Dentice 2012.

Methods	Randomised, cross‐over trial with concealed allocation, intention‐to‐treat analysis and blinded assessors; investigating the impact of timing of hypertonic saline inhalation in relation to airway clearance techniques. The inhalation blocks were for one day. The three treatments of the allocated timing regimen were performed on each of the three trial days, with no washout day.
Participants	50 adults (mean age 31 years, SD 10, range 18 ‐ 64 years) with a confirmed diagnosis of cystic fibrosis who were clinically stable with an FEV1 within 10% of the best recorded value in the last 6 months. This trial excluded people who were hypertonic saline naïve or previously intolerant, a lung transplant recipient, colonised with Burkholderia cepacia complex, not clinically stable, haemoptysis greater than 60 mL within the last month, thrombocytopenia or pregnancy.
Interventions	4 mL of 6% hypertonic saline was nebulised via an LC Star nebuliser 3 times per day with the allocated timing regimen for that day. Hypertonic saline was nebulised immediately before or after airway clearance or during (with blocks of inhalation and pauses for airway clearance). The airway clearance technique was optimised for each participant on recruitment to the trial and was standardised for all 3 trial days.
Outcomes	The primary outcome was the change in FEV1 and FVC (in litres and percentage of the predicted value) recorded prior to and two hours following the middle treatment session of each trial day. Symptom scores at the end of each intervention arm were also recorded: perceived effectiveness, tolerability and satisfaction rated on a 100 mm visual analogue scale. Adverse events and adherence were also recorded.
Notes	PEDro Score: 8/10 [Eligibility criteria: yes; random allocation: yes; concealed allocation: yes; baseline comparability: yes; blind participants: no; blind therapists: no; blind assessors: yes; adequate follow up: yes; intention‐to‐treat analysis: yes; Between‐group comparisons: yes; point estimates and variability: yes. Note: eligibility criteria item does not contribute to total score].
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random allocation list.
Allocation concealment (selection bias)	Low risk	Sealed opaque envelopes.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Stated "no withdrawals" and intention‐to‐treat analysis used.
Selective reporting (reporting bias)	Low risk	Consistent with the prospectively registered trial protocol.
Other bias	Low risk	None identified.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants were unblinded to the timing regimen.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessors were blinded.