Diagnosis and treatment of lung disease associated with alpha one‐antitrypsin deficiency: A position statement from the Thoracic Society of Australia and New Zealand*

Abstract

AATD is a common inherited disorder associated with an increased risk of developing pulmonary emphysema and liver disease. Many people with AATD‐associated pulmonary emphysema remain undiagnosed and therefore without access to care and counselling specific to the disease. AAT augmentation therapy is available and consists of i.v. infusions of exogenous AAT protein harvested from pooled blood products. Its clinical efficacy has been the subject of some debate and the use of AAT augmentation therapy was recently permitted by regulators in Australia and New Zealand, although treatment is not presently subsidized by the government in either country. The purpose of this position statement is to review the evidence for diagnosis and treatment of AATD‐related lung disease with reference to the Australian and New Zealand population. The clinical efficacy and adverse events of AAT augmentation therapy were evaluated by a systematic review, and the GRADE process was employed to move from evidence to recommendation. Other sections address the wide range of issues to be considered in the care of the individual with AATD‐related lung disease: when and how to test for AATD, changing diagnostic techniques, monitoring of progression, disease in heterozygous AATD and pharmacological and non‐pharmacological therapy including surgical options for severe disease. Consideration is also given to broader issues in AATD that respiratory healthcare staff may encounter: genetic counselling, patient support groups, monitoring for liver disease and the need to establish national registries for people with AATD in Australia and New Zealand.

Alpha-1 Antitrypsin PI M Heterozygotes with Rare Variants: Do They Need a Clinical and Functional Follow-Up?

“…However, the recent implementation of serum AAT dosage and SERPINA-1 genetic testing in patients affected by several respiratory diseases or unexplained dyspnea has increased the detection not only of the already known deficient variants, but also of the new rare PI* alleles [16,23]. We suppose that their number will increase further, as the most recent AATD position statement of the Thoracic Society of Australia and New Zealand has expanded the indication of AATD tests in all patients with chronic airflow obstruction, in asthma patients with persistent airflow limitation, in subjects with emphysema disproportionate to their smoking history or in the presence of liver or skin disease [24]. In addition, the availability of a genotyping test that can be performed not only on dried blood spot samples but also on buccal swabs may implement both the diagnosis of AATD and the identification of new rare PI* allelic variants [25,26].…”

Alpha 1 antitrypsin deficiency - etiology, symptoms in various organs, diagnosis, treatment, prognosis

“…Emphysema and COPD management mostly include symptomatic treatment such as use of inhaled bronchodilators in the event of bronchospastic symptoms, as well as respiratory rehabilitation and oxygen therapy in case of respiratory failure. (23) The patients should cease smoking and avoid exposure to tobacco smoke. Emphasis should also be made to avoid irritants in home and work environments.…”

“…It has demonstrated reduction of the lung density loss measured by computer tomography, but it failed to show improvement in lung function, exacerbation frequency or quality of life. (6,9,23) Although the therapy remains controversial, it has been approved by many national authorities and drug administrations (11,(24)(25)(26) In liver disease promising results were found with use of Fazirsiran -a RNA-interfering drug, which is able to reduce the production of abnormal alpha-1 antitrypsin. The drug appears to be very well-tolerated with no adverse effects.…”

Common conditions that mimic asthma

“…Assess for COPD in all smokers and ex‐smokers with ischaemic heart disease, as tobacco exposure is a risk factor for both. Ask about family history of COPD, emphysema and liver disease, as α‐1 antitrypsin deficiency (about 1% of COPD patients) can lead to early onset emphysema despite little smoking history 20 …”