Abstract
1 Introduction
Emphysema is one of the most prevalent disabling diseases in industrial nations. Despite aggressive medical treatment and physical rehabilitation the progressive nature of the disease is poorly modified by the current medical treatment, the quality of life and prognosis are poor and the 3 year survival rate of patients with end-stage emphysema is only 50-60% [1]. Lung transplantation represents an effective therapeutic option but it is available only for a limited number of cases because many patients with emphysema present with advanced age and associated diseases. Surgical removal of bullae and lung volume reduction have been employed to improve symptoms and exercise tolerance in highly selected patients [2-5]. Although bullectomy and volume reduction are considered two different surgical procedures, both allow the removal of redundant space occupying destructive emphysematous lung, permit a better ventilation and perfusion, decrease dead space and residual volume (RV) and improve chest mechanics with repositioning of the diaphragm and thoracic wall. The understanding of bullous emphysema progressed markedly when a clear distinction was made based on the condition of the underlying parenchyma. De Vries and Wolf [6] proposed a practical classification of bullous emphysema based on the morphological aspect of underlying lung. It is well known that resection of large bullae associated with normal or almost normal lung parenchyma has an excellent outcome. On the other hand, patients with bullae and end-stage emphysema have poorer results in terms of morbidity, mortality and long-term functional results [7,8]. This particular subset of patients, on the basis of clinical symptoms, lung function tests, pathophysiologic derangement and chest wall mechanics is similar to patients with advanced non-bullous emphysema and they are possible candidates for lung volume reduction (LVR) surgery [8]. We compare and analyze retrospectively our experience in lung volume reduction surgery and bullectomy in patients with end-stage emphysema.
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2 Materials and methods
2.1 Group I
Over the last 5 years, we retrospectively analyzed the data of 20 male patients with a mean age of 62 years (ranging from 56 to 72 years) presenting with lung bullae as part of generalized severe emphysema (stage III of the De Vries and Wolf classification) [6], who underwent resection of bullous lesions at our Institution. All these patients were in stage III of the American Thoracic Society staging of chronic obstructive pulmonary disease (COPD) [9] (FEV1≪35% of predictive value). Chest computed tomography (CT) typically demonstrated bilateral multiple bullae, with a diameter usually less than 10 cm; there were no evident signs of compression of the surrounding lung tissue that was morphologically characterized by decreased density and loss of vascular structures (Fig. 1) . A ventilation/perfusion scan also documented multiple perfusion defects and retention of the inhaled radio-tracer. Patients who underwent resection of bullae associated with underlying morphologically normal or almost normal lung parenchyma, with evident signs of compression and vascular crowding, were not included in this study. All included patients were in stage III or IV of the Modified Medical Research Council dyspnea index [10] presenting with disabling dyspnea and severely impaired quality of life. Despite maximal medical therapy 14 of them were on continuous oxygen support (2-5 l/min) and 15 were requiring steroids. Pre-operative evaluation also included spirometry, whole-body plethysmography, blood gas analysis, diffusion capacity test with carbon monoxide, accurate cardiac status assessment and six minute walking test (6MWT). Table 1 shows the pre-operative lung function data.
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2.2 Group II
During the same period of time, 18 patients (16 male and two female) with a mean age of 59 years (range 48-71 years) with end-stage heterogeneous non-bullous emphysema (Fig. 2) were selected and operated on for unilateral lung volume reduction surgery following standard inclusion criteria [11]. General exclusion criteria were age more than 80 years, resting PaCO2 greater than 55 mmHg, pulmonary artery systolic pressure greater than 50 mmHg evaluated by echocardiogram or right cardiac catheterization, unstable coronary artery disease, significant obesity (≫1.25 ideal body weight) or cachexia, tobacco use within 3 months before evaluation, ventilatory dependency and clinical or radiological evidence of chronic bronchitis, bronchiectasis and significant bronchospasm.
