CPAP for Hypoxemic Acute Chest Syndrome in Sickle Cell Disease

Sickle cell disease (SCD) is a severe hemoglobinopathy, considered the first monogenic disease in the world. Acute chest syndrome (ACS), one of the most frequent and serious complications of SCD, is defined by the association of fever and/or acute respiratory symptoms with a new pulmonary infiltrate on chest imaging. ACS is characterized by lung consolidation, severe pulmonary vascular dysfunction, with potential role for regional alveolar hypoxia. Therefore, improving alveolar oxygenation and limiting lung consolidation are key objectives of the treatment of ACS, in addition to ensuring pain relief and giving blood transfusions and antibiotics. Bilevel non-invasive ventilation failed in improving outcomes during ACS (Fartoukh 2010). These results are in accordance with those reported in other forms of acute lung injury (Frat 2015), with conflicting results. Among other explanations, NIV may favour high tidal volume ventilation leading to patient self-inflicted lung injury (P-SILI) (Carteaux 2016). Continuous positive airway pressure (CPAP) is a simple to use and affordable technique for non-invasive ventilatory support, that theoretically exposes to a lower risk of P-SILI (Carteaux 2021). In patients with acute hypoxemic respiratory failure (AHRF), applying a positive pressure to the airway opening has been shown to mitigate the reduction in functional residual capacity and to improve respiratory mechanics and gas exchange. In a randomized controlled trial (RCT) conducted in patients with AHRF, CPAP achieved early physiologic improvement (Delclaux 2000). Recent results also suggest that CPAP reduces the composite outcome of intubation or death in adults with AHRF due to COVID-19 in a large multicentre study (RECOVERY-R) (Perkins 2022). In addition, CPAP can be safely used at early stages in the wards, with a frugal approach, using virtual valves (Carteaux 2021). In patients with SCD, CPAP has shown benefits when used at night in children with sleep apnea (Marshall 2009), or for the peri-operative management (Leff 2007). CPAP is also used in clinical practice for hypoxemic ACS (Heilbronner 2021), but it has not been formally assessed in this setting.

Inclusion Criteria: * SCD patient of all genotypes (SS, SC, S/β0 and S/β+) * Age ≥ 18 years old * Hospitalised for ACS (defined as the association of fever and/or acute respiratory symptoms with a new pulmonary infiltrate on chest imaging) * Requiring supplemental O2 ≥ 2 L/min for SpO2 ≥ 95% * Informed consent from the patient * Affiliated to a social security regime Exclusion Criteria: * Patient having both ACS criteria and need for supplemental O2 ≥ 2 L/min for SpO2 ≥ 95% since more than 48 hours * Requirement for home supplemental O2 or home CPAP / NIV. * Signs of worsening respiratory failure mandating intubation (as defined in (Helms et al., 2024)) * Current enrolment in another interventional research concerning a respiratory support during ACS * Known legal incapacity (patients under guardianship or curatorship) * Exacerbation of asthma, chronic obstructive pulmonary disease or another known or suspected chronic respiratory disease * Absolute contraindications to CPAP, including any of the following: patient not cooperating or opposing the technique, pneumothorax not drained, chest wound blowing, uncontrollable vomiting, upper gastrointestinal bleeding, craniofacial trauma, severe upper airway obstruction, traumatic tetraplegia at the initial phase, cardiac arrest, shock (need for vasopressor), or Coma Glasgow scale \