Control of bronchospasm in patients with chronic obstructive pulmonary diseases.
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Biomedical subjects
Publications and source records attributed to G L Snider.
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The bronchodilator effects of aerosols of a high-dose of terbutaline sulfate (1.5 mg), a low-dose of terbutaline sulfate (0.75 mg), isoproterenol (0.3 mg), and placebo were compared using forced expiratory spirometry, flow-volume curves, and body plethysmography in a double-blind, six-hour, controlled study in 25 patients with reversible airflow obstruction. After isoproterenol therapy, the values peaked at 15 minutes, and none were significantly different (P less than .05) from placebo after the 30-minute observation point. The values for high-dose terbutaline peaked at one hour at a level that exceeded responses to isoproterenol. All values except the forced vital capacity at five and six hours and functional residual capacity at six hours were significantly greater than placebo (P less than .05) at all observation points. The low-dose terbutaline values peaked earlier and at a lower value than the high-dose terbutaline values, and several indexes were significantly greater (P less than .05) than after isoproterenol therapy beyond the two-hour point.
Native pancreatic elastase and guanidinated elastase have similar in vitro and in vivo properties and produce emphysema of similar severity in hamsters. 14C-guanidinated pancreatic elastase (16,000 cpm/0.2 mg) was instilled into the trachea of anesthetized hamsters. Within 24 hours the radiolabel found in the lungs rapidly decreases to 12% of the original 16,000 cpm and to 1% after 96 hours. Most of the radiolabel and elastase activity found in the lungs can be removed by bronchopulmonary lavage up to 48 hours after installation. Although seemingly very small, there is a significant amount of radiolabel (1-2%) which cannot be removed from the lungs by extensive bronchopulmonary lavage.
In order to define the roentgenographic manifestations of pulmonary tuberculosis in the adult, we reviewed a 12 month experience with newly diagnosed patients with active pulmonary tuberculosis in two Boston hospitals. Of 88 patients, 30 (34 per cent) presented with roentgenographic manifestations other than those associated with "usual" postprimary disease. At least 12 patients (13.5 per cent) had primary tuberculosis, including two subjects over 60 years of age. Six patients (6.8 per cent) had disease confined to the lower lung fields, eight patients (9 per cent) had tuberculomas and four (4.5 per cent) had miliary tuberculosis. Twenty per cent of the patients were totally asymptomatic. With the shift of tuberculosis care to community hospitals, knowledge of the varied roentgenographic manifestations is of increasing importance for the practicing internist.
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Intratracheal instillation of pancreatic elastase in hamsters produces emphysema, which progresses for up to one year after the insult. To study this process in more detail, a guanidinated derivative of porcine pancreatic elastase labeled with carbon-14 was prepared that was indistinguishable from unmodified elastase with respect to physicochemical properties and in vitro enzymatic activity. Guanidinated pancreatic elastase exhibits the same emphysema-inducing potency as unmodified pancreatic elastase. Two hours after intratracheal instillation of the [14C] guanidinated elastase, the whole lung retained only 40 per cent of the instilled radioactivity, but after 96 hours one per cent was still present. At 2 hours approximately 90 per cent of the radioactivity in the lungs could be removed by bronchopulmonary lavage, and at 96 hours 28 per cent was removable by this method. More than half of the radiolabeled elastase recovered in the lavage fluid at 2 hours was enzymatically active; enzymatic activity diminished to very small amounts by 96 hours. These data support the concept of the long-term binding of active elastase to lung tissue, a phenomenon that may be involved in the progressive nature of elastase-induced emphysema.
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A single intratracheal instillation of pancreatic elastase in hamsters induces a lesion resembling human panacinar emphysema. This paper reports the occurrence of irreversible goblet cell metaplasia in the bronchial epithelium of hamsters similarly exposed to elastase. The goblet cell change was dose related; a dose of 0.1 mg/100 g body wt or less at 16 days, produced slight or moderate goblet cell metaplasia in fewer than half the animals, whereas 84% of animals treated with a dose between 0.2 and 0.5 mg/100 g body wt developed goblet cell metaplastic lesions, more than half of which were considered to be severe. The percentage of goblet cells in the epithelium of elastase-treated hamsters (32.5) was significantly higher (P less than 0.005) than that of unexposed (12.2) and saline-exposed controls (18.7). All hamsters examined 6 and 12 mo after elastase treatment showed the lesion. The pathogenesis of the changes is unclear but the possibility is raised that the bronchial changes may be due to disturbance of an endogenous protease-antiprotease system. The findings suggest the hypothesis that, under appropriate circumstances, a single pulmonary insult in man could lead to a permanent lung injury demonstrating the anatomic lesions of both chronic bronchitis and panacinar emphysema.
