Spanish Clinical Practice Guidelines for the Diagnosis and Management of Alpha-1 Antitrypsin Deficiency: 2026 Update.

Alpha-1 antitrypsin deficiency (AATD) is a genetic condition characterized by reduced blood levels of alpha-1 antitrypsin (AAT), which confers an increased risk of developing several disorders throughout life, mainly pulmonary emphysema and liver involvement. AATD remains substantially underdiagnosed and is often diagnosed late; consequently, many individuals with severe deficiency do not benefit from disease-specific counseling or tailored care modifications. Since 2015, when the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) published an updated document on the detection and treatment of patients with chronic obstructive pulmonary disease (COPD) associated with AATD, new diagnostic procedures and studies on augmentation therapy have been developed. A systematic review was conducted using the GRADE and ADOLOPMENT frameworks, with an updated literature review that, together with expert opinion, served as the basis for formulating recommendations. Testing for AATD is recommended in all individuals with COPD at the time of diagnosis, in individuals with adult-onset asthma and persistent airflow obstruction, and in individuals with bronchiectasis of unknown etiology. We recommend a 2-step diagnostic approach combining serum AAT levels and characterization of the genetic defect (genotype) or protein abnormality (phenotype) in individuals with AAT concentrations below 116mg/dL, as measured by immunonephelometry, and with a normal C-reactive protein (CRP) level. The panel recommends augmentation therapy for patients with documented severe AATD, with a genotype associated with severe deficiency and AAT levels <57.2mg/dL (<11μmol/L), and with emphysema documented on computed tomography and impaired pulmonary function test results, who are receiving optimal pharmacologic and nonpharmacologic treatment and are not active smokers.