Polysomnography could show whether LVRS patients have fewer respiratory-related arousals, fewer apnea episodes, and a shorter duration of apnea episodes after surgery.

 The resurgence of a surgery nearly 50 years old, lung volume reduction surgery (LVRS), has restored a good quality of life to many people with emphysema.1,2 In this surgery, damaged lung tissue is removed in order to reduce dyspnea. Studies1,2 show that, after the surgery, pulmonary function improves to the point that many people are able to resume everyday activities such as walking, climbing stairs, and getting dressed. Does improved pulmonary function continue into sleep? Indirect evidence3,4 suggests so.

The lungs contain an estimated 300 million alveoli. Each alveolus is surrounded by a network of capillaries. This juxtaposition allows oxygen to diffuse from the alveoli into the capillaries and carbon dioxide to diffuse from the capillary blood into the alveoli. In emphysema, the alveoli are progressively destroyed. One consequence of the destruction is a loss of alveolar elasticity so that the alveoli can easily stretch during inhalation but not recoil sufficiently during exhalation to expel air. Air remains trapped in the alveoli resulting in carbon dioxide being rebreathed with each breath and distention of the alveoli. Distention of the alveoli then increases the volume of the lung. The rib cage expands to compensate for the increased lung size, resulting in a barrel-chested appearance. The increased lung size pushes the diaphragm downward, hindering its ability to rise and fall during respiration. This impaired diaphragmatic motion forces the patient to take shallow breaths. Another complication of the increased lung size is that the rib cage is less able to exert a pulling force on the surface of the lungs during inspiration. Normally, this pulling force would expand the alveoli by causing an inrush of air. With the rib cage less mobile, the alveoli cannot expand sufficiently and gas exchange is impaired.

In an emphysematous lung, blood continues to travel through both healthy and unhealthy lung tissue. The unhealthy tissue returns carbon dioxide-enriched blood to the bloodstream. This triggers rapid breathing in an attempt to reduce the carbon dioxide level quickly. Alveolar damage, however, hinders gas exchange. The result is that the patient gasps for breath upon the least exertion (for example, after walking 2 m).

Emphysema can cause damage in three ways. The most common form of the disease, centriacinar emphysema, affects the acini in the lungs’ upper lobes. An acinus is that portion of a bronchiole that contains the alveoli, alveolar sacs, and alveolar ducts. The damage is localized (discrete areas of damaged lung tissue exist in the midst of normal lung tissue). Centriacinar emphysema affects 95% of people with a diagnosis of emphysema5 and is associated with cigarette smoking.

The second form of the disease, panacinar emphysema, affects up to 5% of people with the disorder6 and is caused by an inherited deficiency of a1-antitrypsin (a protein produced by the liver that protects the lungs). A1-antitrypsin prevents neutrophil elastase (an enzyme) from destroying the protein elastin, which is responsible for the elasticity of the connective tissue (such as the alveoli) in the lungs. Lack of a1-antitrypsin, by allowing neutrophil elastase to destroy elastin, results in generalized damage to the alveoli and alveolar ducts located in the lower lobes.

The third form of the disease, distal (paraseptal) emphysema, results in damage to the alveoli that are located close to the periphery of the lung. The damaged alveoli can distend to the point of becoming bullae, gigantic cysts of 1 cm or more (alveoli normally range in size from 0.125 to 0.35 mm). Bullae fill the lung with dead air space and restrict respiratory motion.

The chronically high blood levels of carbon dioxide seen in emphysema ultimately alter the function of chemoreceptors located in the brain, carotid arteries, and aortic arch. The brain’s chemoreceptors are sensitive to carbon dioxide; the peripheral chemoreceptors (carotid arteries and aortic arch) are sensitive to oxygen. Breathing rate is determined by an interplay between the brain and peripheral chemoreceptors.7 When this is altered by a chronically high carbon dioxide level in emphysema, obstructive sleep apnea, central sleep apnea, and Cheyne-Stokes respiration can result.1,8 These breathing problems can occur because, as the level of carbon dioxide rises, blood becomes more acidic; this, in turn, blunts the response of the brain’s chemoreceptors to changes in carbon dioxide blood levels.

