Efficacy of Topical High Volume Budesonide Nasal Irrigation in Post FESS Patients of Chronic Rhinosinusitis With or Without Nasal Polyposis

Abstract

Chronic rhinosinusitis (CRS) is a chronic inflammatory process of nasal mucosa and paranasal sinuses, lasting more than 12 weeks, without complete resolution of symptoms. CRS is treated medically, followed by Endoscopic sinus surgery (ESS) if necessary, and supplemented by post-operative topical treatment with highly variable clinical outcomes. However, till date there is no consensus on the composition and duration of maximal medical treatment. Despite proven role of topical steroids, the mode of delivery, dose and duration of topical intranasal corticosteroids still remains debatable. Studies found that high volume sinonasal irrigation (> 50 ml) using budesonide is most efficient method but still there is not sufficient data to prove this and results are variable with multiple modifiable factors therefore, this study has been conducted. (1) To determine the difference in mean decrease in Lund-Kennedy endoscopic scores and SNOT-22 scores among post ESS patients with high volume budesonide nasal irrigation nasal cavity and control nasal cavity of chronic rhinosinusitis patients. (2) To determine safety by measuring serum cortisol levels and intra ocular pressure. This is hospital based interventional, randomised, double blind, control trial study. A total of 66 patients of CRS with previous failed medical therapy were included. Same patients nasal cavities were divided into control and case nasal cavities, to avoid demographic bias. All subjects had a baseline SNOT-22 scores (Sino Nasal Outcome Test scores), Lund Kennedy endoscopy score, NCCT PNS score. All patients were undergone ESS procedure. After nasal pack removal, nasal cavities were randomly assigned 1:1 to receive normal saline irrigation (control group) or 1 mg of budesonide irrigation (case group) for transnasal irrigation twice daily for 12 weeks. A total of 66 patients with 132 nasal cavities were included in the study. Out of which 16 were female and 50 were male with mean age 33 year and mean duration of symptoms was 38.19 months. Mean duration of follow up was for 3 months. Mean decrement in SNOT-22 score in control nasal cavity from 52.54(16.309) to 30.06 (18.16) and in endoscopic score from 6.53 (1.33) to 3.93 (1.6) which is statically significant (p value < 0.05) in both scores. Mean decrement in SNOT-22 score in case nasal cavity from 53.73 (15.75) to 21.15 (13.52) and in endoscopic score from 6.74 (1.8) to 2.77 (1.4) which is statically significant (p value < 0.05) in both scores. Decrement in SNOT-22 scores and endoscopy scores in case nasal cavity in comparision to control nasal cavity were compared by student ‘t’ test and found to be statically significant (p value equals to 0.0001). In subjective outcomes 57.57% shows total improvement in control nasal cavities while 72.73% case nasal cavities shows total improvement. Our study shows high volume budesonide irrigation is safe and superior over normal saline irrigation and results were statistically comparable. Still further studies with larger sample size and longer duration of irrigation needed.Based on available evidence, high volume budesonide irrigation is statically safe and superior over normal saline irrigation.

Introduction

Chronic rhinosinusitis (CRS) is a chronic inflammatory process of nasal mucosa and paranasal sinuses, lasting more than 12 weeks, without complete resolution of symptoms [1]. CRS is considered as a spectrum of different diseases with similar clinical presentations that consists of nasal obstruction, rhinorrhea, olfactory changes and facial pain, whose common patho-physiological mechanism is a chronic inflammation [2]. Although not a life-threatening condition, CSR have significant impact on quality of life of affected patients [3]. Till 90′s CRS was treated medically, followed by Endoscopic sinus surgery (ESS) if necessary, and supplemented by post-operative topical treatment with highly variable clinical outcomes [4–6].

Despite proven role of topical steroids, the mode of delivery, dose and duration of topical intranasal corticosteroids still remains debatable [7]. Delivery devices for topical steroid administration are diverse in volume and pressure. Studies found that high volume sinonasal irrigation (> 50 ml) using budesonide is most efficient method but still there is not sufficient data to prove this and results are variable with multiple modifiable and demographic factors therefore, this study has been conducted.

Material and Method

The study include 132 nasal cavities, 66 nasal cavites in each treatment groups at 95% confidence and 80% power to detect the difference of 1.2 ± 1.1 in mean pre and post SNOT-22 and Lund Kennedy scores.

