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Biomedical subjects

Steven C George

Publications and source records attributed to Steven C George.

At least 19 recordsLinked to original sources
PubMed2006

Noninvasive assessment of collagen gel microstructure and mechanics using multiphoton microscopy.

Multiphoton microscopy of collagen hydrogels produces second harmonic generation (SHG) and two-photon fluorescence (TPF) images, which can be used to noninvasively study gel microstructure at depth ( approximately 1 mm). The microstructure is also a primary determinate of the mechanical properties of the gel; thus, we hypothesized that bulk optical properties (i.e., SHG and TPF) could be used to predict bulk mechanical properties of collagen hydrogels. We utilized polymerization temperature (4-37 degrees C) and glutaraldehyde to manipulate collagen hydrogel fiber diameter, space-filling properties, and cross-link density. Multiphoton microscopy and scanning electron microscopy reveal that as polymerization temperature decreases (37-4 degrees C) fiber diameter and pore size increase, whereas hydrogel storage modulus (G', from 23 +/- 3 Pa to 0.28 +/- 0.16 Pa, respectively, mean +/- SE) and mean SHG decrease (minimal change in TPF). In contrast, glutaraldehyde significantly increases the mean TPF signal (without impacting the SHG signal) and the storage modulus (16 +/- 3.5 Pa before to 138 +/- 40 Pa after cross-linking, mean +/- SD). We conclude that SHG and TPF can characterize differential microscopic features of the collagen hydrogel that are strongly correlated with bulk mechanical properties. Thus, optical imaging may be a useful noninvasive tool to assess tissue mechanics.

Biomechanical Phenomena↗
PubMed2006

Airway nitric oxide release is reduced after PBS inhalation in asthma.

Exhaled nitric oxide (NO) is elevated in asthma, but the underlying mechanisms remain poorly understood. Recent results in subjects with asthma have reported a decrease in exhaled breath pH and ammonia, as well as altered expression and activity of glutaminase in both alveolar and airway epithelial cells. This suggests that pH-dependent nitrite conversion to NO may be a source of exhaled NO in the asthmatic airway epithelium. However, the anatomic location (i.e., airway or alveolar region) of this pH-dependent NO release has not been investigated and could impact potential therapeutic strategies. We quantified airway (proximal) and alveolar (peripheral) contributions to exhaled NO at baseline and then after PBS inhalation in stable (mild-intermittent to severe) asthmatic subjects (20-44 yr old; n = 9) and healthy controls (22-41 yr old; n = 6). The mean (SD) maximum airway wall flux (pl/s) and alveolar concentration (ppb) at baseline in asthma subjects and healthy controls was 2,530 (2,572) and 5.42 (7.31) and 1,703 (1,567) and 1.88 (1.29), respectively. Compared with baseline, there is a significant decrease in the airway wall flux of NO in asthma as early as 15 min and continuing for up to 60 min (maximum -28% at 45 min) after PBS inhalation without alteration of alveolar concentration. Healthy control subjects did not display any changes in exhaled NO. We conclude that elevated airway NO at baseline in asthma is reduced by inhaled PBS. Thus airway NO may be, in part, due to nitrite conversion to NO and is consistent with airway pH dysregulation in asthma.

Administration, Inhalation↗
PubMed2006

Epithelial-derived TGF-beta2 modulates basal and wound-healing subepithelial matrix homeostasis.

The epithelium influences the mesenchyme during dynamic processes such as embryogenesis, wound healing, fibrosis, and carcinogenesis. Since transforming growth factor-beta (TGF-beta) modulates these processes, we hypothesized that epithelial-derived TGF-beta also plays a critical role in maintaining the extracellular matrix at basal conditions. We utilized an in vitro model of the epithelial-mesenchymal trophic unit in the human airways to determine the role of epithelial-derived TGF-beta in modulating the extracellular matrix under basal and wound-healing conditions. When differentiated at an air-liquid interface, the human bronchial epithelium produces active TGF-beta2 at a concentration of 50-70 pg/ml, whereas TGF-beta1 is undetectable. TGF-beta2 increases two- to threefold following scrape injury in a dose-dependent fashion and significantly enhances both alpha-smooth muscle actin expression in the underlying collagen-embedded fibroblasts and secretion of tenascin-C into the matrix. Multiphoton microscopy demonstrates substantially enhanced second harmonic generation from fibrillar collagen in the matrix. Pretreatment of the matrix with either sirolimus (2.5 nM) or paclitaxel (10 nM) abolishes the increases in both TGF-beta2 and second harmonic generation in response to epithelial injury. In the absence of the epithelium, exogenous active TGF-beta2 (0-400 pg/ml) produces a biphasic response in the second harmonic signal with a minimum occurring at the epithelial-derived basal level. We conclude that epithelial-derived TGF-beta2 is secreted in response to injury, significantly alters the bulk optical properties of the extracellular matrix, and its tight regulation may be required for normal collagen homeostasis.

