Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

The TH2-polarizing function of atopic interleukin 17 receptor B-positive dendritic cells up-regulated by lipopolysaccharide.

BACKGROUND: Recent studies suggest that epithelial cell (EC)-derived cytokines contribute to allergic airway disease exacerbation. OBJECTIVE: To confirm our hypothesis that atopic dendritic cells (DCs) are activated to up-regulate the receptors of cytokines that mainly derived from ECs and enhance TH2 responses. METHODS: The expressions of interleukin 17 receptor B (IL-17RB) (IL-25 receptor), membrane-bound ST2 (IL-33 receptor), thymic stromal lymphopoietin receptor (TSLPR), granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR), and several functional markers on CD1c+ monocyte-derived DCs (mo-DCs) were detected by flow cytometry. Lipopolysaccharide (LPS)-activated mo-DCs were cocultured with autologous CD4+ T cells, and cytokine production by these T cells was determined by intracellular flow cytometry. RESULTS: LPS activated both nonatopic and atopic mo-DCs to express a higher level of GM-CSFR but only activated atopic mo-DCs to express increased IL-17RB, which was subsequently activated by IL-25 involved with signal transducer and activator of transcription 5 phosphorylation. In addition, LPS increased the expression of the OX40 ligand (OX40L) but decreased inducible costimulator ligand on atopic CD86+ mo-DCs. More importantly, IL-25 further up-regulated OX40L on atopic CD86+ mo-DCs. After coculturing with LPS-activated mo-DCs from atopic individuals, CD4+ T cells had enhanced inflammatory responses by increased production of IL-4, IL-5, IL-13, and interferon γ (IFN-γ). In contrast, further addition of IL-25 led CD4+ T cells to produce higher level of IL-4 but lower level of IFN-γ. CONCLUSION: Atopic IL-17RB+ DCs can be up-regulated by LPS and promote a TH2-type response, implying that the IL-25/IL-17RB pathway may represent a potential molecular mechanism underlying the regulation of ECs on DCs in allergic airway disease.

Immune responses to different patterns of exposure to ovalbumin in a mouse model of allergic rhinitis.

Allergic rhinitis (AR) has been a significant healthcare burden on individuals and society. However, the detailed effect of different patterns of allergen exposure on the development of AR remains controversial. A mouse model of AR was established to address the complex relationships between allergen exposure and the development of AR. Allergic symptom, OVA-specific IgE in serum and nasal lavage fluid, allergic inflammation in nasal tissues were evaluated after intranasal sensitization and challenge of ovalbumin (OVA) in mice treated with two different doses of allergen for different sensitized durations. Exposure to different doses and sensitized durations of OVA were capable of inducing allergic nasal response. Repetitive OVA exposure in the sensitization phase induced the recruitment of eosinophils and goblet cell hyperplasia. The level of OVA-specific IgE in serum depended on OVA exposure and was mediated in a duration-related manner. In addition, mice treated with low-dose OVA for prolonged duration manifested the major features of human local allergic rhinitis. There were dose- and duration-related effects of allergen exposure on the development of AR. LAR was associated with repetitive exposure to low-dose allergen. Thus, allergen avoidance should be an important aim of AR management.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Pre-operative breathing training based on video learning reduces emergence delirium in preschool children: A randomized clinical trial.

