Abstract
Exercise capacity (EC) is a critical outcome in chronic obstructive lung disease (chronic obstructive pulmonary disease (COPD)). It measures the impact of the disease and the effect of specific interventions like pulmonary rehabilitation (PR). EC determines COPD prognosis and is associated with health-care utilization and quality of life. Field walking tests and cardiopulmonary exercise test (CPET) are two ways to measure EC. The 6-minute walking test (6MWT) is the commonest and easiest field test. CPET has the advantage of assessing maximal aerobic capacity. Determinants of EC include age, gender, breathlessness, and lung function. Previous research suggests that socioeconomic status (SES), a meaningful factor in COPD, may also be associated with EC. However, those findings have not been replicated. We aimed to determine whether SES is an independent factor associated with EC in COPD. For this analysis, we used the National Emphysema Treatment Trial (NETT) database. NETT was a multicenter clinical trial where severe COPD patients were randomized to lung volume reduction surgery or medical therapy. Measures used were taken at baseline, postrehabilitation. Patients self-reported their income and were divided in two groups whether it was less or above US$30,000. Patients with a lower income had worse results in 6MWT (
Keywords
Introduction
Exercise capacity (EC) is a critical outcome in chronic obstructive lung disease (chronic obstructive pulmonary disease (COPD)). 1 It measures the impact of the disease and tests the effect of specific interventions. 1 –3 EC determines COPD prognosis due to its relation with hospitalizations for exacerbations and all-cause mortality. 4,5 Importantly, from a patient-centered focus, it is related to health-care utilization, quality of life (QoL), and symptoms. 3
Field walking tests and cardiopulmonary exercise test (CPET) are two ways to measure EC. Among those, the 6-minute walking test (6MWT) is the commonest and easiest. 1,2,6 CPET has the advantage of assessing maximal aerobic capacity and contributes better to the differential diagnosis. 7 EC determinants are many, 6,8 including age, breathlessness, and lung function.
Socioeconomic status (SES), a meaningful factor in COPD related to QoL, 9 physical activity, 10 completion of pulmonary rehabilitation (PR), and all-cause mortality, 11 may also predict EC. Recent data show that SES also influences EC, with lower income patients having poorer results 12 ; however, that finding has never been replicated.
Our aim is to determine whether income is an independent factor associated with EC in COPD, which would raise its importance as a meaningful factor to be assessed.
Methods
The present analysis used the National Emphysema Treatment Trial (NETT) database. 13 This multicenter trial randomized severe COPD patients with no significant comorbidities to lung volume reduction surgery or medical therapy, after 6–10-week PR. 13,14 Smoking cessation, biochemically validated, was required at least 6 months before randomization. Patients were divided in two groups whether their annual reported income was less or above US$30,000, a limit chosen following data of US census bureau and Pew Research center. 15,16
EC was measured by the 6MWT and maximal watts during CPET, following the American Thoracic Society Guidelines (ATS). 6,17 Pulmonary function tests followed ATS. 18,19
Statistical analyses, associations between income and categorical variables, were tested between income groups using χ2tests. Associations between income level and continuous variables were tested between groups using Wilcoxon tests. The association between income and 6MWT as well as income and CPET was explored using linear models adjusted for marital status, loneliness, age, gender, FEV1% predicted, modified medical research council scale (MMRC), smoking pack years, and education. All analyses were tested with 5% type I error rates with no adjustments for multiple testing. Analyses were carried out using SAS version 9.4.
Results
In total, 1218 patients completed PR and were analyzed using baseline data. Table 1 shows population’s characteristics and Tables 2 and 3 show the models designed to determine the independent association between income and EC.
Characteristics of all 1206 patients at baselinea.
a Base-line measurements were obtained after rehabilitation but before randomization.
bLoneliness was measured by asking subjects “Do you feel lonely or socially isolated now or in the last 3 days?” An answer was either “yes” or “no.” 20
c Maximum load (watts) was chosen to measure exercise capacity during CPET.
d The follow-up period was 2 years.
Income as a determinant of 6MWT, adjusted for age, sex, Post FEV1% predicted, MMRC, loneliness, married status, smoking pack years, and education beyond high school.
DF: degrees of freedom; Pr > |
aLoneliness and isolation was measured by asking subjects “Do you feel lonely or socially isolated now or in the last 3 days?” An answer was either “yes” or “no.” 20
bEducation was determined by dividing patients into two groups: those who had education levels beyond high school and those who did not.
