Holme, Jayne (2011)
M.D. thesis, University of Birmingham.
Four clinical studies in subjects with alpha-1 antitrypsin deficiency were undertaken.
The first examined CT densitometry and health status in 4 groups with discordant pulmonary physiology. It demonstrated that subjects with an isolated gas transfer abnormality had more emphysema, the least basal predominant emphysema and a worse health status than those with normal physiology. Subjects with an isolated spirometry abnormality had the most basal emphysema.
The second study examined the age at which radiological, physiological and health status measures started to deviate from values expected for a normal population, and concluded that CT densitometry and gas transfers measures were the first to deviate from normal, while spirometry was the last.
The third study examined the relationship of γ-glutamyl transferase to physiology, symptoms, mortality and liver disease in alpha-1 antitrypsin deficiency, and demonstrated associations between γ-glutamyl transferase and spirometry, mortality and cirrhosis after correction for associated factors.
The final study described subjects with the PiSZ phenotype compared to matched PiZ subjects. CT revealed emphysema (mainly panacinar) in 46% of PiSZ index and 15% of non-index subjects. Health status was impaired in PiSZ subjects, who had less lower zone emphysema, better health status, pulmonary physiology and symptom profile compared with PiZ subjects.
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