| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
* From the Department of Radiology (Dr. Hoffman and Mr. Blakewood), University of Iowa Carver College of Medicine, Iowa City, IA; and Department of Biostatistics (Dr. Gaughan) and Division of Pulmonary and Critical Care Medicine (Dr. Criner), Temple University School of Medicine, Philadelphia, PA.
Details of National Emphysema Treatment Trial membership and locations are given in the Appendix.
Correspondence to: Wissam Chatila, MD, FCCP, Associate Professor of Medicine, Temple University School of Medicine, Division of Pulmonary and Critical Care Medicine, 737 PP, 3401 N Broad St, Philadelphia, PA 19140; e-mail: chatilw{at}temple.tuhs.edu
Abstract
Background: Emphysema is the only smoking-related disease in which white patients have higher prevalence and higher attributable mortality rates than African-American patients. Epidemiologic studies have not addressed, nor explained, the observed racial differences in emphysema.
Study objectives: To determine whether white and African-American patients differ with respect to the magnitude, anatomic distribution, and physiologic impairments of emphysema.
Patients: Characteristics of patients with severe and very severe emphysema enrolled in the National Emphysema Treatment Trial were examined and compared. Patient demographics, cardiopulmonary function, quality of life, and severity/distribution of the emphysema by quantitative CT were analyzed.
Results: Of the 1,218 patients enrolled in the trial, 42 were African American (3.4%) and 1,156 were white (95%). African Americans were younger (mean age ± SD, 63 ± 7 years vs 67 ± 6 years) and smoked less (26 ± 14 cigarettes per day vs 32 ± 14 cigarettes per day) than white patients (p = 0.01). There was no difference between the two racial groups in pulmonary function (FEV1, 27 ± 6% predicted vs 27 ± 7% predicted), gas exchange (PaO2, 66 ± 11 mm Hg vs 65 ± 10 mm Hg), and exercise (33 ± 14 W vs 36 ± 21 W), respectively. Quality of life measures were similar between the groups, but African Americans had a lower socioeconomic status, lower education level, and fewer were married. Radiographic analysis of the extent of emphysema in African Americans, who were matched with selected white patients, revealed significantly less emphysema in the former group and different distribution of severe emphysema.
Conclusions: African Americans with emphysema were younger and had a similar degree of lung impairment as the white study population despite smoking less. In a subgroup of matched patients, the severity and distribution of emphysema by quantitative radiographic analysis were different.
Key Words: African American • COPD • CT • emphysema • epidemiology • pulmonary function testing • radiography
The prevalence of COPD is known to be different between African Americans and whites. Murphy et al1 and Massaro et al2 were the first to suggest that COPD is a disease of white men rather than African Americans. Large epidemiologic surveys confirmed that COPD is the only smoking-related disease in which the prevalence and mortality are higher in white patients than African-American patients (prevalence, 6.3% vs 3.9% for chronic bronchitis, 3.5% vs 1% for emphysema,34 and mortality rates of 47/100,000 vs 21/100,000; respectively).4 In addition to smoking, the recent executive summary of the Global Initiative for Chronic Obstructive Lung Disease5 highlights the role of airway hyperresponsiveness and low socioeconomic status as risk factors for the development of COPD. Interestingly, all three factors are more prevalent in African Americans678; paradoxically, COPD is more common in white patients.34 Epidemiologic studies fail to explain whether the observed racial differences are due to genetic differences in susceptibility to smoking; physiologic differences between the races (eg, variability of lung volumes); confounding factors such as differences in smoking behavior (debut, amount, duration); environmental exposure; or to sampling of the patient population. Selection and survivor effects could potentially bias the estimates of COPD prevalence rates in favor of the white population. For example, smaller numbers of African Americans in studies and surveys,4 which may in part be due to increased smoking-related cardiovascular/cancer mortality, could lead to underestimation of their relative risks, thereby contributing to the observed racial gap.
There are no studies that have characterized the severity and nature of chronic obstructive airway diseases, particularly with respect to the presence and magnitude of emphysema in the different racial groups. One possibility is that if white subjects were more susceptible to smoking, they would not only have a higher prevalence of COPD but also more severe COPD, or an earlier presentation than African Americans. This was not found in a retrospective study9 of racial differences in COPD patients being evaluated for surgical intervention; although African Americans were similarly affected, they smoked less, began smoking later in life and, more importantly, presented with symptoms at a younger age than did whites. Moreover, a gender/race meta-analysis by Vollmer and colleagues10 of eight large population-based studies failed to demonstrate a difference in the rate of smoking-related decline in lung function between African-American and white populations.
