RESUMEN
BACKGROUND: Introduction of novel therapies for cystic fibrosis (CF) raises the question of whether traditional treatments can be withdrawn. Nebulized hypertonic saline (HS) potentially could be discontinued in patients receiving dornase alfa (DA). RESEARCH QUESTION: In the era before modulators, did people with CF who are F508del homozygous (CFF508del) and who received DA and HS have better preserved lung function than those treated with DA only? STUDY DESIGN AND METHODS: Retrospective analysis of the Cystic Fibrosis Foundation Patient Registry data (2006-2014). Among 13,406 CFF508del with data for at least 2 consecutive years, 1,241 CFF508del had spirometry results and were treated with DA for 1 to 5 years without DA or HS during the preceding (baseline) year. Absolute FEV1 % predicted change while receiving DA and HS, relative to treatment with DA only, was the main outcome. A marginal structural model was applied to assess the effect of 1 to 5 years of HS treatment while controlling for time-dependent confounding. RESULTS: Of 1,241 CFF508del, 619 patients (median baseline age, 14.6 years; interquartile range, 6-53 years) received DA only and 622 patients (median baseline age, 14.55 years; interquartile range, 6-48.1 years) were treated with DA and HS for 1 to 5 years. After 1 year, patients receiving DA and HS showed FEV1 % predicted that averaged 6.60% lower than that in patients treated with DA only (95% CI, -8.54% to -4.66%; P < .001). Lower lung function in the former relative to the latter persisted throughout follow-up, highlighting confounding by indication. After accounting for baseline age, sex, race, DA use duration, baseline and previous year's FEV1 % predicted, and time-varying clinical characteristics, patients treated with DA and HS for 1 to 5 years were similar to those treated with DA only regarding FEV1 % predicted (year 1: mean FEV1 % predicted change, +0.53% [95% CI, -0.66% to +1.71%; P = .38]; year 5: mean FEV1 % predicted change, -1.82% [95% CI, -4.01% to +0.36%; P = .10]). INTERPRETATION: In the era before modulators, CFF508del showed no significant difference in lung function when nebulized HS was added to DA for 1 to 5 years.