STUDY OBJECTIVE: Emergence delirium is a common complication in preschool children after general anesthesia and may result in undesirable complications. This study aimed to determine whether breathing training after watching an informative video during the pre-operative visit could reduce the incidence of emergence delirium in preschool children after otorhinolaryngologic surgery under general anesthesia. DESIGN: A single-center, double-blinded, randomized controlled trial. SETTING: Perioperative care. PATIENTS: A total of 170 children undergoing otorhinolaryngologic surgery, aged 3-7 years, ASA physical status I or II were involved. INTERVENTIONS: Patients were randomized to receive breathing training during the pre-operative visit (Training group) or to receive pre-operative visit only (Control group) the day before surgery. MEASUREMENTS: Emergence delirium was measured by the Pediatric Anesthesia Emergence Delirium score during the anesthesia recovery time. Data regarding extubation time and post-anesthesia care unit stay time were collected. MAIN RESULTS: Children who received breathing training during the pre-operative visit had a significantly lower incidence of emergence delirium than those who only underwent the pre-operative visit (10.4% vs. 35.1%, P < 0.001). The awakening time score and the maximum score in the post-anesthesia care unit were significantly lower in the training group compared with the control group [4.4 ± 3.4 vs. 6.9 ± 4.2, P < 0.001 and 5.0 (5.0) vs 7.0 (7.0), P = 0.001, respectively]. We found no differences in the extubation time and post-anesthesia care unit stay time between groups. CONCLUSIONS: We concluded that breathing training based on video learning during the pre-operative visit in preschool children undergoing otorhinolaryngologic surgery could significantly decrease the incidence of emergence delirium. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Reference number: ChiCTR1900026162); registered on September 24, 2019.

Removal of tracheobronchial foreign bodies via suspension laryngoscope and Hopkins telescope in infants.

OBJECTIVES: Tracheobronchial foreign body aspiration is a life-threatening accident in infants, and is still a formidable clinical emergency to both otorhinolaryngologists and anesthesiologists. In this study, we attempted to assess the safety and ease of tracheobronchial foreign body removal in infants via suspension laryngoscopy and Hopkins telescopy under general anesthesia with endotracheal intubation. METHODS: The retrospective clinical study from 2006 to 2010 included 50 infants with foreign body aspiration, of whom 35 underwent suspension laryngoscopy and Hopkins telescopy and the other 15 underwent rigid bronchoscopy. All of the procedures were under general anesthesia with endotracheal intubation. RESULTS: All of the patients underwent temporary extubation. The foreign body was successfully removed in 46 cases and was not found in the other 4 cases. The mean operation time in the rigid bronchoscopy group was 13.20+/-9.01 minutes, and that in the Hopkins telescopy group was 5.79+/-3.54 minutes. The oxygen saturation level was below 90% in 17 cases, of which 7 were in the rigid bronchoscopy group and 10 were in the Hopkins telescopy group. The vital signs, including the partial pressure of carbon dioxide in expiratory gas and the heart rate, were stable in all cases. CONCLUSIONS: Foreign body removal in infants via suspension laryngoscopy and Hopkins telescopy under general anesthesia with endotracheal intubation should be promoted, since it is relatively safe and easy for both anesthesiologists and otorhinolaryngologists to perform and has a remarkable success rate.

Frontal sinus cerebrospinal fluid leaks: repair in 15 patients using an endoscopic surgical approach.

OBJECTIVES: To clarify the utility of a safe and effective endoscopic procedure for closing frontal sinus cerebrospinal fluid (CSF) leaks. METHODS: A retrospective review of all 15 patients seen at our hospital from 2002 to 2008 whose CSF leak originated within the frontal sinus or frontal recess. A transnasal endoscopic or combined transfrontal endoscopic approach was used to repair the CSF leak. RESULTS AND SURGICAL OUTCOMES: Four defects originated in the frontal recess and 11 involved the posterior wall of the frontal sinus. Nine patients were repaired by a direct endoscopic approach and 4 patients were repaired after widening the frontal recess endoscopically. Two patients were repaired using the combined transfrontal and transnasal approach. The leak was stopped in 14 cases (93%) after the first operation. One patient (7%) required a second repair 1 month after initial surgery and has remained well after 27 months. Complications included a frontal lobe abscess and a frontal sinus obstructive mucocele. These 2 patients were successfully treated without further complications. Patient follow-up ranged from 4 to 44 months (mean 30 months). CONCLUSIONS: Most frontal CSF leaks can be successfully closed by an endoscopic surgical approach.

Clinical Characteristics and Endoscopic Endonasal Removal of Foreign Bodies within Sinuses, Orbit, and Skull Base.

