Sleep tight, keep the oxygen right

The search for clinical and laboratory findings that predict the severity of sickle cell disease has been, in some ways, overly successful. Studies have associated future adverse events with unusually severe anemia, low fetal hemoglobin (HbF) levels, high white cell counts, and early complications. Determining which of these factors is most closely linked to outcome becomes increasingly important for the development of effective therapy.

In this issue, Hargrave and colleagues (page 846) have added nocturnal hypoxemia to the list of causative, and potentially treatable, factors. Extending their previous work that demonstrated a relationship between nocturnal hypoxemia and central nervous system complications in sickle cell disease, the investigators now show a remarkable link between nocturnal hypoxemia and painful crises. In 95 children and adolescents, a variety of measures of nocturnal hypoxemia are significantly associated with the number of inpatient days for management of pain. Mean oxygen saturation during sleep emerges as the key predictor of painful crises after adjusting for such factors as total hemoglobin level, HbF level, and white cell count. For each increase of one unit in the mean nocturnal oxygen saturation between 85% and 100%, the number of inpatient days for pain falls by 0.83. The study also provides an important note of caution for those who favor surgical solutions. Tonsillectomy and adenoidectomy did not reduce the frequency of crises in patients with upper airway obstruction unrelated to recurrent infections.

For many decades, sickle cell disease represented the classic gap between an understanding of the pathophysiology of a disease and the development of effective treatment. Investigators have closed this gap as chronic transfusion therapy, prophylactic penicillin, HbF enhancers, bone marrow transplantation, membrane-active agents, and hemorheological drugs have entered clinical trials or clinical practice. An important outgrowth of these developments is the need to determine which approach has a sufficiently broad therapeutic impact to prevent many of the major complications of sickle cell disease and, therefore, to improve the overall quality and length of life of affected patients. Hargrave et al are presently taking the crucial next step to determine whether the overnight administration of oxygen is beneficial and deserves a place in the rapidly developing armamentarium of new treatments for sickle cell disease.