Income as a determinant of watts in CPET, adjusted for age, sex, Post FEV1% predicted, mMRC, loneliness, married status, smoking pack years and education beyond high school.
DF: degrees of freedom; Pr > |
aLoneliness and isolation was measured by asking subjects “Do you feel lonely or socially isolated now or in the last 3 days?”. An answer was either “yes” or “no.” 20
bEducation was determined by dividing patients into two groups: those who had education levels beyond high school and those who did not.
The association between 6MWT and income (Table 2) remained significant after adjusting for meaningful confounders such as sex, age, Post BD FEV1% predicted, MMRC, marriage, loneliness, smoking pack years, and education beyond high school (yes or no). We also found a significant association between income and maximal load in watts on CPET (Table 3) validating the 6MWT results. In addition, our results showed individuals with low income found themselves lonelier (Tables 1 and 2).
Discussion
We found that low income is associated with worse results in the 6MWT after adjusting for meaningful confounders. The latter was further validated using another measure of EC: watts in CPET. Our findings confirm and extend a previous report 12 but in a larger and more characterized cohort of severe COPD, using two different EC measures.
Given the 6MWT’s prognostic significance, 4 –6 our findings are important because usually income is not taken into account in COPD evaluation, despite being a factor that is easily obtainable, and conveys information about patients’ overall social condition. Plausible explanations for our results might include that financial constrains may limit patients’ access to programs like PR, as stated by previous publications. 21 –23 The fact of finding low-income participants more lonely suggests another social, yet critical repercussion of low income. Loneliness is independently related to poorer outcomes and higher health-care utilization in COPD (article in press).
Limitations
Given that NETT selected severe emphysema COPD patients without significant comorbidities, our results may limit generalizability.
Conclusions
In severe COPD patients, low income is independently associated with EC. Our results may be of importance to fully assess patients with severe COPD addressing social determinants of health.
Footnotes
Authors’ note
Complete list of the NETT Research Group members: Members of the NETT Research Group are as follows: Office of the Chair of the Steering Committee, University of Pennsylvania, Philadelphia, PA: Alfred P. Fishman, M.D. (Chair); Betsy Ann Bozzarello; Ameena Al-Amin. Clinical centers: Baylor College of Medicine, Houston, TX: Marcia Katz, M.D. (Principal Investigator); Carolyn Wheeler, R.N., B.S.N. (Principal Clinic Coordinator); Elaine Baker, R.R.T., R.P.F.T.; Peter Barnard, PhD, R.P.F.T.; Phil Cagle, M.D.; James Carter, M.D.; Sophia Chatziioannou, M.D.; Karla Conejo-Gonzales; Kimberly Dubose, R.R.T.; John Haddad, M.D.; David Hicks, R.R.T., R.P.F.T.; Neal Kleiman, M.D.; Mary Milburn-Barnes, C.R.T.T.; Chinh Nguyen, R.P.F.T.; Michael Reardon, M.D.; Joseph Reeves-Viets, M.D.; Steven Sax, M.D.; Amir Sharafkhaneh, M.D.; Owen Wilson, PhD; Christine Young, P.T.; Rafael Espada, M.D. (Principal