The correlation of lung structure with function.
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Animals↗
Biomedical subjects
N Berend
Publications and source records attributed to N Berend.
Correlations of maximum expiratory flow with small airway dimensions and pathology.
Pressure-volume and maximum expiratory flow-volume curves with air and a He-O2 mixture were performed in 25 excised human lungs. Small airway dimensions were measured, and the degree of various small airway lesions and emphysema was graded. Correlations were then made between the maximum flow (Vmax) at a transpulmonary pressure (PL) of 5 cmH2O and these measurements and scores. Small airway dimensions correlated poorly with Vmax. However, significant correlations were obtained between Vmax and the inflammation score (P less than 0.05), fibrosis score (P less than 0.05), and emphysema grade (P less than 0.01) but not smooth muscle hyperplasia or pigmentation. Neither the increase in flow with He-O2 nor the volume of flow correlated significantly with any small airway measurement or score.
Airway Obstruction↗
Exponential analysis of pressure-volume relationship in excised human lungs.
Eighty excised human lungs were placed in a volume-displacement plethysmograph, and expiratory pressure-volume (PV) data points were obtained between transpulmonary pressures of 30 and 0 cmH2O. An exponential function of the form V = A - Be-KP was fitted to the PV data points (V is the volume at pressure P, A is the maximal lung volume at infinite pressure, B is A minus the intercept of the exponential on the volume axis, and K is a shape constant directly related to lung compliance). Thirty-two lungs were emphysema-free and 48 lungs had emphysema ranging from grade 2 to grade 80. In the emphysema-free lungs the exponential fit was excellent in terms of r2, but systematic deviations from the PV data occurred in both young and old lungs. Both K and B/A were significantly age related (P less than 0.01). In the emphysematous lungs the exponential fit was equivalent to that in the emphysema-free lungs although, again, systematic deviations from the PV data occurred. With age constant, K (P less than 0.01) but not B/A was significantly correlated with the emphysema grade. However, the overlap with values of K in the emphysema-free lungs was too great for K to be useful in the diagnosis of emphysema.
Adult↗
The effect of positive end-expiratory pressure on functional residual capacity: role of prostaglandin production.
It has been shown that lung distension can generate prostaglandins. To test the hypothesis that there may be a prostaglandin-mediated peripheral (alveolar duct) bronchodilator effect contributing to the increase in functional residual capacity (FRC) observed with positive end-expiratory pressure (PEEP), we applied PEEP to 8 beagle dogs at 2, 5, 5, 7.5, and 10 cm H2O, and measured FRC at each level and immediately after cessation of PEEP. This experiment was then repeated after the intravenous administration of indomethacin 10 mg/kg. The results indicate a significant reduction of FRC (p less than 0.05) at 5, 7.5, and 10 cm PEEP after the administration of indomethacin. Furthermore, FRC initially failed to return to baseline immediately after cessation of PEEP but did so after indomethacin. We conclude that endogenous prostaglandin production of PEEP but did so after indomethacin. We conclude that endogenous prostaglandin production may be partially responsible for the elevation of FRC with PEEP.
Animals↗
Lobar pressure-volume characteristics of excised human lungs.
The pressure-volume (P-V) characteristics were investigated in 14 excised left human lungs and their individual lobes. Comparison of the upper and lower lobar P-V curves of the emphysema-free and emphysematous lungs showed no significant difference when plotted as per cent lobar volume at a transpulmonary pressure (PL) of 30 cm H2O (V30). However, when in the emphysematous lungs the more severely involved lobes were compared with the less severely involved lobes, significant differences in the PL 60-90% V30 were found, the more severely involved lungs exhibited a higher PL. The mean linear intercepts were identical in the upper and lower lobes of the emphysema-free lungs indicating equal distension and validating expression of the P-V data as per cent V30. However, in he emphysematous lungs, in which the upper lobes were more severely involved, the linear intercepts tended to be larger in the upper lobes and the ratio of upper to lower lobe V30 tended to be larger than in the emphysema-free lungs. Thus, in the emphysematous lungs, comparison of the lobar P-V curves expressed as per cent V30 may not be valid.
Adolescent↗
Exponential analysis of lobar pressure-volume characteristics.
In 19 excised left human lungs, seven of which were emphysema-free, lobar pressure-volume (P-V) characteristics were analysed by fitting to the P-V data an exponential of the form V=A-Be-KPL (where V is the volume at a transpulmonary pressure (PL), A is the theoretical lung volume at infinite PL, B is the difference between A and the intercept of the fitted exponential on the volume axis and K is a shape constant). In the emphysema-free lungs there was no difference in the B/A ratio expressed as a percentage, indicating an identical position of the P-V curves of the upper and lower lobes. However the upper lobes had significantly (p less than 0.025) higher values for K than the lower lobes indicating greater compliance. In 10 emphysematous lungs the upper lobes were more severely involved than the lower lobes. In these lungs the difference in K between upper and lower lobes had been abolished suggesting that the less emphysematous lower lobes had increased compliance relatively more than the upper lobes.
