The acute respiratory distress syndrome (ARDS) consists on a lack of breath due to fluid overload in the lungs that is not produced by a heart desease. Some people with this condition may need to be intubated and connected to invasive mechanical ventilation, but less severe cases may need supplementary oxygen that can be delivered with non-invasive devices, such as CPAP (continuous positive airway pressure) or HFNO (high flow nasal oxygenation). CPAP consists on a facemask that provides oxygen-enriched air at a high pressure, whereas HFNO consists on nasal cannula that provides oxygen-enriched air at a high flow.

Patients with ARDS may present with high respiratory efforts that can eventually damage their own lungs and contribute to the development of a phenomenon known as patient self-inflicted lung injury (P-SILI). Previous research has identified that CPAP may be successful in attuenuating P-SILI compared to HFNO, but it is not known whether this attenuation actually results into a reduction in lung injury in real patients.

In this multicentre trial, 120 non-intubated patients with stablished ARDS will be randomly assigned to receive oxygen-enriched air through either CPAP or HFNO for 48 hours plus standard intensive care. The primary goal of this study is to determine the pulmonary effect of CPAP and HFNO through lung injury biomarkers that can be detected in blood, such as sRAGE (soluble Receptor of Advanced Glycation End-products), angiotensin-II, interleukin-6 and interleukin-10. It will also be studied whether CPAP reduces 48-hour traqueal intubation rate, 90-day traqueal intubation rate and 90-day mortality.

Identifying that CPAP attenuates lung injury in spontaneously breathing ARDS patients will help clinicians to better understand this condition and to better treat this patients, so they do not evenutally need traqueal intubation and connection to invasive mechanical ventilation.

The acute respiratory distress syndrome (ARDS) is defined as an acute hypoxemic respiratory failure with non-cardiogenic pulmonary opacities. This condition has been recently extended to non-intubated patients. Patients under non-invasive respiratory support might present with high transpulmonary pressures, pulmonary strain and pendelluft, which contribute to the development of patient self-inflicted lung injury (P-SILI). Previous studies have identified that continuous positive airway pressure (CPAP) is successful in attenuating P-SILI effectors compared to high flow nasal oxygenation (HFNO). However, it remains uncertain whether this attenuation actually results into a reduction in lung injury and improved clinical outcomes.

This is a multicentre, randomised, open-label, controlled trial. 120 non-intubated patients with established ARDS will be randomly assigned to receive non-invasive respiratory support with either CPAP 12 cmH2O or HFNO 50 L/min for 48 hours plus standard intensive care. The primary outcome is biological lung injury evaluated through the epithelial pulmonary dysfunction biomarker sRAGE (soluble Receptor of Advanced Glycation End-products). Secondary outcomes include plasmatic pulmonary dysfunction biomarkers (angiotensin-II, interleukin-6, interleukin-10), P-SILI effectors (pulmonary strain, pendelluft, transpulmonary pressure), 48-hour traqueal intubation rate, 90-day traqueal intubation rate and 90-day mortality. All analyses will be conducted according to the intention-to-treat principle.

This study will assess the potential role of CPAP in attenuating P-SILI effectors and inflicting less biological lung injury compared to HFNO. This physiologic effect may lead to lower rates of traqueal intubation and mortality. This project will provide new knowledge on the respiratory management of non-intubated ARDS patients, a subject where evidence is lacking.

Inclusion Criteria:

• PaO2/FiO2 ratio <300 mmHg with FiO2 >40% and PEEP ≥5 cmH2O (CPAP) or flow ≥30 L/min (HFNC).
• Bilateral pulmonary opacities observed in the chest X-ray, thoracic computerized tomography (CT) scan or lung ultrasonography (bilateral B lines)
• <7 days from the pulmonary insult to symptom onset and criteria 1 and 2
• Not meeting the aforementioned criteria for >24 hours prior to study inclusion.

Exclusion Criteria:

• Age <18 years or >80 years
• History of chronic respiratory failure or interstitial pulmonary disease
• Acute cardiogenic pulmonary edema after echocardiographic evaluation
• Having received either invasive mechanical ventilation or non-invasive mechanical ventilation (NIV)
• Atelectasis, pleural effusion, pulmonary masses or nodules as the primary finding in thoracic imaging.
• "Do not intubate, do not resuscitate" orders
• Presenting significant nasal obstruction.