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Transepithelial nasal potential difference in patients with, and at risk of acute respiratory distress syndrome
  1. Rob Mac Sweeney1,2,
  2. Kiran Reddy3,4,
  3. Jane C Davies5,6,
  4. Mike Parker7,
  5. Barry Kelly1,
  6. J Stuart Elborn2,
  7. John Conlon2,
  8. Rejina M Verghis2,
  9. Carolyn S Calfee8,9,
  10. Michael A Matthay8,
  11. Eric W F W Alton5,10,
  12. Daniel F McAuley1,2
  1. 1 Intensive Care Unit, Royal Victoria Hospital, Belfast, UK
  2. 2 Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK
  3. 3 Department of Anaesthesia, Intensive Care, and Pain Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
  4. 4 Department of Medicine, University College Dublin, Dublin, Ireland
  5. 5 National Heart and Lung Institute, Imperial College London, London, UK
  6. 6 Department of Paediatric Respiratory Medicine, Royal Brompton and Harefield NHS Foundation Trust, London, UK
  7. 7 Department of Computing and Information Science, Anglia Ruskin University, Chelmsford, Essex, UK
  8. 8 Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, San Francisco, California, USA
  9. 9 Department of Anesthesia, University of California, San Francisco, San Francisco, California, USA
  10. 10 Department of Respiratory Medicine, Royal Brompton Hospital, London, UK
  1. Correspondence to Professor Daniel F McAuley, Royal Victoria Hospital, Belfast, Belfast, UK; d.f.mcauley{at}


Background Impaired alveolar fluid clearance, determined in part by alveolar sodium transport, is associated with acute respiratory distress syndrome (ARDS). Nasal sodium transport may reflect alveolar transport. The primary objective of this prospective, observational study was to determine if reduced nasal sodium transport, as measured by nasal potential difference (NPD), was predictive of the development of and outcome from ARDS.

Methods NPD was measured in 15 healthy controls and in 88 patients: 40 mechanically ventilated patients defined as ‘at-risk’ for ARDS, 61 mechanically ventilated patients with ARDS (13 who were previously included in the ‘at-risk’ group) and 8 ARDS survivors on the ward.

Results In at-risk subjects, maximum NPD (mNPD) was greater in those who developed ARDS (difference –8.4 mV; 95% CI –13.8 to –3.7; p=0.005) and increased mNPD predicted the development of ARDS before its onset (area under the curve (AUC) 0.75; 95% CI 0.59 to 0.89). In the ARDS group, mNPD was not significantly different for survivors and non-survivors (p=0.076), and mNPD was a modest predictor of death (AUC 0.60; 95% CI 0.45 to 0.75). mNPD was greater in subjects with ARDS (−30.8 mV) than in at-risk subjects (−24.2 mV) and controls (−19.9 mV) (p<0.001). NPD values were not significantly different for survivors and controls (p=0.18).

Conclusions Increased NPD predicts the development of ARDS in at-risk subjects but does not predict mortality. NPD increases before ARDS develops, is greater during ARDS, but is not significantly different for controls and survivors. These results may reflect the upregulated sodium transport necessary for alveolar fluid clearance in ARDS. NPD may be useful as a biomarker of endogenous mechanisms to stimulate sodium transport. Larger studies are now needed to confirm these associations and predictive performance.

  • ARDS
  • critical care
  • pulmonary oedema

Data availability statement

Data are available on reasonable request. De-identified participant data are freely available from Dr Kiran Reddy ( on reasonable request.

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Data availability statement

Data are available on reasonable request. De-identified participant data are freely available from Dr Kiran Reddy ( on reasonable request.

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  • Presented at This work was performed at the Royal Victoria Hospital, Belfast and Belfast City Hospital, Northern Ireland.

  • Contributors All authors conceived the study. RMS led the conduct of the study. RMS wrote the first draft of the manuscript and KR wrote subsequent drafts. All authors contributed to editing the manuscript and approved the final version.

  • Funding This work was supported by HSC Research & Development grant number EAT/3724/07. Northern Ireland Public Health Agency, Research and Development Division; Intensive Care Society of Ireland.

  • Competing interests Outside the submitted work, MAM reports grants from Roche/Genentech, personal fees from Novartis Pharmaceuticals, personal fees from Pliant Therapeutics, personal fees from Johnson & Johnson Pharmaceuticals, grants from Quantum Leap Health Organization, personal fees from Citius Pharmaceuticals, grants from the California Institute of Regenerative Medicine, grants from the Department of Defense, and grants from NHLBI. CSC reports grants from NIH. Outside the submitted work, she reports grants and personal fees from Roche/Genentech, grants and personal fees from Bayer, personal fees from Quark Pharmaceuticals, personal fees from Prometic, personal fees from Gen1e Life Sciences, personal fees from Vasomune, and grants from Quantum Leap Healthcare Collaborative. Outside the submitted work, DFMcA reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim, Bayer, Novartis and Eli Lilly, and from sitting on a DMEC for a trial undertaken by Vir Biotechnology. In addition, his institution has received funds from grants from the NIHR, Wellcome Trust, Innovate-UK and others. In addition, DFMcA has a patent issued to his institution for a treatment for ARDS. DFMcA is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. His spouse has received personal fees from the California Institute for Regenerative Medicine outside the submitted work.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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