Background: Severe alpha-1-antitrypsin deficiency (AATD) is a known risk factor for early development of emphysema and COPD. By the Swedish national screening program within the years 1972- 74 a cohort of individuals with severe AATD (PiZZ) was identified and regularly followed up. The aim of this study was to investigate alveolar volume (V-A) and the ratio V-A/Total lung capacity (V-A/TLC) for the detection of signs of hyperinflation and ventilation heterogeneity in PiZZ individuals compared with an age-matched control group (phenotype PiMM), randomly selected from the population registry.

Methods: All study participants underwent pulmonary function tests (PFT) including dynamic spirometry and total lung capacity (TLC), residual volume (RV), functional residual capacity (FRC) and alveolar volume (V-A). They answered a questionnaire on smoking habits and symptoms. Quality of life was assessed by answering the Saint George<acute accent>s Respiratory Questionnaire (SGRQ).

Results: Fifty-six PiZZ and 66 PiMM individuals participated in the study. The PiZZ individuals had a significantly lower V-A/TLC ratio (p=0.004) and significantly higher RV (p< 0.001) and RV/TLC ratio (p=0.001) than the PiMM individuals. The 13 PiZZ ever-smokers had a significantly higher TLC (p=0.025), RV (p=0.003) and FRC (p=0.003) and a significantly lower V-A/TLC ratio (p=0.006) than the 24 PiMM ever-smokers. No significant differences in RV, TLC, V-A, and V-A/TLC ratio were found between the never-smoking PiZZ and PiMM individuals. The ratio RV/TLC was significantly higher in the PiZZ never-smokers than in the PiMM never-smokers (p=0.026).

Conclusion: At the age of 42 the PiZZ ever-smokers have signs of hyperinflation and ventilation heterogeneity.