Emerging concepts in sickle cell disease acute chest syndrome

Sickle cell disease (SCD) is a globally prevalent inherited hemoglobinopathy marked by chronic hemolysis, vaso-occlusion, and systemic inflammation, leading to significant acute and chronic complications. Acute chest syndrome (ACS), a leading cause of morbidity and mortality in people with SCD (pwSCD) is often associated with vaso-occlusive pain episodes (VOE). Despite its clinical significance, the pathogenesis of ACS remains incompletely understood. This review synthesizes current knowledge on ACS in SCD, highlighting known and emerging risk factors, evolving concepts in pathophysiologic causes, current diagnostic and phenotyping challenges, and discusses new approaches to preventative and therapeutic treatment regimens. We describe the significant disparities in care and outcomes in low- and middle-income countries (LMIC), emphasizing the need for improved access to multidisciplinary subspecialty SCD care, including newborn screening and access to therapeutics. Finally, we identify key research gaps that need to be addressed to advance our understanding and management of ACS in a diverse healthcare landscape. Overall, this review aims to inform clinical practice and guide future research toward reducing the burden of ACS in pwSCD across the globe. Ultimately, advancing ACS management requires a paradigm shift toward resource-adaptable, precision-based care.