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

; (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.

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.

Exclusion criteria included: (1) systemic corticosteroid

use within 3 months of HPA axis testing (ie, within

the study period)

; 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).

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 (

) serum corti-

sol levels. The normal range for

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.

such, all patients with

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.

Outcomes

The primary outcome measure was

serum cortisol lev-

els. Levels greater than 500 nmol/L indicated no evidence

of HPA axis suppression. An

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

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.

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

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

serum cortisol level was 431.2

146.88 nmol/L. Nineteen patients had

serum cortisol

International Forum of Allergy & Rhinology, Vol. 6, No. 3, March 2016

153