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Past, present and future of the therapy of emphysema.

Senile atrophic emphysema was for a long time a term used to describe the pulmonary structure of elderly people. Since emphysema occurs mostly in elderly people, it was understood as the premature occurrence of a more or less normal ageing process. Therefore, almost no therapy seemed to be possible. Later emphysema was thought to be the consequence of airway obstruction, where the narrowed bronchi behave as check valves, so that the trapped air leads to overinflation and rupture of the alveoli. Thus bronchodilators were tried in the prevention of emphysema. This concept was partially successful, but also without bronchial obstruction emphysema can develop and progress. Experiments by Gross suggested that emphysema is a self-digesting process in the course of inflammatory defence of the body. Thus the inflammatory process itself became the target of the therapy. Additional therapy was tried by teaching special types of breathing and by breathing exercises, but had rather small success. Today our interest is focused on the imbalance of oxidants and antioxidants as the main reason for the self-digesting process. We hope to correct this imbalance, but we must be careful not to block a useful defence mechanism of the body.

Humans↗

Genetic influences in the development of emphysema in persons with normal serum proteins.

This review has failed to uncover convincing evidence to support the existence of familial emphysema in patients with normal serum proteins. Although a large number of studies have documented that non-A1PI hereditary factors are important in the development of nonspecific chronic obstructive pulmonary disease, it is far less certain that emphysema accounts for this familial occurrence. To the contrary, most existing evidence fails to support this possibility. Nevertheless, the issue remains unsettled and incompletely studied. Further investigations should include a major effort to identify young persons, 20 to 45 years of age, with emphysema alone but without A1PI deficiency. Based on prior reports, 76 it is likely that such persons will be found. As emphasized by Kazazian, "this is the group that should be studied for the presence of a single mutant gene in the homozygous state." 42 It is possible that several or many rare single-gene causes of emphysema await discovery. Careful family studies of young emphysematous subjects are indicated as well to determine whether emphysema-producing genes also constitute a risk factor in heterozygous persons. If such patients and families are discovered, further hypotheses will have to be drawn-up and carefully investigated to attempt a better understanding of the etiology and pathogenesis of emphysema.

ABO Blood-Group System↗

[Quantification of pulmonary emphysema with computerized tomography. Comparison with various methods].

Computed Tomography (CT) has been proved to be the most accurate imaging modality to diagnose emphysema in vivo. Our study was aimed at comparing different CT methods for pulmonary emphysema quantification in patients with severe chronic obstructive pulmonary disease (COPD). Forty-six consecutive inpatients affected with COPD underwent high resolution CT (HRCT). Three scans were acquired at 3 preselected anatomic levels at both full inspiration and expiration. Three different observers were asked to subjectively evaluate, under blind conditions, the extent alone and both the severity and the extent of emphysema on the 6 scans. HRCT findings were also analyzed quantitatively by measuring the mean CT number in Hounsfield Units (HU) and the % of lung area with CT numbers < -900 HU (pixel index). Quantitative CT data were compared with reference values obtained in 7 normal nonsmokers. The CT visual score of emphysema exhibited medium-high interobserver reproducibility with correlation coefficients ranging from 0.80 to 0.96 and a good correlation with pulmonary function tests, particularly relative to the assessment of the extent of emphysema alone as expressed by one observer. CT quantification demonstrated an excellent correlation with functional indices of expiratory airflow, lung volumes and diffusion coefficients (p < 0.001). The expiratory measurements were better than the inspiratory ones while the analysis of both CT number and pixel index gave comparable results. Only the CT expiratory quantitative data allowed to differentiate the patients affected with COPD from the controls. In conclusion, the severity of emphysema as expressed by CT correctly reflects the functional impairment of patients with severe COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Pulmonary angiotensin converting enzyme activity in elastase induced emphysema.

Pulmonary emphysema would be expected to reduce angiotensin converting enzyme (ACE) activity due to diminished capillary bed. However, transpulmonary angiotensin conversion has been found to be unaffected or marginally reduced in emphysema. In the present study we examined the activity of ACE in an experimental model of emphysema. Vmax and Km of ACE were determined in lung homogenates of six hamsters with elastase-induced emphysema and seven control hamsters. In the emphysematous lungs, ACE activity was significantly elevated due to marked increase in Vmax (19.2 +/- 1.7 vs. 4.9 +/- 1.6 nmol/min/mg protein for emphysematous and control lungs, P < 0.01). The Km of ACE was unaffected by emphysema. We suggest that the increase in ACE activity may be an adaptive change to enable adequate metabolic activity in the face of progressive reduction in pulmonary capillary surface area in emphysema.

