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Increased vascular permeability precedes cellular inflammation as asthma control deteriorates


Khor, YH and Teoh, AKY and Lam, SM and Mo, DCQ and Weston, S and Reid, DW and Walters, EH, Increased vascular permeability precedes cellular inflammation as asthma control deteriorates , Clinical and Experimental Allergy, 39, (11) pp. 1659-1667. ISSN 0954-7894 (2009) [Refereed Article]

DOI: doi:10.1111/j.1365-2222.2009.03349.x


Background Airway microcirculation is abnormal in asthma but the role of vascular changes in asthma deteriorations remains poorly defined. We prospectively assessed the vascular changes accompanying worsening of asthma control by using an inhaled corticosteroid (ICS)dose-reduction model. Objectives To evaluate airway vascularity, vascular permeability and expression of vascular endothelial growth factor (VEGF) in early asthma deterioration induced by ICS back-titration. Methods Twenty mild-to-moderate persistent symptomatic asthmatics on low-to-moderate ICS were recruited and treated with 4 weeks of high-dose fluticasone propionate (1000 mg/day) to achieve symptom control. This was followed by dose reduction to half of the pre-study doses for 4–8 weeks until the symptoms began to return. Endobronchial biopsy and bronchoalveolar lavage (BAL) samples were obtained after both treatment periods. Results Vascularity as measured by the number and size of blood vessels, as well as VEGF expression did not change following ICS reduction. Even on high-dose ICS, perivascular albumin staining and BAL microalbumin levels in asthmatic subjects, as markers of permeability, were elevated when compared with normal subjects and both further increased significantly after ICS reduction. There was a significant association between changes in vascular leakiness and clinical deterioration. Increases in airway albumin correlated with previously reported increases in airway wall infiltration with T lymphocytes. Conclusions Our results suggest that airway vascular leakage is a major pathophysiologic feature of early asthma deterioration, occurring before recrudescence of cellular inflammation.

Item Details

Item Type:Refereed Article
Keywords:asthma, vascular endothelial growth factor, vascular remodelling
Research Division:Biomedical and Clinical Sciences
Research Group:Cardiovascular medicine and haematology
Research Field:Respiratory diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Khor, YH (Dr Yet Khor)
UTAS Author:Teoh, AKY (Mr Alan Teoh)
UTAS Author:Lam, SM (Ms Sue Lam)
UTAS Author:Mo, DCQ (Mr Daniel Mo)
UTAS Author:Weston, S (Mr Steven Weston)
UTAS Author:Reid, DW (Dr David Reid)
UTAS Author:Walters, EH (Professor Haydn Walters)
ID Code:60229
Year Published:2009
Web of Science® Times Cited:41
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-01-25
Last Modified:2012-12-12

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