Role of Inflammatory Markers in Ventilatory Limitation and Muscle Dysfunction in Obstructive Lung Disease in the Well Functioning Elderly

Sachin Yende ^1*, Grant W Waterer ², Elizabeth Tolley ³, Anne Newman ⁴, Doug Bauer ⁵, Dennis Taaffe ⁶, Robert Jensen ⁷, Robert Crapo ⁷, Susan Rubin ⁸, Michael Nevitt ⁸, Eleanor Simonsick ⁹, Suzanne Satterfield ³, Tamara Harris ⁹ and Stephen Kritchevsky ¹⁰

¹ The University of Pittsburgh, United States
² University of Western Australia, Perth, Australia
³ The University of Tennessee, United States
⁴ University of Pittsburgh, PA, United States
⁵ University of California, San Francisco, California, United States
⁶ The University of Queensland, Australia
⁷ LDS Hospital and University of Utah, Salt Lake City, Utah, United States
⁸ University of California, SF, CA, United States
⁹ National Institute on Aging, Bethesda, MA, United States
¹⁰ Wake Forest University, Winston Salem, NC, United States

^* To whom correspondence should be addressed. E-mail: yendes{at}upmc.edu.

Accepted 18 October 2005

Abstract

Background: Inflammatory markers are elevated in Chronic Obstructive Pulmonary Disease (COPD) and hypothesized to play an important a role in muscle dysfunction and exercise intolerance.

Methods: The Health, Aging, and Body Composition study is a prospective observational cohort of well functioning 70-79 year participants. We conducted a cross-sectional analysis of the baseline data to examine the association of inflammatory markers with ventilatory limitation, muscle strength, and exercise capacity; and compared these associations among participants with and without obstructive lung disease (OLD).

Measurements and results: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometry in 268 participants and 2005 participants had normal spirometry. Among participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 v 108.9 Nm, P=0.02), lower maximum inspiratory pressure (64.7 v 74.2 cm of water, P<0.0001), higher systemic interleukin (IL)-6 levels (2.6 v 2.2 pg/ml, P<0.0001) and C-reactive protein levels (3.5 vs 2.5 mg/L, P<0.0001) compared to those with normal spirometry. In participants with OLD and normal spirometry FEV1 was associated with IL-6 [adjusted regression co-efficients(â)=-5.3(95% CI=- 9.1,-1.5)] and -3.1(95% CI=-4.3,-1.9), respectively. IL- 6 and TNF were also associated with quadriceps strength among participants with OLD and normal spirometry [â=-6.4(95% CI=-12.8,-0.03) and -3.4(95% CI=-5.4,- 1.3), respectively for IL-6 and â=-10.1 (95% CI=- 18.7,-1.5), and -3.8 (95% CI=--7,-0.6), respectively for TNF]. IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups.

Conclusions: In the well functioning elderly, IL- 6 was associated with reduced FEV1, quadriceps strength, and exercise capacity in participants with and without OLD.

Keywords: IL6, TNF, inflammatory markers, obstructive lung disease, skeletal muscle

