Azithromycin for Children Hospitalized With Asthma

Asthma is a chronic lung condition that accounts for over 130,000 pediatric hospitalizations
nationally at a cost of almost 1.4 billion dollars. Atypical pathogens have been implicated
both in initiating asthma and triggering acute asthma exacerbations. Azithromycin, a
macrolide antibiotic, is known to have antibacterial activity against atypical pathogens and
gram positive bacteria. More recently, macrolides have been increasingly used and effective
against gram negative bacteria and inflammation in the lungs of patients with chronic
respiratory illnesses. This effect may be secondary to the immunomodulatory effects
macrolides possess, in addition to their anti-bacterial effects. In long-term therapy with
macrolides, patients with asthma have shown improved bronchiolar hyperreactivity, spirometry,
symptoms, and quality of life. However, studies of short-term treatment in the acute setting
and in children are limited. Some practitioners use azithromycin in the treatment of acute
asthma, despite limited data.

The investigators propose a double-blind, randomized, placebo-controlled trial of
azithromycin in children aged 4-12 years with persistent asthma hospitalized with acute
asthma exacerbations. Children will be enrolled within 12 hours of admission and will be
randomized to receive three days of either azithromycin or placebo suspension (10mg/kg/dose,
max of 500mg). The primary outcome measure will be length of stay (LOS). Secondary outcome
measures will include: days of school/work missed, readmission rates, return to medical care
rates, recurrence of symptoms, and steroid courses. In the future, patients may also be
approached to enroll in the "Mechanism Subset Study" a separate pilot and feasibility study
which will require two blood samples and two nasal aspirate samples and will test for
atypical pathogens, interleukin-8 levels, and neutrophil/eosinophil counts. The average
length of stay for patients in this age range with asthma in 2011 at our institution was 3.0
days. The investigators will enroll to achieve a power of 80%, with an alpha of 0.05, which
will require 107 patients in each group to detect a 16 hour (0.67 day) difference in the
primary outcome, LOS. This study hypothesizes that azithromycin treatment in children
hospitalized with acute asthma will decrease LOS.

Inclusion Criteria:

- 4-12 years of age

- Admission diagnosis of asthma at the Children's Hospital at Montefiore

- History of persistent asthma (as defined by National Heart, Lung, and Blood Institute)

Exclusion Criteria:

- Concurrent bacterial infection requiring antibiotics

- Antibiotics received within previous 2 weeks

- Contraindication to azithromycin (including allergy to macrolides)

- Chronic lung disease other than asthma (including bronchopulmonary dysplasia, cystic
fibrosis, bronchiectasis) or home oxygen requirement

- Immunodeficiency (primary or acquired)

- Chronic systemic steroid use

- Invasive or non-invasive mechanical ventilation required acutely as result of current
asthma admission

- Significant cardiac co-morbidity (including hemodynamically significant cardiac
disease or arrhythmia)

- Liver disease (hepatitis)

- Pregnancy

- Seizure disorder, currently on anti-epileptic medication)

- Receiving albuterol every 4 hours (q4h) at the time of enrollment

- Previous enrollment in study