Investigator 1996–2002); Rose Butanda (1999–2001); Minnie Ellisor (2002); Pamela Fox, M.D. (1999–2001); Katherine Hale, M.D. (1998–2000); Everett Hood, R.P.F.T. (1998–2000); Amy Jahn (1998–2000); Satish Jhingran, M.D. (1998–2001); Karen King, R.P.F.T. (1998–1999); Charles Miller III, PhD (1996–1999); Imran Nizami, M.D. (Co-Principal Investigator, 2000–2001); Todd Officer (1998–2000); Jeannie Ricketts (1998–2000); Joe Rodarte, M.D. (Co-Principal Investigator 1996–2000); Robert Teague, M.D. (Co-Principal Investigator 1999–2000); Kedren Williams (1998–1999). Brigham and Women’s Hospital, Boston, MA: John Reilly, M.D. (Principal Investigator); David Sugarbaker, M.D. (CoPrincipal Investigator); Carol Fanning, R.R.T. (Principal Clinic Coordinator); Simon Body, M.D.; Sabine Duffy, M.D.; Vladmir Formanek, M.D.; Anne Fuhlbrigge, M.D.; Philip Hartigan, M.D.; Sarah Hooper, E.P.; Andetta Hunsaker, M.D.; Francine Jacobson, M.D.; Marilyn Moy, M.D.; Susan Peterson, R.R.T.; Roger Russell, M.D.; Diane Saunders; Scott Swanson, M.D. (Co-Principal Investigator, 1996–2001). Cedars-Sinai Medical Center, Los Angeles, CA: Rob McKenna, M.D. (Principal Investigator); Zab Mohsenifar, M.D. (Co-Principal Investigator); Carol Geaga, R.N. (Principal Clinic Coordinator); Manmohan Biring, M.D.; Susan Clark, R.N., M.N.; Jennifer Cutler, M.D.; Robert Frantz, M.D.; Peter Julien, M.D.; Michael Lewis, M.D.; Jennifer Minkoff-Rau, M.S.W.; Valentina Yegyan, B.S., C.P.F.T.; Milton Joyner, B.A. (1996–2002). Cleveland Clinic Foundation, Cleveland, OH: Malcolm DeCamp, M.D. (Principal Investigator); James Stoller, M.D. (Co-Principal Investigator); Yvonne Meli, R.N., (Principal Clinic Coordinator); John Apostolakis, M.D.; Darryl Atwell, M.D.; Jeffrey Chapman, M.D.; Pierre DeVilliers, M.D.; Raed Dweik, M.D.; Erik Kraenzler, M.D.; Rosemary Lann, L.I.S.W.; Nancy Kurokawa, R.R.T., C.P.F.T.; Scott Marlow, R.R.T.; Kevin McCarthy, R.C.P.T.; Priscilla McCreight, R.R.T., C.P.F.T.; Atul Mehta, M.D.; Moulay Meziane, M.D.; Omar Minai, M.D.; Mindi Steiger, R.R.T.; Kenneth White, R.P.F.T.; Janet Maurer, M.D. (Principal Investigator, 1996–2001); Terri Durr, R.N. (2000–2001); Charles Hearn, D.O. (1998–2001); Susan Lubell, P.A.-C. (1999–2000); Peter O’Donovan, M.D. (1998–2003); Robert Schilz, D.O. (1998–2002). Columbia University, New York, NY in consortium with Long Island Jewish Medical Center, New Hyde Park, NY; Mark Ginsburg, M.D. (Principal Investigator); Byron Thomashow, M.D. (Co-Principal Investigator); Patricia Jellen, M.S.N., R.N. (Principal Clinic Coordinator); John Austin, M.D.; Matthew Bartels, M.D.; Yahya Berkmen, M.D.; Patricia Berkoski, M.S., R.R.T. (Site coordinator, LIJ); Frances Brogan, M.S.N., R.N.; Amy Chong, B.S., C.R.T.; Glenda DeMercado, B.S.N.; Angela DiMango, M.D.; Sandy Do, M.S., P.T.; Bessie Kachulis, M.D.; Arfa Khan, M.D.; Berend Mets, M.D.; Mitchell O’Shea, B.S., R.T., C.P.F.T.; Gregory Pearson, M.D.; Leonard Rossoff, M.D.; Steven Scharf, M.D., PhD (Co-Principal Investigator, 1998–2002); Maria Shiau, M.D.; Paul Simonelli, M.D.; Kim Stavrolakes, M.S., P.T.; Donna Tsang, B.S.; Denise Vilotijevic, M.S., P.T.; Chun Yip, M.D.; Mike Mantinaos, M.D. (1998–2001); Kerri McKeon, B.S., R.R.T., R.N. (1998–1999); Jacqueline Pfeffer, M.P.H., P.T. (1997–2002). Duke