The Departments of Emergency Medicine and Hematology at the Icahn School of Medicine at Mount Sinai have been awarded a $4 million grant from the National Institutes of Health toward further study of inhaled corticosteroids to treat sickle cell disease (SCD) in individuals who do not have asthma. The IMPROVE 2 study is a one-year randomized, placebo-controlled trial involving 80 SCD patients.
According to the U.S. Centers for Disease Control and Prevention, SCD affects 100,000 Americans and is more prevalent in certain ethnic groups, such as African Americans and Hispanic Americans. The Healthcare Cost and Utilization Project, a database consortium sponsored by the federal government, reports that per-patient health care costs in the U.S. are higher for SCD than any other disease, with total expenditures exceeding $2.4 billion. The disease causes the production of abnormal hemoglobin, a protein inside red blood cells that attaches to oxygen in the lungs and carries it to the rest of the body. Healthy red blood cells are flexible, but in SCD, abnormal hemoglobin forms long rods and distorts the red cells into a sickle shape. The repeated damage to red cells causes the blood to become inflamed and sticky and to break down faster, causing pain attacks, infections, stroke, and early death. The only organ in the body that can reverse sickling is the lung, but it is highly inflamed in SCD, which is why researchers thought to use inhaled steroids as a treatment.
Over the last decade, researchers at Mount Sinai have demonstrated that pulmonary inflammation is present in mice and humans with SCD. Furthermore, those with symptoms of more inflammation in the lungs are four times more likely to die prematurely. In Mount Sinai's first study of inhaled steroids for SCD, a triple-blind randomized trial of 52 patients called IMPROVE 1, inhaled steroids that are FDA-approved for other conditions were shown to reduce systemic inflammation, hemolysis, and daily pain.
The research team will include experts in hematology, pulmonology, and immunology and will be led by Jeffrey Glassberg, MD, Associate Professor of Emergency Medicine and of Medicine (Hematology, and Medical Oncology) at the Icahn School of Medicine at Mount Sinai.
"In sickle cell disease, the interaction between the lung and red blood cells represents a potentially high-value therapeutic target," said Dr. Glassberg. "Hydroxyurea is the primary FDA-approved drug for treatment, but it is underutilized due to side effects, stigma, and fertility concerns. Other promising drugs are coming, but their costs, efficacy, and scalability are hard to predict at this point. Inhaled corticosteroids offer a creative new approach with the potential to dramatically improve patient outcomes."
Dr. Glassberg says patients with SCD will often end up in the emergency department because they experience excruciating pain. He says alternative treatments will improve patient care, reduce ED visits, and lower healthcare expenditures.
Dr. Glassberg is director of the Mount Sinai Comprehensive Program for Sickle Cell Disease, a specialized clinic that offers clinical and psychosocial services to patients in New York City, which has the largest population of SCD patients in the country. The team includes physicians, nurses, and social workers who specialize in the treatment of sickle cell disease.