Bronchial Cross-sectional Area Research Articles

Thoracic Morphology and Bronchial Narrowing Are Related to Pulmonary Function in Adolescent Idiopathic Scoliosis.

In adolescent idiopathic scoliosis (AIS), lung function impairment is not necessarily related to the coronal spinal deformity. Recently, right-sided bronchial narrowing has been reported in thoracic AIS. The aim of this study was to describe the relation of chest and spinal deformity parameters, bronchial narrowing, and lung volumes with pulmonary function in preoperative AIS. Spinal radiographs, low-dose computed tomographic (CT) scans of the spine including the chest, and pulmonary function tests were retrospectively collected for 85 preoperative patients with thoracic AIS in 2 centers and were compared with 14 matched controls. Three-dimensional lung and airway reconstructions were acquired. Correlation analysis was performed in which radiographic spinal parameters, CT-based thoracic deformity parameters (rib-hump index [RHi], spinal penetration index, endothoracic hump ratio, hemithoracic-width ratio), lung volume asymmetry, and bronchial cross-sectional area were compared with percent-of-predicted spirometry results. Forty-one patients (48%) had a percent-of-predicted forced expiratory volume in 1 second (FEV1%) or percent-of-predicted forced vital capacity (FVC%) of <65%, and 17 patients (20%) had obstructive lung disease. All thoracic deformity parameters correlated significantly with FEV1% and FVC%; RHi was found to be the best correlate (rs = -0.52 for FEV1% and -0.54 for FVC%). Patients with AIS with impaired pulmonary function had hypokyphosis, a larger rib hump, increased spinal and thoracic rotation, a narrower right hemithorax, and increased intrusion of the spine into the chest. Spinal intrusion correlated with right-sided bronchial narrowing, relative right lung volume loss, and decreased FEV1% and FVC%. Multivariate regression including spinal and thoracic deformity parameters, lung volume asymmetry, and airway parameters could explain 57% of the variance in FEV1% and 54% of the variance in FVC%. Chest intrusion by the endothoracic hump is related to right-sided bronchial narrowing and lung function loss in preoperative AIS. The findings support the theory that ventilatory dysfunction in thoracic AIS is not only restrictive but frequently has an obstructive component, especially in patients with hypokyphosis. RHi is the most predictive chest parameter for lung function loss. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Segmental bronchi collapsibility: computed tomography-based quantification in patients with chronic obstructive pulmonary disease and correlation with emphysema phenotype, corresponding lung volume changes and clinical parameters.

Global pulmonary function tests lack region specific differentiation that might influence therapy in severe chronic obstructive pulmonary disease (COPD) patients. Therefore, the aim of this work was to assess the degree of expiratory 3rd generation bronchial lumen collapsibility in patients with severe COPD using chest-computed tomography (CT), to evaluate emphysema-phenotype, lobar volumes and correlate results with pulmonary function tests. Thin-slice chest-CTs acquired at end-inspiration & end-expiration in 42 COPD GOLD IV patients (19 females, median-age: 65.9 y) from November 2011 to July 2014 were re-evaluated. The cross-sectional area of all segmental bronchi was measured 5 mm below the bronchial origin in both examinations. Lung lobes were semi-automatically segmented, volumes calculated at end-inspiratory and end-expiratory phase and visually defined emphysema-phenotypes defined. Results of CT densitometry were compared with lung functional tests including forced expiratory volume at 1 s (FEV1), total lung capacity (TLC), vital capacity (VC), residual volume (RV), diffusion capacity parameters and the maximal expiratory flow rates (MEFs). Mean expiratory bronchial collapse was 31%, stronger in lobes with homogenous (38.5%) vs. heterogeneous emphysema-phenotype (27.8%, P=0.014). The mean lobar expiratory volume reduction was comparable in both emphysema-phenotypes (volume reduction 18.6%±8.3% in homogenous vs. 17.6%±16.5% in heterogeneous phenotype). The degree of bronchial lumen collapsibility, did not correlate with expiratory volume reduction. MEF25 correlated weakly with 3rd generation airway collapsibility (r=0.339, P=0.03). All patients showed a concentric expiratory reduction of bronchial cross-sectional area. Changes in collapsibility of 3rd generation bronchi in COPD grade IV patients is significantly lower than that in the trachea and the main bronchi. Collapsibility did not correlate with the reduction in lung volume but was significantly higher in lobes with homogeneous vs. heterogeneous emphysema phenotype. Changes in the 3rd generation bronchial calibres between inspiration and expiration are not predictive for the degree of small airway collapsibility and related airflow limitation.

Impact of endobronchial coiling on segmental bronchial lumen in treated and untreated lung lobes: Correlation with changes in lung volume, clinical and pulmonary function tests.

