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Am. J. Respir. Crit. Care Med., Volume 158, Number 4, October 1998, 1277-1285

Severity of Airflow Limitation Is Associated with Severity of Airway Inflammation in Smokers

ANTONINO DI STEFANO, ARMANDO CAPELLI, MIRCO LUSUARDI, PIERO BALBO, CINZIA VECCHIO, PIERO MAESTRELLI, CRISTINA E. MAPP, LEONARDO M. FABBRI, CLAUDIO F. DONNER, and MARINA SAETTA

Salvatore Maugeri Foundation, IRCCS, Medical Center of Rehabilitation, Division of Pulmonary Disease, Veruno; Division of Internal Medicine, Gattinara; Institute of Occupational Medicine, University of Padova, Padova; Institute of Pulmonary Diseases, University of Ferrara, Ferrara, Italy

To investigate the relationship between airflow limitation and airway inflammation in smokers, we examined paraffin-embedded bronchial biopsies obtained from 30 smokers: 10 with severe airflow limitation, eight with mild/moderate airflow limitation, and 12 control smokers with normal lung function. Histochemical and immunohistochemical methods were performed to assess the number of inflammatory cells in the subepithelium and the expression of CC chemokines macrophage inflammatory protein (MIP)-1alpha and -1beta in the bronchial mucosa. Compared with control smokers, smokers with severe airflow limitation had an increased number of neutrophils (p < 0.02), macrophages (p < 0.03), and NK lymphocytes (p < 0.03) in the subepithelium, and an increased number of MIP-1alpha + epithelial cells (p < 0.02). When all smokers were considered together, the value of FEV1 was inversely correlated with the number of neutrophils (r = -0.59, p < 0.002), macrophages (r = -047, p < 0.012), NK-lymphocytes (r = -0.51, p < 0.006) in the subepithelium, and with the number of MIP-1alpha + epithelial cells (r = -0.61, p < 0.003). We conclude that in smokers the severity of airflow limitation is correlated with the severity of airway inflammation and that severe airflow limitation is associated with an increased number of neutrophils, macrophages, NK lymphocytes, and MIP-1alpha + cells in the bronchial mucosa.




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Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease
Thorax, October 1, 2002; 57(10): 847 - 852.
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A. Di Stefano, G. Caramori, T. Oates, A. Capelli, M. Lusuardi, I. Gnemmi, F. Ioli, K.F. Chung, C.F. Donner, P.J. Barnes, et al.
Increased expression of nuclear factor-{kappa}B in bronchial biopsies from smokers and patients with COPD
Eur. Respir. J., September 1, 2002; 20(3): 556 - 563.
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 Am. J. Respir. Crit. Care Med.Home page
T. Harju, R. Kaarteenaho-Wiik, Y. Soini, R. Sormunen, and V. L. Kinnula
Diminished Immunoreactivity of {gamma}-Glutamylcysteine Synthetase in the Airways of Smokers' Lung
Am. J. Respir. Crit. Care Med., September 1, 2002; 166(5): 754 - 759.
[Abstract] [Full Text] [PDF]

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I S Patel, T A R Seemungal, M Wilks, S J Lloyd-Owen, G C Donaldson, and J A Wedzicha
Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations
Thorax, September 1, 2002; 57(9): 759 - 764.
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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.
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C. Sohy, C. Pilette, M.S. Niederman, and Y. Sibille
Acute exacerbation of chronic obstructive pulmonary disease and antibiotics: what studies are still needed?
Eur. Respir. J., May 1, 2002; 19(5): 966 - 975.
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M Tanino, T Betsuyaku, K Takeyabu, Y Tanino, E Yamaguchi, K Miyamoto, and M Nishimura
Increased levels of interleukin-8 in BAL fluid from smokers susceptible to pulmonary emphysema
Thorax, May 1, 2002; 57(5): 405 - 411.
[Abstract] [Full Text] [PDF]