In this study, we sought to separate the confounding effects of smoking behavior on severity of lung disease in African-American and white patients, and examined the association between race and the extent of emphysema in a specific, well-defined patient population: enrollees of the National Emphysema Treatment Trial (NETT).11 Severity, distribution, and physiologic impact of emphysema were evaluated by a battery of cardiopulmonary function tests, quantitative CT of the chest, and quality of life questionnaires. The results of this study may help in understanding host factors involved in the development of severe emphysema, and may aid in shaping antismoking policies that target African Americans.
Materials and Methods
The NETT is a multicenter, randomized clinical trial of optimal medical therapy vs optimal medical therapy plus lung volume reduction surgery in the treatment of severe emphysema. The design and methods of the NETT have been described previously and are summarized below.11 All analyzed data were obtained from the baseline prerehabilitation assessment during the first or second visit to NETT centers, except for some chest CT scans that were collected after rehabilitation.
Patient Selection
The inclusion criteria were as follows: FEV1 
45% of predicted value, and if age 
70 years, FEV1 15% of predicted; total lung capacity (TLC) 100% of predicted; residual volume (RV) 150% of predicted; PaCO2 60 mm Hg ( 55 mm Hg in Denver), with patients at rest and breathing room air; PaO2 45 mm Hg ( 30 mm Hg in Denver), with patients at rest and breathing room air; ability to walk > 140 m (459 feet) in 6 min; ability to complete 3 min of pedaling on a bicycle ergometer without a load; and abstinence from smoking for 6 months before randomization. Lung function was tested according to the guidelines of the American Thoracic Society. For race adjustment, predicted values of Crapo were used, multiplying by 0.88 for African Americans to correct for their smaller lung volumes.121314 Patients were excluded if they had other medical conditions that made them unsuitable for surgery or prohibited them from follow-up. All patients provided written informed consent, and the study was approved by the institutional review board at each center.
Patient Data
The initial evaluation included 6-min walk distance15; postbronchodilator pulmonary function tests; maximal exercise capacity during cycle ergometry while receiving 30% oxygen; echocardiography; radionuclide pharmacologic (dobutamine) cardiac stress testing; arterial blood gas measurement; and lung perfusion scanning. Patients also responded to a battery of general and disease-specific self- administered quality of life scales16: the Quality of Well-being (QWB) scale, the Short Form-36, St. George’s Respiratory Questionnaire (SGRQ), and the University of California, San Diego Shortness of Breath Questionnaire. Other collected variables included demographics, medications, and smoking habits (type, debut, duration, amount, quit age).
Diagnostic Imaging Studies:
The severity and distribution of emphysema were determined from CT scans of the chest obtained during full inspiration. Spiral CT scans were acquired with a collimation ranging from 3 to 10 mm, with the majority of the centers having a slice collimation 5 mm. Data were evaluated using the standard reconstruction kernel but were not complete for all patients because of early archiving problems, not meeting a set of minimum criteria for matching the prescribed scanning protocol, or missing images from the data sets. Image analysis was done using a custom-built software package (Pulmonary Analysis Software Suite; University of Iowa; Iowa City, IA) after segmenting and dividing the lung according to previously reviewed methods for defining upper, middle, lower, core, and peel regions.17181920
Once segmented, the lung was divided into three equal apical-to-basal regions (upper, middle, lower) and, in the implementation used for this study, the peel consisted of the outer 1.5 cm of lung identified in three-dimensional space. The image voxels within the lung field were then labeled as being emphysema-like based on their reconstructed image gray scale representing the radiograph attenuation coefficient or Hounsfield Unit (HU); the HU of air is – 1,000, of blood is approximately 55, and that of water is 0. Because lung is largely composed of only two densities (air and tissue), the voxel density within the lung field can be translated into a percentage of air and percentage of tissue value.21 The distribution of the number of voxels at each HU within lung fields has been termed the density histogram and is traditionally plotted with number of voxels on the y-axis, with HU values < 950 corresponding to severe emphysema.22 HU values of – 910 and – 850 have approximately corresponded to moderate and mild emphysema regions, respectively.2223242526 In addition to the density histogram, the 
value (the negative slope) from the log-log relationship of hole size vs percentage of holes (with hole membership defined as voxels at – 950 HU, – 910 HU, or – 850 HU) was evaluated in this study because it has been shown also to represent severity of emphysema22 based on the concept that as emphysema progresses, there is a tendency of small holes to mechanically destabilize a lung region, such that small holes merge into larger holes rather than additional small holes accumulating. African-American patients were matched with white patients (1:1) according to gender, height (± 12 cm), age (± 3 years), number of cigarettes smoked per day (± 10 cigarettes), and age started smoking (± 3 years). When more than one match was identified, the match that was closest in age and closest in height was chosen.
