scholarly journals Airway closure on imaging relates to airway hyperresponsiveness and peripheral airway disease in asthma

2012 ◽  
Vol 113 (6) ◽  
pp. 958-966 ◽  
Author(s):  
Catherine E. Farrow ◽  
Cheryl M. Salome ◽  
Benjamin E. Harris ◽  
Dale L. Bailey ◽  
Elizabeth Bailey ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Airway Hyperresponsiveness ◽  
Airway Disease ◽  
Forced Expiratory Volume ◽  
Emission Computed Tomography ◽  
Airway Closure ◽  
Methacholine Challenge ◽  
Peripheral Airways ◽  
Ventilation Heterogeneity ◽  
Peripheral Airway

The regional pattern and extent of airway closure measured by three-dimensional ventilation imaging may relate to airway hyperresponsiveness (AHR) and peripheral airways disease in asthmatic subjects. We hypothesized that asthmatic airways are predisposed to closure during bronchoconstriction in the presence of ventilation heterogeneity and AHR. Fourteen asthmatic subjects (6 women) underwent combined ventilation single photon emission computed tomography/computed tomography scans before and after methacholine challenge. Regional airway closure was determined by complete loss of ventilation following methacholine challenge. Peripheral airway disease was measured by multiple-breath nitrogen washout from which Scond (index of peripheral conductive airway abnormality) was derived. Relationships between airway closure and lung function were examined by multiple-linear regression. Forced expiratory volume in 1 s was 87.5 ± 15.8% predicted, and seven subjects had AHR. Methacholine challenge decreased forced expiratory volume in 1 s by 23 ± 5% and increased nonventilated volume from 16 ± 4 to 29 ± 13% of computed tomography lung volume. The increase in airway closure measured by nonventilated volume correlated independently with both Scond (partial R2 = 0.22) and with AHR (partial R2 = 0.38). The extent of airway closure induced by methacholine inhalation in asthmatic subjects is greater with increasing peripheral airways disease, as measured by ventilation heterogeneity, and with worse AHR.

scholarly journals Peripheral ventilation heterogeneity determines the extent of bronchoconstriction in asthma

2017 ◽  
Vol 123 (5) ◽  
pp. 1188-1194 ◽  
Author(s):  
Catherine E. Farrow ◽  
Cheryl M. Salome ◽  
Benjamin E. Harris ◽  
Dale L. Bailey ◽  
Norbert Berend ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Three Dimensional ◽  
Methacholine Challenge ◽  
Airway Narrowing ◽  
Nitrogen Washout ◽  
Airway Function ◽  
Ventilation Imaging ◽  
Before And After ◽  
Ventilation Heterogeneity ◽  
Peripheral Airway

In asthma, bronchoconstriction causes topographically heterogeneous airway narrowing, as measured by three-dimensional ventilation imaging. Computation modeling suggests that peripheral airway dysfunction is a potential determinant of acute airway narrowing measured by imaging. We hypothesized that the development of low-ventilation regions measured topographically by three-dimensional imaging after bronchoconstriction is predicted by peripheral airway function. Fourteen asthmatic subjects underwent ventilation single-photon-emission computed tomography/computed tomography scan imaging before and after methacholine challenge. One-liter breaths of Technegas were inhaled from functional residual capacity in upright posture before supine scanning. The lung regions with the lowest ventilation (Ventlow) were calculated using a thresholding method and expressed as a percentage of total ventilation (Venttotal). Multiple-breath nitrogen washout was used to measure diffusion-dependent and convection-dependent ventilation heterogeneity (Sacin and Scond, respectively) and lung clearance index (LCI), before and after challenge. Forced expiratory volume in 1 s (FEV1) was 87.6 ± 15.8% predicted, and seven subjects had airway hyperresponsiveness. Ventlow at baseline was unrelated to spirometry or multiple-breath nitrogen washout indices. Methacholine challenge decreased FEV1 by 23 ± 5% of baseline while Ventlow increased from 21.5 ± 2.3%Venttotal to 26.3 ± 6.7%Venttotal ( P = 0.03). The change in Ventlow was predicted by baseline Sacin ( rs = 0.60, P = 0.03) and by LCI ( rs = 0.70, P = 0.006) but not by Scond ( rs = 0.30, P = 0.30). The development of low-ventilation lung units in three-dimensional ventilation imaging is predicted by ventilation heterogeneity in diffusion-dependent airways. This relationship suggests that acinar ventilation heterogeneity in asthma may be of mechanistic importance in terms of bronchoconstriction and airway narrowing. NEW & NOTEWORTHY Using ventilation SPECT/CT imaging in asthmatics, we show induced bronchoconstriction leads to the development of areas of low ventilation. Furthermore, the relative volume of the low-ventilation regions was predicted by ventilation heterogeneity in diffusion-dependent acinar airways. This suggests that the pattern of regional airway narrowing in asthma is determined by acinar airway function.

