Increased vascular permeability precedes cellular inflammation as asthma control deteriorates.
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.


OBJECTIVE
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 microg/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.
Respiratory Research Group, Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia. yethkhor@gmail.com
Y H
YH
Khor
A K Y
AK
Teoh
S M
SM
Lam
D C Q
DC
Mo
S
S
Weston
D W
DW
Reid
E H
EH
Walters
D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002199:Capillary Permeability / Q000187:drug effects*; D005260:Female; D000068298:Fluticasone; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000730:Androstadienes; D015415:Biomarkers; D001993:Bronchodilator Agents; D012709:Serum Albumin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068298:Fluticasone