All had severely impaired quality of life despite maximal medical treatment. Oxygen support (2-5 l/min) was needed in 15 patients and 16 were taking a regular dose of prednisone (mean daily dose of 10 mg). Pre-operative evaluation was similar to that accomplished for bullous patients. Pre-operative lung function data are reported in Table 1. Patients with evidence of homogeneous emphysema were not included in this study. Heterogeneity was evaluated by CT scan of the chest (decreased density, loss of vascular structures) and by lung ventilation/perfusion study. Upper lobe predominance heterogeneity was found in 15 patients, and upper lobe plus apical segment of the lower lobe heterogeneity was found in the remaining.
2.3 Pulmonary rehabilitation
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Pulmonary rehabilitation was not routinely performed pre-operatively because many patients lived far away from our hospital and cannot receive an adequate rehabilitation program with their local medical centres. All patients of both groups began rehabilitation immediately before and after operation. Our rehabilitative program included education in breathing techniques, anxiety control, muscle exercises, cycling and walking.
2.4 Surgical technique
Electrocardiographic monitoring, and radial arterial and central venous cannulation were routine in all cases. An epidural catheter was placed to provide adequate post-operative analgesia and also for intra-operative anaesthetic management, in order to reduce inhalational anaesthetic and systemic narcotic drugs. Selective airway intubation with a left sided double lumen tube was used and a stand-by for high frequency jet ventilation was made in case of necessity. Pulse oxymetry and capnography were monitored during the operation. All operations were unilateral in both groups and performed thoracoscopically. Three to four intercostal ports have been used to accomplish operations. After complete lung mobilization, lung reduction was performed on the target areas, as determined pre-operatively on the basis of CT and isotope imaging, reducing the overall volume of the lung by 20-30%. Bullectomy and lung reduction were performed using 45 mm endoscopic staplers. Large bullae still hyperinflated were opened for deflation to gain more space and better visualization of the pleural cavity. During the operation, all efforts were applied to prevent or minimize air leakage. Bovine pericardium, pleural tent or surgical glues were used singularly or in combination, to reduce the pleural space and to reinforce the mechanical sutures. In some cases lower pulmonary ligament was transected to allow a better lung re-expansion. Two chest tubes were left in place and connected to a water seal chamber under mild suction.
2.5 Statistical analysis
Baseline pre-operative data and functional results are expressed as the mean±standard deviation.
The paired Student’s t-test was used for analyzing the relationship between pre-operative and post-operative data, with P≪0.05 considered statistically significant. Differences between two groups were compared with ANOVA (one way analysis of variance) and P≪0.05 was considered significant.
3 Results
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No intra-operative complications developed in either group. The mean operative time for the unilateral procedures was similar in both groups (107±25 min in Group I and 100±22 min in Group II, P≫0.05). We had to convert thoracoscopy to thoracotomy in one patient during lung volume reduction because of complete obliteration of the pleural space. This patient had a significant air leak after operation and developed empyema, re-intubation and mechanical ventilation for respiratory insufficiency and sepsis that caused his demise after 25 days after the operation. Our policy was to achieve immediate post-operative extubation, however all but one in the first group and all but two in the second group were extubated in the operating room. The remaining two were extubated after 24 and 36 h, respectively. No patient required re-intubation and none died in the bullous group. One patient developed contralateral pneumothorax that required an emergency chest tube drainage. Post-operative complications, reported in Table 2 , were similar in both groups. Air leak was the most frequent problem. Prolonged air leak (≫7 days) developed in 46% (7/15) of the bullous group and in 44% (8/18) of the non-bullous emphysema group, however the difference was not statistically significant (P≫0.05). The mean chest tube drainage time was 8.2 days (range 5-19 days) for Group I and 8.5 days (range 5-20 days) for the LVR group (P≫0.05). The median length of post-operative hospital stay for Group I was 18 days ranging from 10 to 28 days, similar for that observed in Group II, 17 days ranging from 11 to 29 days (P≫0.05). Both groups were homogeneous for demographic characteristics, pre-operative lung function data and degree of respiratory derangement. Post-operative lung function data recorded after 6 and 12 months were available for 19 patients in Group I (one patient died in the post-operative period) and 17 patients in Group II (one patient died of a stroke 10 months after the operation). The mean FEV1 had risen significantly in both groups (P≪0.05). Similar improvements were noted in FVC, while the FEV1/FVC ratio was slightly modified. Total lung capacity (TLC) and RV (Pleth) were reduced in both groups, whereas RV evaluated by helium dilution techniques did not change significantly. Limited improvement in the diffusion capacity of carbon monoxide (DLCO) was also observed. The mean air oxygen tension did not change after the operation; slight reduction of the PaCO2 level was observed. The mean six minutes walking distance increased markedly in both groups (Tables 3 and 4) . No statistically significant differences of respiratory functional results, recorded after 6 and 12 months after the operation, were observed between the two groups (Table 5) .
