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Overview of the pathology of emphysema in humans.

In summary, emphysema in smokers should not be considered a single entity with predictable clinical and functional abnormalities. Decreases in flow are the ultimate abnormalities seen in COPD with emphysema; however, the pathophysiology of the flow alterations are vastly different in CLE and PLE. Based on the present understanding of emphysema, it could be predicted that the short-term results of pneumonectomy might produce some improvement in flows in CLE but not in PLE. Any improvement, however, may be short-lived, because the new mechanical conditions resulting from the removal of emphysematous lung would destroy the remaining lung at an accelerated rate, thus returning to the prior emphysematous state.

Bronchi↗

The surgical treatment of emphysema. The Brompton approach.

The vast majority of patients suffering with emphysema cannot be helped by surgery. A fortunate minority, consisting of specific subsets of patients, can benefit, but to do so the surgeon must have a flexible approach and select the optimal procedure for each patient. There is no one operation that is ideal in all circumstances. A major exploratory thoracotomy remains the approach of choice in specific situations (1) when dealing with the rare patient who has a congenital air cyst in the context of otherwise normal lungs. Local excision usually is possible but lobectomy may be necessary; (2) when dealing with an infected bulla in which the situation can only be ascertained at operation, where adhesions may cause difficulty and drainage may prove inappropriate, and lung resection is necessitated; and (3) when operating for a pneumothorax in which the situation can only be assessed at operation, and control of air leak is mandatory by ligation, bullectomy, or intracavitary drainage. The future role of video-assisted operations in this context must await the longer follow-up of larger series. In the elective management of patients with emphysema, those with a dominant bulla we continue to treat by intracavitary drainage. The Brompton technique offers a simple, safe, and effective therapeutic option in carefully selected patients. We believe the advantages to be threefold. Firstly, the use of CT scanning, important in patient selection, allows one to plan the incision so that a minithoracotomy can be performed, reducing the morbidity and mortality formerly associated with thoracotomy in patients with poor respiratory reserve. Secondly, the approach obviates the need to resect adjacent lung tissue, which in a generalized and progressive disease may be physiologically of disproportionate importance. Finally, pleurodesis allows any future recurrent bullae to be intubated and drained percutaneously under local anesthetic with minimal risk of pneumothorax. In those patients who have generalized emphysema without significant bullae, the role of volume-reduction surgery is being investigated. We await longer-term follow-up but fear that with wider application this major operation will accumulate significant mortality. Transplantation remains an option that must be limited to the youngest patients and those who are close to the terminal phase of their illness.

Drainage↗

[Effect of theophylline on disturbances of ventilation and of gas exchange during exercise in patients with pulmonary emphysema].

Factors limiting exercise were studied in 23 patients with pulmonary emphysema, and the effects of theophylline on exercise tolerance and on hypercapnic ventilatory response were studied in 16 patients with pulmonary emphysema. Exercise in these patients was limited by inability to increase tidal volume and by disturbances of gas exchange, as indicated by low PaO2, high AaDO2, and high PaCO2 during exercise, and by low diffusing capacity. Theophylline increased tidal volume during exercise, but it did not improve oxygenation during exercise. Theophylline improved exercise tolerance and hypercapnic ventilatory response. The percent increases in VEmax and in VO2max after theophylline administration correlated significantly with the percent increase in the ratio of mouth occlusion pressure to PACO2 during rebreathing. These results indicate that exercise tolerance in patients with pulmonary emphysema can be improved by theophylline, probably because of an increase in ventilatory drive.

Aged↗

The pathogenesis of emphysema: the elastase:antielastase hypothesis 30 years later.

Thirty years ago the concept of the elastase:antielastase hypothesis was introduced. Neutrophil elastase:A1PI balance was found to be critical, predisposing patients deficient in A1PI to panacinar emphysema; however, the causative elastases in common cigarette-induced pulmonary emphysema are unclear. Several members of the serine, cysteine, and metalloproteinase families have been identified in inflammatory and resident lung cells. We propose to use gene-targeted mice, deficient in individual elastases to determine the relative contribution of candidate elastases to cigarette-smoking-related emphysema. This does not guarantee that humans will respond to cigarette smoke with the same array of elastases as mice. However, these studies may guide labor intensive therapeutic trials with specific proteinase inhibitors and ultimately lead to rational therapy.

