TC O'Shaughnessy, TW Ansari, NC Barnes and PK Jeffery
Lung Pathology Unit, Imperial College, London, United Kingdom.

In order to determine whether the airway inflammatory cells of chronic obstructive pulmonary disease (COPD) are different from those seen in asthma, we have studied a subepithelial zone, 100 microns deep to the epithelial reticular basement membrane in bronchial biopsies taken from five normal nonsmoking subjects without chronic bronchitis or asthma (FEV1 percentage of predicted [mean +/- SD] 105.7 +/- 25.3), 11 subjects with chronic bronchitis alone (FEV1 percentage of predicted 98.5 +/- 12.9), and 13 subjects with chronic bronchitis in whom there was also evidence of airflow limitation (i.e., COPD; FEV1 percentage of predicted 59.7 +/- 10.0). Using immunohistochemical markers, we counted distinct types of inflammatory cell and expressed them as [median and range] per mm basement membrane. When there was airflow limitation we found significantly increased numbers of CD3+ T lymphocytes (COPD 22.3 [2.6 to 68.2] versus normal 3.7 [1.5 to 16.3]; p < 0.05), an increased number of CD8+ cells (COPD 19.3 [1.8 to 45.5] versus normal 2.3 [0.9 to 4.2]; p < 0.01), and increased expression of HLA-DR (COPD versus normal; p = 0.01). There was also an increased number of CD68+ cells (i.e., macrophages) (COPD 7.4 [0.4 to 16.9] versus normal 0.7 [0 to 2.6]; p < 0.01; COPD versus chronic bronchitis alone 2.7 [0 to 12.8]; p < 0.05). There were no significant differences between the groups in the numbers of subepithelial neutrophils, mast cells, eosinophils or B lymphocytes. There were weak but significant negative associations between the CD8+ T-cell subset (r = -0.42), neutrophils (r = -0.46), and eosinophils (r = -0.53) and FEV1 percentage of predicted in all the chronic bronchitic smokers (p < 0.05). The data confirm the involvement of subepithelial T lymphocytes and macrophages in smoking-induced airflow limitation and provide novel data which support the view that COPD is distinct from asthma with respect to the predominance of the CD8+ T-cell subset in this smoking-related condition.

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				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. [Abstract] [Full Text] [PDF]

				Y. Qiu, J. Zhu, V. Bandi, R. L. Atmar, K. Hattotuwa, K. K. Guntupalli, and P. K. Jeffery Biopsy Neutrophilia, Neutrophil Chemokine and Receptor Gene Expression in Severe Exacerbations of Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., October 15, 2003; 168(8): 968 - 975. [Abstract] [Full Text] [PDF]

				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. [Abstract] [Full Text] [PDF]

				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. [Full Text] [PDF]

				K Amin, A Ekberg-Jansson, C-G Lofdahl, and P Venge Relationship between inflammatory cells and structural changes in the lungs of asymptomatic and never smokers: a biopsy study Thorax, February 1, 2003; 58(2): 135 - 142. [Abstract] [Full Text] [PDF]

				L. M. Fabbri, M. Romagnoli, L. Corbetta, G. Casoni, K. Busljetic, G. Turato, G. Ligabue, A. Ciaccia, M. Saetta, and A. Papi Differences in Airway Inflammation in Patients with Fixed Airflow Obstruction Due to Asthma or Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 418 - 424. [Abstract] [Full Text] [PDF]

				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. [Abstract] [Full Text] [PDF]

				A J White, S Gompertz, and R A Stockley Chronic obstructive pulmonary disease * 6: The aetiology of exacerbations of chronic obstructive pulmonary disease Thorax, January 1, 2003; 58(1): 73 - 80. [Abstract] [Full Text] [PDF]

				A.S. Buist Similarities and differences between asthma and chronic obstructive pulmonary disease: treatment and early outcomes Eur. Respir. J., January 1, 2003; 21(39_suppl): 30S - 35s. [Abstract] [Full Text] [PDF]

				K. Hattotuwa, E. A. Gamble, T. O'Shaughnessy, P. K. Jeffery, and N. C. Barnes Safety of Bronchoscopy, Biopsy, and BAL in Research Patients With COPD Chest, December 1, 2002; 122(6): 1909 - 1912. [Abstract] [Full Text] [PDF]

				M J Gizycki, K L Hattotuwa, N Barnes, and P K Jeffery Effects of fluticasone propionate on inflammatory cells in COPD: an ultrastructural examination of endobronchial biopsy tissue Thorax, September 1, 2002; 57(9): 799 - 803. [Abstract] [Full Text] [PDF]

				W.-D. Kim, W.-S. Kim, Y. Koh, S.-D. Lee, C.-M. Lim, D.-S. Kim, and Y.-J. Cho Abnormal Peripheral Blood T-Lymphocyte Subsets in a Subgroup of Patients With COPD* Chest, August 1, 2002; 122(2): 437 - 444. [Abstract] [Full Text] [PDF]

				G T Verhoeven, J P J J Hegmans, P G H Mulder, J M Bogaard, H C Hoogsteden, and J-B Prins Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness Thorax, August 1, 2002; 57(8): 694 - 700. [Abstract] [Full Text] [PDF]

				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]

				R A O'Donnell and A J Frew Is there more than one inflammatory phenotype in asthma? Thorax, July 1, 2002; 57(7): 566 - 568. [Full Text] [PDF]

				K. L. Hattotuwa, M. J. Gizycki, T. W. Ansari, P. K. Jeffery, and N. C. Barnes The Effects of Inhaled Fluticasone on Airway Inflammation in Chronic Obstructive Pulmonary Disease: A Double-Blind, Placebo-controlled Biopsy Study Am. J. Respir. Crit. Care Med., June 15, 2002; 165(12): 1592 - 1596. [Abstract] [Full Text] [PDF]

				M. Saetta, M. Mariani, P. Panina-Bordignon, G. Turato, C. Buonsanti, S. Baraldo, C. M. Bellettato, A. Papi, L. Corbetta, R. Zuin, et al. Increased Expression of the Chemokine Receptor CXCR3 and Its Ligand CXCL10 in Peripheral Airways of Smokers with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., May 15, 2002; 165(10): 1404 - 1409. [Abstract] [Full Text] [PDF]

				R. E. K. Russell, S. V. Culpitt, C. DeMatos, L. Donnelly, M. Smith, J. Wiggins, and P. J. Barnes Release and Activity of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 by Alveolar Macrophages from Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Cell Mol. Biol., May 1, 2002; 26(5): 602 - 609. [Abstract] [Full Text] [PDF]

				M. G. Cosio, J. Majo, and M. G. Cosio Inflammation of the Airways and Lung Parenchyma in COPD* : Role of T Cells Chest, May 1, 2002; 121 (2009): 160S - 165S. [Abstract] [Full Text] [PDF]