EDITORIALS
APRIL 2000
A Aerosol treatment of acute asthma: And the winner
is…
Treatment of acute asthma in children
has evolved from the relatively inva-
sive and uncomfortable process of re-
peated epinephrine injections to the
effective and largely painless practice
J Pediatr 2000;136:428-31.
Copyright © 2000 by Mosby, Inc.
0022-3476/2000/$12.00 + 0 9/18/105149
doi:10.1067/mpd.2000.105149
428
THE JOURNAL OF PEDIATRICS
of aerosolizing β-adrenergic agonists.
Unfortunately, administering inhaled
airways is complex and a multitude of
inhalation devices are on the market,
there are essentially 2 mechanisms for
ED Emergency department
MDI Metered-dose inhaler
SVN Small-volume jet nebulizer
VHC Valved holding chamber
See related article, p. 497.
medications, especially in ill young chil- administering aerosolized bronchodila-
dren, is not a simple endeavor. Although tors: the metered-dose inhaler and the
the science of particle deposition in the small-volume jet nebulizer. In spite of
THE JOURNAL OF PEDIATRICS
VOLUME 136, NUMBER 4
a large and ever-growing body of evi-
dence in support of the equivalence of
both techniques in the management of
acute asthma, only the SVN enjoys ex-
ceptional popularity.
The development of inhaled β2-
receptor–selective adrenergic agonists
spawned a revolution in the manage-
ment of acute asthma. The ease of use
and efficacy of the SVN rapidly led to
its place as the “gold standard” modali-
ty for treatment of acute asthma. The
added convenience and portability of
β-agonist in MDI form further ce-
mented inhaled bronchodilators as the
cornerstone of acute asthma manage-
ment. Unfortunately, the possible asso-
ciation of rising asthma death rates and
MDI β-agonist use, coupled with the
significant difficulty in mastering prop-
er MDI technique, drove the inhaler
into some disfavor. Development of the
valved holding chamber or “spacer”
and documentation of its efficacy, as
well as partial exoneration of daily use
of inhaled β-agonists, have again pop-
ularized the MDI.1,2
Although the difficulties in using an
MDI are widely known, a common fal-
lacy holds that SVN use is far less sen-
sitive to vagaries in patient technique.
The caveat in use of any inhalation de-
vice is that technique is everything.
Proper SVN use, resulting in maximal
airway deposition of medication, re-
quires use of a mouthpiece and not a
mask (or even worse, tubing held in
front of the child’s nose). As with the
MDI, inhalation should be slow and
deep, followed by a few-second breath
hold. Few children younger than 4
years of age, and especially those who
are already acutely ill, will or can
breathe in such a fashion. Appropriate
technique with SVN is not so different
from correct MDI use, which is further
complicated by difficulties with “hand-
breath coordination.” Use of a VHC,
which allows large, non-respirable par-
ticles to rain out and provides more
time to inhale the respirable cloud of 1-
to 5-µm particles, obviates most of
these difficulties and enhances the like-
lihood of a reasonable dose of medica-
tion reaching the lower airways.
Data from a number of studies indi-
cate that use of β-agonists from an
MDI or MDI plus VHC is as effective
as use of an SVN for treating acute
asthma.3-6 Two recently conducted
randomized clinical trials add further
support to the equivalence argument of
the MDI and SVN. Schuh et al6 com-
pared efficacy of 2 puffs or 6 to 10
puffs delivered by MDI plus VHC and
0.15 mg/kg albuterol delivered by
SVN in resolving mild asthma attacks
in children aged 5 to 17 years. All
groups showed comparable improve-
ment in forced expiratory volume in 1
second. In this issue of The Journal,
Leversha et al7 identified MDI-deliv-
ered albuterol (600 µg) as equivalent
and by some measures superior to
SVN-delivered albuterol (2.5 mg) for
treating moderate to severe asthma at-
tacks in children aged 1 to 4 years.
Children treated with the MDI had
greater reduction in wheeze after the
first treatment only, and fewer patients
in this group were admitted to the hos-
pital (33% in the MDI group and 60%
in the SVN group). The unusually
large number of patients admitted to
the hospital in the SVN group is well
beyond that reported in other studies8
and may be explained in part by inadver-
tent unblinding of study investigators,
inconsistent application of admission cri-
teria, chance, or a truly less effective
treatment. However, there was no sig-
nificant difference between groups in
the absolute change in clinical score
over the entire study period, the out-
come on which the study was powered.
In both studies, patients and families
overwhelmingly preferred the MDI to
the SVN.
The equivalent performance of the
MDI plus VHC and SVN is difficult to
dispute in view of the data presented in
these and other studies. Perhaps the
question to ask is not why the MDI
works as well as it does but why the
SVN does not perform better. A num-
ber of factors should be considered.