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Airwaves

Wisia Wedzicha
Thorax 2006 61: 1. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• He, J-Q, Foreman, M G, Shumansky, K, Zhang, X, Akhabir, L, Sin, D D, Man, S F P, DeMeo, D L, Litonjua, A A, Silverman, E K, Connett, J E, Anthonisen, N R, Wise, R A, Pare, P D, Sandford, A J (2009). Associations of IL6 polymorphisms with lung function decline and COPD. Thorax 64: 698-704 [Abstract] [Full Text]  
• Dufresne, V., Knoop, C., Van Muylem, A., Malfroot, A., Lamotte, M., Opdekamp, C., Deboeck, G., Cassart, M., Stallenberg, B., Casimir, G., Duchateau, J., Estenne, M. (2009). Effect of Systemic Inflammation on Inspiratory and Limb Muscle Strength and Bulk in Cystic Fibrosis. Am. J. Respir. Crit. Care Med. 180: 153-158 [Abstract] [Full Text]  
• Bolton, C. E, Cockcroft, J. R, Sabit, R., Munnery, M., McEniery, C. M, Wilkinson, I. B, Ebrahim, S., Gallacher, J. E, Shale, D. J, Ben-Shlomo, Y. (2009). Lung function in mid-life compared with later life is a stronger predictor of arterial stiffness in men: The Caerphilly Prospective Study. Int J Epidemiol 38: 867-876 [Abstract] [Full Text]  
• Barnes, P. J., Celli, B. R. (2009). Systemic manifestations and comorbidities of COPD. Eur Respir J 33: 1165-1185 [Abstract] [Full Text]  
• Butcher, S. J., Lagerquist, O., Marciniuk, D. D., Petersen, S. R., Collins, D. F., Jones, R. L. (2009). Relationship between ventilatory constraint and muscle fatigue during exercise in COPD. Eur Respir J 33: 763-770 [Abstract] [Full Text]  
• Rasmussen, F., Mikkelsen, D., Hancox, R. J., Lambrechtsen, J., Nybo, M., Hansen, H. S., Siersted, H. C. (2009). High-sensitive C-reactive protein is associated with reduced lung function in young adults. Eur Respir J 33: 382-388 [Abstract] [Full Text]  
• Butland, B. K., Strachan, D. P., Rudnicka, A. R. (2008). C-reactive protein, obesity, atopy and asthma symptoms in middle-aged adults. Eur Respir J 32: 77-84 [Abstract] [Full Text]  
• Eisner, M. D., Iribarren, C., Yelin, E. H., Sidney, S., Katz, P. P., Ackerson, L., Lathon, P., Tolstykh, I., Omachi, T., Byl, N., Blanc, P. D. (2008). Pulmonary Function and the Risk of Functional Limitation in Chronic Obstructive Pulmonary Disease. Am J Epidemiol 167: 1090-1101 [Abstract] [Full Text]  
• Meador, B. M., Krzyszton, C. P., Johnson, R. W., Huey, K. A. (2008). Effects of IL-10 and age on IL-6, IL-1{beta}, and TNF-{alpha} responses in mouse skeletal and cardiac muscle to an acute inflammatory insult. J. Appl. Physiol. 104: 991-997 [Abstract] [Full Text]  
• Hardin, B. J., Campbell, K. S., Smith, J. D., Arbogast, S., Smith, J., Moylan, J. S., Reid, M. B. (2008). TNF-{alpha} acts via TNFR1 and muscle-derived oxidants to depress myofibrillar force in murine skeletal muscle. J. Appl. Physiol. 104: 694-699 [Abstract] [Full Text]  
• Sin, D. D, Reid, W D. (2008). Is inflammation good, bad or irrelevant for skeletal muscles in COPD?. Thorax 63: 95-96 [Full Text]  
• Sin, D. D., Man, S. F. P. (2008). Interleukin-6: A Red Herring or a Real Catch in COPD?. Chest 133: 4-6 [Full Text]  
• Hancox, R. J, Poulton, R., Greene, J. M, Filsell, S., McLachlan, C. R, Rasmussen, F., Taylor, D R., Williams, M. J A, Williamson, A., Sears, M. R (2007). Systemic inflammation and lung function in young adults. Thorax 62: 1064-1068 [Abstract] [Full Text]  
• Tkac, J., Man, S. F. P., Sin, D. D. (2007). Review: Systemic consequences of COPD. Ther Adv Respir Dis 1: 47-59 [Abstract]  
• Calverley, P. M. (2007). . ERR 16: 89-90 [Full Text]  
• Rabe, K. F., Beghe, B., Luppi, F., Fabbri, L. M. (2007). Update in Chronic Obstructive Pulmonary Disease 2006. Am. J. Respir. Crit. Care Med. 175: 1222-1232 [Full Text]  
• Fogarty, A. W, Jones, S., Britton, J. R, Lewis, S. A, McKeever, T. M (2007). Systemic inflammation and decline in lung function in a general population: a prospective study. Thorax 62: 515-520 [Abstract] [Full Text]  
• Supinski, G. S., Callahan, L. A. (2007). Free radical-mediated skeletal muscle dysfunction in inflammatory conditions. J. Appl. Physiol. 102: 2056-2063 [Abstract] [Full Text]  
• Donaldson, G. C. (2007). C-reactive Protein: Does It Predict Mortality?. Am. J. Respir. Crit. Care Med. 175: 209-210 [Full Text]  
• Dahl, M., Vestbo, J., Lange, P., Bojesen, S. E., Tybjaerg-Hansen, A., Nordestgaard, B. G. (2007). C-reactive Protein As a Predictor of Prognosis in Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 175: 250-255 [Abstract] [Full Text]  
• Sin, D. D., Man, S. F. P. (2006). Pharmacotherapy for Mortality Reduction in Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc 3: 624-629 [Abstract] [Full Text]  
• Donohue, J F (2006). Ageing, smoking and oxidative stress.. Thorax 61: 461-462 [Full Text]  
• Wouters, E. F. M. (2006). The systemic face of airway diseases: the role of C-reactive protein.. Eur Respir J 27: 877-879 [Full Text]  
• Sin, D D, Man, S F P (2006). Skeletal muscle weakness, reduced exercise tolerance, and COPD: is systemic inflammation the missing link?. Thorax 61: 1-3 [Full Text]