2016 Section 5 Green Book

Safety of budesonide irrigations

High-volume sinonasal budesonide irrigations have been shown to be effective and safe in the short-term (less than 8 weeks), including those with challenging phenotypes. 5,13–16 However, the safety of long-term use is less clear. Given that CRS patients often require prolonged daily maintenance therapy using high-volume sinonasal budesonide irrigations to optimize disease control, the objective of this study was to evaluate the impact of long-term budesonide irrigations on the hypothalamic-pituitary-adrenal (HPA) axis. Patients and methods Study design This study was a cross-sectional cohort analysis. Patients who were being managed with twice daily high-volume sinonasal budesonide irrigations for CRS were retrospec- tively identified and recruited from 2 tertiary level rhinology clinics between March 2014 and July 2015. Inclusion crite- ria included: (1) adult patients (age greater than 18 years); (2) a history of a guideline-based diagnosis of CRS 17 ; (3) previous ESS; (4) twice daily high-volume sinonasal budes- onide irrigation (concentration of 1 mg per irrigation; total daily dose of 2 mg); and (5) a minimum of 12 months duration. A total daily dose of 2 mg was chosen as in- clusion criteria so the cohort would represent patients on a high dose of budesonide, assuming that a higher dose would be more likely to reveal associated systemic side ef- fects. Patients were placed on budesonide irrigation at the discretion of the treating physician, based on the degree of sinonasal mucosal inflammation. Patients had been in- creased to twice daily dosing after once daily dosing failed to control these factors. As this is an off-label use of this medication, all patients had previous trialed topical in- tranasal corticosteroid sprays. Patients were required to have a history of ESS to ensure adequate penetration of ir- rigations through the paranasal sinuses to ensure sinonasal exposure to budesonide. 11 Patients began budesonide irri- gations 1 week postoperatively and as such, the date of the previous ESS was chosen as time 0 (Rudmik et al. 18 ). Exclusion criteria included: (1) systemic corticosteroid use within 3 months of HPA axis testing (ie, within the study period) 19 ; and (2) the presence of any of the following comorbid diseases, ciliary dysmotility, cystic fibrosis, oral steroid-dependent inflammatory disease, sarcoidosis, or systemic vasculitis condition. Any systemic corticosteroid use within 3 months has the potential to alter HPA axis testing and provide false positives (ie, patients would appear suppressed when they are not). 19 The institutional “A pRoject Ethics Community Consen- sus Initiative” (ARECCI) (formerly The Alberta Research Ethics Community Consensus Initiative) Ethics Screening Tool categorized this project as a quality improvement and evaluation study, and as such was exempt from institutional ethics. HPA testing Eligible patients were sent for morning ( AM ) serum corti- sol levels. The normal range for AM serum cortisol testing

performed in Alberta Health Services laboratories is 200 to 650 nmol/L. Levels of less than 200 nmol/L warrant further investigation and levels of less than 100 nmol/L are diagnostic of HPA axis suppression. However, in pa- tients on chronic topical steroid therapy, levels of less than 500 nmol/L cannot exclude HPA axis suppression. 19 As such, all patients with AM serum cortisol levels of less than 500 nmol/L were sent for a 250-mg cosyntropin stimu- lation test to rule out exogenous HPA axis suppression. Cosyntropin stimulation tests were considered normal if the 60-minute cortisol level was greater than 500 nmol/L. 19 Outcomes The primary outcome measure was AM serum cortisol lev- els. Levels greater than 500 nmol/L indicated no evidence of HPA axis suppression. An AM serum cortisol level of less than 500 nmol/L with a normal cosyntropin stimu- lation test (ie, cortisol level greater than 500 nmol/L at 60 minutes) indicated no evidence of HPA axis suppres- sion. An AM serum cortisol level of less than 500 nmol/L with abnormal cosyntropin stimulation tests (ie, cortisol level less than 500 nmol/L at 60 minutes) were consid- ered diagnostic of HPA axis suppression. 19 Demographic data was retrospectively collected using a chart review and included the following variables: gender, age, asthma history, allergy history, acetylsalicylic acid (ASA) intol- erance, smoking history, disease with or without nasal polyposis, 22-item Sino-Nasal Outcome Test (SNOT-22) scores, Lund-Mackay scores, and duration of budesonide use. Statistical analysis was performed using Stata statistical software (StataCorp LP, College Station, TX). Descriptive statistics (means, SDs, ranges, and frequencies) and distri- butions were assessed for all outcome variables. Results A total of 35 patients met inclusion and exclusion criteria and were enrolled into the study. No eligible patients re- fused to participate and all of those who were enrolled com- pleted the study. At each follow-up visit, budesonide irri- gation compliance was self-reported by the patients—none reported stopping their irrigations. Table 1 outlines the cohort characteristics. The mean duration of high-volume sinonasal budesonide irrigations prior to AM serum cortisol testing was 38.2 months (2.9 years). The mean SNOT-22 score at presentation was 49.1 ± 21.9. At the time of HPA axis testing, the mean SNOT-22 score was 20.5 ± 16.9. Sixty-two percent of patients were taking concurrent in- haled corticosteroids for the treatment of asthma. None of the patients were prescribed concurrent intranasal or ocu- lar corticosteroids. As per study protocol, no patient used systemic corticosteroids in the study period. HPA axis testing outcomes The mean serum AM serum cortisol level was 431.2 ± 146.88 nmol/L. Nineteen patients had AM serum cortisol

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