is unclear. Clinical trials will answer important issues such as duration, selection criteria, precise outcomes and best technique.

Several clinical trials have recently been published. In two of them, patients participated in a program of rehabilitation prior to being randomized to receive surgery or continued medical treatment [13,14]. In a third, patients received either rehabilitation or surgery [15]. In these three trials, only surgical treatment significantly improved the FEVj. Improved exercise capacity occurred after rehabilitation, with further improvements after LVR. Pompeo et al. noted a reduction in dyspnoea following surgery [15] and Geddes et al. (Fig. 14.1) reported improvements in a generic measure of quality of life [13], sustained for 12 months. In the Geddes trial, high mortality in the surgical arm was modified after the entry criteria were changed during the trial [13]. In the Criner et al. trial, significance was only reached after the control group crossed over to receive surgical management [14]. Other randomized trials currently in progress will enable the effects of surgery on functional exercise capacity and health-related quality of life to be compared with rehabilitation alone. The largest ongoing trial is the US National Emphysema Treatment Trial, which has so far only reported on high-risk patients. Last year, the group conducting the trial cautioned that patients with an FEVX below 20% predicted and either a carbon monoxide diffusing capacity below 20% predicted or a homogeneous distribution of emphysema were at high risk for death after surgery. Those who did survive had only small changes in pulmonary function and exercise capacity, with no improvements in their quality of well-being, compared with medically treated patients [16].

Although LVR surgery was never intended as a life-sustaining or life-extending procedure, it will be of importance to know whether it might improve survival. Meyers et al. reported on a group of patients who were considered suitable for the procedure, but who did not undergo it as funding had been withheld by Medicare pending the results of controlled trials [17]. Compared to a similar group of patients who were funded for surgery, the sur vival in the non-funded group was decreased. Brenner et al. [18] reported that in patients who experienced an increase in FEV1 > 0.56L, survival exceeded 95%, whereas survival was < 80% for those with a lesser FEV1 response. These inconclusive observations are interesting and suggest hypotheses for further research.

How does LVR work?

Resection of highly compliant lung increases the elastic recoil of the remaining lung. Airflow is increased, work of breathing is decreased and dyspnoea is improved [19]. These changes occur promptly following surgery [20]. The correlation between improved lung mechanics, reduced dyspnoea and improved health-related quality of life is weak. Brenner et al. [7] noted that although 28% of the patients in their study had minimal improvements in FEV1, many improved in their dyspnoea scores. Leyenson et al. also reported on the poor correlations between quality of life, spirometry and dyspnoea [10]. For some patients, improved ventilation-perfusion relationships after surgery have resulted in improved oxygenation, to the extent that the patient no longer required long-term oxygen therapy [12]. It has become clear that the improvements in HRQL and functional exercise capacity following LVR must be distinguished from the improvements that occur after rehabilitation [12].

How should LVR be done?

The conceptual simplicity of the operation belies the reality. The operation is best performed in specialized centres, as success is dependent on excellent anaesthesia, perioperative analgesia, experienced nursing care and physical therapy, given that the patients are very impaired. Although the operation was first reported as a bilateral procedure via a median sternotomy [21], surgeons quickly progressed to using a thoracoscopic approach, initially unilateral, or staged bilateral procedures, but more recently as bilateral procedures. Direct comparisons have suggested greater benefits following bilateral procedures than following unilateral operations [11,22,23]. Our approach is to offer bilateral volume reduction via a thoracoscopic approach. Patients with upper-lobe predominance are placed in the supine position. Patients requiring lower-lobe resection are placed in the lateral position, which requires turning and redraping between sides. In the absence of a randomized trial comparing median sternotomy with thoracoscopic volume reduction, clinical experience is that VATS is associated with reduced morbidity, less pain, earlier mobilization, a shorter hospital stay and a more rapid return to an exercise program [24-26].

Preoperative rehabilitation is important. We therefore enroll all prospec-

Table 14.1 Criteria for lung volume reduction surgery.

Inclusion criteria Exclusion criteria

'Physiological' age < 75 Class III or IV dyspnoea Significant impairment of ADL FEVj 15%-40% TLC> 120% RV > 180%

Destruction and distention on CXR and CT Correlation between CT and V/Q scan re heterogeneous target zones

'Physiological' age > 75 Paco2>55

Previous thoracic surgery on operable side Steroid use 10 mg/day or more RVSP > 50mmHg

Significant CAD or left ventricular dysfunction Exacerbation episodes requiring antibiotics more than three times in the last 6 months Homogeneous disease

ADL, activities of daily living; CAD, coronary artery disease; CT, computed tomography; CXR, chest X-ray; FEVi, forced expiratory volume in 1 s; TLC, total lung capacity; RV, right ventricle; RVSP, right ventricular systolic pressure.

tive surgical candidates for at least 6weeks of supervised rehabilitation. Postoperatively, we offer supervised rehabilitation for the more marginal patients, but encourage a maintenance program for all patients. This ensures compliance with good health-care habits.

Who should have lung volume reduction surgery?

