Statement 1: Treatment with mucoactive agents should be proposed at the first evidence of pulmonary involvement in order to prevent or slow the decline in lung function through indirect control of inflammation, with reduction of mucus accumulation and, consequently, of the infectious process.
The expert panel reached consensus on starting the use of mucoactive agents in CF patients at the first evidence of pulmonary involvement(Figure 1A ). In final consensus meeting, there was no unanimous response to this statement.
The pathophysiology of CF is characterized by a continuous cycle of obstruction, infection, and neutrophil-dominated inflammation14. In addition, necrosis of neutrophils leads to the accumulation of extracellular DNA and actin, increasing the viscosity of mucous and producing further obstruction. Reduction of high molecular weight DNA into smaller fragments by using dornase alfa has been proposed as a treatment to reduce the mucus viscosity and improve mucus clearance from obstructed airways in CF patients15.
Given the role of the inflammatory process as a driver of irreversible lung destruction, there is an increasing interest in therapies with anti-inflammatory effects to slow disease progression when used early in the course of disease16. Dornase alfa has well-documented beneficial clinical effects on the obstruction and infection components of the disease process and has also shown positive effects on markers of inflammation16.
Dornase alfa was shown to exhert a beneficial effect on metalloproteases in BAL fluid of patients with CF, supporting the positive impact of this mucoactive agent on airway inflammation in CF17. In particular, a randomized trial including 105 CF patients with mild lung disease (FEV1 >80% predicted) demonstrated this potential anti-inflammatory effect. Based on an initial bronchoalveolar lavage, patients were divided into two groups, those with airway inflammation and those without. CF patients with inflammation were then randomized to treatment with dornase alfa or not. In patients treated with dornase alfa, there was no change in inflammatory responses as measured by elastase and IL-8 levels and neutrophils number.
CF patients not treated with dornase alfa and patients who did not have inflammation at baseline all had worsening neutrophilic inflammation on follow-up. In addition, in treated patients FEV1 dropped by 1.99% predicted per year, as compared to a 3.26% predicted drop per year in patients not treated with dornase alfa17.
Statement 2: Treatment with mucoactive agents should be proposed in patients with CF with frequent pulmonary exacerbations of lung disease.The complete agreement of the expert panel on this statement is relevant as it shows that the frequency of exacerbations is considered a marker for the use of mucoactive therapy (Figure 1B ).
In final consensus meeting, there was no unanimous response for this statement.
A recent Cochrane review of randomized and quasi-randomized controlled trials comparing dornase alfa to placebo, standard therapy or other medications that have a positive impact on airway clearance, showed that compared with placebo, therapy with dornase alfa improved lung function in people with CF in trials lasting from one month to two years and led to a decrease in pulmonary exacerbations in trials of six months or longer18.