Physiopathology of pulmonary emphysema. Analysis of structural changes in the pulmonary architecture and therapeutic implications

In the pulmonary emphysema a serious respiratory inadequacy can result from the impossibility of the thoracic cage and of the diaphragm to expand beyond a maximum limit, before that a significnat part of pulmonary parenchyma has been destroyed by the pathogenic process. The resection of part of the lung, selectively in the areas where the emphysematous injuries are more pronounced, brings again the ventilation of the residual pulmonary parenchyma toward more physiological expansion values of the thoracic cage and diaphragm, thus decreasing the respiratory work, improving the ventilation mechanics and the bronchial obstruction. The time duration of the improvement achieved with the lung volume reduction is still to be demonstrated. A clinical and therapeutic analysis of this pathology is carried out.     

Diagnostic accuracy of technologies used in LBP assessment

Postoperative improvement of respiratory function has been reported with lung volume reduction surgery (LVRS) in patients with severe emphysema. Since smoking is an established risk factor for lung cancer, vascular diseases and emphysema, it is not infrequent to find these diseases associated in the same patient. Combined treatment of lung cancer and emphysema has already been reported. Surgical treatment of vascular diseases in emphysematous patients could also benefit from the application of LVRS techniques. We report resection of an aortic aneurysm combined with LVRS in a patient with concomitant thoracic aortic aneurysm and severe emphysema. Respiratory function improved in the postoperative period.     

Respiratory function and surgical reduction of lung volume

Emphysema is characterised by an enlargement of the terminal air spaces. Destructions of alveolar walls lead to a loss of the lung elastic recoil. The driving pressure for expiration is decreased and the outward forces acting on the bronchioles are lost, leading to bronchiolar collapse and airflow limitation. Hyperinflation of the lungs and overdistension of the chest wall cause the respiratory muscles to operate in unfavourable conditions. Patients with advanced emphysema have decreased quality of live: they are dyspneic at rest and are unable to perform exercise. Surgical excision of parts of diffusely emphysematous lungs (Lung Volume Reduction Surgery, LVRS) has been proposed since many years. Expansion of the remaining lung should increase lung elastic recoil and restore the outward forces on the bronchioles. It has been demonstrated that LVRS reduces dyspnea symptoms, improves exercise tolerance and enhances the quality of live. LVRS increases lung elastic recoil, airway conductance and maximal expiratory flow, reduces dynamic hyperinflation and improves the efficiency of the respiratory muscles. These improvements are maintained for at least 12 to 18 months. Preoperative evaluation, surgical-induced modifications of pulmonary functions and postoperative exercise training are exposed.     

Lung volume reduction surgery as an emergency and life-saving procedure

Lung volume reduction surgery (LVRS) is emerging as a promising and unique therapeutic option for rigorously selected patients with severe debilitating emphysema. A 51 yr old man with generalized emphysema developed bilateral pneumothoraces during his first holiday abroad. Due to respiratory insufficiency, intubation and mechanical ventilation were necessary. In total, six chest tubes were inserted but massive air leak persisted and his respiratory condition deteriorated due to bronchopneumonia and sepsis. The patient was transferred to Belgium. As a last resort, bilateral LVRS was performed through a median sternotomy. The most diseased areas of the upper lobes containing the air leak were resected bilaterally and a pleurectomy was associated. Three months after operation, there was a remarkable improvement in spirometric values with an increase in forced expiratory volume in one second of almost 100%. The results were sustained after a follow-up of 18 months. In this dramatic case, lung volume reduction surgery proved to be effective, and was even a life saving procedure.     

