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Cystic fibrosis makes airways more acidic, reduces bacterial killing
Date:7/4/2012

The human airway is a pretty inhospitable place for microbes. There are numerous immune defense mechanisms poised to kill or remove inhaled bacteria before they can cause problems. But cystic fibrosis (CF) disrupts these defenses, leaving patients particularly susceptible to airway infection, which is the major cause of disease and death in CF.

Using a unique animal model of CF, a team of scientists from the University of Iowa has discovered a surprising difference between healthy airways and airways affected by CF that leads to reduced bacterial killing in CF airways. The finding directly links the genetic cause of CF -- mutations in a channel protein called cystic fibrosis transmembrane conductance regulator (CFTR) -- to the disruption of a biological mechanism that protects lungs from bacterial infection.

The study, published in the July 5 issue of Nature, shows that the thin layer of liquid coating the airways is more acidic in newborn pigs with CF than in healthy newborn pigs, and that the increased acidity (lower pH) reduces the ability of the liquid to kill bacteria. Moreover, making the airway liquid less acidic with a simple solution of baking soda restores bacterial killing in CF airways to almost normal levels.

Although the findings suggest that therapies that raise the pH of the airway surface liquid (ASL) may help prevent infection in CF, the researchers strongly caution that this discovery is at an early stage.

"Some have asked us if people with CF should inhale an aerosol that would raise the pH of the ASL," says Joseph Zabner, M.D., UI professor of internal medicine and senior study author. "At this point, we have no idea if that would help. And more importantly, it could be harmful."

"This was a very surprising finding," adds Alejandro Pezzulo, M.D., UI postdoctoral fellow and co-lead author of the study. "There have been many ideas as to what goes wrong in CF, but lack of a good experimental
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Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-356-7124
University of Iowa Health Care
Source:Eurekalert

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