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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The benefits of mechanical ventilation with positive end-expiratory pressure (PEEP) are well documented, especially for patients with acute respiratory failure. PEEP increases functional residual capacity (FRC) and reduces closing volume (CV) and ventilation-perfusion mismatching. Little is known about the effects of PEEP in patients with chronic obstructive pulmonary disease, where closing volume and ventilation-perfusion mismatching are increased. We investigated the effects of PEEP in a canine model of panlobular emphysema (PLE). METHODS. After completion of control-period measurements, PLE was induced in eight dogs by intratracheal application of 20 ml aerosolized 16% papain solution. Three weeks later the effects of continuous positive-pressure ventilation (CPPV, PEEP 10 cmH2O) on gas exchange, FRC, and CV were investigated. Conventional intermittent positive-pressure ventilation (IPPV) served as reference. Measurements of CV were done using both the foreign gas bolus method and the single-breath oxygen test. FRC was determined by the nitrogen dilution technique. RESULTS. The papain-induced emphysema produced a deteriation in oxygenation, enlargement of FRC and CV, and an increase in quasi-static lung compliance. CPPV led to a further increase of FRC, but gas exchange was not improved nor was CV reduced. In the PLE period, mean pulmonary arterial pressures (MPAP) were higher during both modes of ventilation. CPPV tended to increase MPAP and pulmonary capillary wedge pressure when compared with IPPV. Systemic hemodynamic conditions were stable throughout the experiment. CONCLUSIONS. The application of PEEP to emphysematous lungs seemed to enlarge FRC, predominantly in the nondependent rather than in the dependent lung regions, which are prone to airway closure. In patients with emphysema, ventilation with PEEP may further deteriorate the impaired distribution of ventilation and thus counteract any improvement of gas exchange.
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PMID:[The effect of PEEP-ventilation on gas exchange and airway closure in experimental pulmonary emphysema]. 203 21

This project examined the influence of preexisting, experimentally induced pulmonary emphysema on the adverse health effects in rats of chronic inhalation exposure to either nitrogen dioxide or automotive diesel-engine exhaust. Previous reports indicated that humans with chronic lung disease were among those most severely affected by episodic exposures to high concentrations of airborne toxicants. There were no previous reports comparing the effects of chronic inhalation exposure to components of automotive emissions in emphysematous and normal animals. The hypothesis tested in this project was that rats with preexisting pulmonary emphysema were more susceptible than rats with normal lungs to the adverse effects of the toxicant exposures. Young adult rats were housed continuously in inhalation exposure chambers and exposed seven hours per day, five days per week, for 24 months to nitrogen dioxide at 9.5 parts per million (ppm)2, or to diesel exhaust at 3.5 mg soot/m3, or to clean air as control animals. These concentrations were selected to produce mild, but distinct, effects in rats with normal lungs. Pulmonary emphysema was induced in one-half of the rats by intratracheal instillation of the proteolytic enzyme elastase six weeks before the toxicant exposures began. Health effects were evaluated after 12, 18, and 24 months of exposure. The measurements included respiratory function, clearance of inhaled radiolabeled particles, pulmonary immune responses to instilled antigen, biochemistry and cytology of airway fluid, total lung collagen, histopathology, lung morphometry, and lung burdens of diesel soot. The significance of influences of emphysema and toxicant exposure, and interactions between influences of the two treatments, were evaluated by analysis of variance. The elastase treatment resulted in pulmonary emphysema that was manifested by enlarged alveoli and alveolar ducts, and by ruptured alveolar septa. There was no accompanying inflammation and no alterations of bronchioles. The emphysema persisted throughout the study period, with little evidence of progression. Lung weight was increased, physiological lung volumes were enlarged, lung compliance was increased, and airflow was obstructed. Nitrogen dioxide exposure of normal rats caused mild epithelial hyperplasia and a thickening of the walls of terminal bronchioles, an extension of bronchiolar epithelium into proximal alveoli, and inflammation in proximal alveoli. Lung volume and weight and the lung collagen content were increased. Airway fluid indicators of cell damage and oxidant protective mechanisms were increased. Similar effects of nitrogen dioxide exposure were superimposed over the effects of emphysema in emphysematous nitrogen dioxide-exposed rats. Several parameters were affected similarly by nitrogen dioxide exposure and emphysema (for example, increased lung volume), and the combined effects tended to be additive.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Influence of experimental pulmonary emphysema on the toxicological effects from inhaled nitrogen dioxide and diesel exhaust. 248 68

