Comparison of inhaled mannitol/dornase alfa combination and daily dornase alfa alone in children with cystic fibrosis

Abstract

Objectives: Inhaled recombinant human deoxyribonuclease (dornase alfa) and osmotic agents such as inhaled mannitol are used for improving the clearance of secretions of cystic fibrosis (CF) patients. We aimed to evaluate the long-term clinical effects of adding dry powder inhaled (DPI) mannitol in subjects with CF who are taking daily dornase alfa. Method:We conducted a retrospective case-control study on subjects with CF. The effect of DPI mannitol was assessed by comparing DPI mannitol and dornase alfa combination with daily dornase alfa alone in children with CF during a 12-month period. The primary outcome measures of the study were absolute changes in percent predicted forced expiratory volume in 1 s (FEV1) and FEV1 z-scores and the secondary outcomes included other spirometry indices, body mass index, frequency of pulmonary exacerbations, SPO 2 , and sputum microbiology.Result: Of a total of 28 patients who committed to use DPI mannitol treatments during the study period, five had a positive challenge with DPI mannitol and two were aged over 18 years. Therefore, the mannitol treatment group consisted of 21 patients. However, the effect of DPI mannitol was analyzed using 15 patients in the mannitol treatment group who received DPI mannitol for at least 12 months, and 18 patients who only used dornase alfa constituted the control group. The median absolute change in FEV1 between baseline and the third month; and baseline and the 12th month were significantly higher in the mannitol treatment group (p = 0.038, p = 0.004, respectively). When the groups are compared with respect to absolute zscore changes, all spirometry indices, except FVC at the end of 3 months, showed statistically significant improvements in the mannitol treatment group. Some secondary outcomes like pulmonary exacerbation frequency during the study year and median absolute body mass index z-score changes from baseline to the end of the study showed no significant differences between the groups (p = 0.735, p = 0.161, respectively). No colonization changes were observed in the treatment group.Conclusions: This study showed that in those patients who tolerated long-term (12 months) treatment with DPI mannitol and dornase alfa made greater improvements

The effect of Pseudomonas aeruginosa eradication regimens on chronic colonization and clinical outcomes in pediatric patients with cystic fibrosis

“…Viscous airway secretions in CF lead to chronic mucous obstruction, inflammation, and recurrent infections that result in long‐term damage to the airways. Suggested treatments for these problems include airway clearance therapy, deoxyribonuclease (rhDNase), nebulized antibiotics, azithromycin, dry powder inhale mannitol, and hypertonic saline 9,27–29 . In our study, all patients had used airway clearance therapy and rhDNase since before Pa‐IA.…”

“…Suggested treatments for these problems include airway clearance therapy, deoxyribonuclease (rhDNase), nebulized antibiotics, azithromycin, dry powder inhale mannitol, and hypertonic saline. 9,[27][28][29] In our study, all patients had used airway clearance therapy and rhDNase since before Pa-IA. Two patients who had better FEV1 at the last visit versus Pa-CC time used hypertonic saline or dry powder inhaled mannitol.…”

Cystic fibrosis year in review 2022

“…Hypertonic saline use in children between 3 and 6 years of age was associated with less CT scan‐based disease and improved (decreased) LCI values compared to children taking isotonic saline in a 48‐week trial 65 . Dry powder inhaled mannitol used in conjunction with dornase alfa was evaluated in a case‐control study over 12 months, in 15 children aged 6–18 years, showing improved FEV1pp with combination therapy over dornase alfa alone, although no difference was observed for PEx frequency or BMI 66 . Despite not having chronic PA (defined as ≥50% of cultures in past year positive with at least four cultures obtained), one‐third of PwCF were prescribed inhaled antibiotics in the European Cystic Fibrosis Patient Registry and continued use was associated with an increase in adverse outcomes 67 .…”

“…59 with combination therapy over dornase alfa alone, although no difference was observed for PEx frequency or BMI. 66 Despite not having chronic PA (defined as ≥50% of cultures in past year positive with at least four cultures obtained), one-third of PwCF were prescribed inhaled antibiotics in the European Cystic Fibrosis Patient Registry and continued use was associated with an increase in adverse outcomes. 67 Those more likely to remain on inhaled antibiotics were sicker and the strongest predictor was history of chronic PA in the 2 years before baseline.…”

Dornase alfa in Cystic Fibrosis: indications, comparative studies and effects on lung clearance index

“…The combined use of the two drugs resulted in an increase FEV 1 of 1.88% [ 39 ]. Recently a greater improvement in spirometric parameters was showed in a small cohort of CF children using DNAse and mannitol, compared to a control group using DNAse only [ 40 ].…”