What is the deficiency that often leads to Chronic Obstructive Pulmonary Disease (COPD)?

From the Guidelines

Alpha-1 antitrypsin deficiency is the genetic condition that often leads to COPD, as it allows enzymes to break down healthy lung tissue, leading to emphysema, a form of COPD. This hereditary disorder occurs when the body doesn't produce enough alpha-1 antitrypsin (AAT), a protein made in the liver that protects the lungs from damage 1. Without sufficient AAT, enzymes called neutrophil elastase can attack and break down healthy lung tissue, leading to emphysema, a form of COPD. This damage typically appears earlier in life than smoking-related COPD, often before age 40. The deficiency is caused by mutations in the SERPINA1 gene and is inherited in an autosomal codominant pattern.

Some key points to consider in the management of COPD, especially in the context of alpha-1 antitrypsin deficiency, include:

• The importance of confirming a diagnosis of COPD with spirometry, as emphasized in recent guidelines 1
• Evaluating symptom burden, health status, and risk of exacerbations over time
• Implementing pharmacological and nonpharmacological treatments, such as smoking cessation counseling, vaccinations, self-management education, and pulmonary rehabilitation, which are vital for effective comprehensive management of COPD 1
• Considering augmentation therapy for individuals with alpha-1 antitrypsin deficiency, which involves regular infusions of AAT protein to raise blood levels and protect the lungs 1

It's crucial to note that while alpha-1 antitrypsin deficiency accounts for only about 1-3% of all COPD cases, testing for it is recommended in all patients with COPD, especially those who develop the disease at a young age or have a family history of the condition. People with this deficiency should avoid smoking completely, as it accelerates lung damage. Recent guidelines, such as the 2023 Canadian Thoracic Society guideline on pharmacotherapy in patients with stable COPD, provide an update on the optimal approach to the pharmacological treatment of individuals with COPD to alleviate symptoms, improve health status, and prevent exacerbations 1.

From the Research

Deficiency Leading to COPD

• The deficiency that often leads to Chronic Obstructive Pulmonary Disease (COPD) is Alpha-1 antitrypsin deficiency (AATD) 2, 3, 4, 5.
• AATD is a genetic risk factor for COPD, and its biochemical events leading to lung destruction are well understood 2.
• The clinical manifestations of AATD include panacinar emphysema, airway hyperresponsiveness, and bronchiectasis 3.
• AATD is underdiagnosed, and early diagnosis can affect the course of disease and allow for appropriate treatment decisions to be made 2.
• Individuals with AATD experience more profound desaturation with exercise than age-, sex-, race-, and FEV1-matched control subjects with usual COPD 4.

Characteristics of AATD

• AATD is a rare genetic disorder associated with the development of liver and lung disease 5.
• The measurement of the AAT serum level is useful as a screening test for AATD 5.
• Severe AATD increases the risk of venous thromboembolism (VTE) compared to the general population 6.
• Risk factors for incident VTE in AATD individuals include male gender, age, COPD, cancer, and liver disease 6.