Statistical Analysis
Categorical variables were compared using 
2 and Fisher Exact Test. Continuous variables (age, FEV1, TLC, RV) were compared using two-way analysis of variance to evaluate differences between gender and race, and multiple pair-wise comparisons used the Dunn-Bonferroni adjustment to maintain an experiment-wise type I error 0.05. Prior to analysis, continuous data were tested for normality using the Shapiro-Wilk test. If the data for the continuous dependent variables were significantly nonnormal, a "normalized-rank" transformation was applied to the data prior to analysis. If, for a given measure, distribution was not normal, a Wilcoxon rank-sum test was calculated.
Analysis of demographic and pulmonary function variables of the matched patients with their respective quantitative CT variables at different cutoffs (– 950 HU, – 910 HU, – 850 HU) was done using conditional logistic regression to take account of the matching. Means and SDs are presented for all continuous variables. The null hypothesis was that there was no difference in the proportions or measured parameters among race. Differences between group proportions and means (rejection of the null hypothesis) were considered significant if the probability of chance occurrence was < 0.05 using two-tailed tests.
Results
Demographic and Physiologic Racial Differences
Between January 1998 and July 2002, a total of 1,218 patients with severe emphysema were enrolled in the NETT. Forty-two of the patients (3.4%) were African American, and 1,156 patients (95%) were white. The baseline characteristics of these patients are shown in Table 1
. African Americans were younger and less heavy. There was no difference in the severity of the emphysema based on static pulmonary function, gas exchange, exercise performance, and use of steroids. African-American patients in the study had a lower socioeconomic status and a lower level of education, and were less likely to be married (Fig 1
).
|
|
|
|
|
|
CT Distribution and Severity of Emphysema
All 42 African-American patients were matched to white patients, but only 34 of the pairs had complete CT data that permitted extensive quantitative image analysis. No differences were found between the clinical characteristics of the two matched groups (Table 4
). Taking the – 950 HU as cutoff, African-American patients were found to have less severe emphysema based on whole-lung percentage of emphysema (7.0%, p = 0.01) and value (Table 5
); the difference in severity between the two ethnic groups was in both the core and the peel regions (9.2% and 4.6%, respectively; both p < 0.05). In both populations, regions of severe emphysema were more concentrated at the lung apex and lung core. In white patients, the core-peel difference was significantly greater in the lung apex but not at the mid and basilar lung regions than in the African-American patients. In Figure 4
, the frequency distribution of the core-peel percentage of emphysema differences are plotted for the whole lung, lung apex, and lung base. Note that the two frequency distributions for the apical lung are skewed in opposite directions for African-American vs white patients. No differences were noted for mild-to-moderate emphysema regions between the two groups when – 910 HU and – 850 HU were assumed as cutoffs.
|
|
|
Our data show that African-American patients with advanced emphysema presented with impairment comparable to white patients as identified by lung function, exercise, and quality of life measures, and at a younger age despite smoking less. Each gender within the two racial groups was as affected as its counterpart; African-American women were not less severely sick than white women. However, when matched with respect to age, height, smoking, and pulmonary function, African-American patients demonstrated less severe emphysema measured by quantitative CT analysis, especially in the apical lung core, vs white patients. Notably, the enrollment rate of African Americans was much less than that of whites when viewed with respect to prior reports of emphysema prevalence.34
Traditionally, COPD is thought to be a disease of the white population, and the African Americans have been described as "protected" against developing emphysema.27 The prevalence rates of emphysema based on large surveys have consistently revealed a large gap between African Americans and whites. However, as yet the major determinant of the observed difference in prevalence is unclear. Differences in acquired exposures (smoking behavior, environmental exposure, infections, dietary intake), genetic susceptibility, or sampling biases are all possibilities. Few doubt that the answer lies in the complex genotype/environment interactions, but the extent to which each factor plays in the pathogenesis of emphysema is enigmatic. Except for 1-antitrypsin deficiency, no studies have identified other "emphysema genes" that distinguish the remaining 99% patients with emphysema. Studies are starting to unveil some potential genetic markers and risk factors that could be implicated in the pathogenesis of emphysema. Among these are tumor necrosis factor-2829 and matrix metalloproteinase-1 and matrix metalloproteinase-12 polymorphisms.30 Currently, although genetic familial studies are underway, they include few African-American patients.31
Similarly, no studies have addressed the possible role of research artifact and selection bias as contributors to the observed racial differences. Van de Mheen and Gunning-Schepers32 described numerous factors, independent of biological differences, that could account for the significant variability in relative risk of smoking on various smoking-related diseases. Examples of such factors that could contribute to the racial emphysema gap could be related to racial bias in the diagnosis of emphysema, and a higher attrition of African-American patients from nonpulmonary morbidities caused by smoking.4
The reported prevalence of emphysema has been reported to be twofold to threefold higher in white patients than in African-Americans patients,34 but in this study there was a 20 to 1 ratio of white vs African-American patients, consistent with significant underrecruitment of African-American patients. In addition to factors pertaining to patient recruitment and regional or locational sites of treatment, the design of the NETT has probably accentuated the two aforementioned factors because the clinical costs of NETT were paid predominantly by Medicare. It is noteworthy that patients become eligible for Medicare if they are disabled or 65 years old, and that many African Americans in this study were < 65 years old. If African-American patients with emphysema truly tend to present earlier in life than white patients, they would not have been able to enroll in the NETT unless their health insurance companies agreed to pay clinical costs. Moreover, and similar to other large trials,33 patients with significant cardiovascular disease, which is more prevalent in African Americans,4 were excluded.
