Changes In Airway Caliber Research Articles

Quantitative analysis of hyperpolarized 3 He ventilation changes in mice challenged with methacholine

The capability to use high-resolution (3)He MRI to depict regional ventilation changes and airway narrowing in mice challenged with methacholine (MCh) offers the opportunity to gain new insights into the study of asthma. However, to fully exploit the value of this novel technique, it is important to move beyond visual inspection of the images toward automated and quantitative analysis. To address this gap, we describe a postprocessing approach to create ventilation difference maps to better visualize and quantify regional ventilation changes before and after MCh challenge. We show that difference maps reveal subtle changes in airway caliber, and highlight both focal and diffuse regional alterations in ventilation. Ventilation changes include both hypoventilation and compensatory areas of hyperventilation. The difference maps can be quantified by a histogram plot of the ventilation changes, in which the standard deviation increases with MCh dose (R(2) = 0.89). This method of analysis is shown to be more sensitive than simple threshold-based detection of gross ventilation defects.

Airway narrowing assessed by anatomical optical coherence tomography in vitro: dynamic airway wall morphology and function

Regulation of airway caliber by lung volume or bronchoconstrictor stimulation is dependent on physiological, structural, and mechanical events within the airway wall, including airway smooth muscle (ASM) contraction, deformation of the mucosa and cartilage, and tensioning of elastic matrices linking wall components. Despite close association between events in the airway wall and the resulting airway caliber, these have typically been studied separately: the former primarily using histological approaches, the latter with a range of imaging modalities. We describe a new optical technique, anatomical optical coherence tomography (aOCT), which allows changes at the luminal surface (airway caliber) to be temporally related to corresponding dynamic movements within the airway wall. A fiber-optic aOCT probe was inserted into the lumen of isolated, liquid-filled porcine airways. It was used to image the response to ASM contraction induced by neural stimulation and to airway inflation and deflation. Comparisons with histology indicated that aOCT provided high-resolution images of the airway lumen including mucosal folds, the entire inner wall (mucosa and ASM), and partially the cartilaginous outer wall. Airway responses assessed by aOCT revealed several phenomena in "live" airways (i.e., not fixed) previously identified by histological investigations of fixed tissue, including a geometric relationship between ASM shortening and luminal narrowing, and sliding and bending of cartilage plates. It also provided direct evidence for distensibility of the epithelial membrane and anisotropic behavior of the airway wall. Findings suggest that aOCT can be used to relate changes in airway caliber to dynamic events in the wall of airways.

Bronchodilator effects of exercise hyperpnea and albuterol in mild-to-moderate asthma

In asthmatic patients, either bronchodilatation or bronchoconstriction may develop during exercise. In 18 patients with mild-to-moderate asthma, we conducted two studies with the aims to 1) quantify the bronchodilator effect of hyperpnea induced by incremental-load maximum exercise compared with effects of inhaled albuterol (study 1, n=10) and 2) determine the time course of changes in airway caliber during prolonged constant-load exercise (study 2, n=8). In both studies, it was also investigated whether the bronchodilator effects of exercise hyperpnea and albuterol are additive. Changes in airway caliber were measured by changes in partial forced expiratory flow. In study 1, incremental-load exercise was associated with a bronchodilatation that was approximately 60% of the maximal bronchodilatation obtainable with 1,500 microg of albuterol. In study 2, constant-load exercise was associated with an initial moderate bronchodilatation and a late airway renarrowing. In both studies, premedication with inhaled albuterol (400 microg) promoted sustained bronchodilatation during exercise, which was additive to that caused by exercise hyperpnea. In conclusion, in mild-to-moderate asthmatic individuals, hyperpnea at peak exercise was associated with a potent yet not complete bronchodilatation. During constant-load exercise, a transient bronchodilatation was followed by airway renarrowing, suggesting prevalence of constrictor over dilator effects of hyperpnea. Finally, the bronchodilator effect of hyperpnea was additive to that of albuterol.