Amino Acid Sequence↗

Relationship between exercise capacity and the severity of emphysema as determined by high resolution CT.

We investigated the relationship between exercise capacity or exercise-induced hypoxaemia and the severity of pulmonary emphysema in 20 patients with pulmonary emphysema. The patients underwent pulmonary function tests, high resolution computed tomography and incremental treadmill exercise testing. Computed tomography scans were obtained at four levels in the lungs, and emphysema scores were determined by the visual assessment of low attenuation areas as a measure of the severity of parenchymal destruction. The emphysema score correlated significantly with diffusing capacity (r = -0.69) in the pulmonary function tests. Among the exercise test parameters, the emphysema score correlated significantly with the total distance walked (r = -0.74), with maximal oxygen consumption (VO2max) (r = -0.77), with arterial oxygen tension (PaO2) at rest (r = -0.50) and at the maximum workload (r = -0.58), and with the decrement of arterial oxygen tension per litre of oxygen consumed (r = -0.64). These results suggest that exercise capacity and exercise-induced hypoxaemia are related to the extent of destruction of lung parenchyma in patients with pulmonary emphysema.

Aged↗

Experimental emphysema.

This animal model of emphysema exhibits the same abnormalities in respiratory mechanics as those seen in human emphysema. The histologic and radiographic findings also closely resemble changes of panacinar disease. Moreover, the progressive hypoxemia preceding hypercarbia also parallels the clinical course seen in human disease. Drawbacks of this model include the long time period required to develop significant changes and the cost of maintaining the animals for such a time period. Large cystic areas were not noted in our animals and one would have to turn to another model to address the problem of giant bullous emphysema. There is no ideal animal model of pulmonary emphysema, and the usefulness of an experimental model should be judged on how well it answers the specific questions. Significant information has been obtained using various animal models of emphysema in lung transplantation, diaphragmatic function, pulmonary hemodynamics, and in several other areas. The dog appears to be a suitable model for thoracic surgical research on emphysema.

Animals↗

[Quantitative assessment of pulmonary emphysema with computerized tomography. Comparison of the visual score and high resolution computerized tomography, expiratory density mask with spiral computerized tomography and respiratory function tests].

CT is the most accurate method to detect pulmonary emphysema in vivo. We compared prospectively two different methods for emphysema quantitation in 5 normal volunteers and 20 consecutive patients with chronic obstructive pulmonary disease (COPD). All subjects were submitted to function tests and HRCT; three scans were acquired at preselected levels during inspiration. The type and extent of pulmonary emphysema were defined, using the time-honored visual score system, by two independent observers under blind conditions. Disagreements were subsequently settled by consent. All subjects were also examined with expiratory spiral CT, using a density mask program, at two different cut-off levels (-850, -900 HU). Visual score and expiratory spiral density mask values (-850 HU) were significantly correlated (r = 0.86), but the visual extent of emphysema was always higher than shown by expiratory spiral CT. The emphysema extent assessed with both CT methods correlated with the function result of expiratory airflow obstruction and gas diffusion impairment (visual score versus forced expiratory volume in one second: r = -0.81, versus single breath carbon monoxide diffusion: r = -0.78. Spiral expiratory density mask -850 HU versus forced expiratory volume in one second: r = -0.85, versus single breath carbon monoxide diffusion: r = -0.77). When -900 HU was used as the cut-off value for the expiratory density mask, the correlation with single breath carbon monoxide diffusion worsened (r = -0.56). Visual score and expiratory density mask -850 HU gave similar results and permitted COPD patients to be clearly distinguished from normal controls (p < 0.01). Residual lung volume, measured with expiratory spiral CT correlated significantly with residual volume measured with the helium dilution technique (r = 0.66), but CT values were always higher than function results. We believe the true residual volume should lie somewhere in between the CT value and the function results with the helium dilution technique and conclude that the extent of pulmonary emphysema can be confidently assessed with CT methods. Finally, the simple visual score may be as reliable as such highly sophisticated new methods as the spiral expiratory density mask. Expiratory studies offer new insights into different normal and abnormal features of COPD and respiratory impairment.

