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.

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.

Deep breaths, methacholine, and airway narrowing in healthy and mild asthmatic subjects

2002 ◽  
Vol 93 (4) ◽  
pp. 1384-1390 ◽  
Author(s):  
Emanuele Crimi ◽  
Riccardo Pellegrino ◽  
Manlio Milanese ◽  
Vito Brusasco
Keyword(s):  
Forced Vital Capacity ◽  
Healthy Subjects ◽  
Vital Capacity ◽  
Forced Expiratory Volume ◽  
Forced Expiration ◽  
Airway Narrowing ◽  
Significant Difference ◽  
Mild Asthmatic ◽  
Residual Capacity ◽  
Airway Conductance

Deep breaths taken before inhalation of methacholine attenuate the decrease in forced expiratory volume in 1 s and forced vital capacity in healthy but not in asthmatic subjects. We investigated whether this difference also exists by using measurements not preceded by full inflation, i.e., airway conductance, functional residual capacity, as well as flow and residual volume from partial forced expiration. We found that five deep breaths preceding a single dose of methacholine 1) transiently attenuated the decrements in forced expiratory volume in 1 s and forced vital capacity in healthy ( n = 8) but not in mild asthmatic ( n = 10) subjects and 2) increased the areas under the curve of changes in parameters not preceded by a full inflation over 40 min, during which further deep breaths were prohibited, without significant difference between healthy ( n = 6) and mild asthmatic ( n = 16) subjects. In conclusion, a series of deep breaths preceding methacholine inhalation significantly enhances bronchoconstrictor response similarly in mild asthmatic and healthy subjects but facilitates bronchodilatation on further full inflation in the latter.

Mechanical effects of obesity on airway responsiveness in otherwise healthy humans

2009 ◽  
Vol 107 (2) ◽  
pp. 408-416 ◽  
Author(s):  
Roberto Torchio ◽  
Alessandro Gobbi ◽  
Carlo Gulotta ◽  
Raffaele Dellacà ◽  
Marco Tinivella ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Lung Function ◽  
Body Mass ◽  
Airway Hyperresponsiveness ◽  
Healthy Subjects ◽  
Rest Period ◽  
Healthy Humans ◽  
Before And After ◽  
Maximum Expiratory Flow ◽  
Residual Capacity

We investigated whether obesity is associated with airway hyperresponsiveness in otherwise healthy humans and, if so, whether this correlates with a restrictive lung function pattern or a decreased number of sighs at rest and/or during walking. Lung function was studied before and after inhaling methacholine (MCh) in 41 healthy subjects with body mass index ranging from 20 to 56. Breathing pattern was assessed during a 60-min rest period and a 30-min walk. The dose of MCh that produced a 50% decrease in the maximum expiratory flow measured in a body plethysmograph (PD50MCh) was inversely correlated with body mass index ( r2 = 0.32, P < 0.001) and waist circumference ( r2 = 0.25, P < 0.001). Significant correlations with body mass index were also found with the maximum changes in respiratory resistance ( r2 = 0.19, P < 0.001) and reactance ( r2 = 0.40, P < 0.001) measured at 5 Hz. PD50MCh was also positively correlated with functional residual capacity ( r2 = 0.56, P < 0.001) and total lung capacity ( r2 = 0.59, P < 0.001) in men, but not in women. Neither PD50MCh nor body mass index correlated with number of sighs, average tidal volume, ventilation, or breathing frequency. In this study, airway hyperresponsiveness was significantly associated with obesity in otherwise healthy subjects. In obese men, but not in women, airway hyperresponsiveness was associated with the decreases in lung volumes.

scholarly journals Regional airflow obstruction after bronchoconstriction and subsequent bronchodilation in subjects without pulmonary disease

2019 ◽  
Vol 127 (1) ◽  
pp. 31-39 ◽  
Author(s):  
E. T. Geier ◽  
R. J. Theilmann ◽  
G. K. Prisk ◽  
R. C. Sá
Keyword(s):  
Healthy Subjects ◽  
Standard Dose ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Normal Subjects ◽  
Forced Expiratory Volume ◽  
Bronchodilator Therapy ◽  
Ventilation Imaging ◽  
Ventilation Heterogeneity ◽  
Healthy Lung

