PMID- 31129068
OWN - NLM
STAT- MEDLINE
DCOM- 20210726
LR  - 20210726
IS  - 1873-5010 (Electronic)
IS  - 1569-1993 (Linking)
VI  - 19
IP  - 2
DP  - 2020 Mar
TI  - Pilot study to test inhaled nitric oxide in cystic fibrosis patients with 
      refractory Mycobacterium abscessus lung infection.
PG  - 225-231
LID - S1569-1993(19)30104-3 [pii]
LID - 10.1016/j.jcf.2019.05.002 [doi]
AB  - BACKGROUND: Airways of Cystic Fibrosis (CF) patients are Nitric Oxide (NO) 
      deficient which may contribute to impaired lung function and infection clearance. 
      Mycobacterium abscessus (M. abscessus) infection prevalence is increasing in CF 
      patients and is associated with increased morbidity and mortality. Here, we 
      assess the safety and efficacy of intermittent inhaled NO (iNO) as adjuvant 
      therapy in CF patients with refractory M. abscessus lung infection. METHODS: A 
      prospective, open-label pilot study of iNO (160 ppm) administered five times/day 
      during hospitalization (14 days), and three times/day during ambulatory treatment 
      (7 days) was conducted. The primary outcome was safety measured by NO-related 
      adverse events (AEs). Secondary outcomes were six-minute walk distance (6MWD), 
      forced expiratory volume in 1 s (FEV(1)), and M. abscessus burden in airways. 
      RESULTS: Nine subjects were recruited. INO at 160 ppm was well-tolerated and no 
      iNO-related SAEs were observed during the study. Mean FEV1 and 6WMD were 
      increased relative to baseline during NO treatment. M. abscessus culture 
      conversion was not achieved, but 3/9 patients experienced at least one negative 
      culture during the study. Mean time to positivity in M. abscessus culture, and 
      qPCR analysis showed reductions in sputum bacterial load. The study was not 
      powered to achieve statistical significance in FEV1, 6WMD, and bacterial load. 
      CONCLUSIONS: Intermittent iNO at 160 ppm is well tolerated and safe and led to 
      increases in mean 6MWD and FEV1. INO exhibited potential antibacterial activity 
      against M. abscessus. Further evaluation of secondary endpoints in a larger 
      cohort of CF patients is warranted to demonstrate statistical significance.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Bentur, Lea
AU  - Bentur L
AD  - Pediatric Pulmonary Institute and CF Center, Ruth Children's Hospital, Rambam 
      Health Care Campus, POB 9602, Haifa, Israel; Technion-Israel Institute of 
      Technology, Haifa, Israel. Electronic address: l_bentur@rambam.health.gov.il.
FAU - Gur, Michal
AU  - Gur M
AD  - Pediatric Pulmonary Institute and CF Center, Ruth Children's Hospital, Rambam 
      Health Care Campus, POB 9602, Haifa, Israel; Technion-Israel Institute of 
      Technology, Haifa, Israel.
FAU - Ashkenazi, Moshe
AU  - Ashkenazi M
AD  - Pediatric Pulmonary Institute and National CF Center, Edmond and Lily Safra 
      Children's Hospital, Sheba Medical Center, Tel Hashomer 52621, Ramat-Gan, Israel; 
      Pediatric Pulmonary Unit, Soroka University Medical Center POB 151, Beer-Sheva, 
      Israel.
FAU - Livnat-Levanon, Galit
AU  - Livnat-Levanon G
AD  - Pediatric Pulmonology Unit and CF Center, Lady Davis Carmel Medical Center, 
      Haifa, Israel.
FAU - Mizrahi, Marko
AU  - Mizrahi M
AD  - AIT Therapeutics Inc, Garden City, NY 11530, USA.
FAU - Tal, Asher
AU  - Tal A
AD  - AIT Therapeutics Inc, Garden City, NY 11530, USA.
FAU - Ghaffari, Abdi
AU  - Ghaffari A
AD  - AIT Therapeutics Inc, Garden City, NY 11530, USA.
FAU - Geffen, Yuval
AU  - Geffen Y
AD  - Microbiology Laboratory, Rambam Health Care Campus, POB 9602, Haifa, Israel.
FAU - Aviram, Micha
AU  - Aviram M
AD  - Pediatric Pulmonary Unit, Soroka University Medical Center POB 151, Beer-Sheva, 
      Israel.
FAU - Efrati, Ori
AU  - Efrati O
AD  - Pediatric Pulmonary Institute and National CF Center, Edmond and Lily Safra 
      Children's Hospital, Sheba Medical Center, Tel Hashomer 52621, Ramat-Gan, Israel; 
      Sackler Faculty of Medicine, Tel-Aviv University, POB 39040, Tel-Aviv, Israel.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20190523
PL  - Netherlands
TA  - J Cyst Fibros
JT  - Journal of cystic fibrosis : official journal of the European Cystic Fibrosis 
      Society
JID - 101128966
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Bronchodilator Agents)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Adult
MH  - Anti-Bacterial Agents/therapeutic use
MH  - Bacterial Load/*methods
MH  - Bronchodilator Agents/administration & dosage
MH  - Chemotherapy, Adjuvant/methods
MH  - *Cystic Fibrosis/epidemiology/microbiology/physiopathology/therapy
MH  - Female
MH  - Humans
MH  - Israel/epidemiology
MH  - Male
MH  - *Mycobacterium Infections, Nontuberculous/physiopathology/therapy
MH  - Mycobacterium abscessus/drug effects/isolation & purification
MH  - Nitric Oxide/*administration & dosage
MH  - Outcome Assessment, Health Care
MH  - Respiratory Function Tests/*methods
MH  - Respiratory Therapy/methods
MH  - Sputum/microbiology
MH  - Walk Test/methods
OTO - NOTNLM
OT  - Cystic fibrosis
OT  - Inhaled nitric oxide
OT  - Mycobacterium Abscessus
EDAT- 2019/05/28 06:00
MHDA- 2021/07/27 06:00
CRDT- 2019/05/27 06:00
PHST- 2018/11/15 00:00 [received]
PHST- 2019/04/30 00:00 [revised]
PHST- 2019/05/02 00:00 [accepted]
PHST- 2019/05/28 06:00 [pubmed]
PHST- 2021/07/27 06:00 [medline]
PHST- 2019/05/27 06:00 [entrez]
AID - S1569-1993(19)30104-3 [pii]
AID - 10.1016/j.jcf.2019.05.002 [doi]
PST - ppublish
SO  - J Cyst Fibros. 2020 Mar;19(2):225-231. doi: 10.1016/j.jcf.2019.05.002. Epub 2019 
      May 23.