Continuity of airway goblet cells and intraluminal mucus in the airways of patients with bronchial asthma

The aim of this study was to elucidate the mechanism of the formation of the widespread mucous-plugging observed in autopsied lungs from patients with bronchial asthma. We performed morphometric analysis of airways of autopsied lungs from eight patients with bronchial asthma (Group BA), and compared it with those of six chronic bronchitics (Group CB) and four control patients (Control). The following parameters were measured in paraffin sections: volume proportion of bronchial glands to bronchial wall (Gland%); goblet cell granules to total epithelial layer (Goblet %); intraluminal mucus expressed as the mucus occupying ratio (MOR); volume ratio of intraluminal mucus continuous with goblet cells to total intraluminal mucus (Vc/Vtol %); and surface ratio of the contact surface of intraluminal mucus continuous with goblet cells to the total luminal surface (Sc/Stot %). Gland%, Goblet %, and MOR or inflammatory cell numbers in the airway walls both from Group BA and CB were larger than those from the Control group. However, no significant differences were observed between Group BA and CB in Gland%, Goblet %, MOR or inflammatory cell numbers, except for the eosinophil number: i.e. 23 +/- 3, 22 +/- 3 and 6 +/- 2% in Gland%; 22 +/- 9, 5 +/- 4 and 2 +/- 2% in Goblet%; 10 +/- 3, 18 +/- 3 and 0.3 +/- 0.5% in MOR; 199 +/- 68, 10 +/- 3 and 2 +/- 2 cells. mm-2 in eosinophil number of the peripheral airways from Groups BA, CB and Control, respectively. In contrast, marked and significant increases were observed both in Vc/Vtot% and Sc/Stot% in Group BA compared to Groups CB and Control both in central and peripheral airways: i.e. Vc/Vtot% in the peripheral airways was 53 +/- 5, 4 +/- 3 and 0.8 +/- 0.8% from Groups BA, CB and Control, respectively (BA vs CB or BA vs Control, p < 0.01 each). These findings suggest that the continuity of goblet cells and intraluminal mucus or lack of full release of mucus, from goblet cells, is peculiar to asthmatic airways, and may contribute to the formation of mucous-plugs.

This article has been cited by other articles:

				P-R. Burgel and J. A. Nadel Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases Eur. Respir. J., October 1, 2008; 32(4): 1068 - 1081. [Abstract] [Full Text] [PDF]

				C. A. Wu, J. J. Peluso, J. D. Shanley, L. Puddington, and R. S. Thrall Murine Cytomegalovirus Influences Foxj1 Expression, Ciliogenesis, and Mucus Plugging in Mice with Allergic Airway Disease Am. J. Pathol., March 1, 2008; 172(3): 714 - 724. [Abstract] [Full Text] [PDF]

				B. D. Rudd, J. J. Smit, R. A. Flavell, L. Alexopoulou, M. A. Schaller, A. Gruber, A. A. Berlin, and N. W. Lukacs Deletion of TLR3 Alters the Pulmonary Immune Environment and Mucus Production during Respiratory Syncytial Virus Infection J. Immunol., February 1, 2006; 176(3): 1937 - 1942. [Abstract] [Full Text] [PDF]

				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. [Abstract] [Full Text] [PDF]

				V. V. Jain, T. R. Businga, K. Kitagaki, C. L. George, P. T. O'Shaughnessy, and J. N. Kline Mucosal immunotherapy with CpG oligodeoxynucleotides reverses a murine model of chronic asthma induced by repeated antigen exposure Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L1137 - L1146. [Abstract] [Full Text] [PDF]

				J. V. Fahy Goblet Cell and Mucin Gene Abnormalities in Asthma Chest, December 1, 2002; 122(6_suppl): 320S - 326S. [Abstract] [Full Text] [PDF]

				K. Kohri, I.F. Ueki, J-J. Shim, P-R. Burgel, Y-M. Oh, D.C. Tam, T. Dao-Pick, and J.A. Nadel Pseudomonas aeruginosa induces MUC5AC production via epidermal growth factor receptor Eur. Respir. J., November 1, 2002; 20(5): 1263 - 1270. [Abstract] [Full Text] [PDF]