Animals↗

Nontraumatic subcutaneous emphysema in association with rectal carcinoma.

Nontraumatic subcutaneous emphysema is a rare complication of colorectal cancer. To the authors' knowledge, only eight cases have been reported to date. The initiating event was free colonic perforation in seven of the patients and contained colosubcutaneous fistula in the eighth. In nontraumatic subcutaneous emphysema typical fecal flora is cultured, whereas in nontraumatic gas gangrene, a different clinical entity that has a fulminant course, the bacteria are generally clostridial. The authors report a case of nontraumatic subcutaneous emphysema associated with rectal carcinoma and describe the associated computed tomography findings.

Adenocarcinoma↗

[Pulmonary emphysema: surgical indications].

Surgery for pulmonary emphysema, with the exception of lung transplantation, is limited at present to resection of the emphysematous areas. The resection of a unique bulla within an otherwise healthy parenchyma can be indicated in case of complications but rarely in asymptomatic patients. When the bullae are large (i.e. volume greater than one-third of the hemithorax) in a patient suffering from diffuse emphysema, bullectomy is the ideal indication. Mortality varies from 0 to 10%, essentially due to infection or acute respiratory failure. In most patients, the subjective improvement in terms of dyspnea and the objective improvement as measured by spirometry remains significative up to 5 years after surgery. Inversely, surgical resection is classically considered to be contraindicated in patients with small poorly-limited bullae. Recent data would however question this idea since subjective and objective improvement after reduction of the lung volume is still present 1 year after surgery in most patients, even those with severe obstruction. The mechanism is probably related to increased elastic recoil. Even if only temporary improvement can be achieved for a few years, the persisting course of emphysema would suggest that volume reduction should always be entertained as an alternative before lung transplantation.

Humans↗

Subcutaneous emphysema.

A medical emergency, the detection of subcutaneous emphysema requires thorough evaluation to exclude the multitude of disease processes that may demonstrate this clinical finding. Gas gangrene must be considered in the differential diagnosis of all forms of subcutaneous emphysema and infections with some species, such as C. novyi, may not produce gas at all. Isolation of C. septicum from the blood is almost always associated with colon cancer or hematologic malignancies. Nonclostridial gas gangrene in diabetic patients is indistinguishable clinically from clostridial gas gangrene. A unique and true dermatologic emergency is the detection of nontraumatic subcutaneous emphysema of the thigh with or without associated erythema, tenderness, or bullous lesions. This finding is associated with perforated viscus in a retroperitoneal location. Infections with gas-producing organisms continue to be a source of significant morbidity in modern times.

Animals↗

Neutrophil recruitment into the lungs is associated with increased lung elastase burden, decreased lung elastin, and emphysema in alpha 1 proteinase inhibitor-deficient mice.

The possibility that polymorphonuclear leukocytes (PMN) recruited into the lung have the capability to damage alveolar septa was investigated in several strains of mice with different serum alpha 1 proteinase inhibitor levels and PMN lysosomal functions. After an intratracheal instillation of FMLP (200 micrograms), all strains of mice showed a similar PMN influx in alveolar spaces with an increase (approximately 4- to 5-fold) in bronchoalveolar lavage total cell count, which peaked at 24 to 48 hours. At this time, differential cell count in all strains revealed an approximately 40-fold increase in neutrophils. In C57BL/6J and pallid mice but not in NMRI mice, PMN influx was followed by a decrease in lung elastin content (-17% and -37%, respectively) and by the development of significant emphysema (mean linear intercept, +28% and +56%, respectively). The onset of the pulmonary lesion was preceded by a marked increase of neutrophil elastase burden in alveolar interstitium. Compared with NMRI mice, C57BL/6J and pallid mice have lower serum elastase inhibitory capacity levels. The degree of lung destruction was inversely correlated with elastase inhibitory capacity levels. Lung elastin degradation and emphysema may be induced by eliciting PMN into the lungs only in animals with a deficient anti-elastase screen. Compared with C57BL/6J mice, pallid mice showed a significantly greater lung elastin loss and a higher degree of emphysema after FMLP treatment. These differences may be accounted for by the higher baseline levels of interstitial elastase burden. It may be assumed that an enzymatically active elastase was already working on the lung interstitium before FMLP instillation in pallid mice.

