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Ultrasonic Nebulization of Albuterol is
No More Effective Than Jet Nebulization
for the Treatment of Acute Asthma in
Children*
Albert K. Nakanishi, MD;
Bruce K.
Billy M. Lamb, RRT; Charles Foster, RRT; and
Rubin, MD, FCCP
Study objective: Nebulizer systems used to generate therapeutic aerosols vary in their ability to
deliver medication to the airway. In a recent study in 17 adults with stable asthma, albuterol given
using an ultrasonic nebulizer (UN) appeared to produce greater bronchodilatation than the same
dose of albuterol given by a jet nebulizer (JN). The purpose of this study was to determine if the
UN used in that study would produce a better bronchodilator response in children with acute
asthma than the JN system that has been in use at Cardinal Glennon Children's Hospital.
Design: Randomized, prospective, unblinded study.
Setting: An urban university children's hospital emergency department.
Participants: One hundred thirteen children, aged 7 to 16 years, who presented for treatment of
acute moderately severe asthma completed this study.
Interventions:After randomization and exclusion of dropouts, 46 children received albuterol by
UN and 67 were treated by JN.
Measurements: Pulmonary function tests (PFTs) by spirometry, pulse oximetry, and symptom
score at baseline and at 15 and 30 min following a single prescribed treatment.
Results: PFT on entry to the study was the same in both groups (FEVj_; p>0.97). The change in
FEVi after therapy (UN+0.22 L vs JN+0.37 L) was significant (p<0.05) and favored JN. There
was no difference in the improvement in pulmonary function between JN and UN therapy in
children with an initial FEV1/FVC>75% predicted but when FEV1/FVC<75%, the improvement
in FEVx again favored the JN (UN+0.2 vs JN+0.47; p<0.05).
Conclusion: For the treatment of acute exacerbations of asthma in children, there is no greater
bronchodilator response when albuterol is administered by a UN than by a JN.
(CHEST 1997; 111:1505-08)
Key words: aerosol delivery devices; asthma therapy
Abbreviations: JN=jet nebulizer, MDI metered-dose inhaler, PFT.pulmonary
UN ultrasonic nebulizer
saturation
=
by pulse
oximeter;
systems used to generate therapeutic
T^Tebulizer
^ aerosols
in their
to deliver
vary widely
ability
medication to the lower airways.1-4 It was recently
reported that albuterol given using an ultrasonic
nebulizer (UN) (Microstat; Mountain Medical
-*-
Equipment Inc; Littleton, Colo) produced greater
bronchodilatation in 17 adults with stable asthma
when compared to albuterol administered by a jet
*From the Department of Pediatrics (Drs. Nakanishi and Lamb),
St. Louis, University, and Cardinal Glennon Children's Hospital
(Mssr. Lamb and Foster), St. Louis
Manuscript received July 21, 1995; revision accepted January 30,
MD, FCCP, Professor of
Reprint requests: Dr. Bruce K. Rubin,
Pediatrics and
Cardinal Glennon
1997.
Hospital,
Otolaryngology,St.
1465 S Grand
[email protected]. edu
Blvd,
function tests;
Sp02=oxygen
=
Childrens
Louis, MO 63104-1095; e-mail:
nebulizer
(JN) (Medi-Mist;
Mountain Medical
Equipment Inc).5 As the nebulization time using a
UN is shorter than the time required when using a
JN, this could represent a cost savings as well as
over the more com¬
providing
therapeutic benefit
In
the
used
monly JN systems.
hospital setting, these
benefits would be greatest when a bronchodilator is
used to treat acute asthma in the emergency depart¬
ment.
To evaluate if these promising results would also
hold true for children treated for acute asthma, we
studied the bronchodilator response to albuterol
administered using the Microstat UN or the Whisper
Jet (Marquest Medical; Englewood, Colo) JN
CHEST/111 /6/JUNE, 1997
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in
children aged 7 to 16 years treated for moderately
severe asthma in the emergency department.
1505
Materials
and
Methods
study was conducted during a 7-month period in the
Emergency Department of Cardinal Glennon Children's Hospi¬
tal, the pediatric teaching hospital for St. Louis University School
of Medicine. We evaluated 125 children between the ages of 7
and 16 years seeking emergent care for asthma. Patients requir¬
This
ing assisted ventilation or urgent and immediate intervention
were excluded from participation. Patients were excluded from
this study if their baseline respiratory rate was greater than 70
breaths/min, if their initial oxygen saturation by pulse oximeter
(Sp02) was <0.90 in ambient air, if they were reported to be
intolerant of p-agonist medications by their parent or guardian,
or if their initial FEVX was >70% predicted. Patients were also
excluded if they were incapable of performing acceptable and
reproducible pulmonary function tests (PFTs).