To assess the impact of endobronchial coiling on the segment bronchus cross-sectional area and volumes in patients with lung emphysema using quantitative chest-CT measurements. Thirty patients (female = 15; median age = 65.36years) received chest-CT before and after endobronchial coiling for lung volume reduction (LVR) between January 2010 and December 2014. Thin-slice (0.6mm) non-enhanced image data sets were acquired both at end-inspiration and end-expiration using helical technique and 120kV/100-150 mAs. Clinical response was defined as an increase in the walking distance (Six-minute walk test; 6MWT) after LVR-therapy. Additionally, pulmonary function test (PFT) measurements were used for clinical correlation. In the treated segmental bronchia, the cross-sectional lumen area showed significant reduction (p < 0.05) in inspiration and tendency towards enlargement in expiration (p > 0.05). In the ipsilateral lobes, the lumina showed no significant changes. In the contralateral lung, we found tendency towards increased cross-sectional area in inspiration (p = 0.06). Volumes of the treated segments correlated with the treated segmental bronchial lumina in expiration (r = 0.80, p < 0.001). Clinical correlation with changes in 6MWT/PFT showed a significant decrease of the inspiratory volume of the treated lobe in responders only. Endobronchial coiling causes significant decrease in the cross-sectional area of treated segment bronchi in inspiration and a slight increase in expiration accompanied by a volume reduction. • Endobronchial coiling has indirect impact on cross-sectional area of treated segment bronchi • Volume changes of treated lobes correlate with changes in bronchial cross-sectional area • Coil-induced effects reflect their stabilizing and stiffening impact on lung parenchyma • Endobronchial coiling reduces bronchial collapsing compensating the loss of elasticity.

Computed tomographic measures of airway morphology in smokers and never-smoking normals

Bronchial wall area percent (WA% = 100 × wall area/total bronchial cross sectional area) is a standard computed tomographic (CT) measure of central airway morphology utilized in smokers with chronic obstructive pulmonary disease (COPD). Although it provides significant clinical correlations, the range of reported WA% is narrow. This suggests limited macroscopic change in response to smoking or that remodeling proportionally affects the airway wall and lumen dimensions such that their ratio is preserved. The objective of this study is to assess central airway wall area (WA), lumen area (Ai), and total bronchial area (Ao) from CT scans of 5,179 smokers and 92 never smoking normal subjects. In smokers, WA, Ai, and Ao were positively correlated with forced expiratory volume in 1 s (FEV1) expressed as a percent of predicted (FEV1%), and the WA% was negatively correlated with FEV1% (P < 0.0001 for all comparisons). Importantly, smokers with lower FEV1% tended to have airways of smaller cross-sectional area with lower WA. The increases in the WA% across GOLD stages of chronic obstructive pulmonary disease (COPD) can therefore not be due to increases in WA. The data suggest two possible origins for the WA% increases: 1) central airway remodeling resulting in overall reductions in airway caliber in excess of the decreased WA or 2) those with COPD had smaller native airways before they began smoking. In both cases, these observations provide an explanation for the limited range of values of WA% across stages of COPD.

Multidetector-row Computed Tomography Evaluation of Bilateral Bronchial Narrowing Associated with Increased Pulmonary Blood Flow in Children with Congenital Heart Disease

Quantitative assessment of bilateral bronchial narrowing in children with congenital heart disease (CHD) with a left-to-right shunt has not yet been reported. In the present study, main bronchial size was evaluated bilaterally in normal subjects using multidetector-row computed tomography (MDCT), and the feasibility for diagnosis of bronchial narrowing in children with CHD associated with increased pulmonary blood flow was investigated. The short-axis diameter, long-axis diameter, and the cross-sectional area of the bilateral bronchi were measured immediately proximal to the origin of the superior lobar branch in 86 children aged 1-52 months. Subjects were divided into three groups as follows: group 1 (normal subjects; n = 52), group 2 (asymptomatic left-to-right shunt group; n = 25), and group 3 (symptomatic left-to-right shunt group with respiratory insufficiency; n = 9). Age, height, weight, and body surface area were significantly correlated with short- and long-axis bronchial diameters, and bronchial cross-sectional area in group 1. In group 2, the left bronchial cross-sectional area was significantly lower than group 1 (P < .001), whereas the right bronchial area was not significantly different. In group 3, the right bronchial area was significantly lower than that in groups 1 and 2 (P < .05). Although the left bronchial area in group 3 was significantly lower than in group 1 (P < .001), it was not significantly different from that in group 2. Our study suggests that MDCT can be used to quantify bilateral bronchial narrowing. Left main bronchial obstruction develops during the early stage of heart failure, followed by the development of right bronchial narrowing.

