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Emphysema in the Blotchy mouse: a morphometric study.

Inheritance of the Blotchy allele at the X-chromosomal Mottled locus of mice results in changes in the lung which resemble emphysema. Previous studies using measurements of mean linear intercept have recognized emphysema in the hemizygous, Blo/Y, male and homozygous, Blo/Blo, female, but not in the heterozygous, Blo/+, female. The aim of this study was to develop a rapid, accurate method for analysis of emphysema and to establish whether it would identify emphysema in the heterozygote. Lungs from wild type and outbred Blo mice were inflated with fixative at a pressure of 25 cm and then sectioned and stained. Transect lengths across air spaces were measured using computerized image analysis and the results were plotted as histograms. Data were also expressed as cumulative frequencies (ogives) and subjected to statistical analysis by the non-parametric Kolmogorov-Smirnov test. Emphysema was shown by significantly increased (P less than 0.001) transect lengths in the Blo/Blo female and Blo/Y male compared with the wild type controls. The heterozygous Blo/+ mice form an intermediate group significantly different (P less than 0.001) from the wild and blotchy mice. The sensitivity of the method is illustrated by the fact that the Blo/+ female formed an intermediate group between wild type and the Blo/Y male and Blo/Blo female.

Animals↗

Effect of lung volume reduction surgery on pulmonary diffusion capacity in a rabbit model of emphysema.

BACKGROUND: While there is renewed interest in lung volume reduction surgery (LVRS) for treatment of emphysema, many aspects of the operation such as patient selection and surgical end points of excision are uncertain. We studied the effects of LVRS on measured lung volumes and diffusion capacity in an animal model to investigate optimal resection volumes. METHODS: Emphysema was induced in 32 New Zealand white (NZW) rabbits using aerosolized elastase. Helium dilution lung volumes and single breath DLCO were measured concurrently at baseline, following induction of emphysema (preop), and 1 week postoperatively (postop) following LVRS. Bilateral upper and middle lobe stapled lung resections were performed through midline sternotomies with excision of variable amounts of lung tissue from 1.8 to 5.8 g. RESULTS: FRC increased following induction of emphysema and decreased postoperatively. DLCO improved with increasing lung tissue resection up to 3 g of tissue and then decreased as even greater amounts were removed (r = 0.54). CONCLUSIONS: Measured lung volumes increase with development of emphysema and appropriately decrease in response to LVRS in this rabbit model. DLCO improves with moderate resection but then decreases with excessive excision of lung quantities and may help define one physiologic operative end point. In this rabbit model, excision of approximately 30% of lung volume was optimal and prevented further decrease in diffusion capacity.

Animals↗

Elastinolytic activity of alveolar macrophages in smoking-associated pulmonary emphysema.

Current concepts of pathomechanisms leading to acquired emphysema suggest that alveolar macrophages (AM) activated by cigarette smoking may cause an elastase/antielastase imbalance localized to the microenvironment formed by phagocytes and lung tissue. A functional cell assay was used to evaluate the cell-associated elastinolytic activity of AM. AM were obtained by bronchoalveolar lavage from patients with emphysema and from patients with non obstructive chronic pulmonary diseases (non-COPD) and cultured under serum-free conditions in direct contact with 3H-labeled elastin particles. Elastinolytic activity was calculated from the released radioactivity in culture supernatants and expressed as micrograms of 3H-elastin degraded x 10(-5) AM x 72 h-1. AM of patients with emphysema had significantly higher elastinolytic activity compared to that of non-COPD patients (median: 10.8 versus 4.1 micrograms; P < 0.01). Further differentiation of patients revealed the lowest median activity in sarcoidosis (2.3 micrograms). In respect to smoking habits there was a major difference between smokers with emphysema degraded more than twice the amount of elastin than smokers in the non-COPD group (median:11 versus 3.9 micrograms, P = 0.01). From these data we conclude that AM-derived elsatinolytic proteases may be involved in the destruction of lung elastin, which is thought to be the key event occurring in the pathogenesis of pulmonary emphysema.

