Bronchiolitis - Emerging treatments

Novel antiviral compounds

Several antiviral compounds are in clinical development. These include therapies that block the respiratory syncytial virus (RSV) fusion protein (e.g., ziresovir). One double-blind randomised control trial showed a reduction in signs and symptoms of RSV infection in hospitalised infants when treated with ziresovir.[110]

Surfactant

Surfactant deficiency has been reported in infants with bronchiolitis, perhaps as a consequence of airway inflammation and cellular necrosis. Small randomised controlled trials of surfactant therapy in infants with bronchiolitis requiring mechanical ventilation showed improvements in respiratory mechanics, but no effect on the duration of ventilation.[111][112] Further studies on the use of surfactant therapy in bronchiolitis are needed before this treatment can be recommended.[113][114]

Helium-oxygen

Helium-oxygen (heliox) mixtures reduce resistance in the large- and medium-sized airways, where flow is turbulent and density-dependent. They may also help convert turbulent flow areas to laminar ones. Studies involving small sample sizes have demonstrated improved clinical scores with heliox therapy in infants with bronchiolitis.[115][116][117] One large study has demonstrated a decrease in length of therapy in addition to improved clinical score.[118] However, the decrease in length of therapy was only seen when heliox was administered via a tight-fitting face mask or continuous positive airway pressure (nasal cannula was ineffective).[118] Conversely, in a meta-analysis, no reduction in rate of intubation, admissions, or length of stay was observed.[116] Because the concentration of helium needs to be at least 50% for the density-dependent effects of helium-oxygen to be clinically significant, this therapy cannot be used in severely hypoxaemic infants.[44] [ ]

Montelukast

Although montelukast has not been effective in the treatment of acute RSV infections, some trials have suggested a role for this agent in decreasing post-bronchiolitic wheezing.[119] The data remain controversial, and further trials are needed.[5][120][121][122][123][124][125] [ ]

Immunoglobulin

While immunoglobulin has been used to prevent episodes of severe bronchiolitis caused by RSV, it is not licensed for use as a treatment for hospitalised infants with bronchiolitis. One meta-analysis of 8 studies of immunoglobulin involving 906 infants and children aged <3 years, hospitalised with RSV bronchiolitis found no difference in mortality between those who did and did not receive immunoglobulin, but because of the low event rate the authors could not comment on the therapy’s effect on mortality with any certainty.[126] There was also no difference in duration of hospitalisation, need for or duration of mechanical ventilation or supplemental oxygen, need for intensive care, or adverse events between those who did and did not receive immunoglobulin. Different formulations of immunoglobulins were used across studies including anti-RSV immunoglobulin. The authors of the meta-analysis noted that all studies were conducted in high-income countries where mortality from bronchiolitis is low.

Caffeine

Caffeine for apnoea in bronchiolitis has been studied in a young infant population and, while safe, has not been proven to change outcomes. A double-blind randomised controlled trial of single-dose intravenous caffeine did not show reduction in apnoea episodes when compared with placebo.[127]

Vitamin D

The active metabolite of vitamin D (calcitriol) plays a role in both innate and adaptive immunity. Its immunomodulatory function has been examined in terms of improving incidence and severity of bacterial and viral infections, as well as in treatment of severe asthma exacerbations.[128][129] Studies that have examined vitamin D levels in infants and children with acute bronchiolitis have reported conflicting results, but most demonstrate a correlation between lower vitamin D levels and more severe disease.[130] Vitamin D supplementation of infants with bronchiolitis was associated with shorter time to resolution of the disease, faster return to oral feeding, and shorter duration of hospitalisation compared with placebo controls.[131]

Zinc sulfate

Zinc sulfate given to 50 infants with acute bronchiolitis on a general ward shortened duration of hospitalisation, although length of stay for both treatment and control groups was longer than in most other studies.[132]

Inhaled nitric oxide (iNO)

In post hoc analyses of a study designed to assess the safety and tolerability of iNO in 21 infants with bronchiolitis, infants who were hospitalised for more than 24 hours and who received iNO had a shorter length of stay compared with those who did not receive iNO. There was no difference between the two groups in duration of hospitalisation for those discharged in under 24 hours.[133] A subsequent small randomised trial of intermittent high-dose iNO in hospitalised infants with bronchiolitis reported a trend to improved clinical efficacy compared with standard therapy; further research is required.[134] One meta-analysis of these and one additional study showed no significant difference in length of stay between groups who did and did not receive iNO; however, the total number of subjects (n=166) was small and so differences might have been missed. There were more frequent treatment-associated adverse events among the iNO group, including transient oxyhaemoglobin desaturation and restlessness.[135]

Azithromycin

No studies have supported the routine use of macrolide antibiotics in children with bronchiolitis to reduce hospitalisation, duration of supplemental oxygen use, or length of hospital stay.[96] One 2024 meta-analysis of 7 studies provided evidence of low certainty that azithromycin did not prevent the need for intensive care unit care or episodes of recurrent wheezing, but there was moderate-quality evidence that azithromycin use shortened duration of hospitalisation, albeit by only -0.27 days.[136]

Traditional Chinese Medicine

In a double-blind randomised trial of hospitalised infants with acute bronchiolitis (3-24 months old, n=133), Laggera pterodonta, a traditional Chinese medicine, resulted in a greater proportion of children fulfilling discharge criteria at 96 and 120 hours compared with controls.[137] One 2022 meta-analysis of 46 studies showed that the integration of traditional Chinese medicine with Western medicine was more efficacious than Western medicine alone in the treatment of infants with bronchiolitis.[138] Similarly, duration of hospitalisation was shorter, the recurrence rate of bronchiolitis was lower, and there was no difference in adverse events when traditional Chinese medicine was paired with Western medicine. The authors noted that further studies are needed to establish specific protocols for the use of traditional Chinese medicine in clinical practice.