Inhalation patterns and predominant site of bronchoconstriction in healthy subjects

To determine the relationship between changes in density dependence of maximal expiratory flow and changes in the predominant site of bronchoconstriction, we altered the pattern of inhalation of a methacholine aerosol to achieve deposition either centrally (by short choppy breaths) or peripherally (by slow deep breaths). Partial expiratory flow volume curves on air and on 80% helium-20% oxygen (HeO2) were recorded in six healthy subjects before and after each pattern of methacholine inhalation. We varied concentrations of methacholine and number of inhalations to achieve equivalent degrees of bronchoconstriction as assessed by decreases in maximal flow (Vmax) on air, which fell 27% from control values. Vmax on HeO2 also fell after both inhalation patterns. Density dependence (Vmax on HeO2 divided by Vmax on air) decreased following slow deep breaths of bronchoconstrictor aerosol, and increased following short choppy breaths. In three subjects, inhalation of radiolabeled methacholine aerosol confirmed that the slow deep pattern was associated with a diffuse, more peripheral deposition, whereas the short choppy pattern led to central deposition. We conclude that changes in density dependence reflect the predominant site of obstruction after acute methacholine aerosol challenge in healthy subjects.

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Density dependence of maximal expiratory flow before and during tracheal constriction in dogs

Journal of Applied Physiology ◽

10.1152/jappl.1986.60.3.1060 ◽

1986 ◽

Vol 60 (3) ◽

pp. 1060-1066 ◽

Cited By ~ 4

Author(s):

R. G. Castile ◽

O. F. Pedersen ◽

J. M. Drazen ◽

R. H. Ingram

Keyword(s):

Density Dependence ◽

Lung Volumes ◽

Maximal Expiratory Flow ◽

Volume Curve ◽

Before And After ◽

Lower Lung ◽

Flow Volume Curve ◽

Expiratory Flow ◽

Longitudinal Extension ◽

Central Airway

The effect of carbachol-induced central bronchoconstriction on density dependence of maximal expiratory flow (MEF) was assessed in five dogs. MEFs were measured on air and an 80% He-20% O2 mixture before and after local application of carbachol to the trachea. Airway pressures were measured using a pitot-static probe, from which central airway areas were estimated. At lower concentrations of carbachol the flow-limiting site remained in the trachea over most of the vital capacity (VC), and tracheal area and compliance decreased in all five dogs. In four dogs, decreases in choke point area predominated and produced decreases in flows. In one dog the increase in airway “stiffness” apparently offset the fall in area to account for an increase in MEF. Density dependence measured as the ratio of MEF on HeO2 to MEF on air at 50% of VC increased in all five dogs. Increases in density dependence appeared to be related to increases in airway stiffness at the choke point rather than decreases in gas-related airway pressure differences. Lower concentrations produced a localized decrease in tracheal area and extended the plateau of the flow-volume curve to lower lung volumes. Higher concentrations caused further reductions in tracheal area and greater longitudinal extension of bronchoconstriction, resulting in upstream movement of the site of flow limitation at higher lung volumes. Density dependence increased if the flow-limiting sites remained in the trachea at mid-VC but fell if the flow-limiting site had moved upstream by that volume.

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Parenteral vs. inhaled atropine: density dependence of maximal expiratory flow

Journal of Applied Physiology ◽

10.1152/jappl.1982.53.2.392 ◽

1982 ◽

Vol 53 (2) ◽

pp. 392-396 ◽

Cited By ~ 14

Author(s):

J. W. Weiss ◽

E. R. McFadden ◽

R. H. Ingram

Keyword(s):

Density Dependence ◽

Vital Capacity ◽

Human Subjects ◽

Atropine Sulfate ◽

Parenteral Administration ◽

Elastic Recoil ◽

Maximal Expiratory Flow ◽

Parenteral Dose ◽

Before And After ◽

Expiratory Flow

Using forced vital capacity maneuvers, we measured maximal expiratory flow rates (Vmax) and static elastic recoil pressures of the lung [Pst(L)] using quasi-static maneuvers in normal nonsmoking human subjects who were breathing air and after a washing of 80% helium-20% oxygen before and after both inhaled and intravenously administered atropine sulfate. By both routes there were equivalent increases in Vmaxair but different effects on density dependence (DD) of Vmax (DD = ratio of VmaxHeO2 to Vmaxair) and on Pst(L). At 30% of vital capacity, DD decreased from an average of 1.47 to 1.32 (P less than 0.01, paired t test) after inhaled drug and did not change after parenteral administration [1.44 vs. 1.48 (P greater than 0.2)]. After inhalation Pst(L) did not change, but after parenteral administration Pst(L) significantly decreased. We interpret these findings to indicate a predominantly large-airway effect with the inhalation route and a more uniform dilatation after the parenteral dose. These results contrast with beta-adrenergic dilatation following which small-airway effects predominate regardless of route of administration.

