TABLE 1

Characteristics of Included Trials

Study ID and CountrySettingInclusion Criteria of ParticipantsRSV PositivityIntervention and ControlTreatment RegimenOutcomes
Al-Ansari 2010,14 QatarOutpatient (ED)Infants ≤18 mo with moderate to severe bronchiolitis, defined as a prodromal history of viral RTI followed by wheezing and/or crackles and Wang CSS of ≥4.56.1% (96/171)−5 mL 3% saline + 1.5 mg epinephrine (n = 58)Saline solutions given on enrollment and every 4 h thereafter.- Primary: Wang CSS at 48 h.
−5 mL 5% saline + 1.5 mg epinephrine (n = 57)- Secondary: Wang CSS at 24 and 72 h, LOS in ED, revisit to ED, AEs.
−5 mL 0.9% saline + 1.5 mg epinephrine (n = 56)
Anil 2010,15 TurkeyOutpatient (ED)Infants 6 wk to 24 mo with first episode of bronchiolitis, defined by symptoms of upper RTI and presence of bilateral wheezing and/or crackles on auscultation and Wang CSS between 1 and 9.NA−4 mL 3% saline + 1.5 mg epinephrine (n = 39)Saline solutions given at 0 and 30 min.- Primary: Wang CSS at 0, 30, 60, 120 min.
−4 mL 0.9% saline + 1.5 mg epinephrine (n = 38)- Secondary: SAO2 in room air and heart rate at 0, 30, 60 and 120 min, AEs.
−3% saline + 2.5 mg salbutamol (n = 36)
−4 mL 0.9% saline + 2.5 mg salbutamol (n = 36)
−4 mL 0.9% saline (n = 37)
Everard 2014,4 England and WalesInpatientChildren <12 mo with diagnosis of bronchiolitis defined as apparent viral RTI with airway obstruction (hyperinflation, tachypnea, and subcostal recession) and widespread crepitations, needing O2 with SaO2 <92%.84% (179/212)−4 mL 3% saline + standard care (n = 142)HS given every 6 h until primary outcome achieved.- Primary: fit for discharge (75% of usual intake and SaO2 ≥92% for 6 h at room air).
- Standard care (n = 149)- Secondary: actual time to discharge, readmission within 28 d from randomization, healthcare usage, duration of respiratory symptoms postdischarge, ITQoL, AEs.
Florin 2014,31 USAOutpatient (ED)Children <24 mo with first episode of bronchiolitis, defined as first episode of wheezing associated with signs and symptoms of upper RTI and respiratory distress measured by RDAI score between 4 and 15.NA−4 mL 3% saline (n = 31)One dose of saline solutions given at 0 min.- Primary: RACS at 1 h after inhalation.
−4 mL 0.9% saline (n = 31)- Secondary outcomes: vital signs, SaO2, hospitalization rate, physician clinical impression, parental assessment, AEs.
Grewal 2009,13 CanadaOutpatient (ED)Children 6 wk to 12 mo with diagnosis of bronchiolitis, defined as first episode of wheezing and symptoms of viral RTI, initial SAO2 85%–96% and initial RDAI score ≥4.82.2% (37/45)−2.5 mL 3% saline + 0.5 mL 2.25% racemic epinephrine (n = 24)One dose saline solutions given at 0 min.- Primary: RACS 0–120 min, change in SAO2 0–120 min.
−2.5 mL 0.9% saline + 0.5 mL 2.25% racemic epinephrine (n = 24)- Secondary: admission to hospital, return to ED, AEs.
Ipek 2011,17 TurkeyOutpatient (ED)Children <2 y with history of preceding viral upper RTI followed by wheezing and crackles on auscultation and Wang CSS between 4 and 8.NA−4 mL 3% saline + 0.15 mg /kg salbutamol (n = 30)Saline solutions given at 0, 20, 40 min.- Primary: Wang CSS, use of corticosteroid, hospitalization, clinical assessment 48–72 h.
−4 mL 0.9% saline + 0.15 mg /kg salbutamol (n = 30)- Secondary: SAO2, respiratory rate, heart rate.
−4 mL 3% saline (n = 30)
−4 mL 0.9% saline (n = 30)
Jacobs 2014,32 USAOutpatient (ED)Children 6 wk to < 18 mo with bronchiolitis defined as viral RTI and first episode of wheezing, Wang CSS ≥4 and SaO2 >85%.60.3% (41/68)−3 mL 7% saline + 0.5 mL 2.25% racemic epinephrine (n = 52)One dose of saline solutions given at 0 min.- Primary: Wang CSS before and after treatment and at disposition.