Sputum eosinophilia: an early marker of bronchial response to occupational agents

False-negative responses to specific inhalation challenge (SIC) with occupational agents may occur. We explored whether assessing changes in sputum cell counts would help improve the identification of bronchial reactivity to occupational agents during SICs. The predictive value of the changes in sputum cell counts after a negative FEV(1) response to a first challenge exposure to an occupational agent was determined using the changes in airway calibre observed during repeated challenges as the 'gold standard'. The study included 68 subjects investigated for work-related asthma in a tertiary centre. After a control day, the subjects were challenged with the suspected occupational agent(s) for up to 2 h. All subjects who did not show an asthmatic reaction were re-challenged on the following day. Additional challenges were proposed to those who demonstrated a > or = 2% increase in sputum eosinophils or an increase in nonspecific bronchial hyperresponsiveness to histamine after the second challenge day. Six of the 35 subjects without changes in FEV(1) on the first challenge developed an asthmatic reaction on subsequent challenges. ROC analysis revealed that a >3% increase in sputum eosinophils at the end of the first challenge day was the most accurate parameter for predicting the development of an asthmatic response on subsequent challenges with a sensitivity of 67% and a specificity of 97%. An increase in sputum eosinophils is an early marker of specific bronchial reactivity to occupational agents, which may help to identify subjects who will develop an asthmatic reaction only after repeated exposure.

Relationship between improved airflow limitation and changes in airway calibre induced by inhaled anticholinergic agents in COPD

Background:Although airflow limitation improved by inhaled anticholinergic drugs varies among individuals with chronic obstructive pulmonary disease (COPD), the relationship between actual bronchodilation and improved pulmonary function and where in the...

Investigation of Hyperpolarized 3He Magnetic Resonance Imaging Utility in Examining Human Airway Diameter Behavior in Asthma Through Comparison with High-Resolution Computed Tomography

Application of a previously developed model-based algorithm on hyperpolarized (HP) (3)He magnetic resonance (MR) dynamic projection images of phantoms was extended to investigate the utility of HP (3)He MR imaging (MRI) in quantifying airway caliber changes associated with asthma. Airways of seven volunteers were imaged and measured using HP (3)He MRI and multidetector-row computed tomography (MDCT) before and after a methacholine (MCh) challenge. MDCT data were obtained at functional residual capacity and 1 L above functional residual capacity. Comparison of the resultant data showed that HP (3)He MRI did not match MDCT in measuring the ratios of airway calibers before and after the MCh challenge in 37% to 43% of the airways from the first six generations at the two lung volumes tested. However, MDCT did yield the observation that 49% to 69% of these airways displayed bronchodilation following MCh challenge. The current implementation of HP (3)He MRI did not match the MCh-induced postchallenge-to-prechallenge airway caliber ratios as measured with MDCT. Elevated parenchymal tethering due to bronchoconstriction-induced hyperinflation was proposed as a possible explanation for this airway dilation.

Dynamic Hyperinflation with Bronchoconstriction

Symptoms and respiratory function tests may be difficult to assess and interpret in obese patients with asthma, particularly if the asthma is severe. It is unclear whether the dynamic changes that occur during bronchoconstriction differ between obese versus nonobese patients with asthma. To explore whether the changes in airway caliber and lung volumes that occur with acute bronchoconstriction are different in obese and nonobese patients with asthma and whether any differences contribute to the quality and intensity of symptoms. Thirty female patients with asthma were studied. Spirometry, lung volume measurements, and dyspnea scores were obtained before and immediately after bronchoconstriction induced by methacholine, aiming to provoke a reduction in FEV1 of 30%. Body mass index was independently associated with changes in lung volume after adjustment for baseline airway caliber and hyperresponsiveness. Increases in functional residual capacity and decreases in inspiratory capacity were significantly greater in obese participants (P < 0.001 and P = 0.003, respectively). Changes in respiratory function, notably dynamic hyperinflation, are greater in obese individuals with bronchoconstriction. This may potentially alter the perception and assessment of asthma severity in obese patients with asthma.

