Biologics for chronic rhinosinusitis

BACKGROUND: This living systematic review is one of several Cochrane Reviews evaluating the medical management of patients with chronic rhinosinusitis. Chronic rhinosinusitis is common. It is characterised by inflammation of the nasal and sinus linings, nasal blockage, rhinorrhoea, facial pressure/pain and loss of sense of smell. It occurs with or without nasal polyps.   'Biologics' are medicinal products produced by a biological process. Monoclonal antibodies are one type, already evaluated in related inflammatory conditions (e.g. asthma and atopic dermatitis). OBJECTIVES: To assess the effects of biologics for the treatment of chronic rhinosinusitis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; CENTRAL (2019, Issue 9); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 September 2019. SELECTION CRITERIA: Randomised controlled trials (RCTs) with at least three months follow-up comparing biologics (currently, monoclonal antibodies) against placebo/no treatment in patients with chronic rhinosinusitis. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were disease-specific health-related quality of life (HRQL), disease severity and serious adverse events (SAEs). The secondary outcomes were avoidance of surgery, extent of disease (measured by endoscopic or computerised tomography (CT) score), generic HRQL and adverse events (nasopharyngitis, including sore throat). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included eight RCTs. Of 986 adult participants, 984 had severe chronic rhinosinusitis with nasal polyps; 43% to 100% of participants also had asthma. Three biologics, with different targets, were evaluated: dupilumab, mepolizumab and omalizumab. All the studies were sponsored or supported by industry. Anti-IL-4Rα mAb (dupilumab) versusplacebo/no treatment (all receiving intranasal steroids) Three studies (784 participants) evaluated dupilumab. Disease-specific HRQL was measured with the SNOT-22 (score 0 to 110; minimal clinically important difference (MCID) 8.9 points). At 24 weeks, the SNOT-22 score was 19.61 points lower (better) in participants receiving dupilumab (mean difference (MD) -19.61, 95% confidence interval (CI) -22.54 to -16.69; 3 studies; 784 participants; high certainty). Symptom severity measured on a 0- to 10-point visual analogue scale (VAS) was 3.00 lower in those receiving dupilumab (95% CI -3.47 to -2.53; 3 studies; 784 participants; moderate certainty). The risk of serious adverse events may be lower in the dupilumab group (risk ratio (RR) 0.45, 95% CI 0.28 to 0.75; 3 studies; 782 participants; low certainty).  The number of participants requiring nasal polyp surgery (actual or planned) during the treatment period is probably lower in those receiving dupilumab (RR 0.17, 95% CI 0.05 to 0.52; 2 studies; 725 participants; moderate certainty). Change in the extent of disease using the Lund Mackay computerised tomography (CT) score (0 to 24, higher = worse) was -7.00 (95% CI -9.61 to -4.39; 3 studies; 784 participants; high certainty), a large effect favouring the dupilumab group.  The EQ-5D visual analogue scale (0 to 100, higher = better; MCID 8 points) was used to measure change in generic quality of life. The mean difference favouring dupilumab was 8.59 (95% CI 5.31 to 11.86; 2 studies; 706 participants; moderate certainty). There may be little or no difference in the risk of nasopharyngitis (RR 0.95, 95% CI 0.72 to 1.25; 3 studies; 783 participants; low certainty). Anti-IL-5 mAb (mepolizumab) versusplacebo/no treatment (all receiving intranasal steroids) Two studies (137 participants) evaluated mepolizumab. Disease-specific HRQL measured with the SNOT-22 at 25 weeks was 13.26 points lower (better) in participants receiving mepolizumab (95% CI -22.08 to -4.44; 1 study; 105 participants; low certainty; MCID 8.9).  It is very uncertain whether there is a difference in s ymptom severity: on a 0- to 10-point VAS symptom severity was -2.03 lower in those receiving mepolizumab (95% CI -3.65 to -0.41; 1 study; 72 participants; very low certainty). It is very uncertain if there is difference in the risk of serious adverse events (RR 1.57, 95% CI 0.07 to 35.46; 2 studies; 135 participants, very low certainty). It is very uncertain whether or not the overall risk that patients still need surgery at trial end is lower in the mepolizumab group (RR 0.78, 95% CI 0.64 to 0.94; 2 studies; 135 participants; very low certainty). It is very uncertain whether mepolizumab reduces the extent of disease as measured by endoscopic nasal polyps score (scale range 0 to 8). The mean difference was 1.23 points lower in the mepolizumab group (MD -1.23, 95% -1.79 to -0.68; 2 studies; 137 participants; very low certainty). The difference in generic quality of life (EQ-5D) was 5.68 (95% CI -1.18 to 12.54; 1 study; 105 participants; low certainty), favouring the mepolizumab group. This difference is smaller than the MCID of 8 points. There may be little or no difference in the risk of nasopharyngitis (RR 0.73, 95% 0.36 to 1.47; 2 studies; 135 participants; low certainty). Anti-IgE mAb (omalizumab) versus placebo/no treatment (all receiving intranasal steroids) Three very small studies (65 participants) evaluated omalizumab. We are very uncertain about the effect of omalizumab on disease-specific HRQL, severe adverse events, extent of disease (CT scan scores), generic HRQL and adverse effects. AUTHORS' CONCLUSIONS: In adults with severe chronic rhinosinusitis and nasal polyps, using regular topical nasal steroids, dupilumab improves disease-specific HRQL compared to placebo, and reduces the extent of the disease as measured on a CT scan. It probably also improves symptoms and generic HRQL and there is no evidence of an increased risk of serious adverse events. It may reduce the need for further surgery. There may be little or no difference in the risk of nasopharyngitis. In similar patients, mepolizumab may improve both disease-specific and generic HRQL. It is uncertain whether it reduces the need for surgery or improves nasal polyp scores. There may be little or no difference in the risk of nasopharyngitis. It is uncertain if there is a difference in symptom severity and the risk of serious adverse events. We are uncertain about the effects of omalizumab

