Patient Perspectives on Management of Pneumothorax in Lymphangioleiomyomatosis*

CHEST Original Research LYMPHANGIOLEIOMYOMATOSIS Patient Perspectives on Management of Pneumothorax in Lymphangioleiomyomatosis* Lisa R. Young, MD; Khalid F. Almoosa, MD, FCCP; Stacey Pollock-BarZiv, PhD; Meg Coutinho; Francis X. McCormack, MD, FCCP; and Steven A. Sahn, MD, FCCP Study objectives: The American College of Chest Physicians Delphi Consensus Statement on management of spontaneous pneumothorax recommended pleurodesis after the first secondary spontaneous pneumothorax to prevent recurrence, and evaluation of patients perspectives regarding pneumothorax treatment was identified as a future research priority. Patients with lymphangioleiomyomatosis (LAM) are an ideal population for performing these studies, since pneumothorax occurs and recurs more commonly in LAM than in any other chronic pulmonary disorder. Study design and participants: A 23-item questionnaire evaluating opinions of pneumothorax treatment was distributed to 615 patients in the LAM Foundation patient database, with a response rate of 52%. Results: Of respondents, 69% (216 of 314 patients) reported a history of radiographically documented pneumothorax, and 181 patients (84%) reported at least one pleurodesis procedure. Neither a history of pneumothorax nor surgical management of pneumothorax affected reported oxygen use or perception of overall lung function, yet 41% thought that their pneumothorax had contributed to a decline in lung function. Few patients (12%) worried frequently about a pneumothorax developing, but one third made lifestyle modifications due to fear of pneumothorax. Extensive pain associated with chest tube placement and inadequate pain management throughout treatment for pneumothorax were frequent concerns. Only 25% of respondents thought that pleurodesis was appropriate for a first pneumothorax, while 60% favored pleurodesis for a second pneumothorax. Despite the apparent reluctance to undergo pleurodesis, most patients agreed that pleurodesis helps prevent pneumothorax recurrence. One third of patients believed that their physicians did not consider their preferences regarding pneumothorax management. Conclusions: LAM patients and physicians may have different views about the significance of pneumothorax, in that most patients appear to favor a conservative initial approach to pneumothorax management. In conjunction with appropriate pain management, a better understanding of patients perspectives will facilitate cooperative decision making and may ultimately improve clinical outcomes in LAM related to pneumothorax. (CHEST 2006; 129:1267 1273) Key words: lymphangioleiomyomatosis; pleurodesis; pneumothorax; shared decision making; tube thoracostomy; tuberous sclerosis Abbreviations: ACCP American College of Chest Physicians; LAM lymphangioleiomyomatosis; TSC tuberous sclerosis complex Lymphangioleiomyomatosis (LAM) is an uncommon, progressive, cystic lung disease that predominantly affects young women, causing progressive dyspnea and respiratory failure. The histopathologic hallmarks of the disease are dilated distal airspaces and diffuse infiltration of the pulmonary interstitium with atypical smooth-muscle cells, including spaces surrounding airways, vessels, and lymphatics. 1 Pulmonary parenchymal changes consistent with LAM are found in approximately one www.chestjournal.org CHEST / 129 / 5/ MAY, 2006 1267

third of women with tuberous sclerosis complex (TSC), an autosomal-dominant tumor suppressor syndrome. 2 4 LAM also occurs in a sporadic form that is not associated with germline mutations in TSC genes. However, in some patients with sporadic LAM, renal angiomyolipomas and LAM cells in the lung have been shown to contain TSC2 gene mutations. 5 Pneumothorax is a frequent complication of LAM that causes significant morbidity. Two thirds of LAM patients experience a pneumothorax, and 70% of these women will have recurrent pneumothorax, either ipsilateral or contralateral. 6 10 The optimal approach to the treatment and prevention of recurrent pneumothorax in LAM is controversial. Pleural interventions, such as pleurodesis, pleural abrasion, and partial pleurectomy, are often employed to manage recurrent pneumothorax in LAM; however, these procedures themselves are associated with significant morbidity and may influence subsequent candidacy for lung transplantation. Specifically, previous pleural symphysis procedures may increase bleeding complications and the length of hospital stay at the time of lung transplantation, and many centers will not perform transplant on patients with a history of bilateral pleurodesis. 10 12 Most experts agree that pneumothoraces that occur in patients with clinically apparent lung disease should be managed with pleurodesis after the first event. 