- Email: [email protected]
Lung transplantation for COPD: one lung, two lungs, or none?
Comment
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McCance DR, Hanson RL, Charles MA, et al. Comparison of tests for glycated haemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes. BMJ 1994; 308: 1323–28. Engelgau MM, Thompson TJ, Herman WH, et al. Comparison of fasting and 2-hour glucose and HbA1c levels for diagnosing diabetes: diagnostic criteria and performance revisited. Diabetes Care 1997; 20: 785–91. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20: 1183–97. Wong TY, Liew G, Tapp RJ, et al. Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies. Lancet 2008; 371: 736–43. WHO, International Diabetes Federation. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. 2006. http://www.who.int/entity/diabetes/ publications/Definition and diagnosis of diabetes_new.pdf (accessed Jan 15, 2008).
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Levitan EB, Song Y, Ford ES, Liu S. Is nondiabetic hyperglycemia a risk factor for cardiovascular disease? A meta-analysis of prospective studies. JAMA 2005; 293: 194–202. Tirosh A, Shai I, Tekes-Manova D, for the Israeli Diabetes Research Group. Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med 2005; 353: 1454–62. Yu T, Mitchell P, Berry G, Li W, Wang JJ. Retinopathy in older persons without diabetes and its relationship to hypertension. Arch Ophthalmol 1998; 116: 83–89. Wong TY, Mohamed Q, Klein R, Couper DJ. Do retinopathy signs in non-diabetic individuals predict the subsequent risk of diabetes? Br J Ophthalmol 2006; 90: 301–03. Wong TY, Klein R, Islam FM, et al. Diabetic retinopathy in a multi-ethnic cohort in the United States. Am J Ophthalmol 2006; 141: 446–55.
Lung transplantation for COPD: one lung, two lungs, or none?
Custom Medical Stock Photo
See Articles page 744
702
The history of lung transplantation began with the first unsuccessful attempt in 1963 to transplant one lung to treat chronic obstructive pulmonary disease (COPD).1 Subsequent attempts and failures led to the widely held belief that unilateral transplantation in COPD was not physiologically possible because of differences in lung compliance and pulmonary-vascular resistance between the transplanted healthy lung and the native emphysematous lung.2 With this physiological principle in mind, Cooper and colleagues in 1986 used a bilateral transplantation in the first successful treatment of COPD.3 However, transplantation of one lung was subsequently used to treat emphysema in 1989 in France,4 thus disproving previous belief about the physiological limitations of unilateral transplantation in COPD. Over the next two decades, both unilateral
and bilateral transplantation in COPD were shown to improve pulmonary functions,5 exercise capacity,6 and quality of life.7 Whether lung transplantation actually improves survival is debated. Whereas Hosenpud and colleagues8 found a survival benefit in patients with cystic fibrosis and interstitial pulmonary fibrosis treated with lung transplantation, this was not the case in patients with emphysema.8 In today’s Lancet, Gabriel Thabut and colleagues9 compare survival after transplantation of one or two lungs in end-stage COPD in nearly 10 000 patients in the International Society for Heart and Lung Transplantation (ISHLT) registry. This comprehensive study included all reported lung transplantations worldwide, from inception of the registry in 1987 until 2006. Median survival time after bilateral lung transplantation (6·41 years, 95% CI 6·02–6·88) was better than after unilateral procedures (4·59, 4·41–4·76; p<0·0001). However, bilateral lung transplantation had little benefit compared with unilateral for patients who were 60 years and older (hazard ratio 0·95; 95% CI 0·81–1·13). Thabut and colleagues note that similar results have been reported from single-centre reports, and from an earlier analysis of ISHLT registry data. In selected patients, the observation of better survival after transplantation of two lungs rather than one lung is not new, but the strength of Thabut and co-workers’ study lies in the rigorous application of sophisticated statistical methods to adjust for baseline differences that might have skewed the results in favour of bilateral transplantation. Analysis of covariance, propensity-score risk-adjustment, and propensity-based matching all showed better outcomes www.thelancet.com Vol 371 March 1, 2008
Comment
for bilateral than for unilateral transplantation in patients with COPD who were younger than 60 years. Despite rigorous methods, unmeasured differences might exist between recipients of unilateral and bilateral transplants that are not captured in registry data. Short of a randomised trial to compare the two approaches, which will probably never occur, Thabut and colleagues provide the best available evidence for superiority of bilateral over unilateral transplantation of the lung for COPD in younger patients. There are certain characteristics in addition to age, however, that might drive the decision to use unilateral transplantation in patients with COPD. Potential factors include previous thoracic surgery with lung resection, pleurectomy, pleurodesis, pneumonectomy, or coronary-artery bypass-grafting. Very ill patients may be listed for either