Axial distribution heterogeneity of nitric oxide airway production in healthy adults

Kerckx, Yannick; Muylem, Alain Van

doi:10.1152/japplphysiol.91614.2008

Cited by 17 publications

(13 citation statements)

References 28 publications

(68 reference statements)

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“…Important experimental observations by Kerckx and Van Muylem27 have also demonstrated the inhomogeneous distribution of NO production in healthy adults, with the majority of exhaled NO coming from very proximal airways and ‘larger’ peripheral airways of <17 generation, with little contribution from the lung periphery after correcting for axial NO back-diffusion. The response following histamine-induced bronchoconstriction in normal subjects has been studied by Verbanck et al 28 who noted its potential effect to increase convective flow of NO and FeNO at 50 ml/s by a paradoxical decrease in axial back-diffusion of NO.…”

Section: Discussionmentioning

confidence: 99%

Central and peripheral airway/alveolar sites of exhaled nitric oxide in acute asthma

Gelb¹,

George

Silkoff

et al. 2010

Thorax

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Introduction Central airway nitric oxide flux (J' awNO ) and peripheral airway/alveolar nitric oxide concentration (C ANO ) during asthma exacerbation has not been investigated after correction for axial NO back-diffusion. Methods After measuring exhaled NO (fraction of exhaled nitric oxide (F E NO); ppb) at 50, 100, 150 and 200 ml/s, J' awNO (nl/s) and C ANO (ppb) were calculated using the two-compartment model and corrected for axial NO back-diffusion. Fifteen (8 males), non-smoking, patients with moderate-to-severe treated (inhaled corticosteroid (ICS) and inhaled long-acting b 2 -agonist (LABA)) asthma, age 57613 years (mean6SD), were studied at baseline, during exacerbation prior to oral corticosteroid, and during recovery after an 8 day tapering prednisone course. Based on earlier asthma studies without correction, it was hypothesised that with correction for NO axial back-diffusion, the incidence of abnormal J' awNO and C ANO at baseline and after exacerbation would be $30% in 15 patients with asthma with 80% power.Results At baseline when clinically stable, after 180 mg of albuterol, forced expiratory volume in 1 s (FEV 1 ; litres) was 78626% predicted (p¼0.009) with increased F E NO at 50 ml/s (p¼0.01) and J' awNO (p¼0.02), but C ANO was normal compared with the controls. During exacerbation FEV 1 (litres) was 57620% predicted (p¼0.02), with increased F E NO at 50 ml/s (p¼0.01) and J' awNO (p¼0.004), but C ANO was normal. Recovery results were similar to baseline. Two of 15 patients with asthma always had normal exhaled NO gas exchange. Conclusions The central airways were the major site of abnormal NO flux in 13 of 15 patients with moderateesevere asthma when stable and during exacerbation and could be easily detected with abnormal F E NO at 50 ml/s. C ANO was normal. Clinical trial number NCT00576069.Measurement of the fraction of exhaled nitric oxide (F E NO; ppb) is a relatively simple, reproducible and non-invasive test for monitoring airway inflammation.1 Increased F E NO in asthma is accepted as a surrogate for predominantly eosinophilic-mediated inflammation in central airways and increased response to inhaled corticosteroid (ICS).1e5 The currently accepted method of measuring F E NO at a single constant expiratory flow rate, usually 50 ml/s, is incapable of separating out whether the source of increased NO production is the large central airways or the peripheral small airway/ alveolar site, or both. clinically stable asthma. However, two groups independently 12 22 have also demonstrated, both experimentally and theoretically, axial back-diffusion of NO from proximal to peripheral airway/ alveoli, against the direction of exhalation. Furthermore, this may contaminate peripheral airway/alveolar levels, leading to an underestimation of central airway NO flux and an overestimation of peripheral airway/alveolar NO levels. Axial NO back-diffusion has not been previously accounted for in those with asthma with abnormal expiratory airflow limitation.The current prospective outpatient study eva...

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Section: Discussionmentioning

confidence: 99%

Central and peripheral airway/alveolar sites of exhaled nitric oxide in acute asthma

Gelb¹,

George

Silkoff

et al. 2010

Thorax

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“…As the central airway axial diffusion is an important factor determining flow dependency [25] this may indicate that ethanol has a significant axial diffusion and the central airways contribute significantly to total ethanol breath levels. Three subjects with low baseline ethanol levels showed no exhalation flow dependency, suggesting that higher gas levels may be more sensitive flow rate reduction.…”