Inclusion Criteria

Patients diagnosed with CRS, with or without nasal polyps (CRSwNP or CRSsNP, respectively) undergoing endoscopic sino-nasal surgery. The diagnosis of CRS was defined according to search criteria suggested by EPOS 2012 [1]. Previously operated FESS cases were not excluded.

Exclusion Criteria

Other benign disease of nasal cavity like inverted papilloma, patients with pre-operative symptoms and signs of Hypothalamus-Pituitary axis (HPA) dysfunction, patients with clinical signs and symptoms of untreated endocrine disorders such as hypothyroidism, hypopituitarism, hypogonadism, patients with a known history of glaucoma, patients taking drugs that affect cortisol synthesis (mifepristomine, itraconazole, ketoconazole, erythromycin, clarithromycin, cimetidine) or protein binding drugs (estrogens and androgens), Pregnant and/or breast feeding woman, presence of multiple co-morbidities such as poorly controlled diabetes, chronic renal failure, hepatic failure, and patient inable to provide informed consent, and patient who were non-compliance/dropped out from followup and irrigation regime were excluded from study.

Study Design

This is hospital based interventional, randomised, double blind, control trial study done in Department of Otorhinolaryngology of Sawai Man Singh Medical College and Attached Group Hospital, Jaipur, Rajasthan, India, from a period of Jan 2016 to July 2017.

Methodology

The following epidemiological characteristics were evaluated: gender, age, type of CSR, presence of comorbidity and number of previous sino-nasal surgeries. Patients were asked to provide a medical history, the prescription and use of antibiotics and/or systemic corticosteroids, or of other medications that might interfere with the treatment of CRS during topical therapy by irrigation was documented. All subjects had a baseline SNOT-22 scores (Sino Nasal Outcome Test scores), Lund Kennedy endoscopy score, NCCT PNS score and serum cortisol and intraocular pressure measurment. All patients were undergone ESS procedure, with removal of all gross polyps and sufficiently widening the natural ostia of all affected sinuses to allow access for topical medication. After nasal pack removal, nasal cavities were randomly assigned 1:1 (using “chit and box” method) to receive normal saline irrigation (control group nasal cavity) or 1 mg of budesonide irrigation (case group nasal cavity) for transnasal irrigation twice daily for 12 weeks. (Fig. 1). Double blinding was done first, at patient level as they were blinded for which irrigative solution was used as control or case group and second, at follow up endoscopic evaluation with scoring was done by other person unknown to the fact of case or control nasal cavity.

Fig. 1.

Patients were instructed to irrigate in Moffat's position (head down and forwards) and to remain in this position for three minutes after irrigation

Statistical Analysis

The subjective outcomes evaluated were subjective improvement post topical therapy by irrigation. In the end patients were asked if there was improvement of their clinical condition (total improvement, partial improvement, no improvement, worsening).

Objective outcomes evaluated were scores of the SNOT-22 questionnaire in Portuguese [8] and endoscopic classification of Lund-Kennedy [9]. These outcomes were quantitatively and qualitatively evaluated. Quantitative evaluation of objective outcomes involved statistical calculations comparing pre- and post-topical therapy by irrigation. For the qualitative evaluation, the following parameters were used: the minimally important difference of SNOT-22 = 14 points [8]; therefore, differences in post–pre scores between − 7 and + 7 were considered as ‘‘no improvement’’. When pre-post difference scores reached values <  − 7, they were considered as ‘‘improvement’’. In the other hand, pre-post differences > 7 were considered as ‘‘worsening’’. Absolute scores of SNOT-22 (Portuguese version) between 0 and 8 are considered normal [10]; thus, when the patient showed a difference value <  − 7 and scores ≤ 8, were considered as ‘‘complete improvement’’.

As to Lund-Kennedy scores, post-pre differences equals to zero were considered as ‘‘no improvement’’, any negative value in the post-pre difference was regarded as ‘‘improvement’’ and any positive value of the difference as ‘‘worsening’’. A post-topical therapy Lund-Kennedy score = zero was considered ‘‘complete improvement’’.

Quantitative data were summarized in form of mean and standard deviation. The difference in mean of two group were analysed using student ‘t’ test, and difference in mean of more than 2 groups (i.e. mean of difference change in a group over the time) were analysed by ANOVA. For all statistical test, p-values < 0.05 were considered as significant.