Single breath nitrogen washout tests were analyzed in dogs (n = 8) with healthy lungs and after development of emphysema. The animals were in the supine position and studied during anaesthesia and mechanical ventilation (FiO2 = 0.4, FiN2 = 0.6). During controlled expiration with constant flow (VE = 0.15 l/s) onset of phase IV of the alveolar plateau was related to airway closure of dependent lung regions (closing volume CV). In the control state, CV accounted for 6.2 +/- 1.5% VC, and closing capacity (CC) was lower than functional residual capacity (FRC). Likewise, gas exchange was normal in all animals (PaO2 = 24.7 +/- 3.32 kPa, PaCO2 = 5.18 +/- 0.53 kPa, PA-aO2 = 2.6 +/- 0.3 kPa). Panlobular emphysema (PLE) was induced by inhalation of papain (100 mg/kg). After three weeks development of PLE was documented by measurements of lung volumes (functional residual capacity (FRC), expired vital capacity (EVC), total lung capacity (TLC), residual volume (RV], pulmonary mechanics (dynamic and static compliance (Cdyn, Cstat), mean airway resistance (Raw], gas exchange (PaO2, PaCO2, PA-aO2), and by radiomorphological analysis. In the PLE-group, FRC and RV (p less than or equal to 0.05), and Cstat (p less than or equal to 0.01) were significantly elevated. CV increased to 16.2 +/- 2.7% VC (p less than or equal to 0.01) and CC exceeded FRC by 80 ml, indicating that tidal volume breathing took place within the range of closing volume. Oxygenation was significantly impaired (PaO2 = 18.6 +/- 3.72 kPa, PA-aO2 = 6.5 +/- 1.1 kPa, p less than or equal to 0.05), but not CO2-elimination. Pathological analysis by radiomorphological means showed dissiminate parenchymal lesions compatible with emphysema of grade II severity located predominantly in subpleural areas. In dogs with papain-induced PLE, premature closure of dependent airways is enhanced, which is due to structural changes and a loss of elastic recoil in the lungs.
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PMID:Single breath N2 washout in papain-induced pulmonary emphysema. 276 46

We studied the effect of low-protein diet (8% casein) on lung growth in rats from 3 to 7 weeks of age. Their diet was isocaloric with that of control animals fed a diet of 20% casein. The calorie intake of experimental animals was increased during the first 3 weeks of the experiment, but they increased less (about 10%) in body weight, had less protein and less water when the whole body was examined, and had lower serum proteins and decreased urinary hydroxyproline. The experimental animals remained in positive nitrogen balance by maintaining low urinary nitrogen excretion. The lungs of the experimental animals were abnormal, with decreased absolute amounts of hydroxyproline and desmosine and of these relative to unit lung weight. The lungs contained more air per gram of lung tissue, and the volume of air in the lung was increased at all transpulmonary pressures above zero. When corrected for increased total lung capacity, there was a loss of recoil at mid-lung volumes. Saline-filled volume-pressure curves, corrected for lung volume, showed similar loss of recoil. Alveolar multiplication was quantitatively normal, but the experimental animals had larger alveoli. We conclude that the protein deprivation in isocalorically fed animals has a specific effect on lung scleroprotein content, which may be due to diminished synthesis, and this results in both structural and functional abnormalities in the lung. Our results indicate the importance of dietary protein in lung development and possibly as one of the causes of emphysema. Further studies are needed to know whether this would be a problem in infants of Kwashiokor.
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PMID:Connective tissue, mechanical, and morphometric changes in the lungs of weanling rats fed a low protein diet. 279 30