Effect of deep inspiration avoidance on ventilation heterogeneity and airway responsiveness in healthy adults

2011 ◽  
Vol 110 (5) ◽  
pp. 1400-1405 ◽  
Author(s):  
David G. Chapman ◽  
Norbert Berend ◽  
Gregory G. King ◽  
Cheryl M. Salome
Keyword(s):  
Healthy Subjects ◽  
Forced Expiratory Volume ◽  
Airway Responsiveness ◽  
Deep Inspiration ◽  
Airway Closure ◽  
Airway Narrowing ◽  
Before And After ◽  
Ventilation Heterogeneity ◽  
Peripheral Airway ◽  
Diffusion Convection

The mechanisms by which deep inspiration (DI) avoidance increases airway responsiveness in healthy subjects are not known. DI avoidance does not alter respiratory mechanics directly; however, computational modeling has predicted that DI avoidance would increase baseline ventilation heterogeneity. The aim was to determine if DI avoidance increased baseline ventilation heterogeneity and whether this correlated with the increase in airway responsiveness. Twelve healthy subjects had ventilation heterogeneity measured by multiple-breath nitrogen washout (MBNW) before and after 20 min of DI avoidance. This was followed by another 20-min period of DI avoidance before the inhalation of a single methacholine dose. The protocol was repeated on a separate day with the addition of five DIs at the end of each of the two periods of DI avoidance. Baseline ventilation heterogeneity in convection-dependent and diffusion-convection-dependent airways was calculated from MBNW. The response to methacholine was measured by the percent fall in forced expiratory volume in 1 s/forced vital capacity (FVC) (airway narrowing) and percent fall in FVC (airway closure). DI avoidance increased baseline diffusion-convection-dependent airways ( P = 0.02) but did not affect convection-dependent airways ( P = 0.9). DI avoidance increased both airway closure ( P = 0.002) and airway narrowing ( P = 0.02) during bronchial challenge. The increase in diffusion-convection-dependent airways due to DI avoidance did not correlate with the increase in either airway narrowing ( rs = 0.14) or airway closure ( rs = 0.12). These findings suggest that DI avoidance increases diffusion-convection-dependent ventilation heterogeneity that is not associated with the increase in airway responsiveness. We speculate that DI avoidance reduces surfactant release, which increases peripheral ventilation heterogeneity and also predisposes to peripheral airway closure.

scholarly journals Deep inspirations protect against airway closure in nonasthmatic subjects

2009 ◽  
Vol 107 (2) ◽  
pp. 564-569 ◽  
Author(s):  
David G. Chapman ◽  
Norbert Berend ◽  
Gregory G. King ◽  
Brent E. McParland ◽  
Cheryl M. Salome
Keyword(s):  
Protective Effect ◽  
Respiratory System ◽  
Forced Expiratory Volume ◽  
Airway Responsiveness ◽  
Forced Oscillation Technique ◽  
Residual Volume ◽  
Airway Closure ◽  
Airway Narrowing ◽  
Ventilation Heterogeneity ◽  
Peripheral Airway

