Chronic obstructive pulmonary disease is a major problem worldwide with increasing prevalence and morbidity/mortality. Current therapy is based on smoking cessation, maximizing lung function, treating infection and rehabilitation. The increase in knowledge about basic disease mechanisms affords the opportunity to explore new methods for treating this disorder. We propose the development of a clinical center at the University of Maryland to participate in the NIH COPD Clinical Research Network. In addition to describing the patient population and recruitment strategies, we present 2 model proposals for consideration by the network. The first proposal relies on recent findings that there is a strong inflammatory component in patients with end-stage COPD which may lead to weight loss, muscle wasting and increased mortality. A key inflammatory cytokine is tumor necrosis factor alpha (TNFalpha). We propose evaluating the effects of anti-TNFalpha therapy (inflixamab) in moderate to severe COPD patients in a 3-arm randomized blinded trial. Patients will receive 26 weeks of infliximab, 24 weeks inflixamab/12 weeks' placebo or 36 weeks of placebo treatment. Our primary outcome will be 6 minute walking distance, a measure of exercise tolerance. A number of secondary variables including proinflammatory cytokines in sputum and blood, pulmonary physiological and metabolic outcomes, body composition and quality of life (QOL) indices will be measured as well. The second proposal is on the use of inhaled steroids in COPD. Results from previous trials have in general been disappointing. However, there are likely to be subsets of patients who respond. We predict that patients with a prominent airway inflammatory component to their disease will be likely to respond to inhaled steroids and would be candidates for long-term treatment. We will determine if the sputum level of proinflamamtory cytokines is predictive of the response to steroid inhalers in COPD. We will determine if the presence of a single nucleotide substitution in the glucocorticoid receptor has a negative impact on the response. Outcomes from this randomized clinical trial will be gauged in terms of health related QOL. In addition to presenting these formal proposals, we have developed several concept proposals. We have also offered the development of a health cost utilization core for the COPD CRN.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
1U10HL074441-01
Application #
6683761
Study Section
Special Emphasis Panel (ZHL1-CSR-C (M2))
Program Officer
Croxton, Thomas
Project Start
2003-08-15
Project End
2008-07-31
Budget Start
2003-08-15
Budget End
2004-07-31
Support Year
1
Fiscal Year
2003
Total Cost
$791,575
Indirect Cost
Name
University of Maryland Baltimore
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Brown, Kirstin E; Sin, Don D; Voelker, Helen et al. (2017) Serum bilirubin and the risk of chronic obstructive pulmonary disease exacerbations. Respir Res 18:179
Gulcev, Makedonka; Reilly, Cavan; Griffin, Timothy J et al. (2016) Tryptophan catabolism in acute exacerbations of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 11:2435-2446
Wetherbee, Erin E; Niewoehner, Dennis E; Sisson, Joseph H et al. (2015) Self-reported alcohol intake and risk of acute exacerbations of chronic obstructive pulmonary disease: a prospective cohort study. Int J Chron Obstruct Pulmon Dis 10:1363-70
Geiger-Brown, Jeanne; Lindberg, Sarah; Krachman, Samuel et al. (2015) Self-reported sleep quality and acute exacerbations of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 10:389-97
Tayob, Nabihah; Murray, Susan (2015) Nonparametric tests of treatment effect based on combined endpoints for mortality and recurrent events. Biostatistics 16:73-83
Han, MeiLan K; Tayob, Nabihah; Murray, Susan et al. (2014) Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med 189:1503-8
Criner, Gerard J; Connett, John E; Aaron, Shawn D et al. (2014) Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med 370:2201-10
Reed, Robert M; Netzer, Giora; Hunsicker, Lawrence et al. (2014) Cardiac size and sex-matching in heart transplantation : size matters in matters of sex and the heart. JACC Heart Fail 2:73-83
Woodruff, Prescott G; Chatila, Wissam; Connett, John E et al. (2014) Tumour necrosis factor receptor-75 and risk of COPD exacerbation in the azithromycin trial. Eur Respir J 43:295-8
Kunisaki, Ken M; Niewoehner, Dennis E; Connett, John E (2013) Severe vitamin D deficiency: a biomarker of exacerbation risk? : a reply to Heulens. Am J Respir Crit Care Med 187:215-6

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