Some subjects with asthma have ventilation defects that are resistant to bronchodilator therapy, and it is thought that these resistant defects may be due to ongoing inflammation or chronic airway remodeling. However, it is unclear whether regional obstruction due to bronchospasm alone persists after bronchodilator therapy. To investigate this, six young, healthy subjects, in whom inflammation and remodeling were assumed to be absent, were bronchoconstricted with a PC20 [the concentration of methacholine that elicits a 20% drop in forced expiratory volume in 1 s (FEV1)] dose of methacholine and subsequently bronchodilated with a standard dose of albuterol on three separate occasions. Specific ventilation imaging, a proton MRI technique, was used to spatially map specific ventilation across 80% of each subject’s right lung in each condition. The ratio between regional specific ventilation at baseline and after intervention was used to classify areas that had constricted. After albuterol rescue from methacholine bronchoconstriction, 12% (SD 9) of the lung was classified as constricted. Of the 12% of lung units that were classified as constricted after albuterol, approximately half [7% (SD 7)] had constricted after methacholine and failed to recover, whereas half [6% (SD 4)] had remained open after methacholine but became constricted after albuterol. The incomplete regional recovery was not reflected in the subjects’ FEV1 measurements, which did not decrease from baseline ( P = 0.97), nor was it detectable as an increase in specific ventilation heterogeneity ( P = 0.78). NEW & NOTEWORTHY In normal subjects bronchoconstricted with methacholine and subsequently treated with albuterol, not all regions of the healthy lung returned to their prebronchoconstricted specific ventilation after albuterol, despite full recovery of integrative lung indexes (forced expiratory volume in 1 s and specific ventilation heterogeneity). The regions that remained bronchoconstricted following albuterol were those with the highest specific ventilation at baseline, which suggests that they may have received the highest methacholine dose.

Inflation of antishock trousers increases bronchial response to methacholine in healthy subjects

1990 ◽  
Vol 68 (4) ◽  
pp. 1528-1533 ◽  
Author(s):  
J. Regnard ◽  
P. Baudrillard ◽  
B. Salah ◽  
A. T. Dinh Xuan ◽  
L. Cabanes ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Vital Capacity ◽  
Alternative Explanation ◽  
Venous Occlusion ◽  
Forced Expiratory Volume ◽  
Lower Limbs ◽  
Base Line ◽  
Lung Volumes ◽  
Residual Capacity ◽  
Lung Vessels

We studied changes in lung volumes and in bronchial response to methacholine chloride (MC) challenge when antishock trousers (AST) were inflated at venous occlusion pressure in healthy subjects in the standing posture, a maneuver known to shift blood toward lung vessels. On inflation of bladders isolated to lower limbs, lung volumes did not change but bronchial response to MC increased, as evidenced by a greater fall in the forced expiratory volume in 1 s (FEV1) at the highest dose of MC used compared with control without AST inflation (delta FEV1 = 0.94 +/- 0.40 vs. 0.66 +/- 0.46 liter, P less than 0.001). Full inflation of AST, i.e., lower limb and abdominal bladder inflated, significantly reduced vital capacity (P less than 0.001), functional residual capacity (P less than 0.01), and FEV1 (P less than 0.01) and enhanced the bronchial response to MC challenge compared with partial AST inflation (delta FEV1 = 1.28 +/- 0.47 liter, P less than 0.05). Because there was no significant reduction of lung volumes on partial AST inflation, the enhanced bronchial response to MC cannot be explained solely by changes in base-line lung volumes. An alternative explanation might be a congestion and/or edema of the airway wall on AST inflation. Therefore, to investigate further the mechanism of the increased bronchial response to MC, we pretreated the subjects with the inhaled alpha 1-adrenergic agonist methoxamine, which has both direct bronchoconstrictor and bronchial vasoconstrictor effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Crural diaphragm activation during dynamic contractions at various inspiratory flow rates

1998 ◽  
Vol 85 (2) ◽  
pp. 451-458 ◽  
Author(s):  
Jennifer Beck ◽  
Christer Sinderby ◽  
Lars Lindström ◽  
Alex Grassino
Keyword(s):  
Chest Wall ◽  
Functional Residual Capacity ◽  
Healthy Subjects ◽  
Total Lung Capacity ◽  
Inspiratory Flow ◽  
Transdiaphragmatic Pressure ◽  
Flow Rates ◽  
Lung Capacity ◽  
Dynamic Contractions ◽  
Residual Capacity

The purpose of this study was to evaluate the influence of velocity of shortening on the relationship between diaphragm activation and pressure generation in humans. This was achieved by relating the root mean square (RMS) of the diaphragm electromyogram to the transdiaphragmatic pressure (Pdi) generated during dynamic contractions at different inspiratory flow rates. Five healthy subjects inspired from functional residual capacity to total lung capacity at different flow rates while reproducing identical Pdi and chest wall configuration profiles. To change the inspiratory flow rate, subjects performed the inspirations while breathing across two different inspiratory resistances (10 and 100 cmH2O ⋅ l−1 ⋅ s), at mouth pressure targets of −10, −20, −40, and −60 cmH2O. The diaphragm electromyogram was recorded and analyzed with control of signal contamination and electrode positioning. RMS values obtained for inspirations with identical Pdi and chest wall configuration profiles were compared at the same percentage of inspiratory duration. At inspiratory flows ranging between 0.1 and 1.4 l/s, there was no difference in the RMS for the inspirations from functional residual capacity to total lung capacity when Pdi and chest wall configuration profiles were reproduced ( n = 4). At higher inspiratory flow rates, subjects were not able to reproduce their chest wall displacements and adopted different recruitment patterns. In conclusion, there was no evidence for increased demand of diaphragm activation when healthy subjects breathe with similar chest wall configuration and Pdi profiles, at increasing flow rates up to 1.4 l/s.