Aged↗

[A case of bronchial asthma complicated with mediastinal, subcutaneous, peritoneal and epidural emphysema].

A case of a 16-year-old female with bronchial asthma complicated with mediastinal, subcutaneous, peritoneal and epidural emphysema was reported. The patient was admitted to our hospital because of dyspnea. Chest and abdominal X-ray films revealed mediastinal emphysema with peribronchial air sheath, subcutaneous emphysema in the neck and chest, and peritoneal emphysema. CT-scan revealed severe mediastinal, subcutaneous and epidural emphysema. These findings disappeared about 10 days after recovery from the attack. Diagnostic methods and the pathogenesis of air leak were also discussed.

Adolescent↗

[Pneumopericardium with combined emphysema of the skin and mediastinum following tooth extraction].

Emphysemas of the skin in the region of the cheek and face after surgical tooth extraction are relatively rare complications that can eventually lead to formation of an emphysema of the mediastinum and very rarely also to a pneumopericardium. The reason for this is often an instrumentally conditioned pressure increase in the oropharynx if this pressure increase leads to the entry of air into the wound region. There are also other mechanisms resulting in the formation of spontaneous mediastinal emphysema that can lead to a secondary emphysema. Possible reasons for the occurrence of a combined emphysema of the skin, the mediastinum and the pericardium are discussed.

Adult↗

[Subcutaneous and mediastinal emphysema related to facial injuries].

Mediastinal emphysema following facial trauma in the absence of neck, chest or abdominal injury is a rare entity. Mediastinal emphysema associated with fractures of the facial bones or odontological surgery has only been reviewed previously in case reports. This article reviews the etiological and pathogenetic mechanisms of subcutaneous facial/cervical emphysema and mediastinal emphysema associated with fractures of the facial bones. Complications and risk factors in treating fractures of the facial bones when mediastinal emphysema is present are discussed with emphasis on anaesthesiological complications.

Emphysema↗

Extracellular regulated kinase/mitogen activated protein kinase is up-regulated in pulmonary emphysema and mediates matrix metalloproteinase-1 induction by cigarette smoke.

The interstitial collagenase matrix metalloprotein-ase-1 (MMP-1) is up-regulated in the lung during pulmonary emphysema. The mechanisms underlying this aberrant expression are poorly understood. Although cigarette smoking is the predominant cause of emphysema, only 15-20% of smokers develop the disease. To define the signaling pathways activated by smoke and to identify molecules responsible for emphysema-associated MMP-1 expression, we performed several in vitro and in vivo experiments. In this study, we showed that cigarette smoke directly induced MMP-1 mRNA and protein expression and increased the collagenolytic activity of human airway cells. Treatment with various chemical kinase inhibitors revealed that this response was dependent on the extracellular regulated kinase-1/2 (ERK) mitogen activated protein kinase pathway. Cigarette smoke increased phosphorylation of residues Thr-202 and Tyr-204 of ERK in airway lining cells and alveolar macrophages in mice at 10 days and 6 months of exposure. Moreover, analysis of lung tissues from emphysema patients revealed significantly increased ERK activity compared with lungs of control subjects. This ERK activity was evident in airway lining and alveolar cells. The identification of active ERK in the lungs of emphysema patients and the finding that induction of MMP-1 by cigarette smoke in pulmonary epithelial cells is ERK-dependent reveal a molecular mechanism and potential therapeutic target for excessive matrix remodeling in smokers who develop emphysema.

Animals↗

Subcutaneous emphysema and pneumomediastinum complicating tonsillectomy.

