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Original Research: Allergy and Airway |

A Novel Approach to Partition Central and Peripheral Airway Nitric OxideA Novel Method to Partition Exhaled Nitric Oxide

Paolo Paredi, MD, PhD; Sergei A. Kharitonov, MD, PhD; Sally Meah, RGN; Peter J. Barnes, DM, DSc, Master FCCP; Omar S. Usmani, MBBS, PhD
Author and Funding Information

From the Airways Disease Section, National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, England.

Correspondence to: Paolo Paredi, MD, PhD, Airways Disease Section, National Heart and Lung Institute, Dovehouse St, London, SW3 6LY, England; e-mail: p.paredi@imperial.ac.uk


Funding/Support: Dr Usmani is a recipient of a UK National Institute for Health Research (NIHR) Career Development Fellowship. This project was supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton & Harefield NHS Foundation Trust and Imperial College London.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(1):113-119. doi:10.1378/chest.13-0843
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Background:  Determining the site of airways inflammation may lead to the targeting of therapy. Nitric oxide (NO) is a biomarker of airway inflammation and can be measured at multiple exhalation flow rates to allow partitioning into bronchial (large/central airway maximal nitric oxide flux [J’awno]) and peripheral (peripheral/small airway/alveolar nitric oxide concentration [Cano]) airway contributions by linear regression. This requires a minimum of three exhalations. We developed a simple and practical method to partition NO.

Methods:  In 29 healthy subjects (FEV1, 97% ± 3% predicted), 13 patients with asthma (FEV1, 90% ± 4% predicted), 14 patients with COPD (FEV1, 59% ± 3% predicted), and 12 patients with cystic fibrosis (CF) (FEV1, 60% ± 3% predicted), we measured the area under the curve of the NO concentration/exhalation time plot (AUC-NO) at exhalation flow rates of 50, 100, 200, and 300 mL/s. We determined the change of the total AUC-NO production (ΔAUC-NO) among the four different exhalation flow rates and compared these levels to Cano and J’awno indices measured conventionally by linear regression.

Results:  The change in AUC-NO between increasing exhalation flow rates of 50 to 200 mL/s (ΔAUC-NO50-200) was strongly correlated with J’awno in all patient groups as follows: healthy subjects (r = 0.94, P < .001), patients with asthma (r = 0.98, P < .001), patients with COPD (r = 0.93, P < .001), and patients with CF (r = 0.74, P < .05). In all subjects, AUC-NO at an exhalation flow rate of 200 mL/s (AUC-NO200) correlated with Cano (r = 0.69, P < .01).

Conclusions:  The bronchial production of NO can be determined by measuring ΔAUC-NO50-200, whereas AUC-NO200 measures its peripheral concentration. This approach is simple, quick, and does not require sophisticated equipment or mathematical models.

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