Efficacy and Safety of Increasing Doses of Inhaled Albuterol in Children With Acute Wheezing Episodes
Condition: Asthma; Children
MeSH terms: Respiratory Sounds
Study type: Interventional

Summary: 
      Metered dose inhalers with spacers are devices capable of providing higher rates of lung
      deposition of drugs such as beta agonists when compared to conventional nebulizers, but there
      is no consensus about the optimal dose when this is the device of choice and there is
      evidence that younger children need proportionally higher doses of albuterol (in μg/kg) when
      compared to older children. Other factors that may interfere with response to albuterol
      treatment include the genetics of the beta adrenergic receptor (ADRβ2) and infectious
      etiology of the wheezing attack. This study will assess the effectiveness of a dose regimen
      that prioritizes higher doses of albuterol, with doses in μg/kg higher for younger children.
      Security of this new dosing regimen will be assessed by monitoring clinical side effects and
      serum levels of albuterol, but the investigators will also examine the presence of 12
      different respiratory viruses in these patients and evaluate the influence of ADRβ2 receptor
      genetics in the response to albuterol. The primary outcome measure will be the need for
      hospitalization. Secondary outcomes will include a change in clinical score, respiratory rate
      and forced expiratory volume in the first second, the need for additional treatments and
      length of stay in the emergency room for those not hospitalized.
    

Detailed description: 
      This is a prospective, randomized, double blinded, controlled study. The patients will be
      randomly assigned to one of the treatment groups (experimental or control groups).

      The patients will be assessed 1 hour later and every 30 minutes thereafter until discharge.
      Following 4 hours in the emergency room, any patient who do not meet the discharge criteria
      (PRAM score ≤ 3 and SpO2 ≥ 92%) will be admitted to the hospital. Each patient's attending
      physician will determine the need for additional therapies following the first hour.

      Identification of respiratory viruses in the nasal lavage samples wil be performed using the
      CLART PneumoVir® kit.

      Albuterol plasmatic levels will be analyzed via HPLC (High Performance Liquid
      Chromatography).

      To genotype the ADBR2 receptor (blood samples), the gene regions encompassing the Arg16Gly,
      Gln27Glu, and Arg19Cys Thr164Ile polymorphisms will be amplified via PCR. The resultant
      amplimers were then sequenced.

      A sample of 124 patients (62 in each group) was calculated to provide an 80% power with which
      to detect a significant difference of at least 30 minutes in the lengths of stay between the
      groups. The chi-square test will be used to compare hospital admission rates and tremor
      rates. For all other outcomes, t-tests for mean comparisons (variables with a normal
      distribution), a Mann Whitney test (nonparametric data) and ANOVA with repeated measures will
      be used.
    

Intervention name(s): Albuterol - Experimental; Albuterol - Control
Intervention type(s): Drug; Drug
Intervention description(s): The Experimental group will receive higher doses of albuterol in the first hour: 900 mcg (up to 15 kg), 1200 mcg (> 15 to 20 kg), 1500 mcg (> 20 to 25 kg) and 1800 mcg (> 25 kg).; The Control group will receive the following doses of albuterol in the first hour 600 mcg (up to 25 kg) or 1200 mcg (> 25 kg)
Other intervention name(s): Ventolin; Ventolin
Intervention MeSH terms: Albuterol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: asthma; albuterol; metered dose inhalers