Study reference 

Study characteristics 

Patient characteristics  

Intervention (I) 

Comparison / control (C) 

Follow-up 

Outcome measures and effect size  

Comments 

Payares-Salamanca, 2020 

Individual study characteristics deduced from Payares 2020 

PS., study characteristics and results are extracted from the SR (unless stated otherwise) 

SR and meta-analysis of RCTs  

Literature search up to February 2020 

A: Batra, 1997 
Study design: 
A: RCT  
Setting and country:  
A: India  
Source of funding and conflicts of interest: 
A: not reported 

B: Chou, 1995 
Study design: 
B: RCT  
Setting and country:  
B: USA  
Source of funding and conflicts of interest: 
B: not reported 

C: Deerojanawong, 2005 
Study design: 
C: RCT  
Setting and country:  
C: Thailand  
Source of funding and conflicts of interest: 
C: not reported 

D: Delgado, 2003 
Study design: 
D: RCT  
Setting and country:  
D: USA  
Source of funding and conflicts of interest: 
D: not reported 

E: Kerem, 1993 
Study design: 
E: RCT  
Setting and country:  
E: Canada  
Source of funding and conflicts of interest: 
E: not reported 

F: Leelathipkul, 2016 
Study design: 
F: RCT  
Setting and country:  
F: Thailand  
Source of funding and conflicts of interest: 
F: not reported 

G: Maldonado, 1997 
Study design: 
G: RCT  
Setting and country:  
G: Mexico  
Source of funding and conflicts of interest: 
G: not reported 

H: Mandelberg, 2000 
Study design: 
H: RCT  
Setting and country:  
H: Israel  
Source of funding and conflicts of interest: 
H: not reported 

I: Mitselou, 2016 
Study design: 
I: RCT  
Setting and country:  
I: Sweden  
Source of funding and conflicts of interest: 
I: not reported 

J: Ploin, 2000 
Study design: 
J: RCT  
Setting and country:  
J: France  
Source of funding and conflicts of interest: 
J: not reported 

K: Robertson, 1997 
Study design: 
K: RCT  
Setting and country:  
K: Australia  
Source of funding and conflicts of interest: 
K: not reported 

L: Rubilar, 2000 
Study design: 
L: RCT  
Setting and country:  
L: Chili  
Source of funding and conflicts of interest: 
L: not reported 

M: Schuh, 1999 
Study design: 
M: RCT  
Setting and country:  
M: Canada  
Source of funding and conflicts of interest: 
M: not reported 

N: Snider, 2015 
Study design: 
N: RCT  
Setting and country:  
N: USA  
Source of funding and conflicts of interest: 
N: not reported 

O: Vangveravong, 2008 
Study design: 
O: RCT  
Setting and country:  
O: Thailand  
Source of funding and conflicts of interest: 
O: not reported 

A: 2 puffs (200 μg) every 5–10 min up to 60 min, with a commercial spacer (M/s Cipla) with a volume of 750 ml and one‐way valve 

B: Three puffs (270 μg) with a commercial spacer (Aerochamber). Number of treatments were determined by the treating physician, at 20‐min intervals 

C:  2 puffs (200 μg) with a commercial spacer (Babyhaler), with a volume of 350 ml and low resistance valves. No repeated doses were administered. 

D: 3 puffs (270 μg) every 20 min for 1 h, with a commercial spacer (Aerochamber) 

E: 6–10 puffs (600–1000 μg) depending on weight, with a commercial spacer (Vent A. Haler) with a volume of 750 ml and one‐way valve. No repeated doses were administered. 

F: Home‐made spacer with a one‐way valve. Albuterol was administered every 2–6 h depending on symptoms. No other details are provided 

G: 2 puffs (200 μg) every 20 min for two doses. No details of the spacer used were provided 

H: 4 puffs (400 μg) every 20 min for 1 h, with a commercial metal spacer (Nebuchamber), with a volume of 250 ml and low‐resistance valves (with a pressure drop required to open the valve of 1.02–1.27 cm H2O at a flow rate of 15 L/min) 

I: 4–6 puffs (400–600 μg) depending on weight. Treatment repeated up to three times during the first hour with 20–30 min intervals 

J: 1 puff per 2 kg body weight (50 μg/kg), maximum 10 puff, with a commercial spacer (Babyhaler), with a volume of 350 ml and low‐resistance valves. Treatment was repeated three times at 20‐min intervals 

K: 6–12 puff (600–1200 μg) depending on weight, with a commercial spacer (Volumatic). No repeated doses were administered 

L: 2 puffs (200 μg) every 10 min for five doses, with a commercial spacer (Aerocell), with a volume of 500 ml and with a one‐way valve. 

