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Nebulized Saline Solution of Dry Powder Formoterol is Useful for Acute
Bronchospasm
A Pérez Puigbó1, E Capriles Behrens2 and L Giannoni Delgado3.
1. Instituto de Clínicas y Urología Tamanaco. 2. Escuela de Medicina "J.M. Vargas", Caracas. 3. Centro Médico Docente La Trinidad, Medicina Comunitaria. Dos nuevos beta agonistas de efecto prolongado son actualmente usados clínicamente:
salmeterol y formoterol. El primero no ha demostrado efectividad en los casos de asma aguda
mientras que el segundo, Formoterol, comparable en su período de latencia al albuterol, no ha
sido empleado en el manejo de las crisis de asma. En este estudio utilizamos mediciones de flujo
espiratorio pico antes y después de la administración de 12 microgramos de Fumarato de
Formoterol (Foradil®) en polvo seco vía nebulización, inmediatamente después de su diluición en
solución salina estéril, a treinta pacientes con crisis de asma y grados variables de obstrucción
bronquial. Los resultados muestran mejoría significativa a los 5 y 30 minutos después de su
administración, sugiriendo estabilidad de este producto así como un novedoso enfoque costo
efectivo por su menor dosificación y posible impacto sobre la frecuencia de readmisiones debido a
una broncodilatación prolongada.
Palabras Clave: Formoterol, Solución nebulizadora, Manejo de ataque agudo de asma, Agonista
Beta 2 de acción larga.
ABSTRACT
Salmeterol and Formoterol, two new long acting Beta agonists, are being clinically employed.
Salmeterol lacks efficacy in acute asthma while Formoterol, with a latency period similar to
albuterol, has never been used in the acute bronchospastic situation. We measured peak
expiratory flows in 30 acute asthma patients with variable degrees of airway obstruction before and
after administation of 12 micrograms of Formoterol Fumarate (Foradil®) dry powder, nebulized
inmediatly after preparation in sterile saline solution. We found significant improvements at 5 and
30 minutes after administration suggesting stability of this product and a possible new cost
effective approach with a need for less dosing and perhaps an impact on the rate of asthma
readmisions due to the prolonged bronchodilatador effect.
Key Words: Formoterol, Nebulized solution, Asthma acute management, Long acting Beta 2
agonist.
INTRODUCTION
Frequent use of inhaled (either via MDI or by nebulization) short acting beta agonists is the routine
pharmacological treatment for acute asthma exacerbations. Long acting beta agonists have been
used in primary care as valuable adjuncts to maintenance inhaled steroids and for symptom control
with emphasis on nocturnal and exercise induced asthma(1). Formoterol fumarate* (* (+ -) -2´-
hydroxi-5´-[(RS)-1-hydroxi-2-[(RS)-p-methoxy-alfa-methylphenethyl]-amino]ethyl]-formanilidin
dihydrated fumarate), a new long acting (dry powder) beta agonist, also has an acute rapid
bronchodilating effect comparable to albuterol, suggesting its potential use as an occasional
symptom reliever on a pro re nata basis(2). There are patients unable to properly perform
inhalatory efforts because of age, breathing difficulties or other factors and in such instances
administration of a drug via a nebulized solution can prove helpful. We employed formoterol as a
dry powder in saline solution nebulized inmediatly after preparation to patients with acute asthma,
in an open uncontrolled study.
METHODOLOGY
Consecutive patients with asthma, as defined by the American Thoracic Society(3), attending the
emergency room with acute wheezing exacerbations and able to perform a peak expiratory
maneuver were evaluated clinically and with Peak Expiratory Flow (PEF) measurements (Personal
Best®, the best of three measurements in the standing position) before, 5 minutes and 30 minutes
after nebulization with a single dose of 12 micrograms of Formoterol (Foradil®: 1 capsule diluted in
2 ml of sterile saline solution). The pH of the nebulization solution did not differ from sterile normal
saline(4) and was administered inmediately after preparation with a Pari® Jet nebulizer connected
to a De Vilbiss® compressor model 5650 D with an output of 0.15 - 0.35 ml/min. Patients with
clinical evidence of possible bacterial infection such as high fever, purulent bronchitis and or
pneumonitis, as well as those who had received any beta agonists in the previous 4 hours, were
excluded. In those patients unable to use the nebulizer mouth piece, a face mask was used as a
substitute. The protocol and informed consent document were approved by the Institutional Review
Ethical board (Instituto de Clínicas y Urología Tamanaco) and written informed consent was
obtained from all patients or parents prior to participation. The student "t" test was employed for the
statistical analysis.
