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254
D. R. Romano et al.
b
Subjective Outcome Measures:
No signicant difference in average nasal obstruction/congestion score
change at 90days (−1.33 vs−0.67, p=0.137) or 6months (−1.06
vs−0.44, p=0.124)
Signicantly greater improvement in mean NOSE score at 6months
(−25.6 vs−12.2, p=0.021)
Objective Outcome Measures:
Signicantly greater improvement in mean bilateral polyp grade at 7
Results
Sham procedure involved
delivery system insertion
without stent placement;
patients were blinded to group
) Additional study procedures
a
A bioabsorbable, self-expanding,
drug-eluting stent placed in the
patient’s bilateral ethmoid cavities
in a clinic setting (Sinuva®,
(p<0.05), 14 (p<0.05), 30 (p<0.05), 45 (p<0.05), 60 (p<0.05), 90
assignment using a blindfold
and noise-cancelling
headphones during the
procedure and subsequent
endoscopic evaluations
1350-μg mometasone furoate in a
polymer matrix, n=53) vs bilateral
sham insertion (n=47)
−0.1, p=0.016), and 180 (−0.71 vs+0.02, p=0.018) days
(−1.0 vs
as determined by the study site investigators; no signicant difference
at 3months as determined by the blinded, 3-member, review panel
(−0.76 vs−0.38, p=0.099)
Signicantly greater improvement in mean VAS score for percentage
ethmoid obstruction, as determined by either the study site investigators
at 7 (p<0.05), 14 (p<0.05), 30 (p<0.05), 45 (p<0.05), 60
(p<0.05), 90 (−21.5 vs+1.3, p=0.001), and 180 (−16.5 vs+4.96,
Intranasal steroid irrigations
and oral steroids were not
permitted in the 2-week period
before the procedure was
performed
A daily steroid spray (100-μg
mometasone furoate, each side,
once daily) was required
p<0.001) days, or the blinded, 3-member, review panel at 3months
(−17.1 vs−5.6, p=0.010)
Safety Results/Adverse Events:
No clinically signicant increases in intraocular pressure or diagnosed
cataract in either one of the groups
Adverse events were similar between groups and included sinusitis,
asthma, headache, epistaxis, presyncope, nasopharyngitis, and upper
respiratory tract infection
during the follow-up period
Intranasal saline irrigation or
spray was encouraged after the
procedure
Steroid nasal rinses were not
allowed during the 90-day
follow-up period; oral inhaled
corticosteroids were allowed
for asthma control
Implants were removed on day
60 to allow blinding of sinus
surgeons (the blinded,
3-member, review panel) to
group assignment in video
recordings of nasal
endoscopies
Patients ≥18years with a CRS diagnosis
who were candidates for revision sinus
surgery (i.e., recurrent CRS symptoms
Multi-center,
double-blind
randomized
Design Primary inclusion/exclusion criteria Intervention/comparison (n
RESOLVE [89,
90]
Study
Table 22.3 (continued)
and bilateral nasal polyposis [with a
grade≥2 on ≥1 side] with ethmoid
obstruction despite an uncomplicated
bilateral ethmoidectomy performed
>3months ago + ongoing intranasal
steroid irrigation or spray + at least 1
course of systemic steroids in the past
6months)
Polyp grade<4 on each side
No immunodeciency, invasive fungal
sinusitis, acute bacterial sinus infection,
type 1 insulin-dependent diabetes, or oral
controlled trial
steroid-dependent condition
No diagnosis of glaucoma, nuclear
sclerotic or cortical cataracts ≥ grade 3,
or posterior subcapsular cataracts
22 Topical Corticosteroid Therapy inRecalcitrant Chronic Rhinosinusitis
Objective Outcome Measures:
Signicantly lower percentage of sinuses having an endoscopic
indication for postsurgical intervention (i.e., scar tissue debridement or
oral steroid treatment), as determined by either the study site
investigators at 30 (16.0 vs 33.3%, 95% CI −27.9 to −6.7%) and 90
(95% CI −21.0 to −2.4%) days, or a blinded independent reviewer at
30days (11.5 vs 32.8%, 95% CI −35.1 to −7.6%)
Signicant difference in mean VAS score for inammation at 30 (23.1