Airway response to induced muscular contraction in spontaneously breathing rabbits

The airways are thought to dilate during exercise in humans but the time course and mechanisms of the response are not fully described. The aim of the study was to document changes in airway calibre during electrically induced muscular contractions (MC) in spontaneously breathing rabbits. Experiments were also performed after induced bronchoconstriction to assess the effect of change in breathing pattern on airway calibre during MC. Respiratory resistance (R(RS)) was measured in 12 rabbits using the forced oscillation technique at 20 Hz before, during and after 30s MC in control conditions and after methacholine induced bronchoconstriction (Mch). MC was associated with significant decrease in R(RS) both at control and Mch. The MC induced increase in V(E) occurred with significant albeit small change in mean tidal volume (V(T)) at Mch but not control. An augmented breath (AB) occurred in 29/35 MCs and was usually associated with an abrupt drop in R(RS). The decrease in R(RS) induced by AB was significantly larger at Mch compared with control. Passively inflating the lung after MC induced significantly larger decrease in R(RS) than AB during MC. The data indicate bronchodilation by MC in spontaneously breathing rabbits. The mechanisms appear to include AB dependent airway wall stretching as well as removal of cholinergic input to the airway smooth muscle.

Erratum/Notice of Retraction

The American Journal of Neuroradiology has decided to formally retract the article: “Dynamic Upper Airway Soft-Tissue and Caliber Changes in Healthy Subjects and Snoring Patients” by Hüseyin Akan, Tolga Aksöz, Ümit Belet, and Teoman Şeçsen [ ( AJNR Am J Neuroradiol 2004;25:1846–50).][1

Extent and Localization of Changes in Upper Airway Caliber With Varying Concentrations of Sevoflurane in Children

Extent and Localization of Changes in Upper Airway Caliber With Varying Concentrations of Sevoflurane in Children

The influence of episodic hypoxia on upper airway collapsibility in subjects with obstructive sleep apnea

We have previously shown that in subjects with obstructive sleep apnea, repetitive hypoxia is associated with long-term facilitation as manifested by decreased upper airway resistance (Rua). Our objective was to study the influence of long-term facilitation on upper airway collapsibility as measured by the critical closing pressure (Pcrit) model and to determine whether changes in Rua correlated with changes in collapsibility. We studied 13 subjects (10 men, 3 women) with a mean apnea-hypopnea index of 43.9 +/- 24.0 events/h. In the first protocol with 11 subjects, we measured collapsibility using a Pcrit protocol before and after episodic hypoxia. Brief (3 min) isocapnic hypoxia (inspired O(2) fraction = 8%) followed by 5 min of room air was induced 10 times. A sham study without hypoxia was performed on eight subjects. Ventilatory parameters, Rua, and Pcrit before and after episodic hypoxia were measured. At 20 min of recovery, there was no change in minute ventilation but there was a significant decrease in Rua compared with the control period (control, 8.6 +/- 4.8 cmH(2)O.l(-1).s vs. recovery, 5.9 +/- 3.8 cmH(2)O.l(-1).s; P < 0.05). However, there was no change in Pcrit between the control (2.3 +/- 1.9 cmH(2)O) and recovery (2.7 +/- 3.2 cmH(2)O) periods. No changes in Rua or Pcrit were observed in the sham protocol. We conclude that long-term facilitation of upper airway dilators is not associated with changes in upper airway collapsibility in subjects with obstructive sleep apnea. These results corroborate previous evidence that changes in upper airway resistance and caliber can be dissociated from changes in upper airway collapsibility.

Extent and Localization of Changes in Upper Airway Caliber with Varying Concentrations of Sevoflurane in Children

