Management of alpha-1 antitrypsin deficiency (AATD) in the adult according to the recommendations of US Alpha-1 Foundation [31] and European Respiratory Society (ERS) [4]

US Alpha-1 FoundationERS
Augmentation therapy
  • Intravenous augmentation therapy is recommended for:

     individuals with FEV1 ≤65% pred;

     in those with lung disease related to AATD and FEV1 >65% pred, there is need for a discussion with each individual regarding the potential benefits of reducing lung function decline with consideration of the cost of therapy and lack of evidence for such benefit;

     individuals with necrotising panniculitis

  • Intravenous augmentation therapy is not recommended for:

     individuals with the MZ genotype of AATD;

     individuals with lung disease due to AATD who continue to smoke;

     individuals with AATD and emphysema or bronchiectasis who do not have airflow obstruction;

     the treatment of liver disease due to AATD;

     individuals who have undergone liver transplantation

  • Additional recommendations regarding dosing of intravenous augmentation therapy:

     weekly doses higher than the current US FDA-approved dose are not recommended;

     monitoring of trough AAT blood levels to evaluate the adequacy of AAT augmentation dosing is not recommended

  • Several randomised clinical trials in severe AATD have shown intravenous augmentation therapy to reduce the progression of emphysema as assessed by CT densitometry

  • There is no evidence to support efficacy of AAT augmentation therapy in PiSZ, PiMZ or current smokers of any protein phenotype

  • Clinical trials have used fixed doses of AAT determined by body weight; whether individualising dosage based on trough levels for each patient has any benefit requires confirmation

Lung volume reduction surgery and endoscopic bronchial valve placement
  • Surgical volume reduction and endoscopic bronchial valve placement may be considered in selected patients with AATD, but further studies are needed to confirm the role of such therapies

  • The optimal results of these techniques are obtained when a careful appraisal of risks and benefits are performed by a multidisciplinary team experienced in lung volume reduction and AATD

Lung transplantation
  • The survival benefit of lung transplant in AATD patients is not clear

  • In general, patients with AATD have improved quality of life following lung transplantation

  • Referral timing, rate of decline in lung function, health status and social support differ from patient to patient, and will have an influence on the evaluation for transplant

  • The role of post-transplant augmentation therapy in particular needs to be explored

FEV1: forced expiratory volume in 1 s; US FDA: United States Food and Drug Administration; CT: computed tomography.