Am. J. Respir. Crit. Care Med., Volume 164, Number 10, November 2001, S76-S80

Remodeling in Response to Infection and Injury
Airway Inflammation and Hypersecretion of Mucus in Smoking Subjects with Chronic Obstructive Pulmonary Disease

PIERO MAESTRELLI, MARINA SAETTA, CRISTINA E. MAPP, and LEONARDO M. FABBRI

University of Padua, Padua, Italy; University of Ferrara, Ferrara, Italy; and University of Modena and Reggio Emilia, Modena, Italy

Airway epithelium represents the first line of defense against toxic inhalants. In some subjects, cigarette smoking causes airway inflammation, hypersecretion of mucus, and poorly reversible airflow limitation through mechanisms that are still largely unknown. Likewise, it is unclear why only some smokers develop chronic obstructive pulmonary disease (COPD). Two cell types consistently result in relation to chronic airflow limitation in COPD: neutrophils and CD8⁺ cells. Neutrophils are compartmentalized in the mucosal surface of the airways and air spaces, that is, the epithelium and lumen, whereas CD8⁺ cells exhibit a more extensive distribution along the subepithelial zone of the airways and lung parenchyma, including alveolar walls and arteries. This pattern of inflammatory cell distribution is observed in mild or moderate COPD, and in patients who have developed COPD, it is not modified by smoking cessation. The number of neutrophils further increases in the submucosa of patients with severe COPD, suggesting a role for these cells in the progression of the disease. Hypersecretion of mucus is a major manifestation in COPD. Mucus is produced by bronchial glands and goblet cells lining the airway epithelium. Unlike mucous gland enlargement, greater mucosal inflammation is associated with sputum production. Whereas neutrophil infiltration of submucosal glands occurs only in smokers with COPD, goblet cell hyperplasia in peripheral airways occurs both in smokers with or without COPD, suggesting that the major determinant of goblet cell hyperplasia is cigarette smoke itself.

This article has been cited by other articles:

				C. J. Jolley and J. Moxham A physiological model of patient-reported breathlessness during daily activities in COPD Eur. Respir. Rev., June 1, 2009; 18(112): 66 - 79. [Abstract] [Full Text] [PDF]

				B. M. Rollins, M. Burn, R. D. Coakley, L. A. Chambers, A. J. Hirsh, M. T. Clunes, M. I. Lethem, S. H. Donaldson, and R. Tarran A2B Adenosine Receptors Regulate the Mucus Clearance Component of the Lung's Innate Defense System Am. J. Respir. Cell Mol. Biol., August 1, 2008; 39(2): 190 - 197. [Abstract] [Full Text] [PDF]

				C. M. Freeman, J. L. Curtis, and S. W. Chensue CC Chemokine Receptor 5 and CXC Chemokine Receptor 6 Expression by Lung CD8+ Cells Correlates with Chronic Obstructive Pulmonary Disease Severity Am. J. Pathol., September 1, 2007; 171(3): 767 - 776. [Abstract] [Full Text] [PDF]

				M. P. Smit-de Vries, M. van der Toorn, R. Bischoff, and H. F. Kauffman Resistance of quiescent and proliferating airway epithelial cells to H2O2 challenge Eur. Respir. J., April 1, 2007; 29(4): 633 - 642. [Abstract] [Full Text] [PDF]

				C. Bergeron, M. K. Tulic, and Q. Hamid Tools used to measure airway remodelling in research Eur. Respir. J., March 1, 2007; 29(3): 596 - 604. [Abstract] [Full Text] [PDF]

				A. Agrawal, S. Rengarajan, K. B. Adler, A. Ram, B. Ghosh, M. Fahim, and B. F. Dickey Inhibition of mucin secretion with MARCKS-related peptide improves airway obstruction in a mouse model of asthma J Appl Physiol, January 1, 2007; 102(1): 399 - 405. [Abstract] [Full Text] [PDF]

				D. Aronson, I. Roterman, M. Yigla, A. Kerner, O. Avizohar, R. Sella, P. Bartha, Y. Levy, and W. Markiewicz Inverse Association between Pulmonary Function and C-Reactive Protein in Apparently Healthy Subjects Am. J. Respir. Crit. Care Med., September 15, 2006; 174(6): 626 - 632. [Abstract] [Full Text] [PDF]

				O. W. Williams, A. Sharafkhaneh, V. Kim, B. F. Dickey, and C. M. Evans Airway Mucus: From Production to Secretion Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 527 - 536. [Abstract] [Full Text] [PDF]

