Key Point

Lung volume reduction surgery combined with medical treatment in a carefully selected group of patients yields significant gains in lung function, exercise tolerance, and quality of life measures compared with medical treatment alone.

BOSTON—In the mid-1990s, lung volume reduction surgery (LVRS) became a widely used strategy for treating patients with severe emphysema. The mortality rate was acceptable (in the range of 4% to 8%) and the benefits as far as quality of life was concerned were significant.

However, “during the early developmental years, LVRS was performed at times in inappropriate patients or under suboptimal settings, and the ensuing variable results led to questions about the therapeutic value of the procedure,” said Robert L. Berger, MD, Associate Clinical Professor of Surgery at Harvard Medical School in Boston.

In addition, the number of patients who could be considered as candidates for the surgery exceeded one million in the United States alone, and with each surgery costing $30,000 to $35,000, the procedure was implicated as an insupportable financial burden for the health care industry. Thus, health insurers, including Medicare, discontinued their coverage of the procedure—despite its apparent success.

However, noted Dr. Berger, LVRS produced impressive results consistently in a carefully selected population of patients with advanced emphysema. Thus, in response to the intense controversy generated by the denial of a presumably effective palliative treatment, several single-center, randomized clinical trials and the National Emphysema Treatment Trial (NETT)—which had a patient population of 1,218—were undertaken to assess the effectiveness of LVRS. All of these trials, especially NETT, yielded valuable information regarding the use of LVRS, but more data are necessary for definitive conclusions.

The Canadian Lung Volume Reduction (CLVR) surgery study and the Overholt–Blue Cross Emphysema Surgery Trial (OBEST) are two independent, multicenter, randomized clinical trials that compared LVRS plus optimal medical therapy with medical treatment alone. Because the studies were nearly identical in design, patient characteristics, and outcomes, noted Dr. Berger, their results were combined in order to get a larger series with more power. Both studies found that six months after randomization, patients who had undergone LVRS in addition to medical treatment had better lung function and significantly improved exercise capacity than those who were given medical treatment alone.¹

THE COMBINED OBEST/CVLR STUDY

All patients underwent a standardized screening and evaluation process, after which those who qualified for enrollment were randomized either to LVRS plus medical therapy or to medical treatment alone. LVRS involved removal of 20% to 30% of total lung volume, with extubation attempted in the operating room as soon as the patient regained consciousness. Medical treatment consisted of pulmonary rehabilitation, vaccination, oxygen therapy, bronchodilators, and corticosteroids.

In OBEST, patients in the medical treatment group were given the option of receiving LVRS six months after randomization. All patients underwent standardized laboratory tests of lung function, chest radiography, and CT. Health-related quality of life was measured according to the disease-specific chronic respiratory disease questionnaire (CRDQ) and the Medical Outcomes Study 36-item short form.

The primary outcome for CLVR was the Healthy Utility Index score—a measure of health-related quality of life—over the two-year follow-up. In the OBEST study, the objectives were the CRDQ score and change in six-minute walk distance.

Fifty-one patients underwent LVRS plus medical treatment, and 39 received medical treatment alone. Almost all patients had advanced heterogeneous emphysema.

The total six-month mortality rate was 5.7% in the LVRS group and 5.1% in the medical treatment group. During six-month follow-up, the CLVR study hospitalized 50% of the medical patients and 60% of the LVRS patients. In the OBEST study, hospitalization rates were 9% and 12.5% for the medical and LVRS patients, respectively. These differences are attributed to prevailing health care practices in the two countries rather than to differences in patient characteristics or treatment factors, Dr. Berger pointed out.

In the combined-cohort LVRS group, FEV1 increased by 28.8%, while total lung capacity and residual volume decreased by 12.4% and 24.3%, respectively. Pco2 decreased by 2.9 mm Hg, and Dlco rose by 1.11 mm/min/mm Hg at six months. All of these changes (except for Dlco) were statistically significant. In the medical groups of both studies, there were no significant improvements in any measures of pulmonary function.

Six-minute walk distance increased in the LVRS groups by 145.5 feet, and decreased in the medical groups by 57.9 feet.

In the CLVR study, at six months, all domains of the CRDQ showed better results in the LVRS group than in the medical group. The physical component of the Medical Outcomes Study showed a better outcome for the LVRS group, with the most profound increase being a 26-point gain in the physical function domain.

SIGNIFICANT IMPROVEMENT IN THE RIGHT PATIENTS

According to the authors, both of these studies have shown that in carefully selected patients with advanced heterogeneous upper-lobe emphysema pulmonary function, exercise tolerance, and quality of life all improved six months after LVRS.

“Several distinct categories of patients who would most likely benefit from LVRS at the present state of the art have been well defined,” said Dr. Berger, who was the director of the OBEST study. “The ‘predominant upper lobe disease/low exercise tolerance’ cohort has been identified by NETT as the most favorable subgroup and resembles the features of patients regarded as optimal candidates for LVRS prior to launching NETT.” The number of patients who meet the favorable selection criteria is unknown but probably far less than earlier estimates of 500,000.

Both the CLVR and OBEST studies focused on the palliative effects of LVRS—not on survival—with the understanding that in debilitating illness, palliation can be as important as extending life. The authors believe that the argument against the therapeutic value of LVRS is no longer relevant and attention should instead be focused on the economic and ethical concerns surrounding the procedure.

“In the case of LVRS, one must determine the worth of getting a bedridden person out of bed in order to enable him/her to walk, to become more active, and perhaps a working individual in society,” said Dr. Berger. “It is well to remember that the economics of a therapeutic intervention usually apply to the larger universe and are irrelevant to the individual patient who is unable to perform simple daily chores because of a disabling illness. He/she cares much less about economics than about the promise of regaining function from a therapeutic intervention.”

Advances in the surgical procedure could reduce both the risks and costs of LVRS. “Indeed, several nonsurgical approaches are undergoing laboratory and early clinical testing,” Dr. Berger pointed out. “These procedures, performed through a bronchoscope, involve placement of one-way valves, creating pathways in the airway system of the lung, or remodeling the lung through deployment of biologic agents that initiate shrinkage and volume reduction of the diseased lung tissue through scar formation.”

If found to be safe and effective, he continued, “these nonsurgical approaches could revolutionize the field of lung volume reduction for advanced emphysema.”

—Gale Jurasek

Reference
1. Miller JD, Berger RL, Malthaner RA, et al. Lung volume reduction surgery vs medical treatment: for patients with advanced emphysema. Chest. 2005;127:1166-1177.

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