Cells, Cultured↗
PubMed2006

A simple technique to characterize proximal and peripheral nitric oxide exchange using constant flow exhalations and an axial diffusion model.

The most common technique employed to describe pulmonary gas exchange of nitric oxide (NO) combines multiple constant flow exhalations with a two-compartment model (2CM) that neglects 1) the trumpet shape (increasing surface area per unit volume) of the airway tree and 2) gas phase axial diffusion of NO. However, recent evidence suggests that these features of the lungs are important determinants of NO exchange. The goal of this study is to present an algorithm that characterizes NO exchange using multiple constant flow exhalations and a model that considers the trumpet shape of the airway tree and axial diffusion (model TMAD). Solution of the diffusion equation for the TMAD for exhalation flows >100 ml/s can be reduced to the same linear relationship between the NO elimination rate and the flow; however, the interpretation of the slope and the intercept depend on the model. We tested the TMAD in healthy subjects (n = 8) using commonly used and easily performed exhalation flows (100, 150, 200, and 250 ml/s). Compared with the 2CM, estimates (mean +/- SD) from the TMAD for the maximum airway flux are statistically higher (J'aw(NO) = 770 +/- 470 compared with 440 +/- 270 pl/s), whereas estimates for the steady-state alveolar concentration are statistically lower (CA(NO) = 0.66 +/- 0.98 compared with 1.2 +/- 0.80 parts/billion). Furthermore, CA(NO) from the TMAD is not different from zero. We conclude that proximal (airways) NO production is larger than previously predicted with the 2CM and that peripheral (respiratory bronchioles and alveoli) NO is near zero in healthy subjects.

Adult↗
PubMed2006

Exercise-induced bronchoconstriction alters airway nitric oxide exchange in a pattern distinct from spirometry.

Exhaled nitric oxide (NO) is altered in asthmatic subjects with exercise-induced bronchoconstriction (EIB). However, the physiological interpretation of exhaled NO is limited because of its dependence on exhalation flow and the inability to distinguish completely proximal (large airway) from peripheral (small airway and alveolar) contributions. We estimated flow-independent NO exchange parameters that partition exhaled NO into proximal and peripheral contributions at baseline, postexercise challenge, and postbronchodilator administration in steroid-naive mild-intermittent asthmatic subjects with EIB (24-43 yr old, n = 9) and healthy controls (20-31 yr old, n = 9). The mean +/- SD maximum airway wall flux and airway diffusing capacity were elevated and forced expiratory flow, midexpiratory phase (FEF(25-75)), forced expiratory volume in 1 s (FEV(1)), and FEV(1)/forced vital capacity (FVC) were reduced at baseline in subjects with EIB compared with healthy controls, whereas the steady-state alveolar concentration of NO and FVC were not different. Compared with the response of healthy controls, exercise challenge significantly reduced FEV(1) (-23 +/- 15%), FEF(25-75) (-37 +/- 18%), FVC (-12 +/- 12%), FEV(1)/FVC (-13 +/- 8%), and maximum airway wall flux (-35 +/- 11%) relative to baseline in subjects with EIB, whereas bronchodilator administration only increased FEV(1) (+20 +/- 21%), FEF(25-75) (+56 +/- 41%), and FEV(1)/FVC (+13 +/- 9%). We conclude that mild-intermittent steroid-naive asthmatic subjects with EIB have altered airway NO exchange dynamics at baseline and after exercise challenge but that these changes occur by distinct mechanisms and are not correlated with alterations in spirometry.

Adaptation, Physiological↗
PubMed2006

A three-dimensional in vitro model of angiogenesis in the airway mucosa.

