Does the pattern of ventilation distribution predict airway hyperresponsiveness?

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The tendency for airways to narrow too easily when stimulated is called airway hyperresponsiveness (AHR). AHR is an important feature of asthma, but it also occurs in other diseases, such as chronic obstructive pulmonary disease (COPD) - an airway disease caused by smoking, and cystic fibrosis. People who have AHR have more severe respiratory disease, regardless of which disease they have, and are more likely to develop poor lung function in old age and to be hospitalised or die from their disease. If we can understand the causes of AHR we will have a better understanding of why some people with respiratory disease have poor outcomes. We have recently discovered that, in asthma, there is a very close relationship between AHR and the uneven distribution of air within the lungs. We believe that structural changes in the airways that cause this uneven distribution make the airways prone to AHR. This raises the possibility that factors that cause uneven ventilation in other respiratory diseases might also predispose the airways to AHR. If this is true, it suggests that there is a single physiological basis for AHR in a range of different diseases, and would allow us to focus research more closely on the causes of uneven ventilation. In this project we will measure the relationship between AHR and uneven ventilation in people with asthma, COPD or cystic fibrosis. The study is important because older people with asthma, particularly those with permanently narrowed airways, are likely to have more structural changes in their airways than young asthmatics, whereas people with COPD and cystic fibrosis have a different pattern of both structural changes and airway inflammation from that in asthma. The study will tell us whether there is a consistent relationship between AHR and uneven ventilation. If so, this would be extremely strong evidence that the factors that cause uneven ventilation contribute to AHR, and will point the way to studies of new treatments.