Alpha-1 Antitrypsin Deficiency (AATD)

The clinical practice guidelines released by the Alpha-1 foundation based on recommendations of the medical and scientific advisory committee demonstrate how to diagnose a probable case of Alpha-1 Antitrypsin Deficiency (AATD). The latest guideline is based upon clinical recommendations and best practices associated with testing for Alpha-1, Alpha-1 lung, and Alpha-1 liver disease. The current guidelines are updated versions of the 2003 document proposed by the American Thoracic Society (ATS), and European Respiratory Society (ERS).¹

It is recommended that all individuals suffering from the chronic obstructive pulmonary disease (COPD) should get tested for AATD regardless of age or ethnicity. Diagnostic testing is recommended for symptomatic individuals along with genotyping for S and Z alleles. Confirmatory or advanced testing such as expanded genotyping, a1-Antitrypsin Phenotyping (Pi Typing), and a1-Antitrypsin (AAT) level testing is recommended as well. Patients suffering from unexplained bronchiectasis, necrotizing panniculitis, and granulomatosis with polyangiitis are recommended to get tested for AATD as well.

Management Of AATD Patients With Lung Disease

Patients with a past medical history of smoking should be advised for complete cessation. As per guidelines, family members should be educated about risk modification like avoidance of smoking, and individuals with a smoking history should be monitored properly. A computerized tomography (CT) scan is recommended for newly diagnosed AATD patients with abnormal pulmonary function tests. Baseline CT has the potential to identify pulmonary emphysema in the presence of normal or complete pulmonary function tests. It is critical for detecting early panlobular disease which might be helpful in later evaluation. Serial chest CT scanning is not recommended to assess the progression of the disease. The guideline also mentioned that knowledge of chest CT does not improve the clinical outcome of the disease.²

Intravenous Augmentation Therapy For AATD Patients

As per clinical practice guidelines, intravenous augmentation therapy is not recommended for AATD patients undergoing liver disease treatment. Also, AATD diagnosed individuals with emphysema and bronchiectasis, who do not have airflow obstruction, should not undertake intravenous augmentation therapy. Individuals with lung disease related to AATD are recommended for intravenous augmentation therapy if they have forced expiratory volume (FEV1) less than or equal to 65%. While physicians are advised to discuss the cost of the therapy with potential AATD individuals with FEV1 > 65% as there’s a lack of evidence for such benefits. Lastly, individuals with necrotizing panniculitis are also recommended for the therapy mentioned above.³

AATD Patients With Pneumothorax

Current guidelines do not recommend screening patients with pneumothorax for AATD. Some studies suggest that AAT measurement is critical for patients suffering from pneumothorax, while others failed to show relevance because they were unable to prove deficiency of AAT in patients suffering from pneumothorax. Moreover, 7.7% of patients with pneumothorax were found to be deficient in AAT and it was related to phenotype SZ and ZZ. Some researchers support the radiological study of CT scans for patients with pneumothorax as it can detect diffuse cystic lung disease in such patients. Moreover, emphysema was found to be more prevalent among patients with SZ phenotype which could lead to AATD. Overall, studies suggest that patients with primary spontaneous pneumothorax should be screened for AATD as the detection rate was found to be comparable to other conditions.⁴

Screening For AATD Among Bronchiectasis Patients

Guidelines for AATD suggest routine screening for bronchiectasis patients. While a study conducted in the UK with 1600 bronchiectasis patients found that routine screening for AATD would not lead to a high detection rate as the geographical region also matters. Bronchiectasis leads to chronic respiratory symptoms with permanent dilation of the bronchi. AATD can lead to bronchiectasis and it can also lead to airways obstruction wherein augmentation therapy is recommended. Phenotypes PiSZ and PiZZ were found with lower serum alpha 1 antitrypsin (A1AT), which can lead to an increased risk of lung disease. Prior studies showed that patients with the PiZZ genotype were found with 95% bronchiectasis which can affect a mean of 3.7 lobes. 27% of patients were found with bronchiectasis with more than four lobes. Routine testing of A1AT was found beneficial as per a study conducted among UK adults.

Augmentation therapy was recommended for non-smoking patients with reduced lung function, specifically among patients diagnosed with emphysema. Non-smoking patients with the PiMZ phenotype showed a lower risk for lung disease. The study also revealed that the prevalence of other etiologies such as allergic bronchopulmonary aspergillosis (ABPA) is higher than AATD, which questions the clinical guideline recommendations for AATD screening among bronchiectasis patients. Also, the study mentioned that AATD screening among bronchiectasis patients remains unclear as the British Thoracic Society guidelines recommend screening for AATD but do not recommend routinely testing patients for AATD. Overall, the prevalence of AATD among bronchiectasis patients was found to be less than 1% among UK adults. Also, augmentation therapy shows the reduced frequency of hospital admission for patients suffering from acute exacerbation of chronic obstructive pulmonary disease (COPD). It has also been shown to reduce the progression of emphysema.⁵


  1. Clinical practice guidelines. Alpha-1 Foundation. Assessed July 9, 2021
  2. Clinical practice guidelines – the diagnosis and management of alpha-1 antitrypsin deficiency in the adult. COPD Foundation. Assessed July 9, 2021
  3. Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis. 2016 Jun 6;3(3):668-682. doi:  10.15326/jcopdf.3.3.2015.0182 Accessed on July 9, 2021.
  4. Dias E, Farinha I, Costa F. Alpha-1-antitrypsin deficiency (AATD) and spontaneous pneumothorax: guidelines do not recommend screening for AATD in patients with pneumothorax – what did we find in 10 years of clinical evidence? Pulmonology. 2021 Jan-Feb;27(1):80-81. doiI: 10.1016/j.pulmoe.2020.05.014. Epub 2020 Jun 14. Accessed on July 9, 2021.
  5. Carreto L, Morrison M, Donovan J, Finch S, Tan GL, Fardon T, Wilson R, Furrie E, Loebinger M, Chalmers JD. Utility of routine screening for alpha-1 antitrypsin deficiency in patients with bronchiectasis. Thorax. 2020 Jul;75(7):592-593.doi: 10.1136/thoraxjnl-2019-214195. Epub 2020 Apr 17. Accessed on July 9, 2021.

Reviewed by Harshi Dhingra, MD, on 7/1/2021.