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.