Animals↗

A scanning electron microscopic investigation of genetic emphysema in tight-skin, pallid, and beige mice, three different C57 BL/6J mutants.

Three mutants of the C57 BL/6J strain, i.e., the tight-skin (Tsk), pallid (pa), and beige (bg) mice have been reported to develop spontaneous emphysema. However, the pathogenic mechanisms of this lesion may be different in the three mutants. Differences and similarities of these models were investigated by means of scanning electron microscopy. A light microscopic investigation provided the background for the SEM study. C57 BL/6J (control), pa, Tsk, and bg mice were killed when they were 1, 12, and 24 months old. At light microscopic investigation the lungs of the controls appeared normal at all ages. Those of the pa mice had normal appearance at 1 month, showed a few areas of air space enlargement with destruction of alveolar septa at 12 months, and had a generalized enlargement of the air spaces associated with distortion of alveolar septa at 24 months. The Tsk mice had a generalized panlobular emphysema at all ages. The lungs of the bg mice showed at all ages a generalized enlargement of the air spaces not accompanied by changes of the alveolar septa. At scanning electron microscopy the lung parenchyma of control mice was essentially normal at all ages. Both alveolar ducts and alveoli increased in size (the latter also in depth) with age. The number of interalveolar pores (Np) increased by 54% between 1 and 12 months of age and by 49% between 12 and 24 months. The parenchyma of pa mice did not differ significantly from that of the controls at 1 month. At 12 months the alveoli appeared to be larger. At 24 months in some fields alveolar ducts were enlarged, the alveoli were also enlarged and very shallow. Np was not different from controls at 1 month but greater at 12 (+ 49%) and 24 (+ 26%) months. The parenchyma of Tsk mice of all ages appeared distorted with enlargement of alveolar ducts and sacs and with alveoli with a large number of pores. These changes increased with age. Np was larger than the controls at all ages (+ 59% at 1 month, + 119% at 12 months, and + 80% at 24 months). The parenchyma of the bg mice of all ages appeared disorganized with large alveoli of different shapes. There was a deterioration with age. No difference in Np was seen at any age between bg and control mice. Parenchymal changes characterized by distortion and enlargement of alveolar ducts and sacs were observed, even if with different onset and extent, in all mutants. However, an increase in Np, which is considered to represent the early development of emphysema, was found only in Tsk and pa mice. In Tsk mice, high Np values were observed at all ages, whereas in pa mice Np was increased only late in life when the pulmonary lesion develops. These differences indicate different pathogenetic mechanisms for these three mutants.

Aging↗

The effect of activated alveolar macrophages on experimental lung emphysema development. III. Morphological analysis of the lung tissue and alveolar macrophages in situ.

Morphological (in light and transmission electron microscope) as well as morphometrical analysis of the lungs was performed on experimental, papain-induced lung emphysema. Development of emphysematous changes was studied seven days after a single intratracheal instillation of papain solution. The effect of alveolar macrophages (AM) activation by BCG-vaccine on changes in pulmonary tissue was analyzed. In the rats given BCG the number of AM increased and demonstrated enhanced activity. Increase in reticulin fibre density in places of AM cumulation, particularly in BCG+papain-treated rats was observed. The lungs of animals treated with BCG+papain showed enhancing of emphysema comparing with the papain-treated rats. Development of emphysematous changes, especially in BCG+papain-treated rats coexisted with cumulation of activated alveolar macrophages and collagen fibres as well as type II alveolar epithelial cells proliferation. Our data support the inflammatory-repair hypothesis of emphysema pathogenesis and indicate that AM regulate collagen production in the lung. Type II alveolar epithelial cells seem be important in lung injury and repair.

Animals↗

[Long-term follow-up and autopsy of a Japanese patient who had emphysema associated with alpha 1-antitrypsin deficiency].

