PMID- 36169967
OWN - NLM
STAT- MEDLINE
DCOM- 20230203
LR  - 20230215
IS  - 2325-6621 (Electronic)
IS  - 2325-6621 (Linking)
VI  - 20
IP  - 2
DP  - 2023 Feb
TI  - Inhaled Nitric Oxide for the Treatment of Acute Bronchiolitis: A Multicenter 
      Randomized Controlled Clinical Trial to Evaluate Dose Response.
PG  - 236-244
LID - 10.1513/AnnalsATS.202103-348OC [doi]
AB  - Rationale: Inhaled nitric oxide (iNO) has potential antiinflammatory, 
      antimicrobial, and antiviral properties for patients with lower respiratory tract 
      infections. Objectives: We compared the safety and efficacy of iNO administered 
      in two concentrations in addition to standard supportive treatment (SST) compared 
      with SST alone with the aim of improving clinical outcomes of infants with 
      bronchiolitis. Methods: In this prospective, multicenter, double-blind, 
      randomized controlled study, 89 infants hospitalized with moderate to severe 
      bronchiolitis were randomly assigned to three treatment groups: 150 ppm NO plus 
      SST (group 1), 85 ppm NO plus SST (group 2), and the control treatment (O(2)/air 
      plus SST) (group 3). Treatment was given for 40 minutes, four times each day, for 
      up to 5 days. The primary endpoint was time to reach "fit for discharge." This 
      was a composite endpoint composed of both reaching a sustained oxygen saturation 
      >/=92% on room air and reaching a clinical score ⩽5. Secondary endpoints included 
      time to reach sustained oxygen saturation >/=92% on room air, time to clinical 
      score ⩽5, and time to hospital discharge. Safety was assessed by the number of 
      treatment-related adverse events (AEs) or serious AEs. Time-to-event efficacy 
      outcomes were analyzed using a Cox proportional hazards regression model. Hazard 
      ratios (HR) describe how many times more likely an individual is to experience an 
      event, if such an individual receives NO rather than the control treatment during 
      the observational period. Results: Group 1 demonstrated significant efficacy for 
      time to reach fit to discharge compared with groups 2 (HR, 2.11; P = 0.041) and 3 
      (HR, 2.32; P = 0.049). Group 1 also demonstrated significant efficacy for time to 
      hospital discharge compared with groups 2 (HR, 2.01; P = 0.046) and 3 (HR, 2.28; 
      P = 0.043). No significant differences were observed between groups 2 and 3 for 
      either endpoint. There were no differences between treatment groups in time to 
      reach a clinical score ⩽5. The iNO therapy was well tolerated, with no 
      treatment-related serious AEs. Conclusions: Treatment with high-dose intermittent 
      iNO at 150 ppm showed reduced time to clinical improvement compared with 85 ppm 
      or control treatment of hospitalized infants with acute bronchiolitis. The 
      150-ppm iNO dose is well tolerated, with significant benefit compared with both 
      standard therapy and 85 ppm iNO, improving respiratory outcomes and reducing 
      length of stay. Clinical trial registered with www.clinicaltrials.gov 
      (NCT04060979).
FAU - Goldbart, Aviv
AU  - Goldbart A
AUID- ORCID: 0000-0002-7063-4653
AD  - Saban Pediatric Medical Center, Soroka University Medical Center, Faculty of 
      Health Sciences, Ben-Gurion University, Beer Sheva, Israel.
FAU - Lavie, Moran
AU  - Lavie M
AD  - Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Sackler School 
      of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Lubetzky, Ronit
AU  - Lubetzky R
AD  - Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Sackler School 
      of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Pillar, Giora
AU  - Pillar G
AD  - Schneider Children's Medical Center, Petach Tikva, Israel.
FAU - Landau, Daniel
AU  - Landau D
AD  - Carmel Medical Center, Haifa, Israel.
FAU - Schlesinger, Yechiel
AU  - Schlesinger Y
AD  - Shaare Zedek Medical Center, Jerusalem, Israel.
FAU - Spiegel, Ronen
AU  - Spiegel R
AD  - Haemek Medical Center, Afula, Israel.
FAU - Golan-Tripto, Inbal
AU  - Golan-Tripto I
AUID- ORCID: 0000-0001-6259-405X
AD  - Saban Pediatric Medical Center, Soroka University Medical Center, Faculty of 
      Health Sciences, Ben-Gurion University, Beer Sheva, Israel.
FAU - Nahum, Amit
AU  - Nahum A
AD  - Saban Pediatric Medical Center, Soroka University Medical Center, Faculty of 
      Health Sciences, Ben-Gurion University, Beer Sheva, Israel.
FAU - Greenberg, David
AU  - Greenberg D
AD  - Saban Pediatric Medical Center, Soroka University Medical Center, Faculty of 
      Health Sciences, Ben-Gurion University, Beer Sheva, Israel.
AD  - Beyond Air, Rehovot, Israel; and.
AD  - Beyond Air, Garden City, New York.
FAU - Tal, Asher
AU  - Tal A
AUID- ORCID: 0000-0002-5670-8804
AD  - Saban Pediatric Medical Center, Soroka University Medical Center, Faculty of 
      Health Sciences, Ben-Gurion University, Beer Sheva, Israel.
AD  - Beyond Air, Rehovot, Israel; and.
AD  - Beyond Air, Garden City, New York.
LA  - eng
SI  - ClinicalTrials.gov/NCT04060979
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann Am Thorac Soc
JT  - Annals of the American Thoracic Society
JID - 101600811
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Infant
MH  - Humans
MH  - *Nitric Oxide
MH  - Prospective Studies
MH  - Administration, Inhalation
MH  - *Bronchiolitis/drug therapy
MH  - Patient Discharge
OTO - NOTNLM
OT  - bronchiolitis
OT  - nitric oxide
OT  - viral lower respiratory tract infection
EDAT- 2022/09/29 06:00
MHDA- 2023/02/04 06:00
CRDT- 2022/09/28 11:33
PHST- 2022/09/29 06:00 [pubmed]
PHST- 2023/02/04 06:00 [medline]
PHST- 2022/09/28 11:33 [entrez]
AID - 10.1513/AnnalsATS.202103-348OC [doi]
PST - ppublish
SO  - Ann Am Thorac Soc. 2023 Feb;20(2):236-244. doi: 10.1513/AnnalsATS.202103-348OC.