The Comparative Mechanics and Morphology of Airways in Asthma and in Chronic Obstructive Pulmonary Dlsease':' P. D. PARE, B. R. WIGGS, A. JAMES,3 J. C. HOGG, and C. BOSKEN4

Although airway obstruction characterizes the functional defect in patients who have asthma as well as in patients who have chronic obstructive pulmonary disease (COPD), different mechanisms are thought to be responsible for the obstruction. The airway obstruction can be quantitated by measuring airway or pulmonary resistance or by measuring maximal expiratory flow (MEF) from the lungs. The magnitude of the decrease in MEF is most commonly used to quantitate the severity of the obstruction; however, decreases in MEF may be due to a variety of pathogenetic mechanisms. MEF is related to the elastic recoil of the lung, which provides the driving pressure for expiratory flow, the caliber of airways upstream from the points where airways collapse and flow limitation occurs, and the mechanical properties of the airways at the sites of flow limitation. In patients who have asthma, the primary problem is one of airway narrowing alone and there is little evidence for important changes in lung elastic recoil or large airway compliance, whereas in patients with COPD the decrease in MEF is more often caused by a combination of airway narrowing, loss of recoil, and altered airway collapsibility. Pulmonary and airway resistance are more specific measures of airway narrowing because they are less influenced by lung parenchymal recoil and are not influenced by airway collapsibility as flow-limiting segments do not develop during the tidal breathing. In addition, resistance or conductance may be a more pertinent variable to measure since it is the increase in airway resistance that occurs both in asthma and in COPD that causes the increase in the work of breathing in these conditions. Pulmonary resistance can be increased because of an increase in airway or tissue resistance. Pulmonary tissue resistance has long been thought to form a small proportion of total pulmonary resistance in humans, and despite recent studies which show that tissue resistance makes up a substantial percentage of total pulmonary resistance in the dog (1) and the rabbit (2), the traditional view that the major contribution is airway resistance in the human lung has been reinforced by the study of Kariya and coworkers (3). The airway component of pulmonary resistance can increase because of smooth muscle contraction and shortening, airway wall thickening (which encroaches on the airway lumen), a loss of lung elasticity in the lung tissue that surrounds and supports the intraparenchymal airways, obstruction of airways by intraluminal secretions or fibrous obliteration, and/or an increase in the surface tension of the liquid lining the airways (4). AM REV RESPIR DIS 1991; 143:1189-1193

We have recently modified a model that allows calculation of total pulmonary resistance from morphometric measurements of normal airway diameters and lengths and added to the model a dynamic element to assess the effects of the various causes of airway narrowing on total pulmonary resistance. The model employs the geometry of the tracheobronchial tree described by Weibel (5), the fluid dynamics equations of Pedley and coworkers (6), morphometric measurements of airway wall thickness in patients who have asthma (7) or COPD (8), and the analysis of Moreno and colleagues (9). The model is run on a Lotus 1-2-3 spread sheet (Lotus Development Corp., Cambridge, MA) using a personal computer. The input variables are the total inspiratory flow rate, the density and viscosity of the inspired gas, the relationship between airway size and airway wall thickness, and an arbitrarily chosen value for the maximal airway smooth muscle shortening that can occur at any airway generation. The outputs are the regional and overall pulmonary resistance. Using the model, we can calculate the effects of airway wall thickening on airway resistance and examine the important interrelationships between airway wall thickening and airway smooth muscle shortening. To assign values for airway wall thickness to the appropriately sized airway, we use the morphometrically measured airway internal perimeter (Pi) as a marker. James and coworkers (10) have shown that Pi is a constant for a given airway in human lungs despite varying lung inflation and varying smooth muscle contraction. As the smooth muscle contracts or the lung deflates, the Pi folds up rather than shortens (figure 1). In addition, the ratio of airway wall area to Pi remains relatively constant, which allows the relationship between Pi and airway wall area to be used as a measure of airway wall thickness. The measurements of these morphologic parameters have been made on lungs from four groups: (1) the postmortem lungs of 22 subjects who died suddenly of trauma or cardiovascular accidents and who had no history suggestive of significant pulmonary disease, (2) the postmortem lungs of 18subjects who suffered from asthma, (3) the surgically resected lungs or lobes of 30 patients who were having lung resection for a peripheral-pulmonary lesion but who did not have significant airflow obstruction (FEVl/FVC > 75070), and (4) the surgically resected specimens from 30 patients who had parenchymal lesions and who showed significant COPD (FEV l/FVC < 65%). Anthropometric and lung function data on these groups are shown in table 1.