Bronchial Measurements in Patients with Asthma: Comparison of Quantitative Thin-Section CT Findings with Those in Healthy Subjects and Correlation with Pathologic Findings

To analyze and compare computed tomographic (CT) bronchial measurements in patients with asthma and healthy subjects and to correlate bronchial morphometric parameters with functional data and immunohistologic markers of airway remodeling and inflammation. This retrospective study was approved by the institutional review board; patient informed consent was not required. CT and pulmonary function tests were performed in 27 patients separated into two groups: 15 patients with asthma (three men; mean age, 43.1 years +/- 5.3 [standard error of mean]) and 12 healthy subjects (10 men; mean age, 45.0 years +/- 5.4). Endobronchial biopsies were performed in 11 subjects. Bronchial cross-sectional wall area (WA) and lumen area (LA) were measured by using validated software, and wall thickness (WT), total area (TA), WA/LA ratio, and WA/TA ratio were computed. Slope and maximal local slope of each parameter along bronchial generations were calculated. Patients with asthma demonstrated significantly lower LA, TA, and WA and higher WA/LA and WA/TA ratios than healthy subjects downward from the fourth bronchial generation. Correlations existed between slope and maximal local slope of WA/LA and/or WA/TA ratios and functional data reflecting bronchial obstruction (r = 0.46-0.58, P = .001-.025), subepithelial membrane thickness (r = 0.67-0.69, P = .019-.023), smooth muscle layer area (r = 0.75, P = .007), subepithelial layer area (r = 0.81, P = .002), and infiltration of the bronchial wall by inflammatory cells (r = 0.67-0.86, P = .049-.003). Axial reconstructions with orthogonal measurements along the airways enabled by three-dimensional segmentation methods are able to demonstrate significant changes in bronchial morphometry, predicting airflow limitation in asthma, and may have a role in the noninvasive measurement of airway remodeling.

Bronchial Measurement with Three-dimensional Quantitative Thin-Section CT in Patients with Cystic Fibrosis

To prospectively compare bronchial measurements obtained with three-dimensional quantitative thin-section computed tomography (CT) with those obtained with thin-section CT scores in the assessment of the severity of pulmonary cystic fibrosis (CF). Ethics committee approval was obtained. Sixteen patients with CF (mean age, 26.6 years; range, 18-42 years) and five healthy volunteers (mean age, 27.4 years; range, 21-44 years) gave written informed consent, underwent multi-detector row CT and a pulmonary function test (PFT), and were divided into three groups: group A, healthy volunteers; group B, patients with mild CF (forced expiratory volume in 1 second [FEV(1)] > 80%); and group C, patients with severe CF (FEV(1) < 80%). Two observers obtained thin-section CT scores with eight scoring systems. Bronchial cross-sectional wall area (WA), lumen area (LA), airway area, and wall thickness (WT) were measured with customized software and were normalized on the basis of subject body surface. Morphologic characteristics, PFT results, thin-section CT scores, and quantitative measurements were compared among the three groups with analysis of variance. Correlations among bronchial measurements, PFT results, and CT scores were calculated with the Spearman correlation coefficient. Thin-section CT scores were different between group C and either group A or group B (P < .05). WA and WT were significantly different among all groups (P < .05). Interscore correlations and correlations between bronchial parameters and scores were high (r > 0.89, P < .0001). Scores, WA, and WT were significantly correlated with PFT obstructive indexes (P < .047). WA and WT assessed with dedicated software on multi-detector row CT images allow evaluation of the severity of pulmonary CF.

Bronchial reactivity in hyperresponsive patients and healthy individuals: demonstration with high resolution computed tomography

Objective: High resolution computed tomography (HRCT) was used to assess the extent of bronchial reactivity after inhalative bronchoprovocation and dilation in hyperresponsive patients and healthy subjects. Patients and methods: Patients with mild intermittent asthma, 15 with a >20% decrease in FEV 1 and a >10 mmHg (PC 20+) in PaO 2, 12 with a <20% decrease in FEV 1 and a >10 mmHg (PC 20−) in PaO 2 after provocation, and eight healthy humans were included in the study. Changes in cross-sectional area in a total of 1256 bronchi and in bronchial wall area (792 bronchi) were evaluated after histamine-triggered bronchoprovocation and salbutamol-induced bronchodilation at high lung volumes (FVC 80%). Data were compared with the results of pulmonary function tests (FEV 1, PaO 2, PaCO 2). Results: In all groups, a significant decrease in bronchial cross-sectional area ( P<0.001) and a significant increase in bronchial wall area ( P<0.001) were observed subsequent to bronchoprovocation. After bronchodilation, the increase in cross-sectional area ( P<0.001) and the further increase in airway wall area ( P<0.01) were significant in all groups. In PC 20+ and PC 20− asthmatics, significant differences ( P<0.05) in PaO 2, >10 mmHg between baseline and provocation were observed. In healthy persons, the PaO 2 decrease was <10 mmHg ( P>0.05). After histamine provocation, the decrease in FEV 1 was measured in the PC 20+ group, whereas a <20% FEV 1 decrease was found in the PC 20− and the control groups, respectively. No significant correlations were observed between radiological data and the results of pulmonary function tests. Conclusions: HRCT demonstrated bronchial reactivity in hyperresponsive patients and, unexpectedly, in healthy subjects. The applied pulmonary function tests failed to characterize bronchial reactions in the healthy subjects. Based on these results, HRCT is a useful tool by which to achieve a comprehensive understanding of the pathophysiological processes in asthmatic patients.