vs 35.6, 95% CI −18.3 to −6.4), but not 90 (26.0 vs 31.9, 95% CI
−11.3 to 0.3) days
Signicantly lower prevalence of restenosed or occluded frontal sinuses
(i.e., frontal sinus patency grade≥1) at 30 (13.3 vs 36.0%, 95% CI
−33.5 to −11.9%) and 90 (23.2 vs 40.6%, 95% CI −28.6 to −6.1%)
days
Signicant difference in average frontal sinus opening diameter at 30
(6.3 vs 4.5mm, 95% CI 1.3 to 2.5mm) and 90 (5.7 vs 4.7mm, 95% CI
0.2 to 1.7mm) days
Signicant difference in mean frontal sinus LM score at 90days (0.7 vs
0.9, 95% CI −0.3 to −0.1)
Safety Results/Adverse Events:
No device-related adverse events
Objective Outcome Measures:
Signicantly lower percentage of sinuses having an endoscopic
indication for postsurgical intervention (i.e., scar tissue debridement or
oral steroid treatment) at 30days, as determined by either the study site
investigators (16.5 vs 41.8%, p<0.0001) or a blinded independent
reviewer (38.8 vs 62.7%, p=0.0070)
Signicant difference in mean VAS score for inammation at 30days
(24.7 vs 41.3, p<0.0001)
Signicantly lower prevalence of restenosed or occluded frontal sinuses
at 30days (21.1 vs 46.1%, p=0.0002)
Signicant difference in average frontal sinus opening diameter at
30days (5.9 vs 4.4mm, p<0.0001)
Safety Results/Adverse Events:
No device-related adverse events
Extent of surgery included at
least a bilateral frontal
sinusotomy (Draf IIa or IIb,
using traditional sinus
instruments, a balloon, or
both), with ≥5-mm frontal
sinus opening
Post-operative care included a
10-day antibiotic course; saline
nasal sprays or irrigation were
encouraged
Oral inhaled corticosteroids
were allowed for asthma
control; after 14days, steroid
nasal sprays were permitted
Implants were removed on
day-21 to allow blinding of a
sinus surgeon (the blinded
independent reviewer) to group
assignment in video recordings
of nasal endoscopies
Extent of surgery included at
least a bilateral frontal
sinusotomy (Draf IIa or IIb,
using traditional sinus
instruments, a balloon, or
both), with ≥5-mm frontal
sinus opening
Post-operative care included a
10-day antibiotic course; saline
nasal sprays or irrigation were
encouraged
Oral inhaled corticosteroids
were allowed for asthma
control; after 14days, steroid
(continued)
nasal sprays were permitted
Implants were removed on
day-21 to allow blinding of a
sinus surgeon (the blinded
independent reviewer) to group
assignment in video recordings
of nasal endoscopies
255
A bioabsorbable, self-expanding,
drug-eluting stent placed in the
patient’s left or right frontal sinus
opening (Propel® contour, 370-μg
mometasone furoate in
polylactide-co-glycolide [PLGA],
n=80) vs surgery alone without
stent on the other side (n=80)
(Intrapatient comparison, with
Adult patients undergoing endoscopic
sinus surgery for CRSwNP or CRSsNP
Evidence of bilateral frontal sinus
disease on computed tomography
imaging (i.e., LM score≥1 per side)
No immunodeciency, invasive fungal
sinusitis, acute bacterial sinus infection,
type 1 insulin-dependent diabetes or oral
steroid-dependent condition
Multi-center,
single-blind
randomized
controlled trial
Luong, etal.
(2018) [74]
treatment side randomized)
A bioabsorbable, self-expanding,
drug-eluting stent placed in the
patient’s left or right frontal sinus
opening (Propel® mini, 370-μg
mometasone furoate in
polylactide-co-glycolide [PLGA],
n=67) vs surgery alone without
stent on the other side (n=67)
(intrapatient comparison, with
Adult patients undergoing endoscopic
sinus surgery for CRSwNP or CRSsNP
Evidence of bilateral frontal sinus
disease on computed tomography
imaging (i.e., LM score≥1 per side)
No immunodeciency, invasive fungal
sinusitis, acute bacterial sinus infection,
type 1 insulin-dependent diabetes, or oral
steroid-dependent condition
Multi-center,
single-blind
randomized
controlled trial
Smith, etal.
