Effect of airway smooth muscle tone on airway distensibility measured by the forced oscillation technique in adults with asthma

2012 ◽  
Vol 112 (9) ◽  
pp. 1494-1503 ◽  
Author(s):  
Vanessa J. Kelly ◽  
Nathan J. Brown ◽  
Scott A. Sands ◽  
Brigitte M. Borg ◽  
Gregory G. King ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Lung Volume ◽  
Forced Oscillation ◽  
Muscle Tone ◽  
Forced Oscillation Technique ◽  
Airway Closure ◽  
Lung Volumes ◽  
Volume Relationship ◽  
Residual Capacity

Airway distensibility appears to be unaffected by airway smooth muscle (ASM) tone, despite the influence of ASM tone on the airway diameter-pressure relationship. This discrepancy may be because the greatest effect of ASM tone on airway diameter-pressure behavior occurs at low transpulmonary pressures, i.e., low lung volumes, which has not been investigated. Our study aimed to determine the contribution of ASM tone to airway distensibility, as assessed via the forced oscillation technique (FOT), across all lung volumes with a specific focus on low lung volumes. We also investigated the accompanying influence of ASM tone on peripheral airway closure and heterogeneity inferred from the reactance versus lung volume relationship. Respiratory system conductance and reactance were measured using FOT across the entire lung volume range in 22 asthma subjects and 19 healthy controls before and after bronchodilator. Airway distensibility (slope of conductance vs. lung volume) was calculated at residual volume (RV), functional residual capacity (FRC), and total lung capacity. At baseline, airway distensibility was significantly lower in subjects with asthma at all lung volumes. After bronchodilator, distensibility significantly increased at RV (64.8%, P < 0.001) and at FRC (61.8%, P < 0.01) in subjects with asthma but not in control subjects. The increased distensibility at RV and FRC in asthma were not associated with the accompanying changes in the reactance versus lung volume relationship. Our findings demonstrate that, at low lung volumes, ASM tone reduces airway distensibility in adults with asthma, independent of changes in airway closure and heterogeneity.

scholarly journals Respiratory system reactance reflects communicating lung volume in chronic obstructive pulmonary disease

2019 ◽  
Vol 126 (5) ◽  
pp. 1223-1231 ◽  
Author(s):  
Stephen Milne ◽  
Kanika Jetmalani ◽  
David G. Chapman ◽  
Joseph M. Duncan ◽  
Claude S. Farah ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Respiratory System ◽  
Lung Volume ◽  
Forced Oscillation ◽  
Chronic Obstructive ◽  
Forced Oscillation Technique ◽  
Obstructive Pulmonary Disease ◽  
Volume Relationship ◽  
Residual Capacity

Respiratory system reactance (Xrs) measured by the forced oscillation technique (FOT) is theoretically and experimentally related to lung volume. In chronic obstructive pulmonary disease (COPD), the absolute volume measured by body plethysmography includes a proportion that is inaccessible to pressure oscillations applied via the mouth, that is, a “noncommunicating” lung volume. We hypothesized that in COPD the presence of noncommunicating lung would disrupt the expected Xrs-volume relationship compared with plethysmographic functional residual capacity (FRCpleth). Instead, Xrs would relate to estimates of communicating volume, namely, expiratory reserve volume (ERV) and single-breath alveolar volume (VaSB). We examined FOT and lung function data from people with COPD ( n = 51) and from healthy volunteers ( n = 40). In healthy volunteers, we observed an expected inverse relationship between reactance at 5 Hz (X5) and FRCpleth. In contrast, there was no such relationship between X5 and FRCpleth in COPD subjects. However, there was an inverse relationship between X5 and both ERV and VaSB. Hence the theoretical Xrs-volume relationship is present in COPD but only when considering the communicating volume rather than the absolute lung volume. These findings confirm the role of reduced communicating lung volume as an important determinant of Xrs and therefore advance our understanding and interpretation of FOT measurements in COPD. NEW & NOTEWORTHY To investigate the determinants of respiratory system reactance (Xrs) measured by the forced oscillation technique (FOT) in chronic obstructive pulmonary disease (COPD), we examine the relationship between Xrs and lung volume. We show that Xrs does not relate to absolute lung volume (functional residual capacity) in COPD but instead relates only to the volume of lung in communication with the airway opening. This communicating volume may therefore be fundamental to our interpretation of FOT measurements in COPD and other pulmonary diseases.