BACKGROUND: Subcutaneous emphysema and pneumomediastinum are very rare complications of tonsillectomy. OBJECTIVES: To report on a case study and a literature review of these conditions; to discuss the management and controversial causes. DESIGN: Case study and literature review. METHODS: A case is presented of subcutaneous emphysema and pneumomediastinum complicating tonsillectomy. All published reports of these complications dating back to 1910 are reviewed. RESULTS: An additional 30 cases of subcutaneous emphysema and 9 of pneumomediastinum have been reported following tonsillectomy. This group of 32 patients with emphysematous complications included 17 male patients, 14 female, and a child of unknown sex. The mean age was 18.6 years (range, 2-65 years). All tonsillectomies were performed with a cold technique except our case. Subcutaneous emphysema was first noted intraoperatively in 8 patients (25%) a mean of 3.5 hours (range, 10 minutes to 14 hours) after the procedure in 18 patients (56%) and not until the next morning in 6 patients (19%). Most cases resolved without specific treatment or significant sequelae. Some cases were life-threatening and required urgent intervention. Others were misdiagnosed, which resulted in unnecessary surgery. CONCLUSION: Subcutaneous emphysema and pneumomediastinum are rare occurrences following tonsillectomy that should alert one to the possibility of more serious complications.

Adult↗

Risk factors for hypercarbia, subcutaneous emphysema, pneumothorax, and pneumomediastinum during laparoscopy.

OBJECTIVE: To determine independent predictors for the development of hypercarbia, subcutaneous emphysema, pneumothorax, and pneumomediastinum during laparoscopy. METHODS: We reviewed 968 laparoscopic cases between January 1, 1997, and December 31, 1998. Patients who had hypercarbia (end-tidal carbon dioxide of 50 mmHg or greater), pneumothorax/pneumomediastinum, and subcutaneous emphysema were compared with controls according to age, operative time, type of surgery, extraperitoneal or intraperitoneal approach, preexisting medical conditions, body mass index, sex, use of Hasson technique, and number of surgical ports. Maximum positive end-tidal CO(2) (PETCO(2)) was added as an independent variable for subcutaneous emphysema, pneumothorax, and pneumomediastinum. Data were analyzed using univariate analysis and then subjected to multivariate analysis using multiple logistic regression analysis. RESULTS: Incidence rates were 5.5% for hypercarbia, 2.3% for subcutaneous emphysema, and 1.9% for pneumothorax/ pneumomediastinum. Independent risk factors for development of hypercarbia were operative time greater than 200 minutes (odds ratio [OR] 2.02), patient age greater than 65 years (OR 2.19), and Nissen fundoplication surgery (OR 3.18). Predictors of the development of subcutaneous emphysema were PETCO(2) greater than 50 mmHg (OR 3.49), operative time greater than 200 minutes (OR 5.27), and the use of six or more surgical ports (OR 3.06). Variables that predicted the development of pneumothorax and/or pneumomediastinum were PETCO(2) greater than 50 mmHg (OR 4. 15) and operative time greater than 200 minutes (OR 20.49). CONCLUSION: Longer operative times, higher maximum measured end-tidal CO(2), greater number of surgical ports, older patient age, and Nissen fundoplication surgery predispose patients to hypercarbia-related complications during laparoscopy.

Adult↗

[Spontaneous cervical emphysema: a case report].

Spontaneous cervical subcutaneous emphysema, without any aetiology found in the clinical history, is far less common than subcutaneous cervical emphysema following trauma, surgery, or infectious cervical processes. In this recent case report, the authors describe a young woman who developed a cervical subcutaneous emphysema. No responsible factor had been found. Radiological investigations revealed a pneumomediastinum, which is an uncommon but a serious complication of cervical emphysema. The CT-scan highlighted a rupture of the crico-thyroid membrane, from which the air had followed the fascial planes up to the neck and the mediastinum. The authors describe the treatment and clinical course. They put forward an embryological hypothesis regarding the spontaneous crico-thyroid membrane rupture. A congenital fragility of this area could exist which could explain its breach. The pathogenesis and management of spontaneous cervical emphysema are discussed in the light of diverses articles about this subject. The radiological or surgical explorations which may be used in this aetiological diagnosis and treatment are given.

Adult↗

Subcutaneous emphysema from an axillary wound that resulted in pneumomediastinum and bilateral pneumothorax in a horse.

