The UK Oscillation study (UKOS) was a large multicenter trial in the UK of high-frequency compared to conventional ventilation; 800 babies <29 weeks gestation were randomized, if they were intubated from birth and were less than 1 hour old, to HFO or conventional ventilation. The study basically showed no differences in anything in terms of clinical outcomes. Mortality and BPD were almost identical in the 2 groups, sub-groups were the same, and secondary outcomes were also not different. Six hundred babies survived, and most were followed up for some short/moderate term outcomes, which were also not different.
A new publication from the group reports the very long term pulmonary outcomes of 320 of those (nearly 600) survivors, who were seen at 11 to 14 years of age. 240 of them had pulmonary function testing. Many aspects of pulmonary function were better in the HFO group compared to the conventional group; including the FEF50, The FEV, the PEF, the DLco, and the lung resistance. Functional/educational outcomes were mostly the same between groups with none being worse with HFO.
The major limitation of the study is, obviously, the losses to follow up, relatively small advantages of conventional ventilation among the infants not followed would completely wipe out these differences, so we need to be very careful in interpreting these results. However, it certainly suggests that very long term pulmonary outcomes from the 2 types of ventilator approaches show no major disadvantage of high frequency, and it may have an advantage.
How could long term outcome be better if there wasn’t any improvement in BPD? I think the answer to this question, in part, has to do with diagnostic categories, and how we define outcomes. Lung injuries in preterm babies are a continuum, from none to profound: division into BPD/Not BPD is entirely arbitrary as far as clinical outcomes in the long term are concerned. 36 weeks of oxygen requirement was chosen as a cut-off in Andy Shennan’s cohort, because it was more closely associated with having adverse respiratory outcomes (which included symptoms at discharge, O2 at term, readmission for respiratory problems etc) than did O2 need at 28 days. The definition was not intended to predict extremely long term outcomes; and even though we now also have the refinement suggested by Bancalari and Jobe, that is into categories of mild, moderate, and severe, there is still no good data about whether the division into moderate or severe is a better discriminant of very long term pulmonary outcomes.
Certainly this study (with the limitations of possible bias introduced by ‘low’ follow up percentage) suggests that HFO might reduce lung injury, even though there was no effect on which babies are classified as being BPD (compared to being Not BPD). I think, however, that it is not surprising that that permanent structural/vascular impacts on the very preterm lung are not accurately predicted by something as simplistic as oxygen requirements at 36 weeks. Other indices of lung injury might be much more useful than just deciding yes/no on the diagnosis of BPD, based on need for oxygen.