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G G King

Publications and source records attributed to G G King.

At least 19 recordsLinked to original sources
PubMed2006

Airway dimensions measured from micro-computed tomography and high-resolution computed tomography.

Volume averaging results in both over- and underestimation of airway dimensions when they are measured by high-resolution computed tomography (HRCT). The current authors calibrated computerised measurements of airway dimensions from HRCT against a novel three-dimensional micro-computed tomography (CT) standard, which has a 50-fold greater resolution, as well as against traditional morphometry. Inflation-fixed porcine lung cubes were scanned by HRCT and micro-CT. A total of 59 lumen area (Ai), 30 wall area (A(aw)) and 11 lumen volume (Vi) measurements were made. Ai was measured from the cut surface of 11 airways by morphometry. Airways in scanned images were matched using branching points. After calibration, the errors of Ai, A(aw) and Vi HRCT measurements were determined. The current authors found a systematic, size-dependent underestimation of Ai and overestimation of A(aw) from HRCT measurements. This was used to calibrate an HRCT measurement algorithm. The 95% limits of agreement of subsequent measurements were +/-3.2 mm2 for Ai, +/-4.3 mm2 for A(aw), and +/-11.2 mm3 for Vi with no systematic error. Morphometric measurements agreed with micro-CT (+/-2.5 mm2) without systematic error. In conclusion, micro-computed tomography image data from inflation-fixed airways can be used as calibration standards for three-dimensional lumen volume measurements from high-resolution computed tomography, while morphometry is acceptable for two-dimensional measurements. The image dataset could be used to validate other developmental three-dimensional segmentation algorithms.

Animals↗
PubMed2005

The effects of body weight on airway calibre.

Increased wheeze and asthma diagnosis in obesity may be due to reduced lung volume with subsequent airway narrowing. Asthma (wheeze and airway hyperresponsiveness), functional residual capacity (FRC) and airway conductance (Gaw) were measured in 276 randomly selected subjects aged 28-30 yrs. Data were initially adjusted for smoking and asthma before examining relationships between weight and FRC (after adjustment for height), and between body mass index (BMI = weight.height(-2)) and Gaw (after adjustment for FRC) by multiple linear regression, separately for females and males. For males and females, BMI (+/-95% confidence interval) was 27.0+/-4.6 kg.m(-2) and 25.6+/-6.0 kg.m(-2) respectively, Gaw was 0.64+/-0.04 L.s(-1).cmH2O(-1) and 0.57+/-0.03 L.s(-1).cmH2O(-1), and FRC was 85.3+/-3.4 and 84.0+/-2.9% of predicted. Weight correlated independently with FRC in males and females. BMI correlated independently and inversely with Gaw in males, but only weakly in females. In conclusion, obesity is associated with reduced lung volume, which is linked with airway narrowing. However, in males, airway narrowing is greater than that due to reduced lung volume alone. The mechanisms causing airway narrowing and sex differences in obesity are unknown.

Adult↗
PubMed2004

Heterogeneity of narrowing in normal and asthmatic airways measured by HRCT.

Asthmatic airway narrowing is heterogeneous and contributes to airway hyperresponsiveness. The present study compared heterogeneity of narrowing during methacholine challenge in asthmatics and normal subjects using high-resolution computed tomography (HRCT). The current authors defined heterogeneity as variability in narrowing greater than the repeatability of measurement. Airways of <2 mm diameter were compared with larger airways from baseline and postmethacholine HRCT of the right lower lung in 13 normals (seven had repeat baseline scans) and seven asthmatics. The coefficient of repeatability was calculated from repeat scans (RepAi) and was compared with heterogeneity of narrowing measured by the variability in narrowing from pre versus postmethacholine scans (VardeltaAi). Forced expiratory volume in one second decreased 27+/-6% and 24+/-8% in normals and asthmatics, respectively. Airways >2 mm narrowed more heterogeneously in asthmatics (VardeltaAi=+/-0.85 mm) compared with normals (VardeltaAi=+/-0.67 mm), with both being greater than the measure of repeatability (RepAi=+/-0.16 mm). Small airway narrowing was not heterogeneous in asthmatics (VardeltaAi=+/-0.59 mm) or normals (VardeltaAi=+/-0.53 mm) compared with repeatability (RepAi=0.51 mm). It is possible to study heterogeneity of airway narrowing in small and large airways using high resolution computed tomography. Airway narrowing is heterogeneous in the large airways of asthmatics and normals, being greater in asthmatics.

