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Basic Science Study
Comparison of short nozzle and long nozzle
spray in sinonasal drug delivery:
a cadaveric study
Mustafa Kapadia, MBBS, MS(ENT), DNB
1,2
,
Precious Eunice R. Grullo, MD, MPH
1,3,4
, and Muaaz Tarabichi, MD
1,2
Abstract
The aim of this study is to compare the delivery site of topical drugs using the short nozzle and the long nozzle. Fourteen fresh
frozen cadaver heads were obtained. All cadaver specimens underwent bilateral endoscopic wide maxillary antrostomy, frontal
sinusotomy, and complete sphenoethmoidectomy. The right nasal cavity of each cadaver was sprayed with radiolabeled saline
using the short nozzle (short nozzle group), while the left nasal cavity was sprayed using the long nozzle (long nozzle group). The
distribution of radioactive saline within the sinus cavities was determined using single-photon emission computed tomography/
computed tomography. The distribution of the radiolabeled saline in reference with the maxillary line, vestibule, maxillary,
ethmoid, sphenoid, and frontal sinus was compared between the 2 groups using Fisher exact test. The number of specimens that
demonstrated radioactivity above the maxillary line is higher in the long nozzle group (14 cadavers, 100%) compared to short
nozzle group (9 cadavers, 64.3%; p¼.02). There are fewer specimens that demonstrated deposition of radioactive saline in the
vestibule in the long nozzle group (6 cadavers, 42.86%) compared to short nozzle group (13 cadavers, 92.86%; P¼.006).
Compared to short nozzle group, there are more specimens demonstrating radioactivity in the maxillary, ethmoid, sphenoid, and
frontal sinus in the long nozzle group, but the differences were not statistically significant (p¼0.241, 0.347, 0.126, 0.5). Compared
to short nozzle, long nozzle more frequently delivers intranasal drugs beyond the maxillary line and less frequently in the vestibule.
These findings support the hypothesis that the use of long and narrow nozzle, instead of the conventional short nozzle, can
improve sinonasal drug delivery in post-endoscopic sinus surgery nose.
Keywords
intranasal spray, endoscopic sinus surgery, nasal drug delivery
Introduction
Intranasal corticosteroids (INCS) play a significant role in the
medical management of chronic rhinosinusitis (CRS). Several
evidence-based guidelines
1,2
concur in recommending its use
to improve objective and subjective outcomes in CRS with
nasal polyposis. There is evidence supporting the benefit of
INCS in CRS without nasal polyposis but this has been an
inconsistent finding.
1,2
One of the main advantages of INCS is the potential to
achieve high concentration to the ciliated sinonasal mucosa.
However, the complex sinonasal anatomy, aggravated by the
pathology, serves as a barrier to effective sinonasal drug deliv-
ery.
3
The delivery of the INCS from the bottle to the sinonasal
mucosa is not ensured by the direct insertion of a device to the
nostril. Thus, the effectiveness of INCS is not maximized.
Effective sinonasal drug delivery requires adequate access
and appropriate delivery method. To provide adequate access,
sinus surgery is required.
4
Very minimal drug is delivered to
nonoperated sinuses.
5
After sinus surgery, sinonasal drug deliv-
ery is improved.
5
Sinus surgery not only removes the disease
burden but also provides access for the INCS to the reach the
sinuses, thus increasing the effectiveness of INCS.
1,6,7
Different devices have been used to deliver INCS postopera-
tively. Intranasal sprays are commonly used because of the ease
of application and availability of many INCS in this formula-
tion.
4
Intranasal sprays also offer high reproducibility of
1
Tarabichi-Stammberger Ear and Sinus Institute Dubai, United Arab
Emirates
2
Department of Otolaryngology, American Hospital Dubai, United Arab
Emirates
3
Department of Otorhinolaryngology, College of Medicine, University of the
Philippines - Philippine General Hospital Manila, Philippines
4
Department of Otorhinolaryngology, Rizal Medical Center, Pasig, Philippines
Received: March 14, 2019; revised: April 05, 2019; accepted: April 05, 2019
Corresponding Author:
Precious Eunice R. Grullo, MD, MPH, Department of Otorhinolaryngology,
College of Medicine, University of the Philippines-Manila, Taft Ave, Ermita,
Manila, Philippines.
Email: prgrullo@up.edu.ph
Ear, Nose & Throat Journal
2019, Vol. 98(7) E97–E103
ªThe Author(s) 2019
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/0145561319846830
journals.sagepub.com/home/ear
delivered drug dose.