The lungs and lobes were fixed for histologic examination by inflation with or submersion in formalin, and multiple sections were examined. All nonalveolated airways that were cut in reasonable cross section (ratio of shortest to longest diameter> 0.33) were examined, and the Pi, defined as the luminal border of the epithelium, was traced. Internal area (Ai) was the area inside Pi. External perimeter (Pe), defined as the outermost border of the smooth muscle layer, was also traced, and the wall area (WA) was calculated as the difference between the internal area and external area (Ae): WA = Ae - Ai The relationship between Pi and the square root of WA for the groups is shown in figure 2. The relationship was virtually identical for the airways from the postmortem and surgical control lungs (Gp 1 + 3), so the data from those groups have been combined to represent one control group. The square root of WA is used to linearize the relationship. It is apparent that the wall areas of the asthmatic subjects are larger over the entire range of airway sizes than are the wall areas of the control subjects and that those of the COPD group are intermediate between the asthmatic and control groups. To determine which components of the airway walls were thickened in the different groups, we point-counted the airway walls; table 2 shows the contribution of the different wall components to the absolute and relative wall areas for airways of different size. The areas of all three components of the wall were increased in both the asthmatics and the chronically obstructed patients. By applying these morphometrically determined relationships between Pi and WA to the model, we can now test for their contribution to the difference in airway mechanics that have been described in asthmatics and in patients with COPD. Four differences have been suggested: (1) greater response to inhaled pharmacologic smooth muscle constrictors in asthma than in COPD; (2) greater response to inhaled pharmacologic bronchodilators in asthma than in COPD; (3) less response of resistance to changes in lung elastic recoil in I From the University of British Columbia Pulmonary Research Laboratory, S1. Paul's Hospital, Vancouver, British Columbia, Canada. 2 Supported by the Medical Research Council of Canada. 3 Research Fellow of the Lung Association of British Columbia. 4 Research Fellow of the Canadian Lung Association.

1189

1190

PARE, WIGGS, JAMES, HOGG, AND BOSKEN

"RElAXED"

CONTRACTED

Fig. 1. A contracted (or deflated) airway and its "relaxed" counterpart. The internal perimeter (Pi) is the same in the contracted (Pic) and in relaxed (Pi r) states. Wall area (WA) is also comparable in contracted (WAc) and relaxed (WAr) states. External perimeter (Pe), external area (Ae), and internal area (Ai) obviously change with contraction (or deflation).

TABLE 1 ANTHROPOMETRIC AND LUNG FUNCTION DATA ON FOUR GROUPS OF SUBJECTS'

Mean age, yr Women, % FEV 1/FVC% FEV 1 , % pred Smoking, pack-yr

Group 1

Group 2

52 ± 19 50

34.4 ± 23

Group 3 64.9 ± 14 76.6 ± 101 ± 45 ±

9.1 3.6 19 36

Group 4 64.4 ± 16 54.9 ± 71 ± 70 ±

8.0 6.2 14 42

, Group 1 = 22 subjects who died suddenly of trauma or cardiovascular accidents and who had no history of significant pulmonary disease; Group 2 = 18 subjects who suffered from asthma; Group 3 = 30 patients who were having lung resection for a peripheral pulmonary lesion but who did not have significant airflow obstruction (FEV1/FVC > 75%); Group 4 = 30 patients who had parenchymal lesions and who showed significant capo (FEV 1/FVC < 65%).

3.00

2.40

Fig. 2. The square root of wall area is plotted against the airway internal perimeter for membranous bronchioles of obstructed (COPD), asthmatic, and normal patients. The airway walls of asthmatics are thickened compared with those of both normal and obstructed patients.

.".

E



1.80

Gl Q)

.

The comparative mechanics and morphology of airways in asthma and in chronic obstructive pulmonary disease.

The Comparative Mechanics and Morphology of Airways in Asthma and in Chronic Obstructive Pulmonary Dlsease':' P. D. PARE, B. R. WIGGS, A. JAMES,3 J. C...
608KB Sizes 0 Downloads 0 Views