Bronchial asthma is an inflammatory disease characterized by chronic intermittent bronchoconstriction. A key feature of the disease is structural changes in the airway wall (airway remodeling) consistent with tissue growth and chronic wound healing including angiogenesis. The epithelium directs mesenchymal processes during both embryogenesis and wound healing, and thus we hypothesized that the bronchial epithelium plays a critical role in directing angiogenesis. To study angiogenesis in the airways, we have developed a three-dimensional (3-D) in vitro model of the airway mucosa that consists of normal differentiated human bronchial epithelial cells (NHBE), normal human lung fibroblasts (NHLF), and human umbilical vein endothelial cells (HUVEC). The HUVEC are coated on dextran beads and suspended in a fibrin gel approximately 2mm beneath a confluent monolayer of NHLF which are just beneath the confluent monolayer of differentiated NHBE. In the presence of fibroblasts, visible capillaries reaching lengths of up to 1mm sprout from the HUVEC-coated beads. Over 11 days in culture, the bronchial epithelium produces transforming growth factor-beta2 (TGFbeta2, 60pg/ml), significantly increases vascular endothelial growth factor (VEGF) more than 6-fold to a concentration of 1.85ng/ml, but does not significantly impact total network formation. Exogenous TGFbeta2 stimulates VEGF production in a dose-dependent fashion (0-400pg/ml) through a MAPK-dependent pathway, but also inhibits capillary network formation. We conclude that the bronchial epithelium produces biologically relevant concentrations of VEGF and TGFbeta2 in a 3-D model of the airway mucosa that may be useful in probing mechanisms of angiogenesis in asthma.

Bronchi↗
PubMed2006

Personal and ambient air pollution is associated with increased exhaled nitric oxide in children with asthma.

BACKGROUND: Research has shown associations between pediatric asthma outcomes and airborne particulate matter (PM). The importance of particle components remains to be determined. METHODS: We followed a panel of 45 schoolchildren with persistent asthma living in Southern California. Subjects were monitored over 10 days with offline fractional exhaled nitric oxide (FeNO), a biomarker of airway inflammation. Personal active sampler exposures included continuous particulate matter < 2.5 microm in aerodynamic diameter (PM2.5), 24-hr PM2.5 elemental and organic carbon (EC, OC), and 24-hr nitrogen dioxide. Ambient exposures included PM2.5, PM2.5 EC and OC, and NO2. Data were analyzed with mixed models controlling for personal temperature, humidity and 10-day period. RESULTS: The strongest positive associations were between FeNO and 2-day average pollutant concentrations. Per interquartile range pollutant increase, these were: for 24 microg/m3 personal PM2.5, 1.1 ppb FeNO [95% confidence interval (CI), 0.1-1.9]; for 0.6 microg/m3 personal EC, 0.7 ppb FeNO (95% CI, 0.3-1.1); for 17 ppb personal NO2, 1.6 ppb FeNO (95% CI, 0.4-2.8). Larger associations were found for ambient EC and smaller associations for ambient NO2. Ambient PM2.5 and personal and ambient OC were significant only in subjects taking inhaled corticosteroids (ICS) alone. Subjects taking both ICS and antileukotrienes showed no significant associations. Distributed lag models showed personal PM2.5 in the preceding 5 hr was associated with FeNO. In two-pollutant models, the most robust associations were for personal and ambient EC and NO2, and for personal but not ambient PM2.5. CONCLUSION: PM associations with airway inflammation in asthmatics may be missed using ambient particle mass, which may not sufficiently represent causal pollutant components from fossil fuel combustion.

Adolescent↗
PubMed2005

Examining axial diffusion of nitric oxide in the lungs using heliox and breath hold.