Upon registration in the emergency department, eligible pa¬
tients were evaluated and information was obtained including
patient age, usual medications, duration of exacerbation, medi¬
cations taken at home for this exacerbation, and time of last
(3-agonist dose. Informed consent was obtained and each patient
was instructed in the performance of a forced expiratory maneu¬
by a certified pulmonary function technologist. This study was
approved by the St. Louis University Institutional Review Board
ver
for Human Research.
Those who consented to participate were randomized into one
of two parallel treatment groups. Patients enrolled on odd days
were randomized to the JN group. Patients treated on even days
were enrolled in the UN group. This was done to simplify device
use by the treating respiratory therapist in the emergency
department. It was not possible to blind the respiratory therapists
administering the (3-agonist therapy because of obvious differ¬
ences in the two nebulizer systems.
The JN group received 0.15 mg/kg of albuterol nebulizer
solution (to a maximum of 5 mg or 1 mL) diluted in 2 mL of
normal saline solution through a compressor-driven, hand-held
JN (Whisper Jet, Marquest Medical) with oxygen administered at
a flow rate of 8 L/min. The UN group received the same dose of
albuterol in 2 mL of normal saline solution administered through
the Microstat UN and a breath-actuated hand-held device. All
subjects were instructed to take slow inhalations from functional
residual capacity (FRC) until the medication was completely
nebulized.
Height, weight, heart rate, respiratory rate, and Sp02 (in
ambient air) were measured for each study participant on entry to
the study. Vital signs were also obtained 15 and 30 min after the
aerosol treatment. A flow volume loop (Respiradyne model
5-7905; Sherwood Medical; St. Louis) was obtained and evalu¬
ated following American Thoracic Society guidelines6 and re¬
corded at the start of the aerosol treatment and at 15 and 30 min
after the treatment. A symptom score was calculated based on
respiratory pattern, accessory muscle use, inspiratory breath
sounds, oxygen requirement, cyanosis, expiratory wheezing, and
level of consciousness. The scoring was done by a study physician
(A.K.N.) and was measured at baseline, 15 min and 30 min after
the albuterol treatment.
Each patient was also given 2 mg/kg of oral methylpred¬
nisolone on enrollment in the study (maximum dose, 60 mg), and
oxygen was administered when needed to keep SpO2^0.94. No
xanthine medications were given. The study concluded after one
albuterol treatment, following which patients who required fur¬
ther bronchodilator therapy received albuterol by either JN or
metered-dose inhaler (MDI) with a valved holding chamber as isN
our usual emergency department routine.
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Data Analysis
Collected data were analyzed using a statistics package (Stat4.5; Abacus Concepts Inc., Berkeley, Calif). Analyses of
treatment effects were made by calculating two-tailed unpaired t
tests and were considered significant at the p<0.05 level. Differ¬
ences in symptom scores and side effects were assessed by x2
View
analysis.
Results
After randomization and exclusion of 12 dropouts,
total of 113 patients completed the study.46
children received albuterol by UN and 67 were
treated by JN. Twelve patients (9 UN and 3 JN) were
excluded from the study due to unwillingness to
PFTs after therapy despite adequate per¬
perform
formance of PFTs on enrollment and randomization.
Clinical scoring of asthma severity and baseline PFT
results were similar on entry for the two study groups
(Table 1). No patient in either treatment arm re¬
admission to hospital.
quired
The change in FEVX after aerosol therapy was
and favored JN (UN+0.22 L vs
significant (p=0.035)
There
was
no difference in PFT result
JN+0.37 L).
improvement between JN-treated and UN-treated
children who had an initial FEV1/FVC>75% pre¬
dicted, but when FEV1/FVC<75% predicted, the
improvement in FEVX again favored JN (UN+0.2 vs
a
JN+0.47; p=0.04).
There were no significant differences in symptom
between groups after treatment. No adverse
events were noted with either therapy. There was a
trend toward a greater patient report of tremor after
JN when compared with UN (x2=0.14).
scores
DISCUSSION
This study demonstrated that for the therapy of
acute, moderately severe asthma in children, there is
Table 1.Patient Demographics by Treatment
P
Value
UN
JN
Initial asthma score
Initial FVC, % predicted
Initial FEVX, %
10.1±3.3
26 (57)
3.0±2.1
41.0±19.9
36.1±18.5
11.0±3.1
39 (60)
2.4±3.2
45.1±19.5
38.1±16.9
Percent change FVC
Percent change FEVX
Percent change FEF25.75
22.9±26.4
22.4±25.7
40.7±55.7
31.7±43.1
36.6±42.7
58.8+87.8
Patient age, yr
Male patients, No. (%)
predicted
Group*
0.16
0.78
0.10
0.28
0.56
0.21
0.04
0.22
*AU values given as mean ±1 SD. FEF25_75=forced expiratory flow
rate between 25% and 75% of the FVC.