University Medical Center, Durham, NC: Neil MacIntyre, M.D. (Principal Investigator); R. Duane Davis, M.D. (Co-Principal Investigator); John Howe, R.N. (Principal Clinic Coordinator); R. Edward Coleman, M.D.; Rebecca Crouch, R.P.T.; Dora Greene; Katherine Grichnik, M.D.; David Harpole, Jr, M.D.; Abby Krichman, R.R.T.; Brian Lawlor, R.R.T.; Holman McAdams, M.D.; John Plankeel, M.D.; Susan Rinaldo-Gallo, M.E.D.; Sheila Shearer, R.R.T.; Jeanne Smith, A.C.S.W.; Mark Stafford-Smith, M.D.; Victor Tapson, M.D.; Mark Steele, M.D. (1998–1999); Jennifer Norten, M.D. (1998–1999). Mayo Foundation, Rochester, MN: James Utz, M.D. (Principal Investigator); Claude Deschamps, M.D. (Co-Principal Investigator); Kathy Mieras, C.C.R.P. (Principal Clinic Coordinator); Martin Abel, M.D.; Mark Allen, M.D.; Deb Andrist, R.N.; Gregory Aughenbaugh, M.D.; Sharon Bendel, R.N.; Eric Edell, M.D.; Marlene Edgar; Bonnie Edwards; Beth Elliot, M.D.; James Garrett, R.R.T.; Delmar Gillespie, M.D.; Judd Gurney, M.D.; Boleyn Hammel; Karen Hanson, R.R.T.; Lori Hanson, R.R.T.; Gordon Harms, M.D.; June Hart; Thomas Hartman, M.D.; Robert Hyatt, M.D.; Eric Jensen, M.D.; Nicole Jenson, R.R.T.; Sanjay Kalra, M.D.; Philip Karsell, M.D.; Jennifer Lamb; David Midthun, M.D.; Carl Mottram, R.R.T.; Stephen Swensen, M.D.; Anne-Marie Sykes, M.D.; Karen Taylor; Norman Torres, M.D.; Rolf Hubmayr, M.D. (1998–2000); Daniel Miller, M.D. (1999–2002); Sara Bartling, R.N. (1998–2000); Kris Bradt (1998–2002). National Jewish Medical and Research Center, Denver, CO: Barry Make, M.D. (Principal Investigator); Marvin Pomerantz, M.D. (Co-Principal Investigator); Mary Gilmartin, R.N., R.R.T. (Principal Clinic Coordinator); Joyce Canterbury; Martin Carlos; Phyllis Dibbern, P.T.; Enrique Fernandez, M.D.; Lisa Geyman, M.S.P.T.; Connie Hudson; David Lynch, M.D.; John Newell, M.D.; Robert Quaife, M.D.; Jennifer Propst, R.N.; Cynthia Raymond, M.S.; Jane Whalen-Price, P.T.; Kathy Winner, O.T.R.; Martin Zamora, M.D.; Reuben Cherniack, M.D. (Principal Investigator, 1997–2000). Ohio State University, Columbus, OH: Philip Diaz, M.D. (Principal Investigator); Patrick Ross, M.D. (Co-Principal Investigator); Tina Bees (Principal Clinic Coordinator); Jan Drake; Charles Emery, PhD; Mark Gerhardt, M.D., PhD; Mark King, M.D.; David Rittinger; Mahasti Rittinger. Saint Louis University, Saint Louis, MO: Keith Naunheim, M.D. (Principal Investigator); Robert Gerber, M.D. (Co-Principal Investigator); Joan Osterloh, R.N., M.S.N. (Principal Clinic Coordinator); Susan Borosh; Willard Chamberlain, D.O.; Sally Frese; Alan Hibbit; Mary Ellen Kleinhenz, M.D.; Gregg Ruppel; Cary Stolar, M.D.; Janice Willey; Francisco Alvarez, M.D. (Co-Principal Investigator, 1999–2002); Cesar Keller, M.D. (Co-Principal Investigator, 1996–2000). Temple University, Philadelphia, PA: Gerard Criner, M.D. (Principal Investigator); Satoshi Furukawa, M.D. (Co-Principal Investigator); Anne Marie Kuzma, R.N., M.S.N. (Principal Clinic Coordinator); Roger Barnette, M.D.; Neil Brister, M.D.; Kevin Carney, R.N., C.C.T.C.; Wissam Chatila, M.D.; Francis Cordova, M.D.; Gilbert D’Alonzo, D.O.; Michael Keresztury, M.D.; Karen Kirsch; Chul Kwak, M.D.; Kathy Lautensack, R.N., B.S.N.; Madelina Lorenzon, C.P.F.T.; Ubaldo Martin, M.D.; Peter