction after alcohol consumption than those without allergic rhinitis.