Adult↗
Collateral ventilation in excised human lungs.
Pressure-volume (PV) curves and single-breath nitrogen (SBN) washout traces were obtained in 32 excised human lungs. Comparison of the volumes at the onset of phage IV of the SBN traces (V phase IV) and the volumes at the inflection points (VIP) of the PV curves revealed V phase IV to be significantly larger than VIP. We postulated that V phase IV was caused by bulk airway closure and that the difference between V phase IV and VIP was due to collateral ventilation. To test this we correlated V phas IV -- VIP with age and emphysema grades of the lungs. Significant correlations were obtained, demonstrating that with increasing age and emphysema grade V phase IV -- VIP also increased. This is consistent with the documented evidence for decreased resistance to collateral ventilation with increasing age and emphysema. In addition, in a total of 86 lungs we demonstrated that with increasing age and emphysema there is an increasing incidence of total lack of sigmoid deviation in the PV curve.
Adolescent↗
Correlation between lung structure and function in a canine model of emphysema.
To correlate lung structure and function in an animal model of emphysema, 17 dog lungs were treated with intrabronchial instillation of papain (range of concentration 0.5-5%); the contralateral lungs served as controls. The lungs were inflated to the volume at a transpulmonary pressure (PL) of 25 cmH2O (V25), and static pressure-volume and maximal expiratory flow-volume curves were obtained. Eight pairs of lungs were processed for histology at a PL of 5 cmH2O, and eight pairs of lungs were processed at a PL of 25 cmH2O. Significant loss of elastic recoil was found in the papain-treated lungs, between 30 and 90% predicted V25 (P less than 0.02). However, there was no correlation between the mean linear intercept corrected to predicted lung volume (indicative of alveolar destruction) and loss of elastic recoil. There was a significant reduction of maximal flow (Vmax) between 20 and 90% predicted V25. However, the reduction in Vmax was commensurate with the reduction of elastic recoil, since there was no significant change in resistance of the upstream segment between 30 and 70% predicted V25. Airway morphometry demonstrated no significant differences in small airway dimensions between control and emphysema-treated lungs. In both control and papain-treated lungs, small airway dimensions changed relatively more than lung volume a PL of 25 and 5 cmH2O.
Animals↗
Single-breath nitrogen test in excised human lungs.
Pressure-volume curves and simulated single-breath nitrogen tests were performed on 32 excised left human lungs and the slope of phase III, and phase IV plus minimal volume, expressed as percent of the lung volume at a transpulmonary pressure of 30 cmH2O (closing capacity), was calculated. The lungs were graded as to the degree of emphysema and degree of peripheral airways disease. Peripheral airway dimensions were also measured. The closing capacity expressed as percent predicted in vivo was significantly correlated with the total pathological scores (P less than 0.01) and inflammation scores (P less than 0.01) as well as the transpulmonary pressures at the onset of phase IV (P less than 0.01). Correlations with the emphysema grade were not significant. The slopes of phase III were highly variable even among normal lungs and could not be shown to correlate with airways disease or emphysema.
Adolescent↗
Lobar distribution of bronchiolar inflammation in emphysema.
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Adult↗
Small airways disease: reproducibility of measurements and correlation with lung function.
Three measurements of small airway dimensions and a measurement of lesions in small airways were made in 32 human lungs obtained at autopsy in order to assess the intraobserver and interobserver variability of these measurements and their interrelationships. The same measurements were then made in 22 lobes resected in patients with known lung function. Small airway dimensions were smaller in surgically resected lobes compared to autopsy lungs suggesting persistence of muscle tone in the surgical specimens.
Airway Obstruction↗
The maximum expiratory flow-volume curve with air and a low-density gas misture. An analysis of subject and observer variability.
The subject and intra- and inter-observer variability of three measurements derived from the maximal expiratory flow-volume (MEFV) curve with air and helium-oxygen (HeO2) mixture was determined in ten normal subjects who produced curves in the morning and afternoon of three consecutive days and again on one day a month later. The measurements examined were the maximum flow at 50% vital capacity (V50), the percentage increases in V50 when breathing the He-O2 mixture (delta V50), and the volume at which the curves on air and He-O2 first meet or intersect (VisoV). The delta V50 and VisoV were shown to have a greater degree of variability than the V50 and, in the case of VisoV, this was contributed to significantly by the observer variability. The within-subject variability of the delta V50 and VisoV was so great that the usefulness of these tests in following changes in lung function of individual patients must be questioned.
Adult↗
Maximum volumes in excised human lungs: effects of age, emphysema, and formalin inflation.