Effects of propofol on bronchoconstriction and bradycardia induced by vagal nerve stimulation.

Vagolysis has been considered as a mechanism by which propofol produces bronchodilation. However, it has also been suggested that propofol-induced bradycardia may result from increased vagal tone. In this study, we have determined whether propofol has vagolytic effects on both the airway and cardiovascular system. Mongrel dogs were anesthetized with pentobarbital. Bronchoconstriction was assessed by measuring changes in a bronchial cross-sectional area (BCA) using a bronchoscopic method. Heart rate (HR) and direct arterial blood pressure were also monitored. Vagal nerve stimulation (VNS) was performed for 60 s to produce both bronchoconstriction and bradycardia. To determine the effect of propofol on VNS-induced bronchoconstriction and bradycardia (n = 7), 0 (saline), 2.0 and 20 mg/kg propofol were administered intravenously at 20-min intervals with VNS commenced 5 min later. In addition, to determine if propofol-induced bradycardia is due to a vagomimetic action, two groups of six dogs were given 20 mg/kg propofol with or without 0.2 mg/kg atropine pre-treatment. HR was measured before and 5 min after propofol. Propofol 20 mg/kg significantly inhibited VNS-induced bronchoconstriction. Although propofol per se significantly reduced HR (24%) and blood pressure (37%), the reduction in HR produced by VNS after 20 mg/kg propofol did not differ from that after saline or the lower dose of propofol (2 mg/kg). As atropine pre-treatment did not attenuate propofol-induced bradycardia, this response is unlikely to be simply due to vagomimetic actions. Propofol has vagolytic effects on the airway but does not worsen bradycardia produced by parasympathetic stimulation.

Differential effects of thiopental on methacholine- and serotonin-induced bronchoconstriction in dogs

Thiopental sometimes causes bronchospasm during induction of anaesthesia. In addition, we have reported previously that thiopental produced transient bronchospasm, which was blocked by atropine pretreatment, and worsened histamine-induced bronchoconstriction in dogs. Previous in vitro reports suggest that synthesis of contractile cyclooxygenase products, such as thromboxane A(2), may be involved in the mechanism of bronchospasm. However, the in vivo spastic effects have not been defined comprehensively. Twenty-seven mongrel dogs were anaesthetized with pentobarbital. Bronchoconstriction was elicited with methacholine (0.5 microg kg(-1)+5.0 microg kg(-1) min(-1); Mch group, n=7) or serotonin (10 microg kg(-1)+1 mg kg(-1) h(-1); 5HT group, n=20), and assessed as percentage changes in bronchial cross-sectional area (BCA, basal=100%) using a bronchoscope. In the 5HT group, dogs were subdivided into four groups of five each: S-5HT, I-5HT, 5HT-S and 5HT-A. In the S-5HT and I-5HT groups, 30 min before serotonin infusion dogs were given saline and indomethacin respectively at 5 mg kg(-1) i.v. In all groups, 30 min after bronchoconstrictor infusion started, dogs were given thiopental at doses between 0 (saline) and 20 mg kg(-1). In the 5HT-S and 5HT-A groups, dogs were given saline or atropine 0.2 mg kg(-1) i.v. 5 min after thiopental 20 mg kg(-1). Methacholine and serotonin reduced BCA by about 50 and 40% respectively. Thiopental 20 mg kg(-1) increased and decreased BCA by about 20 and 10% in the Mch and 5HT groups respectively. Indomethacin and atropine did not attenuate the potentiation of serotonin bronchoconstriction produced by thiopental. The present study indicates that thiopental may attenuate or worsen bronchoconstriction induced by muscarinic or serotonin receptor stimulation, respectively. The synthesis of contractile cyclooxygenase products and cholinergic stimulation may not be involved in the contractile effect of thiopental on serotonin bronchoconstriction.