The use of health care services by people with diabetes in rural areas

Stapled lung volume reduction surgery (LVRS) has recently been described for treatment of emphysema. Many questions arise regarding physiologic mechanisms of response from surgical treatment of emphysema. The objective of this study was to develop an animal model for the study of lung volume reduction surgery in diffuse heterogeneous emphysema. We hypothesized that elastic recoil would increase, static respiratory system compliance would decrease, and expiratory flows would increase after lung volume reduction surgery in animals with emphysema. In the study, emphysema was induced in 31 New Zealand White rabbits (3-5 kg) with endotracheally aerosalized porcine elastase (10,000-12,000 U). Lateral thoracotomies were performed 4-6 weeks postinduction under general anesthesia and mechanical ventilatory support. Stapled volume reduction was performed on the right lower lobe using a standard multirow pediatric stapler (U.S. Surgical). Pulmonary function tests were performed at baseline (preinduction), before stapling LVRS (postemphysema induction), immediately post stapling LVRS, and 1 week poststapling. Static respiratory system compliance, flow, conductance and forced expiratory flows, and peak flows at 20 and 40 cm3 of exhaled volume were analyzed. Animals were sacrificed 1 week poststapling, and bilateral lungs were harvested for histopathology. Diffuse but heterogeneous pulmonary emphysema was seen in these animals treated with high-dose aerosolized elastase. Static compliance increased, while expiratory flows and conductance decreased after induction of emphysema. Immediately post stapled volume reduction therapy, animals had decreased static compliance. By 1 week following surgery, animals showed increased forced expiratory flows and decreased expiratory resistance, although compliance was similar to preoperative levels. In conclusion, we describe initial results in an animal model of obstructive emphysema suitable for the study of lung volume reduction surgery. Changes in pulmonary function indicate that unilateral lower lobe LVRS increases airway conductance in the rabbits. Findings from LVRS studies in animal models such as this may help explain clinical improvement following LVRS in humans.     

Surgical treatment of severe emphysema: lung transplantation or volume reduction?

In recent years, lung transplantation (LT) and volume reduction surgery (LVRS) have been proposed for selected patients with end-stage pulmonary emphysema. Retrospectively, we analyzed the perioperative time course of 30 patients with emphysema who underwent either LVRS (n = 17) or LT (n = 13). In the LVRS group, patients were significantly older, presented less severe functional disability and all but one could be extubated at the end of surgery. In contrast, patients undergoing LT required postoperative mechanical ventilation (19 +/- 11 hrs) and had a prolonged hospital stay (37 [25-60] days vs 19 [11-42] days in LVRS patients) due to reperfusion lung edema, infection, hemorrhage and acute rejection. Six months postoperatively, forced expiratory volume in 1 second was improved and was significantly larger after LT compared with LVRS (+200% vs +63%). Our preliminary results suggest that, although LT produces greater functional improvement, LVRS is associated with lower surgical risk and is an alternative therapy in selected patients with severe emphysema.     

The diaphragm in emphysema

Because of hyperinflation, the diaphragm of emphysematous patients operates at a disadvantageous position which affects its mechanical arrangement, modifies the configuration of its zone of apposition, increases its radius of curvature, and decreases its muscle fiber length below optimal configuration. The diaphragm in emphysema therefore displays a suboptimal configuration limiting its ability to function properly but shows no inherent structural insufficiency, unless its contractility is impaired by significant arterial blood gas anomalies or severe malnutrition. The demand imposed on the diaphragm in emphysema is increased by both hyperinflation and air-flow obstruction. With altered performance of the diaphragm and increased demand, force reserve is diminished and diaphragmatic fatigue may occur; this imbalance is targeted in some treatment modalities of emphysema such as pulmonary rehabilitation programs and lung volume reduction surgery.     

Two-year results after lung volume reduction surgery in alpha1-antitrypsin deficiency versus smoker's emphysema

Lung volume reduction surgery (LVRS) improves exercise capacity and relieves dyspnoea in patients with smoker's emphysema (SE). It is unclear, however, whether LVRS similarly improves lung function in alpha1-antitrypsin-deficiency emphysema (alpha1 E). To address this question, this study prospectively compared the intermediate-term functional outcome in 12 consecutive patients with advanced alpha1E and 18 patients with SE who underwent bilateral LVRS. Before surgery there were no statistically significant differences between the two groups in the six-minute walking distance, dyspnoea score, respiratory mechanics or lung function data, except for the forced expiratory volume in one second, which was lower in the deficient group (24 versus 31% of the predicted value; p<0.05). In both groups, bilateral LRVS produced significant improvements in dyspnoea, the six-minute walking distance, lung function and respiratory mechanics. In the alpha1E group, the functional data, with the exception of the six-minute walking distance, returned to baseline at 6-12 months postoperation and showed further deterioration at 24 months. The functional status of the SE group remained significantly improved over this period. In conclusion, the functional improvements resulting from bilateral lung volume reduction surgery are sustained for at least 2 yrs in most patients with smoker's emphysema, but this type of surgery offers only short-term benefits for most patients with alpha1E.     

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.     