Criteria for LVR surgery include stable patients with severe emphysema and minimal bronchitis, hyperinflation with gas trapping at total lung capacity and dyspnoea during activities of daily living. More specific criteria are summarized in Table 14.1. We confirm emphysema by high-resolution computed tomography (CT)—with blinded grading on a five-point scale by an experienced radiologist — and identify heterogeneity both by CT and by ventilation-perfusion scan. Ventilation curves are displayed separately for each zone (upper middle and lower) on both sides. Perfusion (%) and the slope of the xenon washout curve (visual) are helpful in identifying target zones.

Although patients with homogeneous disease will respond to LVR surgery [27], patients in whom the distribution of emphysema is heterogeneous tend to experience greater improvements in postoperative FEV1 than those with homogeneous disease. We therefore include heterogeneity among our selection criteria. Upper-lobe predominance appears to result in greater improvements than lower-lobe predominance [28], although patients with lower-lobe disease (especially a1-antitrypsin-deficient patients) have derived benefit from the procedure. Patients with the most preoperative hyperinflation appear to enjoy the greatest improvements in dyspnoea [7]. High inspira-tory flow resistance has been associated with a limited benefit from LVR surgery [29].

Who should not have lung volume reduction?

Previous lung surgery, extensive pleural adhesions, pulmonary hypertension, hypercapnia and very severe impairments (FEV1 < 0.4L) or disability (6-min walk < 250 m) are the main exclusion criteria (Table 14.1). We also exclude individuals in whom the presence of associated medical conditions such as cardiovascular disease, connective-tissue disease or severe osteoporosis might compromise their mobility or quality of life. As with any experimental procedure, clear guidelines are balanced by a careful patient assessment at a combined end-stage emphysema clinic in which each patient is seen by a thoracic surgeon and a respiratory specialist.

What is the role of lung transplantation?

Lung transplantation offers substantial palliation of dyspnoea and improved quality of life, although it may not extend survival [30]. It is usually reserved for patients with end-stage disease and severe dyspnoea despite maximal medical management. Most candidates are seriously considered when their FEV1 falls below 20% of predicted. Single-lung transplantation (SLT) is the more frequently performed procedure, although bilateral sequential transplantation offers superior functional results and may improve long-term survival [31]. LVR may be offered prior to transplantation, or may be combined with SLT.

Should lung transplantation be unilateral or bilateral?

The operative mortality for bilateral lung transplantation varies widely. One transplant centre reported 30-day mortality rates of 10% for single-lung transplantation and 22% for bilateral lung transplantation [32]. Additional early mortality led to a very poor 1-year survival of only 35% after bilateral lung transplantation, although in this report one-third of the bilateral lung transplants were performed with the older en-bloc technique, which employs a single tracheal anastomosis. In contrast, another transplant centre reported excellent results following bilateral lung transplantation. The 60-day mortality was only 3.5%, as compared with 21.3% for single-lung transplants [33]. Divergent clinical experiences and multidisciplinary learning curves inevitably influence the selection of the procedure.

Actuarial 1-year survival rates of 93% for single-lung transplantation and 71% for bilateral lung transplantation have been reported [31]. Bilateral transplantation resulted in greater improvements in FEV1 and FVC, although the FEVj/FVC ratio, arterial blood gases and 6-min walk did not differ significantly between bilateral lung transplantation (BLT) and SLT. Functional equivalence between BLT and SLT has also been reported for exercise capacity, including measurements of dyspnoea at rest and during peak exercise [34]. Although SLT may provide sufficient pulmonary reserve to maintain normal blood gases, should the graft deteriorate, single-lung recipients become impaired more rapidly than double-lung recipients. Therefore, the long-term mortality appears to favour the bilateral procedure. Bilateral transplants can be performed with marginal lungs that are not always suitable for SLT [35]. Our centre currently uses bilateral procedures for 80% of transplantations for emphysema.

Who should have lung transplantation?

Candidates are required to be ambulatory and to have rehabilitation potential, as judged by their preoperative participation and progress in rehabilitation. Adequate nutritional status (preoperative weight within 80-120% of ideal body weight) is a prerequisite, as is a suitable psychosocial profile and support system. The goal of the selection process is to identify patients in the most appropriate risk category for whom current impairment, disability and handicap or dismal life expectancy justify the risk of operation. Put another way, patients must be severely compromised and deteriorating despite optimal medical management. Generally accepted objective guidelines for patients with emphysema include: New York Heart Association functional class III, FEV1 < 20% of predicted, rapid decline in FEV1, hypoxia, and hypercapnia [36]. Factors such as weight loss, frequent respiratory infections and repeated hospitalization are also considered.

Who should not have lung transplantation?

Contraindications to lung transplantation are not specific to emphysema. Absolute contraindications include current or recent malignancy, significant disease affecting other organ systems, extrapulmonary infection, substance abuse and significant psychiatric illness. Relative contraindications are becoming less prohibitive with additional surgical experience. For example, previous thoracic surgery complicates but does not prohibit transplantation. Moderate steroid usage is now considered acceptable. Combined coronary bypass and lung transplantation is possible for highly selected recipients. Ventilator dependence remains a contraindication, although a patient previously listed for transplantation who develops respiratory failure requiring ventilation will still be considered if a suitable organ becomes available soon after mechanical ventilation is initiated.

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