(2016) [75]
treatment side randomized)
256
b
Results
Subjective Outcome Measures:
Septoplasty was permitted for
Signicant difference in the average total nasal symptoms (5.47 vs
6.41, p=0.001) and nasal obstruction scores (0.92 vs 1.35, p<0.01) at
8weeks; no signicant differences in other average nasal symptom
scores
Objective Outcome Measures:
Signicant difference in mean LKES at 4 (3.21 vs 3.80, p=0.001), 8
(1.96 vs 2.77, p<0.001), and 12 (1.05 vs 2.05, p<0.001) weeks;
severe nasal septal deviation
A stent was placed in the
frontal recess if the frontal
sinus was well aerated with a
frontal ostium diameter of
≥10mm in the anterior–
posterior direction
subscores for crusting at 2 (1.53 vs 0.98, p<0.001) and 8 (0.20 vs 0.36,
p<0.01) weeks; scarring at 4weeks (0.26 vs 0.41, p<0.05); discharge
at 12weeks (0.30 vs 0.73, p<0.001); and edema at 2 (1.35 vs 1.65,
p<0.01), 4 (0.95 vs 1.30, p<0.001), 8 (0.74 vs 1.03, p<0.01), and 12
(0.65 vs 1.00, p<0.01) weeks; no signicant differences in other
endoscopic scores
No signicant difference in the total nasal volume or resistance,
Post-operative care included
saline nasal sprays or
irrigations, and mucolytics and
leukotriene receptor
antagonists if medically
indicated
Steroid nasal sprays were
vs 35.0, p=0.032) sinuses at
minimal cross-sectional area, or nasal nitric oxide levels at 2, 4, 8, or
12weeks
Signicantly lower median disease volumetric score in the ethmoid
(25.0 vs 30.0, p=0.011) and frontal (31.0
8weeks
Signicantly lower median eosinophil count in the ethmoid sinus
mucosa at 4weeks (30.0 vs 60.0, p=0.011)
Safety Results/Adverse Events:
allowed after surgery; oral
steroids were not permitted
during the follow-up period
No signicant difference in morning plasma cortisol levels at 4 or
12weeks
No device-related adverse events
D. R. Romano et al.
) Additional study procedures
a
A bioabsorbable, drug-eluting stent
placed in the patient’s left or right
ethmoid sinus cavity ± a second
stent in the frontal recess
(Xiangtong®, 652-μg mometasone
18 to 65-year-old patients undergoing a
full house endoscopic sinus surgery,
endoscopic middle turbinate resection,
and polypectomy for bilateral eCRSwNP
(dened as CRSwNP in which polyp
Design Primary inclusion/exclusion criteria Intervention/comparison (n
Multi-center,
single-blind
randomized
controlled trial
Study
Wang, etal.
