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.