4
However, most commercially available
intranasal spray devices have short nozzles. Commercially
available short nozzles usually deliver drugs in the vestibule
and have limited distribution to the sinus mucosa.
3,7,8
It is our
hypothesis that a longer and narrower nozzle can deliver INCS
to the sinus mucosa up to the olfactory cleft. The aim of this
study is to compare the delivery site of INCS using the short
nozzle and the long nozzle.
Patients and Methods
Cadaver Specimens
The hospital ethics committee approved this study. Fourteen
fresh frozen cadaver heads were obtained. The cadaver speci-
mens were left to thaw for 48 hours at room temperature before
sinus dissection and spraying with radiolabeled saline.
Cadaver Dissection
All cadaver specimens underwent bilateral endoscopic wide
maxillary antrostomy, frontal sinusotomy, and complete sphe-
noethmoidectomy. The cadaver dissection was performed by
multiple practicing otolaryngologists who were instructed on
the technique, supervised, and assisted by the first and third
authors during hands-on training course on endoscopic sinus
surgery. After dissection, all cadaver heads were inspected to
ensure completeness of endoscopic sinus surgery. Cadavers
with septal deviation were excluded from the study.
Administration of Radiolabeled Saline
The contents of a commercially available steroid nasal spray
bottle was emptied and replaced with 10 mL of normal saline
mixed with 15 mCi of Technetium-99m. A commercially avail-
able short nozzle (Figure 1) and a custom-made long nozzle
(Figure 2) were connected to the nasal spray bottle.
Each cadaver head was secured in a position with the
faceup oriented parallel to the ground. Priming of nasal
sprays was done by releasing 2 to 3 sprays until fine mist
appeared. To minimize bias, only one author administered
the radiolabeled saline on both sides in all the cadaver
heads.
The right nasal cavity of each cadaver was sprayed using the
short nozzle (short nozzle group), while the left nasal cavity
was sprayed using the long nozzle (long nozzle group). Table 1
summarizes the characteristics of the short and long nozzle.
Both nozzles have similar nozzle orifice diameter. On the right
side, the short nozzle was inserted 2 cm into nasal vestibule
until its shoulder. The short bottle was angled at 45from the
nasal floor and 15from the nasal septum. Two spray puffs
were administered delivering 0.14 mL of radioactive saline per
spray. On the left side, the long nozzle was inserted 3.5 cm
from the limen nasi, at 45angle from the nasal floor and 15
from the nasal septum. The spray bottle was held upside down
and 2 spray puffs were administered delivering 0.14 mL of
radioactive saline per spray.
Assessment of Radiolabeled Saline Using Single-Photon
Emission Computed Tomography/Computed
Tomography
Five minutes after the administration of radiolabeled saline, single-
photon emission computed tomography/computed tomography
(SPECT/CT; Symbia Intevo; Siemens, Washington, D.C.) was
performed and assessed by a blinded nuclear radiologist to deter-
mine delivery of radioactive saline within the sinonasal regions.
Outcome Measure
The primary outcome is the distribution of the radiolabeled
saline in reference with the maxillary line. Maxillary line is
Figure 1. Short nozzle spray.
Figure 2. Long nozzle spray.
E98 Ear, Nose & Throat Journal 98(7)
defined as the axial line passing through M point at the level of
superior margin of maxillary sinus ostium. Secondary out-
comes are the distribution to the following sinonasal regions:
vestibule, maxillary sinus, ethmoid sinus, sphenoid sinus, and
frontal sinus.
Single-photon emission computed tomography/computed
tomography/CT images are assessed qualitatively by an inde-
pendent nuclear radiologist. Results are categorized as positive
or negative. For the primary outcome, positive result means the
presence of >10%radioactivity detected above the maxillary
line, while negative result means 10%radioactivity detected
above the maxillary line. For the secondary outcome, positive
result means presence >10%radioactivity detected in the sino-
nasal region being studied, while negative result means 10%
radioactivity detected in that sinonasal region. Figure 3 shows
the percent radioactivity scheme and the representative
SPECT/CT images with their corresponding assessment.
Statistical Analysis
Data were treated as nominal and analyzed using Fisher exact
test. A pvalue <.05 was considered statistically significant.
Results
All 14 cadaver heads were well preserved through freezing
with a near normal quality of the soft tissue. All had negative
serological testing for infectious diseases. No other medical
history was available. All cadaver specimens were adults by
visual inspection.