Table 22.3 (continued)
(2023) [76]
furoate in polylactide-co-glycolide
[PLGA], n=95) vs surgery alone
without stent on the other side
(n=95)
(intrapatient comparison, with
treatment side randomized)
tissue shows either (1) proportion of
eosinophils >27% of total inltrating
cells or (2)>55 eosinophils/hpf)
No cataract, glaucoma,
immunodeciency, acute fungal sinus
infection, acute bacterial sinus infection,
an oral steroid-dependent condition, or
severe diabetes or hypertension
22 Topical Corticosteroid Therapy inRecalcitrant Chronic Rhinosinusitis
Objective Outcome Measures:
Signicantly lower percentage of sinuses meeting criteria for
postsurgical intervention (i.e., endoscopic middle turbinate
lateralization score≥3, or adhesion or polyp score≥2) at 30days, as
determined by either the study site investigators (33.7 vs 66.3%,
p<0.0001) or a blinded, 3-member, review panel (14.38 vs 75.00%,
p<0.0001)
Lower frequency of polyp formation (i.e., polyp grade≥2) at 14
(16.57 vs 44.75%, p<0.0001), 30 (22.65 vs 54.14%, p<0.0001), and
90 (6.78 vs 25.42%, p<0.0001) days, as determined by the study site
investigators
No signicant difference in the percent of sinuses with a lateralized
middle turbinate at 14 (0.00 vs 0.00%), 30 (0.55 vs 0.55%, p=1.00), or
90 (0.00 vs 0.00%) days, as determined by the study site investigators
Signicantly lower percentage of sinus cavities with severe adhesions
at 90 (7.63 vs 25.42%, p=0.0003), but not 14 (0.00 vs 0.00%) or 30
(0.55 vs 2.21%, p=0.0833) days, as determined by the study site
investigators
Safety Results/Adverse Events:
No signicant difference in average intraocular pressure at 14 (15.54 vs
15.68, p>0.05), 30 (15.09 vs 15.30, p>0.05), or 90 (14.97 vs 14.87,
p>0.05) days
No signicant difference in apparent lens opacities at 14, 30, or 90days
No device-related adverse events occurred during the follow-up period
Subjective Outcome Measures:
No signicant difference in mean SNOT-22 scores at 8–10days (29.9
vs 29.1, p=0.9248), 20days (21.6 vs 9.7, p=0.0528), 1month (10.6
vs 7.1, p=0.4871), or 3months (12.0 vs 13.3, p=0.8087)
Objective Outcome Measures:
Signicant difference in mean VAS score for right- and left-sided
middle turbinate lateralization at 8–10days (1.73 vs 0.38, p=0.0399;
2.45 vs 0.43, p=0.0231), but not at 20days (2.00 vs 1.38, p=0.4187;
2.10 vs 2.23, p=0.8853), 1month (3.00 vs 0.80, p=0.1396; 2.38 vs
0.40, p=0.0730), or 3months (1.67 vs 2.20, p=0.7325; 1.17 vs 1.00,
p=0.8666)
Post-operative care included a
7-day antibiotic course
Saline nasal sprays and
intranasal saline irrigations
were allowed before and after
surgery
After 30days, steroid nasal
sprays were permitted
Extent of surgery included ≥ a
total ethmoidectomy, maxillary
antrostomy, and middle
turbinate management
Post-operative care included
oral steroids, antibiotics, and
budesonide irrigations
Spacers were removed at
8–10days to enable blinded
review of nasal endoscopy
video recordings
257
(continued)
Signicantly lower percentage of patients with a perfect-"0” VAS for
left-sided middle turbinate lateralization (i.e., totally medialized middle
turbinate; 27.3 vs 71.4%, p=0.030); no signicant difference on the
right side (36.4 vs 76.9%, p=0.095)
No signicant difference in mean LKES on the left or right at
8–10days (1.45 vs 1.43, p=0.9457; 1.73 vs 1.23, p=0.3436), 20days
(1.70 vs 2.08, p=0.4384; 1.56 vs 2.08, p=0.3144), 1month (1.75 vs
1.60, p=0.8514; 2.28 vs 2.40, p=0.8993), or 3months (1.83 vs 1.50,
p=0.4848; 2.33 vs 1.17, p=0.1204)
A bioabsorbable, drug-eluting stent
placed in the patient’s left or right
ethmoid sinus cavity (BISORB®,
652-μg mometasone furoate in
polylactide-co-glycolide [PLGA],
n=181) vs non-steroid
impregnated, bioabsorbable packing
on the other side (NasoPore®,
n=181)
(intrapatient comparison, with
treatment side randomized)
CRS patients undergoing bilateral
endoscopic sinus surgery
18–65years of age
Bilateral CRSwNP or CRSsNP diagnosis
Not using immunosuppressive agents
No diabetes, glaucoma, acute fungal
sinus infection, acute bacterial sinus
infection, ocular hypertension, or
autoimmune disease
Multi-center,
single-blind
randomized
controlled trial
Huang, etal.