Airway closure with high PEEP in vivo

2000 ◽  
Vol 89 (3) ◽  
pp. 956-960 ◽  
Author(s):  
Robert H. Brown ◽  
Wayne Mitzner
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Functional Residual Capacity ◽  
Lung Volume ◽  
Transpulmonary Pressure ◽  
High Peep ◽  
Airway Closure ◽  
Residual Capacity

When airway smooth muscle is contracted in vitro, the airway lumen continues to narrow with increasing concentrations of agonist until complete airway closure occurs. Although there remains some controversy regarding whether airways can close in vivo, recent work has clearly demonstrated that, if the airway is sufficiently stimulated with contractile agonists, complete closure of even large cartilaginous conducting airways can readily occur with the lung at functional residual capacity (Brown RH and Mitzner W. J Appl Physiol 85: 2012–2017, 1998). This result suggests that the tethering of airways in situ by parenchymal attachments is small at functional residual capacity. However, at lung volumes above functional residual capacity, the outward tethering of airways should increase, because both the parenchymal shear modulus and tethering forces increase in proportion to the transpulmonary pressure. In the present study, we tested whether we could prevent airway closure in vivo by increasing lung volume with positive end-expiratory pressure (PEEP). Airway smooth muscle was stimulated with increasing methacholine doses delivered directly to airway smooth muscle at three levels of PEEP (0, 6, and 10 cmH2O). Our results show that increased lung volume shifted the airway methacholine dose-response curve to the right, but, in many airways in most animals, airway closure still occurred even at the highest levels of PEEP.

Effects of lung volume and surface forces on maximal airway smooth muscle shortening

1994 ◽  
Vol 77 (4) ◽  
pp. 1755-1762 ◽  
Author(s):  
A. James ◽  
G. Pearce-Pinto ◽  
D. Hillman
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Lung Volume ◽  
Muscle Layer ◽  
Surface Forces ◽  
Krebs Solution ◽  
Airway Closure ◽  
Lung Volumes ◽  
Muscle Shortening ◽  
Outer Perimeter

The effects of lung volume and surface forces on airway smooth muscle shortening were studied in isolated perfused rat lungs. The lungs were inflated via the trachea with gas or Krebs solution (n = 12 each) to volumes equivalent to gas inflation pressures of 5 (low), 15 (medium), and 25 (high) cmH2O (n = 4 each). At each volume, two of the four lungs were perfused with methacholine (10(-2) M) and then all were perfused with Formalin for fixation. The amount of smooth muscle shortening present in transverse sections of the airways was determined by comparing the observed outer perimeter of the smooth muscle layer with its calculated relaxed perimeter. In the control lungs, mean shortening was < or = 10% in all groups except the liquid-filled lungs at low lung volumes [33 +/- 12% (SD)]. In the methacholine-stimulated lungs, mean shortening was between 45 and 56% at medium and low lung volumes in gas- and liquid-filled lungs, respectively, and approximated the degree of shortening required to cause airway closure. At high lung volume, less shortening was observed in the methacholine-stimulated lungs, either liquid (34 +/- 17%) or gas filled (16 +/- 19%; P < 0.05 compared with liquid filled). The effects of lung volume in liquid-filled lungs and the differences in response between gas- and liquid-filled lungs demonstrate, respectively, that both lung tissue recoil and surface forces act to oppose shortening of maximally stimulated smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway smooth muscle tone increases airway responsiveness in healthy young adults

2017 ◽  
Vol 312 (3) ◽  
pp. L348-L357 ◽  
Author(s):  
Morgan Gazzola ◽  
Katherine Lortie ◽  
Cyndi Henry ◽  
Samuel Mailhot-Larouche ◽  
David G. Chapman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Airway Responsiveness ◽  
High Dose ◽  
Forced Oscillation Technique ◽  
Single High Dose ◽  
Healthy Humans

Force adaptation, a process whereby sustained spasmogenic activation (viz., tone) of airway smooth muscle (ASM) increases its contractile capacity, has been reported in isolated ASM tissues in vitro, as well as in mice in vivo. The objective of the present study was to assess the effect of tone on airway responsiveness in humans. Ten healthy volunteers underwent methacholine challenge on two occasions. One challenge consisted of six serial doses of saline followed by a single high dose of methacholine. The other consisted of six low doses of methacholine 5 min apart followed by a higher dose. The cumulative dose was identical for both challenges. After both methacholine challenges, subjects took a deep inspiration (DI) to total lung capacity as another way to probe ASM mechanics. Responses to methacholine and the DI were measured using a multifrequency forced oscillation technique. Compared with a single high dose, the challenge preceded by tone led to an elevated response measured by respiratory system resistance (Rrs) and reactance at 5 Hz. However, there was no difference in the increase in Rrs at 19 Hz, suggesting a predominant effect on smaller airways. Increased tone also reduced the efficacy of DI, measured by an attenuated maximal dilation during the DI and an increased renarrowing post-DI. We conclude that ASM tone increases small airway responsiveness to inhaled methacholine and reduces the effectiveness of DI in healthy humans. This suggests that force adaptation may contribute to airway hyperresponsiveness and the reduced bronchodilatory effect of DI in asthma.