Adult↗

Retained fetal lung liquid in congenital lobar emphysema: a possible predictor of polyalveolar lobe.

The purpose of this study was to determine whether retention of fetal lung liquid is more prevalent in polyalveolar congenital lobar emphysema than in conventional congenital lobar emphysema. Two patients with congenital lobar emphysema were prospectively identified in a 3-year period. Twenty-five such patients were identified in a retrospective study covering 39 years. Medical records were available for 22 patients who had 23 emphysematous lobes. Both babies from the prospective study and six subjects from the retrospective group had respiratory symptoms and underwent chest X-ray in the first day of life. Six of the eight babies with respiratory symptoms and chest imaging in the first day of life had retention of fetal lung liquid in an emphysematous lobe. All six of these lobes were polyalveolar. The lobe in one child was a polyalveolar lobe but without retained fetal lung liquid, and one child exhibited conventional lobar emphysema also without retained fetal lung liquid. One polyalveolar lobe caused no neonatal symptoms and was not imaged until the child was 3 months old. No baby with conventional lobar emphysema was shown to have retained fetal lung liquid. There seems to be a correlation between polyalveolar lobe and onset of respiratory symptoms in the first day of life. Retention of fetal lung liquid within the affected lobe was documented only in cases of polyalveolar lobe.

Female↗

mRNA expression of basic fibroblast growth factor from a single intratracheal instillation of papain-induced emphysema in rats.

The relations between mRNA expression of basic fibroblast growth factor (bFGF) and the changes in collagen I and collagen III in pulmonary tissues from a single intratracheal instillation of papain-induced emphysema in rats were investigated. Wistar rats (n = 42) were randomly divided into normal group and emphysema model 1, 3, 5, 7, 15, 30-day groups (n = 6 in each group). The rat model of emphysema was induced by a single intratracheal instillation of papain. The results of immunohistochemistry SABC and in situ hybridization with bFGF probe were quantitatively analyzed to examine the changes of collagen I and collagen III and bFGF mRNA expression in lung tissues and the percent of positive expression of bFGFmRNA in alveolar macrophages. The results were as follows: (1) In the emphysema model groups the optical densities of collagen I and collagen III began to increase after 3 days, reached the highest at the 7th day, and began to reduce at the 15th day; (2) No expression of bFGFmRNA in pulmonary tissues was detectable in the normal group. The positive expression of bFGFmRNA was detectable in lung tissues one day after the intratracheal instillation of papain. The average optical densities reached the peak (41.895 +/- 7.017) at the 7th day, significantly higher than in the normal group (0.581 +/- 0.139, P < 0.01). The positive expression of bFGFmRNA in lung tissues began to reduce at the 15th day; (3) Positive expression of bFGFmRNA in alveolar macrophages of instillation papain rats was detectable 3 days after the intratracheal instillation of papain, and reached the highest at the 7th day with the percent of positive expression of bFGF mRNA in alveolar macrophages being 70.13 +/- 11.21, higher than in the normal group (5.12 +/- 0.18, P < 0.01); (4) The expression of bFGF mRNA in the lung tissues and macrophages was positively related with the changes in collagen I and collagen III (P < 0.01 or P < 0.05) respectively. It was suggested that the up-regulation of bFGF mRNA expression during the development of emphysema can lead pulmonary interstitial fibrosis, which may take part in the injury and repair and the lung tissue reconstruction.

Animals↗

Unilateral subcutaneous emphysema after percutaneous tracheostomy.

PURPOSE: Percutaneous tracheostomy techniques are widely used in intensive care units. Subcutaneous emphysema is a rare but well recognized complication associated with this procedure. We report an unusual presentation of sc emphysema after percutaneous tracheostomy. The clinical features, diagnosis and postulated mechanism are discussed. CLINICAL FEATURES: A 39-yr-old man had percutaneous tracheostomy done after prolonged intubation in the intensive care unit. Subcutaneous emphysema developed over the right neck fever mimicking deep sc infection resulted in neck exploration. No obvious lesion was found in the tracheobronchial tree. CONCLUSION: Subcutaneous emphysema occurring after percutaneous tracheostomy could occur without significant injury to the tracheobronchial tree. We postulate that air leaking from the tracheostomy site might have been prevented by the snug fit between the tracheostomy tube and the skin, resulting in accumulation in the neck. Asymmetric dilatation of the trachea may explain the unilateral localization of the sc emphysema.

