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Am. J. Respir. Crit. Care Med., Volume 164, Number 10, November 2001, S28-S38

Remodeling in Asthma and Chronic Obstructive Lung Disease

PETER K. JEFFERY

Imperial College at the Royal Brompton Hospital, London, United Kingdom

Asthma and chronic obstructive lung disease (COPD) are both inflammatory conditions of the lung associated with structural "remodeling" inappropriate to the maintenance of normal lung function. The clinically observed distinctions between asthma and COPD are reflected by differences in the remodeling process, the patterns of inflammatory cells and cytokines, and also the predominant anatomic site at which these alterations occur. In asthma the epithelium appears to be more fragile than that of COPD, the epithelial reticular basement membrane (RBM) is significantly thicker, there is marked enlargement of the mass of bronchial smooth muscle, and emphysema does not occur in the asthmatic nonsmoker. In COPD, there is epithelial mucous metaplasia, airway wall fibrosis, and inflammation associated with loss of surrounding alveolar attachments to the outer wall of small airways: bronchiolar smooth muscle is increased also. Emphysema is a feature of severe COPD: in spite of the destructive process, alveolar wall thickening and focal fibrosis may be detected. The hypertrophy of submucosal mucus-secreting glands is similar in extent in asthma and COPD. The number of bronchial vessels and the area of the wall occupied by them increase in severe corticosteroid-dependent asthma: it is likely that these increases also occur in severe COPD as they do in bronchiectasis. Pulmonary vasculature is remodeled in COPD. In asthma several of these structural alterations begin early in the disease process, even in the child. In COPD the changes begin later in life and the associated inflammatory response differs from that in asthma. The following synopsis defines and compares the key remodeling processes and proposes several hypotheses.




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Laminin-311 (Laminin-6) Fiber Assembly by Type I-like Alveolar Cells
J. Histochem. Cytochem., June 1, 2006; 54(6): 665 - 672.
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 Am J Health Syst PharmHome page
D. M. Schreck
Asthma pathophysiology and evidence-based treatment of severe exacerbations.
Am. J. Health Syst. Pharm., May 15, 2006; 63(10 Suppl 3): S5 - 13.
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 Eur Respir JHome page
P. W. Jones and A. G. N. Agusti
Outcomes and markers in the assessment of chronic obstructive pulmonary disease.
Eur. Respir. J., April 1, 2006; 27(4): 822 - 832.
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 Am. J. Respir. Crit. Care Med.Home page
W. R. Henderson Jr., G. K. S. Chiang, Y.-t. Tien, and E. Y. Chi
Reversal of Allergen-induced Airway Remodeling by CysLT1 Receptor Blockade
Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 718 - 728.
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N. I. Chaudhary, A. Schnapp, and J. E. Park
Pharmacologic Differentiation of Inflammation and Fibrosis in the Rat Bleomycin Model
Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 769 - 776.
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J.-M. Tournier, K. Maouche, C. Coraux, J.-M. Zahm, I. Cloez-Tayarani, B. Nawrocki-Raby, A. Bonnomet, H. Burlet, F. Lebargy, M. Polette, et al.
{alpha}3{alpha}5{beta}2-Nicotinic Acetylcholine Receptor Contributes to the Wound Repair of the Respiratory Epithelium by Modulating Intracellular Calcium in Migrating Cells
Am. J. Pathol., January 1, 2006; 168(1): 55 - 68.
[Abstract] [Full Text] [PDF]