Effects of three different L-type Ca2+entry blockers on airway constriction induced by muscarinic receptor stimulation

The crucial role of L-type Ca(2+) channels in airway smooth muscle contraction suggests that these channels could be an important therapeutic target. There are three separate drug binding sites on this channel: those for dihydropyridines, benzothiazepines and phenyl alkylamines. In this study, we examined the effects of the dihydropyridines nifedipine and nicardipine, the benzothiazepine diltiazem, and the phenylalkylamine verapamil on airway constriction. Tension of guinea-pig tracheal strips was measured isometrically in vitro with a force displacement transducer. Strips were precontracted with carbachol 10(-7) M with or without 4-aminopyridine 10(-3) M, a voltage-sensitive K(+ )channel blocker. Then, nifedipine 10(-8)-10(-4) M, diltiazem 10(-8)-3 x 10(-4) M or verapamil 10(-8)-3 x 10(-4) M was added cumulatively to the organ bath (n=6 each). The bronchial cross-sectional area of pentobarbital-anaesthetized dogs was assessed using a bronchoscopy method. Bronchoconstriction was elicited with methacholine 0.5 micro g kg(-1) plus 5 micro g kg(-1) min(-1), and then nicardipine 0-1000 micro g kg(-1), diltiazem 0-3000 micro g kg(-1) or verapamil 0-3000 micro g kg(-1) were given i.v. (n=7 each). In the in vitro experiments, nifedipine and diltiazem fully reversed carbachol-mediated tracheal contraction with logIC(50) values of 4.76 (SEM 0.22) (mean 17.5 micro M) and 4.60 (0.33) (mean 24.8 micro M), respectively. Although verapamil 10(-6)-10(-4) M reversed the contraction by 87.2%, strip tension re-increased by 18.1% following maximal relaxation with verapamil 3 x 10(-4 )M. This re-increase was almost fully abolished by pretreatment with 4-aminopyridine. In the in vivo experiments, nicardipine and diltiazem dose-dependently reversed methacholine-induced bronchoconstriction, with logID(50) values of 3.22 (0.05) (mean 0.60 mg kg(-1)) and 1.85 (0.32) (mean 14.0 mg kg(-1)), respectively. Verapamil worsened methacholine-induced bronchoconstriction. Although supraclinical doses of dihydropyridines and benzothiazepines can produce airway relaxant effects, these agents are unlikely to be used in the treatment of bronchoconstriction. In addition, verapamil may aggravate airway constriction.

Mild intermittent asthma: CT assessment of bronchial cross-sectional area and lung attenuation at controlled lung volume.

To evaluate, with thin-section computed tomography (CT), changes in bronchial cross-sectional area and lung attenuation induced by bronchial stimulation in patients with mild intermittent asthma, at a given lung volume monitored with pneumotachography. Twelve patients with mild intermittent asthma who were nonsmokers (National Institutes of Health staging) and six nonsmoking healthy volunteers, age and sex ratio-matched, were examined by using helical thin-collimation CT at the level of basal bronchi at 65% of total lung capacity. Three sets of acquisitions were obtained: at baseline and after inhalation of methacholine and then salbutamol. Cross-sectional areas of bronchi greater than 4 mm(2) were segmented and calculated from CT images. Lung attenuation was measured in the anterior, lateral, and posterior areas of the right lung parenchyma. Gas trapping was evaluated by using thin-section CT at residual volume in six of the patients with asthma. Statistical analysis included two factors repeated-measurement analysis of variance and Mann-Whitney and Kruskal-Wallis nonparametric tests. Bronchial cross-sectional areas and lung attenuation did not vary significantly compared with baseline values following bronchial challenge in healthy volunteers or patients with asthma. However, in patients with asthma, bronchial cross-sectional areas were significantly smaller than in healthy volunteers, except after inhalation of salbutamol. Lung attenuation and anteroposterior attenuation gradient were significantly higher in patients with asthma than in healthy patients (P <.001). Air-trapping scores were significantly higher after methacholine challenge. Helical thin-collimation CT at controlled lung volume and at full expiration associated with bronchial challenge may help evaluate bronchoreactivity and inflammation in mild intermittent asthma.

Spasmolytic effects of colforsin daropate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

We have previously found that agents increasing intracellular cAMP levels of smooth muscles, such as PDE3 inhibitors, aminophylline and prostaglandin E1, produce both bronchodilation and pulmonary vasodilation in serotonin-induced pulmonary hypertension and bronchoconstriction models. In the present study we have simultaneously evaluated the spasmolytic effects of colforsin daropate, a novel forskolin derivative, on serotonin-induced pulmonary hypertension and bronchoconstriction. Ten mongrel dogs were anesthetized with pentobarbital. The pulmonary hypertension and bronchoconstriction were elicited with serotonin (10 microg/kg + 1 mg x kg(-1) x h(-1)) and assessed as percentage changes in pulmonary vascular resistance (PVR) and bronchial cross-sectional area (BCA) (basal = 100%). Initially, the relaxant effects of colforsin daropate (0-300 microg/kg) were determined. The PVR and BCA were assessed before and 30 min after serotonin infusion began and 5 min after each dose of colforsin daropate. To determine whether colforsin daropate-induced relaxation is independent of plasma catecholamine, propranolol 0.4 mg/kg was given following colforsin daropate 300 microg/kg i.v. Colforsin daropate reversed both pulmonary hypertension and bronchoconstriction dose-dependently: -logED50 (95% confidence intervals, mean ED50) for pulmonary hypertension and bronchoconstriction 5.44 (5.08-5.80, 3.6 microg/kg) and 4.90 (4.06-5.20, 12.5 microg/kg), respectively. However, colforsin daropate (>or= 30 microg/kg) produced a more pronounced systemic than pulmonary vasodilation. Although colforsin daropate (>or= 30 microg/kg) significantly increased plasma catecholamines, propranolol did not reverse the relaxant effects. Colforsin daropate may attenuate bronchoconstriction and pulmonary hypertension. In addition, as beta-blockade did not change the attenuation, the relaxant effects may be independent of plasma catecholamines.