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Density-Dependence of Maximal Expiratory Flow Rates before and after Bronchodilators in Patients with Obstructive Airways Disease

Clinical Science ◽

10.1042/cs0510133 ◽

1976 ◽

Vol 51 (2) ◽

pp. 133-139

Author(s):

J. J. Wellman ◽

E. R. McFadden ◽

R. H. Ingram

Keyword(s):

Density Dependence ◽

Lung Volumes ◽

Flow Rates ◽

Maximal Expiratory Flow ◽

Before And After ◽

Group A ◽

Obstructive Airways Disease ◽

Expiratory Flow ◽

Group B ◽

Expiratory Flow Rates

1. Gas-density-dependence of maximal expiratory flow rates (V̇max), defined as the ratio of V̇max while breathing helium/oxygen (80:20) to V̇max. while breathing air at the same lung volume, was examined in relation to other measurements of airways obstruction in patients with obstructive airways disease before and after administration of bronchodilators. 2. Seventeen patients showed a 45% or greater increase in specific conductance(sGaw) after bronchodilator therapy (group A) and thirteen patients demonstrated a lesser response (group B). 3. Before the administration of bronchodilators, the degree of obstruction in the two groups was not different as measured by lung volumes, sGaw, forced expiratory volume in 1 s, and flow rates high in the vital capacity; yet the maximal mid-expiratory flow rate and the degree of density-dependence were significantly lower in group B. 4. After bronchodilators, both groups of patients showed significant improvements in sGaw flow rates and lung volumes. However, group A patients showed a significant increase in density-dependence whereas group B patients did not. 5. Increased density-dependence after bronchodilators in the group A patients was associated with an increase in the computed resistance of the upstream segment with air and a decrease in resistance with helium/oxygen. These changes could be explained by a more mouthward movement of equal pressure points, and therefore a further increase in the relative contribution of the larger density-dependent airways to limitation of flow. 6. The fact that density-dependence was not altered after bronchodilators in the group B patients suggests that the site of limitation of flow did not change appreciably. The shift in the pressure—flow curve for the upstream airways was such that the computed resistance of these airways fell. Thus it appears that the airways comprising the upstream segment were dilated.

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Bronchodilatation, lung recoil, and density dependence of maximal expiratory flow

Journal of Applied Physiology ◽

10.1152/jappl.1982.52.4.874 ◽

1982 ◽

Vol 52 (4) ◽

pp. 874-878 ◽

Cited By ~ 4

Author(s):

J. W. Weiss ◽

E. R. McFadden ◽

R. H. Ingram

Keyword(s):

Density Dependence ◽

Vital Capacity ◽

Human Subjects ◽

Beta Agonist ◽

Elastic Recoil ◽

Maximal Expiratory Flow ◽

Before And After ◽

Normal Human ◽

Expiratory Flow ◽

Expiratory Flow Rates

Using normal human subjects we have measured maximal expiratory flow rates with air (Vmaxair) and after a washin of 80% He-20% O2 (VmaxHeO2) and static elastic recoil pressures of the lung [Pst(L)] both before and after administration of a beta-agonist, terbutaline. The effects of inhaled drug were compared with those of the subcutaneously administered agent, each given in doses to produce maximal bronchodilatation as assessed by increases in Vmaxair in the mid-vital capacity. Although there was a significant yet modest decrease in Pst(L) only after injection of the agent, density dependence (DD), assessed as the ratio of VmaxHeO2 to Vmaxair, increased significantly and comparably after either route of administration. A modest decrease in Pst(L), therefore, did not affect the changes in DD.

