Background Alpha-1 antitrypsin deficiency (AATD) is an autosomal co-dominant condition characterised by decreased protein concentration and activity at both serum and tissue levels. Few works have investigated whether the type of SERPINA1 gene phenotype in patients with severe asthma can influence asthma symptoms and disease control.

Aim The primary outcome of the study is to assess whether the presence of a non-MM genotype of SERPINA1 in patients with severe asthma may be associated with disease control, a different systemic and airway inflammation, lung function and comorbidities prevalence compared to severe asthma patient with a homozygous phenotype (MM).

Methods This is a retrospective study conducted in an Italian reference asthma clinic. Asthmatic patients belonging to GINA step 5 were analysed. The collected variables were comorbidities, sputum and systemic eosinophils and neutrophils, asthma control questionnaire, number of exacerbations, pulmonary functionality, and serum alpha 1 antitrypsin concentration. A p-value of less than 0.05 was considered statistically significant.

Results Out of 24 patients enrolled, 12 (50%) were non-MM and 12 (50%) were MM. Asthmatics with non-MM genotype, had lower serum alpha 1 antitrypsin concentration compared to MM group (p=0.016). They had higher emphysema and bronchiectasis prevalence than MM group (p= 0.047 and p= 0.034). Lung function variables, treatment with inhaled corticosteroids, inflammatory biomarkers, ACQ and exacerbation in the previous years were not significantly different.

Conclusion Asthmatic patients with non-MM genotype differ from the MM group for serum alpha 1 antitrypsin concentration and for the presence of chest comorbidities.