Adult↗
PubMed2003

Self-organization in a multicore fiber laser array.

We explain an observed spontaneous transition to the high-brightness, in-phase array state of a seven-core ytterbium-doped fiber laser array [IEEE Photonics Technol. Lett. 13, 439 (2001)]. The responsible mechanism is nonlinear refraction, and either in-phase or antiphase array modes can be selected by control of pump intensity. The phenomenon appears to be robust and scalable.

Journal Article↗
PubMed2003

Airway re-narrowing following deep inspiration in asthmatic and nonasthmatic subjects.

After bronchoconstriction, deep inspiration (DI) causes dilatation followed by airway re-narrowing. Re-narrowing may be faster in asthmatic than nonasthmatic subjects. This study investigated the relationship between re-narrowing and the magnitude of both DI-induced dilatation and the volume-dependence of respiratory system resistance (Rrs) during tidal breathing. In 25 asthmatic and 18 nonasthmatic subjects the forced oscillation technique was used to measure Rrs at baseline and after methacholine challenge, during 1 min of tidal breathing, followed by DI to total lung capacity (TLC) and passive return to functional residual capacity (FRC). Dilatation was measured as the decrease in Rrs between end tidal inspiration and TLC, re-narrowing as Rrs at FRC immediately after DI, as per cent Rrs at end-tidal expiration, and volume dependent tidal fluctuation as the difference between mean Rrs at end-expiration and end-inspiration. Asthmatic subjects had greater re-narrowing, less dilatation, and greater tidal fluctuations both at baseline and after challenge. Re-narrowing correlated with baseline tidal fluctuation and inversely with dilatation. Both baseline tidal fluctuation and dilatation were significant independent predictors of re-narrowing. Following deep inspiration-induced dilatation, faster airway re-narrowing in asthmatic than nonasthmatic subjects is associated not only with reduced deep inspiration-induced dilatation but also with some property of the airways that is detectable prior to challenge as an increased volume dependence of resistance.

Adult↗
PubMed2001

Airway narrowing associated with inhibition of deep inspiration during methacholine inhalation in asthmatics.

Reduced bronchodilatation in response to deep inspiration (DI) has been demonstrated in asthmatics. We have previously shown that inhibition of DI for 10 min or more during methacholine inhalation increases airway narrowing in normals. We tested the hypothesis that inhibition of DIs during methacholine inhalation in asthmatics would not affect the magnitude of airway narrowing. We administered the PC(15) dose of methacholine to eight asthmatics every 5 min for 5 doses and measured spirometry after each dose. On four separate days, subjects received either 2, 3, 4, or 5 doses selected randomly, but DIs were inhibited during the challenge and spirometry was measured only at the start and after the final dose. Geometric mean PC(15) was 1.6 mg/ml. Mean values for FEV(1) (+/- SEM) after Doses 2 through 5 were 84 +/- 4, 78 +/- 6, 79 +/- 5, and 81 +/- 3% of baseline, respectively, when DIs were allowed. During inhibition of DIs, they were 73 +/- 6, 67 +/- 5, 64 +/- 6, and 61 +/- 7% of baseline values. Decreases in FEV(1) after Doses 4 and 5 were significantly greater when DIs were inhibited (p < 0.05). We conclude that in this group of asthmatics, inhibition of DI for 15 min is associated with increased airway narrowing in response to methacholine inhalation, and therefore, DI may be an important factor limiting induced airway narrowing in asthmatics as well as in normal subjects.

