Alpha-1 antitrypsin deficiency and asthma exacerbations

Over the past decades, numerous scientific studies have demonstrated that specific genetic variants in the SERPINA1 gene are implicated in the development of severe respiratory diseases. However, their role in asthma exacerbations or attacks had not been thoroughly investigated. In an article recently published in the international journal Pulmonology, we report for the first time an association between variants of this gene and asthma exacerbations.

Specifically, reduced blood levels of alpha-1 antitrypsin (AAT) — a protein encoded by the SERPINA1 gene — are associated with a higher risk of asthma exacerbations in a cohort of asthma patients recruited on the island of La Palma. AAT, the second most abundant protein in human serum, plays a crucial role in protecting lung tissue during inflammatory processes. Accordingly, adequate levels of this protein exert a protective effect, while its deficiency correlates with an increased incidence of asthma crises. Additionally, a significant association was found between the PiZ* genetic variant of SERPINA1 and the risk of exacerbations. This variant, previously recognized as the main cause of severe alpha-1 antitrypsin deficiency (AATD), leads to a marked reduction in circulating AAT levels.

Notably, the PiZ* variant is highly prevalent in European populations, including the Canary Islands. Our study confirmed this genetic association in asthma patients from La Palma, and the finding was further validated in an independent cohort of patients of Canarian ancestry, although not in patients from other regions of Mainland Spain. This difference may be related to the high prevalence of asthma in the Canary Islands.

These findings underscore the potential of personalized medicine to address complex health challenges, particularly in populations with unique genetic characteristics, such as the Canarian population. In this context, routine measurement of AAT levels in asthma patients, along with genetic screening for variants associated with AATD, could serve as a preventive strategy, especially in individuals with a history of exacerbations. This approach would allow for the identification of carriers of deleterious SERPINA1 variants and enable more intensive clinical monitoring to reduce the risk of future asthma crises.

Finally, the possibility of using AAT replacement therapy—currently approved for the treatment of severe AATD—as a therapeutic intervention to prevent severe asthma exacerbations, particularly in refractory patients from the Canary Islands, warrants further investigation.