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

Abstract

(1) Background: 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 (PI*MR). (2) Methods: In this observational study, in a cohort of PI*MR heterozygotes, we evaluated respiratory functional parameters at baseline and at one-year follow-up. Moreover, we compared such parameters with those of the PI*MZ and PI*MS patients. (3) Results: A total of 60 patients were recruited; 35 PI*MR, 11 PI*MZ and 14 PI*MS. At the annual follow-up, the PI*MR and PI*MZ patients demonstrated a significantly higher FEV₁ decline than the PI*MS group (p = 0.04 and p = 0.018, respectively). The PI*MR patients showed a significant increase in DLCO annual decline in comparison with the PI*MS group (p = 0.02). At baseline, the PI*MR smoking patients, compared with nonsmokers, showed statistically significant lower values of FEV₁, FEV₁/FVC and DLCO (p = 0.0004, p < 0.0001, p = 0.007, respectively) and, at the one-year follow-up, they displayed a significantly higher FEV₁ and DLCO decline (p = 0.0022, p = 0.011, respectively). PI*MR heterozygotes with COPD showed a significantly higher FEV₁, FEV₁/FVC and DLCO annual decline in comparison with healthy PI*MR (p = 0.0083, p = 0.043, p = 0.041). (4) Conclusions: These results suggest that PI*MR heterozygotes, particularly smokers with COPD, have a greater annual decline in respiratory functional parameters and need to be monitored.

Keywords: PI*M heterozygotes; alpha-1 antitrypsin deficiency; diffusing capacity of the lung for carbon monoxide; functional follow-up; rare allelic variants of gene SERPINA-1; spirometry.

Figure 1

Chest high-resolution CT scan; axial view of upper lobes (A) and lower lobes (B) of lungs of an active smoking patient with M/MProcida genotype; axial view of upper lobes (C) and lower lobes (D) of lungs of a never smoker patient with M/I genotype.

Figure 2

FEV₁, FEV₁/FVC and DLCO in the protease inhibitor (PI*) MZ, MS and MR groups. Abbreviations: FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; DLCO, diffusing capacity of the lung for carbon monoxide.

Figure 3

Annual FEV₁, FEV₁/FVC and DLCO decline in the protease inhibitor (PI*) MZ, MS and MR groups. Abbreviations: ∆, decline; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; DLCO, diffusing capacity of the lung for carbon monoxide; *, p-value < 0.05.

Figure 4

Baseline FEV₁, FEV₁/FVC and DLCO in the protease inhibitor (PI*) MR smoking and nonsmoking subgroups. Abbreviations: FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; DLCO, diffusing capacityof the lung forcarbon monoxide; **, p-value < 0.01; ****, p-value < 0.0001.

Figure 5

FEV₁, FEV₁/FVC and DLCO decline in the protease inhibitor (PI*) MR smoking and nonsmoking subgroups. Abbreviations: FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; DLCO, diffusing capacity of the lung for carbon monoxide; *, p-value < 0.05; **, p-value < 0.01.

Figure 6

FEV₁, FEV₁/FVC and DLCO mean decline in the PI*MR healthy, pre-COPD and COPD subgroups. Abbreviations: ∆, decline; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; DLCO, diffusing capacity of the lung for carbon monoxide; (* p-value < 0.05; ** p-value < 0.01).