Administration, Inhalation↗
PubMed2001

Pulmonary embolism: comparison of gadolinium-enhanced MR angiography with contrast-enhanced spiral CT in a porcine model.

RATIONALE AND OBJECTIVES: The purpose of this study was to compare gadolinium-enhanced magnetic resonance (MR) angiography with contrast material-enhanced computed tomography (CT) for the detection of small (4-5-mm) pulmonary emboli (PE), with a methacrylate cast of the porcine pulmonary vasculature used as the diagnostic standard. MATERIALS AND METHODS: In 15 anesthetized juvenile pigs, colored methacrylate beads (5.2 and 3.8 mm diameter-the size of segmental and subsegmental emboli in humans) were injected via the left external jugular vein. After embolization, MR angiographic and CT images were obtained. The pigs were killed, and the pulmonary arterial tree was cast in clear methacrylate, allowing direct visualization of emboli. Three readers reviewed CT and MR angiographic images independently and in random order. RESULTS: Forty-nine separate embolic sites were included in the statistical analysis. The mean sensitivity (and 95% confidence intervals) for CT and MR angiography, respectively, were 76% (68%-82%) and 82% (75%-88%) (P > .05); the mean positive predictive values, 92% (85%-96%) and 94% (88%-97%) (P > .05). In this porcine model, PE were usually seen as parenchymal perfusion defects (98%) with MR angiography and as occlusive emboli (100%) with CT. CONCLUSION: MR angiography is as sensitive as CT for the detection of small PE in a porcine model.

Animals↗
PubMed2001

Fexofenadine decreases sensitivity to and montelukast improves recovery from inhaled mannitol.

We studied, separately, the effects of the histamine antagonist, fexofenadine hydrochloride, and the leukotriene antagonist, montelukast sodium, and their placebos on airway sensitivity to and recovery from inhaled mannitol in subjects with asthma. Two 180-mg doses of fexofenadine were taken over 14 h, and three 10-mg doses of montelukast over 36 h, with the last dose 5 h before challenge. Fexofenadine reduced sensitivity to mannitol and the PD(15) was (mean [95% confidence interval] 138 [95, 201]) mg versus placebo (51 [25, 106] mg) (p < 0.001). The final percent reduction in FEV(1) with fexofenadine was 20.8 +/- 5.4% and not different from placebo (20.1 +/- 5.3%) (p = 0.7); however, recovery was slower with fexofenadine compared with placebo (p < 0.001). By contrast, montelukast had no effect on sensitivity to mannitol and the PD(15) was 71 [36, 144] mg versus placebo (87 [51, 148] mg (p = 0.35). The total dose of mannitol delivered and the final percent reduction in FEV(1) with montelukast were 171 +/- 142 mg and 21 +/- 4% and for placebo were 182 +/- 144 mg and 20 +/- 5% (p = 0.35, p = 0.59, respectively). However, recovery of FEV(1) to baseline was faster with montelukast, with the area under the percent reduction FEV(1)-versus-time curve reduced (220 +/- 121% change.min) compared with placebo (513 +/- 182% change.min) (p < 0.001). We conclude that whereas histamine is important for the initial airway response, leukotrienes are important in sustaining the airway response to inhaled mannitol.

Acetates↗
PubMed2000

An analysis algorithm for measuring airway lumen and wall areas from high-resolution computed tomographic data.

