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Title: The involvement of the lung periphery in cystic fibrosis : an exploration using multiple-breath nitrogen washout and helium-3 diffusion magnetic resonance
Author: Al-Khathlan, Noor Ali
ISNI:       0000 0004 5351 1963
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2015
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Background: The assessment of cystic fibrosis (CF) lung disease requires sensitive, repeatable and safe markers of early involvement of peripheral airways. Multiple-breath washout (MBW) and hyperpolarised 3He magnetic resonance (3HeMR) have been demonstrated to be more sensitive to early changes than spirometry. Limited research has explored longitudinal changes in lung clearance index (LCI), and none has looked at phase III slope indices, markers of ventilatory inhomogeneity derived from MBW. The dimensions of lung microstructure using 3HeMR in children with CF have also not been investigated. Aims: To monitor longitudinal changes in LCI and phase III slope indices in comparison with conventional lung function measures in children with CF and to estimate the dimensions of the lung periphery using 3HeMR. Methods: Serial measurements of MBW indices, spirometry and plethysmography were obtained from 27 children with CF over a 4-year period. Single 3HeMR measurements were obtained from 18 patients. Results: LCI showed the highest change over time and was the earliest to deteriorate with age, being elevated in all children at seven years. Conversely, the preliminary results of the association between VI arising from the conducting and acinar airways (Scond, Sacin) with age have shown that Scond reached an asymptote with a maximum of 0.10 L-1 and did not increase further with increasing disease severity. This limits the ability to follow these indices longitudinally. 3HeMR showed that the apparent diffusion coefficient, a marker of alveolar size, was significantly lower in CF patients than controls with no difference in alveolar sleeve depth or radius. Conclusion: These findings highlight the significance of LCI in the early detection of functional changes in CF. The unexpected outcomes from 3He MR may be attributable to physiological or technical factors. Alternatively, they may suggest that CF does not cause structural damage to the acini in the early stages of the disease, but instead that it predominantly affects airways within the conducting zone.
Supervisor: Beardsmore, Caroline; Gaillard, Erol Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available