The mechanism by which deep inspirations protect against increased airway responsiveness in nonasthmatic subjects is not known. The aim was to investigate the role of airway closure and airway narrowing in deep inspiration bronchoprotection. Twelve nonasthmatic and nine asthmatic subjects avoided deep inspirations (DI) for 20 min, then took five DI expired to functional residual capaciy (DI-FRC) or, on a separate day, no DI (no DI) before inhaling a single dose of methacholine. On another day, eight nonasthmatic subjects took five DI expired to residual volume (DI-RV). Peripheral airway function was measured by respiratory system reactance (Xrs), using the forced oscillation technique, and by forced vital capacity (FVC) as an index of airway closure. Respiratory system resistance (Rrs) and forced expiratory volume in 1 s (FEV1)/FVC were measured as indexes of airway narrowing. In nonasthmatic subjects, DI-FRC reduced the response measured by FEV1 ( P = 0.019), Xrs ( P = 0.02), and FVC ( P = 0.0005) but not by Rrs ( P = 0.15) or FEV1/FVC ( P = 0.52) compared with no DI. DI-RV had a less protective effect than DI-FRC on response measured by FEV1 ( P = 0.04) and FVC ( P = 0.016). There was no difference between all protocols when the response was measured by Xrs ( P = 0.20), Rrs ( P = 0.88), or FEV1/FVC ( P = 0.88). DI had no effect on methacholine response in asthmatic subjects. DI protect against airway responsiveness through an effect on peripheral airways involving reduced airway closure. The protective effect of DI on FEV1 and FVC was abolished by expiration to residual volume. We speculate that the reduced airway closure is due to reduced baseline ventilation heterogeneity and/or reduced airway surface tension.

Quantitative computed tomography detects peripheral airway disease in asthmatic children

2005 ◽  
Vol 40 (3) ◽  
pp. 211-218 ◽  
Author(s):  
Neal Jain ◽  
Ronina A. Covar ◽  
Melanie C. Gleason ◽  
John D. Newell ◽  
Erwin W. Gelfand ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Quantitative Computed Tomography ◽  
Airway Disease ◽  
Asthmatic Children ◽  
Peripheral Airway

scholarly journals Distal Airway Impairment in Obese Normoreactive Women

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Grégory Marin ◽  
Anne Sophie Gamez ◽  
Nicolas Molinari ◽  
Djamila Kacimi ◽  
Isabelle Vachier ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Total Population ◽  
Forced Expiratory Volume ◽  
Overweight And Obesity ◽  
Airway Hyperreactivity ◽  
Obese Women ◽  
Methacholine Challenge ◽  
Response Slope ◽  
Distal Airway ◽  
Challenge Tests

Background. Asthma-like symptoms are frequent in overweight and obesity, but the mechanism is unclear when airway hyperresponsiveness (AHR) is lacking. In this study, we focused on obese women with a clinical suspicion of asthma but negative methacholine challenge and tested distal airway hyperreactivity, explored by Forced Vital Capacity dose-response slope (FVC DRS).Objective. To question AHR at the distal airway level in obese women.Methods. A total of 293 symptomatic obese and nonobese women free of treatment were investigated. Methacholine challenge tests were undertaken, and patients were divided according to their results to the test. In hyperreactive and nonhyperreactive patients and in our total population, correlations, regression analyses, and analyses of covariance were performed to compare distal airway hyperreactivity in three groups of body mass index (BMI).Results. After adjusting for age and baseline respiratory values, the relationship between FVC and FEV1 (forced expiratory volume in one second) DRS was influenced by BMI, with a lower slope in obese than overweight and normal patients in our total population (P=0.008) and in our nonhyperreactive one (P=0.028).Conclusion. Distal airway hyperresponsiveness was observed in symptomatic wheezing obese women negative to methacholine challenge.

Airway closure is the predominant physiological mechanism of low ventilation seen on hyperpolarized helium-3 MRI lung scans

2020 ◽  
Author(s):  
Kris Nilsen ◽  
Bruce R. Thompson ◽  
Natalie Zajakovski ◽  
Michael Kean ◽  
Benjamin E. Harris ◽  
...  
Keyword(s):  
Physiological Mechanism ◽  
Forced Oscillation Technique ◽  
Physiological Measures ◽  
Airway Closure ◽  
Methacholine Challenge ◽  
Hyperpolarized Helium ◽  
Variate Analysis ◽  
Ventilation Heterogeneity ◽  
Mri Scans ◽  
Helium 3

