Bronchiolitis is defined as an infection of the small airways. It is also the most common manifestation of acute lower respiratory infection (ALRI) in early infancy, and is the leading cause of global child mortality. Viral bronchiolitis is currently the most common reason for pediatric hospital admission in the US, accounting for almost 20% of all-cause infant hospitalizations. Viral etiology is the main cause, and among the respiratory viruses, respiratory syncytial virus (RSV) is believed to be the most important viral pathogen causing ALRI in young children. Worldwide, it is estimated that 60,000 to 199,000 children younger than 5 years die yearly from RSV-associated ALRI, with 99% of these deaths occurring in developing countries. The disease is common mainly in the first year of life. The clinical signs and symptoms are consistent with hypoxia,difficulty breathing, coryza, poor feeding, cough, wheeze and crepitations on auscultation, and in some cases respiratory failure.
No specific treatment is approved for bronchiolitis-associated viral infection and, currently, only supportive treatment such as oxygen (O2) and inhalations of hypertonic saline or steroids with or without beta agonist drugs are being used. Subjects with hypoxemia should be hospitalized for O2 supplementation and supportive treatment. It is estimated that in the year 2005, 3.4 (2.8–4.3) million young children worldwide developed RSV-associated severe ALRI necessitating hospitalization.
Hospitalization for bronchiolitis is expensive, with US hospital charges alone having exceeded $1 billion in 2006. These charges in part reflect length of stay (LOS) in the hospital. In a recent study of approximately 300 infants with acute bronchiolitis, the median LOS (measured as time to “fit for discharge”) was 3.2 days.
We have conducted a double-blind, randomized, single-center, 2-arm study. The primary objectives were to study the safety and tolerability of 160 ppm NO intermittent inhalation treatment in 2- to 12-month old subjects admitted to hospital and diagnosed with acute bronchiolitis. The planned secondary objectives were to assess the efficacy of NO intermittent inhalation treatment (in addition to standard O2 treatment) compared to standard O2 treatment alone, assessed as the LOS, clinical score improvement, and length of standard O2 treatment.