Study ID and Country | Setting | Inclusion Criteria of Participants | RSV Positivity | Intervention and Control | Treatment Regimen | Outcomes |
---|---|---|---|---|---|---|

Al-Ansari 2010,^{14} Qatar | Outpatient (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} Turkey | Outpatient (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: SAO_{2} 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 Wales | Inpatient | Children <12 mo with diagnosis of bronchiolitis defined as apparent viral RTI with airway obstruction (hyperinflation, tachypnea, and subcostal recession) and widespread crepitations, needing O_{2} with SaO_{2} <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 SaO_{2} ≥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} USA | Outpatient (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, SaO_{2}, hospitalization rate, physician clinical impression, parental assessment, AEs. | |||||

Grewal 2009,^{13} Canada | Outpatient (ED) | Children 6 wk to 12 mo with diagnosis of bronchiolitis, defined as first episode of wheezing and symptoms of viral RTI, initial SAO_{2} 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 SAO_{2} 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} Turkey | Outpatient (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: SAO_{2}, respiratory rate, heart rate. | |||||

−4 mL 3% saline (n = 30) | ||||||

−4 mL 0.9% saline (n = 30) | ||||||

Jacobs 2014,^{32} USA | Outpatient (ED) | Children 6 wk to < 18 mo with bronchiolitis defined as viral RTI and first episode of wheezing, Wang CSS ≥4 and SaO_{2} >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 Canada | Inpatient | Children ≤18 mo with history of preceding viral upper RTI, wheezing or crackles on chest auscultation, plus either SaO_{2} 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 SaO_{2} ≥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} China | Outpatient (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} China | Inpatient | Wheezing 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} China | Inpatient | Children <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} Israel | Inpatient | Children ≤12 mo with clinical presentation of viral bronchiolitis, temperature >38°C and SaO_{2} ≥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} Italy | Inpatient | Children under 24 mo with diagnosis of bronchiolitis, defined as first episode of wheezing and clinical symptoms of viral RTI, SAO_{2} <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} Nepal | Inpatient | Children >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 SaO_{2} ≥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 O_{2}, feeding adequately, minimal or absent of wheezing, crackles, and retractions, S_{a}O_{2} ≥95% at room air for 4 h and severity score was < 4). |

−4 mL 0.9% saline (n = 36) | - Secondary: duration of supplemental O_{2}, clinical scores. | |||||

Pandit 2013,^{34} India | Inpatient | Children 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, SaO_{2}, heart rate, number of add on treatment, AEs. | |||||

Sarrel 2002,^{9} Israel | Outpatient (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} India | Inpatient | Children 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} Israel | Inpatient | Children ≤12 mo with clinical presentation of viral bronchiolitis leading to hospitalization and SaO_{2} ≥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 Netherlands | Inpatient | Children 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 O_{2}, no tube-feeding or intravenous fluids). |

−4 mL 6% saline + 2.5 mg salbutamol (n = 83) | - Secondary: transfer to ICU, duration of supplemental O_{2} or tube-feeding, AEs. | |||||

−4 mL 0.9% saline + .·5 mg salbutamol (n = 80) | ||||||

Tinsa 2014,^{27} Tunis | Inpatient | Children 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 O_{2}, adequate fluid intake, Wang CSS <3), AEs. | |||||

−4 mL 0.9% saline (n = 26) | ||||||

Wu 2014,^{30} USA | Outpatient (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} Nepal | Outpatient (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: S_{a}O_{2,} 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} USA | Inpatient | Children 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} Argentina | Inpatient | Children 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 O_{2}, AEs. |

ITQoL, Infant Toddler Quality of Life; NA, not applicable; RACS, Respiratory Assessment Change Score; RTI, respiratory tract infection; SaO

_{2}, oxygen saturation.