Unventilated airway is time-dependently constricted in paralyzed dogs.

Apnea has been reported to produce bronchoconstriction and to cause hypoxia, hypercapnia, and modulation of vagal afferent nerves, which also change airway tone. In this study, the authors determined the mechanism of apnea-induced bronchoconstriction. Twenty-eight dogs anesthetized and paralyzed were assigned to four groups (n = 7 each): apnea after artificial ventilation with 50% and 100% O2 groups (apnea-50% O2 and apnea-100% O2 groups, respectively), an apnea plus vagotomy group (fraction of inspired oxygen [FiO2] = 1.0), and a one-lung ventilation group (FiO2 = 1.0). The trachea was intubated with a single- or double-lumen tube in the three apnea groups or the one-lung ventilation group, respectively. The bronchial cross-sectional area (BCA) was assessed by the authors' bronchoscopic method. In the apnea-100% O2 and apnea plus vagotomy groups, a respirator was turned off for 5 min to produce apnea. In the apnea-50% O2 group, apnea was produced for 3 min. In the one-lung ventilation group, the right lumen was blocked for 5 min, and 15 min later, the left lumen was blocked for 5 min. BCA, arterial oxygen tension (PaO2), and arterial carbon dioxide tension (PaCO2) were assessed every minute. The BCA in intact dogs time-dependently decreased by approximately 20% and 40% at 3 and 5 min after apnea started, respectively, whereas they did not in vagotomized dogs. In the apnea-50% O2 and apnea-100% O2 groups, bronchoconstriction could occur without hypoxemia, although hypercapnia was observed in all dogs. In the one-lung ventilation group, despite the fact that PaCO2 increased by only 2 mmHg without hypoxemia, unventilated BCA time-dependently decreased by 33.6 +/- 10.3%, whereas ventilated BCA did not. The current study suggests that the unventilated airway may constrict spontaneously. In addition, the airway constriction could be vagally mediated but not due to hypoxia and hypercapnia.

Bronchoconstrictive and relaxant effects of lidocaine on the airway in dogs.

Intravenous lidocaine commonly is used to treat ventricular arrhythmias and to attenuate reflex airway constriction and intracranial pressure elevation during airway manipulation in intensive care units. There is much controversy as to the actions of lidocaine on the airway, so the aim of this study was to compare, in detail, the actions of lidocaine with those of bupivacaine and procaine on airway caliber and the associated changes in plasma catecholamine concentrations in the dog. Prospective, randomized, controlled experimental in vivo and in vitro study. A university research laboratory. Mongrel dogs. In the first experiment, we evaluated the effects of intravenous local anesthetics--lidocaine 0-10 mg/kg (n = 7), bupivacaine 0-2.5 mg/kg (n = 7), or procaine 0-20 mg/kg (n = 7)--on basal airway tone. In second experiment, histamine (10 microg/kg + 500 microg x kg(-1) x hr(-1), n = 6), serotonin (10 microg/kg + 500 microg x kg(-1) x hr(-1), n = 7), and methacholine (0.5 microg/kg + 300 microg x kg(-1) x hr(-1), n = 7) were infused to determine the effects of lidocaine (0-10 mg/kg) on agonist-induced bronchoconstriction. In addition, the actions of lidocaine on vagal nerve stimulation were examined (n = 7). Bronchial cross-sectional area at the third bronchial bifurcation of dogs was monitored continuously through a fiberoptic bronchoscope. In the first experiment, all local anesthetics produced a dose-dependent decrease in basal bronchial cross-sectional area. In the second experiment, lidocaine significantly potentiated histamine and serotonin-induced bronchoconstriction. In contrast, lidocaine antagonized methacholine- and vagal nerve stimulation-induced bronchoconstriction. We have clearly demonstrated that lidocaine may produce direct bronchoconstriction and worsen some agonist-induced bronchoconstriction, but it prevents reflex airway constriction. Therefore, we suggest that this agent be used with caution in asthmatics.

