Secondhand Smoke Exposure Worsens Cystic Fibrosis

Cystic fibrosis (CF) is a fatal disorder that affects more than 30,000 individuals in the United States, with the major cause of illness and death being progressive obstructive lung disease. "Despite public health warnings, including a recent U.S. surgeon general's report stating that there is no risk-free level of secondhand smoke exposure, substantial numbers of individuals with CF are exposed to secondhand smoke. Unfortunately, published studies have been inconsistent in associating poorer clinical outcomes in patients with CF with secondhand smoke exposure," the authors write.

"We're really surprised that such a small genetic change can double the negative effects of secondhand smoke on lung function in these patients," says Garry Cutting, M.D., a professor of pediatrics and medicine and member of the McKusick-Nathans Institute of Genetic Medicine. "It's always been suspected that secondhand smoke is detrimental to lung disease patients, and now we have a handle on one specific gene that clearly makes it worse for those with CF."

Of the 812 participants in the study, 188 were exposed to secondhand smoke at home. The participants were recruited between 2000 and 2006 as part of the U.S. Cystic Fibrosis Twin and Sibling Study and the Cystic Fibrosis Foundation Data Registry.

The research team found that secondhand smoke exposure was associated with decreased lung function in CF patients, measured by how much air a person could breathe out in the first second of expiration. According to Cutting, any secondhand smoke exposure reduced lung function by 10 percent.

"We know by observation that some patients tend to do worse than others, so we wondered if genes played a clear role in how CF patients react to secondhand smoke," says Cutting.

The research team went on to compare patient lung function with their particular genetic variant of CF as well as the genetic variant of another gene, TGFbeta1, which has been shown to affect the severity of CF and asthma.

CF patients who also carried particular TGFbeta1 mutations fared twice as badly in lung function when exposed to secondhand smoke compared with those who were not exposed. According to Cutting, secondhand smoke exposure is roughly equivalent to 7 years of lung function decline.

"This means that a 17-year old CF patient with a TGFbeta1 mutation and exposed to secondhand smoke would have lung function similar to that of a 24-year-old who wasn't exposed to secondhand smoke," says Cutting. "This gene-environment interaction drastically accelerates reduced lung function."

Journal reference: JAMA. 2008;299[4]:417-424

Authors on the paper are J. Michael Collaco, Lori Vanscoy, Lindsay Bremer, Kathryn McDougal, Scott Blackman, Amanda Bowers, Kathleen Naughton, Jacky Jennings, Jonathan Ellen and Cutting, all of Hopkins.

The research was funded by the National Heart, Lung, and Blood Institute, the Cystic Fibrosis Foundation and the Flight Attendant Medical Research Institute.