Weber 1999.

Methods	‐ Prospective, randomised, double‐blind, placebo‐controlled study. ‐ Comparison of ipratropium bromide and albuterol vs. albuterol alone. ‐ Randomisation was accomplished using a random numbers table. ‐ Allocation concealment was reported and discussed as pharmacy controlled.
Participants	‐ Patients presenting to the ED with an exacerbation of asthma, who had a PEF < 70% of the predicted value. ‐ Set in the United States. ‐ Ages: 18 years or older. ‐ Asthma exacerbation severity of presenting patients estimated as severe.
Interventions	‐ Single dose of combination inhaled therapy. Study interventions provided via nebuliser. ‐ First group received ipratropium bromide (1.0 mg/hour) and albuterol (10 mg/hour) taken continuously over a three hour period. ‐ Second group received albuterol (10 mg/hour) alone taken continuously over a three hour period. ‐ Additional co‐interventions provided in the ED included oral prednisone and albuterol (2.5 mg) provided to all patients upon presentation to the ED. Supplemental oxygen was given if patients S0₂ was < 90%.
Outcomes	‐ Primary outcomes included pulmonary function, hospitalisation and ED length of stay. ‐ Seconary outcomes included vital signs, symptom scores, and adverse events. ‐ Outcome measurements were performed at baseline, as well as one, two, and three hours after the start of treatment.
Notes	‐ Contacted primary author who stated that they no longer had access to the original data.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random numbers tables. Quote (p. 938): "The combination and control treatments were prepared by the hospital pharmacy in random sequence using a random number table..."
Allocation concealment (selection bias)	Unclear risk	Central allocation, pharmacy‐controlled. Quote (p. 938): "The combination and control treatments were prepared by the hospital pharmacy..."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind study. Study medications placed in consecutively numbered identical brown‐tinted bottles. Treating physicians, respiratory therapist, patients and investigators were blind to treatment. Quotes (pp. 938‐9): "The combination and control treatments were prepared by the hospital pharmacy in random sequence using a random number table and were placed in identical 4‐oz brown‐tinted bottles, which were then numbered consecutively." "The RT, treating physician, and patient were blinded to treatment, and the code for drug assignment was not known to the investigators until data for all patients had been entered into the study database."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Physicians, and respiratory therapists were blinded to treatment. Code for drug assignment were unknown to the study investigators until all of the patients data have been entered into the study database. Quote (p. 939): "The RT, treating physician, and patient were blinded to treatment, and the code for drug assignment was not known to the investigators until data for all patients had been entered into the study database."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No information provided on why most screened patients were not enrolled into the study. Quote (p. 939): "There were 465 patients who presented to the ED with acute bronchospasm during the study period but were not enrolled in the study."
Selective reporting (reporting bias)	Unclear risk	No protocol available.
Other bias	High risk	Ipratropium bromide and pharmacy costs provided by Boehringer Ingelheim. No statement provided on influence of funding on preparation of the manuscript. Quote (p. 937): "Ipratropium bromide and pharmacy costs were provided by Boehringer Ingelheim.

Abbreviations: 
 ATS ‐ American Thoracic Society
 COPD ‐ chronic obstructive pulmonary disease 
 ED ‐ emergency department
 FEV ‐ forced expiratory volume
 ICU ‐ intensive care unit
 IV ‐ intravenous
 MDI ‐ metered‐dose inhaler
 PEF ‐ peak expiratory flow
 RCT ‐ randomised controlled trial