Study yields new cystic fibrosis findings

A new study of newborn screening for cystic fibrosis has added provocative findings to the complicated picture of early intervention against the disease.

The latest publication from this 17-year study by research groups at UW–Madison and the Medical College of Wisconsin shows that infants diagnosed with CF shortly after birth are at risk for infection with the bacterium responsible for most deaths of patients.

The researchers also say that use of certain oral antibiotics as preventive therapy – an approach commonly used at CF treatment centers – may increase the risk of infection with that bacterium.

The findings, published in the June 12 Journal of the American Medical Association, illustrate the complexities involved with newborn screening for CF, the most common potentially lethal genetic disease among Caucasians. The JAMA study was conducted by Susan West, associate professor of microbiology at the School of Veterinary Medicine, and other colleagues from UW–Madison and the Medical College of Wisconsin in Milwaukee. Philip Farrell, dean of the Medical School, is the principal investigator for the overall project.

The Wisconsin CF Neonatal Screening Project, which began in 1985, was designed to assess the benefits and risks of newborn screening for the disease. Considered the “gold standard” of pediatric clinical trial designs, it is the largest prospective randomized investigation involving children in the U.S. since the polio vaccine field trials of 1954. The study has been supported by the National Institutes of Health for 17 years and has clearly shown the value of a randomized trial to carefully assess risks and benefits.

For the majority of CF patients, the most serious problem is irreversible lung damage from recurrent respiratory infections. These patients are especially susceptible to infection with the common bacterium Pseudomonas aeruginosa, which has been implicated in up to 90 percent of CF patient deaths. National statistics indicate that about 25 percent of CF patients are infected with the organism in the first year of life, and about 80 percent by the age of 18. Once infection is established, it may be nearly impossible to eradicate, even with IV antibiotic therapy. P. aeruginosa is also resistant to most antibiotics given orally.

The study involved 68 newborns in the project’s screened group (those diagnosed with CF shortly after birth). After parental consent was obtained, the youngsters were enrolled at one of two CF treatment centers and received standard therapy — aggressive nutritional and respiratory intervention. None of the infants had irreversible lung damage when they entered the study, so the research team was able to assess different ways to detect infection as it developed.

The findings were surprising and provocative. Most patients in the study had developed antibodies to P. aeruginosa six to 12 months before it was found in respiratory secretions. In addition, the researchers found a “center effect”: infants treated in clinics in which they mixed with older CF patients had a higher risk of lung infection with P. aeruginosa than those treated in separate clinics dedicated solely to infants and young children with CF. And, perhaps most disconcerting, the researchers learned that the increased risks of P. aeruginosa infection associated with oral antibiotics might counteract the potential benefits of early diagnosis.

“This study was designed to better understand the early stages of the P. aeruginosa lung infection,” says West. “Having more precise knowledge of how the infection develops will help physicians develop better treatment regimens.”

To reduce some of the risks associated with early CF detection, the researchers propose several changes in current treatment. First, states and provinces planning to institute newborn screening for CF should consider treating infants and young children in clinics that are separate from older children with CF. Second, broad use of “preventive” antibiotics should be curbed in favor of a tailored approach based on the particular respiratory status of each patient. They also recommend that blood tests to measure antibodies to P. aeruginosa be conducted on these patients diagnosed early to monitor their infections status carefully.

“This group of patients has confirmed some of our early suspicions and concerns about the infection risk in young children with CF,” says Farrell, one of the study’s authors. “These results confirm other studies that say the final judgment about early intervention in CF hasn’t been made yet. Early treatment of CF children has risks as well as benefits. Now that we have a better understanding of the natural course of P. aeruginosa, we need to look at how that risk of infection can be reduced.”