3-Methylindole (3-MI) is a metabolite of tryptophan which causes acute pulmonary edema and emphysema in ruminants when administered orally or intravenously. 3-MI is metabolized by mixed-function oxidases to a reactive intermediate which may play a role in 3-MI-induced pneumotoxicity. Electron spin-trapping techniques have been used to investigate the in vitro and in vivo formation of free radicals during 3-MI metabolism by goat lung. A nitrogen-centered free radical of 3-MI has been generated from 3-MI in goat lung microsomal incubations. Although a nitrogen-centered free radical can be generated chemically from most of the indolic compounds, only the 3-MI free radical can be generated enzymatically. The formation of the nitrogen-centered 3-MI free radical was followed by the appearance of a carbon-centered lipid radical in microsomal preparations. The findings that an identical carbon-centered free radical was generated by FeSo4 in the microsomal system in the absence of 3-MI and that malonaldehyde formation is stimulated by 3-MI in microsomes led to the conclusion that 3-MI metabolism induces lipid peroxidation of microsomal membranes. The formation of 3-MI-induced lipid radicals was inhibited by vitamin E and glutathione. A carbon-centered radical was spin trapped in vivo in the lungs of goats infused with 3-MI. This radical had the same splitting constants as the carbon-centered lipid radical trapped in microsomal incubations containing 3-MI. This finding indicates that the metabolism of 3-MI in goat lung in vivo generates a lipid radical.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of free radicals in the mechanism of 3-methylindole-induced pulmonary toxicity: an example of metabolic activation in chemically induced lung disease. 300 1

A knowledge of the relationship between nutrition and the respiratory system applied in chronic airflow obstruction (BCO) enables a better understanding of the increased frequency (30 to 50%) of protein-energy malnutrition (MEP) in this population. The physiology of the wasting in chronic airflow obstruction seems to relate to hypermetabolism (HMB) which is not compensated by an increased alimentary intake. The HMB is linked to a rise in the work of the respiratory muscles whose efficiency is altered by intrathoracic hyperinfiltration and also the consequences of MEP on the mass and function of the respiratory muscles. In the animal MEP induced by alimentary restrictions leads to a model of pulmonary emphysema and to the diminution of the synthesis of surfactant. This emphysema seems to be principally due to an alteration of the process of protein synthesis and to a diminution of lysyl-oxydase activity. The nutrients (utilised notably by the venous route) have their own pharmacological role, and in addition they have an effect on the natural equilibrium of the energy and nitrogen balance. Lipids (rich in polyunsaturated fatty acids) intervene in the synthesis of prostaglandins, and exercise some effects on the inflammatory process and the activity in the bronchial and vascular smooth muscles. Based on this fact they have been used for their anti-inflammatory role at the pulmonary level in the treatment of mucoviscidosis. The administration of amino acids changes ventilation by acting on the central neuro-muscular command mechanism (VT/TI). The perfusion of amino acids enables a restoration of the chemo-sensitivity to oxygen and to CO2 abolished by the prolonged restricted diet. Finally the partial pressure of oxygen ought to be interpreted with respect to meal times because an oral dose of glucose can provoke an increase in the PaO2 of around 10 mmHg for healthy subjects and those with BCO. A preventive and therapeutic attitude vis a vis BCO should take account of the relationship between nutrition and the respiratory system in parallel with a correction of hypoxaemia in order to avoid the development of wasting.
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PMID:[Malnutrition and chronic obstructive bronchopathies]. 314 Mar 15

The purpose of this study was to examine the impact of nutritional support on nitrogen-energy relationships and functional parameters in malnourished patients with emphysema. Malnourished patients without lung disease served as the control group. Ten ambulatory, stable patients with emphysema and six patients without lung disease received an infusion of 5% dextrose (baseline) plus electrolytes (D5W) for two days, which was followed by an enteral or a parenteral infusion of either a carbohydrate-based (CB, 53% carbohydrate) or a fat-based diet (FB, 55% fat) for 1 wk each, in a randomized cross-over design. All patients had greater than 10% weight loss. Caloric intake was set at 1.7 times the resting energy expenditure (REE) as measured during the baseline period. The REE of patients with emphysema was 23 and 27% above that of the control group during baseline and refeeding periods, respectively. The increased REE was met primarily by an increased carbohydrate oxidation. During the infusion of D5W, N balance was lower in patients with emphysema, but during repletion N balance was similar in both groups of patients. Two weeks of nutritional support with either a CB or a FB diet increased body weight, N balance, and arm muscle area and improved maximal inspiratory pressure, skeletal muscle strength, and endurance-strength (using quadriceps, hamstring, and handgrip) to a similar degree in malnourished patients with and without lung disease. In other stress states, such as infection, it has been shown that hypermetabolism, hypercatabolism, and preferential fat oxidation occur concomitantly. Patients with emphysema are unusual because, although they are hypermetabolic, they are not hypercatabolic and do not demonstrate preferential fat oxidation.
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PMID:Nitrogen and energy relationships in malnourished patients with emphysema. 314 7

