Forced Deflation Research Articles

Chronic airflow obstruction: Evolution of disordered function in cigarette smokers

Measurements of the mechanical behaviour of the lung, which reflect lung structure, have been used to elucidate the evolution of chronic airflow obstruction in male cigarette smokers and subjects with pulmonary emphysema. The exponent K, from a single exponential function fitted to static pressure-volume data, is an index of lung distensibility directly related to the size of peripheral airspaces. Elastic recoil pressure is inversely related to K. Conductance measured during forced and interrupted deflations of the lungs reflects the dimensions of airways. K increased abnormally with age in smokers suggesting an increase in the airspace size caused by the effects of cigarette smoke which probably acts by intensifying elastase activity in lung tissue. Decreased conductance implying narrowing of airways is found in young smokers, but conductance rises and airways become more distensible in older smokers. A progressive increase in K (with decrease in recoil pressure) and a decrease in conductance are responsible for the advancement of severe airflow obstruction in cigarette smokers.

1760 BRONCHIAL REACTIVITY IN PREMATURE INFANTS WITH BPD

Bronchodilators generally are not considered useful in infants, presumably because of poor airway smooth muscle development. On the other hand, bronchial reactivity has been suspected in infants with chronic lung disease such as BPD. We investigated to see when such a reactivity develops postnatally in patients who are mechanically ventilated in the neonatal ICU. In 22 prematurely born infants (BW: 1118 ± 350(SD)gm; GA:27.7 ± 2.4 wk; PNA: 46.5 ± 30.7 days) with RDS/BPD, maximum expiratory flowvolume curves by forced deflation (DFVC; Pediatr Res 11:220,1977) were obtained on 63 separate occasions. At each testing DFVC were examined in 3 conditions: baseline (BL), after saline nebulization (NSS) as a placebo, and after 10 minutes of 0.25% isoetharine nebulization (bronchodilator BD). At BL all infants showed decreased maximum expiratory flow at low lung volumes (Vmax25), indicating lower airway obstruction. Forced vital capacity (FVC) was also decreased (29.3 ± 12.8 ml/kg). Following NSS and lung inflation 12% of infants showed an increase (>20%) in FVC, indicating recruitment of airspaces. After BD 79% showed an increase (>20% of NSS) in Vmax25. The mean response in Vmax25 at the same lung volume from TLC was 320 ± 249% of NSS (maximum: 1270%) (p< .001), indicating marked bronchodilation. The youngest responder was a 17-day-old and the most premature who responded was 28 weeks PCA. Thus the course of a majority of premature infants with chronic ventilatory failure is complicated by marked bronchial hyperreactivity. (Supported in part by grants: NIH HL25810; ALA of PA).

Mechanism of reduced maximum expiratory flow in methacholine-induced bronchoconstriction in dogs.

Airway sites of flow limitation ["choke points" (CP)] were identified during forced deflation in open-chest dogs before (C) and after (B) bronchoconstriction was produced by nebulizing a solution of methacholine chloride into their airways. CP were identified in two respective groups. In group I (n = 8) a retrograde catheter was used to locate CP and in the other a Pitot static tube (group II, n = 5), CP were identified at multiple lung volumes (VL) over the lower one-half of total lung capacity. Both groups showed similar findings at each condition. At B, corresponding values of maximum expiratory flow (Vmax) at each VL decreased to about 10% of those at C. Movement of CP relative to their original location varied at each VL and, especially at the lower VL, showed little peripheral movement. In group I, equal pressure points were also measured and were found to move peripherally at all the measured VL. In group II, cross-sectional area (A*) and airway compliance (K) at CP were estimated. During bronchoconstriction, A* decreased at the respective VL, and airways became less compliant. The reduction in Vmax could be explained in terms of changes in A* and K as described by wave-speed theory, and Vmax decreased because A* decreased. The decrease in A* was related in part to an increase in viscous pressure losses that reduced total pressure at CP and also in part to a change in the pressure-area behavior of bronchi at CP. Their relative effects on reducing A* and Vmax were examined.