The nasal cavity demonstrated evidence of radioactivity on
all SPECT/CT performed after nasal spray. Figure 4 shows
representative SPECT/CT images following administration of
radiolabeled saline and their corresponding assessment.
In the short nozzle group, 5 (35.7%) cadavers demonstrated
radioactivity limited below the maxillary line, while 9 (64.3%)
cadavers demonstrated radioactivity above the maxillary line,
reaching the cribriform plate. In the long nozzle group, all
14 (100%) cadavers demonstrated radioactivity above the
maxillary line, reaching the cribriform plate. The number of
cadavers demonstrating radioactivity above the maxillary line
is significantly higher in the long nozzle group compared to the
short nozzle group (p¼.02; Table 2).
Thirteen (92.86%) cadavers demonstrated radioactivity in
the vestibule in the short nozzle group. This is significantly
higher compared to 6 (42.86%) cadavers demonstrating radio-
activity in the vestibule in the long nozzle group (p¼.006;
Table 3).
Compared to short nozzle group, more cadavers demon-
strated radioactivity in the 4 individual sinuses in the long
nozzle group, but this is not statistically significant (Table 3).
The ethmoid and sphenoid sinuses are the most frequently
delivered sites (10 cadavers, 71.43%) in the long nozzle group,
while the ethmoid and frontal sinus are the most frequently
delivered sites (8 cadavers, 57.14%) in the short nozzle
group. In both groups, maxillary sinus least demonstrated
Table 1. Comparison Between the Short and Long Nozzle.
Characteristics Short Nozzle Long Nozzle
Length from the shoulder 2.5 cm 9 cm
Orifice diameter 0.2 mm 0.2 mm
Nozzle diameter 1 cm
(near the shoulder)
0.5 cm
(near the nozzle tip)
0.3 cm
Depth of insertion from limen
nasi
2cm 3.5cm
Angle of insertion from nasal
floor
3045
Angle of insertion from septum 1515
Dose of radioactive saline
delivered per spray
0.14 mL 0.14 mL
Figure 3. Percent radioactivity scheme and representative single-
photon emission computed tomography/computed tomography
(SPECT/CT) images of various cadaveric heads following administra-
tion of radiolabeled saline and their corresponding results. Positive
result means presence >10% radioactivity detected in the sinonasal
region being studied, while negative result means 10% radioactivity
detected in that sinonasal region. A, Sagittal cut showing positive
result in the sphenoid and ethmoid sinus, and negative result in the
frontal sinus. B, Coronal cut showing positive result in the left ethmoid
and negative result in the right ethmoid and bilateral maxillary sinus.
Kapadia et al E99
radioactivity. No cadaver in the short nozzle group, and only 2
(14.29%) in the long nozzle group demonstrated radioactivity
in the maxillary sinus.
Discussion
The clinical effect of intranasal corticosteroid is limited by its
inadequate distribution to the sinus mucosa.
3,9
In order to
improve sinonasal drug delivery, adequate access must be
achieved and appropriate delivery method must be utilized. It
is well established that sinus surgery removes anatomical bar-
riers providing more access to the sinus mucosa and olfactory
cleft.
1,2,6-8,10
This translates clinically to greater polyp size
reduction in patients who underwent sinus surgery with post-
operative INCS compared to patients who received INCS but
did not undergo sinus surgery.
1,2,11
Postoperatively, intranasal sprays are commonly used
because of ease of administration.
3
Many INCS are available
in spray formulation.
3
Despite these advantages, sprays have
been shown to have less sinus delivery compared to sinus
delivery methods such as direct sinus cannulation or postopera-
tive sinonasal irrigation.
11,5
The proportion of INCS delivered
to the sinuses has been measured to be less than 1%delivered to
the nasal cavity.
8
Even after surgery, nasal sprays have incon-
sistent sinus distribution.
8
However, these studies use the com-
mercially available spray with short nozzle.
5,12
Short nozzles can only be inserted intranasally until the
spray shoulder depositing a large portion of INCS into the
region anterior to the nasal valve area called the vestibule.
3,13
In a computational fluid dynamics study simulating nasal spray
parameters of commercially available nasal sprays, >90%of
the drug particles were deposited in the nasal vestibule.
14
The
nasal vestibule is lined by nonciliated squamous epithelium,
has no mucociliary action, low vascularization, and poor per-
meability.