In obstructive sleep apnea, the upper airway intermittently collapses and blocks airflow. Although why this occurs is not completely known, one thought8 is that a chronically high carbon dioxide level or chronically low oxygen level may impair the transmission of signals from the brain to the nerves that maintain the tone of the upper airway muscles. This may result in weak muscle tone, allowing the airway to collapse during sleep.

In central apnea, the brain does not send a signal to breathe. This may result from a misperception of carbon dioxide or oxygen levels. The brain responds as if the blood were hyperoxic or hypocapnic. Normally, hypocapnia or hyperoxia would cause a momentary pause in breathing to allow the oxygen level to fall or the carbon dioxide level to rise to normal levels. In central apnea, neither hyperoxia nor hypocapnia exists before the brain signals a pause.

In Cheyne-Stokes breathing, the patient takes increasingly deep breaths, which then become increasingly shallow. Sometimes breathing diminishes to the point of a central apnea or central pause. Eventually, increasingly deep breaths resume and the pattern repeats. An impaired chemoreceptor response to the continually changing carbon dioxide and oxygen levels may result in the waxing and waning breathing pattern.

A recent American Lung Association survey6 found that 50% of respondents had sleep difficulties as a result of their emphysema. Sleep is often interrupted or delayed by factors such as frequent respiratory-related arousals, coughing, shortness of breath, and having to clear excessive mucus.

For some people, nighttime use of supplemental oxygen helps to lessen respiratory problems. Medications such as bronchodilators also help to reduce symptoms. Researchers, however, have long looked for something that could give more effective relief of symptoms, particularly dyspnea. In recent years, much hope has focused on LVRS.

With damaged lung tissue removed, less carbon dioxide-laden blood is returned to circulation. The healthy tissue that remains can then oxygenate blood more efficiently, and symptoms of emphysema improve. Ciccone et al2 reported that Otto Brantigan was the first surgeon to remove the damaged portions of the lung in people with emphysema. He began performing the surgery in the 1950s. Unfortunately, the lungs leaked air at the sutures after surgery. This complication, plus a high death rate (18%), caused him to abandon the surgery in 1960.

A little more than 3 decades later, improvements in surgical instrumentation (such as the surgical stapler) and anesthesia made it possible for Cooper et al9 to revive the surgery successfully in 1995. The surgical stapler can quickly cut and close incisions in lung tissue. The stapler uses porcine or bovine pericardium to close the holes left by staples, thereby reducing air leaks and increasing survival rates.

One of two methods is used to perform LVRS: video-assisted thoracoscopy surgery (VATS) or median sternotomy. In VATS, tissue is removed through a small incision between the ribs. In median sternotomy, tissue is removed through a traditional midline incision. The tissue removed constitutes approximately 20% to 30% of the upper lobes.

Because of Cooper et al’s success, other surgeons began to perform this surgery. Problems arose soon after its reintroduction, however. Other physicians did not have the same rate of success with the surgery; air leaks remained hard to control and patients died at a higher rate than reported initially. Since many people undergoing the surgery were Medicare beneficiaries, reports of these problems caused Medicare to withdraw payment in 1996 and call for a study on the efficacy of the surgery. The National Emphysema Treatment Trial (NETT)10 began in January 1998 and continued through July 2002. NETT was sponsored by the Health Care Financing Administration (now the Centers for Medicare & Medicaid Services) in conjunction with the National Heart, Lung and Blood Institute and the Agency for Healthcare Research and Quality. Patients were enrolled by 17 clinics. After meeting study criteria, subjects were randomized to receive LVRS (through VATS or median sternotomy) or to undergo standard medical therapy (drugs and pulmonary rehabilitation) for emphysema. LVRS was performed on 608 subjects, while 610 subjects received nonsurgical standard therapy.

Patients were examined 90 days, 1 year, and 2 years after surgery to determine whether pulmonary function and quality of life improved in the subjects who had undergone surgery and how long the effects of surgery lasted. Pulmonary function tests such as spirometry and the 6-minute walk test were used to test objectively for improvement in pulmonary function. Subjective improvements in health and quality of life were studied using three questionnaires covering respiratory symptoms, well-being, and shortness of breath.

The NETT study found that the LVRS subjects’ pulmonary function test results improved dramatically after surgery, compared with those of subjects who received standard medical therapy. Subjectively, 33% of LVRS subjects felt that they had a better quality of life after surgery, compared with 9% of the medical therapy group. The NETT study found that the beneficial effects of the surgery last up to 5 years.