A 49-year-old woman was found to have emphysema associated with alpha 1-antitrypsin deficiency in February 1975. She was followed until her death in October, 1994. The Pi phenotype was M null and the genotype was M malton. She had been on home oxygen therapy since 1987. An autopsy revealed the typical bullous lungs with panacinar emphysema. We know of no previous case in Japan of emphysema associated with alpha 1-antitrypsin deficiency.

Aged↗

Thoracoscopic surgery for lung cancer complicated by emphysema in elderly patients. Report of three cases.

We have experienced three elderly cases who underwent thoracoscopic surgery for lung cancer complicated by emphysema. Cases 1, 2 and 3, respectively aged 76, 78 and 80 years, had required the oxygen therapy preoperatively. Allowing for poor pulmonary reserve, a thoracoscopic partial pulmonary resection for lung cancer combined with Nd-YAG laser pneumoplasty for emphysema was designed. The respective values of forced expiratory volume in one second (FEV 1.0) for cases 1 and 2 increased from 470 and 820 to 860 and 1620 ml. Reductions in residual volumes (RV) for cases 1, 2 and 3 were from 2770, 4940 and 5230 to 2370, 4500 and 3250 ml. The degrees of respiratory failure in the Hugh-Jones classification for cases 1, 2 and 3 were up-graded from V, IV and IV, respectively, to III, II and II, postoperatively. In conclusion, our thoracoscopic treatment, designed for elderly patients with poor pulmonary reserve, allows improvement of emphysema as well as resection of lung cancer.

Aged↗

[A case of premature emphysema with hereditary alpha-1-antiproteinase deficiency].

A case of alpha-I-antiproteinase (AIPI) hereditary deficiency (serum concentration 34 mg%, determined by NOR-Partigen Assay F-my Behringer) in 41 years old patient with premature emphysema, confirmed by phenotyping (isoelectrofocusing in polyacrylamide gel) phenotype PiZ is presented. Lung function tests showed considerable decrease (FEV1 = 1,2 l., i.e. 34% pred., FEF50% = 0.55 l., i.e. 12% pred., diffusing capacity DLCO = 12.8 ml/min/mmHg, i.e. 43% pred.). Computed tomography revealed huge emphysematous bullae mainly in supradiaphragmatic parts of the lungs. The authors discuss the difficulties in diagnosing homozygotes with A1P1 deficiency. They suggest screening of severe hereditary deficiency in persons with emphysema in age interval 30-55 years. The presented case of premature emphysema and AIPI deficiency (confirmed by phenotyping variant Z) is the first in the polish literature.

Adult↗

[Morphogenesis of emphysema in occupational lung diseases (clinico-anatomical comparisons)].

The distinction of pneumoconiosis and occupational (dust) bronchites in the clinic of occupational lung pathology required morphological justification of such divisions. Examinations of 37 fatal cases with dust pathology of the lungs showed that in two thirds of the cases predominantly obstructive bronchitis forms of emphysema and compensatory perinodular forms of emphysema in silicosis could be diagnosed morphologically. A less marked diffuse character of emphysema in focal forms of pneumoconiosis is conducive to the inclusion of compensatory mechanisms preventing the development of pneumonial and cardial insufficiency.

Bronchi↗

Volume reduction surgery in the native lung after single lung transplantation for emphysema.

The natural history of emphysema suggests that progression of disease in the native lung may contribute to late deterioration in respiratory function after single lung transplantation. In this report, we describe our experience with unilateral volume reduction surgery in three single lung transplant recipients with emphysema. Each patient had had a late decline in lung function with a recurrence of symptoms. Chest radiographs demonstrated hyperinflation of the native lungs with encroachment on the grafts. Serial pulmonary function testing documented progressive reduction in expiratory flows with increases in residual volumes. Exercise testing confirmed severe intolerance to maximal exercise. Unilateral volume reduction surgery was undertaken at 36, 39, and 55 months after transplantation without incident. Radiographs obtained after the procedures demonstrated restoration of normal diaphragmatic contour, decreased aeration of the native lungs, and improved inflation of the allografts. Exercise testing at 3 months documented a mean improvement in maximal oxygen consumption of 35%. Expiratory flows improved by a mean of 60%. Quantitative ventilation and perfusion scans, however, were essentially unchanged. This experience suggests that unilateral volume reduction surgery may be considered as an alternative strategy in single lung transplant recipients with emphysema who exhibit clinically significant functional deterioration. Differentiation of the adverse effects of hyperinflation of the native lung from other potential causes of late deterioration might not be necessary but may be predictive of the degree of functional improvement after volume reduction. The relief of thoracic overdistention seems to play a primary role in the improvement pulmonary function.

