Abstract | BACKGROUND: OBJECTIVE: We sought to determine whether SR asthma is accompanied by decreased airflow reversibility and could lead to airway remodeling. METHODS: Spirometric results were evaluated for 40 asthmatic patients defined as having SR or steroid-sensitive (SS) asthma on the basis of a 1-week course of oral prednisone. Twenty-three asthmatic patients underwent bronchoscopy with collection of bronchoalveolar lavage (BAL) fluid to analyze markers of airway remodeling in BAL fluid and cells. RESULTS:
Prednisone significantly improved FEV(1) percent predicted in SS asthma (62.0% +/- 10.9% [mean +/- SD] to 79.4% +/- 11.3%, P < .001) but not in SR asthma (66.9% +/- 10.0% to 65.9% +/- 12.1%). The bronchodilator response was significantly greater in the SS than in the SR group (Delta FEV(1) percent predicted, 33.5% +/- 22.5% vs 15.2% +/- 7.9%; P = .001), regardless of inhaled corticosteroid use. No difference in amounts of matrix metalloproteinase ( MMP) 9, PMN elastase, or vascular endothelial growth factor was found in BAL fluid from both groups. Tissue inhibitor of metalloproteinases (TIMP) 1 levels were, however, significantly less in BAL fluid of patients with SR asthma compared with those in patients with SS asthma (921.9 +/- 313.4 vs 2267.0 +/- 456.8 pg/mL, P < .05), resulting in significantly higher MMP-9/TIMP-1 ratios in the BAL fluid of patients with SR asthma (0.24 +/- 0.04 vs 0.11 +/- 0.03, P < .01). Finally, dexamethasone treatment induced TIMP-1 mRNA in BAL fluid cells from patients with SS asthma (P < .01) but not in cells from patients with SR asthma. CONCLUSION: CLINICAL IMPLICATIONS: SR asthma might lead to irreversible airways disease.
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Authors | Elena Goleva, Pia J Hauk, Juri Boguniewicz, Richard J Martin, Donald Y M Leung |
Journal | The Journal of allergy and clinical immunology
(J Allergy Clin Immunol)
Vol. 120
Issue 5
Pg. 1065-72
(Nov 2007)
ISSN: 1097-6825 [Electronic] United States |
PMID | 17900681
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Adrenal Cortex Hormones
- Bronchodilator Agents
- RNA, Messenger
- Tissue Inhibitor of Metalloproteinase-1
- Vascular Endothelial Growth Factor A
- Dexamethasone
- Leukocyte Elastase
- Matrix Metalloproteinase 9
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Topics |
- Adrenal Cortex Hormones
(therapeutic use)
- Adult
- Asthma
(drug therapy, pathology)
- Bronchi
(pathology)
- Bronchoalveolar Lavage Fluid
(chemistry)
- Bronchodilator Agents
(therapeutic use)
- Dexamethasone
(therapeutic use)
- Drug Resistance
- Female
- Humans
- Leukocyte Elastase
(analysis, metabolism)
- Male
- Matrix Metalloproteinase 9
(analysis, metabolism)
- Middle Aged
- RNA, Messenger
(analysis, metabolism)
- Spirometry
- Tissue Inhibitor of Metalloproteinase-1
(analysis, genetics, metabolism)
- Vascular Endothelial Growth Factor A
(analysis, metabolism)
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