Alpha-1 Antitrypsin PI M Heterozygotes with Rare Variants: Do They Need a Clinical and Functional Follow-Up?

: Few data are available on the risk of airway dysfunction in protease inhibitor (PI*) M heterozygotes carrying rare null or deficient allelic variants of the gene SERPINA-1 (PIMR). : In this observational study, in a cohort of PIMR heterozygotes, we evaluated respiratory functional parameters at baseline and at one-year follow-up. Moreover, we compared such parameters with those of the PIMZ and PIMS patients. : A total of 60 patients were recruited; 35 PIMR, 11 PIMZ and 14 PIMS. At the annual follow-up, the PIMR and PIMZ patients demonstrated a significantly higher FEV decline than the PIMS group ( = 0.04 and = 0.018, respectively). The PIMR patients showed a significant increase in DLCO annual decline in comparison with the PIMS group ( = 0.02). At baseline, the PIMR smoking patients, compared with nonsmokers, showed statistically significant lower values of FEV, FEV/FVC and DLCO ( = 0.0004, < 0.0001, = 0.007, respectively) and, at the one-year follow-up, they displayed a significantly higher FEV and DLCO decline ( = 0.0022, = 0.011, respectively). PIMR heterozygotes with COPD showed a significantly higher FEV, FEV/FVC and DLCO annual decline in comparison with healthy PIMR ( = 0.0083, = 0.043, = 0.041). : These results suggest that PIMR heterozygotes, particularly smokers with COPD, have a greater annual decline in respiratory functional parameters and need to be monitored.