Measurement of exhaled nitric oxide by three different techniques.

Robbins, Richard; Floreani, Anthony A.; Essen, Susanna G. Von; Sisson, Joseph H.; Hill, Gary E.; Rubinstein, Israel; Townley, Robert G.

doi:10.1164/ajrccm.153.5.8630613

Cited by 109 publications

(79 citation statements)

References 14 publications

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“…The strength of the evidence, and hence the validity of the finding, is based on both practical and theoretical grounds. Higher levels of exhaled NO in asthma have been consistently found by several independent investigators using different techniques of measurement [18,22,23]. Theoretical considerations are also consistent with the raw data.…”

supporting

confidence: 79%

“…As NO is synthesized by many lung cells, it could originate from virtually anywhere in the respiratory tract, from alveolar space to the nose. Several recent and carefully conducted studies have clearly shown how the techniques of measurement are likely to affect the amount and origin of exhaled NO [16][17][18][19][20]. This prompted the European Respiratory Society, in 1997, to issue specific recommendations for the measurement of exhaled and nasal NO [21], an initiative which was followed in 1998 by the American Thoracic Society.…”

mentioning

confidence: 99%

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Measuring exhaled nitric oxide: not only a matter of how--but also why--should we do it?

Dinh-Xuan¹,

Texereau²

1998

Eur Respir J

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The biological functions of nitric oxide are so diverse and complex that it is now becoming increasingly difficult to delineate briefly the physiological roles and pathophysiological implications of this seemingly simple messenger molecule [1]. In respiratory medicine, NO can either be viewed as a paracrine factor (derived from endothelium, epithelium, nerves, inflammatory cells, etc), a therapeutic gas or a marker of inflammation [2]. Amongst other paracrine factors, the endothelium-derived NO has, in its own right, a central role to play in the modulation of pulmonary vascular tone [3]. As a gaseous molecule, NO has been extensively investigated in clinical settings and used as inhalational therapy to relieve pulmonary hypertension and/or refractory hypoxaemia in adults and infants [4]. Although there are many questions that still remain to be properly answered [5], the use of inhaled NO has undoubtedly revived interest in molecules that can selectively reduce both pulmonary vascular resistance and intrapulmonary shunt. As a radical molecule, NO is highly reactive and readily combines with an array of biological molecules, ranging from reactive oxygen species to haeme moiety containing proteins [6]. This explains why measurement of NO in biological systems was often fraught with difficulties in the early days [7]. Since 1991, however, measurement of in vivo NO production in humans have been proven to be technically feasible by means of ex vivo manoeuvres, i.e. by sampling the exhaled breath and analysing it for NO content using a chemiluminescent NO analyser [8]. As the technique is noninvasive, it was immediately applied to patients, especially those with bronchial asthma, to assess endogenous production of NO by the lung [9][10][11]. Soon, the accumulating evidence suggested that measurement of exhaled NO could be viewed as a new lung function test [12] to monitor airway inflammation in asthma [13] and other conditions associated with inflammation of the respiratory tract [14]. It is still difficult to know the actual source of the endogenous NO that is detected in the exhaled air [15]. As NO is synthesized by many lung cells, it could originate from virtually anywhere in the respiratory tract, from alveolar space to the nose. Several recent and carefully conducted studies have clearly shown how the techniques of measurement are likely to affect the amount and origin of exhaled NO [16][17][18][19][20]. This prompted the European Respiratory Society, in 1997, to issue specific recommendations for the measurement of exhaled and nasal NO [21], an initiative which was followed in 1998 by the American Thoracic Society.In contrast with the ongoing technical debate on how to measure exhaled NO, it seems that a consensus has been reached on the diagnostic value of NO measurement in asthma. Compelling evidence clearly demonstrates that asthmatic subjects who are not treated with inhaled glucocorticoids have on average higher amounts of exhaled NO as compared with healthy controls [9-14, 18, 21]. The strength of the e...

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supporting

confidence: 79%

mentioning

confidence: 99%

Measuring exhaled nitric oxide: not only a matter of how--but also why--should we do it?