Flow-volume curves of excised right and left rabbit lungs

Static pressure-volume (PV) curves and flow-volume (VV) curves of excised right and left rabbit lungs obtained by forced and passive deflation were compared. Deflation PV curves in which the volume was expressed as either ml/lung weight or percent total lung capacity were nearly identical between right and left lungs. Descending limbs of the forced VV curves in which the flow divided by vital capacity (VC) was plotted against %VC generally agreed between right and left lungs, although peak flow tended to be higher in left lungs. However, the flow obtained during passive deflation was higher in left lungs over most of the deflation suggesting that the resistance of proximal airways per unit volume is lower in left than in right lungs.

Pressure outside the extrapulmonary airway in dogs.

We have measured the static and dynamic transmural pressures of extrapulmonary airways during positive pressure lung inflation in anesthetized dogs suspended in the standing position. Thin, fluid-filled catheters measured pressures within and on the anterior surface of the airways in the mediastinum and neck. The change from mediastinal to cervical static extra-airway pressures (Pea) was not abrupt but occurred through the thoracic outlet and the root of the neck. The static Pea in the mediastinum was more positive than pleural pressure when lung volume was increased with positive pressures. During forced deflation equal pressure points (EPP) were in labor bronchi from which airway narrowing extended towards the mouth. Under these conditions, the dynamic mediastinal Pea mouthward of the EPP remained close to pleural pressures even at high volumes. This suggested that forces of restitution generated in the surrounding tissues by the narrowing of the airways did have a small effect in reducing the pressure affecting their anterior surface.

The Distinction Between Lung Maturation and Limited Injury in Human Airways: Functional and Morphometric Studies in Postmortem Examination of Lungs

M orphologic alterations occur in the maturing and aging lung. These morphologic alterations are reflected in functional changes which, in the case of the aging lung, are qualitatively similar to those observed in advanced chronic obstructive pulmonary disease (COPD). Any study which attempts to evaluate the morphologic and functional changes of COPD must differentiate that part contributed by disease from that contributed by normal maturation and aging. In this report we attempt to characterize some of the functional and morphologic alterations in the airways of human nondiseased lungs over a wide age range as a basis for understanding additional changes which may be produced by disease, particularly those in early COPD. Studies of mechanics and morphometry were performed in postmortem examination of human lungs. Left lungs are obtained from male victims of sudden nonhospital death on whom autopsies were performed in the coroner’s office. Usual causes of death include traffic accidents, myocardial infarction and exsanguinating gunshot wounds. Stringent criteria are used in selecting the lungs. Lungs heavier than 450 gm are not accepted because they usually have microscopic evidence of edema. Similarly, lungs with hemorrhage, large pleural rents or excessive bronchial secretions are not used. Mechanics are studied immediately after obtaining the lung, and in all cases are completed within 24 hours of the person’s death. The lung is suspended by a bronchial cannula in a glass plethysmograph. Measurements of lung mechanics include static elastic recoil pressures, total pulmonary resistance by the method of Mead and Whittenberger,’ dynamic compliance and flow volume plots from passive and forced deflations. Barium sulfate is then insufflated into the bronchial tree and the mean diameter of all segmental bronchi is determined from the bronchogram. This value is considered a relative measure of the size of the central airways. The lung is inflated and fixed in formalin at 25-cm water pressure. Lung slices are carefully examined, and the amount of emphysema, if present, is determined by point count. Random histologic sections are obtained from which the number and mean diameter of all membranous bronchioles of less than 2 mm in diameter are determined. Mucous plugging in the peripheral airways is evaluated by quantitatively determining the proportion of bronchiolar lumen occupied by mucus on histologic section. Approximately 50 bronchioles are evaluated in each lung. The proportion of bronchial mucous gland is quantitatively determined from sections of lobar bronchi. The results reported are from the first 26 lungs studied. The age of the donors ranges from 10-82 years. Mild emphysema, less than 10 percent by gross point count, is present in five lungs. The population studied can be considered a reasonable cross section of an urban population, consisting of persons with normal and mildly diseased lungs. The relationship between the flow resistive properties of the lungs and measurements of airway caliber at different levels of the bronchial tree can be summarized as follows: A statistically significant (p <0.05) but weak correlation (R 0.39) is found between mean segment diameter and the reciprocal of pulmonary resistance, conductance. In contrast, a very close correlation (R 0.90) is found between mean bronchiole diameter and pulmonary conductance. This suggests that mean bronchiole diameter is the main determinant of variations in pulmonary conductance in normal and mildly diseased human lungs. The determination of pulmonary conductance, or resistance, is more sensitive than either maximal expiratory flow rates or dynamic compliance in detecting bronchiolar narrowing. Bronchial mucous gland hyperplasia is one of the pathologic abnormalities described in chronic bronchitis. When mucous glands occupy 15 percent or more of the bronchial wall, they are considered hyperplastic. The percentage of mucous glands in the bronchial wall exceeded this value in 6 of the 26 lungs studied (range 16.1 to 24.1 percent). Functional parameters are not significantly different in this group as compared to the other lungs studied. Emphysema or bronchiolar narrowing is not present in these six lungs, and the amount of mucus in the lumens of the peripheral airways is not increased. No age-related changes are seen in the percentage of bronchial mucous glands in this study. The bronchial mucous gland hyperplasia is not related to any functional abnormalities in this study and is not associated with other pathologic changes commonly found with COPD. The size of the central airways, as reflected by the mean segmental bronchial diameter does not change significantly beyond the age of 20 years (Fig 1). In contrast, highly significant age-related changes occur in the mean diameter of the membranous bronchioles (Fig 2). Maximal bronchiole diameter is not reached until well into the third decade of life, with a variable decrease thereafter. Matsuba and Thurlbeck,2 using nearly iden-

