Statement 6: In CF patients with evidence of lung
disease, dornase alfa should be preferred to other mucoactive agents, in
order to achieve long-term stabilization/improvement of lung function.
The experts reached consensus also on the choice of dornase alfa as the
most appropriate mucoactive agent in CF patients with evidence of lung
disease (Figure 3B ). In final consensus meeting, there was
unanimous response for this statement.
According to the most recent version of the European CF Society (ECFS)
document on standard of care, the only mucus degrading agent that has
proven efficacy in CF is dornase alfa32. The authors
reached this conclusion after performing a systematic review of
available evidence. Studies demonstrated improvements in lung function
and a reduction in pulmonary exacerbations in patients regardless of
disease severity.
In addition, evidence from an analysis of a large database suggests that
dornase alfa reduces lung function decline33.
Statement 7: In CF patients with inadequate
response or intolerance to dornase alfa therapy, the use of the
combination of dornase alfa and hypertonic solution or hypertonic
solution alone should be considered .
Italian CF experts reached consensus also on this statement in light of
the different mechanisms of action of the different mucoactive agents
(Figure 3C ). In final consensus meeting, there was unanimous
response for this statement.
Mucoactive drugs fall into two categories, either mucolytic or
hyperosmolar. Dornase alfa, a mucolytic agent, and hypertonic saline and
mannitol, both hyperosmolar agents, have all been shown to benefit CF
patients.
Dornase alfa reduces the viscoelasticity of sputum by breaking down DNA
released by neutrophils which flood into infected airways in a fruitless
attempt to clear the airway lumen of infecting
bacteria34.
Nebulised hypertonic saline in CF treatment is available at a
concentration of 3% to 7% sodium chloride. Increasing salt
concentrations on the luminal side of the respiratory epithelium is
thought to hydrate the viscous mucus, thereby improving mucociliary
clearance and hence lung function31,35,36.
Mannitol, an alternative hyperosmolar therapy, when inhaled, draws water
into the airways by creating an osmotic gradient and has been shown to
increase mucociliary clearance in CF and other obstructive airways
diseases37-39.
In conclusion, the mechanism of action of hyperosmolar agents differs
from that of dornase alfa and both approaches are complementary in
improving mucus clearance in patients with CF40.
Careful assessment of the appropriateness of a mucoactive therapy must
take place not earlier than six months after its initiation. Accurate
assessment, discussion and monitoring will help to choose guiding the
most appropriate agent or combination of agents for each patient with
CF.