13 In 2002, the LAM Foundation, a research and advocacy organization dedicated to LAM patients, commissioned a group of LAM physicians and researchers (The LAM Pleural Disease Consensus Group) to address the management of pneumothorax in LAM. With growing physician interest in earlier pleural symphysis, concern emerged about whether or not LAM patients would accept such recommendations for more aggressive management. At the 2003 Annual LAMposium Patient Conference, 46 women with LAM participated in a informal audience survey. When questioned about their willingness to accept pleurodesis for management of *From the Department of Medicine (Drs. Young, Almoosa, and McCormack), Division of Pulmonary and Critical Care Medicine, University of Cincinnati, Cincinnati, OH; The University of Toronto (Dr. Pollock-BarZiv), Toronto, Canada; The LAM Foundation (Ms. Coutinho), Cincinnati, OH; and Department of Medicine (Dr. Sahn), Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC. Manuscript received August 30, 2005; revision accepted October 22, 2005. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Lisa Young, MD, University of Cincinnati, Division of Pulmonary and Critical Care, 231 Albert Sabin Way, 6053 Medical Sciences Building, Cincinnati, OH 45267-0564; e-mail: Lisa.Young@cchmc.org. their first pneumothorax, with the potential goal of improvement in long-term outcomes, the subjects seemed reluctant to consider more aggressive treatment options. Given the initial patient response to these recommendations, we designed a questionnaire to more formally evaluate LAM patients views on pneumothorax and its management. Our ultimate goal is to incorporate patients perspectives into shared decision making in pneumothorax management to improve quality of life and long-term health outcomes for LAM patients. Materials and Methods A 23-item questionnaire was designed to evaluate patient opinions regarding various pneumothorax treatment options. After ethics board approval by the Institutional Review Board at the University of Cincinnati, the LAM Foundation distributed the survey to all registered patients in their database (n 615 at time of study initiation). Background sociodemographic and medical information (age, diagnosis of TSC), current clinical state (use of supplemental oxygen), and history and treatment of pneumothorax (number of pneumothoraces confirmed by chest radiography, treatment received) were recorded. Participants were asked to rate their level of worry regarding pneumothorax from never worry to always worry and report behavioral and lifestyle modifications (exercise avoidance to prevent pneumothorax). Opinions regarding pleurodesis options and decision making regarding pneumothorax treatment were also sought, but only from patients with a history of pneumothorax. Participants were then provided with specific published background information relating the incidence of pneumothorax and frequency of pneumothorax recurrence and were told that evidence indicated that pleurodesis reduced recurrence by approximately 50%. 10,14 16 This was followed by a series of questions asking them to indicate their preference for treatment options (observation, chest tube, chest tube with pleurodesis, surgical options, not sure) for a first and second pneumothorax. Surveys were returned to the LAM Foundation, and tabulated responses were provided to the investigators. Parametric data were analyzed using Student t test, and proportions were compared using 2 analysis; p 0.05 was considered statistically significant for all analyses. Results Respondent Characteristics Three hundred eighteen questionnaires (52%) were returned to the LAM Foundation, and 4 questionnaires were excluded from final analysis due to incomplete responses. A majority of study participants (75%) lived in the United States or Canada (6.4%), although surveys were returned from LAM patients residing in 18 other countries. The respondents demographic characteristics were similar to those of the overall LAM Foundation database, with a mean age of 48.2 years at the time of survey response, and a TSC prevalence of 12% (Table 1). Fifty-five percent of respondents characterized their 1268 Original Research

