The best practice in diagnosis of pulmonary diseases in α1-antitrypsin deficiency (AATD) according to the recommendations of the US Alpha-1 Foundation [31] and the European Respiratory Society (ERS) [4]

US Alpha-1 FoundationERS
Laboratory testing for AATD
  • All individuals with COPD regardless of age or ethnicity; all individuals with unexplained chronic liver disease; all individuals with necrotising panniculitis, granulomatosis with polyangiitis, or unexplained bronchiectasis should be tested for AATD

  • Parents, siblings and children, as well as extended family of individuals identified with an abnormal gene for AAT, should be provided genetic counselling and offered testing for AATD

  • For family testing after a proband is identified, AAT level testing alone is not recommended, because it does not fully characterise disease risk from AATD

  • For diagnostic testing of symptomatic individuals, genotyping for at least the S and Z alleles is recommended

  • Advanced or confirmatory testing should include Pi-typing, AAT level testing and/or expanded genotyping

  • Quantitative determination of AAT levels in blood is a crucial first test to identify AATD

  • Quantitative deficiency must be supported by qualitative tests to identify the genetic mutation(s) causing AATD

  • Protein phenotyping by isoelectric focusing identifies variants where AAT is present in the sample including the rarer variants F, I and P, etc.

  • Genotyping allows a rapid and precise identification/exclusion of S and Z alleles and other variants, where specific primers are available

  • Gene sequencing remains necessary for those cases where a null variant or a deficient variant other than Z or S is suspected

  • Testing of relatives of identified patients should be considered after appropriate counselling

  • Genetic testing should be carried out only after informed consent is given and in accordance with the relevant guidelines and legislation

Pulmonary function testing
  • Initial evaluation with complete lung function testing is recommended

  • Annual follow-up of adults with at least a spirometry test is recommended

  • Since the lung disease associated with AATD often starts as purely parenchymal destruction, more complete pulmonary function testing (including measures of diffusing capacity) may be considered

  • Annual measurement of lung function including post-bronchodilator FEV1 and gas transfer provides information about disease progression

Chest CT scanning
  • In newly diagnosed patients who are symptomatic and/or have abnormal pulmonary function testing, a baseline CT scan of the chest is recommended

  • Serial chest CT scanning to monitor progression of disease is not recommended

  • Lung densitometry, as performed in observational cohort studies and randomised clinical trials, is the most sensitive measure of emphysema progression

  • The correlation between change in lung density and any short-term change in measures of pulmonary function is weak; however, in the longer term, CT lung density decline correlates with reduction in FEV1 and health status

  • The role of CT in the follow-up of patients in routine clinical practice requires further validation

CT: computed tomography; COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in 1 s.