13,15
Thus, the anteriorly deposited drugs will drip
out of the nose and will not be absorbed.
16
In this study, the
radiolabeled saline was delivered to the vestibule in 13
(92.86%) cadavers in the short nozzle group (Figure 4B). Five
of these cadavers demonstrated radioactivity below the max-
illary line. Another study
17
reported <20%of topical drugs
delivered beyond the vestibule and no drug delivered to the
sinuses, when using intranasal spray with short nozzle.
Figure 4. Representative single-photon emission computed tomography/computed tomography (SPECT/CT) images of various cadaveric heads
following administration of radiolabeled saline and their corresponding results. Coronal cut at the maxillary sinus ostium (A), the left shows
positive result, and the right shows negative result. Coronal cut at the nasal vestibule (B), the left shows negative result, and the right shows
positive result. Coronal cut at the maxillary sinus (C), the left shows positive result, and the right shows negative result. Coronal cut at the area
of the ethmoid sinus (D), the left shows positive result, and the right shows negative result. Coronal cut at the sphenoid sinus (E), the left shows
positive result, and the right shows negative result. Sagittal cut at the frontal sinus showing positive result (F) and negative result (G).
Table 2. Comparison of Radioactive Saline Delivery Between Short
Nozzle and Long Nozzle in Reference to Maxillary Line.
Type of Nozzle
Above Maxillary Line Below Maxillary Line
n%n%
Short nozzle 9 64.3 5 35.7
Long nozzle 14 100 0 0
pvalue .02
E100 Ear, Nose & Throat Journal 98(7)
In order to minimize anterior INCS deposition to the vesti-
bule, a longer and narrower nozzle was designed to replace the
short nozzle. In this study, the radiolabeled saline was deliv-
ered to the vestibule in 6 (42.86%) cadavers in the long nozzle
group. In addition, the radiolabeled saline reached above the
maxillary line, reaching up to the cribriform plate (Figure 4A)
in all cadavers in the long nozzle group.
Several studies
14,17
suggested that the key to optimize nasal
drug delivery is to bypass the nasal valve area, which is an
important anatomical barrier in sinonasal drug delivery. The
nasal valve area has a limited dimension and mismatched geo-
metry.
3
It is the narrowest segment of the nasal passage measur-
ing 0.54 +0.13 cm
2
each side in acoustic rhinometry studies.
18
In addition, the triangular nasal valve opening does not match
the circular plume created by the spray. Once a spray is actuated,
a hollow spray cone is formed with drug particles mainly at the
periphery.
7
Particles at the lower and wider part of the triangle
will penetrate the valve, while the majority of drug particles will
impinge anterior to the nasal valve area and drip out.
7
The nasal valve area is located 2 to 3 cm from the nasal
opening.
18
A short nozzle, even if inserted deeply up to 2 cm,
will not be able to bypass this area. Because the long nozzle is
inserted 3.5 cm from the tip, it bypasses the nasal valve area,
ensuring that intranasal medication will reach the sinonasal
mucosa.
Nozzle orifice diameter is another factor affecting nasal
drug distribution. A smaller orifice diameter produces a nar-
rower spray cone angle which allows greater percentage of
droplets to penetrate the nasal valve.
14
Larger orifice diameter
creates wider spray cone angle and larger spray pattern which
deposits majority of the particles anterior to the nasal valve
region.
14,19,20
In order to control for the confounding effect
of the nozzle orifice diameter, the 2 nozzles in this study have
similar orifice diameter.
Anatomic variations such as septal deviation can also affect
drug deposition. Drug delivery is significantly diminished on
the side of obstruction.
21
Another study
22
showed that the cor-
rection of septal deviation improves nasal drug delivery. In
order to minimize the confounding effect of septal deviation,
cadavers that were included in the study have no septal
deviation.
For INCS to be effective in CRS, it should be delivered to
the sinonasal mucosa, which is lined mainly by respiratory
epithelium, has very high vascularization and good permeabil-
ity.
9
In this study, the delivery to the sinuses increased when
long nozzle was used compared to short nozzle, although the
difference is not significant.
Scintigraphic methods have been used to assess sinonasal
drug delivery.
23-27
Among the radiopharmaceuticals available,
Tc99m is commonly used because of its short half-life of 6
hours, high-efficiency detection and low radiation exposure.
28
Intranasally administered Tc99m labeled solutions were com-
monly assessed using 2-dimensional (2D) gscintigraphy.
