Adde 2004.

Study characteristics
Methods	RCT. Design: open label, cross‐over with 4 weeks in each treatment arm and a 2‐week washout period in between. Location: Brazil (single centre).
Participants	Total participants: n = 18, 5 male and 13 female. CF diagnosis: not stated. Age: mean (SD) 14.8 (4.8) years, range 8.7 to 25.8 years. Baseline characteristics Airway colonisation: Pseudomonas aeruginosa = 17 Staphylococcus aureus = 12 Haemophylus influenzae = 1 Shwachman score: median (range) 65 (55 – 90). Pancreatic insufficiency: n = 17. Previous use of rhDNase: n = 15. Continuous inhaled gentamicin therapy: n = 11.
Interventions	Group 1: HS 6% 10 mL. Group 2: rhDNase 2.5 mg 2x daily. Both trial drugs were delivered by a Pari LC Plus nebulizer with a Proneb® compressor, by a mouthpiece. The first inhalation was done in the hospital, for technique supervision, checking of immediate side effects, post‐medication PFT and measurement of nebulization time. Salbutamol (400 mcg) was given prior to inhalation, twice daily, in both arms of the trial. All the other treatment for CF was unchanged. While in the rhDNase arm of the trial the participant was asked to do a normal saline nebulization (5 mL) at another time during the day.
Outcomes	Change in FEV1, sputum culture bacterial growth, in vitro studies of mucus, symptom score, satisfaction with treatment.
Notes	Abstract only, but some additional information from authors. No sample size calculation stated.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	No detail provided in abstract, but additional information from authors confirmed use of a random numbers table.
Allocation concealment (selection bias)	Low risk	No detail provided in abstract, but additional information from authors confirmed that for each potential participant the selected sequence of treatment was defined and written in a piece of paper which was then put into numbered envelopes that were kept in the hospital pharmacy. After participants were recruited and informed consent obtained the first envelope was opened and read to see the allocated treatment.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Double blind, participant blinding was attempted by masking the taste of the solutions with quinine sulphate but additional info states "as participants were well aware of the medication flavour of HS this could not be masked".
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not discussed.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Did not report withdrawals. Additional data provided stated that 1 participant (not included in the analysis) had to stop treatment with HS due to severe dyspnoea during its nebulization.
Selective reporting (reporting bias)	Unclear risk	Abstract only.
Other bias	Low risk	2‐week washout period in between treatment arms. No sample size calculation stated.