This study will be conducted as a randomized, double blinded, controlled trial. The control
group will receive albuterol delivered by a nebulizer along with placebo treatments
delivered by a metered dose inhaler (MDI) with a spacer +/- mask. The experimental group
will receive albuterol delivered by MDI with spacer +/- mask along with placebo treatments
given by a nebulizer. Parents, participants, study personnel, nursing staff, and
respiratory therapists will not know the treatment assignments of participants. The primary
outcome will be changes over time in an asthma severity score, the Clinical Asthma Score
(CAS) (Parkin et al. 1996). The secondary outcomes will be total number of albuterol
treatments received in the hospital, time it take to give treatments, time till subjects'
albuterol treatments are given at four hour intervals, and the costs of the two types of
treatments. The study hypothesis is that albuterol delivered by metered dose inhaler with
spacer is non-inferior to albuterol delivered by nebulizer in the treatment of children
hospitalized with moderate to severe asthma exacerbations.
Studies looking at the use of beta-2-agonists given by MDIs with a spacer and mask in
children greater than 2 years have described fewer side effects than when the same
medications are given as nebulizers. Patients have less tachycardia, vomiting, and oxygen
desaturation (Kerem et al. 1993, Chou, Cunningham and Crain 1995, Lin and Hsieh 1995,
Pendergast et al. 1989, Fuglsang and Pedersen 1986).
In the emergency department setting, Rubilar et. al found that albuterol delivered by MDI
with spacer and mask had equal efficacy to albuterol delivered by a nebulizer in treating
acute wheezing in children less than 2 years of age. (Rubilar, Castro-Rodriguez and Girardi
2000) Chou et. al found that in children greater than 2 years old with acute asthma
exacerbations, MDIs had the same efficacy as nebulizers but with a shorter delivery time and
fewer side effects.(Chou et al. 1995)
All children who meet criteria to be participants in the study will be approached for
possible study enrollment in the ED. No outside recruiting will be done. Once consent has
been obtained and patients are enrolled, they will be randomized to either albuterol by MDI
with placebo nebulizer treatments or albuterol by nebulizer with placebo MDI treatments.
Subjects will be randomized to one of the two treatment arms in a 1:1 randomization process.
This will be done using a prepared assignment log developed using a random number generator.
Children in the control arm will receive albuterol via nebulizer and placebo by MDI with
spacer +/- mask. Children in the experimental arm will receive albuterol by MDI and placebo
All MDI treatments will be given with a spacer +/- mask. Subjects will receive 6 puffs if
they are < 30 kg and 10 puffs if they are > 30 kg. If they are in the control group, puffs
will be placebo. If they are in the experimental group, puffs will be albuterol (90
micrograms per puff).
For the nebulizer treatments, patients in the control group will receive 2.5 mg albuterol
(if <30 kg) or 5 mg of albuterol (if 30 kg or greater) in 3 ml of normal saline. Patients
in the experimental group will receive nebulizer treatments as 3 ml of normal saline.
Nebulized treatments will be delivered with room air unless the subjects are on oxygen.
All study medication will be administered by clinical nursing staff or respiratory
therapists. The frequency at which albuterol is given will be determined by the subject's
primary medical team. For all subjects, MDI treatments will be given first followed by
Nursing staff will record a Clinical Asthma Score (CAS) (Parkin et. al 1996) on admission
and every 4 hours during hospitalization up to 72 hours or discharge (whichever comes
first). Nursing staff will also record the total number of albuterol treatments given and
the time required to give each treatment. Patients' total length of stay will be calculated.
A cost analysis will be done to determine if there are any differences in the costs to the
hospital of the two delivery devices. This analysis will include the costs of the albuterol
and delivery devices and the labor costs related to nursing or respiratory therapists' time
to administer the medications. Information on subjects' baseline level of asthma severity
will also be collected at the beginning of the study.
All study patients will be given prednisolone, prednisone or solumedrol at a dose of 1
mg/kg/dose twice a day for a total of 5 days. The length of steroid treatment can be
extended beyond 5 days if felt to be clinically indicated by the subject's attending
Controller medications such as long acting beta-2-agonists, inhaled corticosteroids, and
leukotriene inhibitors will be given at the discretion of the subject's in patient
attending. All controller medications used before and during hospitalization will be
recorded as part of the study data.
- Children 1 to 18 years of age with a known history of asthma being admitted to Akron
Children's Hospital general medical floor for the treatment of moderate to severe
- Children who have a concurrent pneumonia or bronchiolitis (diagnosed clinically or by
- Have a diagnosis of chronic lung disease (ex. cystic fibrosis, bronchopulmonary
dysplasia, chronic aspiration)
- Have cyanotic congenital heart disease, a congenital anomaly of the respiratory
tract, or who are tracheostomy or ventilator dependent.
- Children who are determined by the Emergency Department (ED) or general pediatrics
service to need ICU level care on admission will also be excluded.
- Children will also be excluded if their legal guardian does not speak English as all
consent forms will be written and reviewed with guardians in English.
- Children will also be excluded if their legal guardians disagree on consent to
participate, or if a child 9 years or older and their legal guardians disagree on