Invasive Fungal Rhinosinusitis versus Bacterial Rhinosinusitis with Orbital Complications: A Case-Control Study

BACKGROUND: Invasive fungal rhinosinusitis with orbital complications (IFSwOC) is a life-threatening condition. The incidence of mortality has been reported to be up to 80 percent. This study was conducted to determine the risk factors, presentations, clinical, and imaging findings that could help to manage this condition promptly. METHODS: We conducted a case-control study of 100 patients suffering from rhinosinusitis with orbital complications. The risk factors, clinical presentations, radiological findings, medical and surgical managements, durations of hospital stay, and mortality rate data were collected. RESULTS: Sixty-five patients were diagnosed with IFSwOC, while the other thirty-five patients composed the control group. The most important risk factor for IFSwOC was diabetes mellitus. Visual loss and diplopia were the significant symptom predictors. The significant clinical predictors were nasal crust, oculomotor nerve, and optic nerve involvement. The CT findings of IFSwOC were sinus wall erosion and hyperdensity lesions. The mortality rate was 25.71 percent in the IFSwOC group and 3.17 percent in the control group. CONCLUSIONS: Invasive fungal rhinosinusitis with orbital complications is symptomatic of a high mortality rate. The awareness of a patient's risk factors, the presenting symptoms, signs of fungal invasion, and aggressive management will determine the success of any treatment procedures

Total Endoscopic Submandibular Sialoadenectomy Using a 3-Port Supraclavicular Approach: A New Technique

OBJECTIVES: The objective of this pilot study was to report the feasibility and safety of a new 3-port supraclavicular approach in endoscopic submandibular sialoadenectomy. METHODS: We reported the safety, surgical feasibility, and aesthetic features of the total endoscopic submandibular sialoadenectomy (submandibular gland excision) using a 3-port supraclavicular approach in our institute from December 2018 to January 2020. RESULTS: Endoscopic submandibular sialoadenectomy using a 3-port supraclavicular approach was performed in 2 patients with intraglandular sialolithiasis. No major adverse events occurred in this study. The patient's satisfaction score was high (more than 8; range: 0-10). CONCLUSIONS: The 3-port supraclavicular approach submandibular sialoadenectomy is a feasible method that permits a relatively good surgical scarring and minimal adverse effects

The sensitivity and specificity of methylene blue spray to identify the parathyroid gland during thyroidectomy

