Long 2014.

Methods	Randomised, single‐centre, open‐label, controlled clinical trial in Shanghai, China
Participants	Inclusion criteria: People aged 18 to 65 years with severe acute exacerbations of asthma. A severe asthma exacerbation was defined as at least 1 of the following: need for systemic corticosteroids, or an increase from a stable maintenance dose, for at least 3 days and/or hospitalisation or ED visit because of asthma requiring systemic corticosteroids. Exclusion criteria: People with antibiotic use within the previous 14 days, psychiatric disorders or other inability to give written informed consent, not being available for follow‐up, severe immunosuppression, heart failure, cystic fibrosis, active tuberculosis, pregnancy, and chest radiography–confirmed pneumonia Included in this study: 180/216 screened individuals were eligible for the study (90 intervention group, 90 non‐intervention group); 169 finished the follow‐up.
Interventions	Guiding antibiotic decisions in people with acute severe exacerbation of asthma Algorithm used in this study: Antibiotic treatment was strongly discouraged when serum PCT level was less than 0.1 μg/L; antibiotic treatment was discouraged when serum PCT level was less than 0.25 μg/L; and antibiotic treatment was encouraged when serum PCT level was higher than 0.25 μg/L. When antibiotics were withheld from participants, a second measurement of the PCT level was mandatory within 6 to 24 hours for safety reasons. The use of antibiotics was recommended if this second measurement was higher than 0.25 μg/L. Physicians were permitted to overrule the algorithm, but they had to indicate the reasons for overruling. The control group received antibiotic according to the discretion of the treating physician, who was unaware of the participant’s PCT levels.
Outcomes	antibiotic use, expressed as rate of antibiotic prescriptions in percentage and relative risk of antibiotic exposure measures of treatment success length of hospital stay clinical, laboratory, and spirometry outcomes at discharge results of spirometry at the 12‐month follow‐up examination, as well as the results of the Asthma Control Test, the results of the Asthma Quality of Life Questionnaire at the 12‐month follow‐up visit clinical events during the 12‐month follow‐up period, including numbers of asthma exacerbations, ED visits, hospitalisations, and need for systemic corticosteroid use for treatment of asthma
Notes	Funding: The study was sponsored by a grant from the Shanghai Fifth People’s Hospital Science Foundation and Minhang District Natural Science Foundation of Shanghai. The funding bodies had no involvement in the design, collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. Follow‐up time: 12 months Registration: ChiCTR‐TRC‐12002534
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Allocation to either intervention was conducted according to computer‐generated random numbers produced by an independent statistician.
Allocation concealment (selection bias)	Low risk	After randomisation, an opaque, sealed, sequentially numbered envelope containing the PCT or control protocol was prepared for each participant according to group assignment.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Open‐label study with blinding of PCT level in the control group
Blinding of outcome assessment (detection bias) All outcomes	High risk	No blinding of outcome assessment mentioned in the study.
Incomplete outcome data (attrition bias) All outcomes	Low risk	169/180 participants completed 1‐year follow‐up visit (11 participants lost to follow‐up).
Selective reporting (reporting bias)	Low risk	Outcomes correspond to study protocol. Trial registered (ChiCTR‐TRC‐12002534).
Other bias	Low risk	High adherence to PCT algorithm (93.3%)