approach with donor availability determining the procedure. Finally, the ethical principle of beneficence (doing the best for individual patients with bilateral transplantation) will continue to be in conflict with that of justice (providing greater equality of access through unilateral-lung transplantation) as long as donor organs remain in short supply. Alternatives to lung transplantation exist, including lung-volume reduction either surgically10 or with bronchoscopic placement of one-way endobronchial valves.11,12 Medical therapy, especially smoking cessation, and enrolment in pulmonary rehabilitation programmes are appropriate alternatives to lung transplantation. Lung transplantation is an imperfect solution for COPD and other diseases, with a 5-year survival rate of about 50%.13 There is a limited supply of organs suitable for transplantation and patients, usually not those with COPD, die on waiting lists. Diminution of demand
through smoking-prevention programmes is a far better alternative to lung transplantation. E Clinton Lawrence McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA [email protected] I declare that I have no conflict of interest. 1 2
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Hardy JD, Webb WR, Dalton ML Jr, Walker GR Jr. Lung homotransplantation in man. JAMA 1963; 186: 1065–74. Stevens PM, Johnson PC, Bell RL, Beall AC Jr, Jenkins DE. Regional ventilation and perfusion after lung transplantation in patients with emphysema. N Engl J Med 1970; 282: 245–49. Cooper JD, Patterson GA, Grossman R, Maurer J. Double-lung transplant for advanced chronic obstructive lung disease. Am Rev Respir Dis 1989; 139: 303–07. Mal H, Andreassian B, Pamela F, et al. Unilateral lung transplantation in end-stage pulmonary emphysema. Am Rev Respir Dis 1989; 140: 797–802. Levine SM, Anzueto A, Peters JI, et al. Medium term functional results of single-lung transplantation for endstage obstructive lung disease. Am J Respir Crit Care Med 1994; 150: 398–402. Williams TJ, Patterson GA, McClean PA, Zamel N, Maurer JR. Maximal exercise testing in single and double lung transplant recipients. Am Rev Respir Dis 1992; 145: 101–05. Gross CR, Savik K, Bolman RM 3rd, Hertz MI. Long-term health status and quality of life outcomes of lung transplant recipients. Chest 1995; 108: 1587–93. Hosenpud JD, Bennett LE, Keck BM, Edwards EB, Novick RJ. Effect of diagnosis on survival benefit of lung transplantation for end-stage lung disease. Lancet 1998; 351: 24–27. Thabut G, Christie JD, Ravaud P, et al. Survival after bilateral versus single lung transplantation for patients with chronic obstructive pulmonary disease: a retrospective analysis of registry data. Lancet 2008; 371: 744–51. Cooper JD, Trulock EP, Triantafillou AN, et al. Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg 1995; 109: 106–16. Reilly J, Washko G, Pinto-Plata V, et al. Biological lung volume reduction: a new bronchoscopic therapy for advanced emphysema. Chest 2007; 131: 1108–13. Strange C, Herth FJ, Kovitz KL, et al. Design of the Endobronchial valve for emphysema palliation trial (VENT): a non-surgical method of lung volume reduction. BMC Pulm Med 2007; 7: 10. Trulock EP, Christie JD, Edwards LB, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-fourth official adult lung and heart-lung transplantation report—2007. J Heart Lung Transplant 2007; 26: 782–95.
Reduced mortality with home-based HIV treatment in Uganda In today’s Lancet, Jonathan Mermin and colleagues1 present a prospective cohort study in rural Uganda in which they delivered highly active antiretroviral treatment (HAART) to HIV-infected people in their homes. In the years preceding HAART initiation, several supporting interventions were serially introduced (table), including daily co-trimoxazole prophylaxis for all people with HIV, provision of insecticide-treated bednets, and a home-based safe-water system for all households of HIV-infected people. Co-trimoxazole www.thelancet.com Vol 371 March 1, 2008
plus HAART (phase 3+3a in table) reduced mortality in HIV-infected adults to five per 100 person-years from 27 per 100 person-years in phase 1 before treatment. Through home-based delivery by lay staff, the Ugandan non-governmental AIDS support organisation (TASO), which hosted this study, extended HAART to remote rural communities, where clinic capacity would otherwise have precluded access and compliance. As might be expected from a package of care targeting multiple synergic diseases,2 the mortality reduction
See Articles page 752
703
1
2
3 4
5
McCance DR, Hanson RL, Charles MA, et al. Comparison of tests for glycated haemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes. BMJ 1994; 308: 1323–28. Engelgau MM, Thompson TJ, Herman WH, et al. Comparison of fasting and 2-hour glucose and HbA1c levels for diagnosing diabetes: diagnostic criteria and performance revisited. Diabetes Care 1997; 20: 785–91. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20: 1183–97. Wong TY, Liew G, Tapp RJ, et al. Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies. Lancet 2008; 371: 736–43. WHO, International Diabetes Federation. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. 2006. http://www.who.int/entity/diabetes/ publications/Definition and diagnosis of diabetes_new.pdf (accessed Jan 15, 2008).