High-resolution computed tomography (HRCT) has been used to examine airway narrowing. We developed an automated computed tomographic image analysis algorithm (computed tomographic airway morphometry; CTAM) to measure airway lumen area (Ai ), airway wall area (Awa), and airway angle of orientation. Tubes of varying size were embedded in Styrofoam and then scanned at angles between 0 degrees and 50 degrees to assess the accuracy of measurements made with CTAM. Two excised pig lungs were fixed in inflation, sectioned, and scanned. Ai and Awa were measured planimetrically from the cut surfaces to optimize CTAM measurement parameters. In CTAM, Ai was defined according to an airway-size-dependent threshold value, and total Awa was determined through a score-guided erosion method. Results were compared with measurements made through a previously validated method (manual method). CTAM provided accurate measurements of the tubes' Ai values at all angles; Awa was overestimated in direct relation to airway size. The manual method underestimated Ai and overestimated Awa in a manner directly related to airway size as well as to airway angle of orientation. In the excised lung, the mean errors of Ai and Awa measurements made with CTAM were 0.52 +/- 0.24 mm(2) and 0.17 +/- 0.32 mm(2) (mean +/- SEM), respectively. Ai errors with the manual method were similar, but Awa was overestimated to a greater degree (6.3 +/- 0.38 mm(2); p < 0.01) and the error was proportional to Awa (r = 0.64; p < 0.01). CTAM allows accurate measurements of airway dimensions and angle of orientation.

Airway Resistance↗
PubMed2000

Spiral computed tomography is comparable to angiography for the diagnosis of pulmonary embolism.

The use of spiral computed tomography (CT) for the diagnosis of pulmonary embolism has been compared to angiography, the current gold standard. However, the accuracy of pulmonary angiography has never been evaluated against an independent gold standard. The aim of this study was to compare contrast-enhanced spiral CT to pulmonary angiography for the detection of subsegmental-sized pulmonary emboli by using a methacrylate cast of porcine pulmonary vessels as an independent gold standard. We studied 16 anesthetized, juvenile pigs and injected colored methacrylate beads (3.8 mm, small; 4.2 mm, large) via the jugular vein. After embolization spiral CT (3 mm and 1 mm collimation), and pulmonary angiography were performed. Pigs were killed and the pulmonary arterial tree was cast using methacrylate. Spiral CT and angiography were interpreted independently by two radiologists. Sensitivity and 95% confidence intervals for 3 mm and 1 mm collimation CT and angiography, respectively, were: 82% (73 to 88%), 87% (79 to 93%), 87% (79 to 93%) (p = 0.42). Positive predictive values and 95% confidence intervals for 3 mm and 1 mm collimation CT and angiography, respectively, were: 94% (86 to 94%), 81% (73 to 88%), and 88% (80 to 93%). There was no difference between spiral CT and angiography for detection of subsegmental-sized pulmonary emboli. We conclude that spiral CT is comparable to angiography for detection of pulmonary emboli.

Angiography, Digital Subtraction↗
PubMed1999

The mechanics of exaggerated airway narrowing in asthma: the role of smooth muscle.

Although non-specific bronchial hyperresponsiveness (NSBH) is a basic mechanism underlying the excessive, labile airway narrowing which is characteristic of asthma, its mechanism remains unknown. It is still unclear if the phenomenon is due to fundamental changes in the phenotype of the smooth muscle or is caused by structural and/or mechanical changes in the non-contractile elements of the airway wall or by alterations in the relationship of the airway wall to the surrounding lung parenchyma. Although airway wall remodeling may contribute to NSBH there is increasing evidence that the bronchodilating response to cyclic and periodic stretch is impaired in asthma. There are at least two different mechanisms by which periodic length and force oscillations could influence airway smooth muscle shortening and airway narrowing. These processes which have been called 'perturbed equilibrium of myosin binding' and 'plasticity' have different biochemical and mechanical mechanisms and consequences. They have the potential to interact and to have a fundamental effect on the shortening capacity of airway smooth muscle and its ultimate ability to cause excessive airway narrowing.

Animals↗
PubMed1999

Perception of bronchodilation in subjects with asthma and smokers with airflow limitation.