A 5-year-old Thoroughbred gelding was examined because of a small axillary wound sustained 5 days earlier and had resulted in extensive subcutaneous emphysema. Three days after admission, the horse's respiratory rate had increased to 72 breaths/min, and the horse appeared anxious and distressed. Thoracic radiography revealed pneumomediastinum and severe bilateral pneumothorax. Tube thoracostomy was performed on both hemithoraxes. The drains were connected to one-way suction valves and suction devices to decompress the thorax. A nasopharyngeal catheter was inserted, and oxygen insufflation was started. Cross ties were placed on the horse to limit movement, and the wound was packed. The horse improved within 30 minutes after initiating treatment. The horse was released 15 days after the development of pneumothorax, at which time the pneumothorax had resolved, the wound was no longer open, and the subcutaneous emphysema had greatly decreased. Although subcutaneous emphysema is usually regarded as a temporary cosmetic disfigurement, it can lead to serious complications such as pneumothorax. This case demonstrates that subcutaneous emphysema can lead to a life-threatening pneumothorax if the pressure is great enough to migrate through the mediastinum and into the pleural cavity. Horses with subcutaneous emphysema should be kept in confinement and monitored for the development of pneumothorax.

Animals↗

The trypsin-induced leucostasis which leads to emphysema in the hamster is not due to contaminating endotoxins.

Intravenous injection of trypsin in the rat induces early lung leucostasis and emphysema of delayed onset. This report confirms that this emphysema is not rat-specific and that the leucostasis is not related to the presence of contaminating endotoxin in the trypsin. In hamsters (n = 37), leucostasis did not occur when they were injected with heat-treated trypsin, but numerous granulocytes were sequestered in the vessels of hamsters receiving a fresh solution of trypsin. In these hamsters, the number of granulocytes harvested by lavage increased significantly (1.87 x 10(6) per ml, P < 0.001) compared with hamsters injected with either heat-denatured trypsin (0.89) or saline (0.86), or compared with controls (0.86). Emphysema was inconstantly observed in hamsters 6 or 12 weeks after injection with trypsin for 1 h. It was frequently (17/20) present and always (20/20) well developed (intercept + 180 per cent) in the 2-h perfused hamsters whose lungs were abnormally heterogeneous (index + 100 per cent) relative to the seven controls and to the nine saline-injected hamsters. The efficiency of trypsin in triggering emphysema (percentage of hamsters having abnormal values of intercept) was dependent on the time of perfusion. This form of experimental emphysema is thus considered to be due to an endotoxin-independent leucostasis.

Animals↗

Stereological methods: a new approach in the assessment of pulmonary emphysema.

In order to develop a reliable and sensitive method for studying the development and progression of pulmonary emphysema, we compared stereological indices with the usual index for grade of emphysema, i.e., the mean linear intercept (Lm), in elastase-induced emphysema in mice. The Lm and stereological indices, including volumes of total lung tissue (V(lt)), airspaces (V(air)), and surface area of alveolar walls (S(alv)), were determined in 5-microns, H&E-stained, paraffin-embedded lung sections from elastase- (n = 7) or saline-treated (n = 8) mice. The indices were measured by point counting, using Cavalieri's principle (V(lt)) and V(air)) or by counting intersections of alveolar walls with test lines of a known length (S(alv) and Lm). Elastase treatment resulted in a significant increase of Lm and of V(air), both indicating airspace enlargement, and in a significant decrease of V(lt) and S(alv), indicating destruction of alveolar walls. Between each of the stereological indices and the Lm, significant correlations were found when all lungs were included, but not when the emphysematous lungs were considered separately. We conclude that stereological methods can be powerful morphometric tools for studying pulmonary emphysema development and progression, since they give information not only about the grade of airspace enlargement but also about the grade of destruction of alveolar walls. Based on this unique property, stereological methods also allow a distinction between pulmonary emphysema and unrelated conditions with dilatation of airspaces only.

Animals↗

Emphysema: the challenge of the remodelled lung.

Emphysema is recognized as the component of chronic obstructive airways disease that is responsible for airways obstruction. Different patterns of emphysema are, however, recognized, suggesting possible different pathogenetic processes within the lung. This, coupled with the associated idea of susceptibility factors to the development of emphysema, has led to studies of genes that may be involved in the defence of the lung from proteolytic and oxidative damage. These studies have been driven by the goal of finding a treatment for emphysema, but appear to have lost sight of the fundamental remodelling of the lung that has occurred in patients with emphysema and the fact that it is not a single morphological entity.

Genetic Therapy↗