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7
8
9
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Levitan EB, Song Y, Ford ES, Liu S. Is nondiabetic hyperglycemia a risk factor for cardiovascular disease? A meta-analysis of prospective studies. JAMA 2005; 293: 194–202. Tirosh A, Shai I, Tekes-Manova D, for the Israeli Diabetes Research Group. Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med 2005; 353: 1454–62. Yu T, Mitchell P, Berry G, Li W, Wang JJ. Retinopathy in older persons without diabetes and its relationship to hypertension. Arch Ophthalmol 1998; 116: 83–89. Wong TY, Mohamed Q, Klein R, Couper DJ. Do retinopathy signs in non-diabetic individuals predict the subsequent risk of diabetes? Br J Ophthalmol 2006; 90: 301–03. Wong TY, Klein R, Islam FM, et al. Diabetic retinopathy in a multi-ethnic cohort in the United States. Am J Ophthalmol 2006; 141: 446–55.
Lung transplantation for COPD: one lung, two lungs, or none?
Custom Medical Stock Photo
See Articles page 744
702
The history of lung transplantation began with the first unsuccessful attempt in 1963 to transplant one lung to treat chronic obstructive pulmonary disease (COPD).1 Subsequent attempts and failures led to the widely held belief that unilateral transplantation in COPD was not physiologically possible because of differences in lung compliance and pulmonary-vascular resistance between the transplanted healthy lung and the native emphysematous lung.2 With this physiological principle in mind, Cooper and colleagues in 1986 used a bilateral transplantation in the first successful treatment of COPD.3 However, transplantation of one lung was subsequently used to treat emphysema in 1989 in France,4 thus disproving previous belief about the physiological limitations of unilateral transplantation in COPD. Over the next two decades, both unilateral
and bilateral transplantation in COPD were shown to improve pulmonary functions,5 exercise capacity,6 and quality of life.7 Whether lung transplantation actually improves survival is debated. Whereas Hosenpud and colleagues8 found a survival benefit in patients with cystic fibrosis and interstitial pulmonary fibrosis treated with lung transplantation, this was not the case in patients with emphysema.8 In today’s Lancet, Gabriel Thabut and colleagues9 compare survival after transplantation of one or two lungs in end-stage COPD in nearly 10 000 patients in the International Society for Heart and Lung Transplantation (ISHLT) registry. This comprehensive study included all reported lung transplantations worldwide, from inception of the registry in 1987 until 2006. Median survival time after bilateral lung transplantation (6·41 years, 95% CI 6·02–6·88) was better than after unilateral procedures (4·59, 4·41–4·76; p<0·0001). However, bilateral lung transplantation had little benefit compared with unilateral for patients who were 60 years and older (hazard ratio 0·95; 95% CI 0·81–1·13). Thabut and colleagues note that similar results have been reported from single-centre reports, and from an earlier analysis of ISHLT registry data. In selected patients, the observation of better survival after transplantation of two lungs rather than one lung is not new, but the strength of Thabut and co-workers’ study lies in the rigorous application of sophisticated statistical methods to adjust for baseline differences that might have skewed the results in favour of bilateral transplantation. Analysis of covariance, propensity-score risk-adjustment, and propensity-based matching all showed better outcomes www.thelancet.com Vol 371 March 1, 2008
Comment
for bilateral than for unilateral transplantation in patients with COPD who were younger than 60 years. Despite rigorous methods, unmeasured differences might exist between recipients of unilateral and bilateral transplants that are not captured in registry data. Short of a randomised trial to compare the two approaches, which will probably never occur, Thabut and colleagues provide the best available evidence for superiority of bilateral over unilateral transplantation of the lung for COPD in younger patients. There are certain characteristics in addition to age, however, that might drive the decision to use unilateral transplantation in patients with COPD. Potential factors include previous thoracic surgery with lung resection, pleurectomy, pleurodesis, pneumonectomy, or coronary-artery bypass-grafting. Very ill patients may be listed for either approach with donor