Evidence map›Paper›PMID 28750737›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017

Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis.

Robert P Howlin, Katrina Cathie, Luanne Hall-Stoodley, Victoria Cornelius, Caroline Duignan, Raymond N Allan, Bernadette O Fernandez, Nicolas Barraud, Ken D Bruce, Johanna Jefferies and 17 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 1 pooled it
15.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

90 citing papers in PubMed, 1 synthesis or guideline pooled it, 201 citations in OpenAlex.

  1. Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis.The Cochrane database of systematic reviews · 2020
    Pooled it
  2. Review
  3. Article
  4. Development of a light-induced gas phase nitric oxide generator and its use in killing biofilm bacteria in vitro and ex vivo.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
  5. UnderstandingMicroorganisms · 2026
    Review
  6. Article
  7. Antimicrobial Resistance: The Answers.British journal of biomedical science · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Frontiers in microbiology · 2025
    Article
  13. The adaptability ofFrontiers in cellular and infection microbiology · 2025
    Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors at 12 institutions in 4 countries.

Robert P HowlinNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK; Centre for Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK; Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Katrina CathieNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK; Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Luanne Hall-StoodleyMicrobial Infection and Immunity, The Ohio State University College of Medicine, Columbus, OH 43210-2210, USA; Southampton NIHR Wellcome Trust Clinical Research Facility, Southampton SO16 6YD, UK.
Victoria CorneliusNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; Imperial College London School of Public Health, London SW7 2AZ, UK.
Caroline DuignanNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK; Centre for Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Raymond N AllanNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK; Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK; Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton SO17 1BJ, UK; Southampton NIHR Wellcome Trust Clinical Research Facility, Southampton SO16 6YD, UK.
Bernadette O FernandezFaculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Nicolas BarraudCentre for Marine Bio-Innovation and School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Ken D BruceKings College London Institute of Pharmaceutical Science, London WC2R 2LS, UK.
Johanna JefferiesNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK; Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK; Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton SO17 1BJ, UK; Public Health England, Southampton SO17 1BJ, UK.
Michael KelsoIllawarra Health and Medical Research Institute and School of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia.
Staffan KjellebergCentre for Marine Bio-Innovation and School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia; Singapore Centre on Environmental Life Sciences Engineering and Nanyang Technological University, School of Biological Sciences, Singapore 637551, Singapore.
Scott A RiceCentre for Marine Bio-Innovation and School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia; Singapore Centre on Environmental Life Sciences Engineering and Nanyang Technological University, School of Biological Sciences, Singapore 637551, Singapore.
Geraint B RogersKings College London Institute of Pharmaceutical Science, London WC2R 2LS, UK; Infection and Immunity Theme, South Australia Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia; Flinders University School of Medicine, Bedford Park, Adelaide, SA 5042, Australia.
Sandra PinkNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK.
Caroline SmithNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK.
Priya S SukhtankarFaculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton SO17 1BJ, UK; Southampton NIHR Wellcome Trust Clinical Research Facility, Southampton SO16 6YD, UK.
Rami SalibNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK; Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK; Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Julian LeggNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK.
Mary CarrollNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK.
Thomas DanielsNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK.
Martin FeelischNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK; Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK; Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Paul StoodleyNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK; Microbial Infection and Immunity, The Ohio State University College of Medicine, Columbus, OH 43210-2210, USA; National Centre for Advanced Tribology at Southampton, Faculty of Engineering, University of Southampton, Southampton SO17 1BJ, UK.
Stuart C ClarkeNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK; Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK; Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton SO17 1BJ, UK; Public Health England, Southampton SO17 1BJ, UK.
Gary ConnettNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK.
Saul N FaustNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK; Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK; Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton SO17 1BJ, UK; Southampton NIHR Wellcome Trust Clinical Research Facility, Southampton SO16 6YD, UK. Electronic address: s.faust@soton.ac.uk.
Jeremy S WebbNIHR Southampton Respiratory Biomedical Research Centre, Southampton SO16 6YD, UK; University Hospital Southampton NHS Foundation Trust, Southampton SO16, 6YD, UK; Centre for Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK; Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK.
NIHR Southampton Respiratory Biomedical Research Unit · GBUniversity of Southampton · GBUniversity Hospital Southampton NHS Foundation Trust · GBUNSW Sydney · AUImperial College London · GBKing's College London · GBNIHR Wellcome Trust Southampton Clinical Research Facility · GBPublic Health England · GBSingapore Centre for Environmental Life Sciences Engineering · SGSouth Australian Health and Medical Research Institute · AUThe Ohio State University · USUniversity of Wollongong · AU

Funding

Biotechnology and Biological Sciences Research CouncilWellcome Trust
6 · The paper itself

Abstract

Despite aggressive antibiotic therapy, bronchopulmonary colonization by Pseudomonas aeruginosa causes persistent morbidity and mortality in cystic fibrosis (CF). Chronic P. aeruginosa infection in the CF lung is associated with structured, antibiotic-tolerant bacterial aggregates known as biofilms. We have demonstrated the effects of non-bactericidal, low-dose nitric oxide (NO), a signaling molecule that induces biofilm dispersal, as a novel adjunctive therapy for P. aeruginosa biofilm infection in CF in an ex vivo model and a proof-of-concept double-blind clinical trial. Submicromolar NO concentrations alone caused disruption of biofilms within ex vivo CF sputum and a statistically significant decrease in ex vivo biofilm tolerance to tobramycin and tobramycin combined with ceftazidime. In the 12-patient randomized clinical trial, 10 ppm NO inhalation caused significant reduction in P. aeruginosa biofilm aggregates compared with placebo across 7 days of treatment. Our results suggest a benefit of using low-dose NO as adjunctive therapy to enhance the efficacy of antibiotics used to treat acute P. aeruginosa exacerbations in CF. Strategies to induce the disruption of biofilms have the potential to overcome biofilm-associated antibiotic tolerance in CF and other biofilm-related diseases.

Indexed as

AdolescentAdultAnti-Bacterial AgentsBacterial LoadBiofilmsCystic FibrosisDose-Response Relationship, DrugHumansMiddle AgedNitric OxidePseudomonas aeruginosaPseudomonas InfectionsRandomized Controlled Trials as TopicSputumTime FactorsYoung AdultAnti-Bacterial AgentsNitric Oxidecystic fibrosisnitric oxidePseudomonas aeruginosa

Identifiers

PMID28750737
PMCPMC5589160
OpenAlexW2724107058

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.