Rising, MS; Scott Schartel, M.D.; John Travaline, M.D.; Gwendolyn Vance, R.N., C.C.T.C.; Phillip Boiselle, M.D. (1997–2000); Gerald O’Brien, M.D. (1997–2000). University of California, San Diego, San Diego, CA: Andrew Ries, M.D., M.P.H. (Principal Investigator); Robert Kaplan, PhD (Co-Principal Investigator); Catherine Ramirez, B.S., R.C.P. (Principal Clinic Coordinator); David Frankville, M.D.; Paul Friedman, M.D.; James Harrell, M.D.; Jeffery Johnson; David Kapelanski, M.D.; David Kupferberg, M.D., M.P.H.; Catherine Larsen, M.P.H.; Trina Limberg, R.R.T.; Michael Magliocca, R.N., C.N.P.; Frank J. Papatheofanis, M.D., PhD; Dawn Sassi-Dambron, R.N.; Melissa Weeks. University of Maryland at Baltimore, Baltimore, M.D. in consortium with Johns Hopkins Hospital, Baltimore, M.D.: Mark Krasna, M.D. (Principal Investigator); Henry Fessler, M.D. (Co-Principal Investigator); Iris Moskowitz (Principal Clinic Coordinator); Timothy Gilbert, M.D.; Jonathan Orens, M.D.; Steven Scharf, M.D., PhD; David Shade; Stanley Siegelman, M.D.; Kenneth Silver, M.D.; Clarence Weir; Charles White, M.D. University of Michigan, Ann Arbor, MI: Fernando Martinez, M.D. (Principal Investigator); Mark Iannettoni, M.D. (Co-Principal Investigator); Catherine Meldrum, B.S.N., R.N., C.C.R.N. (Principal Clinic Coordinator); William Bria, M.D.; Kelly Campbell; Paul Christensen, M.D.; Kevin Flaherty, M.D.; Steven Gay, M.D.; Paramjit Gill, R.N.; Paul Kazanjian, M.D.; Ella Kazerooni, M.D.; Vivian Knieper; Tammy Ojo, M.D.; Lewis Poole; Leslie Quint, M.D.; Paul Rysso; Thomas Sisson, M.D.; Mercedes True; Brian Woodcock, M.D.; Lori Zaremba, R.N. University of Pennsylvania, Philadelphia, PA: Larry Kaiser, M.D. (Principal Investigator); John Hansen-Flaschen, M.D. (Co-Principal Investigator); Mary Louise Dempsey, B.S.N., R.N. (Principal Clinic Coordinator); Abass Alavi, M.D.; Theresa Alcorn, Selim Arcasoy, M.D.; Judith Aronchick, M.D.; Stanley Aukberg, M.D.; Bryan Benedict, R.R.T.; Susan Craemer, B.S., R.R.T., C.P.F.T.; Ron Daniele, M.D.; Jeffrey Edelman, M.D.; Warren Gefter, M.D.; Laura Kotler-Klein, M.S.S.; Robert Kotloff, M.D.; David Lipson, M.D.; Wallace Miller, Jr, M.D.; Richard O’Connell, R.P.F.T.; Staci Opelman, M.S.W.; Harold Palevsky, M.D.; William Russell, R.P.F.T.; Heather Sheaffer, M.S.W.; Rodney Simcox, B.S.R.T., R.R.T.; Susanne Snedeker, R.R.T., C.P.F.T.; Jennifer Stone-Wynne, M.S.W.; Gregory Tino, M.D.; Peter Wahl; James Walter, R.P.F.T.; Patricia Ward; David Zisman, M.D.; James Mendez, M.S.N., C.R.N.P. (1997–2001); Angela Wurster, M.S.N., C.R.N.P. (1997–1999). University of Pittsburgh, Pittsburgh, PA: Frank Sciurba, M.D. (Principal Investigator); James Luketich, M.D. (Co-Principal Investigator); Colleen Witt, M.S. (Principal Clinic Coordinator); Gerald Ayres; Michael Donahoe, M.D.; Carl Fuhrman, M.D.; Robert Hoffman, M.D.; Joan Lacomis, M.D.; Joan Sexton; William Slivka; Diane Strollo, M.D.; Erin Sullivan, M.D.; Tomeka Simon; Catherine Wrona, R.N., B.S.N.; Gerene Bauldoff, R.N., M.S.N. (1997–2000); Manuel Brown, M.D. (1997–2002); Elisabeth George, R.N., M.S.N. (Principal Clinic Coordinator 1997–2001); Robert Keenan, M.D. (Co-Principal Investigator 1997–2000); Theodore Kopp, M.S. (1997–1999); Laurie Silfies (1997–2001). University of