Qualitative data were summarized in form of proportion. The difference in proportion would be analysed using chi-square test. The level of significance would be kept 95% for all statistical analysis.

Safety Assessment

Safety was assed primarily based on change in plasma cortisol level and intraocular pressure which were measured before starting the intervention as baseline and at the end of 12 week.

Results and Analysis

Out of total 66 patients, 76% were male (n = 50) and 24% were female (n = 16). Mean age was 33 years (range = 15–68) and average duration of symptoms was 38.2 months (range = 4–180). Among 66 patients, two patients (3.03%) were diagnosed with asthma and two with past history of TB (3.03%). To avoid the effect of multiple modifiable factors i.e., age, duration of disease, co morbidities, phenotype of CRS, same patient’s both nasal cavities were randomly selected by chit-box method into control and case nasal cavities. In control group (n = 66), two nasal cavities (3.03%) and in case group (n = 66) three nasal cavities (4.55%) had previously underwent FESS and again present with recurrence of polyposis.

All control and case nasal cavities pre-op SNOT-22 score and endoscopic score was taken as baseline and ESS was performed. Following irrigation regimen in both control and case nasal cavities, follow-up was done at 1 week, 3 week and 12 week period with SNOT-22 score and endoscopic examination.

Comparison of Results in Control and Case Nasal Cavities

Objective Result

The qualitative results were comparable between control nasal cavity to case nasal cavity. For SNOT-22 among normal saline irrigating nasal cavities, 18 (27.3%) reported no improvement; 48(72.7%) reported improvement, out of these 3 (4.54%) were came to normal. While in budesonide irrigating nasal cavities, 8 (12.1%) reported no improvement; 54 (81.8%) reported improvement, with 5 (7.57%) were came to normal.

For Lund-kennedy endoscopic scores among budesonide irrigating nasal cavities 5 (7.57%) shows no improvement; 61 (92.4%) shows improvement, out of which 3 (4.54%) shows complete improvement. When compared with normal saline irrigating nasal cavities 10 (15.1%) shows no improvement; 56 (84.8%) shows improvement with 1 (1.5%) were came normal. (Table 1).

Table 1.

Qualitative results of SNOT-22 and endoscopy scores

Criteria	Groups	Improvement	No improvement (same)	Normal
SNOT-22 score	Case (n = 66)	54 (81.8%)	8 (12.1%)	5 (7.57%)
	Control (n = 66)	48 (72.7%)	18 (27.3%)	3 (4.54%)
Lund-Kennedy score	Case (n = 66)	61 (92.4%)	5 (7.6%)	3 (4.54%)
	Control (n = 66)	56 (84.8%)	10 (15.15%)	1 (1.5%)

In quantitative results SNOT-22 scores decreased in control nasal cavities from mean (SD) 52.54 (16.31) to 30.06 (18.16) with significant p value and in case nasal cavities from 53.73 (15.75) to 21.15 (13.52) with a significant p value. But decrement in case nasal cavities from control nasal cavities is compared by student ‘t’ test and found to be significant with p value equals to 0.0001. (Table 2) Endoscopy scores in control nasal cavities decreased from mean (SD) 6.53 (1.33) to 3.93 (1.6) with significant p value and in case nasal cavities from 6.74 (1.8) to 2.77(1.4) with a significant p value. But decrement in case nasal cavities from control nasal cavities is compared by student ‘t’ test and found to be significant with p value equals to 0.0001. (Table 2).

Table 2.

Quantitative assessment of objective outcomes between control and case nasal cavities

Variable	Groups	Pre-op mean (SD)	3 month Mean (SD)	Difference (post–pre) Mean(SD)	P value
SNOT-22	Control	52.54 (16.31)	30.06 (18.16)	− 22.48 (15.99)	0.0001
	Case	53.73 (15.75)	21.15 (13.52)	− 32.57 (17.18)
Endoscopy score	Control	6.53 (1.33)	3.93 (1.6)	− 2.59 (1.75)	0.0001
	Case	6.742 (1.8)	2.77 (1.4)	− 3.97 (1.82)

Subjective Results

After topical therapy by irrigation, we asked questions for subjective outcomes to all 66 patients for their both nasal cavities differently after 12 weeks and result are shown in Table 3.

Table 3.