−3 mL 0.9% saline + 0.5 mL 2.25% racemic epinephrine (n = 49)- Secondary: hospitalization rate, proportion of admitted patients discharged at 23 h, LOS, AEs.
Kuzik 2007,12 Abu Dhabi and CanadaInpatientChildren ≤18 mo with history of preceding viral upper RTI, wheezing or crackles on chest auscultation, plus either SaO2 of 94% in room air or significant respiratory distress as measured by RDAI score ≥4.68.8% (55/80)−4 mL 3% saline (n = 47)3 doses given every 2 h, followed by every 4 h for 5 doses, followed by every 6 h until discharge.- Primary: LOS defined as time between study entry and time at which the infant either reached protocol-defined discharge criteria (RDAI score < 4 and SaO2 ≥95% in room air for 4 h) or discharged by attending physician, whichever came first.
−4 mL 0.9% saline (n = 49)- Secondary: AEs.
Li 2014,35 ChinaOutpatient (Ambulatory care unit)Children 2–18 mo with first episode of bronchiolitis (Wang CSS ≥4).NA−2 mL 3% saline (n = 42)Saline solutions given twice daily for 3 d.- Primary: Wang CSS 24, 48, 72 h after treatment.
−2 mL 5% saline (n = 40)- Secondary: AEs.
−2 mL 0.9% saline (n = 42)
Luo 2010,18 ChinaInpatientWheezing infants with mild to moderate viral bronchiolitis, measured by Wang CSS.69.9% (65/93)−4 mL 3% saline + 2.5 mg salbutamol (n = 50)Saline solutions given every 8 h until discharge.LOS (discharge decided by attending physician), time for resolution of wheezing, cough, pulmonary moist and crackles, Wang CSS, AEs.
−4 mL 0.9% saline + 2.5 mg salbutamol (n = 43)
Luo 2011,19 ChinaInpatientChildren <24 mo with first episode of wheezing diagnosed as moderate to severe bronchiolitis according Wang CSS.73.2% (82/112)−4 mL 3% saline (n = 57)3 doses given every 2 h, followed by every 4 h for 5 doses, followed by every 6 h until discharge.LOS (discharge decided by attending physician), time for resolution of wheezing, cough, pulmonary moist and crackles, Wang CSS, AEs.
−4 mL 0.9% saline (n = 55)
Mandelberg 2003,10 IsraelInpatientChildren ≤12 mo with clinical presentation of viral bronchiolitis, temperature >38°C and SaO2 ≥85%.87% (47/52)−4 mL 3% saline + 1.5 mg epinephrine (n = 27)Saline solutions given every 8 h until discharge.- Primary: LOS (discharge decided by attending physician), Wang CSS.
−4 mL 0.9% saline + 1.5 mg epinephrine (n = 25)- Secondary: radiograph score, AEs.
Miraglia 2012,16 ItalyInpatientChildren under 24 mo with diagnosis of bronchiolitis, defined as first episode of wheezing and clinical symptoms of viral RTI, SAO2 <94% in room air and significant respiratory distress measured by Wang CSS.82.1% (87/106)- ? mL 3% saline + 1.5 mg epinephrine (n = 52)Saline solutions given every 6 h.- Primary: LOS defined as time between study entry and time of discharge.
- ? mL 0·9% saline + 1.5 mg epinephrine (n = 54)- Secondary: Wang CSS on each treatment day.
Ojha 2014,33 NepalInpatientChildren >6 wk to <24 mo with first episode of bronchiolitis defined as wheezing associated with upper RTI, tachypnea, increased respiratory effort, clinical scoring of respiratory distress ≥4 and SaO2 ≥85%.NA−4 mL 3% saline (n = 36)Saline solutions given every 8 h until discharge.- Primary: LOS calculated from time of entry to time of discharge (no supplemental O2, feeding adequately, minimal or absent of wheezing, crackles, and retractions, SaO2 ≥95% at room air for 4 h and severity score was < 4).
−4 mL 0.9% saline (n = 36)- Secondary: duration of supplemental O2, clinical scores.
Pandit 2013,34 IndiaInpatientChildren 2–12 mo with acute bronchiolitis defined as short history of cough with or without fever <7 d and first episode of wheezing.NA−4 mL 3% saline + 1 mL adrenaline (n = 51)3 doses given every 1 h, followed by every 6 h until discharge.- Primary: LOS (discharge criteria: respiratory rate <60/min, without retractions and wheezing).
−4 mL 0.9% saline + 1 mL adrenaline (n = 49)- Secondary: improvement in RDAI score, respiratory rate, SaO2, heart rate, number of add on treatment, AEs.
