Acute chest syndrome (ACS) is one of the leading causes of death and hospitalization among patients with sickle cell disease [42] . Approximately 70% of patients (adults or children) with ACS are hypoxic [43] . Indeed, patients with sickle cell disease are prone to infarctive crises. Thoracic bone infarction (usually in the ribs) in such patients leads to pain, splinting, hypoventilation, and the clinical signs of ACS. In situ red blood cell sickling in the lung vasculature is possibly a consequence of hypoventilation with subsequent infarction of lung parenchyma. NPPV has been proposed as a therapeutic option for patients with ACS. By improving patient oxygenation, NPPV could prevent progression from painful crisis to ACS, and ultimately to ARDS. Three retrospective studies reported favorable outcomes in children with ACS treated with NPPV (Table 1) [22, 27, 28] .