Subjective outcomes after 12 week of irrigation

Subjective outcomes	Control nasal cavities (n = 66)	Case nasal cavities (n = 66)
Total improvement	38 (57.57%)	48 (72.73%)
Partial improvement	22 (33.3%)	13 (19.6%)
Same (no improvement)	6 (9.1%)	5 (7.57%)
Worsen	0	0
Total	66 (100%)	66 (100%)

Safety Assessment

Plasma cortisol levels varied in the normal range in all participants at baseline (normal 5–25 ug/dl). No symptom of adrenal suppression was noted in any of the participants, and no serious adverse events were reported during the study.

Even the intra-ocular pressure was with in normal range (normal 12–22 mmhg) in bedesonide irrigating nasal cavity with a mean of 16.31mmhg in the starting to 16.26mmhg at the end of 3 month. (Table 4).

Table 4.

Safety assessment

Variable		Pre-op	Post-op	P value
IOP	Case nasal cavities	16.315 (2.47)	16.26 (2.59)	0.910
	Control nasal cavities	16.36 (2.68)	16.21 (2.69)	0.749
Serum cortisol		11.41 (3.49)	11.16 (3.67)	0.700

Representative Case

Figure 2

Fig. 2.

A 17 year male diagnosed with bilateral CRSwNP with left side nasal cavity as control nasal cavity and right side nasal cavity as case nasal cavity underwent FESS. Endoscopic scores in both nasal cavity were 7 (a,b) which decrease to 2 (c) after 12 week irrigation with normal saline but decrease to 1 (d) in budesonide irrigated nasal cavity. NCCT preoperatively shows pansinusitis in bilateral nasal cavity, post irrigation scores decrease from 12 to 4 in control nasal cavity and 12 to 3 in case nasal cavity (e,f). SNOT-22 scores in control nasal cavity decrease from 64 to 24 and 64 to 14 in case nasal cavity

Discussion

Chronic rhinosinusitis (CRS) is a common disease resulting from inflammation of the sinonasal mucosa [1, 11]. The objective of CRS treatment is to achieve and maintain control of the disease, which is defined as a state in which patients have no symptoms (or their symptoms do not bother them), combined with nasal endoscopy showing healthy or almost healthy mucosa, and in need only of topical nasal medication [1].

Topical steroid is currently used for treatments of CRS, both chronic rhinosinusitis without polyps (CRSsNP) and chronic rhinosinusitis with polyps (CRSwNP). Topical administration of the drug to inflamed tissue allows an increased local concentration with less systemic absorption, enhancing therapeutic efficacy and prevention of disease relapse without causing the adverse effects of systemic steroids [12].

The edematous inflammatory mucosa and ostiomeatal occlusion often seen in CRS allows 1% of solution volume to enter the sinus cavities before surgery [13]. Recent meta-analyses reveal that topical steroid is effective for sinonasal symptoms for patients with CRSwNP[14] by decreasing polyp size [15, 16], and preventing polyp recurrence[15] but the influence of delivery and sinus surgery are important factors in effectiveness. For this reason, surgery has been considered an essential step in treating CRS, by opening spaces and allow for an adequate distribution of the drug through nasal cavities. [6, 13, 17] Sinus surgery greatly affects the amount of corticosteroid, which comes into contact with paranasal sinus mucosa[12, 13, 18, 19]. Greatest distribution is likely to be achieved when a wide post-ESS corridor has been created regardless of delivery method [12, 17].

Simple nasal delivery methods such as drops, sprays, aerosols, nebulizers and atomizers provide good nasal cavity contact but deliver a low volume of steroid with low pressure. Nasal irrigation, with squeeze bottles and NETI pots, along with direct sinus cannulation, are likely to provide better delivery to the sinuses, especially in the post–sinus surgery setting [18–20]. Devices delivering high volume (neti pots, squeeze bottles, and bulb syringes) with high pressure (squeeze bottles and bulb syringes) improve the delivery of topical medication into the paranasal sinuses and provide better options for treating chronic sinus mucosal inflammation [13, 18, 19, 21, 22]. This high volume irrigation technique have been shown improved delivery of topical medication and recommended for managing patients with CRS, especially those who have undergone endoscopic sinus surgery (ESS) [7, 18, 20, 23–25].

