0
Correspondence |

How to Assess Alveolar Nitric OxideHow to Assess Alveolar Nitric Oxide: A Quest of the Grail? FREE TO VIEW

Lauri Lehtimäki, MD, PhD; Simona M. Cristescu, PhD; Alain Van Muylem, PhD; Marieann Högman, PhD; Anh Tuan Dinh-Xuan, MD, PhD
Author and Funding Information

From the Medical School (Dr Lehtimäki), University of Tampere; Life Science Trace Gas Facility (Dr Cristescu), Molecular and Laser Physics, Institute for Molecules and Materials, Radboud University; Chest Department (Dr Van Muylem), Erasme University Hospital, Université Libre de Bruxelles; Centre for Research and Development (Dr Högman), Uppsala University/County Council of Gävleborg; and Assistance Publique-Hôpitaux de Paris (Dr Dinh-Xuan), Université Paris Descartes, Hôpital Cochin, Service de Physiologie.

CORRESPONDENCE TO: Lauri Lehtimäki, MD, PhD, Medical School, FIN 33014 University of Tampere, Tampere, Finland; e-mail: lauri.lehtimaki@uta.fi


FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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


Chest. 2014;146(6):e234-e235. doi:10.1378/chest.14-1189
Text Size: A A A
Published online
To the Editor:

We read with interest the recent article in CHEST (January 2014) by Paredi et al1 proposing a new method to assess peripheral and central sources of exhaled nitric oxide (NO). Development of this topic is needed, because alveolar NO concentration (Cano) is a promising measure of peripheral lung inflammation.2 The authors assessed the area under the curve (AUC) of exhaled NO profiles at exhalation flow rates of 50 and 200 mL/s, stating that AUC50-200 is a substitute for large central airway maximal NO flux (J’awno) and that AUC200 reflects Cano. However, there are some concerns regarding the validity of the method used.

First, the authors state that the conventional methods used to calculate J’awno and Cano require mathematics that are too complex and involve too many measurements of fraction of exhaled NO concentration (Feno).1 However, the linear method to calculate J’awno and Cano can be used based on Feno measured at two exhalation flow rates and using simple regression analysis.3 If three or more flow rates are used, the linear fit can be controlled by the r value. Paredi et al1 needed to use graphics software to assess AUC for each individual measurement instead of using the plateau NO concentration provided by the NO analyzer. The use of the plateau value is recommended4 because it is more repeatable than AUC, which can be severely affected at the beginning of exhaled NO profiles by contamination from nasal or ambient NO (Fig 1) or by inaccuracy in the exhalation flow rate at the beginning.

Figure Jump LinkFigure 1 –  Area under the curve of an exhaled nitric oxide (NO) profile may be severely influenced if exhalation flow rate varies in the beginning or if inhaled air contains high amounts of NO because of a high ambient NO concentration or nasal inhalation (dotted line) as compared with inhaling NO free air (solid line). However, the plateau value is repeatable and is not affected by such external factors. FENO = fraction of exhaled NO concentration; ppb = parts per billion.Grahic Jump Location

Feno at an exhalation flow rate of 0.05 L/s is a good marker of central airways NO dynamics,5 and Cano is the clinically most important addition we gain from modeling NO dynamics. But this is where the AUC method fails, because the variation in AUC200 was explained only modestly by Cano (r2, 0.36-0.62). This is understandable, because in a patient with asthma and Cano 2.5 parts per billion (ppb), airway wall NO concentration 150 ppb, and airway NO diffusing capacity 15 pL/s/ppb, we can calculate3 that 81% of the total NO output at a flow rate of 200 mL/s originates from conducting airways and only 19% from the alveoli. Thus, Cano cannot be estimated reliably based on a Feno measurement at any single achievable exhalation flow rate; instead, calculations based on Feno at multiple flow rates are needed.

Standardization of the methods to assess J’awno and Cano is necessary to facilitate research and to allow comparisons among studies. The European Respiratory Society is, therefore, preparing guidelines on this topic, and easy-to-use calculation tools will be made freely available.

References

Paredi P, Kharitonov SA, Meah S, Barnes PJ, Usmani OS. A novel approach to partition central and peripheral airway nitric oxide. Chest. 2014;145(1):113-119. [CrossRef] [PubMed]
 
Tiev KP, Hua-Huy T, Rivière S, et al. High alveolar concentration of nitric oxide is associated with alveolitis in scleroderma. Nitric Oxide. 2013;28:65-70. [CrossRef] [PubMed]
 
George SC, Högman M, Permutt S, Silkoff PE. Modeling pulmonary nitric oxide exchange. J Appl Physiol (1985). 2004;96(3):831-839. [CrossRef] [PubMed]
 
American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005;171(8):912-930. [CrossRef] [PubMed]
 
Högman M, Thornadtsson A, Hedenstierna G, Meriläinen P. A practical approach to the theoretical models to calculate NO parameters of the respiratory system. J Breath Res. 2014;8(1):016002. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  Area under the curve of an exhaled nitric oxide (NO) profile may be severely influenced if exhalation flow rate varies in the beginning or if inhaled air contains high amounts of NO because of a high ambient NO concentration or nasal inhalation (dotted line) as compared with inhaling NO free air (solid line). However, the plateau value is repeatable and is not affected by such external factors. FENO = fraction of exhaled NO concentration; ppb = parts per billion.Grahic Jump Location

Tables

References

Paredi P, Kharitonov SA, Meah S, Barnes PJ, Usmani OS. A novel approach to partition central and peripheral airway nitric oxide. Chest. 2014;145(1):113-119. [CrossRef] [PubMed]
 
Tiev KP, Hua-Huy T, Rivière S, et al. High alveolar concentration of nitric oxide is associated with alveolitis in scleroderma. Nitric Oxide. 2013;28:65-70. [CrossRef] [PubMed]
 
George SC, Högman M, Permutt S, Silkoff PE. Modeling pulmonary nitric oxide exchange. J Appl Physiol (1985). 2004;96(3):831-839. [CrossRef] [PubMed]
 
American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005;171(8):912-930. [CrossRef] [PubMed]
 
Högman M, Thornadtsson A, Hedenstierna G, Meriläinen P. A practical approach to the theoretical models to calculate NO parameters of the respiratory system. J Breath Res. 2014;8(1):016002. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543