Vascularity in asthmatic airways: relation to inhaled steroid dose.

BACKGROUND There is an increase in vascularity in the asthmatic airway. Although inhaled corticosteroids (ICS) are an effective anti-inflammatory treatment in asthma, there are few data on any effects on structural changes. METHODS Endobronchial biopsy specimens from seven asthmatic subjects not receiving ICS and 15 receiving 200-1500 microg/day beclomethasone dipropionate (BDP) were immunohistochemically stained with an anti-collagen type IV antibody to outline the endothelial basement membrane of the vessels. These were compared with biopsy tissue from 11 non-asthmatic controls (four atopic and seven non-atopic). RESULTS There was a significant increase in the density of vessels (number of vessels/mm2 of lamina propria) in the asthmatic subjects not on ICS compared with non-asthmatic controls (mean 485 (interquartile range (IQR) 390-597) versus 329 (IQR 248-376) vessels/mm2, p<0.05; 95% CI for the difference 48 to 286). There was no significant difference between asthmatic subjects on ICS and those not on ICS or control subjects in the number of vessels/mm2 (mean 421 (IQR 281-534)). However, patients who received >/=800 microg/day BDP tended to have a reduced number of vessels/mm2 compared with patients not on ICS and those receiving </=500 microg/day BDP (mean 366 (IQR 153-608) versus 494 (IQR 391-583), p = 0.08; 95% CI for the difference -31 to 288). Similarly, there was an increase in the percentage of lamina propria occupied by vessels in asthmatic patients not on ICS compared with controls (mean 15.6% (IQR 13.1-18.0) versus 10.1% (IQR 8.4-13.3), p<0.01; 95% CI for the difference 2.4 to 9.3) but a significant decrease in the percentage of lamina propria occupied by vessels was detected in asthmatic patients on ICS (mean 11.4% (IQR 9.1-14.9), p<0.01; 95% CI for the difference 0.7 to 7.7) compared with those not on ICS. The density of vessels correlated significantly with both airway hyperresponsiveness and percentage change in forced expiratory volume in one second (FEV1) after bronchodilator (r = -0. 38 for PD20 methacholine and r = 0.49 for change in percentage FEV1 after bronchodilator versus number of vessels/mm2, p<0.05). CONCLUSION These findings suggest that ICS, especially at higher doses, may reduce airway wall vascularity in asthmatic subjects but further longitudinal intervention studies are required to confirm this suggestion.

[1]  J. Widdicombe,et al.  Effects of inflammatory and other mediators on airway vascular beds. , 2015, The American review of respiratory disease.

[2]  J. Wilson,et al.  Increased vascularity of the bronchial mucosa in mild asthma. , 1997, American journal of respiratory and critical care medicine.

[3]  A. Casalini,et al.  Effect of short-term treatment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthma: a placebo-controlled study. , 1997, American journal of respiratory and critical care medicine.

[4]  H. Wieland,et al.  Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids. , 1997, American journal of respiratory cell and molecular biology.

[5]  J. Wilson,et al.  The measurement of reticular basement membrane and submucosal collagen in the asthmatic airway , 1997, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[6]  A. James,et al.  Bronchial blood vessel dimensions in asthma. , 1997, American journal of respiratory and critical care medicine.

[7]  E. Walters,et al.  Effect of high dose inhaled fluticasone propionate on airway inflammation in asthma. , 1995, American journal of respiratory and critical care medicine.

[8]  R. Davies,et al.  Effect of inhaled beclomethasone dipropionate on expression of proinflammatory cytokines and activated eosinophils in the bronchial epithelium of patients with mild asthma. , 1994, The Journal of allergy and clinical immunology.

[9]  M. Calderón,et al.  Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma. , 1994, American journal of respiratory and critical care medicine.

[10]  P. Paré,et al.  Small airways dimensions in asthma and in chronic obstructive pulmonary disease. , 1993, The American review of respiratory disease.

[11]  J. Wilson,et al.  The lack of distensibility of asthmatic airways. , 1993, The American review of respiratory disease.

[12]  S. Durham,et al.  Prednisolone treatment in asthma is associated with modulation of bronchoalveolar lavage cell interleukin-4, interleukin-5, and interferon-gamma cytokine gene expression. , 1993, The American review of respiratory disease.

[13]  D. Hendrick,et al.  Measurement of airway responsiveness to methacholine: relative importance of the precision of drug delivery and the method of assessing response. , 1993, Thorax.

[14]  E. R. Mcfadden,et al.  Vascular volume expansion and thermally induced asthma. , 1993, The European respiratory journal.

[15]  C. Cross,et al.  Corticosteroid administration modifies ozone-induced increases in sheep airway blood flow. , 1992, The American review of respiratory disease.

[16]  P. Paré,et al.  A model of airway narrowing in asthma and in chronic obstructive pulmonary disease. , 1992, The American review of respiratory disease.

[17]  McFadden Er,et al.  Microvasculature and airway responses. , 1992 .

[18]  A. Wanner,et al.  Effect of histamine on tracheal mucosal perfusion, water content and airway smooth muscle in sheep. , 1991, Respiration physiology.

[19]  W. Abraham,et al.  Late-phase bronchial vascular responses in allergic sheep. , 1990, Journal of applied physiology.

[20]  M. Tanemura,et al.  Hyperreactive site in the airway tree of asthmatic patients revealed by thickening of bronchial muscles. A morphometric study. , 1990, The American review of respiratory disease.

[21]  D. Connolly,et al.  Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. , 1989, The Journal of clinical investigation.

[22]  C. Boyd,et al.  Pressure-induced connective tissue synthesis in pulmonary artery segments is dependent on intact endothelium. , 1989, The Journal of clinical investigation.

[23]  R. Matran,et al.  Bronchial hyperresponsiveness to methacholine in patients with impaired left ventricular function. , 1989, The New England journal of medicine.

[24]  S. Holgate,et al.  SUBEPITHELIAL FIBROSIS IN THE BRONCHI OF ASTHMATICS , 1989, The Lancet.

[25]  D. McDonald,et al.  Neurogenic inflammation in the respiratory tract: actions of sensory nerve mediators on blood vessels and epithelium of the airway mucosa. , 1987, The American review of respiratory disease.

[26]  J. M. Fouke,et al.  Heat and water flux in the intrathoracic airways and exercise-induced asthma. , 1987, Journal of applied physiology.

[27]  E. R. Mcfadden,et al.  Postexertional airway rewarming and thermally induced asthma. New insights into pathophysiology and possible pathogenesis. , 1986, The Journal of clinical investigation.

[28]  R. Stoughton,et al.  Method for Comparing Percutaneous Absorption of Steroids , 1962 .

[29]  M. Dunnill THE PATHOLOGY OF ASTHMA, WITH SPECIAL REFERENCE TO CHANGES IN THE BRONCHIAL MUCOSA , 1960, Journal of clinical pathology.

[30]  E. R. Mcfadden,et al.  Microvasculature and airway responses. , 1992, The American review of respiratory disease.

[31]  P. D’Amore,et al.  Mechanisms of endothelial growth control. , 1992, American journal of respiratory cell and molecular biology.

[32]  P. Howarth,et al.  Effect of inhaled platelet-activating factor on bronchial inflammation in atopic non-asthmatic subjects. , 1992, International archives of allergy and immunology.

[33]  U Ackermann-Liebrich,et al.  Air pollution and respiratory symptoms in preschool children. , 1992, The American review of respiratory disease.

[34]  H. Shepard,et al.  Macrophage-induced angiogenesis is mediated by tumour necrosis factor-α , 1987, Nature.