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Am. J. Respir. Crit. Care Med., Volume 164, Number 3, August 2001, 469-473

Amplification of Inflammation in Emphysema and Its Association with Latent Adenoviral Infection

IVAN RETAMALES, W. MARK ELLIOTT, BERNARD MESHI, HARVEY O. COXSON, PETER D. PARE, FRANK C. SCIURBA, ROBERT M. ROGERS, SHIZU HAYASHI, and JAMES C. HOGG

University of British Columbia McDonald Research Laboratories, St. Paul's Hospital, Vancouver, British Columbia, Canada; and Divisions of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh Medical Center and School of Medicine, Pittsburgh, Pennsylvania

This study examines the hypothesis that the cigarette smoke-induced inflammatory process is amplified in severe emphysema and explores the association of this response with latent adenoviral infection. Lung tissue from patients with similar smoking histories and either no (n = 7), mild (n = 7), or severe emphysema (n = 7) was obtained by lung resection. Numbers of polymorphonuclear cells (PMN), macrophages, B cells, CD4, CD8 lymphocytes, and eosinophils present in tissue and airspaces and of epithelial cells expressing adenoviral E1A protein were determined using quantitative techniques. Severe emphysema was associated with an absolute increase in the total number of inflammatory cells in the lung tissue and airspaces. The computed tomography (CT) determined extent of lung destruction was related to the number of cells/m2 surface area by R2 values that ranged from 0.858 (CD8 cells) to 0.483 (B cells) in the tissue and 0.630 (CD4 cells) to 0.198 (B cells) in the airspaces. These changes were associated with a 5- to 40-fold increase in the number of alveolar epithelial cells expressing adenoviral E1A protein in mild and severe disease, respectively. We conclude that cigarette smoke-induced lung inflammation is amplified in severe emphysema and that latent expression of the adenoviral E1A protein expressed by alveolar epithelial cells influenced this amplification process.

Keywords: emphysema; lung inflammation; latent adenoviral infection; cigarette smoking




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J. C. Hogg, F. Chu, S. Utokaparch, R. Woods, W. M. Elliott, L. Buzatu, R. M. Cherniack, R. M. Rogers, F. C. Sciurba, H. O. Coxson, et al.
The Nature of Small-Airway Obstruction in Chronic Obstructive Pulmonary Disease
N. Engl. J. Med., June 24, 2004; 350(26): 2645 - 2653.
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 Eur Respir JHome page
J.D. Newell Jr, J.C. Hogg, and G.L. Snider
Report of a workshop: quantitative computed tomography scanning in longitudinal studies of emphysema
Eur. Respir. J., May 1, 2004; 23(5): 769 - 775.
[Abstract] [Full Text] [PDF]

