Comparison of recommendations from American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines (2003), US Alpha-1 Foundation guidelines (2016) and ERS statement (2017)

ATS/ERS statement (2003) [1]US Alpha-1 Foundation guidelines (2016) [13]ERS statement (2017) [14]
Diagnostic tests
  • AAT serum levels should not be viewed in isolation

  • Phenotyping or targeted genotyping may be utilised

  • Phenotyping may be insufficient to detect rare variants and sequencing may be required

  • Targeted genotyping for S and Z alleles as a minimum

  • Initial tests can be confirmed by phenotyping, quantitation of AAT serum levels and/or expanded targeted genotyping

Establishing AAT serum levels is a crucial first test, but must be supported by qualitative evidence of a mutation
Phenotyping and genotyping can both be used to establish mutation(s) present
Gene sequencing is necessary when a null or rare variant is suspected
Who should be tested?
 Testing for index case
  • Emphysema with early onset (<45 years) or without recognised risk factors, e.g. smoking, or with basilar hyperlucency

  • Bronchiectasis or liver disease with unknown aetiology

  • Necrotising panniculitis and anti-proteinase 3-positive vasculitis

  • Family history of emphysema, bronchiectasis, panniculitis or liver disease

  • COPD or unexplained bronchiectasis, regardless of age/ethnicity

  • All individuals with liver disease of unknown aetiology

  • All patients with granulomatosis with polyangiitis/necrotizing panniculitis

  • COPD or adult-onset asthma

 Familial testing
  • Recommended for siblings of index cases with severe deficiency

  • Should be discussed with offspring or distant relatives of individuals with severe deficiency, and siblings, offspring, parents and distant relatives of individuals with intermediate deficiency

  • Parents, sibling, offspring and extended family should be offered genetic counselling and testing

  • AAT level testing alone is not recommended when testing family members

  • Test parents of index case only if a null gene is suspected

  • Test partner of index case; if PI*MZ is found, test offspring of index case

  • Test sibling(s) of index case; if PI*MZ is found, test partner of sibling(s), if further PI*MZ is found, test offspring of sibling(s)

 Population screening
  • Screening of any age group should be discouraged; screening of active smokers with normal spirometry is not recommended

  • Full lung function testing at baseline and spirometry at yearly intervals

  • Regular liver function testing requires investigation

  • Baseline and annual spirometry

  • CT scan at baseline; serial CT scanning not recommended

  • Monitor for liver disease annually: liver ultrasound and AST, ALT, GGT, albumin, bilirubin and INR

  • Importance of multidisciplinary approach highlighted

  • Baseline: assess lung physiology and conduct routine liver function and blood tests

  • Up to 3 months: reassess and collate data; monitor exacerbation diary, initiate smoking cessation

  • Up to 6 months: assess full physiology, QoL assessment, routine blood tests

  • 6–12 months: continue monitoring, initiate AAT therapy as appropriate

  • FEV1 and DLCO are useful to monitor disease progression

AAT therapy utilisation
  • Symptomatic individuals with FEV1 35–65% pred

  • Symptomatic individuals with FEV1 ≤65% pred (strongest recommendation); treatment can be considered outside of this range

  • Symptomatic individuals (no FEV1 range given)

 Not recommended
  • PI*MZ individuals and current smokers

  • PI*MZ and current smokers

  • Emphysema/ bronchiectasis without airflow obstruction

  • PI*MZ, PI*SZ and current smokers

AAT: α1-antitrypsin; COPD: chronic obstructive pulmonary disease; CT: computed tomography; AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: γ-glutamyltransferase; INR: international normalised ratio; QoL: quality of life; FEV1: forced expiratory volume in 1 s; DLCO: diffusing capacity of the lung for carbon monoxide