Hyperpolarized helium-3 MRI (3He MRI) provides detailed visualization of low- (hypo- and non-) ventilated lung. Physiological measures of gas mixing may be assessed by multiple breath nitrogen washout (MBNW) and of airway closure by forced oscillation technique (FOT). We hypothesize that in patients with asthma, areas of low-ventilated lung on 3He MRI are the result of airway closure. Ten control subjects, ten asthma subjects with normal spirometry (non-obstructed), and ten asthmatic subjects with reduced baseline lung function (obstructed) attended two testing sessions. On visit one, baseline plethysmography was performed followed by spirometry, MBNW and FOT assessment pre- and post-methacholine challenge. On visit two, 3He MRI scans were conducted pre- and post-methacholine challenge. Post methacholine the volume of low ventilated lung increased from 8.3% to 13.8% in the non-obstructed group (p = 0.012) and from 13.0% to 23.1% in the obstructed group (p=0.001). In all groups, the volume of low ventilation from 3He MRI correlated with a marker of airway closure in obstructive subjects, Xrs (6Hz) and the marker of ventilation heterogeneity Scond with r2 values of 0.61 and 0.56 respectively. The change in Xrs (6Hz) correlated well (r2 = 0.45), while the change in Scond was largely independent of, the change in low ventilation volume (r2=0.13). The only significant predictor of low ventilation volume from the multi-variate analysis was Xrs (6Hz). This is consistent with the concept that regions of poor or absent ventilation seen on 3He MRI are primarily the result of airway closure.

Respiratory system reactance is an independent determinant of asthma control

2013 ◽  
Vol 115 (9) ◽  
pp. 1360-1369 ◽  
Author(s):  
Vanessa J. Kelly ◽  
Scott A. Sands ◽  
R. Scott Harris ◽  
Jose G. Venegas ◽  
Nathan J. Brown ◽  
...  
Keyword(s):  
Asthma Control ◽  
Respiratory System ◽  
Lung Volume ◽  
Strong Predictor ◽  
Closing Volume ◽  
Forced Oscillation Technique ◽  
Airway Closure ◽  
Lung Volumes ◽  
Ventilation Heterogeneity ◽  
Peripheral Airway

The mechanisms underlying not well-controlled (NWC) asthma remain poorly understood, but accumulating evidence points to peripheral airway dysfunction as a key contributor. The present study tests whether our recently described respiratory system reactance (Xrs) assessment of peripheral airway dysfunction reveals insight into poor asthma control. The aim of this study was to investigate the contribution of Xrs to asthma control. In 22 subjects with asthma, we measured Xrs (forced oscillation technique), spirometry, lung volumes, and ventilation heterogeneity (inert-gas washout), before and after bronchodilator administration. The relationship between Xrs and lung volume during a deflation maneuver yielded two parameters: the volume at which Xrs abruptly decreased (closing volume) and Xrs at this volume (Xrscrit). Lowered (more negative) Xrscrit reflects reduced apparent lung compliance at high lung volumes due, for example, to heterogeneous airway narrowing and unresolved airway closure or near closure above the critical lung volume. Asthma control was assessed via the 6-point Asthma Control Questionnaire (ACQ6). NWC asthma was defined as ACQ6 > 1.0. In 10 NWC and 12 well-controlled subjects, ACQ6 was strongly associated with postbronchodilator (post-BD) Xrscrit ( R2 = 0.43, P < 0.001), independent of all measured variables, and was a strong predictor of NWC asthma (receiver operator characteristic area = 0.94, P < 0.001). By contrast, Xrs measures at lower lung volumes were not associated with ACQ6. Xrscrit itself was significantly associated with measures of gas trapping and ventilation heterogeneity, thus confirming the link between Xrs and airway closure and heterogeneity. Residual airway dysfunction at high lung volumes assessed via Xrscrit is an independent contributor to asthma control.

Does increased baseline ventilation heterogeneity following chest wall strapping predispose to airway hyperresponsiveness?

