Comparison of feasibility and estimates of central and peripheral nitric oxide parameters by different mathematical models

Our plain-English summary of Comparison of feasibility and estimates of central and peripheral nitric oxide parameters by different mathematical models, by T. Karvonen, H. Kankaanranta, S. Saarelainen, et al (Journal of Breath Research, 2017).

The study

• Authors: T. Karvonen, H. Kankaanranta, S. Saarelainen, E. Moilanen, L. Lehtimäki
• Journal: Journal of Breath Research
• Published: 2017;11(4):047102
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Assessment of the central and peripheral nitric oxide (NO) dynamics of the lung provides information on the severity and anatomical site of pulmonary inflammation. Several mathematical methods for calculating alveolar and bronchial NO parameters have been introduced. Our aim was to compare these methods.

Methods: The study included 69 healthy adults, 66 healthy children, 73 asbestos-exposed subjects and 72 subjects with chronic obstructive pulmonary disease (COPD). Exhaled NO was measured at multiple flow rates and we used five mathematical methods (Tsoukias and George, Pietropaoli, Condorelli, Högman and Meriläinen, and Silkoff) to estimate alveolar and bronchial NO parameters.

Results: The Högman and Meriläinen method was less frequently feasible than the other methods but it had the highest degree of agreement with the measured data. The methods were most often feasible in healthy or asbestos-exposed adults but distinctly more infrequently in children and adults with COPD, suggesting difficulties in NO measurements in these groups. The linear methods (Tsoukias and George, Pietropaoli) yielded higher alveolar NO concentration and lower bronchial NO flux than the two non-linear methods (Högman and Meriläinen, Silkoff) and a linear method with correction for axial back-diffusion of NO (Condorelli).

Conclusion: In differentiating central and peripheral NO sources we recommend using linear methods, as low flow rates are not needed and the feasibility of the methods is good. If bronchial wall NO concentration (C awNO) and diffusing capacity (D awNO) are of interest, non-linear methods are needed, and we recommend using the Högman and Meriläinen method as only three flow rates are needed. However, the agreement between the model and measured data needs to be checked in real time to ensure feasibility. If the subject has difficulties with the extremely low or high flow rates, we then recommend using the Silkoff method to improve feasibility, but more flow rates and measurements are then needed and the agreement between the model and the measured data may be poorer.

In plain English

This study compared five mathematical methods, named after Tsoukias and George, Pietropaoli, Condorelli, Silkoff, and Högman and Meriläinen. Each method uses nitric oxide in exhaled breath, measured at several breathing flow rates, to estimate how much of it comes from the lung's air sacs (alveolar) and how much from the airways (bronchial). The authors describe this as a way to learn the site of lung inflammation. They reused data from their earlier studies of 69 healthy adults, 66 healthy children, 72 adults with COPD, and 73 non-smoking men with a history of moderate to severe occupational asbestos exposure. The study did not examine asbestos-related disease. The methods worked most often in healthy and asbestos-exposed adults. In the asbestos-exposed men, 66 to 73 of 73 gave usable results, depending on the method. The methods worked less often in children and in people with COPD. The Högman and Meriläinen method gave usable results least often, but when it worked it matched the measured data best. Differences between methods in the estimates were usually quite small. The authors recommended linear methods for separating airway and air-sac sources. They noted that the study had no young adults and no real-time check of how well the data fitted the models.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Methods-comparison study reanalysing exhaled nitric oxide data from the authors' previously published studies, comparing five mathematical calculation methods
• Who was studied: 69 healthy adults, 66 healthy children, 72 adults with chronic obstructive pulmonary disease (COPD) and 73 adults with previous asbestos exposure, from the authors' earlier studies in Tampere, Finland (all measured with the same analyzer at the same research center)
• Exposure: The asbestos-exposed group were non-smoking men with a history of moderate to severe occupational asbestos exposure and no other known respiratory disease. Fiber types and jobs are not stated. The main comparison was between the five calculation methods applied to exhaled nitric oxide measured at multiple flow rates.
• Main results:
  • Feasibility (usable results) of all methods was best in healthy adults and in adults with asbestos exposure. In the asbestos-exposed group, successful results out of 73 were 71 (Tsoukias and George), 73 (Pietropaoli), 70 (Condorelli), 69 (Silkoff) and 66 (Högman and Meriläinen).
  • Feasibility was poorer in healthy children and poorest in subjects with COPD. In COPD, successful results ranged from 23 of 72 (Högman and Meriläinen) to 55 of 72 (Silkoff).
  • In children and subjects with COPD, the Högman and Meriläinen method was feasible significantly less often than the other methods.
  • Overall, the Högman and Meriläinen method appeared to agree best with the measured data.
  • The linear methods tended to give higher alveolar NO concentration and lower bronchial NO flux estimates than the non-linear methods, but the absolute differences were quite small and not all statistically significant.
  • In 56 healthy adults with all successful flow rates, the choice of flow rates affected feasibility of the Högman and Meriläinen method: 44 versus 33 successful results (p=0.008) for 10, 100, 400 versus 20, 100, 400 ml/s, and 33 versus 48 (p=0.000) for 20, 100, 400 versus 10, 100, 300 ml/s.
• The authors' conclusion: The authors concluded that linear methods are recommended for separating central and peripheral NO sources. The Högman and Meriläinen method is recommended if bronchial wall NO concentration and diffusing capacity are of interest, with a real-time check of fit. The Silkoff method is recommended when subjects have difficulty with extremely low or high flow rates.
• Limitations the authors state:
  • The study included only young children and older adults, with no young adults, and NO parameters vary with age.
  • Flow rates used were not standardized, which the authors note is a possible source of error.
  • There was no real-time check of the fit between measured NO data and the mathematical methods.
  • There is no gold standard for NO parameters, so it is hard to say which method gives the best estimates.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, COPD, Diffusing Capacity (DLCO).

Related studies

• Increased alveolar nitric oxide concentration and high levels of leukotriene B(4) and 8-isoprostane in exhaled breath condensate in patients with asbestosis — H. Lehtonen, P. Oksa, et al. (2007)
• Fractional exhaled nitric oxide concentration is increased in asbestosis and pleural plaques — A. Sandrini, A.R. Johnson, et al. (2006)
• Mechanisms of asbestos-induced nitric oxide production by rat alveolar macrophages in inhalation and in vitro models — T.R. Quinlan, K.A. BeruBe, et al. (1998)
• Participation of nitric oxide and iron in the oxidation of DNA in asbestos-treated human lung epithelial cells — C.C. Chao, S.H. Park, et al. (1996)
• Nitric oxide (NO) synthase activity in the lung and NO synthesis in alveolar macrophages of rats increased on exposure to asbestos — H. Iguchi, S. Kojo, et al. (1996)
• Dual role of inducible nitric oxide synthase in acute asbestos-induced lung injury — M. Dörger, A.M. Allmeling, et al. (2002)

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