Table 1 Demographics and Characteristics of Respondents* Variables Overall Respondents Pneumothorax No Pneumothorax p Value Respondents. 314 (100) 216 (69) 98 (31) Mean age, yr 48.2 0.56 46.4 0.69 52.2 0.88 0.001 TSC LAM 39 (12) 21 (10) 18 (18) 0.03 Living in the United States. 235 (75) 154 (71) 81 (83) 0.03 Reported lung function of good to excellent 173 (55) 119 (55) 54 (55) 0.95 Oxygen use 102 (32) 68 (31) 34 (35) 0.57 Previous lung transplantation 42 (13) 34 (16) 8 (8) 0.068 *Data are presented as No. (%) or mean SD unless otherwise indicated. lung function as either good, very good, or excellent, and 32% reported supplemental oxygen use that was either continuous, intermittent during sleep, or during exercise. Sixty-nine percent of respondents had a history of radiographically documented pneumothorax, with 18.5% reporting only 1 pneumothorax, 51% with 2 to 5 occurrences, 24.5% with 6 to 10 occurrences, and 6% reporting 10 pneumothoraces. In total, pneumothorax was recurrent in 81% of those respondents with history of pneumothorax. As compared to respondents without a history of pneumothorax, those patients with a history of pneumothorax were younger (46.4 years vs 52.2 years, p 0.001). Respondents with TSC were less likely to have experienced a pneumothorax (risk ratio, 0.53; confidence interval, 0.3 to 0.95; p 0.03). Interestingly, only 65% of US respondents had a history of pneumothorax, in comparison to 88% of the non-us respondents (p 0.03). Reported Impact of Pneumothorax Several questions assessed patients perceptions of the impact of pneumothorax on their health. Although 41% of respondents thought that pneumothorax had contributed to a decline in lung function, reported oxygen use and subjective self-assessment of lung function were not affected by respondent history or number of pneumothoraces. When respondents were asked to rank their greatest fears about LAM, only 11% reported pneumothorax, while 32% answered death, 19% answered shortness of breath, and 13% answered the need for lung transplant. Few respondents (12%) reported frequently worrying about development of a pneumothorax (Fig 1). Furthermore, those respondents with a history of recurrent pneumothorax were not more likely to report worrying about pneumothorax recurrence than those respondents who had experienced only one pneumothorax (p 0.37, data not shown). Yet, one third of all survey participants reported a lifestyle modification due to fear of a pneumothorax. Most respondents with a history of pneumothorax had extensive and often repeated experience with the various interventions employed for pneumothorax management (Table 2). For example, 174 individuals had undergone chest tube placement a total of 546 times (mean, 3.3 interventions per patient), and repeated pleurodesis was also a common experience. Thirty-five respondents (16%) had been successfully treated with either observation and oxygen administration only or tube thoracostomy for a pneumothorax and had never required more definitive interventions. When compared to those respondents who had undergone pleurodesis (n 181), the 35 individuals managed conservatively characterized their lung function similarly (52% vs 55% reported good to excellent ), and an equal number reported chronic supplemental oxygen utilization (data not shown). Interestingly, although most respondents were treated initially with chest tubes, the vast majority eventually underwent some form of pleurodesis (84%). Opinions Regarding Treatment for Pneumothorax Opinions regarding treatment for pneumothorax were solicited from those patients with a history of pneumothorax. As shown in Figure 2, very few of these respondents believed that pleurodesis was the most appropriate management for a first pneumothorax, with most choosing conservative options of observation/oxygen (16%) or chest tube drainage (46%). Regarding a second pneumothorax, 60% selected some form of pleurodesis, with half choosing chest tube pleurodesis and half choosing surgical pleurodesis. Yet, 23% were averse to pleurodesis to treat a second pneumothorax, with 6% of respondents selecting observation or oxygen and 17% selecting chest tube drainage only. Those respondents without personal experience of pleurodesis (n 35) tended to select more conservative initial management strategies, as only 3 respondents (9%) selected pleurodesis for a first pneumothorax, and only 26% selected pleurodesis for a second pneumothorax (data not shown). Comments about experiences with pneumothorax www.chestjournal.org CHEST / 129 / 5/ MAY, 2006 1269

Figure 1. Most LAM patients denied worrying about recurrent pneumothoraces. LAM patients who had a history of pneumothorax were asked the following question: How often do you worry about developing a pneumothorax? Respondents were asked to select from the five response choices listed. PTX pneumothorax. included frequent responses related to perceptions of their physicians lack of knowledge about LAM, extensive pain associated with chest tube placement, and inadequate pain management throughout their treatment. Frequent comments also detailed experiences with complications of chest tube placement and prolonged hospitalizations with ongoing air leaks. One third of respondents believed that their physicians did not consider their preferences regarding pneumothorax management. After statements in the written survey of published data relating