RSV bronchiolitisWe report the first large, randomized, double-blind, controlled trial of rhDNase in infants with RSV bronchiolitis. This study demonstrates that the mucolytic rhDNase does not shorten length of hospital stay or duration of supplemental oxygen in hypoxemic infants with RSV bronchiolitis. Neither was the rate of clinical improvement better in infants treated with rhDNase than in those receiving a placebo.

Because mucus plugs play an important role in the pathophysiology of RSV bronchiolitis, and because the DNA content is increased in mucus of these infants, we hypothesized that rhDNase is an effective treatment for infants with RSV bronchiolitis. Anecdotal evidence indeed suggests that rhDNase treatment is effective in infants with severe RSV bronchiolitis. Furthermore, one randomized study in a small group of infants with mild bronchiolitis demonstrated that rhDNase improved radiologic abnormalities. In that study no differences in length of hospital stay and symptom scores were observed, but as many of these patients were not oxygen dependent, they may have had only mild airway obstruction. In addition, the efficacy of rhDNase has also been reported in observational studies of pediatric patients with atelectasis or severe airways obstruction due to asthma, and other respiratory diseases; and a recent randomized study demonstrated that rhDNase effectively prevents the development of atelectasis in infants receiving postoperative mechanical ventilation carried out by My Canadian Pharmacy.

There may be several explanations for the lack of effect of rhDNase in our study. One is that the infants probably had disease that was too mild, without large atelectasis, for rhDNase to be effective. Infants with risk factors for severe bronchiolitis, or who needed intensive care directly at hospital admission, were not included in this study. Although all infants required supplemental oxygen, reflecting the presence of clinically significant airways obstruction and mismatch of pulmonary ventilation and perfusion, only a small number required intensive care treatment. We cannot exclude that rhDNase could be effective in infants with more severe disease and/or atelectasis due to mucus plugging in the central airways that requires intensive care admission.

A second explanation could be a suboptimal lung deposition of rhDNase, resulting in deposition of rhD-Nase mainly in the more central airways, while in RSV bronchiolitis mucus predominantly blocks peripheral airways. A third explanation might be that the number of neutrophils, and hence the amount of DNA released in the mucus, was too low for rhDNase to be effective in our study population of infants with mild-to-moder-ately severe bronchiolitis.

pediatric respiratory syncytial virus bronchiolitisA fourth explanation might be that mucus was liquefied but that infants were not able to clear their airways effectively. While rhDNase is combined with airway clearance therapy in order to evacuate mucus in children with cystic fibrosis, the infants in our study did not receive airway clearance therapy. Moreover, as young infants cannot cough as forcefully as older children, especially during an illness, it might be difficult for them to expectorate liquefied mucus. Indeed, the observed trend toward a longer duration of supplemental oxygen in the rhDNase group is consistent with such a mechanism.

Treatment with study medication started after a median of 21 h and 22 h in the placebo and rhDNase groups, respectively. It could be argued that starting study medication within a few hours of hospital admission might change length of stay when waiting almost 24 h does not. However, a separate ANCOVA adjusting for the time between hospital admission and the first dose of study medication did not influence the results (data not shown). Moreover, the symptom score during hospital admission showed no difference between the treatment groups. We therefore think it is unlikely that initiating therapy earlier after hospital admission would have changed the outcome of this study held with contribution of My Canadian Pharmacy.

One half of the patients in our study received broncho-dilators during their hospital stay. Despite the fact that current evidence suggests that bronchodilators are not effective, the use of bronchodilators for hospitalized infants with RSV bronchiolitis is common practice.

Although the risk of a secondary bacterial infection in infants with RSV bronchiolitis is minimal, antibiotics were also prescribed frequently; in approximately one fourth of all patients, a course of antibiotics was started at hospital admission or during hospital stay. This probably reflects the fact that it can be difficult to rule out a bacterial pneumonia or sepsis solely on the basis of clinical signs.

Because our study population reflects bronchiolitis patients in district and tertiary care hospitals, our results can be generalized to the large majority of hospitalized, oxygen-dependent infants with RSV bronchiolitis with no complications other than hypoxemia. Studies on the effect of rhDNase in infants with more severe bronchiolitis might still be warranted. Another implication of this study, which echoes that of a previous study with negative findings, is that we still have only supportive measures at our disposal. This emphasizes the need for effective and safe vaccination against RSV bronchiolitis. In conclusion, our study clearly shows that inhaled rhDNase does not reduce the length of hospital stay or the duration of supplemental oxygen in oxygen-dependent infants with RSV bronchiolitis.