BACKGROUND: Foreign bodies within the sinuses, orbit, and skull base (FBSOS) are rare; hence, diagnosis and management guidelines are lacking. Endoscopic sinus surgery (ESS) removal is preferred because of the less invasiveness and minimal morbidity. This study was designed to summarize clinical experience with ESS management of FBSOS. METHODS: We retrospectively reviewed clinical manifestations, imaging findings, treatment, and outcomes in consecutive patients with ESS removal of FBSOS between 2004 and 2015 at a tertiary academic medical center. The Chi-square test was performed to compare the infection rate between wooden and nonwooden FBSOS. RESULTS: There were 23 male and five female patients, with median age of 11 years. FBSOS were located within the sinuses (86%), orbit (75%), and skull base/intracranial region (46%). Wooden FBSOS had a significantly higher risk of infection (78%) compared with nonwooden FBSOS (5%, P < 0.05). Contrast-enhanced computed tomography (CT) plus three-dimensional reconstruction was sensitive in all cases. Twenty-seven (96%) FBSOS were removed by ESS alone, while 1 (4%) FBSOS was removed using the combined ESS and lateral cervical approach. Four of the nine intracranial penetrating FBSOS patients had intraoperative cerebrospinal fluid (CSF) leak and received endoscopic CSF leak repair. Twelve (43%) patients suffered complications (meningitis, diplopia, and vision loss). CONCLUSIONS: ESS is a minimally invasive, safe, and promising surgical approach for FBSOS removal. Contrast-enhanced CT is effective in preoperative diagnosis and intraoperative guidance. Wooden FBSOS had higher risk of infection, thus antibiotics are recommended.

Probiotics enhance the effect of allergy immunotherapy on regulating antigen specific B cell activity in asthma patients.

Immune regulatory system dysfunction plays a role in the pathogenesis of asthma. The therapeutic effect of allergic asthma is to be improved. The immune regulatory function of probiotics has been recognized. This study tests a hypothesis that Clostridium butyricum (CB) enhances the effect of allergen specific immunotherapy (AIT) on asthma. In this study patients with allergic asthma were treated with AIT or/and CB for six months. The therapeutic effect and IgE production of the patients were observed. The results showed that administration with AIT alone alleviated the asthma symptoms; but the serum levels of interleukin (IL)-4, IL-5, IL-13 and specific IgE were not altered, which was markedly improved by the administration with CB plus AIT. Such effects were maintained only for two months in the patients treated with AIT alone; but maintained more than 12 months in those patients treated with both AIT and CB. CB facilitated AIT to induce IL-10+ B cells (B10 cells) in asthma patients. AIT/CB therapy converted antigen specific B cells to antigen specific regulatory B cells. Butyrate modulated the gene transcription of IgE and IL-10 in the allergen specific B cells. In conclusion, administration of CB can enhance the therapeutic effect of AIT in the treatment of allergic asthma via facilitating generation of B10 cells.

Extensive versus functional endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps and asthma: A 1-year study.

BACKGROUND: Functional endoscopic sinus surgery (FESS) is considered to be the standard procedure for chronic rhinosinusitis with nasal polyps (CRSwNP). However, for CRSwNP that accompanies asthma, the results are not satisfying. Extensive endoscopic sinus surgery (EESS) aimed at reducing the inflammatory load has been indicated as a viable option for refractory chronic rhinosinusitis. OBJECTIVE: To evaluate the clinical outcomes and safety of EESS (middle turbinate and superior turbinate resection and total ethmoidectomy) for patients with CRSwNP and with asthma. METHODS: This was a prospective, single-institute cohort study conducted in a tertiary teaching hospital. Patients with CRSwNP and with asthma who were proceeding to surgery were enrolled. There were 23 patients in the EESS group and 24 patients in the FESS group. The preoperative disease severity was evaluated by the visual analog scale (VAS), Lund-Kennedy (L-K) endoscopy score, computed tomography Lund-Mackay score, asthma control test (ACT), and pulmonary function test. Clinical outcomes were comparatively evaluated between the two groups after a 1-year follow-up by using the VAS score, the postoperative endoscopic score (E score), L-K score, ACT score, and pulmonary function test. RESULTS: The disease severity (general VAS score, endoscopic L-K score, computed tomography score, ACT score) showed no significant differences between the two groups before surgery (p > 0.05). One year after surgery, both groups achieved significant improvement in the VAS score and endoscopic L-K score. The EESS group showed better improvement in the olfactory VAS score and E score compared with the FESS group (mean [standard deviation] change of olfactory VAS, 6.00 ± 3.67 versus 3.30 ± 3.44, p = 0.015; mean [standard deviation] E score, 0.31 ± 0.18 versus 0.66 ± 0.26, p < 0.001). No significant differences were found in the change of general nasal symptom VAS score, other individual VAS scores (nasal congestion, discharge, headache and/or facial pain), L-K score, ACT score, and pulmonary function between the two groups (p > 0.05). CONCLUSION: EESS for patients with CRSwNP and with asthma may help to improve the subjective olfaction and endoscopic appearance.