Based on a systemic review of the evidence by Thomas et al.[25] it is recommended that a high-volume delivery technique is the optimal delivery technique and should be used in the topical management of patients with CRS, especially after ESS. Also, guidelines published by the AAOHNS in 2007 and a Cochrane review by Harvey et al. in 2009 have clearly established the benefits of nasal saline irrigation for patients with CRS [11, 26]. Benefits include improved mucociliary function, decreased nasal mucosal edema, and mechanical removal of infectious debris, allergens, mucus, and bacteria from the sinus and nasal cavities. Irrigation may also reduce reliance on other sinus medications, the number and frequency of acute exacerbations of CRS, and symptoms related to CRS.

When mixed with saline and applied topically to the nasal cavity via a nebulizer or irrigation device, budesonide has been shown to reduce polyp size and symptoms in patients with CRSwNP[27] and is thought to deliver a more potent dose of topical steroid to the mucosal lining than other intranasal steroid sprays on the market. Several formulations have been reported and they have been shown to have no significant effect on the hypothalamic-pituitary-adrenal axis even with long-term use [28–30].

In our study of CRSsNP or CSRwNP post ESS nasal cavities by the end of 12 week treatment period assessment of SNOT-22 score and Lund–Kennedy score was significantly reduced in budesonide treated nasal cavities compared with that seen with normal saline treated nasal cavities and the differences was statistically significant.

Recent publised studies [12, 31–34] suggest budesonide irrigation results decrease in SNOT-20, SNOT-22 and endoscopy score. Our results are comparable with published literature on high volume budesonide irrigation.

The early studies involved low-volume irrigation [27]; however, low-volume irrigation methods can-not reach paranasal sinuses [13], and are clearly inferior to high-volume irrigation, [22] as demonstrated in the present study.

Nader et al. [32] in 2010 did a retrospective cohort study in 71 post ESS patients, there was 61% improvement in symptoms by absence of nasal obstruction and anosmia after high volume irrigation and also 61% improvement in endoscopis scores.

Snidvog et al. [17] in 2012 did a prospective study in 111 patients with high volume irrrigation for 3 months and they found 94.6% improvement in SNOT-22 scores with significant p value and 94.6% improvement in endoscpic scores with significant p value. Results found in this study were more than any of other studies.

Jang et al. [33] in 2013 did rerospective study in 60 patients and show 55% improvement in SNOT-20 sores with p < 0.05 and 56% improvement in endoscopic scores but p > 0.05 (p = 0.08).

Eduard et al. [34] in 2015 did an interventional trial in 16 patients and shows 75% improvement in both SNOT-22 and endoscopic scores with significant p value in both score.

Our results comparable with these as there was 81.8% improvement in SNOT-22 score which is more than Eduard et al. [34] and Jang et al. [33] studies but less than Snidvog et al. [17].

For endoscopic results our study shows 92.4% improvement which is more than Eduard et al. [34] and Jang et al. [33] studies but less than Snidvog et al. [17]. (Table 5).

Table 5.

Studies comparing results of high-volume budesonide nasal irrigation in CRSwNP or CRSw/oNP

Study	Study design	N	ESS	Volume	Duration (months)	Subjective result	SNOT-22	Endoscopy
Steinke et al. [31] (2009)	Prospective –Pilot	8		.5 mg x BID	3	VAS 75% improve
Nader et al. [32] (2010)	Retrospective	71	Yes	BID			61% improve	61% improve
Rotenberg et al.[36] (2011)	RCT Double blind Placebo controlled	60	Yes	1 mg/240 ml x BID	12	QOL intergroup- no difference, intragroup-improve		Inter-p > 0.05 intra p < 0.01
Snidvongs et al.[17] (2012)	Prospective	111	Yes	1 mg x BID	3	Likert scale 94.6% improve	94.6% improve, p value significant	94.6% improve, p value significant
Jang et [33] (2013)	Retrospective	60	Yes	0.5 mg/88 ml x BID	13.4		(SNOT-20) 55% improve p < 0.05	56% improve, p = 0.08
Eduardo et al. [34] (2015)	Prospective	16		1 mg/500 ml x BID	3	81.3% improve	75% improve p = 0.006	75% improve, p = 0.01
Our study (2017)	RCT	66	Yes	1 mg/500 ml x BID	3	92.4% improve	8p1.8% improve p < 0.05	92.4% improve p < 0.05

The corticosteroid dose is another variable that should be considered: the studies [12, 17, 34] used 1 mg/day of budesonide or betamethasone, same as in the present study, patients used budesonide 1 mg/day in 500 ml NS with twice a day irrigation results are comparable but in study of Jang et al. [33] they use 0.5 mg in 88 ml and irrigate twice a day there was improvement in SNOT-20 and Lund-Kennedy score but only 55% and 56% respectively. (Table 5).

