Summary of findings for the main comparison. Antibiotics compared to placebo or usual care for exacerbations of asthma.

Antibiotics compared to placebo/usual care for acute asthma
Patient or population: acute asthma exacerbation Setting: emergency department Intervention: antibiotics Comparison: placebo/usual care
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo/usual care	Risk with antibiotics
ICU/HDU admission ‐ not reported	‐	‐	‐	‐	‐	One respiratory arrest in the placebo group in Shapiro 1974. No other studies reported this outcome
Symptom score at 10 days. Measured on a 7‐point scale (0 to 6) ; lower score denotes fewer symptoms	Mean symptom score at 10 days ranged from 2 to 2.20 points	MD 0.34 points lower (0.60 lower to 0.08 lower)	‐	(2 RCTs)	⊕⊕⊕⊝a,d MODERATE
All adverse events	42 per 100	41 per 100 (33 to 50)	OR 0.99 (0.69 to 1.43)	506 (3 RCTs)	⊕⊕⊝⊝ LOWb,c,d,e,f	2 studies in adults and 1 small old study in children with status asthmaticus
Serious adverse events Duration 3 days to 3 weeks	2 per 100	2 per 100 (0 to 45)	RD 0.00 (‐0.03 to 0.03)	502 (3 RCTs)	⊕⊕⊝⊝ LOWa,d,g,	Anticipated absolute effects were calculated using the figures in Figure 1. This is a re‐presentation of the results, but to 4 dp, which allows the calculation to be done
Mortality ‐ not reported	‐	‐	‐	‐	‐	No deaths were reported in any of the studies
Length of hospital stay, days	Mean length of hospital stay was 2.6 days	MD 0.1 days lower (0.53 lower to 0.33 higher)	‐	43 (1 RCT)	⊕⊝⊝⊝ VERY LOWd,h,I,j	1 study reported medians and IQRs and found no significant differences, although data were skewed
Relapse after index presentation ‐ not reported	‐	‐	‐	‐	‐
PEFR (GIV) Duration 10 days	Mean PEFR (GIV) ranged from 19.6 to 26.9 L/min (mean difference from baseline)	MD 23.42 L/min (mean difference from baseline) higher (5.23 higher to 41.6 higher)	‐	469 (2 RCTs)	⊕⊕⊕⊝ MODERATEa,d,
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DP: decimal places; GIV: generic inverse variance; HDU: high dependency unit; ICU: intensive care unit; IQR: interquartile range; MD: mean difference; OR: odds ratio; PEFR: peak expiratory flow rate; RCT: randomised controlled trial; RD: risk difference; RR: risk ratio.
GRADE Working Group grades of evidence. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

^a‐1 indirectness. Studies mostly recruited from hospital or emergency department. Therefore this review may represent more severe exacerbations and does not apply to people attending the GP and requesting antibiotics. The review does not apply to people who have already received a course of antibiotics.

^bNo downgrade for risk of bias. One small study excluded 6 participants post hoc, but excluding this study from the meta‐analysis did not affect the results.

^cNo downgrade. I² = 0. Different antibiotics were given in each study.

^dNo downgrade. Only six RCTs have been published on antibiotics for asthma exacerbation. This strongly suggests that unpublished data exist or that clinical trials are seriously lacking for this common intervention.

^e‐1 imprecision. Confidence intervals include the possibility of important benefit and risk of harm.

^f‐1 indirectness. Studies mostly recruited from hospital or emergency department. Therefore this review may represent more severe exacerbations and does not apply to people attending the GP and requesting antibiotics. The review does not apply to people who have already received a course of antibiotics. One small study recruited children with status asthmaticus in 1974, when asthma management was different.

^g‐1 imprecision. Few events.

^h‐1 risk of bias. Study before good reporting standards introduced. Concerns over study, which excluded six participants, and it is not clear from which arm they were excluded.

ⁱ‐1 indirectness. Participants were all children with status asthmaticus, and the study was conducted before current asthma management had been introduced (e.g. they all received IV adrenaline).

^j‐1 imprecision. One small study was included.