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.
- Inheritance is codominant, so each allele contributes to the circulating phenotype; severe deficiency is commonly associated with two high-risk alleles, but genotype–risk relationships are not perfectly binary.
- Lung injury reflects insufficient antiprotease activity, whereas liver disease is driven principally by retention of misfolded protein within hepatocytes; this explains why augmentation cannot treat the hepatic mechanism.
- Complete smoking avoidance is the highest-value intervention, including support to stop smoking and practical reduction of occupational dust, fume and second-hand smoke exposure.
- Manage airflow obstruction, exacerbations, hypoxaemia and rehabilitation according to standard COPD or bronchiectasis guidance while maintaining specialist surveillance for an unusually rapid trajectory.
- Human AAT augmentation has a UK marketing authorisation for selected severe deficiency, but NICE NG115 does not recommend routine AAT replacement therapy for COPD; eligibility and access require specialist commissioning review, not ad hoc prescribing.
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.
- Refer confirmed severe or clinically significant disease for respiratory and, where indicated, liver or genomic assessment, then document genotype, concentration and organ phenotype in an accessible care record.
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.Avoid reflex escalation without checking smoking, adherence, technique and pulmonary rehabilitation. Inhaled corticosteroid use depends on exacerbation and eosinophilic or asthmatic features and can increase pneumonia risk.
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.Do not initiate in routine practice outside a recognised commissioning or research pathway. Confirm genotype and progression, exclude IgA-related hypersensitivity risk as directed, monitor infusion reactions, and remember that augmentation does not treat hepatic polymer accumulation.