M: 6–10 puffs (600–1000 μg) depending on weight (higher dose MDI group) or two puffs (200 μg) (low‐dose MDI group), with a commercial metal spacer (Aerochamber), with a volume of 140 ml and low resistance valves. No repeated doses were administered 

N: No details of the doses of albuterol nor the spacer used were provided 

O: 6 puffs (600 μg) with a commercial spacer (Volumatic). Treatment was repeated three times at 20‐min intervals 

A: 0.15 mg/kg (max 5 mg) diluted in 3ml of normal saline, using jet nebulizer at a flow rate of 6 L per min. Three doses given at 20 min intervals 

B: 0.15 mg/kg (max 5 mg) diluted in 3ml of normal saline, using jet nebulizer at a flow rate of 6 L per min. Number of treatments were determined by the treating physician, at 20‐min intervals 

C: 0.03 ml/kg diluted in 2.5 ml of normal saline using jet nebulizer at a flow rate of 6 L per min. No repeated doses were administered. 

D: 0.15 mg/kg diluted in 3ml of normal saline, using a jet nebulizer at a flow rate of 6 L per min. Three doses given at 20 min intervals 

E: 0.15 mg/kg (max 5 mg) diluted in 3ml of normal saline, using jet nebulizer at a flow rate of 6–10 L per min. No repeated doses were administered. 

F: Albuterol was administered every 2–6 h, depending on symptoms. No other details are provided 

G: 0.15 mg/kg (max 5 mg) every 20 min for two doses, using jet nebulizer at a flow rate of 3 L per min 

H: 2.5 mg diluted in 1.5 ml of normal saline using jet nebulizer at a flow rate of 5 L per min (with an output of 3ml in 6 min, and an MMAD of 0.5–4 μm range). Three doses given at an interval of 20 min 

I: 4ml (Ventolin 5 mg/ml) continuous nebulization for 1 to 2 min, every 15 min for two doses, using jet nebulizer 

J: 150 mg/kg diluted in 4ml of normal saline using an ultrasonic nebulizer at a flow rate of 8 L per min (particle size of 0.5–5 μm). Treatment was repeated three times at 20‐min intervals 

K:  2.5–5mg of albuterol (depending on weight) diluted in 2.5 ml of normal saline using jet nebulizer at a flow rate of 5 L per minute. No repeated doses were administered 

L: 0.25 mg/kg (max 5 mg) diluted in 3.5 ml of normal saline using jet nebulizer at a flow rate of 7 L per min. Treatment was repeated three times at 20‐min intervals 

M: 0.15 mg/kg (max 5 mg) every 20 min for two doses, using jet nebulizer. No repeated doses were administered 

N: No details of the NEB administration were provided 

O: 0.03 ml/kg (max 1 ml) diluted in 3ml of normal saline using jet nebulizer at a flow rate of 6–8 L per min. Treatment was repeated three times at 20‐min intervals 

End-point of follow-up: not reported in SR 

For how many participants were no complete outcome data available? Not reported in SR 

1. (Length of) admission 

Defined as hospital admission 

A: RR (95% CI): 9.00 (95% CI: 0.51 to 160.17) 

D: RR (95% CI): 0.24 (95% CI: 0.08 to 0.69) 

E: RR (95% CI): 0.78 (95% CI: 0.30 to 2.07) 

I: RR (95% CI): 1.37 (95% CI: 0.50 to 3.79) 

J: RR (95% CI): 1.03 (95% CI: 0.15 to 6.88) 

M: RR (95% CI): 1.50 (95% CI: 0.27 to 8.34) 

N: RR (95% CI): 0.93 (95% CI: 0.66 to 1.32) 

O: RR (95% CI): 3.00 (95% CI: 0.13 to 69.09) 

Pooled effect (random effects model): 

RR 0.89 [95% CI 0.55 to 1.46] favoring MDI 

Heterogeneity (I2): 32% 

2. Side effects 

Defined as nausea 

A: RR (95% CI) 0.38 (0.17 to 0.83) 

D: RR (95% CI) 1.41 (0.60 to 3.32) 

J: RR (95% CI) 0.34 (0.04 to 3.13) 

M: RR (95% CI) 1.00 (0.07 to 15.26) 

N: (95% CI) 0.78 (0.39 to 1.54) 

Pooled effect (random effects model): 