Perception of the efficacy of bronchodilators in relieving airflow obstruction is a likely determinant of compliance with treatment in patients prescribed these drugs on an 'as needed' basis. This study aimed to determine whether bronchodilator-induced improvements in lung function are associated with improvements in breathing difficulty in subjects with asthma or smokers with airflow limitation. Twenty smokers with airflow limitation and 16 subjects with previously physician-diagnosed asthma received salbutamol (200 micrograms) and ipratropium bromide (80 micrograms). Spirometry and lung volumes were measured before and 40 min after bronchodilator. Subjects recorded changes in 'difficult breathing' on a visual analogue scale (VAS). After bronchodilator, forced expiratory volume in 1 s (FEV1) increased by 23.0 +/- 6.4% of baseline (mean +/- 95% CI) in smokers, and by 25.2 +/- 8.5% in the asthmatics, while VAS improved by 31 +/- 23% in smokers and 45 +/- 25% in asthmatics. However, these changes were not significantly correlated in either smokers (r = -0.04) or asthmatics (r = 0.15). In the asthmatic subjects, good perceivers (> 25% improvement in VAS) had greater improvements in lung volumes, as percentage predicted, than did poor perceivers. In the smokers, changes in lung function did not differ significantly between good and poor perceivers. Improvement in FEV1, as percentage predicted, was significantly correlated with improvement in VAS in good perceivers (asthma: r = 0.78, P < 0.01; smokers: r = 0.68, P < 0.05), but not in poor perceivers. Asthmatic subjects had good perception of improvements in lung function. However, in smokers with airflow limitation there is little correlation between improvement in lung function and sensation of breathing difficulty. In these subjects symptoms appear to be an unreliable guide for 'as needed' use of bronchodilators.

Aged↗
PubMed1999

Do subjects with asthma have greater perception of acute bronchoconstriction than smokers with airflow limitation?

OBJECTIVE: Smokers who develop chronic airflow limitation (CAL) do not usually present for medical attention until their lung disease is well advanced. In contrast, asthmatic subjects experience acute symptoms and present for care early in the course of their disease. The aim of this study was to determine whether subjects with asthma differ from smokers with CAL in their ability to perceive acute methacholine-induced bronchoconstriction. METHODOLOGY: Thirteen subjects with diagnosed asthma and 10 current smokers with CAL, defined as forced expiratory volume in 1 s (FEV1) < 75% predicted and FEV1/forced vital capacity < 80%, with no previous diagnosis of asthma, were challenged with methacholine. Symptom severity was recorded on a Borg scale. Lung volumes were measured before challenge and after the FEV1 had fallen by 20%. RESULTS: After methacholine falls in FEV1 were similar in the asthmatic subjects and smokers. The regression lines relating change in FEV1 to symptom score were significantly steeper in asthmatic subjects than smokers (0.13 +/- 0.04, 0.03 +/- 0.04, respectively, P < 0.01). At 20% fall in FEV1 there were no significant differences between asthmatic subjects and smokers in the magnitude of change of lung volumes. CONCLUSIONS: In asthmatic subjects, symptoms are closely related to change in FEV1. In smokers with CAL, symptoms change little during bronchial challenge despite large changes in FEV1. The differences in perception between the two subject groups are not due to differences in acute hyperinflation during challenge. We propose that heavy smokers may adapt to poor lung function, or may have damaged sensory nerves as a result of prolonged cigarette smoking.

Aged↗
PubMed1999

Time course of increased airway narrowing caused by inhibition of deep inspiration during methacholine challenge.

Inhibition of deep inspiration (DI) enhances methacholine-induced airway narrowing in normal subjects. However, the time course over which excessive airway narrowing develops during inhibition of DI is not known. We hypothesized that the development of enhanced airway narrowing when DI is inhibited is time dependent. Ten normal volunteers (five males and five females) inhaled five doses of methacholine (16 mg/ml for 2 min) at 5-min intervals during an initial methacholine challenge. FEV(1) was measured at baseline and after each dose. On four subsequent days, the subjects again inhaled two, three, four, or five doses, in random order, without DIs during the challenge. FEV(1) was measured only at baseline and after the last dose. Baseline FEV(1) was normal in all subjects. The maximal mean percent decrease in FEV(1) after the initial challenge was 10 +/- 1.5%, but was 28 +/- 6.0% when DIs were inhibited throughout the five inhalations (p < 0.01). The difference in decrease in FEV(1) between days with and without DI became significant after 10 min (three doses), and remained stable thereafter when the response plateaued. The reversal of airway narrowing after three DIs was incomplete after 15 min (four doses). In conclusion, the increased airway narrowing associated with inhibition of DI during airway smooth-muscle contraction occurs after 10 min in normal subjects, at which time the response plateaus. However, the ability of DI to reverse airway narrowing appears to diminish progressively.

