Caroline Deppisch1, Gloria Herrmann1, Ute Graepler-Mainka1, Hubertus Wirtz2, Susanne Heyder3, Corinna Engel1, Matthias Marschal4, Christopher C Miller5, Joachim Riethmüller6,7. 1. Comprehensive Cystic Fibrosis Center, Children's Clinic, Tübingen, Germany. 2. Medizinische Klinik I, Pneumologie, Universität Leipzig, Leipzig, Germany. 3. Klinik Schillerhöhe, Robert Bosch Krankenhaus GmbH, Gerlingen, Germany. 4. Institute of Medical Microbiology and Hygiene, Universitätsklinikum Tübingen, Tübingen, Germany. 5. Nitric Oxide Laboratory, Division of Respiratory and Infectious Diseases, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. 6. Comprehensive Cystic Fibrosis Center, Children's Clinic, Tübingen, Germany. joachim.riethmueller@med.uni-tuebingen.de. 7. University Childrens' Hospital, Universitätsklinikum Tübingen, Hoppe-Seyler-Str. 1, 72076, Tübingen, Germany. joachim.riethmueller@med.uni-tuebingen.de.
Abstract
BACKGROUND: Individuals with cystic fibrosis (CF) receive antibiotics continuously throughout their entire life which leads to drug resistant microbial lung infections which are difficult to treat. Nitric oxide (NO) gas possesses antimicrobial activity against a wide variety of microorganisms in vitro, in vivo in animal models and a phase I study in healthy adults showed administration of intermittent 160 ppm NO to be safe. METHODS: We assessed feasibility and safety of inhaled NO in eight CF patients who received 160 ppm NO for 30 min, three times daily for 2 periods of 5 days. RESULTS: The NO treatment was safe and in none of the patients were serious drug-related adverse events observed which caused termination of the study. The intention-to-treat analysis revealed a significant mean reduction of the colony forming units of all bacteria and all fungi, while mean forced expiratory volume 1 s % predicted (FEV1) relative to baseline increased 17.3 ± 8.9 % (P = 0.012). CONCLUSIONS: NO treatment may improve the therapy of chronic microbial lung infections in CF patients, particularly concerning pathogens with intrinsic or acquired resistance to antibiotics.
BACKGROUND: Individuals with cystic fibrosis (CF) receive antibiotics continuously throughout their entire life which leads to drug resistant microbial lung infections which are difficult to treat. Nitric oxide (NO) gas possesses antimicrobial activity against a wide variety of microorganisms in vitro, in vivo in animal models and a phase I study in healthy adults showed administration of intermittent 160 ppm NO to be safe. METHODS: We assessed feasibility and safety of inhaled NO in eight CFpatients who received 160 ppm NO for 30 min, three times daily for 2 periods of 5 days. RESULTS: The NO treatment was safe and in none of the patients were serious drug-related adverse events observed which caused termination of the study. The intention-to-treat analysis revealed a significant mean reduction of the colony forming units of all bacteria and all fungi, while mean forced expiratory volume 1 s % predicted (FEV1) relative to baseline increased 17.3 ± 8.9 % (P = 0.012). CONCLUSIONS: NO treatment may improve the therapy of chronic microbial lung infections in CFpatients, particularly concerning pathogens with intrinsic or acquired resistance to antibiotics.
Authors: Bevin B McMullin; Dean R Chittock; Diane L Roscoe; Harjinder Garcha; Lexin Wang; Christopher C Miller Journal: Respir Care Date: 2005-11 Impact factor: 2.258
Authors: J R Riordan; J M Rommens; B Kerem; N Alon; R Rozmahel; Z Grzelczak; J Zielenski; S Lok; N Plavsic; J L Chou Journal: Science Date: 1989-09-08 Impact factor: 47.728
Authors: J M Rommens; M C Iannuzzi; B Kerem; M L Drumm; G Melmer; M Dean; R Rozmahel; J L Cole; D Kennedy; N Hidaka Journal: Science Date: 1989-09-08 Impact factor: 47.728
Authors: Katelyn P Reighard; Camille Ehre; Zachary L Rushton; Mona Jasmine R Ahonen; David B Hill; Mark H Schoenfisch Journal: ACS Biomater Sci Eng Date: 2017-05-15
Authors: Hyun Koo; Raymond N Allan; Robert P Howlin; Paul Stoodley; Luanne Hall-Stoodley Journal: Nat Rev Microbiol Date: 2017-09-25 Impact factor: 60.633
Authors: Jackson R Hall; Kaitlyn R Rouillard; Dakota J Suchyta; Micah D Brown; Mona Jasmine R Ahonen; Mark H Schoenfisc Journal: ACS Biomater Sci Eng Date: 2019-11-13
Authors: Gergely Lautner; Blake Stringer; Elizabeth J Brisbois; Mark E Meyerhoff; Steven P Schwendeman Journal: Nitric Oxide Date: 2019-02-05 Impact factor: 4.427
Authors: 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; Michael Kelso; Staffan Kjelleberg; Scott A Rice; Geraint B Rogers; Sandra Pink; Caroline Smith; Priya S Sukhtankar; Rami Salib; Julian Legg; Mary Carroll; Thomas Daniels; Martin Feelisch; Paul Stoodley; Stuart C Clarke; Gary Connett; Saul N Faust; Jeremy S Webb Journal: Mol Ther Date: 2017-07-24 Impact factor: 11.454