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

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.

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Effect of methacholine on peripheral lung mechanics and ventilation heterogeneity in asthma

Journal of Applied Physiology ◽

10.1152/japplphysiol.01198.2012 ◽

2013 ◽

Vol 114 (6) ◽

pp. 770-777 ◽

Cited By ~ 31

Author(s):

Sue R. Downie ◽

Cheryl M. Salome ◽

Sylvia Verbanck ◽

Bruce R. Thompson ◽

Norbert Berend ◽

...

Keyword(s):

Frequency Dependence ◽

Forced Vital Capacity ◽

Vital Capacity ◽

Lung Mechanics ◽

Forced Oscillation Technique ◽

Airway Closure ◽

Asthmatic Patients ◽

Ventilation Heterogeneity ◽

Trapped Gas ◽

Lung Periphery

The forced oscillation technique (FOT) and multiple-breath nitrogen washout (MBNW) are noninvasive tests that are potentially sensitive to peripheral airways, with MBNW indexes being especially sensitive to heterogeneous changes in ventilation. The objective was to study methacholine-induced changes in the lung periphery of asthmatic patients and determine how changes in FOT variables of respiratory system reactance (Xrs) and resistance (Rrs) and frequency dependence of resistance (Rrs5-Rrs19) can be linked to changes in ventilation heterogeneity. The contributions of air trapping and airway closure, as extreme forms of heterogeneity, were also investigated. Xrs5, Rrs5, Rrs19, Rrs5-Rrs19, and inspiratory capacity (IC) were calculated from the FOT. Ventilation heterogeneity in acinar and conducting airways, and trapped gas (percent volume of trapped gas at functional residual capacity/vital capacity), were calculated from the MBNW. Measurements were repeated following methacholine. Methacholine-induced airway closure (percent change in forced vital capacity) and hyperinflation (change in IC) were also recorded. In 40 mild to moderate asthmatic patients, increase in Xrs5 after methacholine was predicted by increases in ventilation heterogeneity in acinar airways and forced vital capacity ( r2 = 0.37, P < 0.001), but had no correlation with ventilation heterogeneity in conducting airway increase or IC decrease. Increases in Rrs5 and Rrs5-Rrs19 after methacholine were not correlated with increases in ventilation heterogeneity, trapped gas, hyperinflation, or airway closure. Increased reactance in asthmatic patients after methacholine was indicative of heterogeneous changes in the lung periphery and airway closure. By contrast, increases in resistance and frequency dependence of resistance were not related to ventilation heterogeneity or airway closure and were more indicative of changes in central airway caliber than of heterogeneity.

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.01618.2011 ◽

2012 ◽

Vol 113 (6) ◽

pp. 958-966 ◽

Cited By ~ 28

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.

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Respiratory system reactance is an independent determinant of asthma control

Journal of Applied Physiology ◽

10.1152/japplphysiol.00093.2013 ◽

2013 ◽

Vol 115 (9) ◽

pp. 1360-1369 ◽

Cited By ~ 22

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.

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Hyperpolarized Helium-3 Magnetic Resonance Imaging Ventilation Heterogeneity in Chronic Obstructive Pulmonary Disease.

10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a6202 ◽

2009 ◽

Author(s):

MA Kirby ◽

AR Wheatley ◽

DG McCormack ◽

G Parraga

Keyword(s):

Magnetic Resonance Imaging ◽

Chronic Obstructive Pulmonary Disease ◽

Magnetic Resonance ◽

Pulmonary Disease ◽

Chronic Obstructive ◽

Resonance Imaging ◽

Obstructive Pulmonary Disease ◽

Hyperpolarized Helium ◽

Ventilation Heterogeneity ◽

Helium 3

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Deep inspirations protect against airway closure in nonasthmatic subjects

Journal of Applied Physiology ◽

10.1152/japplphysiol.00202.2009 ◽

2009 ◽

Vol 107 (2) ◽

pp. 564-569 ◽

Cited By ~ 19

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.

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