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Alpha-1 Antitrypsin PI M Heterozygotes with Rare Variants: Do They Need a Clinical and Functional Follow-Up?
Anna Annunziata1, Giuseppe Fiorentino1, Marco Balestrino2
1Department of Intensive Care, Azienda Ospedaliera di Rilievo Nazionale dei Colli, 80131 Naples, Italy.
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.
Insights
Individuals with alpha-1 antitrypsin deficiency (PI*MR) experience accelerated lung function decline, especially smokers with COPD. Monitoring respiratory health is crucial for this group.
Area of Science:
- Pulmonary Medicine
- Genetics
- Respiratory Health
Background:
- Limited data exists on airway dysfunction in alpha-1 antitrypsin deficiency (PI*MR) heterozygotes with rare SERPINA-1 gene variants.
- Understanding the respiratory risks associated with PI*MR is critical for early intervention.
Purpose of the Study:
- To evaluate respiratory functional parameters in PI*MR heterozygotes.
- To compare the respiratory decline in PI*MR heterozygotes with PI*MZ and PI*MS genotypes.
Main Methods:
- Observational study of PI*MR heterozygotes with one-year follow-up.
- Assessment of respiratory parameters including FEV1, FEV1/FVC, and DLCO.
- Comparison with PI*MZ and PI*MS patient groups.
Main Results:
- PI*MR and PI*MZ groups showed significantly higher FEV1 decline than PI*MS.
- PI*MR patients exhibited increased DLCO annual decline compared to PI*MS.
- Smokers and those with COPD within the PI*MR group demonstrated significantly worse respiratory parameter decline.
Conclusions:
- PI*MR heterozygotes, particularly smokers with COPD, experience a greater annual decline in respiratory function.
- Regular monitoring of respiratory parameters is recommended for PI*MR heterozygotes.
- This study highlights the importance of genetic screening for alpha-1 antitrypsin deficiency.