the frequency of pneumothorax and recurrence, participants were then asked to respond to the following direct statement: If a LAM patient has a pneumothorax, I think that she should have surgery to treat the pneumothorax. In this direct context, most respondents (72%) disagreed. When the item was repeated for treatment for a second Table 2 Pneumothorax Management Experienced by Respondents Interventions Patients (n 216), No. (%) Total Interventions, No. Observation or oxygen 85 (39) 226 Chest tube or needle aspiration 174 (81) 546 Pleurodesis via chest tube 97 (45) 149 Surgical pleurodesis 153 (71) 244 Any pleurodesis 181 (84) 393 pneumothorax, 58% agreed that surgery was appropriate (Fig 3). Those respondents with personal experience with surgical pleurodesis were more likely to favor aggressive management choices, as 33% of this subset said they agreed with the recommendation for surgery for a first pneumothorax (odds ratio, 2.2; confidence interval, 1.1 to 4.3; p 0.017), and 66% agreed for a second pneumothorax (odds ratio, 2.7; confidence interval, 1.5 to 5.0; p 0.0005, data not shown). Furthermore, most respondents (78%) did agree that surgical treatment helps to prevent recurrence of pneumothorax in LAM, while 26% of respondents believed that the risks associated with surgery outweighed the benefits. Discussion The management of pneumothorax in LAM remains problematic for both physicians and patients, with a majority of LAM patients experiencing recurrent pneumothorax. This study was performed to examine LAM patients opinions and their reactions to various treatment options. The results of this survey demonstrate important differences between the evolving approach of LAM physicians in favor of early aggressive pleurodesis and the overall preferences of LAM patients for a more conservative approach. Although the respondents had rather extensive experience with pneumothorax and management options, most still preferred conservative treat- 1270 Original Research

Figure 2. LAM patients favored conservative management of pneumothorax. Only those LAM patients who had a history of pneumothorax were asked the following hypothetical question: What do you think is the most appropriate treatment for a first (or second) pneumothorax in a patient with LAM? Respondents were asked to select from the management options listed. See Figure 1 legend for expansion of abbreviation. ment for the first pneumothorax (observation, needle aspiration, or chest tube drainage), as opposed to prevention of recurrence with pleurodesis. In 2001, the American College of Chest Physicians (ACCP) published a Delphi consensus statement on the management of spontaneous pneumothorax, with guidelines for secondary spontaneous pneumothorax focused on patients with COPD. In this guideline, most members (81%) of the panel recommended an intervention to prevent pneumothorax recurrence after the first occurrence, and the remaining 19% of panel members recommended an intervention to prevent recurrence after the second pneumothorax. Further, the panel stated that the preferred management for pneumothorax recurrence prevention is surgery, with a rating level of very good consensus. 13 The recent report 17 from the LAM Pleural Disease Consensus Group also recommends a pleurodesis procedure for the first pneumothorax in LAM patients. However, the results of our present survey suggest that many LAM patients have different preferences for pneumothorax management. Only 25% of LAM patients believed that pleurodesis was appropriate for a first pneumothorax, while 60% favored pleurodesis for a second pneumothorax. LAM patients agreement with the more specific ACCP recommendation for surgical pleurodesis was equally discordant in this survey. The specific reasons for respondents reluctance to undergo early definitive treatment for pneumothorax with pleurodesis remained unclear in this survey, as most patients did agree that pleurodesis helps prevent pneumothorax recurrence. Patients may have different views about the significance of pneumothorax, as only 41% of respondents subjectively reported that pneumothorax had contributed to a decline in lung function. While it remains unknown whether or not pneumothorax is indeed a direct cause of pulmonary disease progression in LAM, a recent crosssectional study of LAM patients by Cohen et al 18 found that a history of pneumothorax was not associated with reported dyspnea, fatigue, or mean FEV 1. Additionally, LAM patients and physicians may have different views about both the outcomes and the morbidity associated with pleurodesis procedures, and importantly about the potential implications for lung transplantation, an issue that was not directly addressed by this study. Specifically, while formal studies in this area are lacking, the varying views among transplant programs regarding prior pleurodesis and subsequent transplant candidacy are an important consideration for both patients and their physicians. Although this survey was not designed to assess pain management, the patients comments suggest that pain control was inadequate in many cases. Certainly, further efforts on the part of physicians www.chestjournal.org CHEST / 129 / 5/ MAY, 2006 1271