availability determining the procedure. Finally, the ethical principle of beneficence (doing the best for individual patients with bilateral transplantation) will continue to be in conflict with that of justice (providing greater equality of access through unilateral-lung transplantation) as long as donor organs remain in short supply. Alternatives to lung transplantation exist, including lung-volume reduction either surgically10 or with bronchoscopic placement of one-way endobronchial valves.11,12 Medical therapy, especially smoking cessation, and enrolment in pulmonary rehabilitation programmes are appropriate alternatives to lung transplantation. Lung transplantation is an imperfect solution for COPD and other diseases, with a 5-year survival rate of about 50%.13 There is a limited supply of organs suitable for transplantation and patients, usually not those with COPD, die on waiting lists. Diminution of demand
through smoking-prevention programmes is a far better alternative to lung transplantation. E Clinton Lawrence McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA [email protected] I declare that I have no conflict of interest. 1 2
3
4 5
6
7
8
9
10
11 12
13
Hardy JD, Webb WR, Dalton ML Jr, Walker GR Jr. Lung homotransplantation in man. JAMA 1963; 186: 1065–74. Stevens PM, Johnson PC, Bell RL, Beall AC Jr, Jenkins DE. Regional ventilation and perfusion after lung transplantation in patients with emphysema. N Engl J Med 1970; 282: 245–49. Cooper JD, Patterson GA, Grossman R, Maurer J. Double-lung transplant for advanced chronic obstructive lung disease. Am Rev Respir Dis 1989; 139: 303–07. Mal H, Andreassian B, Pamela F, et al. Unilateral lung transplantation in end-stage pulmonary emphysema. Am Rev Respir Dis 1989; 140: 797–802. Levine SM, Anzueto A, Peters JI, et al. Medium term functional results of single-lung transplantation for endstage obstructive lung disease. Am J Respir Crit Care Med 1994; 150: 398–402. Williams TJ, Patterson GA, McClean PA, Zamel N, Maurer JR. Maximal exercise testing in single and double lung transplant recipients. Am Rev Respir Dis 1992; 145: 101–05. Gross CR, Savik K, Bolman RM 3rd, Hertz MI. Long-term health status and quality of life outcomes of lung transplant recipients. Chest 1995; 108: 1587–93. Hosenpud JD, Bennett LE, Keck BM, Edwards EB, Novick RJ. Effect of diagnosis on survival benefit of lung transplantation for end-stage lung disease. Lancet 1998; 351: 24–27. Thabut G, Christie JD, Ravaud P, et al. Survival after bilateral versus single lung transplantation for patients with chronic obstructive pulmonary disease: a retrospective analysis of registry data. Lancet 2008; 371: 744–51. Cooper JD, Trulock EP, Triantafillou AN, et al. Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg 1995; 109: 106–16. Reilly J, Washko G, Pinto-Plata V, et al. Biological lung volume reduction: a new bronchoscopic therapy for advanced emphysema. Chest 2007; 131: 1108–13. Strange C, Herth FJ, Kovitz KL, et al. Design of the Endobronchial valve for emphysema palliation trial (VENT): a non-surgical method of lung volume reduction. BMC Pulm Med 2007; 7: 10. Trulock EP, Christie JD, Edwards LB, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-fourth official adult lung and heart-lung transplantation report—2007. J Heart Lung Transplant 2007; 26: 782–95.
Reduced mortality with home-based HIV treatment in Uganda In today’s Lancet, Jonathan Mermin and colleagues1 present a prospective cohort study in rural Uganda in which they delivered highly active antiretroviral treatment (HAART) to HIV-infected people in their homes. In the years preceding HAART initiation, several supporting interventions were serially introduced (table), including daily co-trimoxazole prophylaxis for all people with HIV, provision of insecticide-treated bednets, and a home-based safe-water system for all households of HIV-infected people. Co-trimoxazole www.thelancet.com Vol 371 March 1, 2008
plus HAART (phase 3+3a in table) reduced mortality in HIV-infected adults to five per 100 person-years from 27 per 100 person-years in phase 1 before treatment. Through home-based delivery by lay staff, the Ugandan non-governmental AIDS support organisation (TASO), which hosted this study, extended HAART to remote rural communities, where clinic capacity would otherwise have precluded access and compliance. As might be expected from a package of care targeting multiple synergic diseases,2 the mortality reduction
See Articles page 752
703