Socioeconomic status is another aspect that may have a significant confounding effect on the prevalence of emphysema. This aspect is difficult to control for because it entrains access to health care, level of education, environmental exposure, and possibly respiratory infections. Race and socioeconomic status are closely entwined, and patients with lower levels of income often receive substandard care due to lack of insurance, delay in seeking health care, reliance on hospital clinics and emergency departments, and less referrals to specialists. It is also possible that African Americans with emphysema are underdiagnosed because they are perceived to be "protected" and their symptoms are attributed to other illnesses, including asthma and heart disease. In a national survey, the prevalence of COPD (by history) was found to increase with age in white subjects but not in African Americans, although the age-specific percentage of African Americans having obstructive lung disease by spirometry (FEV1/FVC ratio < 70 and FEV1 < 80% of predicted) was actually similar or higher compared to whites.3 Although no studies are available on racial bias in diagnosing COPD, this tendency has been observed in women,34 a population that was thought to be less susceptible to injury from smoking. The aforementioned observations suggest that COPD/emphysema may be underdiagnosed in African Americans.
Are African Americans less susceptible to pulmonary damage from cigarette smoking than whites, and do they have a different emphysema phenotype despite comparable physiology and impairment? Although prevalence data might suggest a racial discrepancy in susceptibility, this study and a previous report9 from our clinic indicate that there is a group of African-American patients who are as susceptible to emphysema, if not more so, than white patients possibly because of their younger age and lower smoking burden at presentation. Moreover, the meta-analysis performed by Vollmer and colleagues10 in gender/race strata of eight large population-based studies failed to demonstrate a difference in smoking-related decrements in lung function between African-Americans and white patients (excess FEV1 decline attributed to smoking > 10 cigarettes per day, – 7 ± 1.2 mL/yr vs – 10 ± 1.0 mL/yr; p > 0.05) arguing against major differences in susceptibility. Nevertheless, since African Americans may present earlier in life with severe emphysema, one may postulate that the disease burden or phenotypic expression of emphysema are different between the two races. The percentage difference in emphysema severity and distribution between the two groups, based on quantitative CT analysis (Table 5, Fig 4), suggests some variability in lung response to injury caused by smoking, and thus supports the notion of differences in phenotypic expression and burden of disease. To date, no studies have explored racial differences in airway response to cigarette smoking; however, it is noteworthy that African Americans have been shown to have a slower oxidative metabolism of nicotine than whites.3536 Investigations373839 pertaining to variability in inflammatory response between various racial groups started to emerge in an attempt to explain susceptibility and heterogeneity of certain inflammatory conditions.
Despite the multicenter nature of the NETT, this study is still limited because of the homogeneity of enrolled patients and the small number of African Americans, which raises the possibility that sampling bias and referral patterns may have influenced the results. Another limitation of the study is the lack of extensive environmental data, the unavailability of description of the cigarette product, and the inherent limitation of questionnaires to fully characterize the smoking behavior. In addition, outcome was not compared between the two racial groups. However, our goal was neither to establish higher susceptibility of one patient group vs another, nor to examine outcome. First, outcome has been already reported, and race was not found to be a significant factor40; second, the proportion of African Americans will need to be much higher in order to resolve issues pertaining to race and other environmental factors as potential modifiers of emphysema risk and outcome.
Although the study does not resolve the question of susceptibility, it is the first to extensively characterize African-American and white patients with respect to the most important risk factor, smoking. While it was not surprising to find physiologic and functional similarities between the two races, the fact that African-American patients were younger and smoked less than their white counterparts was not expected. Moreover, African-American patients exhibited a phenotypically different disease pattern based on CT imaging than did demographically matched white patients. Further investigation is needed to determine the factors important in inciting, and then modifying the different patterns of emphysema expressed by the two races.
Appendix
NETT Credit Roster
Source of Funding
The NETT is supported by contracts with the National Heart, Lung, and Blood Institute (N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, and N01HR76119), the Centers for Medicare and Medicaid Services (formerly the Health Care Financing Administration); and the Agency for Healthcare Research and Quality.