Dinh-Xuan¹,

Texereau²

1998

Eur Respir J

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“…Instead, previous investigators have found either a positive correlation (7,24,25) or no correlation at all (26,27) between exhaled NO and airway inflammation. In addition, nonadrenergic noncholinergic nerves are not found in the epithelium (28,29), and because NO is rapidly metabolized within the tissue (30) or absorbed by Hb (31)(32)(33), it is doubtful that neuronal NO has the ability to reach the airway lumen. Instead, it is believed that iNOS, which is primarily found apically in the epithelial cells, is responsible for mucosal NO release in the airways (34).…”

Section: Airway Nitric Oxide In Schoolchildrenmentioning

confidence: 99%

Nitric Oxide Airway Diffusing Capacity and Mucosal Concentration in Asthmatic Schoolchildren

Pedroletti

Högman

Meriläinen³

et al. 2003

Pediatr Res

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Asthmatic patients show increased concentrations of nitric oxide (NO) in exhaled air (FENO). The diffusing capacity of NO in the airways (DawNO), the NO concentrations in the alveoli and the airway wall, and the maximal airway NO diffusion rate have previously been estimated noninvasively by measuring FENO at different exhalation flow rates in adults. We investigated these variables in 15 asthmatic schoolchildren (8 -18 y) and 15 agematched control subjects, with focus on their relation to exhaled NO at the recommended exhalation flow rate of 0.05 L/s (FENO 0.05 ), age, and volume of the respiratory anatomic dead space. NO was measured on-line by chemiluminescence according to the European Respiratory Society's guidelines, and the NO plateau values at three different exhalation flow rates (11, 99, and 382 mL/s) were incorporated in a two-compartment model for NO diffusion. The NO concentration in the airway wall (p Ͻ 0.001), DawNO (p Ͻ 0.01), and the maximal airway NO diffusion rate (p Ͻ 0.001) were all higher in the asthmatic children than in control children. In contrast, there was no difference in the NO concentration in the alveoli (p ϭ 0.13) between the groups. A positive correlation was seen between the volume of the respiratory anatomic dead space and FENO 0.05 (r ϭ 0.68, p Ͻ 0.01), the maximal airway NO diffusion rate (r ϭ 0.71, p Ͻ 0.01), and DawNO (r ϭ 0.56, p Ͻ 0.01) in control children, but not in asthmatic children. FENO 0.05 correlated better with DawNO in asthmatic children (r ϭ 0.65, p Ͻ 0.01) and with the NO concentration in the airway wall in control subjects (r Ͻ 0.77, p Ͻ 0.001) than vice versa. We conclude that FENO 0.05 increases with increasing volume of the respiratory anatomic dead space in healthy children, suggesting that normal values for FENO 0.05 should be related to age or body weight in this age group. Furthermore, the elevated FENO 0.05 seen in asthmatic children is related to an increase in both DawNO and NO concentration in the airway wall. Because DawNO correlates with the volume of the respiratory anatomic dead space in control subjects and FENO 0.05 correlates with DawNO in asthmatic children, we suggest that DawNO partly reflects the total NO-producing surface area and that a larger part of the bronchial tree produces NO in asthmatic children than in control children. NO can be measured in exhaled air, and high levels of NO are believed to reflect allergic inflammation in the airways of asthmatic patients (1-3). Correlations between exhaled NO and other markers of airway inflammation such as eosinophils in sputum and blood (4 -6), bronchial hyperresponsiveness (7), and bronchial eosinophilia (5, 8) have been demonstrated. In the lower airways, NO is thought to be produced by iNOS in Received July 8, 2002; accepted December 3, 2002

