What labs should be ordered prior to alpha-1 antitrypsin (A1AT) augmentation therapy with elastin infusion in a patient with a suspected alpha-1 antitrypsin deficiency?

Laboratory Testing Prior to Alpha-1 Antitrypsin Augmentation Therapy

Before initiating alpha-1 antitrypsin (A1AT) augmentation therapy, you must order: serum A1AT level (<11 mmol/L or <0.57 g/L to confirm severe deficiency), SERPINA1 gene sequencing (to confirm the specific genetic variant), pulmonary function testing with post-bronchodilator spirometry (FEV1 must be <80% predicted), high-resolution CT chest (to document emphysema), IgA level (to screen for IgA deficiency which is an absolute contraindication), and baseline inflammatory markers including C-reactive protein. 1, 2, 3

Essential Pre-Treatment Laboratory Tests

Confirmatory Diagnostic Tests

• Serum A1AT protein level must be measured and documented to be <11 mmol/L (0.57 g/L) before starting treatment, as this threshold defines severe deficiency eligible for augmentation therapy. 1

• SERPINA1 gene sequencing is now recommended as the gold standard before embarking on A1AT replacement therapy, given the variability in A1AT protein serum levels and the existence of over 300 genetic variants. 1 This is superior to traditional PCR-based genotyping which only tests for PiS and PiZ alleles and can miss rare variants. 1

• DNA sequencing is particularly critical because some genetic variants (such as Pi*F) produce normal circulating A1AT levels by routine assays but the protein is nonfunctional, representing actual deficiency that would be missed by protein measurement alone. 1

Pulmonary Function and Imaging Requirements

• Post-bronchodilator spirometry with FEV1 measurement is mandatory to establish baseline lung function, as augmentation therapy is indicated only when FEV1 is <80% predicted. 1, 2

• High-resolution CT chest must document the presence of emphysema, as augmentation therapy is specifically indicated for severe hereditary deficiency with clinically evident emphysema—not for A1AT deficiency alone. 2, 3

Safety Screening Tests

• IgA level must be checked to screen for IgA deficiency with anti-IgA antibodies, which represents an absolute contraindication to augmentation therapy due to risk of anaphylaxis. 2

• C-reactive protein (CRP) should be measured as a baseline inflammatory marker, as elevated CRP may indicate active inflammation or infection that could affect treatment decisions. 2

Additional Required Documentation

• Smoking status verification is essential—patients must be nonsmokers for at least 6 months before therapy initiation, as continued smoking negates the protective benefits of augmentation therapy. 1, 2, 3

• Hepatitis A and B vaccination status should be documented, as the 2003 ATS/ERS guidelines recommend these vaccinations for individuals with A1AT deficiency. 1

• Liver function tests (AST, ALT, bilirubin, alkaline phosphatase) should be obtained as baseline, particularly in elderly individuals with A1AT deficiency, though augmentation therapy does not confer benefits for liver disease. 1

Critical Pitfalls to Avoid

The most common error is assuming that A1AT deficiency diagnosis alone justifies augmentation therapy. 2 The presence of emphysema on CT scan is mandatory—augmentation therapy is not indicated for patients without documented emphysema, regardless of their A1AT level or genotype. 2, 3

Another pitfall is relying solely on A1AT protein levels without genetic confirmation. 1 Genetic mutations are invariable, while A1AT levels may vary between repeat tests in the same individual, and some variants produce dysfunctional protein despite normal levels. 1

Do not initiate therapy in patients who have received lung transplantation, as transplanted lungs produce normal A1AT from donor tissue, eliminating the underlying deficiency. 4 Post-transplant augmentation is not indicated for routine maintenance. 4

Evidence Strength Considerations

The 2025 Canadian Thoracic Society guidelines represent the most recent and comprehensive guidance, emphasizing SERPINA1 sequencing over traditional testing methods. 1 This recommendation reflects advances in genetic testing technology and recognition that DNA sequencing allows testing for all 300+ variants in a single assay. 1

The strongest evidence for augmentation therapy efficacy exists for patients with moderate airflow obstruction (FEV1 31-65% predicted), where the German-Danish study showed yearly FEV1 decline of -53 mL in treated versus -75 mL in untreated patients (p<0.02). 2, 3 This underscores why baseline spirometry is essential for appropriate patient selection.