Adult↗

Relative preservation of peripheral lung function in smoking-related pulmonary emphysema: assessment with 99mTc-MAA perfusion and dynamic 133Xe SPET.

In this study the cross-sectional functional differences between the central and peripheral lung in smokers with pulmonary emphysema were evaluated by lung perfusion and dynamic xenon-133 single-photon emission tomography (SPET). The subjects were 81 patients with a long-term smoking history and relatively advanced emphysema, 17 non-smoker patients with non-obstructive lung diseases and six healthy non-smokers. Regional lung functional difference between the peripheral and central lung was assessed in the upper, middle and lower lung zones by technetium-99m macroaggregated albumin SPET and dynamic 133Xe SPET. The distribution of emphysematous changes was assessed by density-mask computed tomography (CT) images which depicted abnormally low attenuation areas (LAAs) of less than -960 Hounsfield units. Two hundred and eighty-eight (59.2%) lung zones of 63 (77.7%) patients with pulmonary emphysema showed relative preservation of lung function in the peripheral lung, with a curvilinear band of normal perfusion (a stripe sign) and a significantly faster 133Xe half-clearance time (T(1/2)) than in central lung (P<0.0001). Of these lung zones, 256 (88.8%) showed central-dominant LAA distributions on density-mask CT images, but the remaining 32 zones did not show any regional preference in LAA distribution. Conversely, 117 (24.0%) lung zones of 19 (23.4%) patients showed periphery-dominant perfusion defects and LAA distributions, with significantly prolonged T(1/2) in the peripheral lung area (P<0.0001). The remaining 81 lung zones of the patients with pulmonary emphysema and all the lung zones of the healthy subjects and patients with non-obstructive lung diseases did not show a stripe sign, and no differences were observed in T(1/2) values and LAA distributions between the central and peripheral lung. Relative preservation of peripheral lung function seems to be a characteristic feature in smoking-related pulmonary emphysema, and may indicate a lower susceptibility of peripheral parenchyma to the development of this disease.

Case-Control Studies↗

Visual classification of emphysema heterogeneity compared with objective measurements: HRCT vs spiral CT in candidates for lung volume reduction surgery.

The aim of this study was to investigate whether spiral CT is superior to high-resolution computed tomography (HRCT) in evaluating the radiological morphology of emphysema, and whether the combination of both CT techniques improves the evaluation in patients undergoing lung volume reduction surgery (LVRS). The material consisted of HRCT (with 2-mm slice thickness) and spiral CT (with 10-mm slice thickness) of 94 candidates for LVRS. Selected image pairs from these examinations were evaluated. Each image pair consisted of one image from the cranial part of the lung and one image from the caudal part. The degree of emphysema in the two images was calculated by computer. The difference between the images determined the degree of heterogeneity. Five classes of heterogeneity were defined. The study was performed by visual classification of 95 image pairs (spiral CT) and 95 image pairs (HRCT) into one of five different classes of emphysema heterogeneity. This visual classification was compared with the computer-based classification. Spiral CT was superior to HRCT with 47% correct classifications of emphysema heterogeneity compared with 40% for HRCT-based classification ( p<0.05). The combination of the techniques did not improve the evaluation (42%). Spiral CT is superior to HRCT in determining heterogeneity of emphysema visually, and should be included in the pre-operative CT evaluation of LVRS candidates.

Adult↗

Elevated platelet activating factor in the tracheal aspirate at birth and signs of intra-uterine inflammation in infants with neonatal pulmonary emphysema.

