A Salty Solution for CF.
by Angela Spivey
Scott Donaldson was, well, wrong. His research study, published in January 2006 in the New England Journal of Medicine, disproved his theory. But he isn’t disappointed. Because being wrong means that an inexpensive, simple treatment fights a deadly disease — cystic fibrosis — better than he imagined.
The treatment? Basically, salt. And a lot of it. It’s hypertonic saline solution, which, at 7 percent sodium chloride, is about eight times saltier than physiologic saline (the stuff used in many hospital IVs).
People with cystic fibrosis (CF) have a hard time clearing the mucus that is supposed to simply trap bacteria and then move out of the lung. In someone with CF, bacteria and thick mucus accumulate, causing debilitating and often life-threatening lung infections.
Past research from Donaldson and veteran CF researcher Richard Boucher has suggested that the problem with CF lungs is that they are dehydrated; they don’t have enough of the layer of salt and water that normally coats the airway surface. The extra-salty hypertonic saline might work for CF, the researchers hoped, by drawing water from surrounding tissues onto the surface of the airway.
This gamma-camera scan shows the initial position and clearing of a radiolabeled tracer shortly after it deposited on the airway surfaces in a human lung. Image: Kirby Zeman.
In one of the first clinical trials of hypertonic saline in CF patients, led by Donaldson, twenty-four patients inhaled the salt solution four times a day, using a nebulizer (a machine that converts liquid medicine into a mist). The researchers measured patients’ mucus clearance and lung function for two weeks before treatment and then periodically during two weeks of treatment.
Half of those patients also inhaled amiloride — a drug that blocks salt absorption and is typically prescribed as a diuretic — before inhaling the saline. The researchers predicted that hypertonic saline alone might be absorbed too quickly to be effective and that the amiloride would keep the saline on the surface of the lungs for longer periods of time.
But that’s where they got a surprise. The patients who inhaled hypertonic saline alone fared better than those who got the combined treatment.
Patients who inhaled only hypertonic saline cleared mucus faster than they did before treatment began, and their lung function, as measured by the volume of air they could expel, improved. They also reported feeling better, with fewer respiratory symptoms.
When the patients who took both amiloride and hypertonic saline did worse than those on saline alone, Donaldson went back to the lab to find out why.
“In the lab, we observed that if we put amiloride on cells before a concentrated salt solution, no water moved out to where the salt was,” he says. “So amiloride blocked the water movement. It turns out that amiloride has a second action that was not known to anyone before. It not only blocks sodium channels but also appears to block water channels, which are little proteins that help conduct movement of water through cells.”
So hypertonic saline, which is cheap and already available by prescription worldwide, seems to work well on its own. A longer, larger trial of 164 patients, conducted by Australian colleagues and published in the same issue of the journal, found similar results. Patients who inhaled hypertonic saline, compared to those who inhaled a much weaker saline solution, showed improved lung function and had fewer flare-ups of their disease.
A 7 percent hypertonic saline solution like that used in the studies isn’t currently produced commercially. But Donaldson gets around that by prescribing for many of his patients a mix of 3 percent and 10 percent solutions, which are both readily available. The Cystic Fibrosis Foundation sells such a prescription kit.
The treatment isn’t recommended for patients with asthmatic symptoms, such as wheezing, which hypertonic saline might aggravate, Donaldson says.
Donaldson and Boucher are now exploring ways to make the treatment better, such as using different types of devices to deliver hypertonic saline and combining it with other treatments. Doctors at Carolina, led by Stephanie Davis, assistant professor of pediatric pulmonology, are testing hypertonic saline for safety in very young CF patients — aged three to five years. “If it proves to be safe, we’ll proceed by testing infants to find out how they tolerate it,” Donaldson says. “We really think this therapy could have the greatest benefit in young kids, before the lung damage that happens with CF occurs.”
For more information about obtaining hypertonic saline for CF, visit the CF Foundation web site at www.cff.org.
Scott Donaldson is assistant professor of medicine at Carolina. Richard Boucher is professor and director of the Cystic Fibrosis Research and Treatment Center. Other authors of the study, all at Carolina, are William Bennett, research associate professor of medicine; Kirby Zeman, research associate at the Center for Environmental Medicine, Asthma, and Lung Biology; Michael Knowles, professor of medicine; and Robert Tarran, assistant professor of medicine.
The UNC study was funded by the Cystic Fibrosis Foundation and the National Heart, Lung and Blood Institute. The Australian study was funded by the Cystic Fibrosis Foundation and led by Peter T.P. Bye, of the Royal Prince Alfred Hospital in Sydney.
Angela Spivey is a freelance writer based in Fayetteville, North Carolina.