Figure 3. LAM patients disagreed with the recommendation for surgical pleurodesis for a first pneumothorax. Survey participants who had a history of pneumothorax were asked to respond to the following statements: If a LAM patient has a first pneumothorax, I think that she should have surgery to treat the pneumothorax. The statement was then repeated with specification of a second pneumothorax. See Figure 1 legend for expansion of abbreviation. will be necessary to effectively communicate recommendations for pneumothorax management to the patients. Patient involvement in decision making is recognized as an integral component of efforts to improve the quality of health care, and research increasingly supports the concept that involving patients actively in decisions leads to improved outcomes, patient adherence, and satisfaction. 19 21 Although growing evidence exists for patient involvement in cancer screening and treatment and in end-of-life care decisions, 22 25 data on facilitating shared decision making for patients with pulmonary diseases has been more limited. The ACCP Delphi Consensus Statement recommended evaluation of patient s perspectives regarding different treatment options for pneumothorax as a priority for future research. 13 It is logical that a collaborative approach between a physician and patient is particularly critical when faced with difficult pleural disease management decisions, especially when the consequences for subsequent transplantation are considerable. This study was designed to assess patients perceptions of their health care and, as such, provides insights into the opinions of a very large number of LAM patients. The results of this study are most reflective of the perspectives of LAM patients in the United States and Canada but may not fully represent the views and experiences of LAM patients in other parts of the world. For example, almost all of the respondents from outside North America had a history of pneumothorax. As pneumothorax occurrence is similar among North American and international patients in the LAM Foundation database, we speculate that this is a respondent bias based on perceived relevance and subsequent impact on the interest and likelihood of returning the questionnaire. Furthermore, it is possible that those respondents who were satisfied with their treatment may have been less motivated to return the questionnaires, thereby also impacting the data available for analysis. Another important limitation of the survey design of this study was that individual medical records were not reviewed for accuracy of responses, and standardized quality of life or dyspnea test instruments were not administered. It is not known whether these results apply to other patient populations with secondary spontaneous pneumothorax. An additional limitation of this study is that the educational information on pneumothorax frequency, recurrence, and treatment options was provided in text form within the survey. It is anticipated that direct conversations with patients would facilitate better explanation of physician rationale, including emphasis on the likelihood of ongoing morbidity from recurrent pneumothorax, with repeated hospitalizations with closed chest thoracostomies that often do not avoid an eventual pleurodesis procedure. While a range of management options may be discussed, as well as the potential implications for lung transplant candidacy, it would be expected that physicians would advise their patients regarding the most suitable specific therapeutic procedure. Consideration would also be given to the benefits of pleurodesis with respect to reducing the risk of untimely symptomatic unilateral or bilateral pneumothorax, as well as providing some insurance against such life-threatening events, particularly for patients who travel frequently. Indeed many patients may defer to the guidance of a trusted physician in an acute setting, and almost all respondents in this survey reported that they would like more education on pneumothorax and management options. However, the LAM patient community is medically sophisticated both with respect to their personal health care and broader advocacy for LAM research. Therefore, it is interesting that a majority of respondents in this survey, despite eventual personal experience with pleurodesis for recurrent pneumothorax, still preferred a conservative initial approach to pneumothorax. We speculate that inadequate pain control may be a major factor in LAM patients hesitancy to undergo early pleurodesis and recommend that improving the approach to pain control should be a primary objective with respect to the care of LAM patients with pneumothorax. 1272 Original Research

