Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study assessed the relationship between nitrogen dioxide inhalation and the development of pulmonary emphysema and investigated how the severity of preexisting emphysema brought about by protease (elastase) instillation into the lung may be augmented by a subchronic exposure to a relatively high concentration of nitrogen dioxide. Lungs of adult Fischer-344 rats were evaluated for emphysematous changes after (1) a single intratracheal instillation of elastase (E), (2) a 25-d exposure to 35 ppm nitrogen dioxide (NO2), and (3) elastase instillation followed by 25-d exposure to 35 ppm NO2 (E + NO2). Rats instilled with sterile normal saline and subsequently exposed to filtered air served as a control group (NS). Residual volumes (RV) of the NO2 and NS groups were virtually identical, whereas the RV of the E and E + NO2 lungs (2.3 and 2.3 ml, respectively) were significantly greater than those of the NS and NO2 lungs (1.3 and 1.4 ml, respectively). Directionally similar changes in the excised lung volumes and total lung capacities were obtained with the E and E + NO2 groups; NO2 alone, however, did not alter these volumetric parameters. No differences in arterial blood gases and pH values, minute ventilation, or breathing frequencies were found among the experimental groups. The mean linear intercept values (MLI) obtained with the NS and NO2 exposed lungs were essentially identical with average values of approximately 62 micron. This morphometric parameter was substantially increased in the E- and E + NO2-exposed lungs; no significant differences, however, were found between the MLI values obtained with the E and E + NO2 lungs (approximately 95 and approximately 97 micron, respectively). From these data, as well as histologic examinations of lung sections for evidence of emphysema, we conclude that (1) a subchronic, moderately high level of NO2 exposure does not produce an irreversible emphysematous lesion in the rat model and (2) exposure of rats to 35 ppm for 25 d after elastase instillation into the lungs does not potentiate protease-induced emphysema or bring about a progression in preexisting emphysema.
 ...
PMID:Nitrogen dioxide exposure and development of pulmonary emphysema. 363 23

The effect of chronic exposure to 2 ppm nitrogen dioxide (NO2) for 8 hr a day, 5 days a week, for 8 weeks was assessed in normal and emphysematous hamsters by measuring (1) lung morphometry (mean linear intercept [Lm] and internal surface area [ISA]), (2) lung mechanics (lung volume, compliance and coefficient of static deflation, pressure-volume curve fitted to an exponential equation), and (3) serum elastolytic activity and protease inhibitor capacity. Emphysema was induced by a single intratracheal injection of 6 IU porcine pancreatic elastase. Four groups of animals were used; Control, NO2-exposed, elastase-treated, and NO2-exposed postelastase. Our results show that NO2 exposure alone induced mild emphysematous lesions whose degree of severity estimated by morphometry increase in Lm and decrease in ISA. P less than 0.01) was of the same order as that of the lesions induced by 6 IU elastase. Exposure to 2 ppm NO2 enhanced elastase-induced emphysema (further increased Lm and further reduced ISA. P less than 0.01). By contrast, study of lung mechanics revealed no difference between the control and NO2-exposed groups or between the elastase-treated animals exposed to NO2 and those not so exposed. This apparent discrepancy between results of morphometry and lung mechanics may be due to the lower sensitivity of lung mechanics parameters and their consequent inability to reflect changes in the emphysematous lesions induced by elastase injection or 2 ppm NO2 inhalation. In vivo, serum elastolytic activity and protease inhibitor capacity were not modified in any group, indicating that either serum does not reflect the degree of protease inhibitor capacity in the alveolar spaces or chronic inhalation of low concentrations of NO2 is not sufficient to cause elastase/antielastase imbalance. Lastly, our results suggest that chronic exposure to 2 ppm NO2 may cause individuals with inherited or acquired emphysematous lesions to develop more severe emphysema.
 ...
PMID:Effect of low-level NO2 chronic exposure on elastase-induced emphysema. 364 60

Thirty-nine excised human lungs were examined to identify early changes in the small airways, their size distribution, and their elastic recoil in relation to mild degrees of emphysema. Elastic recoil measurement, single-breath nitrogen (SBN2) tests, and FEV1 were obtained from 18 lungs with no emphysema and 21 emphysematous lungs with no greater than Grade 5 emphysema score. The mean number of alveolar attachments per brochiole was determined from all the bronchioles cut in cross section. When the 2 groups of lungs were compared, the percentage of predicted elastic recoil of the nonemphysematous lungs was significantly greater at 50, 70, 80, and 90% of TLC than in the mildly emphysematous lungs. The TLC of the emphysematous lungs (% of predicted) was also significantly greater than in the nonemphysematous lungs. Pigment of the small airways was the only pathologic feature that was significantly greater in the emphysematous lungs than in the nonemphysematous lungs. Size distribution in the small airways was similar except for the airways zero to 0.2 mm, which were more frequent in the emphysematous lungs. When data from both groups were combined, elastic recoil was shown to be related to both the number of alveolar attachments (p less than 0.03) and the mean diameter of the small airways (p less than 0.01). We conclude that structural and functional changes in lungs with mild emphysema include reduced elastic recoil, increased lung size, and some size distribution changes in the small airways. Mild emphysema is not associated with air-flow limitation.
 ...
PMID:Mild emphysema is associated with reduced elastic recoil and increased lung size but not with air-flow limitation. 366 40