(2022) [77]
A bioabsorbable, self-expanding,
drug-eluting stent placed in the
bilateral middle meatuses (Propel®,
370-μg mometasone furoate in
polylactide-co-glycolide [PLGA],
n=22) vs Merocel® packs wrapped
in non-latex glove material (n=18)
Adult patients undergoing endoscopic
sinus surgery for CRSwNP or CRSsNP
No previous sinus surgery
No immunodeciency, cystic brosis, or
ciliary disorder
Single-center,
single-blind
randomized
controlled trial
Rawl, etal.
(2020) [114]
258
b
Objective Outcome Measures:
Signicantly lower percentage of sinuses having an endoscopic
indication for postsurgical intervention (i.e., adhesion lysis or oral
steroids) at 30days, as determined by majority opinion of a blinded
panel of sinus surgeons (33.3 vs 46.9%, p=0.028); no signicant
Results
Extent of surgery included ≥
difference as determined by the study site investigators (21.9 vs 31.4%,
bilateral ethmoidectomy; other
turbinate medialization
procedures were not permitted
Peri-operative care included a
p=0.068)
Lower frequency of frank polyposis (i.e., polyp grade≥2) at 30days,
as determined by majority opinion of a blinded panel of sinus surgeons
(18.8 vs 34.1%, p=0.002); no signicant difference when using the
scores from the study site investigators (3.8 vs 7.7%, p=0.344)
No signicant difference in the percent of sinuses with a lateralized
middle turbinate at 30days, as per scores from the study site
14-day antibiotic course;
antibiotic treatment for
suspected infections was
permitted during the follow-up
period
Saline nasal sprays and
intranasal saline irrigations
were allowed after surgery
investigators (1.9 vs 6.7%, p=0.125)
Signicantly lower prevalence of dense or severe adhesions at 30days,
as per scores from the study site investigators (4.8 vs 12.5%, p=0.039)
Safety Results/Adverse Events:
No clinically signicant intraocular pressure or lens opacity changes
from baseline
No steroid nasal sprays or oral
steroids were allowed in the
initial 30-day period after
surgery; oral inhaled
corticosteroids were allowed
for asthma control
Endoscopic assessment was
performed on recordings by a
blinded, 3-member, review
panel, and in real time by the
study site investigators
D. R. Romano et al.
) Additional study procedures
a
A bioabsorbable, self-expanding,
drug-eluting stent placed in the
patient’s left or right ethmoid sinus
cavity (Propel®, 370-μg
Adult patients undergoing endoscopic
sinus surgery for CRSwNP or CRSsNP
after failure of conservative management
LM score≥6
Multi-center,
double-blind
randomized
ADVANCE II
[73]
controlled trial
Design Primary inclusion/exclusion criteria Intervention/comparison (n
Study
Table 22.3 (continued)
mometasone furoate in
polylactide-co-glycolide [PLGA],
n=105) vs a non-eluting PLGA
stent placed on the other side
(n=105)
(Intrapatient comparison, with
treatment side randomized)
No immunodeciency, invasive fungal
sinusitis, acute bacterial sinus infection,
type 1 insulin-dependent diabetes or oral
steroid-dependent condition
No diagnosis of glaucoma, cataracts ≥
grade 3, or posterior subcapsular
cataracts
22 Topical Corticosteroid Therapy inRecalcitrant Chronic Rhinosinusitis
Objective Outcome Measures:
Signicantly lower ethmoid sinus inammation, as measured by mean
VAS score, at 21 (23.2 vs 35.3, p=0.0032), 30 (20.2 vs 30.1,
p=0.0011), and 45 (15.9 vs 24.0, p=0.0022) days; no signicant
difference at 7 (29.6 vs 29.4, p=0.6038), 14 (24.7 vs 31.2,
p=0.0780), or 60 (12.0 vs 17.5, p=0.0855) days
Signicantly lower frequencies of polypoid mucosal changes (i.e.,
polyp grade≥1; 18.4 vs 36.8%, p=0.0391) and dense or severe
adhesions (5.3 vs 21.1%, p=0.0313) at 30days
No signicant difference in the percent of sinuses with a lateralized
middle turbinate at 30days (5.3 vs 15.8%, p=0.2188)
Safety Results/Adverse Events:
No device-related adverse events
Oral steroids were not
permitted in the 14-day period
before surgery; steroid nasal
sprays could be used up until
the day before
Extent of surgery included at
least a bilateral maxillary
antrostomy and
ethmoidectomy; other
turbinate medialization
procedures were not permitted
Peri-operative care included
intravenous dexamethasone
administered before the start of
surgery, a 14-day antibiotic
course (amoxicillin-
clavulanate, 875mg–125mg,
every 12hours), and saline
nasal sprays and/or intranasal
saline irrigations as per
preference of the physician
After 30days, clinicians were
permitted to prescribe steroids
if necessary; no steroid nasal
sprays or oral steroids were
allowed in the initial 30-day
period after surgery
259
A bioabsorbable, self-expanding,
drug-eluting stent placed in the
patient’s left or right ethmoid sinus
cavity (Propel®, 370-μg
mometasone furoate in
polylactide-co-glycolide [PLGA],
n=38) vs a non-eluting PLGA stent
placed on the other side (n=38)
(intrapatient comparison, with
Adult patients undergoing endoscopic
sinus surgery for CRSwNP or CRSsNP
after failure of conservative management
LM score≥3 per side
No immunodeciency, allergic fungal
sinusitis, type 1 insulin-dependent
diabetes or oral steroid-dependent
condition
Multi-center,
double-blind
randomized
controlled trial
Murr, etal.
