AbstractsMedical & Health Science

Differing emphysema distribution in alpha-1-antitrypsin deficiency (A1AD) relates to specific lung function abnormalities. This thesis explores which factors need to be taken into account when defining A1AD phenotypes. Miller’s lung function prediction equations were the most appropriate for our A1AD population as judged from predicting their survival. A1AD phenotypes were defined by Kco and FEV\(_1\)/FVC using these equations. Those with normal lung function and those with isolated Kco abnormality had the least smoking history, least emphysema and best health status whereas those with both indices abnormal had the worst. Those with isolated FEV\(_1\) abnormality had faster Kco decline compared to the normal and the both abnormal groups (p=0.002 and p<0.001) and were more likely to change groups over time. The best univariate predictor of survival was VA%TLC followed by TLco. Multivariate analysis found the hazard ratio (HR) for death was increased with lower TLco (lowest quartile HR 5.44) and with better Kco (highest quartile HR 2.5 compared to lowest quartile). The HR for death for the lowest VA%TLC quartile was 3.42 compared to the best quartile. Relevant lung function equations and cut points can define meaningful distinct physiological phenotypes for A1AD. VA%TLC shows potential as a new index in this context.