LUNG VOLUME, COMPLIANCE, AND ARTERIAL OXYGEN TENSIONS DURING CONTROLLED VENTILATION.

The relationship between total dynamic compliance (lung plus chest wall), functional residual capacity, and alveolar-arterial oxygen gradients (A-a DO2) was studied in paralyzed dogs during constant-volume ventilation with pure oxygen. Rapid changes in functional residual capacity (FRC), produced by forced deflation of the lungs, were associated with a rapid fall in total compliance and rise in A-a DO2. Subsequent hyperinflations (deep breaths) restored compliance to control levels more readily than A-a DO2. Changes in the FRC, measured with a whole-body plethysmograph, were related directly to total compliance and inversely to A-a DO2. Collapse of the terminal regions of the lungs produced by forced deflations was associated with a decrease in total compliance of 36%, and a decrease in FRC of 26% with a simultenaous rise in A-a DO2 to a mean of 547 mm Hg. It is concluded that intermittent deep breaths administered during constant-volume ventilation will not necessarily restore control levels of compliance and A-a DO2 equally well. This difference is probably dependent on altered alveolar surface characteristics or mechanics, or both, secondary to the collapse process, which prevent restoration of structural integrity by a deep breath. total dynamic compliance; functional residual capacity; alveolar-arterial oxygen tension difference; atelectasis; deep breath Submitted on October 31, 1963

PULMONARY EXCHANGE AS RELATED TO ALTERED PULMONARY MECHANICS IN ANESTHETIZED DOGS.

Pulmonary mechanics and gas exchange were studied in supine anesthetized dogs, with and without periodic hyperinflations of the lungs, and after a single forced deflation. After a period without hyperinflations the lung compliance decreased to 66% of control values and patchy atelectasis was observed, but no changes were observed in diffusing capacity (Dl) or per cent venous admixture ( Qva/ Qt). Following a single forced deflation the compliance was 40% of control. Dl was 40% and Qva/ Qt 180% of control values, respectively. These data could be accounted for if there was an accompanying shift of blood flow from atelectatic to nonatelectatic areas, the compensation being very nearly complete for moderate, but less than complete for marked reductions in compliance. Alternative explanations of the apparent compensation are: 1) preferential initial atelectasis of regions with high ventilation-perfusion ratios (as proposed by Farhi) and 2) substantial reductions in compliance without closure of air space, as might result from changes in surface forces with time. aerotonometer; atelectasis; venous admixture; mechanics of breathing; compliance of dog lungs; diffusion capacity of dog lungs; ventilation perfusion; relationships of dog lungs Submitted on October 28, 1963