Problems with plethysmographic estimation of lung volume in infants and young children

1982 ◽  
Vol 53 (3) ◽  
pp. 698-702 ◽  
Author(s):  
P. Helms
Keyword(s):  
Young Children ◽  
Lung Volume ◽  
Airway Resistance ◽  
Pressure Change ◽  
Airway Closure ◽  
Lung Volumes ◽  
Mouth Pressure ◽  
Residual Capacity ◽  
Young Subjects ◽  
Intraesophageal Pressure

In 57 infants and very young children, less than 2 yr of age and with a variety of cardiopulmonary illnesses, problems were encountered in the estimation of lung volume with the plethysmographic technique. In 19 subjects calculated thoracic gas volume (TGV) was found to be consistently larger when airway occlusions were performed at low lung volumes than when performed at higher lung volumes. In 13 infants, changes in intraesophageal pressure (Pes) during airway occlusions were found to be larger than simultaneous changes in mouth pressure. In 25 subjects in whom none of the above changes were observed, total pulmonary resistance (TPR) and airway resistance (Raw) did not differ significantly [mean TPR, 50.1 +/- 27.5 cmH2O X l-1; mean Raw, 48.1 +/- 26.5 (P greater than 0.5)]. In the 13 subjects in whom the delta Pes-to-delta Pm occlusion ratio exceeded 1.05, closest agreement with specific resistance (sRaw) and TPR derived lung volume was found when TGV was calculated with delta Pes rather than mouth pressure change (delta Pm). A similar close agreement with the sRaw TPR derived volume was obtained when TGV was calculated during airway occlusions at the higher lung volume. Two separate lung models are proposed to explain these observations, one with a segmental airway closure and the other with more a generalized airway closure. If plethysmographic techniques are to be used in these young subjects for the estimation of lung volume and airway resistance, possible errors may be reduced by performing airway occlusions at lung volumes above functional residual capacity and noting the delta Pes-to-delta Pm ratio obtained during the occlusion.

Chest wall distortion and discharge of pulmonary slowly adapting receptors

1992 ◽  
Vol 73 (4) ◽  
pp. 1619-1625 ◽  
Author(s):  
S. Iscoe ◽  
S. P. Gordon
Keyword(s):  
Smooth Muscle ◽  
Chest Wall ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Respiratory Neurons ◽  
Lung Inflation ◽  
Smooth Muscle Tone ◽  
Residual Capacity ◽  
Discharge Patterns ◽  
Spontaneously Breathing

We assessed the effects of chest wall distortion, changes in lung volume, and abolition of airway smooth muscle tone on the discharge patterns of 92 pulmonary slowly adapting receptors (SAR) in decerebrate, spontaneously breathing cats. Distortion resulted from their inspiratory efforts against an occluded airway at functional residual capacity and at increased end-expiratory lung volumes. Approximately 40% of SAR increased discharge frequencies during occlusions. Modulation of SAR discharge during occlusions persisted after administration of atropine to eliminate airway smooth muscle tone. Phasic modulation of SAR discharge was eliminated during no-inflation tests after paralyzing the cats and ventilating them on a cycle-triggered pump. We conclude 1) parasympathetic modulation of airway smooth muscle tone makes no obvious contribution to SAR discharge in spontaneously breathing cats; 2) the no-inflation test (withholding of lung inflation during neural inspiration) in paralyzed and ventilated cats is a valid test for the presence of projections from SAR to medullary respiratory neurons; and 3) in the absence of tidal volume changes, distortion stimulates some SAR. Sensory feedback from receptors in the lung, not just those in the chest wall, may therefore provide information about abnormal chest wall configurations.