Previous studies in humans suggest that inhibition of upper airway muscle activity is independent of the dose of inhalational anesthesia. Whether a dose-independent relation applies to changes in airway caliber is unknown. The authors sought to evaluate the configurational changes that lead to upper airway narrowing during inhalational anesthesia with sevoflurane and to determine whether these changes are dose dependent within a clinically relevant dose range. Fifteen children undergoing elective magnetic resonance imaging of the brain were studied. Magnetic resonance images of the upper airway were acquired at sevoflurane concentrations of 0.5, 1.0, and 1.5 minimum alveolar concentration (MAC), administered in random sequence. At least 15 min was allowed for equilibration of inspired and alveolar partial pressures of sevoflurane. Images were acquired in early expiration at the level of the soft palate, base of the tongue, and tip of the epiglottis. Airway cross-sectional area (CSA), anteroposterior, and transverse dimension were determined using image-analysis software. At each anatomical level, pharyngeal CSA decreased progressively with increasing depth of sevoflurane anesthesia (P < 0.001). Increasing the sevoflurane concentration from 0.5 to 1.0 MAC reduced airway CSA by 13-18%, and a further increase to 1.5 MAC resulted in an overall 28-34% reduction in CSA. The reduction in CSA was predominantly due to a decrease in anteroposterior dimension. Increasing the depth of sevoflurane anesthesia resulted in a relatively uniform reduction in pharyngeal caliber at each anatomical level studied. The effect of sevoflurane on upper airway caliber is dose dependent.

Deep Inhalation and Airway Patency in Children

Deep inhalation (DI) induces changes in airway calibre that may last beyond the manoeuvre itself. The mechanisms involve mechanical interaction between conducting airways subjected to parenchymal tethering and lung parenchyma itself. Healthy children usually show small bronchodilation after DI. Increased airway calibre after DI has been documented in wheezy preschool children with mild airway obstruction and, after methacholine challenge, in preschool and school children with normal lung function but has not yet been demonstrated in infants. The DI also induces bronchodilation in children with mild exercise induced airway obstruction. In the presence of severe airway obstruction, the bronchodilatory effect of DI may be blunted or reversed. The bronchodilatory effect of DI appears to be larger in children and adults than infants and elderly and larger in girls than boys. It is inversely related to the degree of airway hyperresponsiveness and the blunted bronchodilatory response to DI in acute or severe asthma is restored by steroid therapy or allergen avoidance. The airway effects of DI may in the future prove a valuable tool in assessing the mechanisms of airway obstruction and reactivity in children. Keywords: Conducting airways, lung parenchyma, respiratory or airway resistance, methacholine, exercise, asthma, bronchodilation, bronchoconstriction, airway responsiveness, lung volume

L’expectoration induite, outil de diagnostic de l’asthme professionnel

The diagnosis of occupational asthma relies mainly on the demonstration of changes in airway calibre and airway responsiveness after exposure to occupational agents in the laboratory or at the workplace. However, spirometry or peak expiratory flow measurements may be open to misinterpretation when they are not performed optimally. As in non-occupational asthma, airway inflammation is one of the main characteristics of occupational asthma. Induced sputum, a non invasive method to assess airway inflammation, has been successfully used in the management of asthma. This article reviews the studies that have investigated and characterized the changes in sputum cell counts occurring in subjects with occupational asthma after exposure to occupational agents in the laboratory or at the workplace in order to assess the place of induced sputum in the investigation of occupational asthma. It also reviews the use of induced sputum during the follow-up of workers with occupational asthma after removal from exposure. This article also describes a new condition identified thanks to the use of induced sputum : occupational eosinophilic bronchitis. In conclusion, induced sputum is a useful tool in the investigation of occupational asthma. Its use on a regular basis in the investigation of occupational asthma also allows for the possibility of diagnosis of overlooked conditions such as occupational eosinophilic bronchitis. Its role in the surveillance of workers at risk to develop occupational asthma remains to be determined.

Mechanisms of limited airway dimension with lung inflation

Airways distend with each inspiration, while a sigh or deep inspiration (DI) leads to a significant or a maximum distension of the airways. Distension of the airways is thought to play an important role in maintaining airway patency. Limited distension of the airways with lung inflation may be a major factor in certain lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). High resolution computed tomography (HRCT) has gained wide acceptance as a diagnostic and investigational radiological tool for the evaluation of airway function. HRCT has been used to measure dynamic changes in airway caliber in vivo that are not detectable by conventional global lung measurements such as airway and lung resistance. HRCT is uniquely capable of imaging and quantifying airway size at different lung volumes. The current paper reviews the use of HRCT to examine the role of lung inflation on airway distension in animal models, and discusses potential mechanisms for limited distension of the airways with lung inflation in individuals with asthma and COPD.

