Surfactant does not help babies with severe bronchiolitis - the largest trial of its kind confirms

University of Liverpool / UKRI Medical Research Council / NIHR

The logic was appealing. Babies with severe bronchiolitis have depleted surfactant in their lungs - the slippery coating that keeps air sacs open and breathing effortless. Premature babies have the same problem, and giving them surfactant is one of neonatology's clearest success stories, saving thousands of lives every year. So why not try surfactant in bronchiolitis?

For years, that reasoning sustained small studies, case series, and clinical optimism. Now the question has been answered definitively. The Bronchiolitis Endotracheal Surfactant Study (BESS), the largest randomized trial of surfactant for bronchiolitis ever conducted, found that the treatment made no difference. Babies who received surfactant spent the same amount of time on ventilators as those who did not.

Six winters, fifteen hospitals, one clear answer

The BESS trial enrolled 232 critically ill babies across 15 children's hospitals in England, Scotland, and Northern Ireland over six consecutive winter seasons from 2019 to 2024. These were among the sickest infants - the roughly one thousand babies each year in the UK whose bronchiolitis is severe enough to require mechanical ventilation in an intensive care unit.

The trial was funded jointly by the UK's Medical Research Council, the National Institute for Health and Care Research, and Chiesi Farmaceutici, an Italian pharmaceutical company that manufactures surfactant products. Its results, published in The Lancet Respiratory Medicine on March 21, 2026, represent the kind of rigorous evidence that smaller studies could never provide.

The primary outcome was straightforward: duration of mechanical ventilation. Surfactant did not reduce it. The treatment was safe - no excess of adverse events appeared in the surfactant group - but it simply did not work for this condition.

Why premature lungs and bronchiolitis lungs are not the same

The negative result, while disappointing, makes biological sense on closer inspection. In premature babies, surfactant deficiency is the primary problem. The lungs have not matured enough to produce adequate amounts of the protein-lipid mixture that reduces surface tension in alveoli. Giving surfactant directly addresses the root cause.

In bronchiolitis, the situation is more complex. The virus - most commonly respiratory syncytial virus (RSV) - triggers inflammation that damages airway epithelial cells, causes mucus plugging, and disrupts surfactant function. But surfactant depletion is a consequence of the viral infection, not the cause of respiratory failure. Replacing surfactant without addressing the underlying viral inflammation and airway obstruction is treating a downstream effect while the upstream problem continues.

Calum Semple, the study's lead investigator from the University of Liverpool and Alder Hey Children's NHS Foundation Trust, put it plainly: the treatment was safe, but it did not make any difference to how long babies stayed on ventilators.

The RSV burden that drives the search for treatments

The urgency behind this trial reflects the scale of the bronchiolitis problem. RSV is the leading cause of infant hospitalization in the UK during winter months. Each year, roughly 25,000 babies are admitted with bronchiolitis. Most recover with supportive care - oxygen, fluids, and monitoring. But about a thousand of the most severely affected require intensive care and mechanical ventilation.

For those thousand babies, there is currently no specific treatment. Clinicians provide supportive care and wait for the immune system to clear the virus. Antiviral drugs for RSV exist but are not widely used in infants. Antibiotics are ineffective because bronchiolitis is viral. Corticosteroids, which help in other respiratory conditions, have been shown in previous trials not to benefit bronchiolitis.

This string of negative trials - steroids do not work, surfactant does not work - is discouraging but also informative. It progressively narrows the field of plausible interventions and reinforces the importance of prevention over treatment.

Prevention through maternal vaccination

On the prevention front, the picture is considerably brighter. A maternal RSV vaccine, given to pregnant women in their third trimester, is now available in the UK. The vaccine stimulates the mother's immune system to produce antibodies against RSV, which are then transferred to the fetus across the placenta. The newborn arrives with a stock of protective antibodies that reduce the risk of severe bronchiolitis in the first months of life.

Semple used the trial's publication as an occasion to encourage uptake of this vaccine, noting that while researchers continue to search for better treatments for sick babies, the most effective current strategy is to prevent severe infection in the first place.

The monoclonal antibody nirsevimab, which provides passive immunity to infants at high risk of severe RSV, offers another preventive option. Together, maternal vaccination and infant immunoprophylaxis may eventually reduce the number of babies who end up in intensive care with bronchiolitis, making the question of how to treat them less urgent.

What the trial could not test

The BESS trial answered the question it was designed to answer, but several related questions remain open. The trial enrolled babies who were already on mechanical ventilation - the most severe cases. Whether surfactant might benefit infants earlier in the disease course, before ventilation is required, was not tested. Some researchers have hypothesized that early surfactant administration, before significant airway inflammation develops, might have different effects than treatment in established disease.

The trial also could not determine whether specific subgroups of babies - perhaps those with particular RSV strains, co-infections, or genetic backgrounds - might benefit from surfactant even though the overall group did not. Subgroup analyses in a 232-patient trial lack statistical power to detect such effects reliably.

The six-winter recruitment period spanned the COVID-19 pandemic, which disrupted RSV circulation patterns in ways that are still being understood. Whether the pandemic years introduced unusual patient characteristics that influenced the results is difficult to assess.

A definitive answer when medicine needed one

Negative trials rarely generate excitement, but they serve a critical function. Before BESS, clinicians faced a genuine uncertainty: should surfactant be used in severe bronchiolitis? Small, underpowered studies had produced mixed signals. Some clinicians used surfactant off-label based on physiological reasoning and fragmentary evidence. Others held off, waiting for better data.

That uncertainty is now resolved. Surfactant does not belong in the treatment of severe bronchiolitis. The resources, both clinical and financial, that might have been directed toward surfactant therapy can be redirected toward more promising avenues - including preventing bronchiolitis through vaccination and developing antiviral treatments that target RSV directly.

The researchers who spent six years running this trial across fifteen hospitals might reasonably be disappointed that their intervention did not work. But in a field littered with treatments adopted on weak evidence and abandoned years later, a definitive negative answer has its own value. It tells the next researcher where not to look, and it tells the clinician at the bedside to focus elsewhere.