Expired Nitric Oxide after Bronchoprovocation and  Repeated Spirometry in Patients with Asthma

Deykin, Aaron; Halpern, Orit; Massaro, Anthony F.; Drazen, Jeffrey M.; Israel, Elliot

doi:10.1164/ajrccm.157.3.9707114

Cited by 128 publications

(118 citation statements)

References 29 publications

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“…To determine the potential impact of nitrogen in the residual volume, each subject also performed the preexpiratory breath hold maneuver with a 20-s breath hold in the presence of heliox without tidal breathing heliox before the maneuver. After measurement of the indexes of NO-exchange dynamics (4,5,25), general spirometry such as FVC, FEV 1, and FEV1 by FVC were measured in all subjects (Vmax229; Sensormedics, Yorba Linda, CA) by using the best performance (see Table 1) from three consecutive maneuvers.…”

Section: Methodsmentioning

confidence: 99%

Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox

Shin

Condorelli

Rose-Gottron

et al. 2004

Journal of Applied Physiology

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Shin, Hye-Won, Peter Condorelli, Christine M. Rose-Gottron, Dan M. Cooper, and Steven C. George. Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox. J Appl Physiol 97: 874 -882, 2004. First published April 30, 2004 10.1152/ japplphysiol.01297.2003.-Exhaled nitric oxide (NO) is a potential noninvasive index of lung inflammation and is thought to arise from the alveolar and airway regions of the lungs. A two-compartment model has been used to describe NO exchange; however, the model neglects axial diffusion of NO in the gas phase, and recent theoretical studies suggest that this may introduce significant error. We used heliox (80% helium, 20% oxygen) as the insufflating gas to probe the impact of axial diffusion (molecular diffusivity of NO is increased 2.3-fold relative to air) in healthy adults (21-38 yr old, n ϭ 9). Heliox decreased the plateau concentration of exhaled NO by 45% (exhalation flow rate of 50 ml/s). In addition, the total mass of NO exhaled in phase I and II after a 20-s breath hold was reduced by 36%. A single-path trumpet model that considers axial diffusion predicts a 50% increase in the maximum airway flux of NO and a near-zero alveolar concentration (CA NO) and source. Furthermore, when NO elimination is plotted vs. constant exhalation flow rate (range 50 -500 ml/s), the slope has been previously interpreted as a nonzero CANO (range 1-5 ppb); however, the trumpet model predicts a positive slope of 0.4 -2.1 ppb despite a zero CANO because of a diminishing impact of axial diffusion as flow rate increases. We conclude that axial diffusion leads to a significant backdiffusion of NO from the airways to the alveolar region that significantly impacts the partitioning of airway and alveolar contributions to exhaled NO. gas exchange; model; exhaled breath NITRIC OXIDE (NO) performs many important functions in the lungs and has been regarded as a potential noninvasive marker of lung inflammation (2). The characteristics of NO gas exchange are unique compared with other endogenous gases because exhaled NO is thought to have a significant alveolar and airway source (6,8,15,22). A two-compartment model is commonly used to characterize NO exchange dynamics for healthy and diseased lungs (9,11,13,20,21,23,24,27,29), by partitioning exhaled NO into airway and alveolar contributions using three flow-independent NO exchange parameters: maximum flux of NO from the airways (JЈaw NO ), the diffusing capacity of NO in the airways (Daw NO ), and the steady-state alveolar concentration (CA NO ). However, the two-compartment model considers only convection of NO in the airways as a transport mechanism and has neglected axial diffusion of NO in the gas phase to preserve mathematical simplicity.Recently, our laboratory (17) and others (31) separately demonstrated theoretically that axial diffusion may play an important role in NO transport. During exhalation, the concentration of NO is higher in the airways compared with the alveoli, creating a gradient for diffusion of NO from the air...

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Section: Methodsmentioning

confidence: 99%

Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox

Shin

Condorelli

Rose-Gottron

et al. 2004

Journal of Applied Physiology

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“…Exhaled breath was collected before lung function measurements because deep inspiration may affect nitric oxide concentration (14). The subjects were instructed to inhale to nearly total lung capacity and exhale through an offline collection device (Vital Capacity Kit for collection of exhaled breath; Sievers Ionics, Boulder, CO).…”

Section: Data Collection and Processingmentioning

confidence: 99%

Cell markers, cytokines, and immune parameters in cement mason apprentices

Carlsten¹,

Roos²,

Kaufman³

et al. 2007

Arthritis & Rheumatism

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Objective. Cement masons are known to have significant silica exposure, and silica exposure and silicosis are thought to increase risk of autoimmune disease. Because the mechanisms remain obscure, with inconclusive reports of systemic immune effects following silica exposure, our goal was to identify potential early markers of silica-related immunologic and respiratory effects. Methods. We conducted a cross-sectional study of cement mason apprentices and electrician (control) apprentices. Demographics, dust exposure history, symptoms, spirometry, exhaled nitric oxide, and blood (for immunoglobulins, cytokines, cell counts, and surface markers) were obtained from 11 cement mason apprentices and a comparison group of 21 electrician apprentices. Results. Masons had significantly higher (P < 0.05) masonry dust exposure (42 versus 9 dust-hour-years), serum interleukin-1␤ (IL-1␤; 12 versus 9 pg/ml), IL-2 (20 versus 8 pg/ml), IL-4 (193 versus 67 pg/ml), IL-10 (44 versus 21 pg/ml), and interferon-␥ (139 versus 65 pg/ml) compared with electricians. In contrast, masons had significantly lower percentages of CD25؉ (12% versus 20%) and CD69؉ (4% versus 9%) lymphocytes. Conclusion. Mason apprentices had higher levels of serum proinflammatory cytokines and lower percentages of CD25؉ and CD69؉ lymphocytes than did electrician apprentices. These preliminary findings suggest that mason apprentices may be at greater risk of a systemic proinflammatory state that is potentially linked to immune dysregulation. Although distinct limitations of this preliminary data are recognized, this is consistent with early biologic effects leading to increased incidence of autoimmune disease among silica-exposed workers. Prospective studies are needed to validate these initial findings and clarify the temporal sequence of observed relationships.

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“…Control studies: possible confounding effects of repeated spirometry and nebulized salbutamol Repeated spirometric manoeuvres (as would occur during histamine challenge) have been shown to cause a reduction in NO levels [7,8] and b 2 -agonists may induce NO production [7,9]. In order to address whether the observed findings were purely related to these factors, 10 subjects in protocol 2 returned for the following studies.…”

Section: Study Design and Subjectsmentioning

confidence: 99%

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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Expired Nitric Oxide after Bronchoprovocation and Repeated Spirometry in Patients with Asthma

Cited by 128 publications

References 29 publications

Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox

Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox

Cell markers, cytokines, and immune parameters in cement mason apprentices

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

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