				A. Xiang, Y. Uchida, A. Nomura, H. Iijima, T. Sakamoto, Y. Ishii, Y. Morishima, K. Masuyama, M. Zhang, K. Hirano, et al. Involvement of thromboxane A2 in airway mucous cells in asthma-related cough J Appl Physiol, February 1, 2002; 92(2): 763 - 770. [Abstract] [Full Text] [PDF]

				P. K. JEFFERY Remodeling in Asthma and Chronic Obstructive Lung Disease Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): S28 - 38. [Abstract] [Full Text] [PDF]

				J. V. FAHY Remodeling of the Airway Epithelium in Asthma Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): S46 - 51. [Abstract] [Full Text] [PDF]

				M. Saetta and G. Turato Airway pathology in asthma Eur. Respir. J., July 2, 2001; 18(34_suppl): 18S - 23s. [Abstract] [Full Text] [PDF]

				A. Nakata, O. Kaminuma, K. Ogawa, H. Fujimura, K. Fushimi, H. Kikkawa, K. Naito, K. Ikezawa, R. W. Egan, and A. Mori Correlation between eosinophilia induced by CD4+ T cells and bronchial hyper-responsiveness Int. Immunol., March 1, 2001; 13(3): 329 - 339. [Abstract] [Full Text] [PDF]

				C. L. ORDOÑEZ, R. KHASHAYAR, H. H. WONG, R. FERRANDO, R. WU, D. M. HYDE, J. A. HOTCHKISS, Y. ZHANG, A. NOVIKOV, G. DOLGANOV, et al. Mild and Moderate Asthma Is Associated with Airway Goblet Cell Hyperplasia and Abnormalities in Mucin Gene Expression Am. J. Respir. Crit. Care Med., February 1, 2001; 163(2): 517 - 523. [Abstract] [Full Text]

				Y. Tesfaigzi, M. J. Fischer, A. J. Martin, and J. Seagrave Bcl-2 in LPS- and allergen-induced hyperplastic mucous cells in airway epithelia of Brown Norway rats Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1210 - L1217. [Abstract] [Full Text] [PDF]

				J. BOUSQUET, P. K. JEFFERY, W. W. BUSSE, M. JOHNSON, and A. M. VIGNOLA Asthma . From Bronchoconstriction to Airways Inflammation and Remodeling Am. J. Respir. Crit. Care Med., May 1, 2000; 161(5): 1720 - 1745. [Full Text]

				P. K. Jeffery Comparison of the Structural and Inflammatory Features of COPD and Asthma Giles F. Filley Lecture Chest, May 1, 2000; 117(5_suppl_1): 251S - 260S. [Abstract] [Full Text] [PDF]

				J. A. Nadel Mechanisms of Airway Hypersecretion and Novel Therapy Chest, May 1, 2000; 117(5_suppl_1): 262S - 266S. [Full Text] [PDF]

				A. TOMKINSON, A. KANEHIRO, N. RABINOVITCH, A. JOETHAM, G. CIESLEWICZ, and E. W. GELFAND The Failure of STAT6-deficient Mice to Develop Airway Eosinophilia and Airway Hyperresponsiveness Is Overcome by Interleukin-5 Am. J. Respir. Crit. Care Med., October 1, 1999; 160(4): 1283 - 1291. [Abstract] [Full Text]

				K. Dabbagh, K. Takeyama, H.-M. Lee, I. F. Ueki, J. A. Lausier, and J. A. Nadel IL-4 Induces Mucin Gene Expression and Goblet Cell Metaplasia In Vitro and In Vivo J. Immunol., May 15, 1999; 162(10): 6233 - 6237. [Abstract] [Full Text] [PDF]

				D. I. Blyth, M. S. Pedrick, T. J. Savage, H. Bright, J. E. Beesley, and S. Sanjar Induction, Duration, and Resolution of Airway Goblet Cell Hyperplasia in a Murine Model of Atopic Asthma: Effect of Concurrent Infection with Respiratory Syncytial Virus and Response to Dexamethasone Am. J. Respir. Cell Mol. Biol., July 1, 1998; 19(1): 38 - 54. [Abstract] [Full Text]