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Increased vascular permeability precedes cellular inflammation as asthma control deteriorates

journal contribution
posted on 2023-05-17, 01:10 authored by Khor, YH, Teoh, AKY, Lam, SM, Mo, DCQ, Weston, S, Reid, DW, Eugene WaltersEugene Walters
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.

History

Publication title

Clinical and Experimental Allergy

Volume

39

Issue

11

Pagination

1659-1667

ISSN

0954-7894

Department/School

Menzies Institute for Medical Research

Publisher

Blackwell Publishing Ltd

Place of publication

9600 Garsington Rd, Oxford, England, Oxon, Ox4 2Dg

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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