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Title: The mechanisms of airway narrowing in asthma
Author: Burns, Graham Paul
Awarding Body: Newcastle University
Current Institution: University of Newcastle upon Tyne
Date of Award: 2003
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In healthy subjects Deep Inspiration (DI) transiently dilates the airways, while many asthmatics show bronchoconstriction by a mechanism which is incompletely understood.I investigated how the method of assessment affects the response. The response as measured by specific airway conductance (SGaw) appeared to contradict that measured by forced expiration. This led to the formulation of a novel hypothesis to explain the asthmatic bronchoconstrictor response: That the negative intra-thoracic pressure associated with DI may temporarily increase airway oedema and thus reduce lumenal diameter. This was tested by comparing the effects of non-forced with forced inspiration (through resistance). In the asthmatic group, forced inspiration produced significantly more bronchoconstriction. Airway hyperresponsivenessin asthma has been attributed to impaired ability of DI to stretch airway smooth muscle. The seminal study `confirming' this, I argue, is flawed. I have re-tested the hypothesis. The asthmatic response was significantly greater than the control response even when DI was prohibited. Asthmatic hyperresponsivenessis therefore not attributable entirely to an abnormal asthmatic response to DI. Many asthmatics display an apparent capacity for unlimited airway narrowing in response to bronchial challenge; most healthy subjects demonstrate a maximal (limited) response. The maximal response measured by a DI independent index represented a greater % change from baseline than the maximal established by a DI dependent index. This suggested some bronchoprotection resulting from DI but also the existence of a distinct mechanism which ultimately limited narrowing. I reasoned that the capacity for unlimited airway narrowing is most likely a function of smaller airways. I investigated indices of small airway function and found they predicted the ultimate response much earlier in challenge than FEV 1, suggesting a possible practical test of the capacity for unlimited narrowing. I postulate that the clearly established but limited relationship between the responses to DI and bronchial challenge may reflect the dependence of the response to DI on the degree of inflammation within the airway wall whereas the response to challenge may be determined by its overall thickness.
Supervisor: Not available Sponsor: Northern & Yorkshire Regional Fellowship, NHS ; Medical Research Council, Clinical Training Fellowship
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Deep inspiration Medicine Human physiology