Notes on a talk given at the Annual CFRI Conference by Frank Accurso, M.D.
Frank Accurso, M.D., Director of the Cystic Fibrosis Center and Professor of Pediatrics at the University of Colorado School of Medicine in Denver, delivered a compelling talk on the status of lung disease in infants and small children with CF and the necessity for early diagnosis and intervention. He noted the increased frequency for which youngsters with CF are statistically at risk for respiratory symptoms and hospitalizations. He has to remind parents frequently that health usually improves after the first year or so. These pulmonary function abnormalities, as well as other pathological evidence, also indicate that lung disease is clearly present in infancy. Until recently, however, it has not been clear whether the lung disease in infants is related to the lung disease of later CF life.
Dr. Accurso reviewed lung disease in children and adults with CF, noting characteristic chronic bacterial infections and the intense neutrophil-dominated inflammation. In CF sputum, pathologists find neutrophils (which are white blood cells called in to fight infection) and neutrophil by-products in abundance. These neutrophil by-products, including proteases and elastases, chemoattractants (which call in other neutrophils), cellular contents of neutrophil such as DNA (DNase counteracts this by-product) and F-actin (Gelsolin will counteract this by-product), and oxygen radicals, further clog CF airways. These neutrophil by-products are thought to bring about the airway destruction (bronchiectasis) so prominent in cystic fibrosis. Additionally, they likely stimulate mucus secretion and increase the viscosity of mucus, contributing to further airway plugging.
Dr. Accurso stressed the importance of this chronic infection and inflammation. He stated (and showed corresponding data) that even asymptomatic children, by the age of one year, when compared to non-CF children, already have pulmonary function test results showing a disparity. Several studies using bronchoalveolar lavage (a method of collecting mucus samples in the lungs, performed under anesthesia) to sample the airway contents of infants and young children with CF have now demonstrated that chronic infection and neutrophil-dominated inflammation in the infant are similar to what is seen in older children and adults. In addition, CT scan studies of the lungs have demonstrated that bronchiectasis can occur in the first couple of years of life. Studies of bronchoalveolar lavage fluid in patients over the age of 12 with mild disease and normal pulmonary function have also indicated ongoing chronic infection and inflammation.
The emerging conclusion from Dr. Accurso's studies is that the "ingredients" for lung damage (chronic infection and inflammation) are present from a young age. This potential for airways injury is present whether or not the CF patient is experiencing any symptoms. To prevent this lung destruction, it will be necessary to begin treatment early in life. To assess the value of any kind of early intervention, tools must be in place that can effectively gauge lung disease in infants and toddlers. Pulmonary function testing, bronchoalveolar lavage and imaging studies should be used along with close clinical following. Finally, the need for early treatment may also lead to the need for early diagnosis, further increasing the demand for neonatal screening.
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