Clinical
Investigations
no advantage to the administration of albuterol using
the Microstat ultrasonic nebulizer system (UN)
when comapred to the same medication delivered by
the JN (Whisperjet). In fact, in the patients with
lower initial FEV1? there appeared to be greater
improvement in PFT results when albuterol was
administered by JN. The trend toward greater
tremor with JN was also consistent with increased
medication absorption across the pulmonary epithe¬
lium, and thus greater pulmonary deposition of
medication.
In earlier studies, the bronchodilator effect of
(3-agonists administered by UN to subjects with
asthma was less when compared to delivery using a
JN. In 20 adults with moderately severe, acute
asthma, the bronchodilating effect of fenoterol was
lot significantly enhanced by UN, and ipratropium
)romide gave significantly less bronchodilatation by
UN than by JN.7 Olivenstein and colleagues8 mea¬
sured PFT results in 19 outpatients with stable
obstructive pulmonary disease after albuterol was
administered by an MDI or by a UN.8 Only MDI
therapy produced a significant increase in FEVX and
the absolute increase from baseline of FEVj^ was
greater for MDI (0.21±0.05 L) com¬
significantly
to
UN
(0.07±0.03 L) (p<0.02). They specu¬
pared
lated that the inferior response to albuterol admin¬
istered by UN was in part due to the superimposed
bronchoconstriction occurring with ultrasonically ad¬
ministered saline solution carrier.
With the development of newer UN technology, a
recent study in 17 adults with stable asthma sug¬
given using a UN (Microstat)
gested thata albuterolincrease
in FEVX than albuterol
produced greater
delivered by a JN (Medi-Mist).5 There are several
reasons why these results differed from our findings.
Children with acute exacerbations of asthma are
dyspneic, and have high in¬
tachypneic,
frequentlyflow
rates compared to adults with stable
spiratory
asthma. These can limit the efficacy of nebulized
treatments. Lack of patient cooperation, coordina¬
tion, and ability to breath-hold also contribute to
ineffective aerosol deposition in the pediatric air¬
way.9-10 Because of these factors, it may be that the
nebulization time using the JN might have
longer
allowed greater opportunity for these children to
inhale the therapeutic aerosol.
There was also a difference in the JN used for each
of these studies. We were unable to obtain the
Medi-Mist JN so we evaluated the JN system in use
at Cardinal Glennon Children's Hospital. The MediMist generates particles with a mass median aerody¬
namic diameter of 3.9 jmm when driven with com¬
(data from
pressed air at a flowthisrate of 6 L/m inefficient
in
manufacturer) making JN relatively
the
to
comparison many JNs, including Whisper Jet.3
However, the most likely reason for the divergent
results obtained was that in the earlier study,5 only 1
mL of saline solution was added as fill volume to the
medication in the JN but 2.5 mL was added to UN.
This would significantly compromise the delivery of
medication from any JN.1 >n>12
We recognize that there are some important lim¬
itations to the interpretation of these results. Be¬
cause the study evaluated the effect of only one
aerosol treatment with UN or a JN, it is possible that
additional improvement could have been realized
with additional UN treatments.
Patient randomization was on an alternating
schedule based on the day of the week. Although this
optimized thedifferent
respiratory therapist efficiency in us¬
the
two
devices for nebulization, it also
ing
created an unequal patient distribution in the two
treatment arms that was not discovered until the end
of the study when analyses were conducted.
The intent of this study was to evaluate UN as a
mode of administering a bronchodilator aerosol in
children with acute asthma and not to compare
other, perhaps more common methods of adminis¬
tering aerosolized (3-agonists such as by MDIs used
with a holding chamber. To disprove the hypothesis
that the Microstat UN was more effective than both
JN and MDI aerosol therapy, and to do so at the
p<0.05 power level, including post hoc adjustments
for multiple group comparisons, we have calculated
that we would need to study more than 300 patients.
Thus, we evaluated the Microstat UN as it compared
to JN in children with acute asthma, rationalizing
that if JN was more efficient than UN, we could also
surmise that MDI therapy would likely be more
efficient than UN.
As different nebulization systems have different
medication outputs, these results do not indicate that
all JNs are superior to UNs for the administration of
bronchodilator drugs, but rather that the specific
nebulization systems tested here, and under the
described test conditions, did not support the use of
the Microstat UN for the treatment of acute asthma
in children.
References
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3. Loffert DT, Ikle D, Nelson HS. A comparison of commercial
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Clinical
Investigations