EDITORIALS
In the study by Leversha et al,7 the
order of medication administration
may have contributed to the response
of the patient. Patients in the MDI
group first received active drug from
an MDI plus VHC (6 puffs) and then
were given a placebo aerosol from
an SVN. Those in the SVN group
received 6 puffs of placebo aerosol,
followed by 2.5 mg of nebulized al-
buterol. Although the authors state
that the medication was administered
when the child was “quiet and cooper-
ative” whenever possible, there is no
indication of the number of children
who cried through either treatment.
Many children become tired or less co-
operative or begin crying before or
during aerosol treatment. Crying sig-
nificantly reduces the amount of med-
ication delivered to the airways.9 A
child who became agitated during
placebo administration might still have
been crying when the active drug was
administered. Paradoxical response to
a component in the placebo inhaler is
also a possibility. Administering med-
ications in random order might have
addressed this issue. Nevertheless, an
inhalation treatment that can be deliv-
ered quickly and quietly may be less
likely to perturb its recipient.
Although the authors do not directly
describe the process of applying the mask
to the child’s face in either group, it is an
important detail. The soft, pliable mask
on the VHC must be firmly held over the
child’s mouth and nose after MDI activa-
tion and kept in place until 5 to 6 breaths
are taken. The SVN mask must also be
kept closely applied to the mouth and
nose for the 10 minutes necessary to com-
plete nebulization. Efficiency of delivery
falls considerably as mask distance from
face increases; moving just 2 cm away
from the face can reduce deposition by as
much as 85%. Unfortunately, it is a com-
mon practice to merely wave the nebuliz-
er tubing or T-piece under the child’s
nose, a practice that results in negligible
airway deposition.
The authors also indicate that some
nebulizers have relatively poor output.
429
 EDITORIALS
Quality control can be a problem with
jet nebulizers; devices may vary signifi-
cantly between and even within lots.
Moreover, the inexpensive, disposable
nebulizers used in most cost-conscious
hospitals and emergency departments
and by most families at home are often
of marginal quality when new and may
be pushed into service beyond their in-
tended use. Nebulizers used in the
study by Leversha et al7 were simple,
unvented updraft models, which may
have come from a “bad lot,” rendering
their output less than optimal. Several
vented, durable, high-efficiency breath-
enhanced nebulizers (eg, PARI LC
Plus; Salter Nebutech) are capable of
generating increased output in a signif-
icantly shorter time.10 Use of such de-
vices adds equipment cost but can save
some medication and personnel cost.
Lastly, the relatively high-dose of
β-agonist delivered to both the airways
and systemically (the amount deposit-
ed in the oropharynx and subsequently
swallowed) could contribute to ad-
verse effect. Albuterol is a racemate
containing a 50:50 mix of R- and
S-albuterol. The S-isomer has no bron-
chodilator action and has a long (ap-
proximately 6-hour) serum half-life.11
Limited data from animal and human
studies suggest that accumulation of
the S-isomer may result in increased
smooth muscle contractility and hyper-
responsiveness to constrictor stim-
uli.11,12 Such an effect remains to be
conclusively demonstrated in the asth-
matic population, but if present, it
could contribute to the continued need
for bronchodilator in patients receiv-
ing frequent, high doses of albuterol
through a nebulizer.
Will the treatment of an acute asth-
ma episode in the ED with repeated
doses from a MDI send a wrong or
right message to families? It is far easi-
er to “abuse and overuse” an MDI
than an SVN because of the time and
effort needed for SVN repeated doses
and the relative ease and speed of MDI
use. If multiple doses of β-agonist from
an MDI work in the hospital, why not
430
at home? And if the dose used in the
ED does not work, how about just a
few more puffs? One hypothesis for
the increase in asthma deaths is abuse
of β-agonist MDIs, resulting in unrec-
ognized progression of attack, delay in
seeking medical attention, paradoxical
bronchospasm, increased airway reac-
tivity, and cardiac arrhythmia. Even
patients with mild intermittent disease
may have a severe exacerbation, such
as those caused by respiratory syncy-
tial virus or influenza. Delay in seek-
ing medical care could be critical.
Overuse of β-agonists from an MDI
may become widespread as more pa-
tients receive frequent doses delivered
in the ED with the same delivery de-
vice available at home. Or will patients
learn that many episodes can be abort-
ed at home with simple measures, such
as a few extra doses from an MDI and
institution of oral corticosteroid treat-
ment? Data collected in our ED over
the past 3 years demonstrate that 20%
to 25% of patients presenting for treat-
ment of acute severe asthma took 2 or
fewer aerosol treatments at home, re-
ceived 2 or fewer aerosols in the ED,
and were successfully discharged.13
Proper home management of these pa-
tients would have prevented an ED
visit altogether.