The volume of air at a transpulmonary pressure (PL) of 25 cmH2O was measured in 28 emphysema-free and 39 emphysematous excised adult lungs and in the lungs of 53 infants and children. In the adult emphysema-free lungs, this volume (V25) was significantly correlated with body length in males but, corrected for body length, not significantly correlated with age in either males or females. V25 was on the average 20 per cent larger than predicted TLC in non-emphysematous lungs in vivo. The lungs were also inflated and fixed with formalin at a constant PL of 25 cm H2O and their volume measured (VL). Marked and variable underinflation compared to V25 occurred in the adult lungs and VL minus lung weight averaged 75% of V25 and 91% of predicted TLC. In infants and children, the ratio of VL minus lung weight to V25 averaged 1.08 with a range of 0.58 to 1.84. The larger the lungs, the smaller the ratio, suggesting that fixation played a role in producing the small VL. In the emphysematous lungs, a significant correlation between the degree of emphysema and V25 was found. However, a statistically significant increase in V25 only occurred when the emphysema grade was greater than 5.
Adolescent↗
Effects of lobectomy on lung function.
The effect of lobectomy on lung function was investigated in 16 patients in whom comprehensive lung function tests were performed before and between six weeks and six months after lobectomy. The operation was well tolerated even by patients with quite severe airways obstruction. The effect of lobectomy on forced flow rates was in keeping with the change in lung volumes. There was no alteration in the distribution of ventilation and the diffusion capacity remained unchanged. The changes in the pressure volume curves were difficult to explain. All patients, even those with nearly "complete" hyperinflation of the remaining lung, had appreciable increases in maximal intrapleural pressure at full inspiration.
Aged↗
Plasma and sputum erythromycin concentrations in chronic bronchitis.
Plasma and sputum concentrations of erythromycin were measured in 10 patients with chronic bronchitis during an eight-day course of a new formulation of erythromycin stearate. The plasma erythromycin levels compared favourably with the minimal inhibitory concentrations for common respiratory pathogens and indicated adequate gastrointestinal absorption when the drug was taken immediately before food. Sputum erythromycin levels were variable and in some patients low or undetectable. Measurable sputum erythromycin levels were approximately 10% of plasma levels with no evidence of accumulation and were of similar order of magnitude to the minimal inhibitory concentrations for common respiratory pathogens except Haemophilus influenzae. There was no correlation between sputum and plasma erythromycin levels. There was a trend for higher erythromycin levels in sputum containing increasing amounts of pus and also when plasma levels increased.
Aged↗
Pressure-volume characteristics of excised human lungs: effects of sex, age, and emphysema.
Static deflationary pressure-volume curves were obtained in 28 emphysema-free (18 male and 10 female) and 39 emphysematous excised human lungs inflated to a maximum transpulmonary pressure (Pl) of 30 cmH2O. In emphysema-free lungs, the lung volumes at Pl 30 cmH2O (V30) were significantly related to body length in males and were significantly larger than predicated total lung capacity in vivo. However, corrected for stature (V30/body length), there was no significant age correlation. In both males and females, highly significant correlations between the PL at 50--90% V30 and age were obtained. There were no significant differences in these regressions between males and females. The emphysematous lungs were divided into three groups with increasing emphysema grades. Progressive decreases in the PL at 50--90% V30 and increases in the V30 were seen in the groups with increasing degrees of emphysema. Significant changes occurred in these measurements even in group 2 with mild emphysema, suggesting that the lesions of emphysema are not directly responsible for these changes.
Adolescent↗
Simple tests in the diagnosis of emphysema and airway narrowing.
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Bronchi↗
The influence of food on the bioavailability of new formulations of erythromycin stearate and base.
1. The effect of food on the bioavailability of two new formulations of erythromycin, 1) erythromycin stearate, 500 mg (Erythrocin, 250 mg capsule-shaped tablets) and 2) erythromycin base, 500 mg (Eryc, 250 mg capsules containing enteric-coated pellets) was studied in 16 healthy subjects. 2. The study was a balanced, randomized Latin square design and was conducted on 4 days. The four treatments were erythromycin stearate immediately before (EB) and after EA) breakfast and erythromycin base immediately before (eB) and after (eA) breakfast. 3. The mean +/- s.d. maximal plasma erythromycin concentrations were 2.09 +/- 1.06, 0.37 +/- 0.40, 1.8+ +/- 1.15 and 1.91 +/- 1.57 micrograms/ml and the mean +/- s.d. times at which these occurred were 1.3 +/- 0.7, 2.3 +/- 0.9, 4.4 +/- 1.9 and 4.3 +/- 1.1 h for EB, EA, eB and eA respectively. 4. The mean +/- s.d. areas under the curves (0 to 8 h) were 4.99 +/- 2.41, 1.04 +/- 1.57, 4.93 +/- 2.98 and 4.98 +/- 3.14 for EB, EA, eB and eA respectively. 5. The bioavailability of erythromycin stearate was significantly reduced by the prior administration of food, whereas the absorption of the base was not inhibited by food.
Adult↗