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 RadioGraphicsHome page
J. F. Bruzzi, M. Remy-Jardin, D. Delhaye, A. Teisseire, C. Khalil, and J. Remy
Multi-Detector Row CT of Hemoptysis
RadioGraphics, January 1, 2006; 26(1): 3 - 22.
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 ChestHome page
B. J. Canning
Anatomy and Neurophysiology of the Cough Reflex: ACCP Evidence-Based Clinical Practice Guidelines
Chest, January 1, 2006; 129(1_suppl): 33S - 47S.
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 Am. J. Respir. Crit. Care Med.Home page
O. S. Usmani, M. F. Biddiscombe, and P. J. Barnes
Regional Lung Deposition and Bronchodilator Response as a Function of {beta}2-Agonist Particle Size
Am. J. Respir. Crit. Care Med., December 15, 2005; 172(12): 1497 - 1504.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
S. Kubo, M. Kobayashi, Y. Masunaga, H. Ishii, Y. Hirano, K. Takahashi, and Y. Shimizu
Cytokine and chemokine expression in cigarette smoke-induced lung injury in guinea pigs
Eur. Respir. J., December 1, 2005; 26(6): 993 - 1001.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
P. Thai, Y. Chen, G. Dolganov, and R. Wu
Differential Regulation of MUC5AC/Muc5ac and hCLCA-1/mGob-5 Expression in Airway Epithelium
Am. J. Respir. Cell Mol. Biol., December 1, 2005; 33(6): 523 - 530.
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 Proc Am Thorac SocHome page
M. A. Giembycz
Phosphodiesterase-4: Selective and Dual-Specificity Inhibitors for the Therapy of Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, November 1, 2005; 2(4): 326 - 333.
[Abstract] [Full Text] [PDF]

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 ChestHome page
J. Moorman, M. Saad, S. Kosseifi, and G. Krishnaswamy
Hepatitis C Virus and the Lung: Implications for Therapy
Chest, October 1, 2005; 128(4): 2882 - 2892.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
R. D. Wang, J. L. Wright, and A. Churg
Transforming Growth Factor-{beta}1 Drives Airway Remodeling in Cigarette Smoke-Exposed Tracheal Explants
Am. J. Respir. Cell Mol. Biol., October 1, 2005; 33(4): 387 - 393.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
B. O. Abonyo, M. S. Alexander, and A. S. Heiman
Autoregulation of CCL26 synthesis and secretion in A549 cells: a possible mechanism by which alveolar epithelial cells modulate airway inflammation
Am J Physiol Lung Cell Mol Physiol, September 1, 2005; 289(3): L478 - L488.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
A. R. Pons, J. Sauleda, A. Noguera, J. Pons, B. Barcelo, A. Fuster, and A. G. N. Agusti
Decreased macrophage release of TGF-{beta} and TIMP-1 in chronic obstructive pulmonary disease
Eur. Respir. J., July 1, 2005; 26(1): 60 - 66.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. S. Faffe, L. Flynt, M. Mellema, T. R. Whitehead, K. Bourgeois, R. A. Panettieri Jr., E. S. Silverman, and S. A. Shore
Oncostatin M causes VEGF release from human airway smooth muscle: synergy with IL-1{beta}
Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1040 - L1048.
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 Am. J. Respir. Crit. Care Med.Home page
S. J. Szefler
Airway Remodeling: Therapeutic Target or Not?
Am. J. Respir. Crit. Care Med., April 1, 2005; 171(7): 672 - 673.
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H Matsumoto, A Niimi, M Takemura, T Ueda, M Minakuchi, R Tabuena, K Chin, T Mio, Y Ito, S Muro, et al.
Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthma
Thorax, April 1, 2005; 60(4): 277 - 281.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
U. Oltmanns, M. B. Sukkar, S. Xie, M. John, and K. F. Chung
Induction of Human Airway Smooth Muscle Apoptosis by Neutrophils and Neutrophil Elastase
Am. J. Respir. Cell Mol. Biol., April 1, 2005; 32(4): 334 - 341.
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 Am. J. Respir. Crit. Care Med.Home page
S. Saglani, K. Malmstrom, A. S. Pelkonen, L. P. Malmberg, H. Lindahl, M. Kajosaari, M. Turpeinen, A. V. Rogers, D. N. Payne, A. Bush, et al.
Airway Remodeling and Inflammation in Symptomatic Infants with Reversible Airflow Obstruction
Am. J. Respir. Crit. Care Med., April 1, 2005; 171(7): 722 - 727.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
J. M. Lofdahl, K. Cederlund, L. Nathell, A. Eklund, and C. M. Skold
Bronchoalveolar lavage in COPD: fluid recovery correlates with the degree of emphysema
Eur. Respir. J., February 1, 2005; 25(2): 275 - 281.
[Abstract] [Full Text] [PDF]

