The "real life" efficacy of dupilumab is independent of initial polyp size and concomitant steroids in CRSwNP.

BACKGROUND: Dupilumab significantly improves symptom control in chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with large polyps at the initiation of treatment (total polyp score (TPS) ≥ 5) have been the focus in published studies. Patients with significant burden of disease but small polyps (TPS ≤ 4) have not yet been evaluated for clinical response. This study set out to evaluate the benefit of dupilumab treatment on cohorts of small (TPS ≤ 4) compared to large polyps (TPS ≥ 5). Furthermore, benefit of concomitant oral and/or nasal steroid therapy has been evaluated. METHODS: 97 patients with CRSwNP, who were begun on dupilumab between January 2020 and October 2021, were included. All patients were followed-up for 6 months. At each visit they underwent nasal endoscopy, smell identification tests and filled out validated patient questionnaires. RESULTS: Significant drops in TPS were seen in both patient groups after 6 months of therapy, dropping from a median score of 3 to 0 and from 6 to 2 in patients with small and large polyps respectively. Furthermore, a linear mixed model calculated a drop of 22% and 24% in TPS per month in patients with small and large polyps respectively with no significant difference in rate of decline. Finally the model showed that neither oral nor nasal steroids influenced the rate of response to dupilumab therapy. CONCLUSIONS: Polyp size at the initiation of dupilumab therapy and whether patients continue to take steroid therapy does not appear to influence effectiveness of dupilumab treatment.

The nasal microbiome in patients suffering from non-steroidal anti-inflammatory drugs-exacerbated respiratory disease in absence of corticosteroids.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease phenotypically classified by the absence (CRSsNP) or presence of nasal polyps (CRSwNP). The latter may also be associated with asthma and hypersensitivity towards non-steroidal anti-inflammatory drugs (NSAID) as a triad termed NSAID-exacerbated respiratory disease (N-ERD). The role of the microbiome in these different disease entities with regard to the underlying inflammatory process and disease burden is yet not fully understood. To address this question, we measured clinical parameters and collected nasal samples (nasal mucosal fluids, microbiome swabs from middle meatus and anterior naris) of patients suffering from CRSsNP (n=20), CRSwNP (n=20) or N-ERD (n=20) as well as from patients without CRS (=disease controls, n=20). Importantly, all subjects refrained from taking local or systemic corticosteroids or immunosuppressants for at least two weeks prior to sampling. The nasal microbiome was analyzed using 16S rRNA gene amplicon sequencing, and levels of 33 inflammatory cytokines were determined in nasal mucosal fluids using the MSD platform. Patients suffering from N-ERD and CRSwNP showed significantly worse smell perception and significantly higher levels of type 2 associated cytokines IL-5, IL-9, Eotaxin and CCL17. Across all 4 patient groups, Corynebacteria and Staphylococci showed the highest relative abundances. Although no significant difference in alpha and beta diversity was observed between the control and the CRS groups, pairwise testing revealed a higher relative abundance of Staphylococci in the middle meatus in N-ERD patients as compared to CRSwNP (p<0.001), CRSsNP (p<0.01) and disease controls (p<0.05) and of Lawsonella in patients suffering from CRSwNP in middle meatus and anterior naris in comparison to CRSsNP (p<0.0001 for both locations) and disease controls (p<0.01 and p<0.0001). Furthermore, we observed a positive correlation of Staphylococci with IL-5 (Pearson r=0.548) and a negative correlation for Corynebacteria and Eotaxin-3 (r=-0.540). Thus, in patients refraining from oral and nasal corticosteroid therapy for at least two weeks known to alter microbiome composition, we did not observe differences in microbiome alpha or beta diversity between various CRS entities and disease controls. However, our data suggest a close association between increased bacterial colonization with Staphylococci and decreased colonization by Corynebacteria as well as increased type 2 inflammation.

Chronic rhinosinusitis symptoms differentially impact the likelihood of major depressive disorders.

OBJECTIVES: The extent to which sinonasal symptoms impact the likelihood of major depressive disorders in chronic rhinosinusitis patients with nasal polyposis (CRSwNP) remains incompletely characterized. In this study, we sought to determine whether individual symptom clusters differentially impact the likelihood of depression in a cohort of CRSwNP patients. METHODS: We retrospectively included 77 patients with CRSwNP. The severity of sinonasal symptoms was assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22) and grouped according to a previously validated four-subdomain structure: nasal, otologic/facial pain, sleep, and emotional subdomains. The likelihood of major depressive disorders was assessed using the Patient Health Questionnaire-2 (PHQ-2). The clinical characteristic of symptom severity (nasal polyp size) and disease-specific information, such as the number of previous sinonasal surgeries, were also collected. RESULTS: The sleep subdomain was most strongly associated with the likelihood of major depressive disorders, followed by the otologic/facial pain subdomain, after controlling for demographics and clinical indicators of symptom severity (nasal polyp size). We found a SNOT-22 score ≥ 30.5 to be an accurate indicator of scoring higher than or equal to 2 on the PHQ-2 in CRSwNP patients. This had a sensitivity of 83.33% and a specificity of 75.47%. CONCLUSION: Distinct sinonasal symptom clusters differentially impact the likelihood of depression in CRSwNP patients. Raising awareness for those with severe sinonasal symptomatology might help identify more patients with a higher probability of comorbid depression.Level of Evidence: 4.

A novel electrosurgical divider: performance in a self-controlled tonsillectomy study.

