Alpha1-Antitrypsin in Lung Diseases: A Cross-Sectional Observational Study

Area of Science:

• Pulmonary Medicine
• Genetics
• Biochemistry

Background:

• Alpha1-antitrypsin (A1AT) deficiency, caused by SERPINA1 mutations, is linked to severe emphysema.
• The role of A1AT levels in various lung pathologies beyond emphysema requires further investigation.

Purpose of the Study:

• To investigate the association between A1AT levels, SERPINA1 gene variants, and diverse lung diseases.
• To explore the influence of A1AT on disease progression and comorbidities.

Main Methods:

• Collected blood samples from healthy individuals and patients with COPD, asthma, ILD, sarcoidosis, and cystic fibrosis.
• Assessed A1AT levels, SERPINA1 polymorphisms (S, Z, M2/M4, 0, eQTL), CT scan findings (emphysema extent), and clinical parameters.
• Analyzed A1AT levels, antielastase activity, and genotype correlations with disease severity and comorbidities.

Main Results:

• A1AT levels differed significantly between smokers and other lung diseases, being lower in sarcoidosis and higher in smokers, COPD, ILD, and CF.
• Emphysema presence and pattern impacted A1AT levels; COPD patients without emphysema had lower levels, while those with central/panlobular emphysema had higher levels.
• Z heterozygotes were more prevalent in severe asthma; eQTL TT genotypes correlated with higher A1AT, emphysema, and bronchitis. A1AT levels correlated with clinical parameters, inversely with FEV1/FVC.

Conclusions:

• A1AT levels are modulated by smoking and various lung diseases, influencing disease severity and progression.
• A1AT plays a role in lung pathologies beyond emphysema and is associated with cardiovascular comorbidities.
• Further research is essential to elucidate A1AT's regulatory mechanisms in lung diseases and comorbidities.