25,26
However, planar scintigraphy provides 2D images without
clear anatomic features especially the maxillary sinuses.
24,25
In this study, SPECT/CT was used to assess radiolabeled saline
deposition. Single-photon emission computed tomography/CT
has been recommended as the scintigraphic imaging of sinona-
sal drug distribution.
27
It provides a 3D image combining the
radioactivity measured using SPECT and the detailed anatomic
images using CT scan. This method is highly advantageous in
evaluating the sinonasal region because the sinonasal anatomic
subsites are very close to each other. Single-photon emission
computed tomography/CT has been shown to accurately assess
drug deposition.
27
Leclerc et al
27
compared the intrasinus
deposition assessed using SPECT/CT to a reference lavage
method. Results showed the SPECT/CT is in agreement with
the reference method unlike 2D planar scintigraphy which
often overestimates drug deposition in the nose.
27
For a nasal spray to effectively deliver INCS from the bottle
to the sinonasal mucosa and olfactory cleft, an appropriately
designed nozzle is needed. It should bypass the nasal valve
area, which limits the delivery of intranasal drugs to the surgi-
cally opened sinus cavities. The use of a long nozzle can help
bypass this area, reaching the regions above the maxillary line
more consistently than the use of short nozzle.
The particle size and plume geometry, consequently nasal
drug delivery, is affected by device properties and formulation
properties.
5,29,30
In this study, only one type of short and long
nozzle nasal spray is used. We recommend further studies
using other short and long nozzle nasal spray with different
device properties.
Nasal drug delivery is not only affected by device properties
but also by formulation properties (viscosity and rheological
behavior). Results in this study could be underestimated
because water was used as the liquid component of the nasal
spray device. Compared to drug formulations, water has lower
viscosity at 1.28 centipoise.
29
Increased viscosity of the liquid
formulation resulted to larger droplet size, narrower plume
angle, lower spray pattern and less vestibule, and nasal valve
deposition.
25,29
Further studies using liquid with viscosity sim-
ilar to nasal formulations are recommended.
Clinical generalizations from this study are limited by the
inability of cadaveric models to reproduce other physiological
Table 3. Comparison of Radioactive Saline Delivery Between Short Nozzle and Long Nozzle in Different Sinonasal Regions.
Type of Nozzle
Vestibule Maxillary Sinus Ethmoid Sinus Sphenoid Sinus Frontal Sinus
n%n%n%n%n%
Short nozzle 13 92.86 0 0 8 57.14 6 42.86 8 57.14
Long nozzle 6 42.86 2 14.29 10 71.43 10 71.43 9 64.29
pvalue .006 .241 .347 .126 .5
Kapadia et al E101
and patient-related factors. Mucociliary clearance, comfort of
use, and patient handling also affect drug delivery of the
INCS.
3,9,13
Further studies on live patients are recommended
to assess patient comfort, safety, and reproducibility of the
insertion depth and angles in clinical setting.
One modification in this study is that the cadaver heads
were placed in a supine position instead of the usual head
upright position. The head supine position was used for both
short and long nasal sprays. There are limited data about the
absorptive capacity of cadaver nasal mucosa to radiolabeled
saline. Some radiolabeled saline may drip to the nasal vesti-
bule after being deposited to the sinonasal mucosa. This
would confound the results. In order to remove this possibil-
ity, the cadaver heads were placed in a supine position. One
limitation of this head position is it could overestimate the
deposition to the sphenoid sinus. Future studies using head
upright position is recommended.
This study demonstrated that in post-endoscopic sinus sur-
gery specimens, long nozzle could deliver radioactive saline
above the maxillary line more frequently and less frequently in
the vestibule, compared to short nozzle. These findings support
the hypothesis that the use of long and narrow nozzle, instead
of the conventional short nozzle, can improve sinonasal drug
delivery in post-endoscopic sinus surgery nose. This suggests
potential for product improvement.
Authors’ Note
The views expressed in the submitted article are of the authors and not
an official position of any institution. Precious Eunice R. Grullo is
now affiliated with Tarabichi-Stammberger Ear and Sinus Institute,
Dubai, United Arab Emirates, Department of Otorhinolaryngology,
College of Medicine, University of the Philippines - Philippine Gen-
eral Hospital, Manila, Philippines and Department of Otorhinolaryn-
gology, Rizal Medical Center, Pasig, Philippines.
Acknowledgments
The authors thank the Nuclear Medicine staff for their assistance
throughout the study.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
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