Exhaled nitric oxide (NO) is highly dependent on exhalation flow; thus exchange dynamics of NO have been described by multicompartment models and a series of flow-independent parameters that describe airway and alveolar exchange. Because the flow-independent NO airway parameters characterize features of the airway tissue (e.g., wall concentration), they should also be independent of the physical properties of the insufflating gas. We measured the total mass of NO exhaled (A(I,II)) from the airways after five different breath-hold times (5-30 s) in healthy adults (21-38 yr, n = 9) using air and heliox as the insufflating gas, and then modeled A(I,II) as a function of breath-hold time to determine airway NO exchange parameters. Increasing breath-hold time results in an increase in A(I,II) for both air and heliox, but A(I,II) is reduced by a mean (SD) of 31% (SD 6) (P < 0.04) in the presence of heliox, independent of breath-hold time. However, mean (SD) values (air, heliox) for the airway wall diffusing capacity [3.70 (SD 4.18), 3.56 pl.s(-1).ppb(-1) (SD 3.20)], the airway wall concentration [1,439 (SD 487), 1,503 ppb (SD 644>)], and the maximum airway wall flux [4,156 (SD 2,502), 4,412 pl/s (SD 2,906)] using a single-path trumpet-shaped airway model that considers axial diffusion were independent of the insufflating gas (P > 0.55). We conclude that a single-path trumpet model that considers axial diffusion captures the essential features of airway wall NO exchange and confirm earlier reports that the airway wall concentration in healthy adults exceeds 1 ppm and thus approaches physiological concentrations capable of modulating smooth muscle tone.

Adult↗
PubMed2004

A new and more accurate technique to characterize airway nitric oxide using different breath-hold times.

Exhaled nitric oxide (NO) arises from both airway and alveolar regions of the lungs, which provides an opportunity to characterize region-specific inflammation. Current methodologies rely on vital capacity breathing maneuvers and controlled exhalation flow rates, which can be difficult to perform, especially for young children and individuals with compromised lung function. In addition, recent theoretical and experimental studies demonstrate that gas-phase axial diffusion of NO has a significant impact on the exhaled NO signal. We have developed a new technique to characterize airway NO, which requires a series of progressively increasing breath-hold times followed by exhalation of only the airway compartment. Using our new technique, we determined values (means +/- SE) in healthy adults (20-38 yr, n = 8) for the airway diffusing capacity [4.5 +/- 1.6 pl.s(-1).parts per billion (ppb)(-1)], the airway wall concentration (1,340 +/- 213 ppb), and the maximum airway wall flux (4,350 +/- 811 pl/s). The new technique is simple to perform, and application of this data to simpler models with cylindrical airways and no axial diffusion yields parameters consistent with previous methods. Inclusion of axial diffusion as well as an anatomically correct trumpet-shaped airway geometry results in significant loss of NO from the airways to the alveolar region, profoundly impacting airway NO characterization. In particular, the airway wall concentration is more than an order of magnitude larger than previous estimates in healthy adults and may approach concentrations (approximately 5 nM) that can influence physiological processes such as smooth muscle tone in disease states such as asthma.

Adult↗
PubMed2004

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

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 = 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 Ca(NO) (range 1-5 ppb); however, the trumpet model predicts a positive slope of 0.4-2.1 ppb despite a zero Ca(NO) 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.

Adult↗
PubMed2004

Characterizing airway and alveolar nitric oxide exchange during tidal breathing using a three-compartment model.

Exhaled nitric oxide (NO) may be a useful marker of lung inflammation, but the concentration is highly dependent on exhalation flow rate due to a significant airway source. Current methods for partitioning pulmonary NO gas exchange into airway and alveolar regions utilize multiple exhalation flow rates or a single-breath maneuver with a preexpiratory breath hold, which is cumbersome for children and individuals with compromised lung function. Analysis of tidal breathing data has the potential to overcome these limitations, while still identifying region-specific parameters. In six healthy adults, we utilized a three-compartment model (two airway compartments and one alveolar compartment) to identify two potential flow-independent parameters that represent the average volumetric airway flux (pl/s) and the time-averaged alveolar concentration (parts/billion). Significant background noise and distortion of the signal from the sampling system were compensated for by using a Gaussian wavelet filter and a series of convolution integrals. Mean values for average volumetric airway flux and time-averaged alveolar concentration were 2,500 +/- 2,700 pl/s and 3.2 +/- 3.4 parts/billion, respectively, and were strongly correlated with analogous parameters determined from vital capacity breathing maneuvers. Analysis of multiple tidal breaths significantly reduced the standard error of the parameter estimates relative to the single-breath technique. Our initial assessment demonstrates the potential of utilizing tidal breathing for noninvasive characterization of pulmonary NO exchange dynamics.

Adult↗
PubMed2004

Modeling pulmonary nitric oxide exchange.