4 Discussion
End-stage emphysema is a disabling disease associated with significant morbidity, mortality and poor quality of life. Medical treatment has limited efficacy since it can not address the anatomical abnormalities that cause the physio-pathological changes seen in emphysema. Emphysema is essentially due to destruction of elastic tissue. The loss of elastic recoil results in expiratory airflow obstruction, and premature closure of peripheral airways due to less airway radial distending forces. Air-trapping and progressive hyperinflation have a significant effect on ventilation and functional respiratory muscle strength. Airflow limitation may be improved by the surgical resection of poorly functioning lung parenchyma, such as is done with bullectomy or lung volume reduction. Disabling breathlessness is the most common indication for surgery. Bullectomy is a well established procedure that in selected patients may significantly improve symptoms, exercise tolerance, and respiratory reserve and eventually treat complications [12,13]. In patients with end-stage emphysema, bullae can be part of a generalized disease (stage III of the De Vries and Wolf classification) and it is well accepted that this presentation of emphysema should be kept separated from bullae associated with normal or almost normal underlying parenchyma (stage I-II of the De Vries and Wolf classification). Some reports have claimed that bullectomy in patients with severe underlying generalized emphysema is not worthwhile and it is associated with a higher incidence of morbidity and mortality [7,8] and long-term follow-up has revealed more rapid deterioration than in patients with localized disease [3]. This functional decline seems to be similar to that recorded after LVR. We believe that the positive effects of bullectomy in patients with end-stage emphysema are mainly due to the reduction of lung volumes and restoration of diaphragmatic and chest wall mechanics rather than lung re-expansion and recruitment of better functional lung tissue. Usually, improvement of FEV1 and DLCO is generally modest; RV and TLC generally decrease. These observations are similar to those seen after lung volume reduction in non-bullous emphysema, and we confirm the theory of Snider [14] that bullectomy in patients with severe emphysema is “a special case of lung volume reduction”.
Bullectomy and lung volume reduction both allow the removal of redundant space occupying poorly functional lung tissue, and improvements seen after surgery can be essentially explained with the reduction of RV and thoracic hyperinflation [15], re-expansion of adjacent better functioning lung tissue, an increase of respiratory muscle strength [16], chest wall mechanics [17] and intra-thoracic haemodynamics [18,19]. Bullae in this subset of patients can be interpreted as a sign of heterogeneous emphysema that is associated with the most favourable clinical outcome after LVR. Volume reduction and bullectomy both yield reduction of RV which was plethysmographically determined. In contrast, RV estimated by helium dilution does not change significantly. In other words both procedures allow space occupying air-trapping lung to be resected. The reduction of RV positively influences the TLC and the forced residual capacity (FRC). Improvement in muscle strength has been clearly demonstrated after bullectomy and pneumoplasty [16-20]. This effect is due to the restoration of the diaphragmatic curvature, and chest wall morphology. The re-expansion of adjacent compressed lung results in recruitment of the underlying airway, vessels and alveoli. This seems demonstrated by the increase of FEV1 and FVC; the FEV1/FVC ratio is only slightly modified. Improvement in dynamic expiratory flow rates can also be explained with the increase of elastic recoil pressure well demonstrated after LVR [21] and bullectomy [22,23].
In conclusion, our experience and many reports in the literature support the hypothesis that the physio-pathological basis of improvement after lung volume reduction and resection of bullae in patients with end-stage emphysema seem to be the same, although the exact mechanisms remain incompletely understood. The effects of surgery on gas exchange and on intra-thoracic hemodynamics have to be studied in more detail as well as the long-term modifications.
References
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