Office of the Chair of the Steering Committee
University of Pennsylvania, Philadelphia, PA: Alfred P. Fishman, MD (Chair); Betsy Ann Bozzarello; Ameena Al-Amin.
Clinical Centers
Baylor College of Medicine, Houston, TX:
Marcia Katz, MD (Principal Investigator); Carolyn Wheeler, RN, BSN (Principal Clinic Coordinator); Elaine Baker, RRT, RPFT; Peter Barnard, PhD, RPFT; Phil Cagle, MD; James Carter, MD; Sophia Chatziioannou, MD; Karla Conejo-Gonzales; Kimberly Dubose, RRT; John Haddad, MD; David Hicks, RRT, RPFT; Neal Kleiman, MD; Mary Milburn-Barnes, CRTT; Chinh Nguyen, RPFT; Michael Reardon, MD; Joseph Reeves-Viets, MD; Steven Sax, MD; Amir Sharafkhaneh, MD; Owen Wilson, PhD; Christine Young PT; Rafael Espada, MD (Principal Investigator 1996–2002); Rose Butanda (1999–2001); Minnie Ellisor (2002); Pamela Fox, MD (1999–2001); Katherine Hale, MD (1998–2000); Everett Hood, RPFT (1998–2000); Amy Jahn (1998–2000); Satish Jhingran, MD (1998–2001); Karen King, RPFT (1998–1999); Charles Miller III, PhD (1996–1999); Imran Nizami, MD (Co-Principal Investigator, 2000–2001); Todd Officer (1998–2000); Jeannie Ricketts (1998–2000); Joe Rodarte, MD (Co-Principal Investigator 1996–2000); Robert Teague, MD (Co-Principal Investigator 1999–2000); Kedren Williams (1998–1999).
Brigham and Women’s Hospital, Boston, MA:
John Reilly, MD (Principal Investigator); David Sugarbaker, MD (Co-Principal Investigator); Carol Fanning, RRT (Principal Clinic Coordinator); Simon Body, MD; Sabine Duffy, MD; Vladmir Formanek, MD; Anne Fuhlbrigge, MD; Philip Hartigan, MD; Sarah Hooper, EP; Andetta Hunsaker, MD; Francine Jacobson, MD; Marilyn Moy, MD; Susan Peterson, RRT; Roger Russell, MD; Diane Saunders; Scott Swanson, MD (Co-Principal Investigator, 1996–2001).
Cedars-Sinai Medical Center, Los Angeles, CA:
Rob McKenna, MD (Principal Investigator); Zab Mohsenifar, MD (Co-Principal Investigator); Carol Geaga, RN (Principal Clinic Coordinator); Manmohan Biring, MD; Susan Clark, RN, MN; Jennifer Cutler, MD; Robert Frantz, MD; Peter Julien, MD; Michael Lewis, MD; Jennifer Minkoff-Rau, MSW; Valentina Yegyan, BS, CPFT; Milton Joyner, BA (1996–2002).
Cleveland Clinic Foundation, Cleveland, OH:
Malcolm DeCamp, MD (Principal Investigator); James Stoller, MD (Co-Principal Investigator); Yvonne Meli, RN, (Principal Clinic Coordinator); John Apostolakis, MD; Darryl Atwell, MD; Jeffrey Chapman, MD; Pierre DeVilliers, MD; Raed Dweik, MD; Erik Kraenzler, MD; Rosemary Lann, LISW; Nancy Kurokawa, RRT, CPFT; Scott Marlow, RRT; Kevin McCarthy, RCPT; Pricilla McCreight, RRT, CPFT; Atul Mehta, MD; Moulay Meziane, MD; Omar Minai, MD; Mindi Steiger, RRT; Kenneth White, RPFT; Janet Maurer, MD (Principal Investigator, 1996–2001); Terri Durr, RN (2000–2001); Charles Hearn, DO (1998–2001); Susan Lubell, PA-C (1999–2000); Peter O’Donovan, MD (1998–2003); Robert Schilz, DO (1998–2002).