Nitric oxide (NO) was first detected in the exhaled breath more than a decade ago and has since been investigated as a noninvasive means of assessing lung inflammation. Exhaled NO arises from the airway and alveolar compartments, and new analytical methods have been developed to characterize these sources. A simple two-compartment model can adequately represent many of the observed experimental observations of exhaled concentration, including the marked dependence on exhalation flow rate. The model characterizes NO exchange by using three flow-independent exchange parameters. Two of the parameters describe the airway compartment (airway NO diffusing capacity and either the maximum airway wall NO flux or the airway wall NO concentration), and the third parameter describes the alveolar region (steady-state alveolar NO concentration). A potential advantage of the two-compartment model is the ability to partition exhaled NO into an airway and alveolar source and thus improve the specificity of detecting altered NO exchange dynamics that differentially impact these regions of the lungs. Several analytical techniques have been developed to estimate the flow-independent parameters in both health and disease. Future studies will focus on improving our fundamental understanding of NO exchange dynamics, the analytical techniques used to characterize NO exchange dynamics, as well as the physiological interpretation and the clinical relevance of the flow-independent parameters.

Animals↗
PubMed2003

Airway diffusing capacity of nitric oxide and steroid therapy in asthma.

Exhaled nitric oxide (NO) concentration is a noninvasive index for monitoring lung inflammation in diseases such as asthma. The plateau concentration at constant flow is highly dependent on the exhalation flow rate and the use of corticosteroids and cannot distinguish airway and alveolar sources. In subjects with steroid-naive asthma (n = 8) or steroid-treated asthma (n = 12) and in healthy controls (n = 24), we measured flow-independent NO exchange parameters that partition exhaled NO into airway and alveolar regions and correlated these with symptoms and lung function. The mean (+/-SD) maximum airway flux (pl/s) and airway tissue concentration [parts/billion (ppb)] of NO were lower in steroid-treated asthmatic subjects compared with steroid-naive asthmatic subjects (1,195 +/- 836 pl/s and 143 +/- 66 ppb compared with 2,693 +/- 1,687 pl/s and 438 +/- 312 ppb, respectively). In contrast, the airway diffusing capacity for NO (pl.s-1.ppb-1) was elevated in both asthmatic groups compared with healthy controls, independent of steroid therapy (11.8 +/- 11.7, 8.71 +/- 5.74, and 3.13 +/- 1.57 pl.s-1.ppb-1 for steroid treated, steroid naive, and healthy controls, respectively). In addition, the airway diffusing capacity was inversely correlated with both forced expired volume in 1 s and forced vital capacity (%predicted), whereas the airway tissue concentration was positively correlated with forced vital capacity. Consistent with previously reported results from Silkoff et al. (Silkoff PE, Sylvester JT, Zamel N, and Permutt S, Am J Respir Crit Med 161: 1218-1228, 2000) that used an alternate technique, we conclude that the airway diffusing capacity for NO is elevated in asthma independent of steroid therapy and may reflect clinically relevant changes in airways.

Adolescent↗
PubMed2003

Impact of high-intensity exercise on nitric oxide exchange in healthy adults.

PURPOSE: After exercise, exhaled NO concentration has been reported to decrease, remain unchanged, or increase. A more mechanistic understanding of NO exchange dynamics after exercise is needed to understand the relationship between exercise and NO exchange. METHODS: We measured several flow-independent NO exchange parameters characteristic of airway and alveolar regions using a single breath maneuver and a two-compartment model (maximum flux of NO from the airways, J'(awNO), pL x s-1; diffusing capacity of NO in the airways, D(awNO), pL x s-1 x ppb-1; steady state alveolar concentration, C(alv,ss), ppb; mean airway tissue NO concentration, C(awNO), ppb), as well as serum IL-6 at baseline, 3, 30, and 120 min after a high-intensity exercise challenge in 10 healthy adults (21-37 yr old). RESULTS: D(awNO) (mean +/- SD) increased (37.1 +/- 44.4%), whereas J'(awNO) and C(awNO) decreased (-7.27 +/- 11.1%, -26.1 +/- 24.6%, respectively) 3 min postexercise. IL-6 increased steadily after exercise to 481% +/- 562% above baseline 120 min postexercise. CONCLUSION: High-intensity exercise acutely enhances the ability of NO to diffuse between the airway tissue and the gas phase, and exhaled NO might be used to probe both the metabolic and physical properties of the airways.