Long-term results of endoscopic sinus surgery-oriented treatment for chronic rhinosinusitis with asthma.

OBJECTIVES/HYPOTHESIS: The aims of this study were to evaluate the efficacy of functional endoscopic sinus surgery (FESS)-oriented multimodality treatment in chronic rhinosinusitis (CRS) patients with asthma and its impact on asthma. STUDY DESIGN: Prospective, nonrandomized cohort. METHODS: Twenty-seven CRS patients with asthma who underwent FESS with postoperative topical corticosteroid spray were evaluated preoperatively; 25 of them were evaluated 1 year and 3 years postoperatively. CRS was evaluated by visual analogue scale, clinical control of CRS, and objective measurement endoscopy Lund-Kennedy scores. Asthma was assessed by subjective asthma control test and asthma control level, also by objective antiasthma medication use and pulmonary function tests. RESULTS: VAS scores of general symptoms (8.09 ± 0.87 preoperatively) were significantly improved at 1 year (2.94 ± 2.21) and 3 years (3.77 ± 2.16) postoperation (P = .000). No difference in these items was found between 1 year and 3 years (P = .463). Endoscopy Lund-Kennedy scores at 1 year (4.34 ± 3.09) and 3 years (5.80 ± 3.38) postoperatively were significantly better (9.33 ± 2.03 preoperatively, P = .000), and there was no difference between 1 year and 3 years of follow-up (P > .05). Significantly, asthma control level improved postoperatively (P = .025). However, antiasthma drug and pulmonary function showed no significant change postoperatively (P > .05). CONCLUSIONS: FESS-oriented multimodality treatment improves CRS with asthma significantly and persistently. Asthma control level improved. Antiasthma medication use and pulmonary function remained stable.

Endoscopic sandwich technique for moderate nasal septal perforations.

OBJECTIVES/HYPOTHESIS: The aim of this article was to describe our surgical technique for the treatment of nasal septal perforations with diameters of 1 to 2 cm. STUDY DESIGN: Retrospective clinical research. METHODS: We reviewed 13 patients with moderate nasal septal perforations (1-2 cm diameter) treated with a sandwich technique (bone or cartilage and quadriceps fascia graft as an interposition graft) by an endoscope-assisted intranasal approach from January 2008 to June 2011. Follow-up periods were 3 months. RESULTS: Thirteen patients were treated with the sandwich technique. Twelve cases (92.3%) were completely healed. One case received incomplete closures without any postoperative symptoms. All patients were found not to have any complications after surgery. CONCLUSIONS: The transnasal endoscopic sandwich technique for repairing moderate nasal septal perforation (1-2 cm) has a high success rate and is easy to perform.

[Efficacy of endoscopic sinus surgery-based on multidisciplinary treatment for chronic rhinosinusitis with asthma].