Aged↗

[Surgical treatment of advanced lung emphysema. Does it really improve treatment results?].

Lung emphysema may be one of the components of chronic obstructive pulmonary disease (COPD). Nearly 60% of patients with advanced chronic respiratory insufficiency with FEV1 < 30% expected, aged > 65 years die within the first 2 years of the disease. The treatment of COPD includes oxygen therapy, lung transplantation and/or lung volume reduction (LVR). The study presents qualification criteria for LVR in reference to oxygen therapy and lung transplantation. Crucial diagnostic features include: CT of the chest with densitometric analysis and lung perfusion scans. Patients with severe but limited dyspnea, disseminated emphysema lesions with fairly untouched areas of normal lung tissue, FEV1% < 30-35%, DLCO < 25% expected, PaCO2 < or = 50 mmHg and PaO2 < or = 50-55 mmHg, appear to be the best candidates for LVR. The results of the study indicate, that in Poland, patients with advanced emphysema, who are treated with oxygen therapy or soon will be qualified this therapy or await lung transplantation might be candidates for LVR. The early results of lung volume reduction are promising and include: decrease in total lung capacity, residual volume and breathing frequency. LVR has been in use for about 3 years and majority of authors still do not possess clinical observations long enough to obtain statistically significant comparison with other methods of treatment. Limited morbidity and low perioperative mortality enable application of LVR even in patients with severe respiratory insufficiency and/or requiring constant oxygen therapy. In conclusion considering all positive aspects of LVR it is necessary to emphasise that for overall assessment of this method a broader clinical material is required including data on duration of clinical improvement.

Aged↗

[Nontraumatic subcutaneous emphysema. Diagnostic and therapeutic problems].

Nontraumatic subcutaneous emphysema is less frequent than traumatic. Its occurrence, unless synchronous with the treatment of spontaneous pneumothorax, usually is the consequence of exacerbation of COPD or of the obstruction of major bronchi. However, in routine clinical practice, the occurrence of subcutaneous emphysema without evident underlying disease, in combination with normal chest x-ray, still is a diagnostic and therapeutic problem. In this study typical mechanisms of this phenomenon are presented; air-trapping at the level of the main bronchus caused by endobronchial tumour growth, progressive destruction of alveoles by diffuse lung disease irrespective of its nature, and mechanism of its occurrence during dealing with the urgent clinical problem in the intensive care unit. This study does not deal with subcutaneous emphysema during the attack of severe asthma assuming it as well known situation that usually does not cause a major therapeutic problem. The sequence of necessary diagnostic and therapeutic steps is discussed taking account of possible pitfalls that usually exist in all of three described pathophysiological situations.

Humans↗

Tumor necrosis factor-alpha induces emphysema-like pulmonary tissue rebuilding. Changes in type II alveolar epithelial cells.

The effect of repeated doses of TNF-alpha on the histological picture of the pulmonary tissue was analyzed in the present study. Special attention was paid to the lung rebuilding processes. TNF-alpha was applied intraperitoneally for two weeks in a dose of 10 micrograms/0.5 ml PBS/24h. Morphological analysis of the pulmonary tissue was performed after 1 and 28 days following the last TNF-alpha dose. The study revealed focal pulmonary tissue rebuilding with emphysema-like changes twenty eight days following termination of TNF-alpha administration. The rebuilding processes included interalveolar septal atrophy, collagen accumulation and damage-repair changes in type II alveolar epithelial cells. It has been demonstrated that apart from the protease-antiprotease hypothesis of the lung emphysema, the inflammatory-repair hypothesis should be considered. Both hypotheses are complementary to each other and interpret the emphysema-like changes as complications of various pathological conditions of the pulmonary tissue.

Animals↗