UNLABELLED: To investigate the pathophysiology of the neonatal pulmonary emphysema, we assayed platelet activating factor (PAF) in the tracheal aspirates of the low birth weight infants. A total of 29 neonates (birth weight <1750 g) who required mechanical ventilation were enrolled. Tracheal aspirates were obtained within 48 h and blood samples collected within 24 h of life. PAF was assayed on the basis of its ability to cause aggregation of washed rabbit platelets. PAF was significantly elevated in four infants who showed pulmonary emphysema within the 1st week of life (median 24 pg/g lipid phosphorus, range 9.9-200) compared with those detected in the other three groups of infants; infants with respiratory distress syndrome (RDS) in whom chronic lung disease (CLD) did not develop (median 1.8 pg/g lipid phosphorus, range 0-30; P < 0.05), infants without RDS nor CLD (median 0.64 pg/g lipid phosphorus, range 0-14; P < 0.05) and infants with other types of CLD (median 1.1 pg/g lipid phosphorus, range 0-1.8; P < 0.01). The four infants who developed pulmonary emphysema within the 1st week of life, had significantly elevated serum IgM and neutrophilia at birth. The increased amount of PAF in the tracheal aspirates shows the presence of inflammation in the lung at birth. The elevated serum IgM level and neutrophilia indicate that the inflammation begins in utero. CONCLUSION: Our data suggest that neonatal pulmonary emphysema is caused by intra-uterine inflammation increasing platelet activating factor in the lungs. Platelet activating factor may play a role in aggravating the process of pulmonary emphysema.

Bronchoalveolar Lavage Fluid↗

Bilateral thoracoscopic stapled volume reduction for bullous vs diffuse emphysema.

BACKGROUND: We compared our results with bullous vs diffuse emphysema by performing a bilateral thoracoscopic stapled volume reduction technique in 15 patients (age 45-80, 10 males, five females). METHODS: Eight patients demonstrated bullous emphysema and seven patients diffuse emphysema. Lung reduction was performed with a bilateral thoracoscopic stapled technique utilizing bovine pericardium in the supine position. RESULTS: Comparison of the bullous versus diffuse groups revealed no significant differences in means for the following variables: length of air leak (7.5 vs 3.3 days); length of stay (8.1 vs 6.5 days); pre-op FEV1, (23% vs 22%); pre-op dyspnea index (3.4 vs 3.6). At 3 months the bullous subset had a highly significant improvement (p < 0.007) in FEV1 (88%) compared with the diffuse subset FEV1 (59%). CONCLUSIONS: These early results suggest that patients with bullous emphysema are at no greater risk and demonstrate a significantly greater improvement in FEV1 than patients with diffuse emphysema.

Adult↗

A new, simple stapling technique for pulmonary emphysema: its effects and safety for improving respiratory function.

PURPOSE: We performed lung volume reduction surgery (LVRS) in an experimental model using a simple stapling technique (SST) for pulmonary emphysema. The technique uses a stapler to isolate the affected lung from the remaining lung instead of removing it. We performed the present experiment using dogs to study the effects and safety of LVRS using the SST. METHODS: Pulmonary emphysema was induced in 12 dogs with papain. They were divided into three groups: those operated on with SST composed the operation (Op) group; those receiving an experimental thoracotomy composed the sham-operation (Sham-op) group; and those not operated on composed the nonoperation (Non-op) group. Respiratory function was compared among the groups before induction of emphysema (baseline), after induction of emphysema (preoperation), and at 8 weeks after the operation (postoperation Op and Sham-op groups only). The lung was removed and histologically examined 8 weeks after the SST operation. RESULTS: In the Op group, alteration in forced expiratory volume (FEV) 0.5%, airway resistance (Raw) and specific airway conductance (sGaw) showed significantly favorable results. Histologically, the isolated area was widely replaced by fibrous tissue with numerous blood vessels in the circumference in the Op group; no signs of infection such as polykaryoleukocytes or microabscesses were observed in any of the samples. CONCLUSION: The LVRS for pulmonary emphysema using a simple stapling technique improved the expiratory flow and alleviated airway resistance. The isolated remaining lung was well organized without any infectious events or secondary adversity, thus demonstrating the safety of this technique. From these results, this technique is therefore suggested to be effective and applicable to clinical use.

