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.

scholarly journals Diagnostic accuracy of FEV1/forced vital capacity ratio z scores in asthmatic patients

2015 ◽  
Vol 136 (3) ◽  
pp. 649-653.e4 ◽  
Author(s):  
Allison Lambert ◽  
M. Bradley Drummond ◽  
Christine Wei ◽  
Charles Irvin ◽  
David Kaminsky ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Asthmatic Patients ◽  
Capacity Ratio ◽  
Z Scores

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.

Heterogeneity of bronchoconstriction does not distinguish mild asthmatic subjects from healthy controls when supine

2008 ◽  
Vol 104 (1) ◽  
pp. 10-19 ◽  
Author(s):  
David A. Kaminsky ◽  
Charles G. Irvin ◽  
Lennart K. A. Lundblad ◽  
John Thompson-Figueroa ◽  
Jeffrey Klein ◽  
...  
Keyword(s):  
Frequency Dependence ◽  
Computerized Tomography ◽  
Forced Oscillation ◽  
Fundamental Property ◽  
Lung Mechanics ◽  
Mild Asthma ◽  
Forced Oscillation Technique ◽  
Healthy Controls ◽  
Space Size ◽  
Air Space

Heterogeneity is a fundamental property of airway constriction; however, whether it is a distinguishing feature of mild asthma is not clear. We used computerized tomography and the forced oscillation technique to compare lung heterogeneity between 18 mildly asthmatic and 19 healthy control subjects at similar levels of bronchoconstriction while subjects were supine. We also assessed the effects of deep inhalation and albuterol on supine lung mechanics. Measures of heterogeneity included lung attenuation, from which we derived a novel index of air-space size, and the frequency dependence of respiratory system resistance between 1 and 20 Hz. We found that asthmatic subjects had airways hyperresponsiveness to methacholine in the sitting position compared with controls, but both groups had similar falls in forced expiratory volume in 1 s after inhaling methacholine while supine. There were no baseline differences between the groups in the frequency dependence of resistance, or lung attenuation, before methacholine, and both groups responded similarly with an increase in air-space size (+9.2% vs. +3.4%), air-space size heterogeneity (+9.8% vs. +4.2%), and frequency dependence of resistance (+76% vs. +86%) after methacholine. Deep inhalation did not affect resistance in either group, but albuterol significantly reduced resistance in both groups. We conclude that both computerized tomography and the forced oscillation technique demonstrate increased heterogeneity of airway narrowing during induced bronchoconstriction while supine and that this heterogeneity is equivalent between subjects with mild asthma and healthy controls when bronchoconstricted to the same degree. Thus heterogeneity appears to be a fundamental feature of bronchoconstriction and is not unique to mild asthma.

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 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.

Relationship between quasi-static pulmonary hysteresis and maximal airway narrowing in humans

1992 ◽  
Vol 72 (6) ◽  
pp. 2075-2080 ◽  
Author(s):  
V. Brusasco ◽  
R. Pellegrino ◽  
B. Violante ◽  
E. Crimi
Keyword(s):  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Transpulmonary Pressure ◽  
Forced Expiratory Volume ◽  
Maximal Response ◽  
Flow Volume ◽  
Airway Narrowing ◽  
Group 2 ◽  
Lung Periphery ◽  
Group 1

Two groups of subjects were studied: one with (group 1: 5 healthy and 4 mildly asthmatic subjects) and another without (group 2:9 moderately and severely asthmatic subjects) a plateau of response to methacholine (MCh). We determined the effect of deep inhalation by comparing expiratory flows at 40% of forced vital capacity from maximal and partial flow-volume curves (MEF40M/P) and the quasi-static transpulmonary pressure-volume (Ptp-V) area. In group 1, MEF40M/P increased from 1.58 +/- 0.23 (SE) at baseline up to a maximum of 3.91 +/- 0.69 after MCh when forced expiratory volume in 1 s (FEV1) was decreased on plateau by 24 +/- 2%. The plateau of FEV1 was always paralleled by a plateau of MEF40M/P. In group 2, MEF40 M/P increased from 1.58 +/- 0.10 at baseline up to a maximum of 3.48 +/- 0.26 after MCh when FEV1 was decreased by 31 +/- 3% and then decreased to 2.42 +/- 0.24 when FEV1 was decreased by 46 +/- 2%. Ptp-V area was similar in the two groups at baseline yet was increased by 122 +/- 9% in group 2 and unchanged in group 1 at MCh end point. These findings suggest that the increased maximal response to MCh in asthmatic subjects is associated with an involvement of the lung periphery.

Nonreversible conductive airway ventilation heterogeneity in mild asthma

2003 ◽  
Vol 94 (4) ◽  
pp. 1380-1386 ◽  
Author(s):  
Sylvia Verbanck ◽  
Daniël Schuermans ◽  
Manuel Paiva ◽  
Walter Vincken
Keyword(s):  
Vital Capacity ◽  
Respir Crit ◽  
Forced Expiratory Volume ◽  
Asthmatic Patients ◽  
Lower Baseline ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout ◽  
Forced Expiratory Flow ◽  
Expiratory Flow ◽  
Lung Zone