This finding can corroborate the concept that high-volume nasal irrigations with budesonide solution not only have the advantage of a drug distribution directly to paranasal sinuses, but also bring the benefit mechanical washings with saline. [23]

The impact of surgery can be separated from the steroid irrigation in our study. As both case and control nasal cavities underwent for ESS though there was improvement in both groups but budesonide treated has more significantly decrease in SNOT-22 and Lund –Kennedy score with P < 0.05 for both SNOT-22 and endoscopy score. However, they are not separate treatments but intended to function together as a combined therapy. Delivery of steroid via nasal irrigation combines the general therapeutic goals of topical management in providing pharmaceutical delivery and simultaneous mechanical lavage [23]. Complete sinus distribution is achieved when a wide post-ESS corridor has been created. High-volume positive-pressure solutions allow pharmaceutical preparations to effectively contact sinus mucosa and enhance the mechanical removal of mucus, inflammatory products, and bacteria/biofilms [35]. In a recent Cochrane meta-analysis, trials studying the effectiveness of topical corticosteroids demonstrated patient variation due to surgical status. These differences have been shown to greatly affect topical delivery and distribution [13, 23]. The meta-analysis of topical steroid vs placebo showed that a subgroup of patients with sinus surgery had greater polyp score reduction than those without [15]. When steroid was administered directly to the sinuses for CRSsNP, symptoms were more improved than with simple nasal delivery [14]. Results of our study are supportive and comparable to above mentioned studies.

Other studies have demonstrated that budesonide inhalation suspension neither suppressed the hypothalamic-pituitary-adrenal axis nor decreased serum and 24-h urinary cortisol levels [28, 29], suggesting that irrigation with budesonide was safe to perform in patients with CRS as an alternative to traditional aerosolized steroid sprays or systemic corticosteroids. Our findings for the safety of budesonide transnasal nebulization in patients with CRSwNP are in accordance with the findings of these studies as there was no change in serum cortisol level and IOP level. (Table 6).

Table 6.

Studies showing saftey outcomes

Study	Study design	Sample size	Budesonide irrigation protocol	HPA	IOP
Bhalla et al. [28] (2008)	Retrospective	18	1 mg/240 BIDx 8 weeks	No evidence of HPA suppression on morning cortisol measurement
Welch et al. [29] (2010)	Prospective	10	ESS, 1 mg/ 240 ml BID × 6 week	No effect on morning serum serum cortisol levels or 24-h urinary cortisol
Kristine et al. [36] (2015)	Cross sectional cohort analysis	35	ESS, 2 mg/day X 2.9 years	No change in morning serum cortisol level
Seiberling et al. [42] (2013)	Prospective	18	0.25 mg/240 ml BID × 4 week		No difference in pre- and post-treatment IOP measurements
Our study (2017)	Prospective	66 nasal cavities	ESS,1 mg /500 ml BID × 3 months	No change in morning serum cortisol level	No difference in pre- and post-treatment IOP measurements

Overall steroid exposure is limited in this approach because most patients receive less than 5% of total drug as a residual in their sinuses equivalent to that delivered by simple nasal sprays [23, 37]. This dosage is equivalent to 0.11 to 0.18 mg of prednisone (0.42 mg topically and assumed 30–40% absorption), which is 40-fold to 70-fold lower than the dosage of 7.5 mg that may result in adrenal suppression. This is contrary to studies using nasal drops, which have reported Cushing syndrome [38, 39] and adrenal suppression [40, 41] induced by betamethasone therapy. For more prolonged use of steroid as high volume irrigation and to established safety, there need to be studies for more duration than our study.

Conclusion

Our study shows high volume budesonide irrigation is safe and superior over normal saline irrigation and results were statistically comparable. Still further studies with larger sample size and longer duration of irrigation needed. Based on available evidence, high volume budesonide irrigation is statically safe and superior over normal saline irrigation.

Declarations

Conflict of interest

The authors declare that they have no conflicts of interest.