We examined the lungs of 48 patients who died in the National Institutes of Health clinical trial of Intermittent Positive-Pressure Breathing. Bronchial lesions were not related either to clinical features or to tests of expiratory flow. In particular, bronchial muscle was not related to the response to bronchodilators or to the variability of flow rates. The degree of emphysema was well related to loss of body weight and was also positively related to right ventricular hypertrophy. It was also the major morphologic correlate of abnormal tests of expiratory flow, the slope of phase III of the single-breath nitrogen test, and increased residual volume. Emphysema was negatively related to bronchodilator response and variability of expiratory flow. The proportion of bronchioles less than 400 microns in diameter and a measurement of irregular bronchiolar shape were related to dyspnea and increased PaCO2 and were also related to abnormal tests of expiratory flow, phase III of the single-breath nitrogen test, and residual volume. The presence of increased muscle and fibrosis in the bronchioles appeared beneficial, being associated with a higher PaO2, a lower PaCO2, less edema, less right ventricular hypertrophy, better flow rates, and lower residual volumes. This may reflect the fact that airways with increased muscle and fibrosis are less markedly narrowed and less distorted. Goblet cell metaplasia appeared to be an important variable, independent of others, and was related to airway resistance. We divided patients into 3 groups according to severity of emphysema, and then into 2 subgroups of lower and higher flow rates in each category.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The National Institutes of Health Intermittent Positive-Pressure Breathing trial: pathology studies. II. Correlation between morphologic findings, clinical findings, and evidence of expiratory air-flow obstruction. 390 49

We studied 47 excised human lungs in order to examine the relationship between the number of alveolar attachments surrounding bronchioles 2 mm or less in diameter and the presence of small airways disease and overall lung function. Expiratory pressure-volume curves, the FEV1, and the single-breath nitrogen washout were obtained from 11 lungs without emphysema and 36 lungs with various degrees of emphysema. The lungs were subsequently inflation-fixed at 20 cm H2O. Gough sections were used to measure emphysema. Six to 10 blocks of tissue were cut at random from a midsagittal slice of lung tissue for the small airways and alveolar attachment study. We measured the inside diameters of all nonrespiratory bronchioles (2 mm or less in diameter) and made corrections for shrinkage during processing. The number of alveolar attachments on the outside wall of the bronchioles cut in cross section were obtained from all the sections observed. The mean number of alveolar attachments per bronchiole was determined for each lung. The histopathologic features of the bronchioles were evaluated by the method of Cosio and coworkers (2). We found a positive correlation between the number of alveolar attachments and the percentage of predicted FEV1 (r = 0.328, p less than 0.03) and the percentage of predicted closing capacity (r = 0.553, p less than 0.01). There was a negative correlation of the mean number of alveolar attachments and the small airways fibrosis score (r = -0.344, p less than 0.02). A correlation also existed between the number of alveolar attachments and the mean internal bronchiolar diameter (r = 0.561, p less than 0.001). We conclude that the alveolar attachments and elastic recoil are related to the size and function of the small airways.
 ...
PMID:Radial traction and small airways disease in excised human lungs. 394 70

Lung volumes in irreversible diffuse obstructive pulmonary syndromes (DOPS(I)) have been studied by using an analog of the lung that simulates an 18-breath nitrogen washout. The functional residual capacity (FRC), the dead space volume (Vd), the distribution of ventilation, as well as the pattern of lung emptying have been measured in normal subjects and those with obstructive syndromes. The Vd increased progressively with severity of the obstructive syndrome, as did FRC. For all subjects, both normal and obstructed, the ratio of Vd/FRC remained relatively fixed with the regression line of Vd upon FRC showing a minimal value for Vd of 67 cm(3). Vd increased by an average value of 33 cm(3) per liter of lung volume above this value. The increase in FRC resulted from the increased volume of the poorly ventilated compartment for the most part. X-ray evidence of emphysema was poorly correlated with the changes in Vd or FRC. A significant increase in anatomical Vd in DOPS(I) makes up an appreciable portion of the total Vd (physiological).
 ...
PMID:Lung volumes in diffuse obstructive pulmonary syndromes. 481 81

