Alpha-1 Antitrypsin Deficiency Targeted Testing and Augmentation Therapy: A Canadian Thoracic Society Clinical Practice Guideline

Abstract

Alpha-1 antitrypsin (A1AT) functions primarily to inhibit neutrophil elastase, and deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD). Severe A1AT deficiency occurs in one in 5000 to one in 5500 of the North American population. While the exact prevalence of A1AT deficiency in patients with diagnosed COPD is not known, results from small studies provide estimates of 1% to 5%. The present document updates a previous Canadian Thoracic Society position statement from 2001, and was initiated because of lack of consensus and understanding of appropriate patients suitable for targeted testing for A1AT deficiency, and for the use of A1AT augmentation therapy. Using revised guideline development methodology, the present clinical practice guideline document systematically reviews the published literature and provides an evidence-based update. The evidence supports the practice that targeted testing for A1AT deficiency be considered in individuals with COPD diagnosed before 65 years of age or with a smoking history of <20 pack years. The evidence also supports consideration of A1AT augmentation therapy in nonsmoking or exsmoking patients with COPD (forced expiratory volume in 1 s of 25% to 80% predicted) attributable to emphysema and documented A1AT deficiency (level ≤11 µmol⁄L) who are receiving optimal pharmacological and nonpharmacological therapies (including comprehensive case management and pulmonary rehabilitation) because of benefits in computed tomography scan lung density and mortality.

CTS position statement: Pharmacotherapy in patients with COPD—An update

“…20 We did not review, COPD related to a1-antitrypsin deficiency, as recommendations on testing and treatment have been addressed in a separate CTS clinical practice guideline. 21 This position statement focuses on the pharmacological therapy of COPD. This position paper will be updated in accordance with the CTS Living Guideline Model www.cts-sct.ca/ guidelines which includes a process for guideline review at least every 3 years to determine whether guideline updates are required.…”

Alpha-1-Antitrypsin Deficiency – Molecular Basis, Clinical Presentation, Therapeutic Options and an Integrative Approach in Diagnostics / DEFICIJENCIJA ALFA-1-ANTITRIPSINA – MOLEKULSKE OSNOVE, KLINIČKE MANIFESTACIJE, TERAPIJSKE MOGUĆNOSTI I INTEGRATIVNI PRISTUP U DIJAGNOSTICI

“…In accordance with the principles of evidence-based medicine, investigation of AATD is primarily indicated in conditions listed in Table III. Screening programs are only recommended for populations with an AATD incidence higher than 1:1 500 (19,20).…”

Alpha-1 antitrypsin deficiency: a commonly overlooked cause of lung disease: Figure 1:

“…11,13 The most recent statement by the Canadian Thoracic Society offered recommendations similar to those in the joint statement by the European Respiratory Society and the American Thoracic Society, but the former group capped the age of screening in patients with COPD at 65 years, based on a review of available screening studies (weak recommendation, lower quality evidence). 10,29 All patients should be informed of the risks of testing for alpha-1 antitrypsin deficiency, including the risk of psychological burden and genetic discrimination.…”

“…We also reviewed published guidelines on alpha-1 antitrypsin deficiency, including the American Thoracic Society/European Respiratory Society's 2003 guidelines 9 and the Canadian Thoracic Society's 2012 guidelines. 10 We reviewed published guidelines on chronic obstructive pulmonary disease, including the American Thoracic Society's 2004 guidelines, 11 the Canadian Thoracic Society's 2008 guidelines 12 and the 2011 update of the Global Initiative for Chronic Obstructive Lung Disease guidelines. 13 We searched the bibliographies of each set of guidelines for relevant articles.…”

“…The American Thoracic Society recommends augmentation therapy for patients with severe alpha-1 antitrypsin deficiency and clinically important obstructive lung disease; 46 the Canadian Thoracic Society also endorses its use for patients with an FEV 1 of 25%-80% of predicted and who have received optimal medical therapy. 10 Similar to other blood products for rare diseases, alpha-1 antitrypsin augmentation therapy is expensive, costing $60 000-$100 000 per year. In Canada, reimbursement is available from some private insurance plans and through the Review provincial formularies of British Columbia, Alberta, Manitoba and Quebec.…”