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.

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.

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.

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.

Positive Expiratory Pressure: A Potential Therapy to Mitigate Acute Bronchoconstriction in the Asthma of Obesity

2021 ◽  
Author(s):  
Swati a. Bhatawadekar ◽  
Anne E. Dixon ◽  
Ubong Peters ◽  
Nirav Daphtary ◽  
Kevin Hodgdon ◽  
...  
Keyword(s):  
Airway Resistance ◽  
Late Onset ◽  
Rescue Therapy ◽  
Pharmacologic Therapy ◽  
Airway Closure ◽  
Airway Narrowing ◽  
Asthma Patients ◽  
Peripheral Airway ◽  
Central Airway ◽  
Positive Expiratory Pressure

Late-onset non-allergic (LONA) asthma in obesity is characterized by increased peripheral airway closure secondary to abnormally collapsible airways. We hypothesized that positive expiratory pressure (PEP) would mitigate the tendency to airway closure during bronchoconstriction, potentially serving as rescue therapy for LONA asthma of obesity. The PC20 dose of methacholine was determined in 18 obese participants with LONA asthma. At each of 4 subsequent visits, we used oscillometry to measure input respiratory impedance (Zrs) over 8 minutes; participants received their PC20 concentration of methacholine aerosol during the first 4.5 minutes. PEP combinations of either 0 or 10 cmH2O either during and/or after the methacholine delivery were applied, randomized between visits. Parameters characterizing respiratory system mechanics were extracted from the Zrs spectra. In 18 LONA asthma patients (14 females, BMI: 39.6±3.4 kg/m2), 10 cmH2O PEP during methacholine reduced elevations in the central airway resistance, peripheral airway resistance and elastance, and breathing frequency was also reduced. During the 3.5 min following methacholine delivery, PEP of 10 cmH2O reduced Ax and peripheral elastance compared to no PEP. PEP mitigates the onset of airway narrowing brought on by methacholine challenge, and airway closure once it is established. PEP thus might serve as a non-pharmacologic therapy to manage acute airway narrowing for obese LONA asthma.

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.

Bronchoprotective effect of simulated deep inspirations in tracheal smooth muscle

2014 ◽  
Vol 117 (12) ◽  
pp. 1502-1513 ◽  
Author(s):  
Christopher D. Pascoe ◽  
Graham M. Donovan ◽  
Ynuk Bossé ◽  
Chun Y. Seow ◽  
Peter D. Paré
Keyword(s):  
Smooth Muscle ◽  
Lung Function ◽  
Airway Smooth Muscle ◽  
Forced Expiratory Volume ◽  
Airway Responsiveness ◽  
Tracheal Smooth Muscle ◽  
Airway Wall ◽  
Methacholine Challenge ◽  
Airway Narrowing ◽  
The Third

Deep inspirations (DIs) taken before an inhaled challenge with a spasmogen limit airway responsiveness in nonasthmatic subjects. This phenomenon is called bronchoprotection and is severely impaired in asthmatic subjects. The ability of DIs to prevent a decrease in forced expiratory volume in 1 s (FEV1) was initially attributed to inhibition of airway narrowing. However, DIs taken before methacholine challenge limit airway responsiveness only when a test of lung function requiring a DI is used (FEV1). Therefore, it has been suggested that prior DIs enhance the compliance of the airways or airway smooth muscle (ASM). This would increase the strain the airway wall undergoes during the subsequent DI, which is part of the FEV1 maneuver. To investigate this phenomenon, we used ovine tracheal smooth muscle strips that were subjected to shortening elicited by acetylcholine with or without prior strain mimicking two DIs. The compliance of the shortened strip was then measured in response to a stress mimicking one DI. Our results show that the presence of “DIs” before acetylcholine-induced shortening resulted in 11% greater relengthening in response to the third DI, compared with the prior DIs. This effect, although small, is shown to be potentially important for the reopening of closed airways. The effect of prior DIs was abolished by the adaptation of ASM to either shorter or longer lengths or to a low baseline tone. These results suggest that DIs confer bronchoprotection because they increase the compliance of ASM, which, consequently, promotes greater strain from subsequent DI and fosters the reopening of closed airways.

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

2013 ◽  
Vol 114 (6) ◽  
pp. 770-777 ◽  
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.

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.