(2011) [72]
treatment side randomized)
of intergroup comparisons, unless otherwise stated
included in the analysis
CI condence interval, CRSwNP/sNP CRS with and without nasal polyposis, eCRSwNP eosinophilic CRSwNP, HR hazard ratio, LKES Lund-Kennedy Endoscopic
Score, LM Lund-Mackay, NOSE Nasal Obstruction Symptom Evaluation, SNOT-22 22-Item Sino-Nasal Outcome Test, VAS visual analog scale
a
b
260
D. R. Romano et al.
postoperative outcomes in blinded, randomized controlled studies [76, 77]. Other
randomized controlled trials have evaluated steroid-impregnated packing materials
[78–84] and calcium alginate packing [85], with mixed results across studies.
Several early studies [86, 87] showed the safety, efcacy, and feasibility of inofce endoscopic steroid-eluting stent placement in the ethmoid cavity of adult
patients with a prior history of sinus surgery. Though there is a case series describing in-ofce placement of absorbable steroid implants in the ethmoid cavity at
5–7days after sinus surgery [87], only one nonabsorbable sinus implant is FDAapproved drug-eluting stent specically developed for in-ofce insertion (Sinuva®).
This sinus implant is a self-expanding stent composed of a mometasone furoateimpregnated polymer, allowing controlled release of 1350 μg of steroid over a
90-day period that was specially designed for in-ofce endoscopic insertion in formerly operated ethmoid cavities, and is intended to be removed at day 90 or before.
Blinded, randomized controlled studies in CRSwNP patients meeting criteria for
revision sinus surgery have shown that in-ofce sinus implant insertion results in
greater improvement in ethmoid obstruction, polyp grade, and NOSE (Nasal
Obstruction Symptom Evaluation) score, compared to sham insertion with continued benet noted at 6-month follow-up [88–90]. Moreover, the percentage of
patients who remained candidates for revision surgery after 90days was considerably reduced with sinus implantation versus placebo (39.0 vs 63.3%, p=0.0004) [88].
A new bioabsorbable nasal mesh (LYR-210®) is currently in phase 3 clinical
testing. This device is a self-expanding, steroid-eluting, elastomeric mesh, intended
for insertion in the middle meatus of CRS patients with no prior history of sinus
surgery, and delivers 2500μg or 7500μg of mometasone furoate over 24weeks.
Phase 2 study results demonstrated improvement in mean MRI score, patient
reported cardinal symptoms, and SNOT-22, as well as lower utilization of rescue
therapy, at 24weeks when compared to sham insertion [91].