				Y. Tesfaigzi Roles of Apoptosis in Airway Epithelia Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 537 - 547. [Abstract] [Full Text] [PDF]

				C. Bergeron and L.-P. Boulet Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation. Chest, April 1, 2006; 129(4): 1068 - 1087. [Abstract] [Full Text] [PDF]

				Y. Chiba, M. Murata, H. Ushikubo, Y. Yoshikawa, A. Saitoh, H. Sakai, J. Kamei, and M. Misawa Effect of Cigarette Smoke Exposure In Vivo on Bronchial Smooth Muscle Contractility In Vitro in Rats Am. J. Respir. Cell Mol. Biol., December 1, 2005; 33(6): 574 - 581. [Abstract] [Full Text] [PDF]

				S. Korn, R. Wiewrodt, Y. C. Walz, K. Becker, E. Mayer, F. Krummenauer, and R. Buhl Characterization of the Interstitial Lung and Peripheral Blood T Cell Receptor Repertoire in Cigarette Smokers Am. J. Respir. Cell Mol. Biol., February 1, 2005; 32(2): 142 - 148. [Abstract] [Full Text] [PDF]

				C. A. Martey, S. J. Pollock, C. K. Turner, K. M. A. O'Reilly, C. J. Baglole, R. P. Phipps, and P. J. Sime Cigarette smoke induces cyclooxygenase-2 and microsomal prostaglandin E2 synthase in human lung fibroblasts: implications for lung inflammation and cancer Am J Physiol Lung Cell Mol Physiol, November 1, 2004; 287(5): L981 - L991. [Abstract] [Full Text] [PDF]

				E. Gensch, M. Gallup, A. Sucher, D. Li, A. Gebremichael, H. Lemjabbar, A. Mengistab, V. Dasari, J. Hotchkiss, J. Harkema, et al. Tobacco Smoke Control of Mucin Production in Lung Cells Requires Oxygen Radicals AP-1 and JNK J. Biol. Chem., September 10, 2004; 279(37): 39085 - 39093. [Abstract] [Full Text] [PDF]

				N. A. Molfino Genetics of COPD Chest, May 1, 2004; 125(5): 1929 - 1940. [Abstract] [Full Text] [PDF]

				K. U. Hong, S. D. Reynolds, S. Watkins, E. Fuchs, and B. R. Stripp Basal Cells Are a Multipotent Progenitor Capable of Renewing the Bronchial Epithelium Am. J. Pathol., February 1, 2004; 164(2): 577 - 588. [Abstract] [Full Text] [PDF]

				E. H. Bel Smoking: A Neglected Cause of Glucocorticoid Resistance in Asthma Am. J. Respir. Crit. Care Med., December 1, 2003; 168(11): 1265 - 1266. [Full Text] [PDF]

				E{-}J.D. Oudijk, J{-}W.J. Lammers, and L. Koenderman Systemic inflammation in chronic obstructive pulmonary disease Eur. Respir. J., November 2, 2003; 22(46_suppl): 5s - 13s. [Abstract] [Full Text] [PDF]

				J. E. Foster, K. Gott, M. R. Schuyler, W. Kozak, and Y. Tesfaigzi LPS-induced neutrophilic inflammation and Bcl-2 expression in metaplastic mucous cells Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L405 - L414. [Abstract] [Full Text] [PDF]

				M. Frohlich, M. Sund, H. Lowel, A. Imhof, A. Hoffmeister, and W. Koenig Independent association of various smoking characteristics with markers of systemic inflammation in men: Results from a representative sample of the general population (MONICA Augsburg Survey 1994/95) Eur. Heart J., July 2, 2003; 24(14): 1365 - 1372. [Abstract] [Full Text] [PDF]

				E Hnizdo and V Vallyathan Chronic obstructive pulmonary disease due to occupational exposure to silica dust: a review of epidemiological and pathological evidence Occup. Environ. Med., April 1, 2003; 60(4): 237 - 243. [Abstract] [Full Text] [PDF]

				M. Laan, O. Prause, M. Miyamoto, M. Sjostrand, A.M. Hytonen, T. Kaneko, J. Lotvall, and A. Linden A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF-{alpha} Eur. Respir. J., March 1, 2003; 21(3): 387 - 393. [Abstract] [Full Text] [PDF]

				M. J. TOBIN Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2001 Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 598 - 618. [Full Text] [PDF]