Modelling resistance and reactance with heterogeneous airway narrowing in mild to severe asthma

2015 ◽  
Vol 93 (3) ◽  
pp. 207-214 ◽  
Author(s):  
Swati A. Bhatawadekar ◽  
Del Leary ◽  
Geoffrey N. Maksym
Keyword(s):  
Frequency Dependence ◽  
Severe Asthma ◽  
Respiratory System ◽  
Upper Airway ◽  
Airway Disease ◽  
Small Airway ◽  
Small Airways ◽  
Airway Narrowing ◽  
Ventilation Heterogeneity

Ventilation heterogeneity is an important marker of small airway dysfunction in asthma. The frequency dependence of respiratory system resistance (Rrs) from oscillometry is used as a measure of this heterogeneity. However, this has not been quantitatively assessed or compared with other outcomes from oscillometry, including respiratory system reactance (Xrs) and the associated elastance (Ers). Here, we used a multibranch model of the human lung, including an upper airway shunt, to match previously reported respiratory mechanics in mild to severe asthma. We imposed heterogeneity by narrowing a proportion of the peripheral airways to account for patient Ers at 5 Hz, and then narrowed central airways to account for the remaining Rrs at 18 Hz. The model required >75% of the small airways to be occluded to reproduce severe asthma. While the model produced frequency dependence in Rrs, it was upward-shifted below 5 Hz compared with in-vivo results, indicating that other factors, including more distributed airway narrowing or central airway wall compliance, are required. However, Ers quantitatively reflected the imposed heterogeneity better than the frequency dependence of Rrs, independent of the frequency range for the estimation, and thus was a more robust measure of small-airway function. Thus, Ers appears to have greater potential as a clinical measure of early small-airway disease in asthma.

scholarly journals Contribution of peripheral airway function to changes in FEV1/FVC and RV/TLC with aging

2018 ◽  
Vol 125 (5) ◽  
pp. 1378-1383 ◽  
Author(s):  
Christopher Htun ◽  
Alun Pope ◽  
Samir Lahzami ◽  
Darren Luo ◽  
Robin E. Schoeffel ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Vital Capacity ◽  
Total Lung Capacity ◽  
Forced Expiratory Volume ◽  
Residual Volume ◽  
Lung Capacity ◽  
Nitrogen Washout ◽  
Airway Function ◽  
Gas Trapping ◽  
Peripheral Airway

Multiple breath nitrogen washout (MBNW) indices provide insight into ventilation heterogeneity globally [lung clearance index (LCI)] and within acinar (Sacin) and conducting (Scond) airways. Normal aging leads to an accelerated deterioration of Sacin in older adults, but little is known about the contribution of peripheral airway function to changes in pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] with aging. We aimed to examine associations between MBNW and FEV1/FVC as well as RV/TLC in healthy adults, and to determine if these relationships differ in older (≥50 yr) versus younger subjects (<50 yr). Seventy-nine healthy adult volunteers aged 23–89 yr with no cardiac or respiratory disease and a smoking history of <5 pack-years underwent spirometry, plethysmography, and MBNW. After adjustment for sex, height, and body mass index, the following relationships were present across the entire cohort: Sacin was inversely related to FEV1/FVC (R2 = 0.22, P < 0.001); Sacin and Scond were positively related to RV/TLC (R2 = 0.53, P < 0.001); on separate analyses, the relationship between Sacin and FEV1/FVC was strongest in the older group (R2 = 0.20, P = 0.003) but markedly weaker in the younger group (R2 = 0.09, P = 0.04); and Sacin and Scond were related to RV/TLC in older (R2 = 0.20, P = 0.003) but not younger subgroups. No relationships were observed between LCI and FEV1/FVC or RV/TLC. Changes in FEV1/FVC and RV/TLC are at least in part due to changes in peripheral airway function with aging. Further studies of the relationships between MBNW and standard pulmonary function indices may prove useful for their combined application and interpretation in obstructive airways disease. NEW & NOTEWORTHY This study explores associations between multiple breath nitrogen washout (MBNW) and standard pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] in healthy adults across a wide range of ages. We have demonstrated statistically significant relationships between MBNW and FEV1/FVC as well as RV/TLC. These findings provide novel evidence of the contribution of peripheral airway function to changes in standard pulmonary function indices with aging.

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