Transient giant negative T wave in acute anterior myocardial infarction predicts R wave recovery and preservation of left ventricular function

Resection of large bullae to decompress adjacent lung tissue with the goal of improving pulmonary function has been an accepted surgical approach for many years. However, the indication for lung volume reduction is not bullous disease but diffuse emphysema and the surgical approach is based on an entirely different concept. The resection of the most affected parts of the emphysematous parenchyma aims at a reduction of the over expansion of the chest with the goal of improving respiratory mechanics. This concept was introduced by Brantigan in 1959, but has failed to gain widespread acceptance until recently. Based on the extensive experience in lung transplantation for patients with end stage emphysema J. D. Cooper reevaluated the idea successfully. He reported remarkable improvements in FEV1 and a reduction in hyperinflation after performing bilateral lung volume reduction through a median sternotomy. During the last 2 years we performed bilateral lung volume reduction in more than 30 patients with diffuse emphysema using video assisted thoracoscopy (VAT) and studied the results prospectively. In the first 20 patients preoperative mean forced expiratory volume in 1 second (FEV1) was 765 ml/sec and improved by a mean of 42% (0-100%) three months postoperatively. This gain in FEV1 was already observed at the end of hospitalisation approximately two weeks after surgery. The 12 minute walking distance improved over 40%. In our highly selected study population we had no perioperative mortality. Lung volume reduction is a palliative treatment of severe pulmonary emphysema. Currently no data is available on the duration of the improvement. In this selected group of patients dyspnea is reduced and pulmonary mechanics are improved, with a resulting increase in quality of life.     

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.     

Lung surface area in various morphologic forms of human emphysema

The relation between lung surface area and the extent and morphologic type of emphysema was examined at autopsy in 69 men. It was found to be conceptually preferable to express the area as internal surface area per unit lung volume (specific surface area) rather than to use the more conventional, inversely related, mean linear intercept for comparison with other morphometric data. In the whole group, fixed inflated lung volume generally increased with increasing per cent involvement of lung parenchyma by emphysema, and total internal surface area decreased, but those changes were not so regular as the decline in specific surface area with increasing per cent emphysema (r=-0.574). Lungs with no emphysema had a significantly higher specific surface area than did lungs with very little emphysema (1 to 9 per cent), suggesting noticeable effects on the physical properties of lung by minimal degrees of this disease at high levels of inflation. The way in which specific surface area decreased with increasing percentage of emphysema was not noticeably different among patients with centrilobular, panlobular, or mixed forms of emphysema, although lungs with only centrilobular emphysema were much more common and had a significantly lower mean percentage of emphysema than did those with only panlobular emphysema; the prevalence and mean percentage of emphysema of the mixed group were intermediate. These observations, coupled with the association of older mean age with increasing percentage of emphysema, were interpreted as support for the concept that many examples of panlobular emphysema are derived from confluence of extensive centrilobular emphysematous lesions.     

Usefulness of computed tomography and scintigraphy in diagnosis of emphysematous bullae in the lung

The x-ray examinations usually do not reveal morbid changes after lung expansion in the treatment of spontaneous pneumothorax. In our observation computed tomography (CT) and scintigraphy enable not only the exact determination of the extent of changes but also they disclose bullae invisible in conventional chest radiographs. 15 patients with cured spontaneous pneumothorax and 10 patients with radiographic evidence of a bulla or bullae were examined. CT scans showed bullae from 3 to 18 cm in diameter involving predominantly the upper lobes. 4 patients had additionally subpleural or intraparenchymal bullae of various degrees. In all patients with cured spontaneous pneumothorax, CT scans revealed intraparenchymal bullae, and in 6 cases bilateral intraparenchymal bullae were revealed. Only in sites of large bullae, no isotopic marker or its low elimination was shown in perfusion and inhalation scintigraphy. 10 patients with giant bullous emphysema were operated; in 6 patients enucleation of bullae, in 3 lobectomy and in one patient bullectomy were performed. CONCLUSION: CT is a method of choice in the diagnosis of lung emphysematous bullae and it enables the detection of the changes undetectable in chest radiographs. Perfusion and inhalation scintigraphy is helpful in the diagnosis of large emphysematous bullae and postoperative follow-up examination.     

