Bloque Entornos

in the previous section, the use of standard INCS is recom- mended for the treatment of CRSsNP. Penetration of sprays

TABLE VII-14. Evidence for CRSsNP management with topical nasal corticosteroids (standard delivery with sprays)

Study Year LOE Study design Study groups Clinical endpoint Conclusions

Snidvongs705 _{2011 1a Meta-analysis INCS 1. Symptom scores; 2.}

QoL; 3. Adverse events

INCS improved symptom scores. No change in QoL. No adverse events Kalish706 _{2009 1a Meta-analysis INCS 1. Overall response to}

treatment; 2. Symptoms

Insufficient evidence to demonstrate a clear benefit with INCS. Possible improvement in symptom scores

Mosges714 _{2011 1b DBRCT 16-week course: 1.}

Mometasone furoate 200

μg BID; 2. Placebo

1. Total symptom score; 2. Patient evaluation treatment response; 3. Endoscopy score; 4. Adverse events

No difference in total symptom score between groups. Significant improvement in endoscopic score Zeng715 _{2011 1b RCT,} single-blinded, treatment comparison study 12-week course: 1. Mometasone furoate 200 μg once daily; 2. Clarithromycin 250 mg once daily 1. Symptom score; 2. Endoscopy score; 3. Overall symptom burden score Improvement in symptom scores and endoscopy scores in both groups

Jorissen712 _{2009 1b DBRCT 6-month course, starting 2}

weeks postsurgery: 1. Mometasone furoate 200 μg BID; 2. Placebo 1. Endoscopic score; 2. Symptom scores; 3. Adverse events No significant difference in total endoscopic score or symptom scores between groups

Dijkstra707 _{2004 1b DBRCT After ESS: 1. Fluticasone}

propionate 400μg BID; 2. Fluticasone propionate 800μg BID; 3. Placebo

1. Symptom scores (VAS); 2. Endoscopy score; 3. CT score (LM)

No reduction in recurrence rate of CRS after ESS

Lund708 _{2004 1b DBRCT 20-week course: 1.}

Budesonide 128μg BID; 2. Placebo 1. Combined symptom scores; 2. Individual symptom score; 3. HR-QoL (SF-36); 4. Peak nasal flow

Budesonide improved combined symptom score, individual symptom scores and peak nasal flow. No change in HR-QoL Giger716 _{2003 1b DBRCT 1. Beclomethasone}

dipropionate 200μg BID; 2. Beclomethasone 400μg morning, saline placebo evening 1. Symptom score; 2. Active anterior rhinometry; 3. Acoustic rhinometry; 4. Morning serum; cortisol; 5. Adverse events Significant reduction in symptom scores in both groups, along with other outcome measures

Parikh711 _{2001 1b DBRCT 16-week course: 1.}

Fluticasone propionate 200

μg BID; 2. Placebo

1. Symptom score; 2. Acoustic rhinometry; 3. Endoscopy scores; 4. Middle meatal swabs; 5. Blood tests

No difference between groups in any outcome measures

Qvarnberg281 _{1992 1b DBRCT 12-week course: 1.}

Budesonide 200μg BID; 2. Placebo 1. Symptom scores; 2. X-ray changes; 3. Microbiology No significant differences in treatment outcomes between groups Sykes709 _{1986 1b DBRCT 2-week course: 1. 20μg}

dexamethasone+120μg tramazoline+100μg neomycin; 2. 20μg dexamethasone, 120μg tramazoline; 3. Placebo 1. Proportion of patients with improved symptoms; 2. Nasal airway resistance; 3. Mucociliary clearance; 4. Sinus X-ray; 5. Bacteriology

Significant increase in patients with improved symptoms in both treatment arms. No difference between active treatment groups

beyond the nasal cavities into the paranasal sinuses has been shown to be limited, however, particularly in preoperative

patients.717, 718_{This fact has led to an increased use of novel}

delivery devices to attempt to improve intrasinus corticos- teroid deposition, and thus potentially clinical outcomes.

Thirty articles were reviewed that addressed nonstandard nasal corticosteroid delivery, with 9 articles included in the final analysis (Table VII-15). Three article addressing the use of corticosteroid/saline sinus irrigations met inclusion criteria, all prospective cohort studies. In the largest study

to date, Snidvongs et al.719 _{published a prospective cohort}

of 111 patients, 49 of whom had a diagnosis of CRSsNP (analyzed separately). Treatment was with once-daily nasal irrigations of 1 mg budesonide/betamethasone in 240 mL of normal saline in the immediate postoperative period. Significant improvements were seen in SNOT-20 scores

(2.3±1.1 vs 1.2±0.9), symptom scores (2.5±1.1 vs 1.4

±1.0), and Lund-Kennedy endoscopy scores (4.3 ± 2.0

vs 1.9±1.6). No adverse outcome analysis was reported.

