Bronchial asthma and airway remodeling markers

Abstract: Asthma is an inflammatory disease with extracellular matrix remodeling and collagen deposition. Vascular alterations have been suggested to contribute to airway hyper responsiveness. Vascular endothelial growth factors and metalloproteinases are mediators of airway inflammation and remodeling in asthma. There are few data regarding the potential effects of anti-asthma treatment on indices of air way remodeling

Objective: This study investigates the role of VEGF, MMP-9 in the pathogenesis of asthma and their role as index of remodeling, markers of inflammation in symptomatic bronchial asthma on low dose ICS. Also we evaluate the role of adding long acting B[2] agonist for 6 weeks in airway remodeling for the symptomatic asthmatic patients on low dose ICS

Methods: VEGF and MMP-9 were measured in sputum of healthy control, and bronchial asthma patients before and after the addition of long acting B[2] agonists. Also we evaluated whether VEGF correlated with MMP-9 in symptomatic bronchial asthma receiving low or moderate dose of ICS

Results: Levels of VEGF and MMP-9 are significantly higher in sputum of bronchial asthma than in healthy controls. The mean level of VEGF, MMP-9 in sputum of bronchial asthma patients on low to moderate dose of ICS was 2500 pg/ml +/- 750, 33.3 ng/ml +/- 16.7. After 6 weeks of treatment with long acting B[2] agonists there was a reduction in the mean levels of both VEGF, MMP-9 1750 pg/ml +/- 250, 27.4 ng/ml +/- 13. Also there was a significant correlation between the levels of VEGF and MMP-9 in healthy subjects and patients with bronchial asthma. There was a significant correlation between both VEGF MMP-9 and the sputum eosinophils and neutrophil in patients with bronchial asthma before adding long acting B[2] agonists

Conclusion: Symptomatic patients with bronchial asthma on a low dose ICS have elevated levels of VEGF, MMP-9. There was an interrelationship between VEGF and MMP-9, this finding suggests that VEGF signaling regulates MMP-9 expression, and plays a critical role in the maintenance of asthma. VEGF, MMP-9 could be considered as important markers of airway remodeling in asthma. The addition of regular long acting B[2] agonist to low or moderate dose ICS in symptomatic bronchial asthma patients had a beneficial effect on the air way remodeling markers in a way that they may potentate the anti-inflammatory effects of ICS on inflammatory cells

Interplay between matrix metalloproteinase-9 and tissue inhibitor of matrix metalloprotinase-1 in acute asthma exacerbation and airway remodeling

Airway inflammation and remodeling of extracellular matrix are important features of asthma. Matrix metalloproteinases [MMPs] are group of enzymes expressed in the airways with their inhibitor [tissue inhibitor of MMPs [TIMP] and they are the key responsible for extra cellular matrix [ECM] degradation. To clarify the role of MMP-9 and TIMP-1 in asthma exacerbation and airway remodeling. The study included 3 groups, group "A" included 22 patients with stable asthma group "B" included 18 patients during asthma exacerbation and group "C" of 18 healthy volunteer served as control. All groups were matching age and sex. Levels of MMP-9 and TIMP-1 were measured in the induced sputum of the 3 groups. Serum IgE skin prick test and PEFR were assessed. MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio increased in both A and B groups in comparison to control [P < 0.001]. During exacerbation MMP-9 and MMP-9/TIMP-1 ratio showed significant increase for both but TIMP-1 did not show significant change when compared to stable asthmatics. There was significant negative correlation between PEFR and MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio. MMP-9 and TIMP-1 play an important role in pathophysiology of asthma exacerbation and airway remodeling. Clearly, a greater understanding of the pathogenesis of asthma is critical to the development of better therapeutic modalities

Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling

Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-β1 (TGF-β1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-β1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-β1.

High resolution computed tomography assessment of airway wall thickness in patients with bronchial asthma

HRCT scanning increasingly used in bronchial asthma. This work was planned to assess the thickness of airway wall in chronic bronchial asthma by using HRCT scanning and its relation to pulmonary function and asthma severity. The study was carried out on 25 chronic asthmatic patients 14 females and 11 males and 10 normal healthy subjects as a control group they were matching as regard age, gender, and height All cases were subjected to the following: complete history taking complete clinical examination, plain chest radiography, pulmonary function tests and HRCT chest scanning at 5 levels; top of aortic arch, at the main carina, 1 cm below main carina, at the level of pulmonary veins, and 2 cm above right hemidiaphragm. Asthmatic patients were classified into severe asthma II cases, moderate asthma 10 cases, and 4 cases as mild asthma, the following data were found: There were no statistically significant difference between cases and control groups -in age, sex or height. There were highly significant increases in FVC, FEV[1], and FEF25-75% and low significance increase in FEV[1]/FVC among cases after use of bronchodilator than before it There was no significant difference in pulmonary function before and after BD among control group There were significant difference between cases and control groups in all pulmonary function results. There were high significant difference between cases and control groups in FEV[1], FVC, FEF 25-75% after use of bronchodilator. There were statistically significant negative association between wall thickness and FEV[1]/FVC and FEF25 75%. There were statistically negative significant correlation between wall area and FEF25-75%, and FEV[1]/FVC- There were significant negative correlation between [thickness/diameter] T/D ratio and FEF 25-75% and FEV[1]/FVC. There were significant correlation between airway wall area and severity of bronchial asthma. No significant correlation between airway wall thickness and FEV[1] but there is negative association between wall thickness and FEF25-75% and FEV[1]/FVC ratio. This study showed strong positive correlation between wall thickness, wall area and asthma severity and duration of asthma There were significant correlation between asthma severity, duration, and thickness of the airway wall and wall area%. Many changes as bronchiectasis, mucoid impaction, emphysema and bronchial dilatation were found in chronic asthmatics