Statement 3: In children with CF without evidence of lung disease, treatment with mucoactive agents should be considered in the presence of early pulmonary abnormalities documented by imaging or tests of pulmonary function, including LCI.
Although in final consensus meeting, there was no unanimous response to this statement, the high level of agreement reached on this aspect regarding the appropriateness of the mucoactive agent prescription in pediatric patients with CF, as shown in Figure 1C, may be related to the importance attributed to the role of airway inflammation in the progression of CF in children without evidence of pulmonary disease19.
In children with CF without evidence of lung disease, in the presence of early pulmonary changes documented by instrumental examinations, starting the mucoactive therapy early is important in order to act on the component of inflammation and obstruction, anticipating the cascade of pathological events that self-maintains in CF. Amin and collaborators demonstrated that the lung clearance index (LCI) is a sensitive and responsive outcome measure that was able to detect a significant treatment effect from dornase alfa in a pediatric cohort with mild lung disease and normal spirometry20.
Importantly, a two-year randomized, placebo-controlled trial of dornase alfa in young CF patients with mild lung function abnormalities demonstrated that this therapy maintains lung function and reduces the risk of exacerbations21. At 96 weeks, patients treated with dornase alfa maintained FEV1 at their baseline value (mean change from baseline ± SE, 0.04% ± 0.8% predicted), whereas patients receiving placebo had a mean decrease from baseline of 3.2% ± 0.8% predicted. Thus, the treatment benefit for FEV1 in patients who received dornase alfa was 3.2% ± 1.2% predicted (P = 0.006). The risk of respiratory exacerbations was reduced by 34% in patients receiving dornase alfa (relative risk 0.66, P = 0.048). The results of this two-year trial support the importance of an early intervention approach in children with CF21.