Role of lung perfusion scintigraphy in relation to chest computed tomography and pulmonary function in the evaluation of candidates for lung volume reduction surgery

Lung perfusion scintigraphy is employed to evaluate patients with severe emphysema who are candidates for lung volume reduction surgery (LVRS). Our purpose was to investigate the role of scintigraphy in relation to chest computed tomography (CT) and lung function in this setting. Six observers blinded to clinical data retrospectively scored preoperative scintigrams of 70 patients undergoing bilateral video-assisted LVRS according to the distribution of lung perfusion as homogeneous, intermediately heterogeneous, or markedly heterogeneous. Heterogeneity of emphysema distribution was also assessed by chest CT. Dyspnea and pulmonary function were measured preoperatively and 3 mo postoperatively. In 42 patients with markedly heterogeneous, in 18 with intermediately heterogeneous, and in 10 with homogeneous perfusion, mean (+/- SE) FEV1 increased by 57 +/- 8% (p < 0.0001), 38 +/- 9% (p < 0.001), and 23 +/- 9% (p = NS) (p = NS for intergroup comparisons). In a multiple regression analysis, functional improvement after LVRS was more closely correlated with preoperative hyperinflation and the degree of emphysema heterogeneity estimated by chest CT than with the degree of perfusion heterogeneity assessed by scintigraphy. In 16 of 22 patients with homogeneous emphysema distribution in the chest CT scintigraphy revealed intermediately or markedly heterogeneous perfusion. We conclude that lung perfusion scintigraphy has a limited role in prediction of outcome, but it may help to identify target areas for resection in LVRS candidates with homogeneous CT morphology.     

The effect of maternal restraint on developmental toxicity of aluminum in mice

We have estimated lung volume, bronchial volume, vessel volume, alveolar surface area and capillary length in patients who died of lung failure due to emphysema and chronic obstructive pulmonary disease (COPD) and in patients with no clinical signs of respiratory disease. Unbiased morphometric methods were applied to the right lung. The patients with emphysema had equal lung volumes and bronchial and vessel volumes compared to the control group. The alveolar surface area and surface density were significantly decreased to about 67%, of control values. The capillary length and length density were significantly decreased to about 68% of control values. The proportional decreases in alveolar surface area and capillary length suggest that compensatory capillary proliferation has not occurred. These unbiased morphometric studies of emphysema have yielded results in end-stage emphysema that are comparable to those previously reported using biased methods. However, the unbiased methods may provide new insights when applied to earlier stages of the disease.     

Effect of global inspiratory muscle fatigue on ventilatory and respiratory muscle responses to CO2

We evaluated the effect of global inspiratory muscle fatigue on ventilation and respiratory muscle control during CO2 rebreathing in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. CO2 response curves were measured before and after fatigue. During CO2 rebreathing, global fatigue caused a decreased tidal volume (VT) and an increased breathing frequency but did not change minute ventilation, duty cycle, or mean inspiratory flow. Both esophageal and transdiaphragmatic pressure swings were significantly reduced after global fatigue, suggesting decreased contribution of both rib cage muscles and diaphragm to breathing. End-expiratory transpulmonary pressure for a given CO2 was lower after fatigue, indicating an additional decrease in end-expiratory lung volume due to expiratory muscle recruitment, which leads to a greater initial portion of inspiration being passive. This, combined with the reduction in VT, decreased the fraction of VT attributable to inspiratory muscle contribution; therefore the inspiratory muscle elastic work and power per breath were significantly reduced. We conclude that respiratory control mechanisms are plastic and that the respiratory centers alter their output in a manner appropriate to the contractile state of the respiratory muscles to conserve the ventilatory response to CO2.     

Lung volume and effectiveness of inspiratory muscles

We related inspiratory muscle activity to inspiratory pressure generation (Pmus) at different lung volumes in five seated normal subjects. Integrated electromyograms were recorded from diaphragmatic crura (Edi), parasternals (PS), and lateral external intercostals (EI). At 20% increments in the vital capacity (VC) subjects relaxed and then made graded and maximal inspiratory efforts against an occluded airway. At any given level of pressure generation, Edi, PS, and EI increased with increasing lung volume. The Pmus generated at total lung capacity as a fraction of that at a low lung volume (between residual volume and 40% VC) was 0.39 +/- 0.15 (SD) for the diaphragm, 0.20 +/- 0.06 for PS, and 0.22 +/- 0.04 for the lateral EI muscles. Our results indicate a lesser volume dependence of the Pmus-EMG relationship for the diaphragm than for PS and EI muscles. This difference in muscle effectiveness with lung volume may reflect differences in length-tension and/or geometric mechanical advantage between the rib cage muscles and the diaphragm.     