Two smaller studies were published by Sachanandani

et al.720 _{and Steinke et al.,}721 _{of 9 and 5 patients, respec-}

tively. Improvements in disease-specific QoL (SNOT-20), symptom scores and endoscopy scores were shown, but the small patient numbers limit the significance of the conclusions. There have been concerns about the potential for increased systemic absorption with subsequent adrenal suppression with corticosteroid irrigation use, yet 2 studies published to date have shown no evidence of this

problem.722, 723

Two studies were identified investigating the use of

MASTs for corticosteroid delivery. Lavigne et al.710 _ran-

domized 20 patients to receive either 256μg budesonide or

placebo via a unilaterally placed MAST for 3 weeks. The budesonide treatment group had a significant improvement in clinical response scores, as well as significant reductions in tissue biopsy eosinophil counts and IL-4 and IL-5 levels compared with placebo. Reported complications were tube migration (3 patients), epistaxis (3 patients), and

1 case of tube infection. Moshaver et al.724 _{reported a}

prospective pilot cohort study of 13 patients who had bilateral MAST tube placement and once daily irriga- tions of tobramycin (10 mL of 0.8 mg/mL) and 0.4 mL of a mixture containing ciprofloxacin (2 mg/mL) and hydrocortisone (10 mg/mL). Significant improvements in both SNOT-16 and endoscopy scores were seen, which were maintained until the final 16-week follow-up. No treatment complications were noted. A significant issue with this method of drug delivery is the invasive nature of the tube insertion via a surgical inferior antrostomy, and the increased treatment time and cost associated with tube placement.

Hansen et al.725_{published a DBRCT of 20 patients using}

a bidirectional spray device. Patients received a 12-week

course of either fluticasone propionate 400μg or placebo

twice daily. Significant improvements in subjective patient symptom scores and peak nasal flow were seen in the corti- costeroid group. Overall RSOM-31 and endoscopy scores

showed no statistically significant changes, however. The main weakness of this study was the small sample size (only one-half of the subjects required by power calculation). Adverse effects were limited to mild epistaxis, cough, and rhinorrhea. No evidence of adrenal suppression was found. One article was identified investigating the use of

mucosal atomization devices (MADs). Thamboo et al.726

randomized 20 patients in an unblinded treatment compar- ison study to a 12-week course of either 1 mg budesonide via MAD, or 1 mg of budesonide in 120 mL of saline ir- rigations. Clinically significant improvements in SNOT-22 scores were seen in both arms, although only in the MAD group did this reach statistical significance. Importantly, a statistically significant difference in stimulated cortisol was seen in the MAD group at 60 days, although this did not reach formal threshold for diagnosis of adrenal suppression.

Shikani et al.727 _{randomized 17 patients in a small}

unblinded trial to a 6-week course of either a combination of nebulized mometasone and culture-directed antibiotics plus weekly endoscopic-guided placement of mometasone and antibiotic-impregnated hydroxyethylcellulose gel or “standard treatment” of oral culture-directed antibiotics and mometasone sprays. Both treatment groups showed equivalent effects, making it difficult to assess the relative impact of corticosteroids vs the antibiotics from this treatment regime, however.

Finally, Furukido et al.713 _{reported a single-blinded}

RCT utilizing the YAMIK sinus catheter. Twenty-five patients were treated with a 1-month course of weekly irrigations of either betamethasone (0.4 mg/mL) or saline. No difference was seen between treatment groups in either symptom scores or sinus X-ray scores. Treatment-related epistaxis was reported in 4 patients.

r

Aggregate Grade of Evidence: Irrigations – C (Level 4: 3

studies), MAD – N/A (Level 1b: 1 study), MAST tubes – B (Level 1b: 1 study, Level 4: 1 study), YAMIK – N/A (Level 1b: 1 study).

r

Benefit: Irrigations – Improvement in health-related

(HR)-QoL, subjective symptom scores and endoscopic appearance in postoperative patients. MAD – Improve- ment in HR-QoL. MAST – Improvement in HR- QoL, subjective symptom scores, and endoscopy scores. YAMIK – No benefit seen.

r

Harm: Irrigations – minor (epistaxis, nasal irritation).