Spasmolytic effect of magnesium sulfate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

Magnesium (Mg2+) has relaxant effects on histamine-induced bronchoconstriction. In addition, Mg2+ has been reported to reduce vascular smooth muscle tone and be clinically useful for treatment of persistent pulmonary hypertension of the newborn. In this study, we evaluated the relaxant effect of Mg2+ on serotonin (5HT)-induced bronchoconstriction and pulmonary hypertension. Seven mongrel dogs were anesthetized with pentobarbital (30 mg x kg(-1) + 2 mg x kg(-1) x h(-1)) and paralyzed by pancuronium (0.2 mg x kg(-1) x h(-1)). Bronchoconstriction and pulmonary hypertension were elicited with 5HT (10 microg x kg(-1) + 1 mg x kg(-1) x h(-1)). Airway caliber was evaluated by changes in bronchial cross-sectional area (BCA) of the 3rd bronchial bifurcation measured by a fiberoptic bronchoscope method as previously reported. Pulmonary hypertension was assessed by changes in pulmonary vascular resistance (PVR). The BCA and PVR were expressed as per cent of the basal level. Thirty minutes after start of 5HT infusion, magnesium sulfate (MgSO4): 0 (saline), 1, 10, 100 and 1000 micromol x kg(-1) was given i.v.. Arterial blood was also collected to measure plasma level of Mg2+ and catecholamines. 5HT increased %PVR to 163+/-25% and decreased % BCA by 39.2+/-4.5%. Plasma level of Mg2+ following MgSO4 1000 micromol x kg(-1) i.v. exceeded its toxic level. The ED50s of MgSO4 (dose producing 50% relaxation of maximal constriction) was 47.8 micromol x kg(-1) and 1.09 mmol x kg(-1) for pulmonary hypertension and bronchoconstriction, respectively. The ratio of %PVR to %SVR was about 1.0 after MgSO4 0-100 micromol x kg(-1) i.v., although the ratio significantly increased after 1000 micromol x kg(-1) i.v.. In dogs, 5HT-induced pulmonary hypertension but not bronchoconstriction was significantly reduced by an iv bolus of MgSO4, resulting in a plasma concentration within the assumed therapeutic level.

Thin-Section CT Evidence of Bronchial Thickening in Children with Stable Asthma: Bronchoconstriction or Airway Remodeling?

Rationale and Objectives The authors performed this study to determine if bronchial wall thickening is present in children with moderate to severe asthma during periods free from clinical bronchoconstriction. Materials and Methods The authors obtained low (radiation) dose thin-section computed tomographic (CT) scans in each of 18 control subjects and 21 children with moderately severe but stable asthma. Spirometry was performed on all subjects at the time of CT scanning. Bronchial wall thickness and bronchial wall area were measured, and the percentage wall area (bronchial wall area divided by bronchial cross–sectional area) was calculated. The authors performed best–fit regression analysis of wall thickness and percentage wall area versus bronchial diameter and qualitative analysis of images for bronchial wall thickening. Results In asthmatic patients, the mean percentage of the predicted forced expiratory volume in 1 second was 0.88 ± 0.09. The best fit regression line that demonstrated the relationship between wall thickness and bronchial diameter for patients with asthma differed significantly from that for control subjects ( P < .005). The regression line that demonstrated the relationship between the percentage wall area and bronchial diameter for patients with asthma differed from that of the control subjects when bronchial wall thickness measurements were used to calculate the percentage wall area ( P < .05). Results of qualitative analysis also showed significantly more bronchial wall thickening in asthmatic patients than in control subjects ( P < .001). Conclusion Bronchial wall thickening detected at thin–section CT in children with moderately severe asthma cannot be attributed solely to bronchoconstriction and may represent airway inflammation or remodeling.

Comparison of relaxant effects of propofol on methacholine-induced bronchoconstriction in dogs with and without vagotomy