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R. A. Stockley
Neutrophils and the Pathogenesis of COPD*
Chest, May 1, 2002; 121 (2009): 151S - 155S.
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W. I. de Boer
Cytokines and Therapy in COPD* : A Promising Combination?
Chest, May 1, 2002; 121 (2009): 209S - 218S.
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T. L. CROXTON, G. G. WEINMANN, R. M. SENIOR, and J. R. HOIDAL
Future Research Directions in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., March 15, 2002; 165(6): 838 - 844.
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G. W. Chalmers, K. J. MacLeod, L. Thomson, S. A. Little, C. McSharry, and N. C. Thomson
Smoking and Airway Inflammation in Patients With Mild Asthma
Chest, December 1, 2001; 120(6): 1917 - 1922.
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 Am. J. Respir. Crit. Care Med.Home page
J. A. Wedzicha
Airway Infection Accelerates Decline of Lung Function in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1757 - 1758.
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 Am. J. Respir. Crit. Care Med.Home page
W. MacNee
Airway Infection Does Not Accelerate Decline in Lung Function in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1758 - 1759.
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P. MAESTRELLI, M. SAETTA, C. E. MAPP, and L. M. FABBRI
Remodeling in Response to Infection and Injury . Airway Inflammation and Hypersecretion of Mucus in Smoking Subjects with Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): S76 - 80.
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M. KURZIUS-SPENCER, D. L. SHERRILL, C. J. HOLBERG, F. D. MARTINEZ, and M. D. LEBOWITZ
Familial Correlation in the Decline of Forced Expiratory Volume in One Second
Am. J. Respir. Crit. Care Med., October 1, 2001; 164(7): 1261 - 1265.
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M. Saetta and G. Turato
Airway pathology in asthma
Eur. Respir. J., July 2, 2001; 18(34_suppl): 18S - 23s.
[Abstract] [Full Text] [PDF]

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U. Costabel
Bronchial Eosinophilia in Exacerbation of Bronchitis . An Allergic Profile of Inflammation?
Am. J. Respir. Crit. Care Med., July 1, 2001; 164(1): 3 - 4.
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A. J. Edgar, E. J. Birks, M. H. Yacoub, and J. M. Polak
Cloning of Dexamethasone-Induced Transcript . A Novel Glucocorticoid-Induced Gene that Is Upregulated in Emphysema
Am. J. Respir. Cell Mol. Biol., July 1, 2001; 25(1): 119 - 124.
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M. SAETTA, G. TURATO, P. MAESTRELLI, C. E. MAPP, and L. M. FABBRI
Cellular and Structural Bases of Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., May 1, 2001; 163(6): 1304 - 1309.
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 Am. J. Respir. Crit. Care Med.Home page
H. TAKIZAWA, M. TANAKA, K. TAKAMI, T. OHTOSHI, K. ITO, M. SATOH, Y. OKADA, F. YAMASAWA, K. NAKAHARA, and A. UMEDA
Increased Expression of Transforming Growth Factor-{beta}1 in Small Airway Epithelium from Tobacco Smokers and Patients with Chronic Obstructive Pulmonary Disease (COPD)
Am. J. Respir. Crit. Care Med., May 1, 2001; 163(6): 1476 - 1483.
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S. Sethi and T. F. Murphy
Bacterial Infection in Chronic Obstructive Pulmonary Disease in 2000: a State-of-the-Art Review
Clin. Microbiol. Rev., April 1, 2001; 14(2): 336 - 363.
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C. PILETTE, V. GODDING, R. KISS, M. DELOS, E. VERBEKEN, C. DECAESTECKER, K. DE PAEPE, J.-P. VAERMAN, M. DECRAMER, and Y. SIBILLE
Reduced Epithelial Expression of Secretory Component in Small Airways Correlates with Airflow Obstruction in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., January 1, 2001; 163(1): 185 - 194.
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A. Hill, S. Gompertz, and R. Stockley
Factors influencing airway inflammation in chronic obstructive pulmonary disease
Thorax, November 1, 2000; 55(11): 970 - 977.
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B. Balbi, M. Majori, S. Bertacco, G. Convertino, A. Cuomo, C. F. Donner, and A. Pesci
Inhaled Corticosteroids in Stable COPD Patients : Do They Have Effects on Cells and Molecular Mediators of Airway Inflammation?
Chest, June 1, 2000; 117(6): 1633 - 1637.
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N. F. Voelkel and R. Tuder
COPD : Exacerbation
Chest, May 1, 2000; 117 (2009): 376S - 379S.
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A. T. HILL, E. J. CAMPBELL, D. L. BAYLEY, S. L. HILL, and R. A. STOCKLEY
Evidence for Excessive Bronchial Inflammation during an Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Patients with alpha 1-Antitrypsin Deficiency (PiZ)
Am. J. Respir. Crit. Care Med., December 1, 1999; 160(6): 1968 - 1975.
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M. SAETTA
Airway Inflammation in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): S17 - 20.
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P J STERK, H W F M DE GOUW, F L M RICCIARDOLO, and K F RABE
Exhaled nitric oxide in COPD: glancing through a smoke screen
Thorax, July 1, 1999; 54(7): 565 - 567.
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