In summary, this study reveals important differences in the views of physicians and LAM patients regarding pneumothorax management. Because of the prevalence of pneumothorax in LAM, LAM is a good model to study pneumothorax in general. With an evolving approach to the management of pleural complications in LAM, it is critically important to work collaboratively with LAM patients in this area to individualize treatment decisions. Better understanding of LAM patients opinions will facilitate shared decision making and the development of patient-centered treatment guidelines that may ultimately improve clinical outcomes with respect to pneumothorax. ACKNOWLEDGMENT: We wish to thank Sue Byrnes, the LAM Foundation staff, and all the patients who are so dedicated to research on LAM. References 1 Sullivan EJ. Lymphangioleiomyomatosis: a review. Chest 1998; 114:1689 1703 2 Franz DN, Brody A, Meyer C, et al. Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med 2001; 164:661 668 3 Moss J, Avila NA, Barnes PM, et al. Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex. Am J Respir Crit Care Med 2001; 164:669 671 4 Costello LC, Hartman TE, Ryu JH. High frequency of pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex. Mayo Clin Proc 2000; 75:591 594 5 Carsillo T, Astrinidis A, Henske EP. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A 2000; 97:6085 6090 6 Kalassian KG, Doyle R, Kao P, et al. Lymphangioleiomyomatosis: new insights. Am J Respir Crit Care Med 1997; 155:1183 1186 7 Urban T, Lazor R, Lacronique J, et al. Pulmonary lymphangioleiomyomatosis: a study of 69 patients. Groupe d Etudes et de Recherche sur les Maladies Orphelines Pulmonaires (GERM O P) Medicine (Baltimore) 1999; 78: 321 337 8 Johnson SR, Tattersfield AE. Clinical experience of lymphangioleiomyomatosis in the UK. Thorax 2000; 55:1052 1057 9 Taylor JR, Ryu J, Colby TV, et al. Lymphangioleiomyomatosis: clinical course in 32 patients. N Engl J Med 1990; 323:1254 1260 10 Almoosa K, Mendez J, Huggins JT, et al. Pneumothorax in lymphangioleiomyomatosis [abstract]. Am J Respir Crit Care Med 2004; 169:A618 11 Boehler A, Speich R, Russi EW, et al. Lung transplantation for lymphangioleiomyomatosis. N Engl J Med 1996; 335: 1275 1280 12 Pechet TT, Meyers BF, Guthrie TJ, et al. Lung transplantation for lymphangioleiomyomatosis. J Heart Lung Transplant 2004; 23:301 308 13 Baumann MH, Strange C, Heffner JE, et al. Management of spontaneous pneumothorax: an American College of Chest Physicians Delphi consensus statement. Chest 2001; 119: 590 602 14 Mendez JL, Nadrous HF, Vassallo R, et al. Pneumothorax in pulmonary Langerhans cell histiocytosis. Chest 2004; 125: 1028 1032 15 Hatz RA, Kaps MF, Meimarakis G, et al. Long-term results after video-assisted thoracoscopic surgery for first-time and recurrent spontaneous pneumothorax. Ann Thorac Surg 2000; 70:253 257 16 Massard G, Thomas P, Wihlm JM. Minimally invasive management for first and recurrent pneumothorax. Ann Thorac Surg 1998; 66:592 599 17 Almoosa KF, Ryu JH, Mendez J, et al. Management of pneumothorax in lymphangioleiomyomatosis: effects on recurrence and lung transplantation. Chest 2006 (in press) 18 Cohen MM, Pollock-Barziv S, Johnson SR. Emerging clinical picture of lymphangioleiomyomatosis. Thorax 2005; 60:875 879 19 Chambers CV, Markson L, Diamond JJ, et al. Health beliefs and compliance with inhaled corticosteroids by asthmatic patients in primary care practices. Respir Med 1999; 93: 88 94 20 Cohen D, Longo MF, Hood K, et al. Resource effects of training general practitioners in risk communication skills and shared decision making competences. J Eval Clin Pract 2004; 10:439 445 21 Heisler M, Vijan S, Anderson RM, et al. When do patients and their physicians agree on diabetes treatment goals and strategies, and what difference does it make? J Gen Intern Med 2003; 18:893 902 22 Cykert S. Risk acceptance and risk aversion: patients perspectives on lung surgery. Thorac Surg Clin 2004; 14:287 293 23 Hirose T, Horichi N, Ohmori T, et al. Patients preferences in chemotherapy for advanced non-small-cell lung cancer. Intern Med 2005; 44:107 113 24 O Connor AM, Drake ER, Fiset V, et al. The Ottawa patient decision aids. Eff Clin Pract 1999; 2:163 170 25 Thompson BT, Cox PN, Antonelli M, et al. Challenges in end-of-life care in the ICU: statement of the 5th International Consensus Conference in Critical Care: Brussels, Belgium, April 2003: executive summary. Crit Care Med 2004; 32: 1781 1784 www.chestjournal.org CHEST / 129 / 5/ MAY, 2006 1273