Sarrel 2002,9 IsraelOutpatient (Ambulatory care unit)Children ≤24 mo with clinical presentation of mild to moderate bronchiolitis and SaO2 <96%.80% (52/65)−2 mL 3% saline + 5 mg terbutaline (n = 33)Saline solutions given every 8 h for 5 d.- Primary: hospitalization rate, Wang CSS.
−2 mL 0.9% saline + 5 mg terbutaline (n = 32)- Secondary: radiograph score, AEs.
Sharma 2012,23 IndiaInpatientChildren 1–24 mo with moderate (Wang CSS 3–6) acute bronchiolitis defined as first episode of wheezing with prodrome of upper RTI.NA−4 mL 3% saline + 2.5 mg salbutamol (n = 125)Saline solutions given every 4 h until discharge.- Primary outcome: LOS defined as time from admission to Wang CSS < 3.
−4 mL 0.9% saline + 2.5 mg salbutamol (n = 123)- Secondary: Wang CSS, AEs.
Tal 2006,11 IsraelInpatientChildren ≤12 mo with clinical presentation of viral bronchiolitis leading to hospitalization and SaO2 ≥85%.80% (33/41)−4 mL 3% saline + 1.5 mg epinephrine (n = 21)Saline solutions given every 8 h until discharge.- Primary: LOS (discharge decided by attending physician), Wang CSS.
−4 mL 0.9% saline + 1.5 mg epinephrine (n = 20)- Secondary: radiograph score, AEs.
Teunissen 2013,24 The NetherlandsInpatientChildren 0–24 mo with moderate to severe (Wang CSS ≥3) bronchiolitis defined as upper RTI with wheezing, tachypnea, and dyspnea.88% (212/241)−4 mL 3% saline + 2.5 mg salbutamol (n = 84)Saline solutions given every 8 h until discharge.- Primary outcome: LOS defined as time between the first dose of medications and clinical decision to discharge (protocol-defined discharge criteria: no supplemental O2, no tube-feeding or intravenous fluids).
−4 mL 6% saline + 2.5 mg salbutamol (n = 83)- Secondary: transfer to ICU, duration of supplemental O2 or tube-feeding, AEs.
−4 mL 0.9% saline + .·5 mg salbutamol (n = 80)
Tinsa 2014,27 TunisInpatientChildren 1 to 12 mo with diagnosis of bronchiolitis, defined as first episode of wheezing associated with acute RTI and Wang score ≥3.NA−4 mL 5% saline (n = 31)Saline solutions given every 4 h until discharge.- Primary: Wang CSS at 30, 60 and 120 min.
−2 mL 5% saline + 2 mL epinephrine (n = 37)- Secondary:: LOS (discharge criteria: no supplemental O2, adequate fluid intake, Wang CSS <3), AEs.
−4 mL 0.9% saline (n = 26)
Wu 2014,30 USAOutpatient (ED)Children <24 mo with first episode of bronchiolitis during bronchiolitis season.62·2% (84/135)−4 mL 3% saline (n = 211)Saline solutions given every 20 min to a maximum of 3 doses. Admitted patients: every 8 h until discharge.- Primary: admission rate, LOS.
−4 mL 0.9% saline (n = 197)- Secondary: RDAI score, need for supplemental therapy, AEs.
NCT01276821,36 NepalOutpatient (ED)Children 6 wk to 2 y with bronchiolitis defined as first episode of wheezing and Wang CSS between 1 and 9.NA−4 mL 3% saline + 1.5 mg epinephrine (n = 50)Saline solutions given at 0, 30 min.- Primary: Wang CSS at 30, 60, 120 min.
−4 mL 0.9% saline + 1.5 mg epinephrine (n = 50)- Secondary: SaO2, respiratory rate, heart rate at 30, 60, 120 min, transfer to ICU, discharge rate after 120 min, revisit to ED within 1 wk, AEs.
NCT01488448,25 USAInpatientChildren 0–12 mo admitted to hospital with a diagnosis of bronchiolitis.NA−4 mL 3% saline (n = 93)Saline solutions given every 4 h until discharge.- Primary: LOS.
−4 mL 0.9% saline (n = 97)- Secondary: readmission within 30 d, transfer to ICU, AEs.
NCT01238848,37 ArgentinaInpatientChildren 1–24 mo hospitalized for first episode of bronchiolitis, with severity score ≥5 and oxygen saturation ≥97%.NA−3 mL 3% saline + albuterol 0·25 mg/kg/day (n = 37)- Primary: LOS.
−3 mL 0.9% saline + albuterol 0.25 mg/kg/day (n = 45)- Secondary: duration of supplemental O2, AEs.
  • ITQoL, Infant Toddler Quality of Life; NA, not applicable; RACS, Respiratory Assessment Change Score; RTI, respiratory tract infection; SaO2, oxygen saturation.