A model of pulmonary capillary gas exchange and venous admixture is presented and the inclusion of this model into a model of the entire respiratory system is discussed. Partial pressure and concentration gradients for nitrogen, helium, oxygen, and carbon dioxide are predicted. The cases of breathing room air and 10% oxygen are studied. In both of these studies the Bohr and Haldane effects are included, and the "physiological" dissociation curves of oxygen and carbon dioxide are predicted for the normal case as blood flows from the venous blood end of the capillary to the arterial blood end. Venous admixture effects are also calculated for both of these cases. The effects of emphysema, pulmonary congestion, and altered cardiac function on the gradients are studied.
 ...
PMID:A theoretical study of pulmonary capillary gas exchange and venous admixture. 575 19

We studied the reparative process after inhalation exposure to 20 ppm of nitrogen dioxide (NO2) in the lungs of hemizygous blotchy male (Blo/g) and heterozygous blotchy female (Bio/+) mice. Age-matched siblings (C3Hf) without the blotchy gene at X-chromosome locus (+/y) and +/+) served as control animals. After exposure to NO2 for 28 days, there was a marked progression in the extent of emphysema in Blo/y mice associated with a significant decrease of internal surface area (p < 0.05) and an increase in the mean linear intercept (p < 0.005). In contrast, +/y, Blo/+, and +/+ mice showed mild airspace enlargement without decrease in internal surface area after similar exposures. Blo/y mice killed 1 month after cessation of NO2 exposure showed a persistent, mild chronic bronchiolitis that was more frequent and of greater severity than that present in control +/y mice. Alveolar macrophages in the Blo/y mice were larger than those in +/y, +/+, and Blo/+ mice both before and after exposure to NO2. Crystalloid inclusions were observed in the enlarged alveolar macrophages of the Blo/g mice only after exposure to NO2, but were not seen in control animals. These observations indicate that the pattern of lung injury and repair after subacute exposure to 20 ppm of NO2 in the Blo/y mouse differs from that present in age-matched siblings in that inherited abnormalities in alveolar macrophage function may exist in addition to the previously described alterations in connective tissue proteins. Both of these alterations may influence the development of emphysema in the blotchy male mouse.
 ...
PMID:Lung injury and repair in the blotchy mouse. Effects of nitrogen dioxide inhalation. 610 12

Human neutrophil elastase and other neutrophil granule constituents are internalized by human alveolar macrophages in vitro via receptor-mediated endocytosis, and immunoreactive neutrophil elastase is detectable within alveolar macrophages freshly harvested from human smokers. To gain insight into the potential role of neutrophil elastase bound by alveolar macrophages in the pathogenesis of connective tissue proteolysis, we have chosen hypoxia as a model of macrophage injury and have studied its effect upon the fate of bound neutrophil elastase. We found (1) that in a 3-h incubation after brief exposure to neutrophil elastase, control alveolar macrophages partially degraded bound enzyme, but they also released intact, enzymatically active, elastase in small amounts; (2) that release of TCA-insoluble radiolabeled elastase and elastase activity was enhanced fivefold and twofold over control, respectively, by alveolar macrophage injury during a 3-h incubation in humidified nitrogen; (3) that enzymatic activity of bound neutrophil elastase was largely masked by human neutrophil elastase-inhibitory activity of macrophage cell extracts. The data suggest (1) that the fate of neutrophil elastase bound to alveolar macrophages may be modulated by the local tissue environment; (2) that noxious agents may cause proteolytic tissue injury in the vicinity of alveolar macrophages by enhancing release of bound neutrophil elastase; (3) that alveolar macrophages may participate in the pathogenesis of centrilobular pulmonary emphysema by serving as a vector for neutrophil elastase, even if elastase activity is not detectable in alveolar macrophage lysates.
 ...
PMID:Hypoxic injury to human alveolar macrophages accelerates release of previously bound neutrophil elastase. Implications for lung connective tissue injury including pulmonary emphysema. 634 81

Data on the respiratory functional responses of animals and humans to inhaled oxidant gases and to pulmonary emphysema were reviewed and compared. Comparisons included responses to short-term inhalation of ozone, nitrogen dioxide, and oxygen and the functional manifestations of chronic emphysema. The comparisons illustrated that animals and humans have qualitatively similar functional responses to the irritant, bronchoconstrictive, and sensitizing effects of acutely inhaled ozone and nitrogen dioxide. Animals and humans responded similarly to the inflammatory and edematous effects of inhaled oxygen. Similar changes in maximal expiratory flow-volume curves, pressure-volume curves, lung volumes, and alveolar-capillary gas exchange occurred in animals and humans with emphysema. These results suggest that similar respiratory functional changes occur in both animals and humans when similar morphological changes result from lung injury. This observation lends confidence to the use of laboratory animals in studies to predict the effects of long-term exposure of humans to inhaled oxidant gases.
 ...
PMID:Respiratory function responses of animals and man to oxidant gases and to pulmonary emphysema. 637 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>