Relation Between Sickle Cell Disease Severity And Lung Problems
Children treated for sickle cell disease have worse symptoms if they are also asthma sufferers, clinicians at Washington University School of Medicine in St. Louis noted. Further, children with asthma often also have breathing disturbances during sleep.
These observations led to an all-out effort to find better treatments for these children and to thoroughly investigate the link between asthma and breathing problems during sleep and the severity of sickle cell disease complications.
About four years ago, Michael R. DeBaun, M.D., associate professor of pediatrics, and Robert C. Strunk, the Donald Strominger Professor of Pediatrics independently found that children with both sickle cell disease and asthma had more hospital admissions and lung complications than children with sickle cell disease alone.
So they established a combined pulmonary/sickle cell disease clinic at St. Louis Children's Hospital, bringing together pediatric lung and blood specialists to evaluate children with sickle cell disease.
This novel team approach has now led to a four-year, $8 million grant from the National Heart, Lung and Blood Institute to investigate asthma and nocturnal hypoxia (low oxygen levels during sleep) in sickle cell disease.
The prevalence of asthma in the African-American urban population in the St. Louis area is about 17 percent, and the scientists' data indicate that the same asthma prevalence holds for children with sickle cell disease.
"When we found that having asthma makes sickle cell disease much worse, we realized you can't consider the two diseases separately in these children," DeBaun says. "So we set up a comprehensive approach to treatment in which each office visit includes a consultation with lung and sickle cell disease specialists."
Originating from a variety of causes, low oxygen levels in the blood of sickle cell patients can initiate episodes of debilitating pain in the arms, legs, back, abdomen, bones, or joints. These episodes can also involve the lungs if they progress to acute chest syndrome-a pneumonia-like condition accompanied by fever, pain and violent coughing. Acute chest syndrome is the leading cause of death and the second most common cause of hospitalization in patients with sickle cell disease.
"Pain and chest episodes can stem from an asthma attack," Strunk explains. "During an asthma attack, mucus accumulates in the lungs and can block airways. We believe that as blood passes the blocked part of the airway, low oxygen levels make some red blood cells 'sickle' and impede blood flow, leading to characteristic sickle cell disease episodes."
Sickle cell disease is the most common disease identified as part of the state mandated newborn screening, occurring in one of 1,800 newborns in America and one of 400 newborns of African-American descent.
The disease stems from variations in the gene for hemoglobin, the oxygen-carrying component of red blood cells. At low oxygen levels, variant hemoglobin clumps together and warps red cells into hard sickle shapes so that they tend to clog up small blood vessels.
Sickle cell disease is also marked by a constant low level of inflammation that contributes to symptom development. These effects have numerous detrimental consequences-anemia, strokes, organ damage, infection, vision problems and slowed growth, for example.
This study will follow at least 400 children with sickle cell disease and specifically address the relation of lung problems to the severity of sickle cell symptoms and the effects of sickle cell disease on the lungs.
Clinicians will look at the children's genetic makeup to evaluate the role of specific genes in sickle cell disease symptoms. The study will include detailed cellular and molecular investigations of the impact of sickle cell complications on the lung using laboratory mice with sickle cell disease.
"Ultimately, we have three objectives," DeBaun says. "We want to treat patients with the best available therapy and we want characterize lung disease and sleep problems and understand them at the cellular, molecular and genetic level in this vulnerable population."
In addition to DeBaun and Strunk, the research team will include Jessica Boyd, M.D., Mario Castro, M.D., Ping An, M.D. Anne Bowcock, Ph.D., and Michael Province, Ph.D., at the University along with a team of investigators from Case Western Reserve University in Cleveland, the Medical College of Wisconsin in Milwaukee and the Institute of Child Health in London.