DISCUSSION
In this large single-centre retrospective study, we sought to identify
factors that can predict HFNC failure in a homogeneous group of infants
hospitalized with severe bronchiolitis. We demonstrated that patients
who experienced a failure of HFNC because of a progressive respiratory
insufficiency showed more frequently a complete upper lobe consolidation
on CXR than infants in whom HFNC allowed to overcome respiratory
distress. They were younger and had a lower PLT/MPV and lymphocyte count
than patients who underwent HFNC only.
In this study, the main feature associated to HFNC failure was the
presence of a complete upper lobe consolidation that affected 90.9% of
patients requiring escalation to MV. These infants were also younger and
the underdeveloped collateral ventilation together with a particularly
acute angle of the right upper lobe bronchus may predispose young
infants to atelectasis [10]. Strong evidence has demonstrated that
age less than 3 months and low body weigh are significant severe
bronchiolitis risk factors [11, 12]. In fact, anatomic factors play
a key role: the neonates and young infants’ airways are small and more
easily get obstructed, causing respiratory distress and therefore the
recourse to mechanical ventilation. In case of a complete lobar
consolidation with airflow obstruction, airways resistance increases and
this aspect as well as the decreased lung compliance may contribute to
respiratory distress [13]. Providing low levels of positive airway
pressure, HFNC could be able to prevent upper airways collapse and to
allow alveolar recruitment. Meanwhile, positive end-expiratory pressure
(PEEP) generated by invasive mechanical ventilation may also help to
overcome airway resistance and atelectasis. Presumably, patients
requiring escalation to MV had a severe ventilation/perfusion (V/Q)
mismatch of an extent, which HFNC was not enough to overcome hypoxia and
respiratory distress.
Considering the timing of the lung involvement, among patients who
needed MV the complete upper lobe consolidation was not sudden: 72.7%
of them had a gradual development of atelectasis on CXR (Figure 2). For
this reason, it could be useful an early identification of consolidation
and a follow up by a simple, non-invasive and easy to perform technique,
such as for example lung ultrasound [14, 15]. This remarkable
evidence is also supported by data from the four patients that arrived
over the same seven epidemics in our Emergency Department in such severe
conditions that underwent MV directly and all had an upper lobe
consolidation on CXR (data not shown). An early identification of these
patients may allow physicians to consider a preventive treatment and to
monitor closely them with a proper recognition of deterioration.
Analysing possible treatments of this condition, ample evidence reports
that the use of recombinant human DNase in the management of severe RSV
bronchiolitis improves clinical conditions and chest radiograph and
leads to resolution of atelectasis [16,17]. Recent reports described
that neutrophil, massively recruited in RSV bronchiolitis, release
neutrophil extracellular traps (NETs) in the extracellular space in
response to several pathogens. NET entraps and facilitates the killing
of microorganisms but excessive NET release has detrimental effects,
causing lung injury [18]. NETs could be degraded by recombinant
human DNase (rhDNase), pointing out that nebulised rhDNase might have a
fundamental role in severe bronchiolitis complicated by atelectasis
[19]. Supporting these data, we report a clinical case of one of
patients enrolled suffering from severe bronchiolitis and supported by
HFNC. CXR showed a segmental upper lobe consolidation, clearly improved
after nebulised rhDNAse (Figure 3).
Another possible therapeutic option comes from several papers evaluating
the clinical utility of chest physiotherapy in infants with
bronchiolitis even if results are conflicting. A recent review shows
that chest physiotherapy does not influence clinical course in
hospitalised infants with acute bronchiolitis [20]. Nevertheless,
since airway clearance techniques improve mobilization and transport of
secretions reducing airway obstructions by mucus plugs [21], chest
physiotherapy could be implemented, particularly in selected infants
with bronchiolitis and CXR consolidation.
The analysis of the clinical severity score at HFNC positioning showed
that infants who required escalation to MV presented a higher disease
severity with an increased respiratory effort, while no differences in
clinical severity score at hospital admission or in days of disease
between the two groups were found. Moreover, HFNC failure was noticed
mostly in infants supported by standard oxygen therapy before starting
HFNC. These findings suggest the importance of not postponing the use of
HFNC; infants with first signs of respiratory distress could benefit
from an early use of HFNC.
When we evaluated laboratory predictors of HFNC failure, we demonstrated
a decreased number of peripheral blood lymphocytes and a low PLT/MPV
ratio in infants with higher disease severity and escalation to
mechanical ventilation. Recent reports showed that PLT/MPV ratio is a
promising biomarker helping to discriminate between sepsis and viral
disease [22]; moreover, lymphocytes depletion is associated to more
severe forms of bronchiolitis [23].
In conclusion, our main finding is that a complete upper lobe
consolidation in young infants is a significant risk factor for HFNC
failure and for the recourse to mechanical ventilation. Further studies
are needed to understand if an early identification of consolidation
following by an adequate follow-up and by proper therapeutic strategies
may further reduce the number of children who require mechanical
ventilation.