Columbia University, New York, NY in Consortium With Long Island Jewish Medical Center, New Hyde Park, NY:
Mark Ginsburg, MD (Principal Investigator); Byron Thomashow, MD (Co-Principal Investigator); Patricia Jellen, MSN, RN (Principal Clinic Coordinator); John Austin, MD; Matthew Bartels, MD; Yahya Berkmen, MD; Patricia Berkoski, MS, RRT (Site coordinator, LIJ); Frances Brogan, MSN, RN; Amy Chong, BS, CRT; Glenda DeMercado, BSN; Angela DiMango, MD; Sandy Do, MS, PT; Bessie Kachulis, MD; Arfa Khan, MD; Berend Mets, MD; Mitchell O’Shea, BS, RT, CPFT; Gregory Pearson, MD; Leonard Rossoff, MD; Steven Scharf, MD, PhD (Co-Principal Investigator, 1998–2002); Maria Shiau, MD; Paul Simonelli, MD; Kim Stavrolakes, MS, PT; Donna Tsang, BS; Denise Vilotijevic, MS, PT; Chun Yip, MD; Mike Mantinaos, MD (1998–2001); Kerri McKeon, BS, RRT, RN (1998–1999); Jacqueline Pfeffer, MPH, PT (1997–2002).
Duke University Medical Center, Durham, NC:
Neil MacIntyre, MD (Principal Investigator); R. Duane Davis, MD (Co-Principal Investigator); John Howe, RN (Principal Clinic Coordinator); R. Edward Coleman, MD; Rebecca Crouch, RPT; Dora Greene; Katherine Grichnik, MD; David Harpole, Jr, MD; Abby Krichman, RRT; Brian Lawlor, RRT; Holman McAdams, MD; John Plankeel, MD; Susan Rinaldo-Gallo, MED; Sheila Shearer, RRT; Jeanne Smith, ACSW; Mark Stafford-Smith, MD; Victor Tapson, MD; Mark Steele, MD (1998–1999); Jennifer Norten, MD (1998–1999).
Mayo Foundation, Rochester, MN:
James Utz, MD (Principal Investigator); Claude Deschamps, MD (Co-Principal Investigator); Kathy Mieras, CCRP (Principal Clinic Coordinator); Martin Abel, MD; Mark Allen, MD; Deb Andrist, RN; Gregory Aughenbaugh, MD; Sharon Bendel, RN; Eric Edell, MD; Marlene Edgar; Bonnie Edwards; Beth Elliot, MD; James Garrett, RRT; Delmar Gillespie, MD; Judd Gurney, MD; Boleyn Hammel; Karen Hanson, RRT; Lori Hanson, RRT; Gordon Harms, MD; June Hart; Thomas Hartman, MD; Robert Hyatt, MD; Eric Jensen, MD; Nicole Jenson, RRT; Sanjay Kalra, MD; Philip Karsell, MD; Jennifer Lamb; David Midthun, MD; Carl Mottram, RRT; Stephen Swensen, MD; Anne-Marie Sykes, MD; Karen Taylor; Norman Torres, MD; Rolf Hubmayr, MD (1998–2000); Daniel Miller, MD (1999–2002); Sara Bartling, RN (1998–2000); Kris Bradt (1998–2002).
National Jewish Medical and Research Center, Denver, CO:
Barry Make, MD (Principal Investigator); Marvin Pomerantz, MD (Co-Principal Investigator); Mary Gilmartin, RN, RRT (Principal Clinic Coordinator); Joyce Canterbury; Martin Carlos; Phyllis Dibbern, PT; Enrique Fernandez, MD; Lisa Geyman, MSPT; Connie Hudson; David Lynch, MD; John Newell, MD; Robert Quaife, MD; Jennifer Propst, RN; Cynthia Raymond, MS; Jane Whalen-Price, PT; Kathy Winner, OTR; Martin Zamora, MD; Reuben Cherniack, MD (Principal Investigator, 1997–2000).
Ohio State University, Columbus, OH:
Philip Diaz, MD (Principal Investigator); Patrick Ross, MD (Co-Principal Investigator); Tina Bees (Principal Clinic Coordinator); Jan Drake; Charles Emery, PhD; Mark Gerhardt, MD, PhD; Mark King, MD; David Rittinger; Mahasti Rittinger.
Saint Louis University, St. Louis, MO:
Keith Naunheim, MD (Principal Investigator); Robert Gerber, MD (Co-Principal Investigator); Joan Osterloh, RN, MSN (Principal Clinic Coordinator); Susan Borosh; Willard Chamberlain, DO; Sally Frese; Alan Hibbit; Mary Ellen Kleinhenz, MD; Gregg Ruppel; Cary Stolar, MD; Janice Willey; Francisco Alvarez, MD (Co-Principal Investigator, 1999–2002); Cesar Keller, MD (Co-Principal Investigator, 1996–2000).