Background: Hypocalcemia is a common complication of thyroidectomy resulting from an injury to the parathyroid gland. Methylene blue, which is a medication and dye that has been used for more than a century, is safe and readily available. The previous study has found that methylene blue spray on the surgical field is absorbed by the parathyroid gland faster than in the perithyroidal area. This study was aimed to evaluate the diagnostic value of methylene blue spray to identify the parathyroid gland during thyroid lobectomy. Methods: Patients who underwent thyroid lobectomy were recruited. After the recurrent laryngeal nerve was identified, methylene blue was sprayed onto the thyroid bed. After 5 min, the thyroid bed was inspected for areas in which the blue color had been rapidly absorbed. Biopsies were conducted for histopathology at both the stained area and the area in which the color had faded. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results: A total of 47 patients participated in this study. The sensitivity of methylene blue spray to identify the parathyroid gland during thyroid lobectomy was 92.31% (95% CI [63.97-99.81]) and specificity was 56.79% (95% CI [45.31-67.76]). The PPV was 25.53% (95% CI [20.34-31.53]) and NPV was 97.87% (95% CI [87.39-99.67]). There were no patients with post-operative hypocalcemia, allergic reactions to the methylene blue, or methylene blue toxicity. Conclusion: The methylene blue spray could serve as a screening tool for identification of the parathyroid gland

Chronic rhinosinusitis and emerging treatment options.

This review describes the epidemiology and various treatments in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Evidence for short-term use of systemic corticosteroids has been shown to be favorable in CRSwNP, but still limited in CRSsNP. Topical corticosteroids improve symptom scores in both CRS subgroups. The role of microbes in CRS is still controversial. Culture-directed antibiotics are recommended for CRSsNP with exacerbation. Long-term use of low dosage antibiotics is recommended for CRSsNP for their anti-inflammatory effects. Other emerging treatment options are also discussed

The minimum effective dose of abobotulinum toxin A injection for allergic rhinitis: A dose-escalation randomized controlled trial

Objective: To find the lowest effective injection dose of abobotulinum toxin A (Dysport) for allergic rhinitis. Study Design: Dose-escalation randomized controlled trial. Methods: We included all patients aged 18 years or older who had persistent allergic rhinitis and positive allergy skin prick test. The patients were randomly allocated to receive 40, 30, or 20 U of abobotulinum toxin A by injection at the inferior turbinate. We followed up on patients for 12 weeks to evaluate nasal symptoms, ocular symptoms, minimum nasal cross-sectional area as measured using acoustic rhinometry, and complications. Results: Seventeen patients were included in this study, with 7 receiving 20 U of abobotulinum toxin A and 5 each receiving 30 U and 40 U. Abobotulinum toxin A significantly improved nasal congestion, rhinorrhea, sneezing, and loss of smell at 40 U (P < .05) and nasal congestion, sneezing, and loss of smell at 30 U (P < .05). However, at a dose of 20 U, only nasal congestion and loss of smell improved (P < .05). Nasal patency had also significantly improved two weeks after treatment at doses of 40 and 30 U (P < .05). Complications included epistaxis (11.8%) and nasal dryness (23.5%). Conclusion: Abobotulinum toxin A at a dose of at least 30 U effectively reduced most nasal symptoms. Level of Evidence: 2. Trial registration: Clinicaltrials.in.th/ TCTR20200526014

A multicenter survey on the effectiveness of nasal irrigation devices in rhinosinusitis patients

Background: Nasal irrigation is widely used as an adjunctive treatment for rhinosinusitis. However, there is little information available regarding the efficacy of the devices used in this procedure. The objective of this study was thus to evaluate the effectiveness of nasal irrigation devices based on the experiences of patients with rhinosinusitis. Methods: We conducted a multicenter survey study between November 2017 and December 2019. The questionnaire was developed based on the available literature and expert opinion and submitted to the otolaryngology residents and staff of each center as well as those in their networks. Results: Four hundred eighteen patients were enrolled in this study: 76 with acute viral rhinosinusitis (18%), 53 with acute bacterial rhinosinusitis (13%), 156 with chronic rhinosinusitis without nasal polyps (37%), and 133 with chronic rhinosinusitis with nasal polyps (32%). We found that high-volume devices were most effective in helping to clear secretion in patients with acute viral rhinosinusitis, chronic rhinosinusitis without nasal polyps, and acute bacterial rhinosinusitis (P = .017, .009, .002, respectively) and in reducing post-nasal drip in those with acute bacterial rhinosinusitis (P = .040). There were no statistically significant differences among devices in patients with chronic rhinosinusitis with nasal polyps. Conclusions: Nasal irrigation with high-volume devices was an effective treatment for rhinosinusitis and was more effective at clearing nasal secretion and reducing post-nasal drip than that with other types of devices. Level of Evidence: 2C