Current treatments for cystic fibrosis (CF) must be used while newer therapies remain under development.
These are the views of Dr Brian O’Sullivan, University of Massachusetts Medical School, USA, and Dr Steven Freedman, Harvard Medical School, Boston, USA, published in Online First (see link for this at the end of this post) and an upcoming edition of The Lancet.
CF is the most common lethal genetic disease in the white population, affecting some 1 in 3000 North Europeans and white Americans. Life expectancy of CF patients has increased from 31 to 37 years in the past decade; and a UK model predicts that a child born with CF today will live to age 50.
The authors say that of the treatments available for CF, hypertonic saline, macrolide antibiotics, and ibuprofen deserve a special mention. Patients given 7% hypertonic saline via nebulisation have better lung function than those given standard saline, because it draws water into the airways and leads to sustained airway hydration, preventing infection.
Azithromycin (a macrolide antibiotic) works by preventing P aeruginosa from forming films and killing it even within its films. It also has anti-inflammatory properties.
Ibuprofen treatment seems to be most effective in younger patients (aged 5-13 years), ie, started before the development of inflammation and severe pathological changes in the lung.
As well as these interventions, airway clearance techniques are used to clear airway secretions. These include percussion (chest massage), and special breathing devices which exert pressure.
Nutrition is also key, with the authors saying: “The benefits of maintaining good nutrition in regard to long-term survival and lung health cannot be overstated.” When pancreatic insufficiency occurs, supplements of both pancreatic enzymes and fat-soluble vitamins must be used.
New horizons for CF treatment are focussing on two classes of drugs in development. "Correctors" transfer more of the mutated CFTR from the cell’s genetic machinery to its correct location on cell membranes, on the basis that it is better to have much more partly-functioning CFTR in place than none at all.
"Potentiators" improve the function of CFTR at the cell membrane.
The authors say: “A cocktail of a corrector and a potentiator might be the ultimate treatment for most patients with cystic fibrosis.”
However, treatment which would correct the actual CFTR mutation — known as gene therapy — has so far been disappointing. This would work via insertion of one copy of normal DNA into the affected cells — but has met with problems due to the poor performance of vectors to transfer the DNA.
Future development of new vectors and better methods of delivery are pre-requisites for gene therapy success.
But the authors say the prospect of gene therapy remains a hope more than a reality.
“The goal in 2009 is to preserve lung function by maximising current treatment regimens, so that patients can benefit fully from future therapies that could correct the basic defect and turn cystic fibrosis into a manageable disease," they conclude.