Canadian Rhinology Working Group consensus statement: biologic therapies for chronic rhinosinusitis.

BACKGROUND: Recent evidence suggests that biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of chronic rhinosinusitis with nasal polyposis (CRSwNP). There remains a population in CRSwNP that despite medical therapy and endoscopic sinus surgery have persistent signs and symptoms of disease. Therefore, biologics, monoclonal antibody agents, could be beneficial therapeutic treatments for these patients. There have been eight randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL-5R, IL-33, and immunoglobulin (Ig)E. However, there are no formal recommendations for the optimal use of biologics in managing Chronic Rhinosinusitis (CRS) within the Canadian health care environment. METHODS: A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. 17 fellowship trained rhinologists across Canada evaluated the 28 original statements on a scale of 1-10 and provided comments. A rating within 1-3 indicated disagreement, 8-10 demonstrated agreement and 4-7 represented being neutral towards a statement. All ratings were quantitively reviewed by mean, median, mode, range and standard deviation. Consensus was defined by removing the highest and lowest of the scores and using the "3 point relaxed system". RESULTS: After three rounds, a total of 11 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with CRS. CONCLUSION: This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of patients with CRS, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years.

The safety and efficacy of short-term budesonide delivered via mucosal atomization device for chronic rhinosinusitis without nasal polyposis.

BACKGROUND: Budesonide is a potent corticosteroid commonly prescribed for management of inflammation in chronic rhinosinusitis (CRS). The standard for prescribing budesonide is via impregnated nasal saline irrigation (INSI), although recently the mucosal atomization device (MAD) has emerged as a theoretically superior method of distributing medication into the sinuses. The MAD atomizes medication into small droplets and this is thought to enhance absorption and improve bioavailability. However, no studies have shown whether enhanced absorption and improved bioavailability of budesonide via MAD causes adrenal suppression. The objective of this study is to determine whether budesonide via MAD affects the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: Twenty CRS patients were recruited from a tertiary rhinology clinic and randomized to take budesonide (1 mg) via MAD or via INSI twice a day for 60 days. The adrenocorticotropic hormone (ACTH) stimulation test and 22-item Sinonasal Outcomes Test (SNOT-22) questionnaire were administered on days 1, 30, and 60 of the study. Plasma budesonide and cortisol levels were simultaneously quantified using a high-performance liquid chromatography-tandem mass spectrometry technique. RESULTS: There was no indication of adrenal suppression in either group (n = 20) based on ACTH stimulation test results nor was there significant plasma budesonide levels detected in either group. Quality of life, as indicated by SNOT-22, did not differ between groups at 60 days (p = 0.404; 95% confidence interval [CI], -37.2 to 15.9), but SNOT-22 scores for patients using MAD did show statistically significant improvement at 60 days compared to baseline (p = 0.02). CONCLUSION: The MAD is likely a safe and effective method of delivering budesonide to the sinuses in the short term.