No evidence of adrenal suppression at studied doses. MAD – Trend toward reduced stimulated cortisol levels. MAST – Invasive insertion, epistaxis. YAMIK – Patient discomfort, epistaxis.

r

Cost: Moderate to high (from US$2.50 per day for budes-

onide respules, MAST US$100 for each tube+variable

costs associated with insertion).

r

Benefits-Harm Assessment: Irrigations – Preponderance

of benefit over harm, with relatively high cost. MAD – Balance of benefit and harm. MAST – Balance of benefit

TABLE VII-15.Evidence for CRSsNP management with topical nasal corticosteroids (nonstandard delivery)

Study Year LOE Study design Study groups Clinical endpoint Conclusions

Thamboo726 _{2014 1b RCT, unblinded Twice daily treatments: 1. 1 mg}

budesonide via mucosal atomization device; 2. 1 mg budesonide in 120 mL saline via large volume irrigation

1. SNOT-22; 2. ACTH stimulation test; 3. Plasma cortisol levels

MAD-delivered budesonide improved SNOT-22. A slight reduction in ACTH-stimulated cortisol levels was seen

Hansen725 _{2010 1b DBRCT Bidirectional spray 12-week}

course: 1. Fluticasone propionate 400μg BID; 2. Placebo

1. RSOM-31; 2. Subjective symptoms; 3. Nasal endoscopy; 4. Peak nasal flow; 5. Acoustic rhinometry; 6. MRI sinuses

Fluticasone improved nasal symptom scores, endoscopic nasal edema, and peak nasal airflow

Furukido713 _{2005 1b RCT,}

single-blinded

1-month course of once-weekly irrigations via YAMIK sinus catheter: 1. Saline solution; 2. Betamethasone (0.4 mg/mL) solution

1. Clinical symptom score; 2. Radiologic (sinus X-ray score); 3. Sinus effusion cytokine levels

No difference between clinical or radiological scores in study groups

Lavigne710 _{2004 1b DBRCT Unilateral MAST catheter with}

3-week daily irrigation with either: 1. 256μg budesonide; 2. Placebo control

1. Nonvalidated clinical response score; 2. Tissue eosinophil counts; 3. Tissue IL-4 and IL-5 levels

Treatment improved clinical response scores and reduced eosinophil counts and IL-4/IL-5 levels Shikani727 _{2013 2b RCT, unblinded 6-week course of oral culture}

directed antibiotics and mometasone spray and: 1. Weekly intrasinus administration of gel impregnated with mometasone and culture-directed antibiotics; 2. nothing

1. Symptom scores; 2. Endoscopy scores; 3. Mucosal biopsy inflammation scores

A combined antibiotic and corticosteroid topical administration protocol is equivalent to standard treatment. Topical treatment did not impact histological score Snidvongs719 _{2012 4 Prospective} case-series Once-daily irrigations of 1 mg budesonide/betamethasone in 240 mL saline

1. Symptom score; 2. SNOT-22; 3. Lund-Kennedy endoscopy score; 4. Need for revision surgery; 5. Need for oral corticosteroids

Improvement in symptom score and SNOT-22 scores in CRSsNP. High tissue eosinophilia predicted better response

Moshaver724 _{2010 4 Prospective,}

cohort, pilot study

Bilateral MAST catheter insertion with 3 weeks’ daily irrigation of Tobramycin (10 mL of 0.8 mg/mL) and CiproxinHCR (0.4 mL of ciprofloxacin 2 mg/mL and hydrocortisone 10 mg/mL) 1. HR-QoL (SNOT-16); 2. Endoscopy scores

Significant reduction in both SNOT-16 and endoscopy scores, continuing to 16-week follow-up

Sachanandani720 _{2009 4 Prospective}

case-series

30-day course of 250μg budesonide diluted into 5 mL of isotonic saline each nostril QID

1. SNOT-20; 2. Adrenal function Topical budesonide improved SNOT-20 scores, and did not affect adrenal function Steinke721 _{2009 4 Prospective, pilot,}

cohort study

3-month course of twice-daily budesonide irrigations (500μg into>100 mL saline)

1. Endoscopy score Budesonide irrigations may improve endoscopy scores

ACTH=adrenocorticotropic hormone; HR=health-related.

and harm. YAMIK – Limited evidence shows preponder- ance of harm over benefit.

r

_{Value Judgments: Early evidence for irrigations is low}

level and there is a higher cost compared to sprays. Strongest evidence of improvement is seen in postop- erative patients.

r

_{Policy Level: Irrigations – Option in postoperative pa-}

tients. MAD – Option. MAST – Option. YAMIK – Rec- ommendation against.

r

_{Intervention: Corticosteroid nasal irrigations are an op-}

tion in CRSsNP. They may be most beneficial in postop- erative patients. The use of MAD or MAST is an option.

Use of the YAMIK device is not recommended based on current evidence.

VII.E.3. CRSsNP Management: Oral

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