Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

low plasma AAT

1st line – smoking cessation, pollution avoidance

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ONGOING
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low plasma AAT
1st line – 

smoking cessation, pollution avoidance

All patients with AAT deficiency should stop smoking and avoid pollution to help protect against respiratory manifestations. There is evidence demonstrating the rate of forced expiratory volume in the first second of expiration (FEV1) decline is worse in smokers compared with non-smokers; however, no significant difference is demonstrated between ex-smokers and non-smokers.[48]

Consider – hepatitis vaccination

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ONGOING
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low plasma AAT
Consider – 

hepatitis vaccination

Additional treatment recommended for SOME patients in selected patient group

Patients with AAT deficiency and a phenotype associated with liver disease (e.g., PI*ZZ, PI*Mmalton, PI*Siiyama) also require hepatitis A and hepatitis B vaccination to help protect against hepatic manifestations.[6][38]

Plus – standard COPD treatment

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ONGOING
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low plasma AAT
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with pulmonary manifestations
Plus – 

standard COPD treatment

Treatment recommended for ALL patients in selected patient group

Lung disease in AAT deficiency should be treated with the same modalities as COPD of alternate aetiologies.[38][45][61]​​

Although the precise regimen is dependent on the patient and the severity of their disease, therapies include short- and long-acting bronchodilators, inhaled corticosteroids, antibiotics, pulmonary rehabilitation, oxygen, and oral corticosteroids.

Consider – AAT augmentation therapy

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ONGOING
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low plasma AAT
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with pulmonary manifestations
Consider – 

AAT augmentation therapy

Additional treatment recommended for SOME patients in selected patient group

Patients with plasma AAT levels <11 micromol/L have inadequate protection against inflammatory lung disease.[7] If they have coexisting airflow obstruction they may benefit from intravenous AAT augmentation therapy, although evidence examining its effectiveness is limited.[8][62][63] 

Guidelines recommend intravenous AAT augmentation therapy in those with AAT deficiency with an FEV1 ≤65% predicted, and that it should continue indefinitely.[38] However, some experts believe that individuals with mild airflow obstruction should receive augmentation therapy, citing the difficulty in detecting statistically significant efficacy in this cohort given the slow rate of decline of control patients.[70] The Global Initiative for Chronic Obstructive Lung Disease advises that never-smokers or ex-smokers with FEV1 between 35% and 60% predicted are most suitable for AAT augmentation therapy.[45] The Canadian Thoracic Society guidelines suggest that augmentation therapy may be considered for non-smoking or ex-smoking patients with COPD and with FEV1 25% to 80% who are otherwise optimised pharmacologically and non-pharmacologically (i.e., pulmonary rehabilitation).[39]

Clinical trial and registry data are almost exclusively from patients with PI*ZZ phenotype; in clinical practice, people with PI*Z/null or PI*null/null genotypes are also evaluated for AAT augmentation. Other genotypes are not considered at risk or likely to benefit from AAT augmentation.[45] Although there is evidence that Z allele heterozygotes may have an increased risk of developing mild COPD, AAT augmentation therapy is not indicated because COPD does not develop in the absence of smoking and smoking cessation is, therefore, thought to be sufficient to prevent progression.[45]

If patients have low plasma AAT but normal lung function, they should not be treated with augmentation therapy as they have no manifestation of the disease.

If patients have low plasma AAT and mild airflow obstruction (FEV1 >85%), hepatitis vaccination and lifestyle changes (smoking cessation, pollution avoidance) are encouraged, and their lung function is monitored. If they lose lung function at an accelerated rate (a change in FEV1 of >120 mL per year), or if FEV1 is <65%, augmentation therapy can be started.[38][64]

One registry study demonstrated a survival benefit of augmentation therapy in patients with severe AAT deficiency, and this was uncoupled from any effect on FEV1 stabilisation/decline.​[73]

The National Institute for Health and Care Excellence in the UK does not recommend AAT replacement therapy for patients with AAT deficiency.[71]

Weekly infusions of purified AAT from pooled human plasma are sufficient for increasing AAT in lung fluid and for protective levels of plasma AAT.[74][75]  

Augmentation therapy carries a risk of anaphylaxis if an individual’s IgA level is near zero, so it is recommended that serum IgA level is measured before considering therapy.[70]

Primary options

alpha1-proteinase inhibitor: 60 mg/kg by intravenous infusion once weekly

Consider – lung transplant

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ONGOING
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low plasma AAT
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with pulmonary manifestations
Consider – 

lung transplant

Additional treatment recommended for SOME patients in selected patient group

Reserved for patients with end-stage lung disease (typically when FEV1 is <25% or there are signs of chronic CO₂ retention).[10]

Around 5% of lung transplants are performed on patients with emphysema secondary to AAT deficiency.[78] The 5-year survival rate following transplant is approximately 50%.[81][82][83]​ Median survival is 6.3 years.[83]

Plus – standard liver disease treatment

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ONGOING
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low plasma AAT
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with hepatic manifestations
Plus – 

standard liver disease treatment

Treatment recommended for ALL patients in selected patient group

Liver disease in AAT deficiency should be treated with the same modalities as liver disease of alternate aetiologies.[6][61]

The precise regimen is patient-specific and dependent on disease severity. It may include monitoring for coagulopathy or worsening LFTs; diuretics for ascites; oesophagogastroduodenoscopy to detect and manage varices; and liver transplantation.

AAT deficiency accounts for approximately 1% of all liver transplants. A characterisation of liver transplantation in AAT-deficient patients in 3 transplant centres revealed a 5-year survival rate of 80% for patients with the ZZ phenotype and 79% for patients with the SZ phenotype.[80]

Plus – alcohol avoidance

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ONGOING
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low plasma AAT
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with hepatic manifestations
Plus – 

alcohol avoidance

Treatment recommended for ALL patients in selected patient group

Alcohol consumption in individuals with AAT deficiency may increase the risk of liver manifestations, especially in patients with PI*ZZ phenotypes.[6] Patients with liver disease should be advised to avoid alcohol or at least limit their alcohol intake to <60 g/day (although there is no evidence that ethanol consumption affects progression of disease).[6][9]

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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