What is a clinically meaningful change in exhaled nitric oxide for children with asthma?
Shona Fielding PhD
Medical Statistics Team, Institute of Applied Health Sciences, University of Aberdeen, UK
Search for more papers by this authorMarielle Pijnenburg PhD
Department of Paediatric Respiratory Medicine and Allergology, Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands
Search for more papers by this authorJohan de Jongste PhD
Department of Paediatric Respiratory Medicine and Allergology, Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands
Search for more papers by this authorKatherine Pike PhD
Clinical and Experimental Science Academic Unit, University of Southampton, Southampton, UK
Respiratory Critical Care and Anaesthesia group, Institute of Child Health, University College London, UK
Search for more papers by this authorGraham Roberts PhD
Clinical and Experimental Science Academic Unit, University of Southampton, Southampton, UK
Search for more papers by this authorHelen Petsky PhD
Department of Respiratory and Sleep Medicine, Queensland's Children's Hospital, Queensland University of Technology, Brisbane, Australia
Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia
Search for more papers by this authorAnne B. Chang PhD
Department of Respiratory and Sleep Medicine, Queensland's Children's Hospital, Queensland University of Technology, Brisbane, Australia
Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia
Search for more papers by this authorMaria Fritsch MD
University Children's Hospital, Vienna, Austria
Search for more papers by this authorThomas Frischer MD
University Children's Hospital, Vienna, Austria
Search for more papers by this authorStanley Szefler PhD
Department of Pediatrics, Breathing Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
Search for more papers by this authorPeter Gergen PhD
National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Search for more papers by this authorFrançoise Vermeulen MD
Department of Paediatrics, Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium
Search for more papers by this authorRobin Vael MD
Department of Paediatrics, Antwerp University Hospital, Antwerp, Belgium
Search for more papers by this authorCorresponding Author
Steve Turner MD
Child Health, University of Aberdeen, UK
Correspondence Professor Steve Turner, Child Health, Royal Aberdeen Children's Hospital, Aberdeen AB25 2ZG, UK.
Email: [email protected]
Search for more papers by this authorShona Fielding PhD
Medical Statistics Team, Institute of Applied Health Sciences, University of Aberdeen, UK
Search for more papers by this authorMarielle Pijnenburg PhD
Department of Paediatric Respiratory Medicine and Allergology, Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands
Search for more papers by this authorJohan de Jongste PhD
Department of Paediatric Respiratory Medicine and Allergology, Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands
Search for more papers by this authorKatherine Pike PhD
Clinical and Experimental Science Academic Unit, University of Southampton, Southampton, UK
Respiratory Critical Care and Anaesthesia group, Institute of Child Health, University College London, UK
Search for more papers by this authorGraham Roberts PhD
Clinical and Experimental Science Academic Unit, University of Southampton, Southampton, UK
Search for more papers by this authorHelen Petsky PhD
Department of Respiratory and Sleep Medicine, Queensland's Children's Hospital, Queensland University of Technology, Brisbane, Australia
Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia
Search for more papers by this authorAnne B. Chang PhD
Department of Respiratory and Sleep Medicine, Queensland's Children's Hospital, Queensland University of Technology, Brisbane, Australia
Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia
Search for more papers by this authorMaria Fritsch MD
University Children's Hospital, Vienna, Austria
Search for more papers by this authorThomas Frischer MD
University Children's Hospital, Vienna, Austria
Search for more papers by this authorStanley Szefler PhD
Department of Pediatrics, Breathing Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
Search for more papers by this authorPeter Gergen PhD
National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
Search for more papers by this authorFrançoise Vermeulen MD
Department of Paediatrics, Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium
Search for more papers by this authorRobin Vael MD
Department of Paediatrics, Antwerp University Hospital, Antwerp, Belgium
Search for more papers by this authorCorresponding Author
Steve Turner MD
Child Health, University of Aberdeen, UK
Correspondence Professor Steve Turner, Child Health, Royal Aberdeen Children's Hospital, Aberdeen AB25 2ZG, UK.
Email: [email protected]
Search for more papers by this authorAbstract
Introduction
Fractional exhaled nitric oxide (FENO) may be a useful objective measurement to guide asthma treatment. What remains uncertain is what change in FENO is clinically significant.
Methods
An individual patient data analysis was performed using data from seven randomized clinical trials which used FENO to guide asthma treatment. The absolute and percentage intra-subject change in FENO measurements over “stable” and also “unstable” 3-month periods were described.
Results
Data were available in 1112 randomized controlled trial participants and ≥1 stable period was present for 665 individuals. The interquartile range (IQR) and limits of agreement (LoA) for change in absolute FENO among individuals whose initial FENO was <50 parts per billion (ppb) were −7 to +9 ppb and −43 to +50 ppb, and for those with initial FENO ≥50 ppb IQR was −29 to +17 ppb and LoA was −80 to +76 ppb. For percentage change in FENO, the IQR and LoA for individuals whose initial FENO was <50 ppb were −33% to +51% and −157% to +215%, and for those with initial FENO ≥50 ppb were −33% to +35% and −159% to +192%. The variation in FENO values for a stable period was similar irrespective of whether it was followed by a stable or unstable period.
Conclusions
Over a 3-month period where FENO is initially <50 ppb, a rise of <10 ppb or of <50% (based on IQR) is unlikely to be related to asthma. When FENO is initially ≥50 ppb an percentage change of <50% (based on IQR) is unlikely to be asthma-related.
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