Adult↗
PubMed1998

Mechanism of methacholine dose-response plateaus in normal subjects.

Normal subjects develop plateaus on dose-response curves produced from inhalation challenge tests with bronchoconstricting agonists. These plateaus occur after only mild degrees of airway narrowing despite the fact that, if unloaded, maximally activated airway smooth muscle (ASM) should be able to cause airway closure. Plateaus may develop because, despite maximal activation, the muscle load provided by lung parenchymal recoil and tidal swings in airway transmural pressure are sufficient to prevent further ASM shortening. Alternatively, progressive ASM activation may occur throughout the plateau, but progressive hyperinflation and/or parenchymal stiffening could increase parenchymal load and attenuate further airway narrowing. In the first case, maximal ASM activation causes the plateau and in the second case the plateau is caused by progressive activation balanced by progressive loading. To test which of these mechanisms is responsible for the plateau, we measured pulmonary resistance (RL) and the maximal, minimal, and mean pulmonary elastic recoil pressure (PELmax, PELmin, and PELmean) during tidal breathing throughout methacholine challenge in 10 normal subjects. PELmean served as our measure of ASM afterload. Subjects swallowed an esophageal balloon and inhaled doubling concentrations of methacholine (1 to 256 mg/ml). RL was measured after each dose, as was PEL. All subjects developed a plateau on the dose-response curve defined by < 25% change in RL over three successive doses. During the RL plateau, there was no significant further increase in PELmean, i.e., PELmean also plateaued. These data are consistent with the hypothesis that maximal activation of ASM is balanced by an equal afterload at the maximal dose-response plateau. Airway hyperresponsiveness could result from a failure of afterload to attenuate muscle shortening after maximal activation.

Adult↗
PubMed1998

Differences in airway closure between normal and asthmatic subjects measured with single-photon emission computed tomography and technegas.

The absence of a maximal dose-response plateau as well as gas trapping and increases in closing capacity (CC) suggest that increased airway closure is an important mechanical abnormality of asthmatic airways. We compared the extent and distribution of airway closure in 13 normal and in 23 asthmatic subjects. Airway closure (LVclosed) was measured with single-photon emission computed tomography (SPECT) and an inhaled Technegas bolus as the percentage of lung volume without Technegas (LVtrans), and with CC, using nitrogen washout. LVclosed was compared in the apical, middle and lower zones, each being of equal vertical height. Values of mean LVclosed +/- 95% confidence interval (CI) were similar in normal (30 +/- 6.0% LVtrans) and asthmatic subjects (30 +/- 7.8% LVtrans). In normal subjects, LVclosed correlated with both age (r = 0.89, p < 0. 01) and CC (r = 0.86, p < 0.01), was more extensive in the lower zone (58 +/- 18.8% LVtrans, p < 0.01) than in the middle and upper zones (17 +/- 8.7% and 26 +/- 8.2 LVtrans, respectively), and increased with age in both the middle and lower zones (r = 0.94 and r = 0.90, respectively, p < 0.01). In asthmatic subjects, LVclosed did not correlate with age; was greatest in the lower zone, intermediate in the middle zone, and lowest in the apical zone (59 +/- 13.2%, 22 +/- 5.8%, and 12 +/- 4.4% LVtrans, respectively, p < 0. 01); and correlated weakly with age in the middle zone only (r = 0. 46, p < 0.05). We conclude that there is a predictable pattern of airway closure in normal subjects and that it is primarily influenced by pulmonary elastic recoil. This pattern is lost in asthmatic subjects. This may be explained by an increased range of closing pressures and a patchy distribution of airway closure, probably secondary to allergic inflammation.

Administration, Inhalation↗