Animals↗

Comparison of methods for evaluation of experimentally induced emphysema.

Four methods to quantify induced emphysema, in a manner economically applicable to large numbers of animals, are compared by correlation analyses. Lung tissue used was from rats pretreated intratracheally with elastase or saline prior to exposure to air or (NH4)2SO4 or NH4NO3 aerosols. The most sensitive quantitative evaluation was from mean chord length (MCL) measurements on scanning electron micrographs (SEM). Four-corner and parallel-line grids provided similar results, and reducing sample size to one selected field per lobe yielded a high degree of reliability for MCL measurements. Alveolar-pore perimeter and area (also measured on SEM photographs) were increased by induced emphysema, but were not reliable indicators for degree of pulmonary involvement. Both subjective score (grading the degree of emphysema) and percentage-area-affected determinations indicated the presence of emphysema, but with less sensitivity than MCL measurements. However, these two subgross methods (performed with a dissecting microscope) provided valuable information on the distribution of pulmonary lesions; emphysema was induced in a nonuniform but consistent and progressive pattern in the two lobes of the lung studied.

Ammonium Sulfate↗

Spontaneous mediastinal emphysema.

OBJECTIVE: Spontaneous mediastinal emphysema is uncommon. Its cause has not been determined precisely, but the entity is usually associated with suddenly raised alveolar pressure. METHODS: Between 1980 and 2001, 114 patients with mediastinal emphysema of various causes were hospitalized in the Wolfson Medical Center. In 22 of these patients (19.3%) the emphysema occurred without an obvious preceding event and was classified as spontaneous. The commonest symptoms and signs were chest pain, dyspnea and subcutaneous emphysema. All patients were kept under observation. Contrast esophagogram was performed in two patients who vomited. Pleural drains were inserted in six patients who had concomitant pneumothorax. RESULTS: All patients recovered and were followed for at least one year. There were no complications and no recurrences. CONCLUSIONS: Spontaneous mediastinal emphysema is usually a benign condition, which can be treated expectantly. The patients should be observed for 24 h. Recurrences are rare.

Adolescent↗

Results of lung volume reduction surgery in patients meeting a national emphysema treatment trial high-risk criterion.

OBJECTIVES: A report from the National Emphysema Treatment Trial indicated that lung volume reduction candidates with a forced expiratory volume in 1 second and a diffusing capacity of carbon monoxide of 20% or less of predicted value were at high risk for mortality and were unlikely to benefit from surgical intervention. This article examines the applicability of the National Emphysema Treatment Trial findings to our own patients. METHODS: We reviewed 280 patients who underwent bilateral lung volume reduction surgery at our institution between January 1993 and December 2001. All patients met our selection criteria, including heterogeneous distribution of emphysema. Of these 280 patients, 20 patients had both a preoperative forced expiratory volume in 1 second and a diffusing capacity of carbon monoxide of less than or equal to 20% of the predicted normal values, thus meeting one National Emphysema Treatment Trial criterion for high risk. Outcomes of the 20 patients were assessed through 5 years after the operation. The survival of the 20 patient cohort was compared with that of the 260 patients not meeting the National Emphysema Treatment Trial high-risk criterion. RESULTS: Ninety-day operative mortality included 1 (5%) patient. In all patients the forced expiratory volume in 1 second increased from 0.46 L (17%) to 0.78 L (32%), a 73% change; the diffusing capacity of carbon monoxide increased from 16% to 27%, a 70% improvement; residual volume decreased from 6.33 L (305%) to 4.26 L (205%), a 33% improvement; and room air arterial partial pressure of oxygen increased from 55 mm Hg to 64 mm Hg. Kaplan-Meier 5-year survivals did not differ between the high-risk and non-high-risk groups. CONCLUSIONS: Patients with a forced expiratory volume in 1 second and a diffusing capacity of carbon monoxide of 20% or less of predicted value might experience improvements in lung function, exercise tolerance, and quality of life with acceptable morbidity and mortality after lung volume reduction surgery.

Aged↗

Computer-aided diagnosis of emphysema in COPD patients: neural-network-based analysis of lung shape in digital chest radiographs.