Adult↗
PubMed2002

Impact of axial diffusion on nitric oxide exchange in the lungs.

Nitric oxide (NO) appears in the exhaled breath and is a potentially important clinical marker. The accepted model of NO gas exchange includes two compartments, representing the airway and alveolar region of the lungs, but neglects axial diffusion. We incorporated axial diffusion into a one-dimensional trumpet model of the lungs to assess the impact on NO exchange dynamics, particularly the impact on the estimation of flow-independent NO exchange parameters such as the airway diffusing capacity and the maximum flux of NO in the airways. Axial diffusion reduces exhaled NO concentrations because of diffusion of NO from the airways to the alveolar region of the lungs. The magnitude is inversely related to exhalation flow rate. To simulate experimental data from two different breathing maneuvers, NO airway diffusing capacity and maximum flux of NO in the airways needed to be increased approximately fourfold. These results depend strongly on the assumption of a significant production of NO in the small airways. We conclude that axial diffusion may decrease exhaled NO levels; however, more advanced knowledge of the longitudinal distribution of NO production and diffusion is needed to develop a complete understanding of the impact of axial diffusion.

Diffusion↗
PubMed2002

Free nitric oxide diffusion in the bronchial microcirculation.

Theoretical mass transfer rates and concentration distributions were determined for transient diffusion of free nitric oxide (NO) generated in vivo from vascular endothelial cells. Our analytical framework is typical of the bronchial circulation in the human pulmonary system but is applicable to the microvascular circulation in general. We characterized mass transfer rates in terms of the fractional mass flux across a boundary relative to the total endothelial NO production rate. NO concentration in the tissue surrounding blood vessels was expressed in terms of fractional soluble guanylate cyclase (sGC) activity. Our results suggest that endothelium-derived free NO is capable of vascular smooth muscle dilation despite its rapid consumption by hemoglobin in blood. An optimal blood vessel radius of 20 microm was estimated for NO signaling. We hypothesize intermittent generation of endothelial NO as a possible mechanism for sGC activation in vascular smooth muscle. This mechanism enhances the efficacy of NO-modulated vascular smooth muscle dilation while minimizing NO losses to blood and surrounding tissue.

Arterioles↗
PubMed2002

Flow-independent nitric oxide exchange parameters in cystic fibrosis.

Exhaled nitric oxide (NO) remains a promising noninvasive index for monitoring inflammatory lung diseases; however, the plateau concentration (C(NO,plat)) is nonspecific and requires a constant exhalation flow rate. We utilized a new technique that employs a variable flow rate to estimate key flow-independent parameters characteristic of NO exchange in a group (n = 9) of 10 to 14 yr-old healthy children and children with cystic fibrosis (CF): maximum flux of NO from the airways (J(NO,max'), pl s(-1)), diffusing capacity of NO in the airways (D(NO,air'), pl s(-1) ppb(-1)), steady-state alveolar concentration (C(alv,ss'), ppb), and mean tissue concentration of NO in the airways (C(tiss,air'), ppb). We determined the following mean (+/- SD) values in the healthy children and patients with CF for J(NO,max'), D(NO,air'), C(alv,ss'), and C(tiss,air'), respectively: 784 +/- 465 and 607 +/- 648 pl s(-1); 4.82 +/- 3.07 and 17.6 +/- 12.1 pl s(-1) ppb(-1); 4.63 +/- 3.59 and 1.96 +/- 1.18 ppb; and 198 +/- 131 and 38 +/- 25 ppb. D(NO,air) is elevated (p = 0.007), and both C(alv,ss) and C(tiss,air) are reduced (p = 0.05 and 0.002, respectively) in CF. In contrast, C(NO,plat) for healthy control subjects and patients with CF are not statistically different at both exhalation flow rates of 50 ml/s (17.5 +/- 11.5 and 11.5 +/- 8.97) and at 250 ml/s (7.11 +/- 5.36 and 4.28 +/- 3.43). We conclude that D(NO,air'), C(tiss,air'), and C(alv,ss) may be useful noninvasive markers of CF.

Adolescent↗