Reported rates of successful deployment of sinus implants are high, and routine
insertion of an implant at the end of surgery is typically straightforward, though
there have been reports of misplaced implants/stents [92]. Studies have shown no
signicant HPA axis suppression or increases in intraocular pressure or cataract
diagnosis with multiple steroid-eluting implants [71, 73, 76, 77, 90, 91]. Devicerelated adverse events are uncommon but can include infection, facial pain/headache, and stent migration with expulsion or oropharyngeal obstruction [93]. These
adverse events should be viewed in context and weighed against possible adverse
outcomes from postoperative interventions (e.g., adhesion lysis or oral steroids) or
primary or revision sinus surgery. The comfort level with in-ofce stent placement
appears to be provider-dependent, with a recent survey showing that in-ofce endoscopic steroid-eluting stent placement is performed by only a minority of rhinologists [94].
There are multiple considerations when determining when to use steroid-eluting
stents in clinical practice. These stents add a considerable expense to patient care
[95] and may be better suited for use in patients at higher risk for surgical or treatment failure. However, subgroup analyses of pooled data from high-quality,
industry- sponsored blinded, randomized, placebo-controlled studies were largely
22 Topical Corticosteroid Therapy inRecalcitrant Chronic Rhinosinusitis
unrevealing as to which specic populations would benet most from steroideluting sinus stents [96–98]. A recent Delphi method study of rhinology experts
revealed general agreement that steroid-eluting stent placement could be considered
in oral steroid-intolerant patients and patients with diabetes (as an alternative to oral
steroids) or extended frontal sinus surgery [99]. Ninety-two percent of experts also
agreed that in-ofce stent placement could be considered in CRSwNP patients with
recurrent stenosis [99]. While drug-eluting stents may have little utility for routine
CRS patients, they are useful tools and benecial in certain scenarios. However,
with the state of the current literature, it is still largely up to individual patients and
clinicians to determine individual risks and benets.
261
Glucocorticoid Insensitivity
One factor that may inuence the efcacy of topical steroid therapy is glucocorticoid resistance. If glucocorticoids are fundamentally ineffective in a subset of
patients with CRS, then better delivery methods will be of little use in these patients.
There are multiple possible mechanisms of glucocorticoid insensitivity in CRS,
including genetic variants in the GR gene [100], disrupted GR function by under- or
overexpression of mucins [101, 102], and P-glycoprotein (a multidrug resistance
protein) overexpression with accelerated efux of intracellular steroid [103].
However, the mechanism that has received the most attention concerns alternative
splicing of the GR pre-mRNA to generate alpha (GRα) and beta (GRβ) isoforms.
GRα is the classical GR isoform that resides in the cellular cytoplasm and mediates
the response to glucocorticoids. Conversely, GRβ does not bind to glucocorticoids,
is only present in the nucleus, and exerts dominant negative effects on GRα as well
as regulates gene expression in a GRα- and steroid-independent manner [28, 29].
Therefore, individual variations in alternative splicing of GR transcripts represent
one hypothesis to explain the poor response to nasal corticosteroids of some patients.
However, current studies have yielded conicting results regarding whether and
how the relative and/or absolute expression of GRα and GRβ is altered in CRSwNP
and CRSsNP tissue relative to control nasal mucosa, following glucocorticoid treatment, and with treatment-resistant CRS [32, 104–113]. Moreover, the comparative
contributions of glucocorticoid resistance and suboptimal topical drug delivery (i.e.,
with simple nasal steroid spray) to the larger problem of refractory CRS are
unknown.
Conclusions
Recalcitrant CRS is the product of an aberrant inammatory response surrounding
the sinonasal mucosa, which results in symptoms that signicantly diminish a
patient’s quality of life. Topical corticosteroids, which provide a localized antiinammatory effect and avoid many of the undesirable side effects of systemic corticosteroids, are an attractive and useful therapy for many of these patients. By
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altering the amount and delivery method of corticosteroid, better topical delivery of
corticosteroids may assist CRS patients with recalcitrant disease, who failed to
respond to initial treatment with intranasal corticosteroid sprays, saline irrigations,
and even surgery. The delivery methods described in this chapter, including intranasal corticosteroid irrigations, exhalation delivery systems, and steroid-eluting
implants, are all useful tools for the treatment of recalcitrant CRS.However, until
more predictive phenotypes or endotypes are described or more robust comparative
RCTs are performed, patients and providers will have to rely on general guidelines,
anecdotal experience, and trial and error in the treatment of this challenging disease.
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