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.