Temple University, Philadelphia, PA:
Gerard Criner, MD (Principal Investigator); Satoshi Furukawa, MD (Co-Principal Investigator); Anne Marie Kuzma, RN, MSN (Principal Clinic Coordinator); Roger Barnette, MD; Neil Brister, MD; Kevin Carney, RN, CCTC; Wissam Chatila, MD; Francis Cordova, MD; Gilbert D’Alonzo, DO; Michael Keresztury, MD; Karen Kirsch; Chul Kwak, MD; Kathy Lautensack, RN, BSN; Madelina Lorenzon, CPFT; Ubaldo Martin, MD; Peter Rising, MS; Scott Schartel, MD; John Travaline, MD; Gwendolyn Vance, RN, CCTC; Phillip Boiselle, MD (1997–2000); Gerald O’Brien, MD (1997–2000).
University of California, San Diego, San Diego, CA:
Andrew Ries, MD, MPH (Principal Investigator); Robert Kaplan, PhD (Co-Principal Investigator); Catherine Ramirez, BS, RCP (Principal Clinic Coordinator); David Frankville, MD; Paul Friedman, MD; James Harrell, MD; Jeffery Johnson; David Kapelanski, MD; David Kupferberg, MD, MPH; Catherine Larsen, MPH; Trina Limberg, RRT; Michael Magliocca, RN, CNP; Frank J. Papatheofanis, MD, PhD; Dawn Sassi-Dambron, RN; Melissa Weeks.
University of Maryland at Baltimore, Baltimore, MD in consortium with Johns Hopkins Hospital, Baltimore, MD:
Mark Krasna, MD (Principal Investigator); Henry Fessler, MD (Co-Principal Investigator); Iris Moskowitz (Principal Clinic Coordinator); Timothy Gilbert, MD; Jonathan Orens, MD; Steven Scharf, MD, PhD; David Shade; Stanley Siegelman, MD; Kenneth Silver, MD; Clarence Weir; Charles White, MD.
University of Michigan, Ann Arbor, MI:
Fernando Martinez, MD (Principal Investigator); Mark Iannettoni, MD (Co-Principal Investigator); Catherine Meldrum, BSN, RN, CCRN (Principal Clinic Coordinator); William Bria, MD; Kelly Campbell; Paul Christensen, MD; Kevin Flaherty, MD; Steven Gay, MD; Paramjit Gill, RN; Paul Kazanjian, MD; Ella Kazerooni, MD; Vivian Knieper; Tammy Ojo, MD; Lewis Poole; Leslie Quint, MD; Paul Rysso; Thomas Sisson, MD; Mercedes True; Brian Woodcock, MD; Lori Zaremba, RN.
University of Pennsylvania, Philadelphia, PA:
Larry Kaiser, MD (Principal Investigator); John Hansen-Flaschen, MD (Co-Principal Investigator); Mary Louise Dempsey, BSN, RN (Principal Clinic Coordinator); Abass Alavi, MD; Theresa Alcorn, Selim Arcasoy, MD; Judith Aronchick, MD; Stanley Aukberg, MD; Bryan Benedict, RRT; Susan Craemer, BS, RRT, CPFT; Ron Daniele, MD; Jeffrey Edelman, MD; Warren Gefter, MD; Laura Kotler-Klein, MSS; Robert Kotloff, MD; David Lipson, MD; Wallace Miller, Jr, MD; Richard O’Connell, RPFT; Staci Opelman, MSW; Harold Palevsky, MD; William Russell, RPFT; Heather Sheaffer, MSW; Rodney Simcox, BSRT, RRT; Susanne Snedeker, RRT, CPFT; Jennifer Stone-Wynne, MSW; Gregory Tino, MD; Peter Wahl; James Walter, RPFT; Patricia Ward; David Zisman, MD; James Mendez, MSN, CRNP (1997–2001); Angela Wurster, MSN, CRNP (1997–1999).
University of Pittsburgh, Pittsburgh, PA:
Frank Sciurba, MD (Principal Investigator); James Luketich, MD (Co-Principal Investigator); Colleen Witt, MS (Principal Clinic Coordinator); Gerald Ayres; Michael Donahoe, MD; Carl Fuhrman, MD; Robert Hoffman, MD; Joan Lacomis, MD; Joan Sexton; William Slivka; Diane Strollo, MD; Erin Sullivan, MD; Tomeka Simon; Catherine Wrona, RN, BSN; Gerene Bauldoff, RN, MSN (1997–2000); Manuel Brown, MD (1997–2002); Elisabeth George, RN, MSN (Principal Clinic Coordinator 1997–2001); Robert Keenan, MD (Co-Principal Investigator 1997–2000); Theodore Kopp, MS (1997–1999); Laurie Silfies (1997–2001).
University of Washington, Seattle, WA:
Joshua Benditt, MD (Principal Investigator), Douglas Wood, MD (Co-Principal Investigator); Margaret Snyder, MN (Principal Clinic Coordinator); Kymberley Anable; Nancy Battaglia; Louie Boitano; Andrew Bowdle, MD; Leighton Chan, MD; Cindy Chwalik; Bruce Culver, MD; Thurman Gillespy, MD; David Godwin, MD; Jeanne Hoffman; Andra Ibrahim, MD; Diane Lockhart; Stephen Marglin, MD; Kenneth Martay, MD; Patricia McDowell; Donald Oxorn, MD; Liz Roessler; Michelle Toshima; Susan Golden (1998–2000).