Propofol has been suggested to have in vivo airway relaxant effects, although the mechanism is still unclear. In this study, we determined whether propofol could antagonize methacholine-induced bronchoconstriction and determined whether vagotomy modifies this relaxant effect. Fourteen mongrel dogs anaesthetized with pentobarbital and pancuronium were assigned to a control group (n=7) and a vagotomy group (n=7). The trachea was intubated with a special endotracheal tube that had a second lumen for insertion of the bronchoscope. Bronchial cross-sectional area, which was monitored continuously through the bronchoscope, was measured with image analysis software. Bronchoconstriction was elicited with methacholine (0.5 microg kg(-1) + 5.0 microg kg(-1) min(-1)) until the end of the experiment. Thirty minutes after the start of methacholine infusion, propofol 0, 0.2, 2.0 and 20 mg kg(-1) was administered. Changes in bronchial cross-sectional area were expressed as percentages of the basal area. Plasma concentrations of propofol and catecholamine were measured by high-performance liquid chromatography. Maximal inhibition (bronchoconstriction = 0%, baseline = 100%) and IC50 (concentration producing 50% inhibition of maximal effect) produced by propofol was obtained from each concentration-response curve using a curve-fitting program. Methacholine decreased bronchial cross-sectional area to 49.3% (95% confidence interval 38.5-60.1%) and 45.3% (34.8-55.7%) of the baseline value. Propofol 20 mg kg(-1) significantly reversed this effect: bronchial cross-sectional area was reduced to 77.8% (66.2-89.6%) and 75.9% (64.0-87.9) in the control and vagotomy groups respectively. The two groups did not differ significantly in the maximal inhibitory effect of propofol [control group, 61.1% (46.3-75.9%), vagotomy group, 64.2% (40.1-88.3%)] or pIC50 [control group 5.03 (4.55-5.51), vagotomy group 4.86 (4.49-5.24)]. Therefore, the relaxant effects of propofol on methacholine-induced bronchoconstriction may not be mediated centrally. Propofol may relax airway smooth muscles directly or through the peripheral vagal pathway.

Spasmolytic effects of prostaglandin E1 on serotonin-induced bronchoconstriction and pulmonary hypertension in dogs.

In this study, we simultaneously evaluated the spasmolytic effects of prostaglandin E1 (PGE1) on serotonin-induced bronchoconstriction and pulmonary hypertension. Eleven mongrel dogs (8-12 kg) anaesthetized with pentobarbital were assigned to two groups: saline (n = 4) and PGE1 (n = 7). Bronchoconstriction and pulmonary hypertension were elicited with serotonin 10 micrograms kg-1 + 1 mg kg-1 h-1 and assessed as the percentage change in bronchial cross-sectional area (BCA) measured by bronchoscopy and pulmonary vascular resistance (PVR), respectively. Thirty minutes after starting the serotonin infusion, saline or PGE1 0 (saline), 0.01, 0.1, 1.0 or 10 micrograms kg-1 i.v. was given. %BCA and %PVR (basal = 100%) were assessed before and 30 min after serotonin, and 30 and 60 min after saline (saline group) or 5 min after each dose of PGE1 (PGE1 group). In the saline group, pulmonary hypertension and bronchoconstriction were stable. In the PGE1 group, PGE1 at > or = 0.1 microgram kg-1 significantly decreased %BCA and 10 micrograms kg-1 almost fully reversed the constriction (from mean (SEM) 56.2% (4.9%) to 94.4% (3.7%)). %PVR was significantly decreased at 10 micrograms kg-1 (from 230% (24%) to 176% (11%)) only. We suggest that PGE1 may produce bronchodilation rather than pulmonary vasodilation.

Milrinone attenuates serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

We determined whether milrinone, a phosphodiesterase III inhibitor, attenuates serotonin-induced (5-hydroxytryptamine [5HT]) pulmonary hypertension (PH) and bronchoconstriction. Dogs were anesthetized with pentobarbital (30 mg/kg + 2 mg. kg(-1). h(-1)). Bronchoconstriction and PH were elicited by 5HT (10 microg/kg + 1.0 mg. kg(-1). h(-1)). Pulmonary vascular resistance was used to assess PH. Bronchoconstriction was also assessed by changes in bronchial cross-sectional area obtained from our bronchoscopic method. At 30 min after 5HT infusion started, seven dogs were given milrinone: 0 (saline), 5, 50, 500, and 5000 microg/kg at 10-min intervals. The other 12 dogs were given milrinone 5000 microg/kg 30 min after 5HT infusion, and 5 min later were given propranolol 0.2 mg/kg (n = 6) or saline (n = 6) IV. The 5HT significantly increased percentage of pulmonary vascular resistance to 208% +/- 27% and decreased percentage of bronchial cross-sectional area to 52% +/- 5% of the basal. Milrinone significantly attenuated both PH and bronchoconstriction in a dose-dependent manner. However, -log 50% effective concentration (mean ED(50) in microg/kg) of milrinone for bronchoconstriction: 4.32 +/- 0.13 (47.6) was significantly smaller than that for PH: 3.84 +/- 0.29 (144.9) (P < 0.01). In addition, the spasmolytic effects of milrinone (5000 microg/kg) were not antagonized by propranolol, although this dose significantly increased plasma catecholamines. In conclusion, milrinone attenuates 5HT-induced PH and bronchoconstriction; however, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than in pulmonary vascular smooth muscle. In addition, the relaxant effects could not be caused by beta-adrenoceptor activation because beta-blocker did not antagonize. We studied the effects of milrinone on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs. Milrinone produces pulmonary vasodilation and bronchodilation, whose effects may not be caused by beta-adrenoceptor activation. In addition, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than that in pulmonary vascular smooth muscle.