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 Early onset of airway derecruitment assessed using the forced oscillation technique in subjects with asthma

2019 ◽  
Vol 126 (5) ◽  
pp. 1399-1408 ◽  
Author(s):  
Kris Nilsen ◽  
Francis Thien ◽  
Cindy Thamrin ◽  
Matt J. Ellis ◽  
G. Kim Prisk ◽  
...  
Keyword(s):  
Lung Volume ◽  
Forced Oscillation ◽  
Lung Mechanics ◽  
Control Group ◽  
Forced Oscillation Technique ◽  
Rapid Reduction ◽  
Control Subjects ◽  
Volume Curve ◽  
Volume Relationship ◽  
Highly Correlated

Derecruitment of air spaces in the lung occurs when airways close during exhalation and is related to ventilation heterogeneity and symptoms in asthma. The forced oscillation technique has been used to identify surrogate measures of airway closure via the reactance (Xrs) versus lung volume relationship. This study used a new algorithm to identify derecruitment from the Xrs versus lung volume relationship from a slow vital capacity maneuver. We aimed to compare two derecruitment markers on the Xrs versus volume curve, the onset reduction of Xrs (DR1vol) and the onset of more rapid reduction of Xrs (DR2vol), between control and asthmatic subjects. We hypothesized that the onset of DR1vol and DR2vol occurred at higher lung volume in asthmatic subjects. DR1vol and DR2vol were measured in 18 subjects with asthma and 18 healthy controls, and their relationships with age and height were examined using linear regression. In the control group, DR1vol and DR2vol increased with age ( r2 = 0.68, P < 0.001 and r2 = 0.71, P < 0.001, respectively). DR1vol and DR2vol in subjects with asthma [76.58% of total lung capacity (TLC) and 56.79%TLC, respectively] were at higher lung volume compared with control subjects (46.1 and 37.69%TLC, respectively) ( P < 0.001). DR2vol correlated with predicted values of closing capacity ( r = 0.94, P < 0.001). This study demonstrates that derecruitment occurs at two points along the Xrs-volume relationship. Both derecruitment points occurred at significantly higher lung volumes in subjects with asthma compared with healthy control subjects. This technique offers a novel way to measure the effects of changes in airways/lung mechanics. NEW & NOTEWORTHY This study demonstrates that the forced oscillation technique can be used to identify two lung volume points where lung derecruitment occurs: 1) where derecruitment is initiated and 2) where onset of rapid derecruitment commences. Measurements of derecruitment increase with age. The onset of rapid derecruitment was highly correlated with predicted closing capacity. Also, the initiation and rate of derecruitment are significantly altered in subjects with asthma.

Airway distensibility and volume recruitment with lung inflation in COPD

2010 ◽  
Vol 109 (4) ◽  
pp. 1019-1026 ◽  
Author(s):  
Simonetta Baldi ◽  
Raffaele Dellacà ◽  
Leonardo Govoni ◽  
Roberto Torchio ◽  
Andrea Aliverti ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Lung Volume ◽  
Muscle Tone ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
High Resolution Computed Tomography ◽  
Lung Inflation ◽  
Control Subjects ◽  
Airway Caliber

The effects of full lung inflation on respiratory conductance (Grs) and reactance (Xrs) were measured in 15 subjects with moderate to severe chronic obstructive pulmonary disease (COPD) and 11 matched healthy control subjects. Airway distensibility was estimated from the ratio of the difference of Grs between functional residual capacity and total lung capacity to the relevant changes in lung volume (ΔGrs/ΔVl) or transpulmonary pressure (ΔGrs/ΔPtp). Similar analysis was applied to Xrs to estimate lung volume recruitment (ΔXrs/ΔVl or ΔXrs/ΔPtp). The extent of emphysema in COPD subjects was estimated from the percentage of low attenuation area (LAA) at high-resolution computed tomography. At baseline, ΔGrs/ΔVl and ΔXrs/ΔVl were significantly less in COPD than control subjects, indicating less distensibility and volume recruitment in the former. In COPD, ΔGrs/ΔPtp and ΔXrs/ΔPtp were uncorrelated with LAA but correlated with 1-s forced expiratory volume and with each other. After albuterol, both ΔGrs/ΔPtp and ΔGrs/ΔVl became significantly and negatively correlated with LAA, while ΔXrs/ΔPtp and ΔXrs/ΔVl decreased significantly independently of LAA. Moreover, ΔGrs/ΔPtp and ΔXrs/ΔPtp with lung inflation were no longer correlated with each other, suggesting that airway distensibility and volume recruitment were affected differently by airway smooth muscle tone. Assuming that Grs mainly reflects airway caliber and Xrs the number of ventilated lung units, we conclude that airway smooth muscle contributes to airway stiffness and ventilation inhomogeneities in COPD subjects with prevailing bronchitis but only to the latter in those with more emphysema. We suggest that changes of airway distensibility and volume recruitment with a bronchodilator may be useful for disease phenotyping.

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