OBJECTIVE: To evaluate the efficacy of endoscopic sinus surgery (ESS)-based on multidisciplinary treatment for patients with chronic rhinosinusitis (CRS) and asthma. METHODS: The study included 25 CRS patients with asthma who received ESS from September 2006 to March 2009, besides surgery, who also used corticosteroid nasal spray, oral macrolide antibiotics and nasal irrigation perioperatively. Evaluation was performed before ESS, 1 year and 3 years post-ESS. Evaluation index included visual analogue scale (VAS) and endoscopy Lund-Kennedy assessment for CRS, and asthma control test (ACT) and pulmonary function tests for asthma. RESULTS: Twenty-three (92%) patients were followed up for 12 months. Twelve (48%) of them were followed up for 36 months. CRS efficacy: VAS of general symptom significantly improved after ESS compared to pre-ESS (8.12 ± 0.60, x(-) ± s), after 1 year (3.20 ± 2.19) and 3 year (3.79 ± 2.32) follow up (both P = 0.000). There was no statistic difference between 1 year and 3 year follow up (P = 0.851). Endoscopy Lund-Kennedy score significantly improved in post-ESS after 1 year (4.35 ± 3.21) and 3 year (5.50 ± 2.64) follow up compared to pre-ESS (9.80 ± 2.10, both P = 0.000), and there was no difference between 1 year and 3 year follow up (P = 0.606). Asthma efficacy: ACT pre-ESS, 1 year and 3 year were 21.96 ± 2.16, 23.61 ± 1.94 and 22.33 ± 3.47, without statistic difference (F = 2.871, P = 0.065). Pulmonary function showed no significant change after surgery (Pre-ESS 74.68 ± 11.09, 1 year 73.27 ± 12.27, 3 year 73.50 ± 7.87, F = 0.076, P > 0.05). CONCLUSIONS: ESS improves CRS with asthma significantly and persistently. Asthma control level, anti-asthma drug dose and pulmonary function remain stable after ESS.

[Transnasal endoscopic frontal sinus surgery using expanded agger nasi approach].

OBJECTIVE: To explore the feasibility of endoscopic modified agger nasi approach for the surgical treatment of frontal sinus diseases. METHODS: The data of patients undergoing modified agger nasi approach for frontal diseases were prospectively collected since January 2009, including demographic data, findings at surgery, presence of postoperative symptoms, endoscopic appearance of the frontal recess and sinus, and complications. RESULTS: Nineteen patients were enrolled from January 2009 to August 2010. Seventeen patients had chronic rhinosinusitis, in which 13 patients (76.5%) completely healed, 3 patients (17.6%) improved and 1 patient (5.9%) failed. Two patients had frontal sinus and anterior ethmoid sinus inverted papilloma, with no recurrence. The patients were followed up from 6 to 24 months, medium 16 months. No severe complication occurred. No frontal recess adhesion was found. Four sides of frontal recess showed stenosis caused by tissue hypertrophy. CONCLUSION: The modified agger nasi approach provides excellent access to frontal recess and frontal sinus, with good effect for preventing re-stenosis after surgery.

[Ophthalmic complication and management of endoscopic sinus surgery].

OBJECTIVE: To investigate the possible reasons and the treating experiences of ophthalmic complications in order to elevate the attention of the nasal endoscopic surgeon. METHODS: This study was involved 8 categories in 22 cases which had typical characteristic of ophthalmic complications of endoscopic sinus surgery, including injury of lamina papyracea, obstructive cyst of frontal and ethmoid sinuses, orbital infection, injuries of lacrimal passages, injury of extraocular muscles, orbital hemorrhage, optic nerve injury and arterial embolism of optic fundi. The patients were given corresponding treatment. RESULTS: Injury of lamina papyracea was cured by medical treatment while orbital infection, injury of lacrimal passages, obstructive cyst of frontal and ethmoid sinuses were completely recovered by endoscopic surgery. In one of the cases, the injured optic nerve had recovered after transnasal optic and orbital apex decompression but the other 6 sides of 6 patients had not been improved. In one case who had suffered from injury of extraocular muscles, their diplopia disappeared mostly, but the other cases had a slight diplopia after surgery. One case who had visual descending caused by orbital hemorrhage recovered. Two cases of visual loss caused by intraorbital hemorrhage and arterial embolism of optic fundi respectively were not improved. CONCLUSIONS: It is very difficult to cure if the patients lose the sight because of optic nerve injury, orbital hemorrhage and the ischemia of orbit, however, if the patients had remnant vision the prognosis should be much better.