Section: Discussionmentioning

confidence: 99%

Standardised exhaled breath collection for the measurement of exhaled volatile organic compounds by proton transfer reaction mass spectrometry

et al. 2013

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BackgroundExhaled breath volatile organic compound (VOC) analysis for airway disease monitoring is promising. However, contrary to nitric oxide the method for exhaled breath collection has not yet been standardized and the effects of expiratory flow and breath-hold have not been sufficiently studied. These manoeuvres may also reveal the origin of exhaled compounds.Methods15 healthy volunteers (34 ± 7 years) participated in the study. Subjects inhaled through their nose and exhaled immediately at two different flows (5 L/min and 10 L/min) into methylated polyethylene bags. In addition, the effect of a 20 s breath-hold following inhalation to total lung capacity was studied. The samples were analyzed for ethanol and acetone levels immediately using proton-transfer-reaction mass-spectrometer (PTR-MS, Logan Research, UK).ResultsEthanol levels were negatively affected by expiratory flow rate (232.70 ± 33.50 ppb vs. 202.30 ± 27.28 ppb at 5 L/min and 10 L/min, respectively, p < 0.05), but remained unchanged following the breath hold (242.50 ± 34.53 vs. 237.90 ± 35.86 ppb, without and with breath hold, respectively, p = 0.11). On the contrary, acetone levels were increased following breath hold (1.50 ± 0.18 ppm) compared to the baseline levels (1.38 ± 0.15 ppm), but were not affected by expiratory flow (1.40 ± 0.14 ppm vs. 1.49 ± 0.14 ppm, 5 L/min vs. 10 L/min, respectively, p = 0.14). The diet had no significant effects on the gasses levels which showed good inter and intra session reproducibility.ConclusionsExhalation parameters such as expiratory flow and breath-hold may affect VOC levels significantly; therefore standardisation of exhaled VOC measurements is mandatory. Our preliminary results suggest a different origin in the respiratory tract for these two gasses.

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“…decrease or increase) result in immediate FENO changes thus impairing its ability to reflect airway inflammation, especially when peripheral airways are involved [9][10][11][12]16]. This is because the vast majority of NO production is concentrated in small conductive airways [15]. Furthermore, in a model using allergen challenge, it was even shown that during the late inflammatory-phase reaction, the reduction of airway calibre completely counteracted the boosting effect of airway inflammation on FENO levels [12].…”

Section: Discussionmentioning

confidence: 99%

“…This is most likely due to the decrease of available epithelial surface, which impairs NO diffusion from the airway epithelium into the airway lumen [13,14]. The involvement of peripheral airways amplifies this reduction because most NO production is concentrated in small conductive airways [15], which represent the vast majority of the total epithelial surface. Moreover, an acute increase of airway calibre was recently shown to also affect FENO values in a manner depending on the site of bronchodilation (i.e.…”

Section: Introductionmentioning

confidence: 99%

Airway calibre variation is a major determinant of exhaled nitric oxide's ability to capture asthma control

et al. 2017

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@ERSpublicationsClinicians must take into account FEV1 changes when using FENO as a marker of asthma control http://ow.ly/XFmp30c4emjCite this article as: Michils A, Haccuria A, Michiels S, et al. ABSTRACT Changes in airway calibre have the potential to modify exhaled nitric oxide fraction (FENO) values and could hamper how FENO captures changes in asthma control. Here, our objective was to assess whether forced expiratory volume in 1 s (FEV1) variations alter the ability of FENO to reflect asthma control.FENO, asthma control (Asthma Control Questionnaire (ACQ)) and FEV1 were measured at least two times in 527 patients during 1819 pairs of visits. Determinants of FENO-ACQ discordance probability were evaluated through a logistic regression analysis. The effectiveness of FENO at capturing either asthma control worsening or improvement between two visits was then assessed by undertaking a stratified receiver operating characteristic curves analysis.When FEV1 and FENO change in the same direction, the odds of FENO-ACQ being discordant are multiplied by 3 ( p<0.001). The area under the curve values were 0.765 (95% CI 0.713-0.805) (improvement; p<0.001) and 0.769 (95% 0.706-0.810) (worsening; p<0.001) or 0.590 (95% 0.531-0.653) (improvement; p=0.001) and 0.498 (95% 0.416-0.567) (worsening; p=0.482) when FEV1 and FENO changed in the opposite or same direction, respectively.The manner in which FENO and FEV1 vary concomitantly when asthma control changes determines the ability of FENO to capture this change: parallel or opposite changes in FEV1 and FENO either decrease or increase this ability to capture asthma control changes.This article has supplementary material available from

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Axial distribution heterogeneity of nitric oxide airway production in healthy adults

Cited by 17 publications

References 28 publications

Central and peripheral airway/alveolar sites of exhaled nitric oxide in acute asthma

Central and peripheral airway/alveolar sites of exhaled nitric oxide in acute asthma

Standardised exhaled breath collection for the measurement of exhaled volatile organic compounds by proton transfer reaction mass spectrometry

Airway calibre variation is a major determinant of exhaled nitric oxide's ability to capture asthma control

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