Should We Test for Alpha-1-Antitrypsin in All COPD Patients?

Alpha-1-Antitrypsin Deficiency

Mutations in the SERPINA1 gene are the cause of insufficient serum levels of AAT or the production of a dysfunctional protein. AAT protects lung parenchyma from proteolytic damage. AAT deficiency (AATD) often leads to the early development of COPD and rapid progression of pulmonary emphysema. The estimated prevalence of AATD in the USA is 1:4000–5000. AATD can also lead to liver damage due to the intracellular accumulation of the Z variant of AAT in hepatocytes (this occurs with a mutation in the form of the 'Z allele' of the AAT gene, which can occur in one or two copies in an individual). This typically results in liver cirrhosis, which carries a risk of hepatocellular carcinoma.

Clinical Manifestations and Detection of AAT Deficiency

The most common clinical manifestation of AATD is thus a respiratory and/or liver disease. The diagnosis of AATD should be part of the supplementary and differential-diagnostic examination after the diagnosis of COPD and liver disease of unclear etiology. According to WHO recommendations, all COPD patients should be tested for AATD regardless of the clinical characteristics of the disease. However, suspicion of AATD is increased by certain signs, particularly the early development of emphysema, the presence of bronchiectasis, and a family history of AATD, COPD, or liver cirrhosis. Patients typically exhibit symptoms reminiscent of asthma (night cough, wheezing, shortness of breath, chest pain or pressure). Therefore, it is advisable to test adults with asthma that is not completely reversible after bronchodilator administration for AATD.

AAT Deficiency Diagnosis

AATD is diagnosed in the laboratory based on blood AAT levels and the determination of AAT genotype and phenotype. Testing serum AAT levels is commonly available. A high risk of emphysema is associated with levels < 0.6 g/l. It should be noted that concentrations of AAT, which is also an acute phase reactant, increase during infections, pregnancy, and following vaccination. Therefore, patients should be tested when clinically stable or concomitantly tested for C-reactive protein. To confirm AATD in individuals with low AAT levels, AAT genotype and phenotype must be determined, either from blood (dried blood spot) or buccal swab. The sample should be sent to a specialized laboratory.

Management of AAT Deficiency

The management of AATD is conducted by a general practitioner in collaboration with an AATD specialist. Treatment is both pharmacological and non-pharmacological. Patients should quit smoking, avoid polluted environments (including workplace exposure), and participate in pulmonary rehabilitation. The treatment of COPD is the same as for patients without AATD. For patients with at least moderate airway obstruction (FEV₁ < 60%) and serum AAT levels <0.5–0.8 g/l, so-called AAT augmentation therapy is recommended - intravenous administration of human purified AAT. It has been shown to slow the decline in lung function and progression of emphysema. Early treatment is crucial. On the other hand, AAT augmentation is not recommended for patients with liver damage because the damage results from the accumulation of AAT polymer.

Further information on the disease and its management can be found, for example, on the website www.alpha1.org.

Conclusion

General practitioners play a crucial role in detecting AATD. They should exclude this genetic disorder in all COPD patients. Diagnosis is made in the laboratory, not clinically. This testing and greater awareness of AATD can significantly help to improve the care of COPD patients and prevent its severe stages.

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Source: Lascano J. E., Campos M. A. The important role of primary care providers in the detection of alpha-1 antitrypsin deficiency. Postgrad Med 2017; 129 (8): 889–895, doi: 10.1080/00325481.2017.1381539.