RR 0.71 [95% CI 0.41 to 1.22] favoring MDI 

Heterogeneity (I2): 27% 

Defined as tremor 

E: RR (95% CI) 0.24 (0.03 to 1.89) 

L: RR (95% CI) 0.33 (0.04 to 3.07) 

M: RR (95% CI) 1.00 (0.07 to 15.26)  

O: RR (95% CI) 1.00 (0.07 to 14.79) 

Pooled effect (random effects model): 

RR 0.45 [95% CI 0.14 to 1.49] favoring MDI 

Heterogeneity (I2): 0% 

Defined as palpitations 

F: Adverse events, palpitations: RR (95% CI) 0.09 (95% CI: 0.01 to 0.64) 

NA  

J: RR (95% CI) 3.09 (0.13 to 73.17) 

N: RR (95% CI) 0.72 (0.58 to 0.90) 

O: Adverse events, palpitations: RR (95% CI) 1.00 (95% CI: 0.16 to 6.35) 

Pooled effect (random effects model): 

RR 0.60 [95% CI 0.22 to 1.64] favoring MDI 

Heterogeneity (I2): 44% 

3. Asthma score 

Defined as pulmonary index score, PIS 

B: MD 0.00 (95% CI: -1.01 to 1.01) 

D: MD -0.70 (95% CI: -1.02 to -0.38) 

L: MD -0.60 (95% CI: -1.26 to 0.06) 

Pooled effect (random effects model): 

MD -0.63 [95% CI -0.91 to -0.35] favoring MDI 

Heterogeneity (I2): 0% 

4. Recurrence 

Not reported 

5. Patient satisfaction 

Not reported 

6. Oral steroid use  

Not reported 

The authors concluded that although delivering 

albuterol through MDI+S was not significantly superior to its delivery through NEB in terms of hospital admission rates, pooled analyses showed a significant reduction in the PIS score and a significantly smaller increase in HR when albuterol was delivered through MDI+S than when it was delivered through NEB. 

The risk of bias of individual studies was assessed differently compared to the systematic review of Cates 2013. 

Level of evidence: GRADE (per comparison and outcome measure) including reasons for down/upgrading 

Sensitivity analyses (excluding small studies; excluding studies with short follow-up; excluding low quality studies; relevant subgroup-analyses); mention only analyses which are of potential importance to the research question 

Heterogeneity: clinical and statistical heterogeneity; explained versus unexplained (subgroupanalysis)

Study reference 

Study characteristics 

Patient characteristics

Intervention (I) 

Comparison / control (C)  

Follow-up 

Outcome measures and effect size   

Comments 

Tabatabaii, 2019 

Type of study: RCT 

Setting and country: children’s hospital emergency department, Iran 

Funding and conflicts of interest: not reported 

Inclusion criteria:

Age 6 months -14 years, wheezing present on auscultation, and a score> 4 on the respiratory distress assessment scale (RDAS). 

Exclusion criteria:

Severe respiratory distress requiring admission in a pediatric intensive care unit, and a patient diagnosed with bronchopulmonary dysplasia, cystic fibrosis or congenital cardiopulmonary disorders. 

N total at baseline:

Intervention: 64 

Control: 54 

Important prognostic factors2:

age ± SD: 

I: 52.5 ± 33.0 months 

C: 39.1 ± 37.9 months 

Sex:  

I: 64.5% M 

C: 63.0% M 

Groups comparable at baseline? Yes 

Metered-dose-inhaler (MDI) + spacer 

Between 2 and 10 puffs of 

salbutamol MDI (depending on weight) at 15-min 

intervals via a valve aerosol-holding chamber device wit  

the aero-chamber masks sealed to their faces and held there for 30 seconds up to five times. 

Nebulizer 

0.15 mg per kg of salbutamol (maximum dose of 2.5 mg), 

up to 5 times every 15 minutes. 

Length of follow-up: 60 minutes 

Loss-to-follow-up: N=0 

Incomplete outcome data: N=0 

1. (Length of) admission 

Not reported 

2. Side effects

Not reported 

3. Asthma score

Defined as clinical asthma score, mean (SD) 

30 min 

I: 6.37 (1.97) 

C: 6.09 (2.01), P=0.34 

45 min 

I: 5.94 (1.99) 

C: 0.69 (1.99), P=0.34 

60 min 

I: 5.42 (1.86) 

C: 5.19 (1.74), P=0.33 

4. Recurrence

Not reported 

5. Patient satisfaction

Not reported 

6. Oral steroid use

Not reported