In a 1996 LVRS study, Yusen et al11 used the Nottingham Health Assessment12 to examine six aspects of life: energy level, pain, emotional reaction, sleep, social isolation, and physical abilities. Examples of sleep-related statements on the Nottingham Health Assessment are “It takes me a long time to get to sleep,” “Worry is keeping me awake at night,” “I wake up feeling depressed,” and “I sleep badly at night.” The investigators found that all aspects of life quality improved greatly, except sleep. That is not to say that sleep became worse. Sleep difficulties did lessen, but not to the same degree as the other health and social problems examined. For example, sleep-difficulty scores decreased (improved) from a presurgical average score of 34 to 14 (on a scale of 100) a year after surgery. In contrast, energy levels improved from a mean score of 65 before surgery to 8 a year later.

Currently, no polysomnographic studies yet exist that examine sleep before and after LVRS, but indirect evidence from work involving other types of lung surgery suggests that a good quality of sleep occurs after LVRS. For example, Brander et al3 found that oxygen desaturation ranged from moderate to mild (78% to 92%) and sleep quality was good in subjects who had undergone thoracoplasty for tuberculosis. Kubota et al4 found that sleep-disordered breathing affected a small portion (37%) of subjects who had undergone either lung resection or thoracoplasty for tuberculosis. In both studies, subjects had undergone surgery decades before the study, suggesting that these findings were of long standing.

To what extent does LVRS reduce sleep-disordered breathing? To what extent are arousals lessened after LVRS? How does each sleep stage affect breathing after LVRS? These and other questions about the impact of LVRS on sleep are yet to be answered. Soon, the answers may be forthcoming: NETT findings are prompting researchers to ask new questions about the surgery.

Regina Patrick, RPSGT, is a contributing writer for RT.

For Further Reading
Humphrey EW, McKeown DL. Manual of Pulmonary Surgery. New York: Springer-Verlag; 1982.
National Emphysema Treatment Trial (NETT). Available at: http://www.clinicaltrials.gov/show/NCT00000606.   Accessed May 12, 2004

Sabiston DC, Spencer FC. Surgery of the Chest. Philadelphia: WB Saunders; 1990:801-814.

1.    O’Brien GM, Furukawa S, Kuzma AM, et al. Improvements in lung function, exercise and quality of life in hypercapnic COPD patients after lung volume reduction surgery. Chest. 1999;115:75-84.
2.    Ciccone AM, Meyers BF, Guthrie TJ, et al. Long-term outcome of bilateral lung volume reduction in 250 consecutive patients with emphysema. J Thorac Cardiovasc Surg. 2003;125:513-525.
3.    Brander PE, Salmi T, Partinen M, Sovijarvi AR. Nocturnal oxygen saturation and sleep quality in long-term survivors of thoracoplasty. Respiration. 1993;60:325-331.
4.    Kubota O, Nishimura K, Inoue Y, et al. The metabolic index of nocturnal hypoxia in patients after lung resection and thoracoplasty [abstract]. Nihon Kyobu Shikkan Gakkai Zasshi. 1991;29:844.
5.    Petty TL. Emphysema. Available at: http://praxis.md/index.asp?page=bhg_report&article_id=BHG01PU01&section=report.   Accessed May 12, 2004.
6.    American Lung Association. Chronic obstructive pulmonary disease (COPD) fact sheet. Available at: http://www.lungusa.org/site/pp.asp?c=dvLUK9O0E&b=35020.   Accessed May 12, 2004.
7.    Alcamo IE. Anatomy and Physiology the Easy Way. Hauppauge, NY: Barron; 1996:364-365.
8.    Prisk GK, Elliot AR, Wes JB. Sustained microgravity reduces the human ventilatory response to hypoxia but not hypercapnia. J Appl Physiol. 2000;88:1421-1430.
9.    Cooper JD, Trulock EP, Triantafillor AN, et al. Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg. 1995;109:106-116.
10.    National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003;348:2059-2073.
11.    Yusen RD, Trulock EP, Pohl MS, et al. Results of lung volume reduction surgery in patients with emphysema. Semin Thorac Cardiovasc Surg. 1996;8:99-109.
12.    Nottingham Health Profile. Available at: http://www.ildannoallapersona.com/allegati/Nottingham%20Health%20Profile.pdf.   Accessed May 12, 2004.