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Am. J. Respir. Crit. Care Med., Volume 156, Number 3, September 1997, 737-743

Bronchoscopic Evaluation of Severe Asthma
Persistent Inflammation Associated with High Dose Glucocorticoids

SALLY E. WENZEL, STANLEY J. SZEFLER, DONALD Y. M. LEUNG, STEVEN I. SLOAN, MICHAEL D. REX, and RICHARD J. MARTIN

Departments of Medicine and Pediatrics, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, Colorado

The role of inflammation in the pathogenesis of severe asthma chronically treated with high doses of glucocorticoids is poorly understood. Despite this, treatment has been aimed at advancing anti- inflammatory and immunomodulator therapy. This study was designed to evaluate both the presence and type of airway inflammation in patients with severe asthma. A prospective bronchoscopic study evaluated 14 severe, high-dose oral glucocorticoid dependent asthmatics. Bronchoalveolar lavage fluid was analyzed for cytology and inflammatory mediators. Endobronchial and transbronchial biopsies were performed in selected patients for morphometric evaluation of macrophage/monocytes, neutrophils, eosinophils and lymphocytes. These results were compared with lavage and endo- and transbronchial biopsy studies in normal controls and patients with moderate asthma. The concentration of eosinophils in bronchoalveolar lavage fluid was highest in the moderate asthmatics not on glucocorticoids, with very little difference between normal controls and severe asthmatics (significant difference among the groups, p = 0.007). In contrast, the severe asthmatics demonstrated a twofold higher concentration of neutrophils in lavage than either the mild-moderate asthmatics, or the normal controls (p = 0.032 among the groups, p < 0.05 between the severe asthmatics and both controls). Similar results were obtained in the endobronchial and transbronchial biopsy specimens, which consistently showed significantly higher numbers of neutrophils in the severe asthmatics than in the control groups. The eicosanoid mediators, thromboxane and leukotriene B4, were also highest in the severe asthma group (differences among the groups, p = 0.019 and p = 0.023, respectively). These findings suggest that inflammation remains in severe symptomatic asthmatics despite treatment with high dose glucocorticoids which may be due to the severity of disease, glucocorticoid treatment, or other as yet undefined factors.




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C. Taube, A. Dakhama, Y.-H. Rha, K. Takeda, A. Joetham, J.-W. Park, A. Balhorn, T. Takai, K. R. Poch, J. A. Nick, et al.
Transient Neutrophil Infiltration After Allergen Challenge Is Dependent on Specific Antibodies and Fc{gamma}III Receptors
J. Immunol., April 15, 2003; 170(8): 4301 - 4309.
[Abstract] [Full Text] [PDF]

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M. K. Tulic and Q. Hamid
Contribution of the Distal Lung to the Pathologic and Physiologic Changes in Asthma: Potential Therapeutic Target Roger S. Mitchell Lecture
Chest, March 1, 2003; 123 (2009): 348S - 355S.
[Abstract] [Full Text] [PDF]

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C. Taube, A. Dakhama, K. Takeda, J. A. Nick, and E. W. Gelfand
Allergen-Specific Early Neutrophil Infiltration After Allergen Challenge in a Murine Model
Chest, March 1, 2003; 123 (2009): 410S - 411S.
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K. Chmura, R. D. Lutz, H. Chiba, M. S. Numata, H.-J. Choi, G. Fantuzzi, D. R. Voelker, and E. D. Chan
Mycoplasma pneumoniae Antigens Stimulate Interleukin-8
Chest, March 1, 2003; 123 (2009): 425S - 425S.
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S. Wenzel
Severe/Fatal Asthma
Chest, March 1, 2003; 123 (2009): 405S - 410S.
[Abstract] [Full Text] [PDF]

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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]

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W. M. Abraham
Of Mice and Men
Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 1 - 4.
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M.M.M. Pizzichini
Is sputum eosinophilia a good or poor predictor of benefit from inhaled corticosteroid therapy in asthma?
Eur. Respir. J., December 1, 2002; 20(6): 1359 - 1361.
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M. Romagnoli, I. Vachier, P. Tarodo de la Fuente, H. Meziane, C. Chavis, J. Bousquet, P. Godard, and P. Chanez
Eosinophilic inflammation in sputum of poorly controlled asthmatics
Eur. Respir. J., December 1, 2002; 20(6): 1370 - 1377.
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P.K. Jeffery, P. Venge, M.J. Gizycki, I. Egerod, R. Dahl, and P. Faurschou
Effects of salmeterol on mucosal inflammation in asthma: a placebo-controlled study
Eur. Respir. J., December 1, 2002; 20(6): 1378 - 1385.
[Abstract] [Full Text] [PDF]

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F. Kanniess, K. Richter, S. Janicki, M.B. Schleiss, R.A. Jorres, and H. Magnussen
Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma
Eur. Respir. J., November 1, 2002; 20(5): 1080 - 1087.
[Abstract] [Full Text] [PDF]

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L. Lehtimaki, H. Kankaanranta, S. Saarelainen, V. Turjanmaa, and E. Moilanen
Increased alveolar nitric oxide concentration in asthmatic patients with nocturnal symptoms
Eur. Respir. J., October 1, 2002; 20(4): 841 - 845.
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M. Le Bourgeois, M. Goncalves, L. Le Clainche, M.-R. Benoist, J.-C. Fournet, P. Scheinmann, and J. de Blic
Bronchoalveolar Cells in Children < 3 Years Old With Severe Recurrent Wheezing*
Chest, September 1, 2002; 122(3): 791 - 797.
[Abstract] [Full Text] [PDF]

