Dr. Steven H. Abman
Director: Pediatric Heart Lung Center
Director: Ventilator Care Program
Co-Director: Pediatric Pulmonary Hypertension
Program Professor: Dept of Pediatrics, University of Colorado, Denver
Dr. John P. Kinsella
Director: Neonatal ECMO Program
Director: Newborn/Young Child Transport Team
Professor: Dept. of Pediatrics, Section of Neonatology, University of Colorado, Denver
Children's doctors' research leads to life-saving treatments for pulmonary hypertension
In 1991, along with their research team, Dr. Steven Abman and Dr. John Kinsella made a miraculous medical discovery. The findings from their research now contribute to saving the lives of critically ill newborns — and hold exciting promise for many other conditions and patient populations. Recently, the doctors shared their findings and touched on the future implications of their work.
"Until recently, babies with persistent pulmonary hypertension often had poor survival and significant long-term medical problems. The condition was considered difficult to treat with any success. No one understood how the disease worked. And no one knew how to treat it. There were large gaps between basic research and the translation of this research to patient populations. At most hospitals, multidisciplinary teams were not working together to address this issue. To fix it, a complete paradigm shift was necessary," said Dr. Abman.
Dr. Kinsella added, "ECMO was the standard treatment, but it didn't address the disease. ECMO provides support for the heart and lungs while the underlying disease improves over time."
Drs. Abman and Kinsella led their team at Children's Hospital Colorado in discovering that low doses of nitric oxide (NO) normally dilate the blood vessels in the lungs at the time of birth, allowing newborns to successfully make the transition to postnatal life.
Nitric oxide (NO) is an important signaling molecule in the body. They found that by using low doses of NO blended with oxygen in a ventilator, doctors could increase blood flow to the lungs in sick newborns with pulmonary hypertension, thereby avoiding the need for oxygenating a newborn's blood through ECMO, a highly invasive and dangerous heart-lung bypass procedure.
The result of this early work was so significant, the National Institute of Health (NIH) awarded a $6 million grant to the team and designated Children's Hospital Colorado in conjunction with the University of Colorado School of Medicine as a specialized center of research—the nation's first devoted to neonatal pulmonary hypertension.
The groundbreaking work of Drs. Abman and Kinsella contributed significantly to the 1999 approval of NO for use in term and near-term newborns with persistent pulmonary hypertension. This led to the widespread acknowledgement that not only is NO safe, it may offer some protection from chronic lung disease, a risk for many babies with breathing problems.
Today, nitric oxide successfully treats most babies with persistent pulmonary hypertension, drastically reducing the use of ECMO worldwide. According to Drs. Abman and Kinsella, here at Children's Hospital Colorado, ECMO is performed "on only four to six babies each year, compared to up to 25 babies prior to the use of NO." Dr. Kinsella notes that "ECMO remains an important treatment for the small number of babies who do not respond to other therapies."
Research changes lives
Drs. Abman and Kinsella's treatment has changed the lives of many patients and their families, including the Culshaw family. Fifteen years ago, Alexa Culshaw was the thirteenth baby to receive NO treatment at Children's Hospital Colorado. Read her story, as told by her father, Peter.
Research shapes lives
Neither Dr. Kinsella nor Dr. Abman entered medical school with the idea that they'd become researchers with a life-saving discovery. In fact, both had pursued pediatric critical care.
"I thought I'd be in the public health arena, or practicing third-world medicine," said Dr. Abman. "But during my residency I became drawn to pediatric critical care, especially newborns with pulmonary hypertension. When it became clear that we didn't know how to fix newborns with persistent pulmonary hypertension, and that none of the treatments were working very well, I wanted to better understand the disease and try to change the course of how we treated these babies."
Dr. Kinsella agrees. "During my training, persistent pulmonary hypertension of the newborn (PPHN) was a condition that was poorly understood and inadequately treated. The discovery and application of inhaled NO as a safe and effective treatment has dramatically changed the outlook for babies with PPHN."
The two doctors joined forces and began working together when they became aware of their mutual interests in sick newborns with heart and lung disease. "What's exciting about research is that you can either read the textbook and treat a patient the way we’ve always treated patients. Or, you can work very hard to find new ways of thinking," said Dr. Abman.
While practicing critical care medicine, the doctors felt they were treating conditions the same way, with the same outcomes. They were driven to better understand the condition, and ultimately, develop a treatment with better outcomes.
"Re-writing textbooks and changing clinical practice with novel therapies requires intensive investigation through carefully designed clinical trials that are based on discoveries from the laboratory," said Dr. Kinsella.
The future of nitric oxide treatment
Currently, Drs. Abman and Kinsella are testing the use of NO in premature babies. Funded by a $7 million grant from the NIH, their study will determine whether a low dose of NO, used early in premature babies who require mechanical ventilation could reduce lung inflammation and minimize the risk of chronic lung disease in newborns with respiratory failure.
Interestingly, "at least three-fourths of patients getting NO treatment are not newborns," said Dr. Kinsella. "In fact, the most frequent use of NO is 'off-label'," added Dr. Abman. Inhaled NO therapy has been used in patients of all ages, from newborns to adults, with diverse causes of pulmonary hypertension. These diseases include acute respiratory distress syndrome, congenital heart disease, sickle cell disease, complications following bone marrow transplantation and many others.
From this experience, the team developed the Pediatric Heart Lung Center, which has launched unique programs in Pediatric Pulmonary Hypertension and Ventilator Care, and encourages inter-disciplinary collaborations in research, patient care, education and training.
Research at Children's Hospital Colorado
Children's Hospital Colorado and its affiliate, the University of Colorado School of Medicine (UCSM), are responsible for virtually all of the pediatric medical discoveries emanating from the Rocky Mountain region. What's more, though research has always been an important focus and commitment, Children's Colorado plans to focus more attention and dollars on research in the next five years than ever before.
Today, UCSM has one of the best-funded pediatric research programs in the country. In 2011, the National Institute of Health (NIH) awarded more than $37 million to the Department of Pediatrics at the UCSM. This funding is part of what makes Children's Colorado a place more doctors look to for better ways to treat the little things and rely on for the big ones.
Learn more about research at Children's Colorado.