Age related development of respiratory abnormalities in non-index α-1 antitrypsin deficient studies

The role of lung function monitoring in subjects identified as having asymptomatic alpha-1 antitrypsin deficiency (AATD) is uncertain. We investigated for the first time the age these tests start to deviate from results expected in a healthy population with particular reference to the group with the best prognosis (non-smokers), and the order in which this occurs.

Spirometry, gas transfer, health status, and CT densitometry for upper and lower zones were examined in relation to age, gender, ascertainment method and smoking in 591 PiZ AATD subjects using two methods. Firstly, determining the earliest age group at which >50% of subjects consistently had actual test results worse than the healthy population mean by data observation, and secondly predicting the age when this occurred using a logistic regression model.

Both methods produced similar results. For non-index subjects, gas transfer and health status deviated from normal before the age of 16, followed by upper zone densitometry and FEV(1):FVC ratio (age 29), and finally lower zone densitometry and FEV(1) (age 37). This order was similar in non-index never smokers, but occurred later (from the age of 29-63).

Gas transfer, health status and CT densitometry deviate from normal from the mid-teens (up to 30 years prior to conventional spirometry) in AATD.