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 Proc Am Thorac SocHome page
J. A. Wedzicha
Role of Viruses in Exacerbations of Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, April 1, 2004; 1(2): 115 - 120.
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 Am. J. Respir. Crit. Care Med.Home page
M. N. Upton, G. D. Smith, A. McConnachie, C. L. Hart, and G. C. M. Watt
Maternal and Personal Cigarette Smoking Synergize to Increase Airflow Limitation in Adults
Am. J. Respir. Crit. Care Med., February 15, 2004; 169(4): 479 - 487.
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 Am. J. Respir. Cell Mol. Bio.Home page
C. S. Robbins, D. E. Dawe, S. I. Goncharova, M. A. Pouladi, A. G. Drannik, F. K. Swirski, G. Cox, and M. R. Stampfli
Cigarette Smoke Decreases Pulmonary Dendritic Cells and Impacts Antiviral Immune Responsiveness
Am. J. Respir. Cell Mol. Biol., February 1, 2004; 30(2): 202 - 211.
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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. Ogawa, W. M. Elliott, F. Hughes, T. J. Eichholtz, J. C. Hogg, and S. Hayashi
Latent adenoviral infection induces production of growth factors relevant to airway remodeling in COPD
Am J Physiol Lung Cell Mol Physiol, January 1, 2004; 286(1): L189 - L197.
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 Am. J. Respir. Cell Mol. Bio.Home page
J. A. Wickenden, M. C. H. Clarke, A. G. Rossi, I. Rahman, S. P. Faux, K. Donaldson, and W. MacNee
Cigarette Smoke Prevents Apoptosis through Inhibition of Caspase Activation and Induces Necrosis
Am. J. Respir. Cell Mol. Biol., November 1, 2003; 29(5): 562 - 570.
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 Am. J. Respir. Crit. Care Med.Home page
M. Saetta, S. Baraldo, and R. Zuin
Neutrophil Chemokines in Severe Exacerbations of Chronic Obstructive Pulmonary Disease: Fatal Chemo-Attraction?
Am. J. Respir. Crit. Care Med., October 15, 2003; 168(8): 911 - 913.
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 Am. J. Respir. Crit. Care Med.Home page
E. Gamble, D. C. Grootendorst, C. E. Brightling, S. Troy, Y. Qiu, J. Zhu, D. Parker, D. Matin, S. Majumdar, A. M. Vignola, et al.
Antiinflammatory Effects of the Phosphodiesterase-4 Inhibitor Cilomilast (Ariflo) in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., October 15, 2003; 168(8): 976 - 982.
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 Eur Respir JHome page
P.J. Barnes, S.D. Shapiro, and R.A. Pauwels
Chronic obstructive pulmonary disease: molecular and cellularmechanisms
Eur. Respir. J., October 1, 2003; 22(4): 672 - 688.
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 ThoraxHome page
A Agusti, W MacNee, K Donaldson, and M Cosio
Hypothesis: Does COPD have an autoimmune component?
Thorax, October 1, 2003; 58(10): 832 - 834.
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 Am. J. Respir. Crit. Care Med.Home page
P. Jeffery, S. Holgate, and S. Wenzel
Methods for the Assessment of Endobronchial Biopsies in Clinical Research: Application to Studies of Pathogenesis and the Effects of Treatment
Am. J. Respir. Crit. Care Med., September 15, 2003; 168(6): S1 - 17.
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 Am. J. Respir. Crit. Care Med.Home page
B. Suki, K. R. Lutchen, and E. P. Ingenito
On the Progressive Nature of Emphysema: Roles of Proteases, Inflammation, and Mechanical Forces
Am. J. Respir. Crit. Care Med., September 1, 2003; 168(5): 516 - 521.
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P. Maestrelli, C. Paska, M. Saetta, G. Turato, Y. Nowicki, S. Monti, B. Formichi, M. Miniati, and L.M. Fabbri
Decreased haem oxygenase-1 and increased inducible nitric oxide synthase in the lung of severe COPD patients
Eur. Respir. J., June 1, 2003; 21(6): 971 - 976.
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 Eur Respir JHome page
W. MacNee and K. Donaldson
Mechanism of lung injury caused by PM10 and ultrafine particles with special reference to COPD
Eur. Respir. J., May 1, 2003; 21(40_suppl): 47S - 51s.
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 Am. J. Respir. Crit. Care Med.Home page
S. Santos, V. I. Peinado, J. Ramirez, J. Morales-Blanhir, R. Bastos, J. Roca, R. Rodriguez-Roisin, and J. A. Barbera
Enhanced Expression of Vascular Endothelial Growth Factor in Pulmonary Arteries of Smokers and Patients with Moderate Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., May 1, 2003; 167(9): 1250 - 1256.
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 Am. J. Respir. Crit. Care Med.Home page
R. E. Walter, A. Beiser, R. J. Givelber, G. T. O'Connor, and D. J. Gottlieb
Association between Glycemic State and Lung Function: The Framingham Heart Study
Am. J. Respir. Crit. Care Med., March 15, 2003; 167(6): 911 - 916.
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P. Boschetto, M. Miniati, D. Miotto, F. Braccioni, E. De Rosa, I. Bononi, A. Papi, M. Saetta, L.M. Fabbri, and C.E. Mapp
Predominant emphysema phenotype in chronic obstructive pulmonary disease patients
Eur. Respir. J., March 1, 2003; 21(3): 450 - 454.
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 ChestHome page
H. Kanazawa, K. Hirata, and J. Yoshikawa
Accelerated Decline of Lung Function in COPD Patients With Chronic Hepatitis C Virus Infection: A Preliminary Study Based on Small Numbers of Patients
Chest, February 1, 2003; 123(2): 596 - 599.
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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. Fujii, J. C. Hogg, N. Keicho, R. Vincent, S. F. Van Eeden, and S. Hayashi
Adenoviral E1A modulates inflammatory mediator expression by lung epithelial cells exposed to PM10
Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L290 - L297.
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 Am. J. Respir. Cell Mol. Bio.Home page
J. J. Atkinson and R. M. Senior
Matrix Metalloproteinase-9 in Lung Remodeling
Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 12 - 24.
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 Am. J. Respir. Crit. Care Med.Home page
J. H. Vernooy, M. Kucukaycan, J. A. Jacobs, N. H. Chavannes, W. A. Buurman, M. A. Dentener, and E. F. Wouters
Local and Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease: Soluble Tumor Necrosis Factor Receptors Are Increased in Sputum
Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1218 - 1224.
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 Am. J. Respir. Cell Mol. Bio.Home page
A. Churg, K. Zay, S. Shay, C. Xie, S. D. Shapiro, R. Hendricks, and J. L Wright
Acute Cigarette Smoke-Induced Connective Tissue Breakdown Requires both Neutrophils and Macrophage Metalloelastase in Mice
Am. J. Respir. Cell Mol. Biol., September 1, 2002; 27(3): 368 - 374.
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 ThoraxHome page
J C Hogg and R M Senior
Chronic obstructive pulmonary disease c 2: Pathology and biochemistry of emphysema
Thorax, September 1, 2002; 57(9): 830 - 834.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
A J Sandford and E K Silverman
Chronic obstructive pulmonary disease * 1: Susceptibility factors for COPD the genotype-environment interaction
Thorax, August 1, 2002; 57(8): 736 - 741.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
Y. Higashimoto, W. M. Elliott, A. R. Behzad, E. G. Sedgwick, T. Takei, J. C. Hogg, and S. Hayashi
Inflammatory Mediator mRNA Expression by Adenovirus E1A-Transfected Bronchial Epithelial Cells
Am. J. Respir. Crit. Care Med., July 15, 2002; 166(2): 200 - 207.
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 Am. J. Respir. Crit. Care Med.Home page
G. Turato, R. Zuin, M. Miniati, S. Baraldo, F. Rea, B. Beghe, S. Monti, B. Formichi, P. Boschetto, S. Harari, et al.
Airway Inflammation in Severe Chronic Obstructive Pulmonary Disease: Relationship with Lung Function and Radiologic Emphysema
Am. J. Respir. Crit. Care Med., July 1, 2002; 166(1): 105 - 110.
[Abstract] [Full Text] [PDF]

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M. Miravitlles
Exacerbations of chronic obstructive pulmonary disease: when are bacteria important?
Eur. Respir. J., July 1, 2002; 20(36_suppl): 9S - 19s.
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