Perception of dyspnea during exacerbation and histamine-related bronchoconstriction in patients with asthma

Numerous studies have been performed concerning the perception of dyspnea during changes in airway caliber provoked in the laboratory setting, but studies of asthma exacerbation are scarce. To investigate whether the perception of dyspnea during histamine-induced bronchoconstriction might be used to identify patients with asthma who sense dyspnea poorly during exacerbation. The perception of dyspnea in 50 patients (45 female, 5 male) with asthma was evaluated at admission with exacerbation and during a stable period. Perceived intensity of dyspnea was estimated using a modified Borg scale. The perception of dyspnea in the stable period 4 to 6 weeks after exacerbation was measured with the histamine challenge test. Perception parameters were defined as the change in Borg score divided by the change in forced expiratory volume in 1 second (FEV1) as a percentage of the baseline FEV1 (deltaBorg/deltaFEV1) and as the Borg score at 20% decrease (PS20Histamine) or increase (PS20Exacerbation) in FEV1. The perception of dyspnea during asthma exacerbation was unrelated to the perception of dyspnea during histamine-induced bronchoconstriction (for deltaBorg/deltaFEV1, beta = .08, P = .50; for PS20, beta = -.11, P = .40). The kappa value for the agreement of poor perceivers at exacerbation and during the stable period was -0.21 (P = .10). However, the intensity of dyspnea caused by histamine-induced bronchoconstriction was lower than that caused by asthma exacerbation (PS20: 1.6 +/- 1.1 vs 2.8 +/- 2.5, respectively, P = .004; deltaBorg/deltaFEV1: 0.08 +/- 0.05 vs 0.21 +/- 0.28, respectively, P = .001). The perception of dyspnea during asthma exacerbation is not correlated with the perception of dyspnea during histamine-induced bronchoconstriction. Therefore, the perception of dyspnea during histamine-induced bronchoconstriction cannot be used to identify the asthmatic patients who perceive dyspnea poorly.

Radiation-induced narrowing of the tracheobronchial tree: An in-depth analysis

Symptomatic narrowing of the tracheobronchial tree is not a common clinical problem after conventional-dose external beam radiation therapy but has been described when higher doses are utilized. This in-depth study quantifies changes in the caliber of the trachea and mainstem bronchi after high-dose external beam radiation therapy (EBRT). As part of an IRB-approved prospective clinical trial to assess for radiation-induced lung injury, patients with thoracic malignancies had pre- and serial post-RT CT scans in the radiation oncology department. This report focuses on 18 enrolled patients who received high-dose (> or = 73.6 Gy) EBRT for NSCLC. The caliber of the trachea, right mainstem bronchus, and left mainstem bronchus were measured utilizing three-dimensional coordinates in axial and coronal planes such that multiple measurements were made of each structure. The decrease in airway caliber was tested for significance using a one-sided Wilcoxon matched-pairs signed-ranks test. The correlation between airway caliber changes, dose, and follow-up interval was tested using the Spearman rank correlation coefficient and the effect of chemotherapy on airway narrowing was evaluated with a one-sided exact Wilcoxon rank sum test. There was no significant narrowing of the trachea for all dose and time points. There were significant decreases in the caliber of both mainstem bronchi on axial measurements (p = 0.07 and 0.005 for right and left mainstem bronchi, respectively). Decrease in airway caliber ranged from 6 to 57% and appeared to be dose dependent (p = 0.08), progressed with increasing time post-RT (p = 0.04), and was worse in patients who also received chemotherapy (p = 0.04). High-dose EBRT (> or = 73.6 Gy) appears to cause narrowing of the mainstem bronchi as early as 3 months post radiation therapy. Additional study is needed to assess the impact of such narrowing on RT-induced pulmonary symptoms.