Agency for Healthcare Research and Quality, Rockville, MD:
Lynn Bosco, MD, MPH; Yen-Pin Chiang, PhD; Carolyn Clancy, MD; Harry Handelsman, DO.
Centers for Medicare and Medicaid Services, Baltimore, MD:
Steven M Berkowitz, PhD; Tanisha Carino, PhD; Joe Chin, MD; JoAnna Baldwin; Karen McVearry; Anthony Norris; Sarah Shirey; Claudette Sikora; Steven Sheingold, PhD (1997–2004).
Coordinating Center, The Johns Hopkins University, Baltimore, MD:
Steven Piantadosi, MD, PhD (Principal Investigator); James Tonascia, PhD (Co-Principal Investigator); Patricia Belt; Amanda Blackford, ScM; Karen Collins; Betty Collison; Ryan Colvin, MPH; John Dodge; Michele Donithan, MHS; Vera Edmonds; Gregory L. Foster, MA; Julie Fuller; Judith Harle; Rosetta Jackson; Shing Lee, ScM; Charlene Levine; Hope Livingston; Jill Meinert; Jennifer Meyers; Deborah Nowakowski; Kapreena Owens; Shangqian Qi, MD; Michael Smith; Brett Simon, MD; Paul Smith; Alice Sternberg, ScM; Mark Van Natta, MHS; Laura Wilson, ScM; Robert Wise, MD.
Cost-effectiveness Subcommittee:
Robert M. Kaplan, PhD (Chair); J. Sanford Schwartz, MD (Co-Chair); Yen-Pin Chiang, PhD; Marianne C. Fahs, PhD; A. Mark Fendrick, MD; Alan J. Moskowitz, MD; Dev Pathak, PhD; Scott Ramsey, MD, PhD; Steven Sheingold, PhD; A. Laurie Shroyer, PhD; Judith Wagner, PhD; Roger Yusen, MD.
Cost-effectiveness Data Center, Fred Hutchinson Cancer Research Center, Seattle, WA:
Scott Ramsey, MD, PhD (Principal Investigator); Ruth Etzioni, PhD; Sean Sullivan, PhD; Douglas Wood, MD; Thomas Schroeder, MA; Karma Kreizenbeck; Kristin Berry, MS; Nadia Howlader, MS.
CT Scan Image Storage and Analysis Center, University of Iowa, Iowa City, IA:
Eric Hoffman, PhD (Principal Investigator); Janice Cook-Granroth, BS; Angela Delsing, RT; Junfeng Guo, PhD; Geoffrey McLennan, MD; Brian Mullan, MD; Chris Piker, BS; Joseph Reinhardt, PhD; Blake Robinswood; Jered Sieren, RTR; William Stanford, MD.
Data and Safety Monitoring Board:
John A. Waldhausen, MD (Chair); Gordon Bernard, MD; David DeMets, PhD; Mark Ferguson, MD; Eddie Hoover, MD; Robert Levine, MD; Donald Mahler, MD; A. John McSweeny, PhD; Jeanine Wiener-Kronish, MD; O. Dale Williams, PhD; Magdy Younes, MD.
Marketing Center, Temple University, Philadelphia, PA:
Gerard Criner, MD (Principal Investigator); Charles Soltoff, MBA.
Project Office, National Heart, Lung, and Blood Institute, Bethesda, MD:
Gail Weinmann, MD (Project Officer); Joanne Deshler (Contracting Officer); Dean Follmann, PhD; James Kiley, PhD; Margaret Wu, PhD (1996–2001).
Other Acknowledgments:
Arthur Gelb, MD, Lakewood Regional Medical Center, Lakewood, CA.
Footnotes
Abbreviations: HU = Hounsfield unit; NETT = National Emphysema Treatment Trial; QWB = Quality of Well-being; RV = residual volume; SGRQ = St. George’s Respiratory Questionnaire; TLC = total lung capacity
Dr. Hoffman is a shareholder of VIDA Diagnostics, which seeks to commercialize the software that may be relevant to this article.
Received for publication December 6, 2005. Accepted for publication January 2, 2006.
References
1-antitrypsin deficiency and smokers with emphysema. Acta Radiol 2004;45,424-430[CrossRef][ISI][Medline] gene polymorphism in chronic bronchitis. Am J Respir Crit Care Med 1997;156,1436-1439 gene promoter polymorphism with the presence of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;163,420-422
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