Several abnormalities of the shape of lung fields (depression and flattening of the diaphragmatic contours, increased retrosternal space) are indicative of emphysema and can be accurately imaged by digital chest radiography. In this work, we aimed at developing computational descriptors of the shape of the lung silhouette able to capture the alterations associated with emphysema. We analyzed two-sided digital chest radiographs from a sample of 160 patients with chronic obstructive pulmonary disease (COPD), 60 of which were affected by emphysema, and from 160 subjects with normal lung function. Two different description schemes were considered: a first one based on lung-silhouette curvature features, and a second one based on a minimal-polyline approximation of the lung shape. Both descriptors were employed to recognize alterations of the lung shape using classifiers based on multilayer neural networks of the feed-forward type. Results indicate that pulmonary emphysema can be reliably diagnosed or excluded by using digital chest radiographs and a proper computational aid. Two-sided chest radiographs provide more accurate discrimination than single-view analysis. The minimal-polyline approximation provided significantly better results than those obtained from curvature-based features. Emphysema was detected, in the entire dataset, with an accuracy of about 90% (sensitivity 88%, specificity 90%) by using the minimal-polyline approximation.

Humans↗

Lobar emphysema due to ductus arteriosus compressing right upper bronchus in an infant with congenital heart disease.

A 1-month-old boy with tetralogy of Fallot, pulmonary atresia, right aortic arch, and right ductus arteriosus, exhibited progressive right upper lobar emphysema since his birth. The emphysema was caused by the right ductus arteriosus compressing the right upper bronchus. After division of the ductus arteriosus the emphysema completely regressed. We should explore the cause of lobar emphysema thoroughly before lobectomy especially when it is extrinsic. The emphysema may regress by eliminating the extrinsic factor.

Bronchi↗

Bilateral lung volume reduction surgery via median sternotomy for severe pulmonary emphysema.

BACKGROUND: Lung volume reduction surgery either via sternotomy or by thoracoscopy has been demonstrated to be effective for selected emphysema patients in North America and Europe. The present study summarizes short-term results of bilateral lung volume reduction performed via median sternotomy for the first consecutive 39 patients with severe diffuse emphysema in Okayama, Japan, from July 1995 to February 1997. METHODS: There were 35 men and 4 women, and the age range was 54 to 74 years with a mean age of 65 years. All were former heavy smokers and none of them had alpha1-antitrypsin deficiency. Only 9 patients (23%) showed a bilateral upper lobe pattern of emphysema. The operation was done through a median sternotomy, and the most emphysematous portions were excised bilaterally with a linear stapling device fitted with strips of bovine pericardium to prevent air leakage. RESULTS: No operative death was encountered. The first 33 patients completed 3-month follow-up assessment, and their mean forced expiratory volume in 1 second had improved by 41% from 735 mL to 1,037 mL. Other parameters of pulmonary function tests, arterial blood gas analysis, 6-minute walking distance, and dyspnea scale also had improved significantly. These improvements lasted for at least a year. CONCLUSIONS: Bilateral lung volume reduction surgery via median sternotomy is a safe and effective procedure for selected severe emphysema patients. Although the pattern of emphysema might be different between countries, the results in Japanese patients were similar to those previously reported in North American and European patients.

Aged↗

Computed tomographic evaluation of gastric emphysema--a report of three cases.

We present three patients, one male and two females, who had gastric emphysema demonstrated by computed tomography (CT) by chance. All patients had adenocarcinoma of the gastric antrum resulting in gastric outlet obstruction. We have classified these as the obstructive type of gastric emphysema. An additional cause in two of our patients could be a recent biopsy at UGI endoscopy. In one patient the emphysema was localized and the diagnosis could only have been made by CT. The two other patients had the usual pattern of extensive mural gas along the greater and lesser curvature of the stomach while dissection of gas into the retroperitoneum was present in one of them. There were no systemic effects attributable to the emphysema in all three patients. This reinforces the belief that gastric emphysema is not infective in origin.

Adenocarcinoma↗