Airway Tone During Exercise in Healthy Subjects: Effects of Salbutamol and Ipratropium Bromide

In healthy subjects changes in airway calibre during exercise are conflicting and smaller than in asthmatics. Methodological differences could explain the discrepancies between the results obtained in healthy subjects. Therefore, our aim was to assess during exercise the changes in airway diameter and the effects of 200 microg salbutamol (SAL) or 40 microg ipratropium bromide (IPR) inhalations versus placebo (PLA), using spirometry and respiratory resistance (Rrs). Eight non-asthmatic subjects exercised 9 min at 70 % of their maximal aerobic power after inhalation of 200 microg SAL, 40 microg IPR, or PLA. Maximal flow-volume curves were obtained before and after inhalations, at 3 (E3) and 6 (E6) minutes of exercise, and during recovery. Rrs were measured by impulse oscillometry before and after inhalation, and immediately at the end of exercise. At rest, FEV (1) increased significantly after inhalation of SAL and IPR. Rrs decreased only after SAL. During exercise FEV (1) increased significantly from rest with SAL and IPR while forced mid expiratory flow (FEF (25 - 75)) increased significantly for all conditions. At E6 the rise of FEV (1) and FEF (25 - 75) were greater with SAL compared to PLA and IPR. In all conditions Rrs increased significantly immediately at the end of exercise as compared to rest but less than during flow-matched hyperpnea. It is concluded that a similar bronchodilation was observed during exercise with and without anticholinergic drug which suggests a withdrawal of parasympathetic control of airways during exercise in healthy subjects. Nevertheless, the bronchodilation observed during exercise is not maximal since it can be reinforced by beta (2)-mimetic drug.

Monitoring changes of human airways by acoustical means

The state of human airways is typically assessed by spirometry, i.e., by measuring airflow during maximum forced expiration. The required effort excludes subjects who cannot or will not perform such maneuvers. Turbulent airflow during normal breathing generates sound that can be recorded at the chest surface. Changes in airway caliber, e.g., by constriction or dilation, and concurrent changes in the tension of the airway walls affect the relation of airflow and breath sounds. This relation is complex and incompletely understood. However, the possibility to assess changes in the state of human airways by the relation of airflow and breath sounds promises an opportunity to develop auxiliary methods to spirometry. Two regions of the human airways have attracted the interest of researchers in respiratory acoustics. Breath sounds over the trachea (windpipe) increase in their airflow-specific intensity on narrowing of the upper airways, e.g., due to abnormal anatomy, infectious causes etc. Furthermore, spectral characteristics of tracheal sounds may indicate the region of abnormality. On the other hand, breath sounds over the chest change in their airflow-specific intensity with constriction of airways in the lung, e.g., due to asthma. It may therefore be possible to monitor the effectiveness of treatment by acoustical means.

Evaluation of the Magnitude of the Bronchodilator Response in Children and Adolescents With Asthma

Bronchodilator response criteria have been determined in adults; however, data applicable to children and adolescents are scarce. We measured pulmonary function in asthmatic patients to determine the bronchodilator response. A blind study. Outpatient clinic of Pneumology Unit, Instituto da Crianca and Center of Asthma Care and Research, University Hospital, University of Sao Paulo Medical School. Sixty patients aged 6 to 20 years (median, 12 years). Spirometry and plethysmography were performed before and after blind placebo and bronchodilator inhalation (400 mug salbutamol by metered-dose inhaler). Approximately 90% of the patients had mild-to-moderate persistent asthma. The mean FEV(1) at baseline was 79.6% of the predicted value. Distribution of variations of the different pulmonary function parameters was analyzed after placebo inhalation. The 95th percentile was adopted as a criterion for a significant bronchodilator response. After the bronchodilator test, the patients were classified based on criteria derived from the placebo inhalation and the American Thoracic Society guidelines. Parameters established as cutoff values were 265 mL, 14.2% and 10% FEV(1) expressed as absolute volume, percentage compared with that at baseline and percentage of the predicted value, respectively, and 55% specific airway conductance (sGaw) expressed as a percentage compared with that at baseline. Based on the spirometric data, 37 patients (61%) had reversibility of obstruction, while 48 patients (80%) were classified as responders based on the analysis of variations in sGaw. The classifications based on variations in FEV(1) expressed as absolute volume and percentage of the predicted value showed a substantial correlation with the international classification. The cutoff values established for the assessment of the bronchodilator response in the present population agree with those reported in the literature. sGaw was the most sensitive parameter for the identification of changes in airway caliber.