Lack of water causes lung disease

USA Today (Society for the Advancement of Education), Oct, 2004

The central problem that causes cystic fibrosis--the most common lethal genetic illness among whites in the U.S., striking roughly one in every 2,000 to 3,000 infants born--has been identified by scientists at the University of North Carolina at Chapel Hill.

Special genetically engineered mice the researchers created revealed that cells lining patients' airways cannot produce the proper amount of surface water and are not wet enough. As a result, airway surfaces are unable to generate a mucus coating sufficiently moist to clear unrelated but disease-causing bacteria and other inhaled contaminants from the lungs.

"With cystic fibrosis, a longstanding debate has occurred over how you go from a defective gene to the disease itself," relates Richard Boucher of the School of Medicine. "There have been a number of intriguing theories, but we think we have established that the lack of water is the fundamental defect."

The physicians compared not having enough water on airway surfaces to those long plastic sheets youngsters slide on at the beach. When the sheets are not wet enough, the children are unable to slide well because of excessive traction. Likewise, airway secretions get bogged down on excessively dry lung surfaces. Then contaminants get trapped in the lungs and increasingly damage them over time.

"It has been unclear how the gene associated with cystic fibrosis, CFTR, which acts as a chloride channel and a regulator of the sodium channel, causes lung disease," notes Marcus Mall, assistant professor in the School of Medicine. "In particular, the relative importance of these two functions has been controversial and difficult to test. This mouse model demonstrated for the first time that accelerated transport of sodium ions alone is sufficient to cause this disease link through dehydration.

"We will use this model for studying factors that ultimately lead to chronic bacterial lung infections, which remain one of the biggest problems for cystic fibrosis patients. We also have planned studies to search for modifier genes that modulate the severity of CF lung disease and may have an impact on the severity of other chronic bronchitic airway diseases in humans."