Ventilation heterogeneity is a major determinant of airway hyperresponsiveness in asthma, independent of airway inflammation

Sue R Downie ^1*, Cheryl M Salome ², Sylvia Verbanck ³, Bruce R Thompson ⁴, Norbert Berend ¹ and Gregory George King ⁵

¹ Woolcock Institute of Medical Research, Australia
² Woolcock Institute of Medical research, University of Sydney, Australia
³ AZ VUB, Belgium
⁴ The Alfred Hospital, Australia
⁵ Department of Respiratory Medicine - RNS hospital, Woolcock Institute of Medical Research, Australia

^* To whom correspondence should be addressed. E-mail: sued{at}woolcock.org.au.

Accepted 11 January 2007

Abstract

Background: Airway hyperresponsiveness is the ability of airways to narrow excessively in response to inhaled stimuli and is a key feature of asthma. Airway inflammation and ventilation heterogeneity have been separately shown to be associated with airway hyperresponsiveness. Objective: To establish if ventilation heterogeneity was associated with airway hyperresponsiveness, independently of airway inflammation in asthmatics, and to determine the effect of inhaled corticosteroids on this relationship. Methods: In 40 asthmatic subjects, airway inflammation was measured by exhaled nitric oxide, ventilation heterogeneity by multiple breath nitrogen washout and airway hyperresponsiveness by methacholine challenge. In 18 of these subjects with uncontrolled symptoms, measurements were repeated after three months treatment with inhaled beclomethasone dipropionate. Results: At baseline, airway hyperresponsiveness was independently predicted by airway inflammation (partial r² = 0.20, p<0.001) and ventilation heterogeneity (partial r² = 0.39, p<0.001). Inhaled corticosteroid treatment decreased airway inflammation (p = 0.002), ventilation heterogeneity (p = 0.009), and airway hyperresponsiveness (p<0.001). After treatment, ventilation heterogeneity was the sole predictor of airway hyperresponsiveness (r² = 0.64, p<0.001). Conclusion: Baseline ventilation heterogeneity is a strong predictor of airway hyperresponsiveness, independent of airway inflammation in asthmatic subjects. Its persistent relationship with airway hyperresponsiveness following anti-inflammatory treatment suggests that it is an important independent determinant of airway hyperresponsiveness. Clinical implication: The strength of the association between ventilation heterogeneity and airway hyperresponsiveness elucidates a possible mechanism of airway hyperresponsiveness in asthma. Consequently, the normalisation of ventilation heterogeneity is a potential goal of therapy that may lead to improved long term outcomes.

Keywords: airway hyperresponsiveness, airway inflammation, asthma, multiple breath nitrogen washout, ventilation heterogeneity

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Articles

Linking ventilation heterogeneity and airway hyperresponsiveness in asthma

Jose Venegas
Thorax 2007 62: 653-654. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Allen, I. C. (2009). Searching for an improved mouse model of allergic airway disease using dual allergen exposures. DMM 2: 519-520 [Full Text]  
• Tarlo, S. M., Malo, J.-L., on behalf of the Third Jack Pepys Workshop on Asth, (2009). An Official ATS Proceedings: Asthma in the Workplace: The Third Jack Pepys Workshop on Asthma in the Workplace: Answered and Unanswered Questions. Proc Am Thorac Soc 6: 339-349 [Abstract] [Full Text]  
• Chapman, D. G., Berend, N., King, G. G., McParland, B. E., Salome, C. M. (2009). Deep inspirations protect against airway closure in nonasthmatic subjects. J. Appl. Physiol. 107: 564-569 [Abstract] [Full Text]  
• Macleod, K A, Horsley, A R, Bell, N J, Greening, A P, Innes, J A, Cunningham, S (2009). Ventilation heterogeneity in children with well controlled asthma with normal spirometry indicates residual airways disease. Thorax 64: 33-37 [Abstract] [Full Text]  
• Lahzami, S., King, G. G. (2008). Targeting small airways in asthma: the new challenge of inhaled corticosteroid treatment. Eur Respir J 31: 1145-1147 [Full Text]  
• Suresh, V., Shelley, D. A., Shin, H.-W., George, S. C. (2008). Effect of heterogeneous ventilation and nitric oxide production on exhaled nitric oxide profiles. J. Appl. Physiol. 104: 1743-1752 [Abstract] [Full Text]  
• Verbanck, S., Kerckx, Y., Schuermans, D., Vincken, W., Paiva, M., Van Muylem, A. (2008). Effect of airways constriction on exhaled nitric oxide. J. Appl. Physiol. 104: 925-930 [Abstract] [Full Text]  
• Verbanck, S., Schuermans, D., Van Malderen, S., Vincken, W., Thompson, B. (2008). The effect of conductive ventilation heterogeneity on diffusing capacity measurement. J. Appl. Physiol. 104: 1094-1100 [Abstract] [Full Text]  
• Kaminsky, D. A., Irvin, C. G., Lundblad, L. K. A., Thompson-Figueroa, J., Klein, J., Sullivan, M. J., Flynn, F., Lang, S., Bourassa, L., Burns, S., Bates, J. H. T. (2008). Heterogeneity of bronchoconstriction does not distinguish mild asthmatic subjects from healthy controls when supine. J. Appl. Physiol. 104: 10-19 [Abstract] [Full Text]  
• Venegas, J. (2007). Linking ventilation heterogeneity and airway hyperresponsiveness in asthma. Thorax 62: 653-654 [Full Text]