Merz 1999.

Methods	Randomised double‐blind placebo controlled trial Blinding of randomisation: yes Blinding of intervention: yes Complete follow‐up: yes Blinding of outcome measurement: can't tell
Participants	Preterm infants with birth weight of 750 to 1500 grams, gestational age of 25 to 32 weeks, ventilator dependency on day 3 of life with a ventilator rate ≥ 15 breaths/min and FiO₂ of > 0.25 to maintain an oxygen saturation of > 90%. 24 infants were enrolled in the study, one infant in the placebo group withdrawn due to severe sepsis 1 day after starting inhalation therapy. Demographic data: values are presented as median (range) Budesonide group: n = 12 Birth weight (g): 1108 (820 to 1420) Gestational age (weeks): 28 (27 to 32) Sex (% male): 42 Age at enrolment (hours): 72 Placebo group: n = 11 Birth weight (g): 1120 (880 to 1480) Gestational age (weeks): 29 (27 to 31) Sex (% male): 45 Age at enrolment (hours): 72 Exclusion criteria: Infants with multiple or severe congenital anomalies such as complex congenital heart disease, suspected chromosomal abnormalities, evidence or even suspected sepsis or pneumonia, IVH grade III or IV at the time of randomisation and infants intubated with an endotracheal tube size < 2.5 mm. Study centre: Aachen, Germany Study period: November 1995 to August 1996
Interventions	Budesonide (Astra Draco, Lund, Sweden) or placebo aerosol were used. Two puffs of budesonide (200 µg/puff) or placebo was administered 4 times a day for a total of 10 days or until the infants were extubated. The aerosol was delivered using metered dose inhaler and an Aerochamber (Aerochamber MV15, Trudell Medical, Ontario, Canada). The spacer was directly connected to the endotracheal tube and the distal end of the spacer was connected to a manual puffer.
Outcomes	Primary outcome: duration of artificial ventilation Secondary outcomes: duration of supplemental oxygen Release of albumin and different inflammatory mediators in the tracheobronchial aspirate fluid Adverse events: frequency of acute infections, hypertension, hyperglycaemia and adrenal suppression was evaluated. CLD was defined as requirement of supplemental oxygen at 28 days of life and at 36 weeks' PMA. Hyperglycaemia was defined as blood glucose > 8.3 mmol/L. Hypertension was defined as systolic and diastolic blood pressure > 2 SD from mean values. Acute infection was suspected if clinical deterioration was observed accompanied by a rise in C‐reactive protein or by ratio of immature to mature granulocytes above 0.2 in complete blood cell count. A corticotropin‐releasing hormone stimulation test (CRH test) was performed on day 14 after completion of the inhalation treatment.
Notes	Infants were ventilated with Stephan respirator HF 300 (Fa. Stephan, Gackenbach, Germany) in the IPPV or IMV mode. To facilitate weaning from the ventilator infants were treated with fluid restriction (120 ml/kg/day). No nebulized bronchodilators or diuretics or supplemental vitamin A or E were used. Infants with respiratory distress syndrome were treated with natural surfactant (Alveofact) up to a maximum of 3 doses. Extubation was performed if the ventilator rate was down to 8 breaths/minute and 2 periods of tracheal continuous positive airway pressure lasting 20 minutes were tolerated. Theophylline or caffeine citrate was used to treat apnoea of prematurity. Infants who could not be weaned from ventilator on day 14 were treated with systemic glucocorticoids after day 14. Dexamethasone was administered intravenously and divided into two doses: starting dose of 0.5 mg/kg/day for the first 3 days followed by 0.3 mg/kg/day of day 4‐6. From day 7 the dose was reduced to 0.1 mg/kg/day and this was administered on alternate day from day 10 to day 16.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised controlled trial Method of sequence generation unknown
Allocation concealment (selection bias)	Low risk	Blinding of randomisation: yes
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding of intervention: yes
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Blinding of outcome measurement: can't tell
Incomplete outcome data (attrition bias) All outcomes	Low risk	Complete follow‐up: yes
Selective reporting (reporting bias)	Unclear risk	The trial was not registered so we cannot tell if there was selective reporting or not.
Other bias	Low risk	Appears free of other bias.