Washington, Seattle, WA: Joshua Benditt, M.D. (Principal Investigator), Douglas Wood, M.D. (Co-Principal Investigator); Margaret Snyder, M.N. (Principal Clinic Coordinator); Kymberley Anable; Nancy Battaglia; Louie Boitano; Andrew Bowdle, M.D.; Leighton Chan, M.D.; Cindy Chwalik; Bruce Culver, M.D.; Thurman Gillespy, M.D.; David Godwin, M.D.; Jeanne Hoffman; Andra Ibrahim, M.D.; Diane Lockhart; Stephen Marglin, M.D.; Kenneth Martay, M.D.; Patricia McDowell; Donald Oxorn, M.D.; Liz Roessler; Michelle Toshima; Susan Golden (1998–2000). Other participants: Agency for Healthcare Research and Quality, Rockville, MD: Lynn Bosco, M.D., M.P.H.; Yen-Pin Chiang, PhD; Carolyn Clancy, M.D.; Harry Handelsman, D.O. Centers for Medicare and Medicaid Services, Baltimore, M.D.: Steven M Berkowitz, PhD; Tanisha Carino, PhD; Joe Chin, M.D.; 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, M.D., PhD (Principal Investigator); James Tonascia, PhD (Co-Principal Investigator); Patricia Belt; Amanda Blackford, Sc.M.; Karen Collins; Betty Collison; Ryan Colvin, M.P.H.; John Dodge; Michele Donithan, M.H.S.; Vera Edmonds; Gregory L. Foster, M.A.; Julie Fuller; Judith Harle; Rosetta Jackson; Shing Lee, Sc.M.; Charlene Levine; Hope Livingston; Jill Meinert; Jennifer Meyers; Deborah Nowakowski; Kapreena Owens; Shangqian Qi, M.D.; Michael Smith; Brett Simon, M.D.; Paul Smith; Alice Sternberg, Sc.M.; Mark Van Natta, M.H.S.; Laura Wilson, Sc.M.; Robert Wise, M.D. Cost Effectiveness Subcommittee: Robert M. Kaplan, PhD (Chair); J. Sanford Schwartz, M.D. (Co-Chair); Yen-Pin Chiang, PhD; Marianne C. Fahs, PhD; A. Mark Fendrick, M.D.; Alan J. Moskowitz, M.D.; Dev Pathak, PhD; Scott Ramsey, M.D., PhD; Steven Sheingold, PhD; A. Laurie Shroyer, PhD; Judith Wagner, PhD; Roger Yusen, M.D. Cost Effectiveness Data Center, Fred Hutchinson Cancer Research Center, Seattle, WA: Scott Ramsey, M.D., PhD (Principal Investigator); Ruth Etzioni, PhD; Sean Sullivan, PhD; Douglas Wood, M.D.; Thomas Schroeder, M.A.; Karma Kreizenbeck; Kristin Berry, M.S.; Nadia Howlader, M.S. CT Scan Image Storage and Analysis Center, University of Iowa, Iowa City, IA: Eric Hoffman, PhD (Principal Investigator); Janice Cook-Granroth, B.S.; Angela Delsing, R.T.; Junfeng Guo, PhD; Geoffrey McLennan, M.D.; Brian Mullan, M.D.; Chris Piker, B.S.; Joseph Reinhardt, PhD; Blake Wood; Jered Sieren, R.T.R.; William Stanford, M.D. Data and Safety Monitoring Board: John A. Waldhausen, M.D. (Chair); Gordon Bernard, M.D.; David DeMets, PhD; Mark Ferguson, M.D.; Eddie Hoover, M.D.; Robert Levine, M.D.; Donald Mahler, M.D.; A. John McSweeny, PhD; Jeanine Wiener-Kronish, M.D.; O. Dale Williams, PhD; Magdy Younes, M.D. Marketing Center, Temple University, Philadelphia, PA: Gerard Criner, M.D. (Principal Investigator); Charles Soltoff, M.B.A. Project Office, National Heart, Lung, and Blood Institute, Bethesda, MD: Gail Weinmann, M.D. (Project Officer); Joanne Deshler (Contracting Officer); Dean Follmann, PhD; James Kiley, PhD; Margaret Wu, PhD (1996–2001).
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The financial support of this work from the NIH Clinical Center (N01HR76101, N01HR76102, N01HR76103, N01HR76104, N0). Dr Benzo is funded by grant K24 HL138150 from the National Institutes of Health, USA.
