Longitudinal lung function study in heterozygous PiMZ phenotype subjects

Abstract

It is a matter of controversy whether subjects who are heterozygous (PiMZ) for alpha1-antitrypsin deficiency are at risk of developing pulmonary emphysema. To assess the role of MZ phenotype in the development of abnormal lung function the authors performed a 10 year follow-up study of 28 PiMZ subjects, compared to 28 matched-paired normal PiMM subjects. Maximal expiratory flows; and mechanical properties of the lungs were studied, in order to determine the changes of the lung function parameters characteristic of pulmonary emphysema. Total lung capacity and residual volume increased, whereas forced expiratory volume in one second, expiratory flows, diffusing capacity of the lungs for carbon monoxide, and static transpulmonary pressures decreased in the PiMZ patients. The majority of the controlled functional parameters were found to deteriorate significantly in PiMZ patients during the 10 year period. Trypsin inhibitory capacity in the PiMZ group (mean±SD) was 0.65±0.17 mg·ml-1 as compared to 1.52±0.3 mg ml-1 in the PiMM group. These changes exceeded the values expected as physiological changes due to ageing. The findings in the present longitudinal study - especially the decrease in elasticity, which is the primary pathophysiological damage in alpha1-antitrypsin deficiency - support the concept that the PiMZ phenotype is a risk factor for the development of pulmonary emphysema at younger age than in those without the deficiency.