A multiple-breath washout technique was used to assess residual ventilation heterogeneity in the conductive and acinar lung zones of asthmatic patients after maximal β2-agonist reversibility. Reversibility was assessed in 13 patients on two separate visits corresponding to a different baseline condition in terms of forced expiratory volume in 1 s [FEV1; average FEV1 over 2 visits: 92 ± 21% of predicted (SE)]. On the visit corresponding to each patient's best baseline, 400 μg salbutamol led to normal acinar ventilation heterogeneity, normal FEV1, and normal peak expiratory flow; i.e., none was significantly different from that obtained in 13 matched controls. By contrast, conductive ventilation heterogeneity and forced expiratory flow after exhalation of 75% forced vital capacity remained significantly different from controls ( P ≤ 0.005 on both indexes). In addition, the degree of postdilation conductive ventilation heterogeneity was similar to what was previously obtained in asthmatic individuals with a 19% lower baseline FEV1and twofold larger acinar ventilation heterogeneity (Verbanck S, Schuermans D, Noppen M, Van Muylem A, Paiva M, and Vincken W. Am J Respir Crit Care Med 159: 1545–1550, 1999). We conclude that, even in the mildest forms of asthma, the most consistent pattern of non-β2-agonist-reversible ventilatory heterogeneity is in the conductive lung zone, most probably in the small conductive airways.

scholarly journals Serum 14-3-3β protein: a new biomarker in asthmatic patients with acute exacerbation in an observational study

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Decai Wang ◽  
Lizong Rao ◽  
Yalan Cui ◽  
Guoting Tang ◽  
Haiming Huang ◽  
...  
Keyword(s):  
Acute Exacerbation ◽  
Normal Control ◽  
Forced Vital Capacity ◽  
Eosinophil Count ◽  
Vital Capacity ◽  
Forced Expiratory Volume ◽  
Normal Control Group ◽  
Control Group ◽  
Clinical Indicators ◽  
Asthmatic Patients

Abstract Background The determination of systemic inflammatory markers is one of the important directions to study the pathogenesis of asthma and improve the diagnosis of asthma. Current studies have found that the 14-3-3 protein family subtypes interact with target proteins to participate in the pathogenesis of a variety of immune inflammatory diseases. However, studies on serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein β (14-3-3β) in asthma are scarce. This study aimed to assess the clinical significance of 14-3-3β in asthmatic patients. Methods We recruited 54 asthmatic patients with acute exacerbation and 50 asthmatic patients with chronic persistent. The normal control group included 54 healthy individuals. Clinical characteristics, clinical indicators [fractional expiratory nitric oxide (FeNO), eosinophil count, forced vital capacity (FVC), percent of predicted FVC (FVC% predicted), forced expiratory volume in one second (FEV1), percent of predicted FEV1 (FEV1% predicted), the ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) and serum 14-3-3β levels were measured to compare among each group. Spearman’s rank correlation coefficient was used to evaluate the correlation between 14-3-3β and clinical indicators. Finally, Receiver-operating characteristic (ROC) curves analysis was used to determine the sensitivity and specificity of 14-3-3β. Results Our results showed that median (interquartile range) of serum 14-3-3β concentration (ng/mL) in acute exacerbation group of asthma (41.18 [33.06–51.76]) was much higher than that in normal control group (24.99 [17.43–29.91]; P < 0.001) and chronic persistent group of asthma (25.88 [21.03–34.55]; P < 0.001). Spearman’s correlation coefficient shows that the serum 14-3-3β level was positively correlated with FeNO (r = − 0.292, P = 0.032) and peripheral blood eosinophil count (r = 0.328, P = 0.016), and was negatively related to FEV1/FVC (r = − 0.293, P = 0.031) in the acute exacerbation group of asthma. At the same time, the serum 14-3-3β level was also negatively associated with FEV1 (r = − 0.297, P = 0.036) in the chronic persistent group of asthma. ROC curve analysis comparing acute exacerbation group of asthma with normal control group demonstrated a significant (P < 0.001) AUC of 0.90 (95% CI 0.85–0.96). Conclusion The serum 14-3-3β protein may become a potential biomarker in asthmatic patients with acute exacerbation.

scholarly journals Effects of rapid saline infusion on lung mechanics and airway responsiveness in humans

2003 ◽  
Vol 95 (2) ◽  
pp. 728-734 ◽  
Author(s):  
Riccardo Pellegrino ◽  
Raffaele Dellacà ◽  
Peter T. Macklem ◽  
Andrea Aliverti ◽  
Stefania Bertini ◽  
...  
Keyword(s):  
Functional Residual Capacity ◽  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Forced Expiratory Volume ◽  
Airway Responsiveness ◽  
Saline Infusion ◽  
Lung Mechanics ◽  
Elastic Recoil ◽  
Lung Volumes ◽  
Residual Capacity

Lung mechanics and airway responsiveness to methacholine (MCh) were studied in seven volunteers before and after a 20-min intravenous infusion of saline. Data were compared with those of a time point-matched control study. The following parameters were measured: 1-s forced expiratory volume, forced vital capacity, flows at 40% of control forced vital capacity on maximal (V̇m40) and partial (V̇p40) forced expiratory maneuvers, lung volumes, lung elastic recoil, lung resistance (Rl), dynamic elastance (Edyn), and within-breath resistance of respiratory system (Rrs). Rl and Edyn were measured during tidal breathing before and for 2 min after a deep inhalation and also at different lung volumes above and below functional residual capacity. Rrs was measured at functional residual capacity and at total lung capacity. Before MCh, saline infusion caused significant decrements of forced expiratory volume in 1 s, V̇m40, and V̇p40, but insignificantly affected lung volumes, elastic recoil, Rl, Edyn, and Rrs at any lung volume. Furthermore, saline infusion was associated with an increased response to MCh, which was not associated with significant changes in the ratio of V̇m40 to V̇p40. In conclusion, mild airflow obstruction and enhanced airway responsiveness were observed after saline, but this was not apparently due to altered elastic properties of the lung or inability of the airways to dilate with deep inhalation. It is speculated that it was likely the result of airway wall edema encroaching on the bronchial lumen.

Simulation of airway closure during forced vital capacity

1989 ◽  
Vol 17 (6) ◽  
pp. 617-631 ◽  
Author(s):  
David Elad ◽  
Shmuel Einav
Keyword(s):  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Airway Closure
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