Mark Dransfield in the UAB Lung Health Center. "We're hoping to apply a drug developed for a few thousand people with cystic fibrosis to up to 10 million people with chronic bronchitis." Mark Dransfield in the UAB Lung Health Center. "We're hoping to apply a drug developed for a few thousand people with cystic fibrosis to up to 10 million people with chronic bronchitis."

From cystic fibrosis to COPD: potentiators and chronic bronchitis

November 05, 2018
By Matt Windsor
Ivacaftor, a drug that has seen remarkable success in cystic fibrosis, could be a treatment for chronic bronchitis, a disease caused largely by smoking that affects millions in the United States.

This is the fifth part of a series exploring breakthroughs in cystic fibrosis research that are paving the way for new treatments to help millions with other diseases, including COPD, asthma and more. Read part one, After cystic fibrosis 'miracle,' researchers are exploring ways to reach millions more, part two, How did we get here? Cystic fibrosis drugs go from 0-90 percent effective in a few short years, part three, Attacking nonsense mutations in cystic fibrosis and a host of other diseases, and part four, Clinical trial for one: the promise of patient-derived assays.


Cystic fibrosis and chronic bronchitis share many similarities. Both are marked by mucus obstruction of the small airways and daily production of sputum. What differs is how many people they affect: while 30,000 Americans have CF, millions have chronic bronchitis, which is caused largely by smoking and is a major cause of chronic obstructive pulmonary disease (COPD). COPD is one of the world’s leading causes of death, “and it’s the only one in the top 10 that’s growing in the United States,” notes Steven Rowe, M.D., director of the UAB Gregory Fleming James Cystic Fibrosis Research Center.

What other patients could benefit?

Once researchers saw how well ivacaftor cleared mucus in CF patients, “we started to think, What other patients could benefit?” Rowe says. Chronic bronchitis was at the top of the list. In his lab, Rowe found that exposing healthy airway cells to cigarette smoke reduced CFTR activity, and that CFTR proteins were present at half the normal level in cells taken from smokers.

A small trial in UAB’s Lung Health Center confirmed those findings, and established a partnership between Rowe’s team and Mark Dransfield, M.D., medical director of the Lung Health Center. CFTR activity was lower than normal in the noses and lungs of patients with chronic bronchitis, Dransfield says. “It seems to be an intermediate phenotype — not as dysfunctional as in CF, but definitely abnormal.” That led to a pilot study in which patients with chronic bronchitis received ivacaftor. Results were promising, and a larger trial is now underway. “In our anecdotal experience, we’ve had some pretty dramatic responses,” Dransfield says. “Some people are saying they have no sputum production, that they feel great.” In a separate larger study reported this year by Rowe with a different compound that potentiates CFTR like ivacaftor, the investigational medicine improved lung function and markers of inflammation, and will be brought forward in much larger studies.

No good therapies

Chronic bronchitis, like CF a decade ago, has no therapies that get to the root of the problem, Dransfield notes. Alabama is particularly hard-hit, ranking second in the nation in chronic bronchitis prevalence. “The hope is this would be the first efficacious treatment” for mucus-clogged patients, Dransfield says. “We’re hoping to apply a drug developed for a few thousand people with cystic fibrosis to up to 10 million people with chronic bronchitis.”


Continue reading the final part of this story, Muco-vision: a new imaging approach for cystic fibrosis, asthma and beyond.