In spite of the documented equiva-
lence of VHC plus MDI and SVN,
families in the United States often face
significant barriers in obtaining a
VHC. Most medical insurers will pay
for prescribed SVNs as durable med-
ical equipment, whereas the VHC is
rarely covered and often not stocked in
pharmacies. Many families are unwill-
ing or unable to spend the $30 to $40
usually charged for a VHC; when com-
pared with the cost of a single ED visit
or hospitalization, such behavior is
penny-wise and pound-foolish. The
VHC may simplify the process of using
an inhaler, but a modicum of attention
must still be paid. The valve on the
spacer may obstruct or malfunction,
the unit must be air-dried after cleaning
to prevent static charge and excessive
THE JOURNAL OF PEDIATRICS
APRIL 2000
medication retention in the chamber,
and doses delivered from the MDI must
be counted to avoid using an empty
cannister.
Improving or maintaining quality of
care while cutting costs was the mantra
of the 1990s and will certainly contin-
ue into this millennium. Use of an
MDI with VHC in the hospital and
home setting has been demonstrated to
be effective and less expensive (in
terms of personnel costs and time)
than use of an SVN to treat acute asth-
ma. Insurers must be convinced to
cover the VHC as readily as most pay
for the SVN. Altering established med-
ical practice and physician behavior,
even in the presence of convincing
data, is always a challenging task; but
patients and physicians must endorse
the MDI plus VHC and use the modal-
ity properly in a number of settings.
Admonition against excessive use of
β-agonists and the benefits of using a
written asthma action plan must be rein-
forced. Lastly, a careful watch must be
kept on asthma morbidity and mortality
rates as the shift to MDI-administered
bronchodilators expands.
Carolyn M. Kercsmar, MD
Pediatric Pulmonary Division
Rainbow Babies & Childrens Hospital
Case Western Reserve University
Cleveland, OH 44106-4948
REFERENCES
1. Drazen JM, Israel E, Boushey HA,
Chinchilli VM, Fahy JV, Fish JE, et al.
Comparison of regularly scheduled
with as-needed use of albuterol in mild
asthma. N Engl J Med 1996;335:841-7.
2. Newhouse MT. Asthma therapy with
aerosols: Are nebulizers obsolete?
A continuing controversy. J Pediatr
1999;135:5-8.
3. Tal A, Golan H, Grauer N, Aviram M,
Albin D, Quastel MR. Deposition pat-
tern of radiolabeled salbutamol inhaled
from a metered-dose inhaler by means
of a spacer with mask in young chil-
dren with airway obstruction. J Pedi-
atr 1996;128:479-84.
4. Williams JR, Bothner JP, Swanton D.
Delivery of albuterol in a pediatric
emergency department. Pediatr Emerg
Care 1996;12:263-7.
THE JOURNAL OF PEDIATRICS
VOLUME 136, NUMBER 4
5. Chou KJ, Cunningham SJ, Crain EF.
Metered-dose inhalers with spacers vs
nebulizers for pediatric asthma. Arch
Pediatr Adolesc Med 1995;149:201-5.
6. Schuh S, Johnson DW, Stephens D,
Callahan S, Winders P, Canny GJ.
Comparison of albuterol delivered by a
metered dose inhaler with spacer ver-
sus a nebulizer in children with mild
acute asthma. J Pediatr 1999;135:22-7.
7. Leversha AM, Campanella SG, Aickin
RP, Asher MI. Costs and effectiveness
of spacer versus nebulizer in young chil-
dren with moderate and severe acute
asthma. J Pediatr 2000;136:497-502.
8. Qureshi F, Pestian J, Davis P, Zarit-
sky A. Effect of nebulized ipratropium
on the hospitalization rates of children
with asthma. N Engl J Med 1998;339:
1030-5.
9. Wildhaber JH, Dore ND, Wilson JM,
Devadason SG, LeSouef PN. Inhala-
tion therapy in asthma: Nebulizer of
pressurized metered-dose inhaler with
holding chamber? In vivo comparison
of lung deposition in children. J Pedi-
atr 1999;135:28-35.
10. Coates AL, Ho SL. Drug administra-
tion by jet nebulization. Pediatr Pul-
monol 1998;26:412-23.
EDITORIALS
11. Nelson HS, Bensch G, Pleskow WW,
DiSantostefano R, DeGraw S, Reasner
DS, et al. Improved bronchodilation
with levalbuterol compared with racemic
albuterol in patients with asthma. J Al-
lergy Clin Immunol 1998;102:943-52.
12. Templeton AGB, Chapman ID, Chil-
vers ER, Morely J, Handley DA. Ef-
fects of S-salbutamol on human isolat-
ed bronchus. Pulm Pharmacol Ther
1998;11:1-6.
13. Myers T, Kercsmar CM. Home asthma
management prior to visiting an inner
city pediatric emergency department
[abstract]. Pediatr Res 1999;45:353A.
431