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“…Therefore, we determined the ability of F E NO, as well as serum CRP, interkeukin-6 (IL-6), and interleukin-8 (IL-8), to independently predict spirometric responses to ICS in patients with severe COPD. (1) a clinical diagnosis of COPD, with a FEV 1 /FVC ratio <70%, and FEV 1 <60% of predicted; (2) age >45 years; (3) cigarette smoking history of >10 pack-years; (4) abstinence from cigarette smoking of at least 6 months, as active smoking can suppress F E NO levels [Robbins et al 1996;; (5) stable clinical status, as evidenced by the lack of hospitalizations, urgent care visits, antibiotics, or changes in medications within four weeks prior to enrollment; and (6) ability to provide informed consent. Exclusion criteria were: (1) a clinical diagnosis of asthma; (2) leukotriene inhibitor use; (3) severe or uncompensated heart failure; (4) the presence of conditions known to elevate CRP levels (such as collagen vascular disease and chronic infection); (5) malignancy requiring active treatment with chemotherapy or radiation therapy, or any co-morbidity making survival greater than one year unlikely; (6) women who were pregnant or lactating; (7) oral corticosteroid use within four weeks prior to enrollment; and (8) participation in another investigational trial within four weeks of enrollment and for the duration of this study.…”

Section: Introductionmentioning

confidence: 99%

Exhaled nitric oxide, systemic inflammation, and the spirometric response to inhaled fluticasone propionate in severe chronic obstructive pulmonary disease: A prospective study

Kunisaki

Rice

Janoff

et al. 2008

Ther Adv Respir Dis

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Background:A subset of patients with chronic obstructive pulmonary disease (COPD) may respond more favorably to inhaled corticosteroids (ICS), but no simple method is currently utilized to predict the presence or absence of ICS responses in patients with COPD. We evaluated the ability of exhaled nitric oxide (F E NO) and serum inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], and interleukin-8 ) to independently predict spirometric responses to ICS in patients with COPD. Methods: Among 60 ex-smokers with severe COPD (mean FEV 1 1.07 L, 36% of predicted), we conducted a single-arm, open-label study. Participants spent four weeks free of any ICS, followed by four weeks of ICS use (fluticasone propionate 500 mcg twice daily). F E NO, CRP, IL-6, IL-8, and pre-bronchodilator spirometry were measured immediately before and after the four weeks of ICS use. Results: Baseline F E NO, CRP, IL-6, and IL-8 showed no correlations to FEV 1 responses to ICS. ICS responders (increase in FEV 1 ≥ 200 mL after four weeks of ICS) did have significantly higher baseline F E NO levels compared with non-responders (46.5 parts per billion [ppb] vs. 25 ppb, p = 0.028). The receiver operating characteristic curve for F E NO to discriminate responders from non-responders had an area under curve of 0.72. Baseline serum inflammatory markers did not differ between responders and non-responders. Conclusion:In ex-smokers with severe COPD, a measure of local pulmonary inflammation, F E NO, may be more closely associated with FEV 1 responses to four weeks of ICS than are standard markers of systemic inflammation, serum CRP, IL-6, and IL-8 Keywords: Androstadienes / tu (therapeutic use), anti-inflammatory agents / tu (therapeutic use), breath tests, C-reactive protein, inflammation / bl (blood), interleukin-6 / bl (blood), interleukin-8 / bl (blood), nitric oxide / du (diagnostic use), pulmonary disease, chronic obstructive Abbreviations ATS = American Thoracic Society AUC = area under curve COPD = chronic obstructive pulmonary disease CRP = C-reactive protein F E NO = fraction of exhaled nitric oxide FEV 1 = forced expiratory volume in one second FVC = forced vital capacity ICS = inhaled corticosteroid IL-6 = interleukin-6 IL-8 = interluekin-8 IQR = interquartile range ppb = parts per billion

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Measurement of exhaled nitric oxide by three different techniques.

Cited by 109 publications

References 14 publications

Measuring exhaled nitric oxide: not only a matter of how--but also why--should we do it?

Measuring exhaled nitric oxide: not only a matter of how--but also why--should we do it?

Nitric Oxide Airway Diffusing Capacity and Mucosal Concentration in Asthmatic Schoolchildren

Exhaled nitric oxide, systemic inflammation, and the spirometric response to inhaled fluticasone propionate in severe chronic obstructive pulmonary disease: A prospective study

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