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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]

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A. James and N. Carroll
Transbronchial biopsy as a tool to evaluate small-airways disease in asthma. Cons
Eur. Respir. J., August 1, 2002; 20(2): 249 - 251.
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S. Balzar, S.E. Wenzel, and H.W. Chu
Transbronchial biopsy as a tool to evaluate small airways in asthma
Eur. Respir. J., August 1, 2002; 20(2): 254 - 259.
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R.E. Louis, D. Cataldo, M.G. Buckley, J. Sele, M. Henket, L.C. Lau, P. Bartsch, A.F. Walls, and R. Djukanovic
Evidence of mast-cell activation in a subset of patients with eosinophilic chronic obstructive pulmonary disease
Eur. Respir. J., August 1, 2002; 20(2): 325 - 331.
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G. P. Currie and B. J. Lipworth
Bronchoprotective Effects of Leukotriene Receptor Antagonists in Asthma* : A Meta-analysis
Chest, July 1, 2002; 122(1): 146 - 150.
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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.
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J Douwes, P Gibson, J Pekkanen, and N Pearce
Non-eosinophilic asthma: importance and possible mechanisms
Thorax, July 1, 2002; 57(7): 643 - 648.
[Abstract] [Full Text] [PDF]

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C. Bonnans, I. Vachier, C. Chavis, P. Godard, J. Bousquet, and P. Chanez
Lipoxins Are Potential Endogenous Antiinflammatory Mediators in Asthma
Am. J. Respir. Crit. Care Med., June 1, 2002; 165(11): 1531 - 1535.
[Abstract] [Full Text] [PDF]

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S A Little, M W Sproule, M D Cowan, K J Macleod, M Robertson, J G Love, G W Chalmers, C P McSharry, and N C Thomson
High resolution computed tomographic assessment of airway wall thickness in chronic asthma: reproducibility and relationship with lung function and severity
Thorax, March 1, 2002; 57(3): 247 - 253.
[Abstract] [Full Text] [PDF]

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L. Michalec, B. K. Choudhury, E. Postlethwait, J. S. Wild, R. Alam, M. Lett-Brown, and S. Sur
CCL7 and CXCL10 Orchestrate Oxidative Stress-Induced Neutrophilic Lung Inflammation
J. Immunol., January 15, 2002; 168(2): 846 - 852.
[Abstract] [Full Text] [PDF]

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H. Nakamura, A. D. Luster, H. Tateno, S. Jedrzkiewicz, G. Tamura, K. J. Haley, E. A. Garcia-Zepeda, K. Yamaguchi, and C. M. Lilly
IL-4 differentially regulates eotaxin and MCP-4 in lung epithelium and circulating mononuclear cells
Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1288 - L1302.
[Abstract] [Full Text] [PDF]

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D. N. R. PAYNE, I. M. ADCOCK, N. M. WILSON, T. OATES, M. SCALLAN, and A. BUSH
Relationship between Exhaled Nitric Oxide and Mucosal Eosinophilic Inflammation in Children with Difficult Asthma, after Treatment with Oral Prednisolone
Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1376 - 1381.
[Abstract] [Full Text] [PDF]

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A. Takaoka, Y. Tanaka, T. Tsuji, T. Jinushi, A. Hoshino, Y. Asakura, Y. Mita, K. Watanabe, S. Nakaike, Y. Togashi, et al.
A Critical Role for Mouse CXC Chemokine(s) in Pulmonary Neutrophilia During Th Type 1-Dependent Airway Inflammation
J. Immunol., August 15, 2001; 167(4): 2349 - 2353.
[Abstract] [Full Text] [PDF]

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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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J.C. Kips
Cytokines in asthma
Eur. Respir. J., July 2, 2001; 18(34_suppl): 24S - 33s.
[Abstract] [Full Text] [PDF]

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K.F. Chung
Cytokines in chronic obstructive pulmonary disease
Eur. Respir. J., July 2, 2001; 18(34_suppl): 50S - 59s.
[Abstract] [Full Text] [PDF]

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P.J. Barnes
Cytokine modulators as novel therapies for airway disease
Eur. Respir. J., July 2, 2001; 18(34_suppl): 67S - 77s.
[Abstract] [Full Text] [PDF]

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P. G. Gibson, J. L. Simpson, and N. Saltos
Heterogeneity of Airway Inflammation in Persistent Asthma : Evidence of Neutrophilic Inflammation and Increased Sputum Interleukin-8
Chest, May 1, 2001; 119(5): 1329 - 1336.
[Abstract] [Full Text] [PDF]

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S. S. Salvi, M. T. Krishna, A. P. Sampson, and S. T. Holgate
The Anti-inflammatory Effects of Leukotriene-Modifying Drugs and Their Use in Asthma
Chest, May 1, 2001; 119(5): 1533 - 1546.
[Abstract] [Full Text] [PDF]

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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.
[Full Text]

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D N R Payne, N M Wilson, A James, H Hablas, C Agrafioti, and A Bush
Evidence for different subgroups of difficult asthma in children
Thorax, May 1, 2001; 56(5): 345 - 350.
[Abstract] [Full Text]


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