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 Ventilation heterogeneity measured by multiple breath inert gas testing is not affected by inspired oxygen concentration in healthy humans

2017 ◽  
Vol 122 (6) ◽  
pp. 1379-1387 ◽  
Author(s):  
Susan R. Hopkins ◽  
Ann R. Elliott ◽  
G. Kim Prisk ◽  
Chantal Darquenne
Keyword(s):  
Oxygen Concentration ◽  
Healthy Subjects ◽  
Phase Iii ◽  
Ventilation Distribution ◽  
Healthy Humans ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout ◽  
Residual Capacity ◽  
Gaussian Fit ◽  
Inspired Oxygen

Multiple breath washout (MBW) and oxygen-enhanced MRI techniques use acute exposure to 100% oxygen to measure ventilation heterogeneity. Implicit is the assumption that breathing 100% oxygen does not induce changes in ventilation heterogeneity; however, this is untested. We hypothesized that ventilation heterogeneity decreases with increasing inspired oxygen concentration in healthy subjects. We performed MBW in 8 healthy subjects (4 women, 4 men; age = 43 ± 15 yr) with normal pulmonary function (FEV1 = 98 ± 6% predicted) using 10% argon as a tracer gas and oxygen concentrations of 12.5%, 21%, or 90%. MBW was performed in accordance with ERS-ATS guidelines. Subjects initially inspired air followed by a wash-in of test gas. Tests were performed in balanced order in triplicate. Gas concentrations were measured at the mouth, and argon signals rescaled to mimic a N2 washout, and analyzed to determine the distribution of specific ventilation (SV). Heterogeneity was characterized by the width of a log-Gaussian fit of the SV distribution and from Sacin and Scond indexes derived from the phase III slope. There were no significant differences in the ventilation heterogeneity due to altered inspired oxygen: histogram width (hypoxia 0.57 ± 0.11, normoxia 0.60 ± 0.08, hyperoxia 0.59 ± 0.09, P = 0.51), Scond (hypoxia 0.014 ± 0.011, normoxia 0.012 ± 0.015, hyperoxia 0.010 ± 0.011, P = 0.34), or Sacin (hypoxia 0.11 ± 0.04, normoxia 0.10 ± 0.03, hyperoxia 0.12 ± 0.03, P = 0.23). Functional residual capacity was increased in hypoxia ( P = 0.04) and dead space increased in hyperoxia ( P = 0.0001) compared with the other conditions. The acute use of 100% oxygen in MBW or MRI is unlikely to affect ventilation heterogeneity. NEW & NOTEWORTHY Hyperoxia is used to measure the distribution of ventilation in imaging and MBW but may alter the underlying ventilation distribution. We used MBW to evaluate the effect of inspired oxygen concentration on the ventilation distribution using 10% argon as a tracer. Short-duration exposure to hypoxia (12.5% oxygen) and hyperoxia (90% oxygen) during MBW had no significant effect on ventilation heterogeneity, suggesting that hyperoxia can be used to assess the ventilation distribution.

Mechanical properties of lungs and chest wall during spontaneous breathing

1980 ◽  
Vol 49 (3) ◽  
pp. 408-416 ◽  
Author(s):  
J. Nagels ◽  
F. J. Landser ◽  
L. van der Linden ◽  
J. Clement ◽  
K. P. Van de Woestijne
Keyword(s):  
Chest Wall ◽  
Healthy Subjects ◽  
Compartment Model ◽  
Simultaneous Increase ◽  
Chronic Obstructive ◽  
Forced Oscillation Technique ◽  
Compartment System ◽  
Lung Volumes ◽  
Obstructive Pulmonary Disease ◽  
Residual Capacity

Using a forced oscillation technique, we measured the resistance (Rrs) and reactance (Xrs) of the respiratory system between 2 and 32 Hz at three different lung volumes in 15 healthy subjects and 7 patients with chronic obstructive pulmonary disease. Rrs and Xrs were partitioned, by means of a pressure recording in the esophagus, into the resistance and reactance of lung and airways (L) and the chest wall. The measurements were validated by checking the adequacy of the frequency response of the esophagus, by the lack of difference between thoracic and mouth flow, by an estimation of the error introduced by the shunt impedance of the cheeks, and by comparisons with the values of pulmonary compliance and resistance determined in the same subjects with classical techniques. In both healthy subjects and patients, the chest wall has a low resistance that increases somewhat at low lung volumes and behaves functionally as a two-compartment system, with low capacitance at frequencies exceeding 4 Hz. Rrs varies with lung volume and is markedly frequency dependent in patients; both phenomena are due primarily to corresponding variations of RL. In healthy subjects, at and above functional residual capacity (FRC) level, the lungs behave as a one-compartment system, the reactance of which is mainly determined by the gaseous inertance, at least beyond 2 Hz. In patients and in healthy subjects breathing below FRC, the observed frequency dependence of resistance and the simultaneous increase in resonant frequency can be simulated satisfactorily by Mead's two-compartment model, assuming a large increase in peripheral airways resistance.

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.

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