Synopsis
Detect inherited alpha-1 antitrypsin deficiency in the right pulmonary or hepatic phenotype, confirm the biochemical result genetically, reduce avoidable lung injury, and counsel relatives while respecting current UK limits on augmentation therapy.
- AAT deficiency is an inherited SERPINA1 disorder in which reduced or dysfunctional circulating antiprotease permits accelerated elastin injury, particularly when tobacco smoke adds oxidant and neutrophil burden.
- Think of it in early-onset emphysema, COPD with little smoking exposure, basal-predominant panlobular destruction, an affected relative, or otherwise unexplained liver disease with compatible pulmonary features.
- Serum AAT is the screening test, but it is an acute-phase protein; measure inflammatory context and confirm a low or suspicious value with phenotype or genotype rather than reporting a concentration alone.
Key red flags
Rapidly worsening breathlessness, hypoxaemia, pleuritic pain or unilateral reduced breath sounds may represent exacerbation, pneumonia, respiratory failure or pneumothorax and needs urgent standard assessment rather than delayed genetic discussion.
Investigation priorities
Screen for a quantitatively deficient circulating protein level.
Management branches
Early or disproportionate COPD, a family history, suggestive liver disease or an unexpectedly low AAT level is identified.
- Measure serum AAT with CRP and relevant clinical context, repeating a borderline sample after inflammation settles when that will not delay a necessary specialist referral.
- Confirm abnormal or discordant findings through phenotype and SERPINA1 genotyping, escalating to broader molecular analysis when a very low level is not explained by common variants.
Key medicines
Usual inhaled treatment for coexisting COPDSelect the named inhaler, device and licensed strength through the current NICE COPD pathway, then prescribe the product-specific dose only after checking inspiratory technique and comorbid asthma features.
Human alpha-1 proteinase inhibitor augmentationThe Respreeza SmPC describes 60 mg/kg intravenously once weekly for licensed candidates, but NICE NG115 does not recommend AAT replacement therapy for routine COPD care in the UK.