RESULTS
Thirty (30) patients (male 11, ages 4 to 62, mean of 25. 6 years), with variable degrees of airway
obstruction were studied. A reduction in the mean PEF value of 47.8% of predicted was found
before treatment, progressing to 27.9% and 19.9% at 5 minutes and 30 minutes respectively. Mean
values for PEF are shown in Table 1.
Table 1.
PEF predicted PEF 0 min
PEF 30 min
DISCUSSION
Two long acting beta agonists, salmeterol and formoterol have been released, differing
substantially in structure, binding to adrenoceptor, B- 2 blockade, onset and mode of action(5).
In stable asthmatics without current symptoms the onset of drug action is less important; however,
in the acute bronchospastic situation salmeterol lacks an inmediate effect while formoterol exibits a
similar rapid onset of action to albuterol (1 to 3 minutes), achieves maximun bronchodilatation
within 2 hours (sustained for up to 12 hours) and has almost no adverse side effects(6). It has been
shown to be 100 times more potent than albuterol "in vitro", without clinically reported tachyphilaxis
and controversial antiinflamatory properties(6).
Foradil® is ussually prescribed for inhalation in a dry powder form with a friendly user device
(Aerolizer®). However, some patients can not perform inhalatory maneuvers for a variety of
reasons such as age or difficult breathing and the nebulized administration of an effective Beta 2
agonist, with both an acute and long lasting effect, might give a beneficial therapeutic option in
such situations. In this short paper, we have demonstrated that asthmatic patients of different ages
with acute wheezing exacerbations of variable severity have a significant improvement of their PEF
using formoterol as a dry powder via a nebulized solution. These results suggest the stability of this
drug in saline solution when it is administered inmediatly after preparation. Theoretically, a need for
less dosing with an impact on the rate of asthma readmisions, because of a prolonged
bronchodilatation, might prove cost effective; this will also allow patients to initiate and better keep
their maintenance medications program.
Acknowledgements
We will like to thank the expert assistance of Dr. Omar Verde with the statistical analysis and Dr.
Marcelo Alfonzo for the critical reading of the manuscript.
REFERENCES
1. Bierman L and Larsson L. Long acting B2 agonists: how are they used in an optimal way?.Resp
Med. 1997; 91: 587-591.
2. Faulds D, Hollingshead LM, Goa KL. Formoterol: a review of its pharmacological properties and therapeutic potentials in obstructive airways desease. Drugs. 1991; 42: 115- 137. 3. American Thoracic Society. Chronic Bronchitis, Asthma and Pulmonary emphysema: A statement by the committee on diagnostic standards for nontuberculous respiratory diseases. Am Rev Resp Dis: 1962; 85: 762-8. 4. Perez Puigbó A, Capriles Hulett A, Rodriguez G, Verde O, Perez Reggetti J. Una nueva forma de administración: reporte preliminar del efecto Broncodilatador inmediato (Foradil) en solución salina via nebulización. XII Congreso de la Sociedad Venezolana de Alergia, Asma e Inmunología, Caracas, Venezuela; 2000; Abstract No 13. 5. D’ Urzo A D. Long acting beta 2 agonists. Role in primary care asthma treatment. Can Fam Physician. 1997; 43: 1773-1777. 6. Bartow RA; Bronden RN. Formoterol: an Update of its pharmacological properties and efficacy in the management of asthma. Drugs. 1998; 55: 303-322.

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