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Partial and Maximal Expiratory Flow-Volume Curves in Normal and Asthmatic Subjects Before and After Inhalation of Metaproterenol

CHEST Journal ◽

10.1378/chest.88.5.697 ◽

1985 ◽

Vol 88 (5) ◽

pp. 697-702 ◽

Cited By ~ 22

Author(s):

Richard B. Berry ◽

Ronald D. Fairshter

Keyword(s):

Flow Volume ◽

Maximal Expiratory Flow ◽

Before And After ◽

Expiratory Flow

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Viscosity and density dependence during maximal flow in man

Journal of Applied Physiology ◽

10.1152/jappl.1980.48.2.313 ◽

1980 ◽

Vol 48 (2) ◽

pp. 313-319 ◽

Cited By ~ 12

Author(s):

B. A. Staats ◽

T. A. Wilson ◽

S. J. Lai-Fook ◽

J. R. Rodarte ◽

R. E. Hyatt

Keyword(s):

Density Dependence ◽

Scaling Laws ◽

Peripheral Resistance ◽

Maximal Flow ◽

Flow Curves ◽

Gas Density ◽

Maximal Expiratory Flow ◽

The Mean ◽

The Relationship ◽

Viscosity Dependence

Maximal expiratory flow curves were obtained from ten healthy subjects white breathing air and three other gas mixtures with different densities and viscosities. From these data, the magnitudes of the dependence of maximal flow on gas density and viscosity were obtained. The scaling laws of fluid mechanics, together with a model for the flow-limiting mechanism, were used to obtain a prediction of the relationship between the density dependence and the viscosity dependence of maximal flow. Although the data for individual subjects were too variable to allow a precise comparison with this prediction, the relationship between the mean density dependence and the mean viscosity dependence of all usbjects agreed with the theoretic prediction. This agreement supports the assumption, which is frequently made, that flow resistance rather than tissue visoelasticity is the dominant contributor to peripheral resistance. Information on the relationships between the pressure drop to the flow-limiting segment and flow, gas density and viscosity, and lung volume were also obtained.

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Analysis of Maximum Expiratory Flow Volume Curves Using Canonical Correlation Analysis

Methods of Information in Medicine ◽

10.1055/s-0038-1635359 ◽

1985 ◽

Vol 24 (02) ◽

pp. 91-100 ◽

Cited By ~ 3

Author(s):

W. van Pelt ◽

Ph. H. Quanjer ◽

M. E. Wise ◽

E. van der Burg ◽

R. van der Lende

Keyword(s):

Correlation Analysis ◽

Canonical Correlation Analysis ◽

Canonical Correlation ◽

Flow Volume ◽

Non Linear ◽

Maximum Expiratory Flow ◽

Expiratory Flow ◽

Relationship Of ◽

The Relationship ◽

Age And Sex

SummaryAs part of a population study on chronic lung disease in the Netherlands, an investigation is made of the relationship of both age and sex with indices describing the maximum expiratory flow-volume (MEFV) curve. To determine the relationship, non-linear canonical correlation was used as realized in the computer program CANALS, a combination of ordinary canonical correlation analysis (CCA) and non-linear transformations of the variables. This method enhances the generality of the relationship to be found and has the advantage of showing the relative importance of categories or ranges within a variable with respect to that relationship. The above is exemplified by describing the relationship of age and sex with variables concerning respiratory symptoms and smoking habits. The analysis of age and sex with MEFV curve indices shows that non-linear canonical correlation analysis is an efficient tool in analysing size and shape of the MEFV curve and can be used to derive parameters concerning the whole curve.

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Pattern and mechanism of airway response to hypocapnia in normal subjects

Journal of Applied Physiology ◽

10.1152/jappl.1979.47.1.8 ◽

1979 ◽

Vol 47 (1) ◽

pp. 8-12 ◽

Cited By ~ 35

Author(s):

C. F. O'Cain ◽

M. J. Hensley ◽

E. R. McFadden ◽

R. H. Ingram

Keyword(s):

Vital Capacity ◽

Normal Subjects ◽

Oxygen Mixture ◽

Flow Volume ◽

Mixture Density ◽

Lung Capacity ◽

Airway Constriction ◽

Maximal Expiratory Flow ◽

Airway Response ◽

Expiratory Flow

We examined the bronchoconstriction produced by airway hypocapnia in normal subjects. Maximal expiratory flow at 25% vital capacity on partial expiratory flow-volume (PEFV) curves fell during hypocapnia both on air and on an 80% helium- 20% oxygen mixture. Density dependence also fell, suggesting predominantly small airway constriction. The changes seen on PEFV curves were not found on maximal expiratory flow-volume curves, indicating the inhalation to total lung capacity substantially reversed the constriction. Pretreatment with a beta-sympathomimetic agent blocked the response, whereas atropine pretreatment did not, suggesting that hypocapnia affects airway smooth muscle directly, not via cholinergic efferents.

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