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A J Knox, J Stocks, and A Sutcliffe
Angiogenesis and vascular endothelial growth factor in COPD
Thorax, February 1, 2005; 60(2): 88 - 89.
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A R Kranenburg, W I de Boer, V K T Alagappan, P J Sterk, and H S Sharma
Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease
Thorax, February 1, 2005; 60(2): 106 - 113.
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 Am. J. Respir. Crit. Care Med.Home page
K. R. Tormanen, L. Uller, C. G. A. Persson, and J. S. Erjefalt
Allergen Exposure of Mouse Airways Evokes Remodeling of both Bronchi and Large Pulmonary Vessels
Am. J. Respir. Crit. Care Med., January 1, 2005; 171(1): 19 - 25.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. D. Reynolds, A. Giangreco, K. U. Hong, K. E. McGrath, L. A. Ortiz, and B. R. Stripp
Airway injury in lung disease pathophysiology: selective depletion of airway stem and progenitor cell pools potentiates lung inflammation and alveolar dysfunction
Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1256 - L1265.
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 Am. J. Respir. Crit. Care Med.Home page
K. Larsen, E. Tufvesson, J. Malmstrom, M. Morgelin, M. Wildt, A. Andersson, A. Lindstrom, A. Malmstrom, C.-G. Lofdahl, G. Marko-Varga, et al.
Presence of Activated Mobile Fibroblasts in Bronchoalveolar Lavage from Patients with Mild Asthma
Am. J. Respir. Crit. Care Med., November 15, 2004; 170(10): 1049 - 1056.
[Abstract] [Full Text] [PDF]

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 Proc Am Thorac SocHome page
P. K. Jeffery
Remodeling and Inflammation of Bronchi in Asthma and Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, November 1, 2004; 1(3): 176 - 183.
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 Am. J. Respir. Crit. Care Med.Home page
R. Leigh, R. Ellis, J. Wattie, D. D. Donaldson, and M. D. Inman
Is Interleukin-13 Critical in Maintaining Airway Hyperresposiveness in Allergen-challenged Mice?
Am. J. Respir. Crit. Care Med., October 15, 2004; 170(8): 851 - 856.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
K. Parameswaran, K. Radford, J. Zuo, L.J. Janssen, P.M. O'Byrne, and P.G. Cox
Extracellular matrix regulates human airway smooth muscle cell migration
Eur. Respir. J., October 1, 2004; 24(4): 545 - 551.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. R. Driskell, X. Liu, M. Luo, M. Filali, W. Zhou, D. Abbott, N. Cheng, C. Moothart, C. D. Sigmund, and J. F. Engelhardt
Wnt-responsive element controls Lef-1 promoter expression during submucosal gland morphogenesis
Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L752 - L763.
[Abstract] [Full Text] [PDF]

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 Occup. Environ. Med.Home page
T Sjaheim, T S Halstensen, M B Lund, O Bjortuft, P A Drablos, D Malterud, and J Kongerud
Airway inflammation in aluminium potroom asthma
Occup. Environ. Med., September 1, 2004; 61(9): 779 - 785.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
M. Roth, P. R.A. Johnson, P. Borger, M. P. Bihl, J. J. Rudiger, G. G. King, Q. Ge, K. Hostettler, J. K. Burgess, J. L. Black, et al.
Dysfunctional Interaction of C/EBP{alpha} and the Glucocorticoid Receptor in Asthmatic Bronchial Smooth-Muscle Cells
N. Engl. J. Med., August 5, 2004; 351(6): 560 - 574.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
P.E. Christie, M. Jonas, C-H. Tsai, E.Y. Chi, and W.R. Henderson Jr
Increase in laminin expression in allergic airway remodelling and decrease by dexamethasone
Eur. Respir. J., July 1, 2004; 24(1): 107 - 115.
[Abstract] [Full Text] [PDF]

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 ChestHome page
J. Tamaoki, E. Tagaya, K. Kawatani, J. Nakata, Y. Endo, and A. Nagai
Airway Mucosal Thickening and Bronchial Hyperresponsiveness Induced by Inhaled {beta}2-Agonist in Mice
Chest, July 1, 2004; 126(1): 205 - 212.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
T. S. Wilkinson, S. Potter-Perigo, C. Tsoi, L. C. Altman, and T. N. Wight
Pro- and Anti-Inflammatory Factors Cooperate to Control Hyaluronan Synthesis in Lung Fibroblasts
Am. J. Respir. Cell Mol. Biol., July 1, 2004; 31(1): 92 - 99.
[Abstract] [Full Text] [PDF]


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