To examine the role of nicotine in the augmentation of elastase-induced emphysema by cigarette smoke, animals that had been pretreated with porcine pancreatic elastase (PPE) were exposed to cigarette smokes that had a five-fold difference in their nicotine concentrations. Young adult female Long-Evans rats were divided into seven groups: (1) untreated controls; (2) low nicotine cigarette smoke exposure (Kentucky 2A1 reference cigarettes; 35.0 mg total particulate matter, 0.42 mg nicotine, and 0.38 mg nitrogen oxides per cigarette); (3) high nicotine cigarette smoke exposure (Kentucky 2R1 reference cigarettes; 38.8 mg total particulate matter, 2.2 mg nicotine, and 0.34 mg nitrogen oxides per cigarette; (4) PPE alone; (5) PPE + sham smoke exposure; (6) PPE + 2A1 smoke exposure; and (7) PPE + 2R1 smoke exposure. Three days after intratracheal administration of PPE (400 IU/kg), animals in the smoke-treated groups were exposed to 10 puffs of cigarette smoke daily, 7 days/wk for 14 wk. Sham-treated animals received room air in place of cigarette smoke. After the exposures, pulmonary function tests were performed under general anesthesia. Whole lungs were examined for gross pathologic changes, and samples of lung tissue were harvested for quantitative morphometry. Cigarette smoke exposure alone did not produce significant changes in pulmonary function or structure. On the other hand, treatment with elastase alone produced a constellation of pulmonary functional and structural changes that were pathognomonic of emphysema. Exposure to 2R1 but not 2A1 cigarette smoke significantly augmented the emphysematous changes produced by PPE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Augmentation of elastase-induced emphysema by cigarette smoke. Effects of reduced nicotine content. 320 80

We evaluated the effect of beta-aminopropionitrile (beta APN) on the nitrogen dioxide (NO2) animal model of emphysema. Rats maintained on a beta APN-supplemented or a regular diet were exposed to 30 ppm NO2 for intervals ranging from 1 to 8 wk. Emphysema development was assessed by histologic evaluation and by changes in lung volume and mean linear intercept values. Evidence of pathologic changes were also documented by clinical and radiographic findings of osteolathyrism. The induction of centriacinar emphysema was attributed specifically to NO2 exposure. Neither the severity of the emphysema nor the time course of its development was altered by the beta APN-supplemented diet. These findings are in marked contrast to those observed with the exogenous elastase model of the disease, and they suggest that elastin synthesis and repair may not modulate elastin destruction in the NO2 model of emphysema.
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PMID:Nitrogen-dioxide-induced emphysema in rats. Lack of worsening by beta-aminopropionitrile treatment. 334 28

We studied the volume of trapped gas (VTG), using a nitrogen washout method, before and after bronchodilation in four groups with theoretically increasing risk of developing pulmonary emphysema: (1) nonsmoking healthy controls (PiMn), (2) nonsmoking subjects with an intermediate alpha 1-antitrypsin deficiency (PiMZn), (3) smoking subjects with normal concentration of alpha 1-antitrypsin, and (4) smoking PiMZ subjects. VTG was the only lung function variable that showed a significant difference between PiMZn and PiMn subjects but only after bronchodilation. Some conventional lung function tests also distinguished smokers from nonsmokers of both genotypes but VTG was the most sensitive test. VTG decreased after salbutamol inhalation in the control group but showed a consecutively larger increase with more risk factors of developing emphysema. An increase in VTG after bronchodilation may be a sign of alveolar abnormality preceding development of clinical lung emphysema.
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PMID:Changes of volume of trapped gas after bronchodilation in subjects with suspected subclinical emphysema. 348


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