Human respiratory muscle actions and control during exercise

We measured pressures and power of diaphragm, rib cage, and abdominal muscles during quiet breathing (QB) and exercise at 0, 30, 50, and 70% maximum workload (Wmax) in five men. By three-dimensional tracking of 86 chest wall markers, we calculated the volumes of lung- and diaphragm-apposed rib cage compartments (Vrc,p and Vrc,a, respectively) and the abdomen (Vab). End-inspiratory lung volume increased with percentage of Wmax as a result of an increase in Vrc,p and Vrc,a. End-expiratory lung volume decreased as a result of a decrease in Vab. DeltaVrc,a/DeltaVab was constant and independent of Wmax. Thus we used DeltaVab/time as an index of diaphragm velocity of shortening. From QB to 70% Wmax, diaphragmatic pressure (Pdi) increased approximately 2-fold, diaphragm velocity of shortening 6.5-fold, and diaphragm workload 13-fold. Abdominal muscle pressure was approximately 0 during QB but was equal to and 180 degrees out of phase with rib cage muscle pressure at all percent Wmax. Rib cage muscle pressure and abdominal muscle pressure were greater than Pdi, but the ratios of these pressures were constant. There was a gradual inspiratory relaxation of abdominal muscles, causing abdominal pressure to fall, which minimized Pdi and decreased the expiratory action of the abdominal muscles on Vrc,a gradually, minimizing rib cage distortions. We conclude that from QB to 0% Wmax there is a switch in respiratory muscle control, with immediate recruitment of rib cage and abdominal muscles. Thereafter, a simple mechanism that increases drive equally to all three muscle groups, with drive to abdominal and rib cage muscles 180 degrees out of phase, allows the diaphragm to contract quasi-isotonically and act as a flow generator, while rib cage and abdominal muscles develop the pressures to displace the rib cage and abdomen, respectively. This acts to equalize the pressures acting on both rib cage compartments, minimizing rib cage distortion.     

MR analysis of lung volume and thoracic dimensions in patients with emphysema before and after lung volume reduction surgery

OBJECTIVE: This study was performed to assess the accuracy of determining lung volume in patients with emphysema using MR imaging and then to investigate changes in thoracic dimensions after lung volume reduction surgery. SUBJECTS AND METHODS: Fast gradient-echo breath-hold MR imaging through the entire thorax at full inspiration and expiration was performed in 21 patients with severe emphysema and was performed again in nine of the patients who underwent surgery. Lung volumes were determined using a semiautomated computerized method of delineating the lungs and summing cross-sectional areas. These summed areas were compared with volumes measured on plethysmography and CT. Postoperative changes in thoracic structure were determined by measuring anteroposterior and transverse lung dimensions and lung height before and after surgery. RESULTS: The correlation coefficients and SEM for determining inspiratory lung volume were MR imaging versus plethysmography, r = .77, SEM = -12% (volume measured as less on MR imaging); CT versus plethysmography, r = .86, SEM = -13% (volume measured as less on CT); and MR imaging versus CT, r = .87, SEM = 4% (volume measured as greater on MR imaging). The correlation coefficients and SEM for determining expiratory volume on MR imaging versus plethysmography were r = .77, SEM = 6% (volume measured as greater on MR imaging). After surgery, decreases were found in all thoracic dimensions, and such decreases were greatest at expiration. CONCLUSION: MR measurements of lung volume are comparable with those of CT and differ from those of plethysmography. Changes in thoracic dimensions after lung volume reduction surgery are consistent with improved respiratory mechanics.     

Function of the diaphragm during exercise]

We evaluated the effect of global inspiratory muscle fatigue (GF) on respiratory muscle control during exercise at 30%, 60%, and 90% of maximal power output in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. Respiratory pressures, breathing pattern, and perceived breathlessness were measured. Induction of GF had no effect on the ventilatory parameters during mild and moderate exercise. It altered, however, ventilatory response to heavy exercise by increasing breathing frequency and minute ventilation, with minor changes in tidal volume. This was accompanied by an increase in perceived breathlessness. GF significantly increased both the tonic and phasic activities of abdominal muscles that allowed 1) the diaphragm to maintain its function while developing less pressure, 2) the same tidal volume with lesser shortening of the rib cage inspiratory muscles, and 3) relaxation of the abdominal muscles to contribute to lung inflation. The increased work performed by the abdominal muscles may, however, lead to a reduction in their strength. GF may impair exercise performance in some healthy subjects that is probably not related to excessive breathlessness or other ventilatory factors. The respiratory system is remarkably adaptable in maintaining ventilation during exercise even with impaired inspiratory muscle contractility.