2012 ◽  
Vol 113 (1) ◽  
pp. 25-30 ◽  
Author(s):  
David G. Chapman ◽  
Norbert Berend ◽  
Karla R. Horlyck ◽  
Gregory G. King ◽  
Cheryl M. Salome
Keyword(s):  
Chest Wall ◽  
Airway Hyperresponsiveness ◽  
Healthy Subjects ◽  
Forced Expiratory Volume ◽  
Airway Responsiveness ◽  
High Dose ◽  
Ventilation Heterogeneity ◽  
Similar Disease ◽  
Residual Capacity ◽  
Diffusion Convection

Baseline ventilation heterogeneity is associated with airway hyperresponsiveness (AHR) in asthma; however, it is unknown whether increased baseline ventilation heterogeneity leads to AHR or both are independent effects of similar disease pathophysiology. Reducing functional residual capacity (FRC) in healthy subjects increases baseline ventilation heterogeneity and airway responsiveness, but the relationship between the two is unclear. The aim was to determine whether an increase in baseline ventilation heterogeneity due to a reduction in FRC correlated with the increase in response to methacholine. In 13 healthy male subjects, ventilation heterogeneity was measured by multiple-breath N2 washout before a cumulative high-dose (0.79–200 μmol) methacholine challenge. On a separate day, the protocol was performed with chest wall strapping (CWS) to reduce FRC. Indexes of ventilation heterogeneity in the convection-dependent (Scond) and diffusion-convection-dependent (Sacin) airways were calculated from the multiple-breath N2 washout. CWS decreased FRC by 15.6 ± 2.7% ( P < 0.0001). CWS increased the percent fall in forced expiratory volume in 1 s during bronchial challenge ( P = 0.006), and the magnitude of this effect was independently determined by the effect of CWS on Sacin and FRC ( radj2 = 0.55, P = 0.02). This suggests that changes in baseline ventilation heterogeneity in healthy subjects are sufficient to increase airway responsiveness, independent of the presence of disease pathology.

scholarly journals EVALUATION OF SMALL AIRWAY REVERSIBILITY AMONG ASTHMATIC PATIENTS WITH NON-OBSTRUCTIVE PATTERNS OF SPIROMETRY

2021 ◽  
Vol 5 (3) ◽  
Author(s):  
Tarig Merghani ◽  
Azza Alawad
Keyword(s):  
Airway Disease ◽  
Forced Expiratory Volume ◽  
Small Airway ◽  
Small Airways ◽  
Asthmatic Patients ◽  
Peripheral Airways ◽  
Flow Parameters ◽  
Small Airway Disease ◽  
Forced Expiratory Flow ◽  
Airway Reversibility

Background: Although the forced expiratory flow parameters are increasingly used in the diagnosis of small airway disease (SAD), the reversibility of these indicators is rarely described. The aim of this study is to evaluate the association of small airways reversibility with the presence of SAD and bronchodilator reversibility (BDR) of the proximal airways. Methods: The forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the indicators of SAD (FEF25%, FEF50%, FEF75%, FEF25-75%, and FEF75-85%) were measured before and 20 minutes after salbutamol administration (200 mcg by using inhaler/Spacer). Positive BDR was accepted when FEV1 or FVC was increased ? 12% and > 200 ml, indicating responsive proximal airways. Positive small airway reversibility was diagnosed when any of the small airway indicators is increased ? 30% above the baseline results. All measurements were performed with the All-flow spirometer (Clement Clarke International, Harlow, UK). Results: Evidence of SAD was found in 62.1% of all participants and in 75.2% of those who showed responsive proximal airways. The positive predictive value of the SAD in diagnosing responsive proximal airways was 67.8%. The reversibility of the small airway indicators showed insignificant association with the FEV1 or FVC BDR. The reversibility of FEF50%, FEF75% and FEF25-75% showed significant association with the diagnosis of SAD, with specificities ranging from 75.5%-81.1%. Conclusion: SAD has a significant association with positive reversibility of both the proximal and the peripheral airways. Further studies are needed to evaluate the clinical significance of positive small airway reversibility in the diagnosis and management of obstructive lung diseases. Keywords: Asthma; Small airway disease; Bronchodilator Reversibility, FEV1, FVC; FEF25-75%

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