In a prospective study, varying the bronchial brushing technique through the flexible fiberoptic bronchoscope was examined for the effects of cellular yield and diagnostic accuracy. The yield of cells obtained from the 1.7-mm brush was increased by more than twofold when the brush and bronchoscope were withdrawn as a unit through the pharynx and nose, (nonwithdrawn brushing), rather than withdrawing the brush alone through the aspiration channel of the bronchoscope (withdrawn brushing). The greater number of total cells in the nonwithdrawn brushing specimen was largely due to squamous cells, and the yield of tumor cells by the two methods was similar. The yield of cells from the same brush withdrawn through a new suction adapter available on the bronchoscope (Olympus BF-B2) was significantly decreased, as compared with the withdrawn brushing. There was a further decrease using a shielded 1-mm brush. In 23 of 30 cases of proven carcinoma, the diagnosis was made by the single withdrawn brushing, and in 26 of the 30 by the single nonwithdrawn brushing, a difference which was not statistically significant. We conclude that diagnostic accuracy is not significantly enhanced by withdrawing the brush and bronchoscope as a unit through the pharynx and nose; use of a small shielded brush offers no advantage over a larger unshielded brush; modifications of flexible bronchoscopes, such as the adapter to improve efficacy of suction, should be evaluated for effects on harvests of cells from bronchial brushes before being put into general use.
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Male hamster weighing 100-140 g were exposed to 50-500 microgram purified elastrase per 100 g body weight by intratracheal injection. The hamster were killed at intervals up to 12 months after treatment, and their lungs were examined grossly and microscopically. At 8 days after treatment, the lungs appeared to have a greater volume than the controls. At 16 days, the lungs remained inflated when the pleural cavity was opened. Alveolar size was increased in proportion to the dose of elastase. From 16 days onward, the emphysematous lesion was well established. The number of goblet cells in the bronchi also increased. Counts of goblet cells as a proportion of all bronchial lining cells showed that goblet cells more than doubled in number in elastase treated hamsters as compared with controls. The mechanism for the two lesions caused by elastase was not clear. It was concluded that the elastase treated hamster is a useful model for studies of the pathogenesis of chronic bronchitis and emphysema in man.
There were two cases of fatal interstitial pneumonia secondary to bleomycin sulfate administration. Although bleomycin pulmonary toxicity is generally thought to be dose-related and occurs infrequently with a total cummulative dose less than 300 to 400 units, the two reactions reported here occurred with doses of 105 and 165 units. Fatal bleomycin-induced pneumonia has been previously reported at these low dosages, and physicians should be aware that this toxic reaction may occur as an idiosyncratic response. Previous thoracic irradiation may be a predisposing factor. Patients receiving bleomycin should be meticulously monitored by interrogation for cough, dyspnea, and chest pain; by auscultation for rales; by serial chest roentgenograms; and by determinations of vital capacity and single-breath carbon monoxide diffusing capacity.
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Lung volumes and quasi-static deflation volume-pressure relationships were measured in male golden hamsters anesthetized with pentobarbital. Volume was measured with a pressure plethysmograph, and pleural pressure was estimated by the use of a water-filled esophageal catheter. Mean body weight +/- SE was 122.3 +/-3.0 g, mean lung weight was 0.74 +/- 0.2 g or about 0.6% of body weight. Mean lung volume at 25 cmH2O transpulmonary pressure (TLC25) was 7.2 +/- 0.14 ml, 9.78 +/- 0.17 ml/g lung weight or 5.92 +/- 0.06 ml/100 g body weight. Mean functional residual capacity was 2.4 +/- 0.06 ml or 33.3% of TLC25. Mean vital capacity was 5.2 +/- 0.13 ml. Mean quasi-static compliance of lung was 0.63 +/- 0.03 ml/cmH2O. Chord compliance of chest wall between lung volumes of 1 and 4 ml above RV was 3.39 +/- 0.53 ml/cmH2O. At FRC, the chest wall recoiled inward, so that pleural pressure was positive (1.4 +/- 0.13 cmH2O) and the lung was resisting further collapse. The slope of the lung's deflation volume-pressure curve changed at FRC, ERV was small (0.36 +/- 0.03 ml), and RV was determined by complete airway closure. Thus the mechanisms determining FRC are unusual and include an influence of airway closure.
Rats were exposed once to a polydisperse aerosol of 0.005 M cadmium chloride for 2 hours. Controls were saline-exposed rats and unexposed rats. Total extractable lipid, malate, lactate, isocitrate, and glucose-6-phosphate dehydrogenases were measured on the organelle-free cytosol from homogenized lungs at periods up to 10 days after exposure. The wet weight, dry weight, ribonucleic acid, and deoxyribonucleic acid content of the lungs were also determined. Ultrastructural appearances were studied at the same time intervals in a separate experiment. Total lipid content, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase activities showed approximate doubling by the fourth day after exposure, this change coinciding with doubling of wet lung weight and total lung deoxyribonucleic acid content. Malate dehydrogenase activity showed a high peak 1 hour after exposure before decreasing to follow the pattern of lactate and glucose-6-phosphate dehydrogenase. The changes found may be a nonspecific reaction to lung injury, comparable with oxygen, ozone, and nitrogen dioxide. These results in Type II cell proliferation, which would enhance glucose-6-phosphate dehydrogenase content and resistance to peroxidation. Lipid accumulation could be a similar response. However, the initial elevation in malate dehydrogenase activity is more in keeping with a specific mitochondrial injury (with some ultrastructural support), perhaps with leakage of mitochondrial enzymes. This suggests that there may be more than one mechanism at work in the injury. It is significant that despite the marked structural and functional changes, none of the rats died after the exposure, which makes the injury a model worthy of further investigation.