Exhaled Nitric Oxide (NO) Is Reduced Shortly after  Bronchoconstriction to Direct and Indirect Stimuli in Asthma

Gouw, H. W. F. M. De; Hendriks, Jan; Woltman, Andrea M.; Twiss, Irene M.; Sterk, Peter J.

doi:10.1164/ajrccm.158.1.9703005

Cited by 121 publications

(84 citation statements)

References 18 publications

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“…The findings of this study support and extend published results on the effect of airway calibre on exhaled NO levels [7,11,12]. This study is the first to demonstrate the distinct relationship between FEV1 and exhaled NO levels in a cross-section of subjects with different airway diameters.…”

Section: Discussionsupporting

confidence: 89%

“…However, the experiments in protocol 2 are very persuasive that it is indeed likely that airway diameter itself is important in this phenomenon. DE GOUW et al [11] who observed similar findings suggested that a decrease in surface area of the airways with bronchoconstriction might be responsible. The authors feel that this is less likely because the same number of epithelial cells will be present after bronchoconstriction although probably in a more convoluted formation.…”

Section: Discussionmentioning

confidence: 75%

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The current single exhalation method of measuring exhaled nitric oxide is affected by airway calibre

Wood

Robson

et al. 2000

Eur Respir J

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The current single exhalation method of measuring exhaled nitric oxide is affected by airway calibre. L.P. Ho, F.T. Wood, A. Robson, J.A. Innes, A.P. Greening. #ERS Journals Ltd 2000. ABSTRACT: The authors have observed that some patients with acute exacerbations of asthma do not have substantially higher levels of exhaled nitric oxide (NO). The study examined whether this could be explained by the effect of airway calibre on exhaled NO.Exhaled NO, height and forced expiratory volume in one second (FEV1) were measured in 12 steroid-naive asthmatics and 17 normal subjects. For comparison, another group of patients with airways disease (34 cystic fibrosis patients) were also studied. In 20 asthmatics (on various doses of inhaled steroids, 0±3,200 mg . day -1 ), exhaled NO was measured before and after histamine challenge (immediately after reaching the provocative concentration causing a 20% fall in FEV1) and in 12 of these patients, also after nebulized salbutamol to restore FEV1 to baseline. Studies were also conducted to examine possible confounding effects of repeated spirometry (as would occur in histamine challenge) and nebulized salbutamol alone in exhaled NO levels. Exhaled NO was measured using a single exhalation method with a chemiluminescence analyser at a constant flow rate and mouth pressure.There was a significant correlation between FEV1 and exhaled NO in steroid naive asthmatics (r=0.9, p<0.001) and cystic fibrosis patients (r= -0.48, p<0.05) but not in normal subjects (r= -0.13, p=0.61). Exhaled NO decreased significantly after histamine challenge and returned to baseline after bronchodilation by nebulized salbutamol (meanSEM: 23.63.6 parts per billion (ppb) (prehistamine), 18.22.7 ppb (posthistamine) and 23.63.8 ppb (postsalbutamol) p=0.001). Repeated spirometry and nebulized salbutamol did not affect exhaled NO measurements significantly.Exhaled nitric oxide levels appear to be lower in circumstances of smaller airway diameter. Hence, within a subject nitric oxide levels may be artefactually decreased during bronchoconstriction. This may be caused by increased airflow velocity in constricted airways when the exhalation rate is kept constant.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 75%

The current single exhalation method of measuring exhaled nitric oxide is affected by airway calibre

Wood

Robson

et al. 2000

Eur Respir J

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“…During normal physiologic circumstances, the distal airways are known to narrow or collapse at the very last part of a forced expiration (16). This could in part cause the declining plateau seen at high flow rates, since airway narrowing will decrease the transit time resulting in reduced NO concentration, as seen during acute bronchoconstriction (17). Another explanation could be that it takes approximately 10 s for alveolar NO concentrations to reach steady state after inhalation (18,19), and this might influence exhaled NO levels significantly at high expiration flow rates when absolute NO levels are low.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Exhaled Nitric Oxide in Schoolchildren at Different Exhalation Flow Rates

Pedroletti

2002

Pediatric Research

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Nitric oxide (NO) in exhaled air is believed to reflect allergic inflammation in the airways. Measured levels of exhaled NO vary with the exhaled flow rate, which therefore must be standardized. The aim of this study was to estimate the optimal exhalation flow rate when measuring NO in exhaled air. We studied 15 asthmatic children (8-18 y) with elevated NO levels and 15 age-matched controls and focused on how the quality of the NO curve profile, the discriminatory power, and the reproducibility were influenced by the exhalation flow rate. We used an on-line system for NO measurements at six different exhalation flow rates in the interval of 11-382 mL/s. The fraction of exhaled nitric oxide (FENO) was highly flow-dependent as was expected. Intermediate flow rates yielded a flat and stable NO plateau and were considerably easier to interpret than those obtained at the highest and lowest flow rates. The ratio of FENO between asthmatics and controls was lower at higher flow rates and a considerable overlap in NO values was demonstrated at all flow rates except 50 mL/s. The reproducibility was much lower at more extreme flow rates and was best at 50 mL/s. We conclude that a target exhalation flow rate of approximately 50 mL/s is to be preferred using the single-breath method for on-line NO measurements in schoolchildren. The presence of nitric oxide (NO) in exhaled air was first reported in 1991 (1) and soon after, it was discovered that asthmatics have higher levels of exhaled NO compared with controls (2, 3). These findings have evoked great interest because monitoring the fraction of expired NO (FENO) may be useful in the management of asthma (4), especially in children, for whom noninvasive methods are preferable (5).It has been shown that NO is mainly synthesized in the epithelial layer in the conducting airways (6 -8). This being the case, the concentration of NO in exhaled air will be highly dependent on exhalation flow rate (9 -11). Thus, there is a need to standardize the NO measurements, particular with respect to flow rate. However, previous (4) and current (12) recommendations on exhalation flow rate have not been based on experimental data, but are compromises based on practical/technical issues.We therefore investigated the quality of the exhaled NO curve profile, the reproducibility, and the discriminatory power of the NO values at six different exhalation flow rates in a sample of asthmatic schoolchildren with elevated levels of NO and age-matched controls. MATERIALS AND METHODS Subjects.Fifteen children (aged 8 -18, mean 14 y), three girls and twelve boys, with asthma and elevated NO levels (Ͼ10 ppb at exhalation flow rate 150 mL/s) were recruited from the Allergy clinic at Astrid Lindgren Children's Hospital, Karolinska Hospital.Thirteen of these children had atopic asthma and were sensitized to furred pets, pollen, or house dust mite. Atopy was evaluated by skin prick testing. Five subjects were steroidnaive. Mean dose of inhaled steroids was 305 g/d in steroidtreated patients. A brief structured i...

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“…This suggested a possible impact of airway calibre reduction on the ability of FENO to capture asthma control. Several studies focusing on airway challenges have demonstrated that a reduction of airway calibre reduces FENO levels in the absence of any inflammatory changes [9][10][11][12]. 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].…”

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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Exhaled Nitric Oxide (NO) Is Reduced Shortly after Bronchoconstriction to Direct and Indirect Stimuli in Asthma

Cited by 121 publications

References 18 publications

The current single exhalation method of measuring exhaled nitric oxide is affected by airway calibre

The current single exhalation method of measuring exhaled nitric oxide is affected by airway calibre

Evaluation of Exhaled Nitric Oxide in Schoolchildren at Different Exhalation Flow Rates

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

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