PURPOSE: Tonsillectomies are among the most common surgeries in otorhinolaryngology. A novel electrosurgical temperature-controlled instrument (device) promises rapid tonsillectomies and might reduce postoperative pain, but comparative studies to assess performance are warranted. METHODS: This randomized self-controlled clinical trial was conducted from October 2019 to October 2020 at the Department of Otorhinolaryngology, Head and Neck Surgery of the Medical University of Vienna. Forty-eight patients underwent a tonsillectomy with the device on one side and using cold-steel with localized bipolar cauterization on the other side (control). Main outcomes were the time for tonsil removal (per side) and the time to stop bleeding (per side). Secondary measurements were postoperative pain, assessed once on day 0 and five times on days 1, 3, 5, 7, and 10. Postoperative bleeding episodes and consequences were recorded. RESULTS: Device tonsillectomies were performed significantly faster than controls; the mean surgical time difference was 209 s (p < 0.001, 95% CI 129; 288). Intraoperative blood loss was significantly lower on the device side (all p < 0.05). Postoperative measurements of pain and bleeding were similar for both sides. Two return-to-theatre secondary bleeding events were recorded for the control side. CONCLUSION: The novel electrosurgical temperature-controlled divider reduced the tonsillectomy surgical time and intraoperative blood loss, with no apparent negative effects on postoperative pain or bleeding, compared to a cold-steel tonsillectomy with localized bipolar cauterization. In time-restricted settings, the device could be beneficial, particularly after familiarization with device handling. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03793816.

Ortho- and retronasal olfactory performance in rhinosurgical procedures: a longitudinal comparative study.

PURPOSE: Testing olfaction should be an integral part of a clinical work-up in rhinosurgical procedures. Importantly, intact olfactory experience also includes retronasally perceived odors (retronasal olfaction). This study aimed at comprehensively assessing olfaction in patients undergoing rhinosurgical procedures in a comparative manner and evaluating relations to patient-reported outcome measurements (PROMs). METHODS: Each nostril odor threshold and discrimination, and birhinal identification were tested using Sniffin' Sticks in 14 subjects assigned for septoplasty (SP), 21 for septorhinoplasty (SRP), and 30 for endoscopic sinus surgery (ESS). The 27-Candy-Smell-Test was used to quantify retronasal abilities. Tests were repeated 3 months after surgery. RESULTS: Olfactory dysfunction was preoperatively present in 21% of SP, in 47.6% of SRP, and in 80% of ESS patients. Odor threshold side differences were most frequently found in SRP. Frequently, SRP and ESS patients showed severely impaired retronasal olfaction. Half of included subjects re-visited after 3 months, but olfactory function did not improve overall and rarely on an individual basis to a meaningful extent. Subjective ratings on nasal patency and PROMs were not associated with olfaction nor with changes in olfactory scores. CONCLUSION: Olfactory function can decisively be impaired a priori not only in patients awaiting sinus surgery, but also in those assigned for functional septorhinoplasty. This impairment may not improve in the short term, which has to be taken into account in patient counseling. This study adds to the current literature on olfaction in rhinosurgery with the extension of retronasal testing.

The association between COVID-19 cases and deaths and web-based public inquiries.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) emerged in December 2019 and rapidly spread globally. Since there is still no specific treatment available, prevention of disease spread is crucial to manage the pandemic. Adequate public information is very important. To assess the optimal timing, the aim of this study was to investigate the association between web-based interest and new cases and deaths due to COVID-19. METHODS: Web-based interest for queries related to 'coronavirus' was assessed between 1 January and 19 June 2020, using Google Trends in Australia, Brazil, Canada, Germany, Italy, South Africa, South Korea, Spain, United Kingdom, and the United States of America. Reliability analysis of the used search terms was performed using the intraclass correlation coefficient. To investigate the association between web-based interest and new COVID-19 cases or deaths, the relative search volume was analysed for correlation with new cases and deaths. RESULTS: Reliability analysis revealed excellent reliability for COVID-19 search terms in all countries. Web-based interest peaked between 23 February and 5 April 2020, which was prior to the peak of new infections and deaths in most included countries. There was a moderate to strong correlation between COVID-19 related queries and new cases or new deaths. CONCLUSION: Web-based interest in COVID-19 peaked prior to the peak of new infections and deaths in most countries included. Thus, monitoring public interest via Google Trends might be useful to select the optimal-timing of web-based disease-specific information and preventive measures.

Differences in men and women suffering from CRSwNP and AERD in quality of life.

PURPOSE: While the overall impact of chronic rhinosinusitis (CRS) on patients' health is diverse, many affected individuals have a substantially impaired quality of life (QoL). The aim of this study was to evaluate the impact of sex-associated differences specifically in the subgroups of CRS with nasal polyps (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) by assessing QoL parameters in women and men separately. METHODS: In a retrospective single-center study, 59 patients with CRSwNP (39 males and 20 females) and 46 patients with AERD (18 males and 28 females) were included. Patient-reported outcome measures (PROM) evaluating QoL via the Sino-Nasal Outcome Test-20 German Adapted Version (SNOT-20 GAV) as well as the total polyp score (TPS) were analysed. RESULTS: There was no significant difference in TPS (p = 0.5550) and total SNOT-20 GAV scores (p = 0.0726) between male or female patients with CRSwNP or AERD. Furthermore, no significant sex differences were found within disease groups regarding the subcategories of the SNOT-20 GAV items. CONCLUSION: Thus, quality of life is severely impaired in patients suffering from various forms of CRS regardless of their sex.