What is the best management approach for alpha 1 anti-trypsin disease patients who smoke?

From the Guidelines

The best management approach for alpha-1 antitrypsin disease patients who smoke is immediate smoking cessation, which is the single most important intervention to reduce morbidity, mortality, and improve quality of life. This is because smoking dramatically accelerates lung damage in these patients by directly inactivating the small amount of functional alpha-1 antitrypsin they produce, while also increasing neutrophil elastase activity, creating a severe protease-antiprotease imbalance that rapidly destroys lung tissue 1.

Key Management Strategies

• Patients should be offered comprehensive smoking cessation support including:
  • Behavioral counseling
  • Nicotine replacement therapy (patches, gum, lozenges)
  • Medications such as varenicline (Chantix) 0.5-1mg twice daily or bupropion SR (Zyban) 150mg twice daily for 12 weeks
• For alpha-1 antitrypsin disease patients with emphysema or COPD, augmentation therapy with intravenous alpha-1 proteinase inhibitor (such as Prolastin-C, Aralast, Zemaira, or Glassia) at 60mg/kg weekly should be considered to slow lung tissue destruction, as it can reduce mortality and slow disease progress 1
• Standard COPD management is also essential, including:
  • Bronchodilators (LABA/LAMA combinations)
  • Inhaled corticosteroids when appropriate
  • Pulmonary rehabilitation
  • Vaccinations (influenza, pneumococcal, COVID-19)
  • Prompt treatment of respiratory infections Given the severe impact of smoking on lung health in alpha-1 antitrypsin disease patients, smoking cessation is paramount and should be addressed urgently to mitigate further lung damage and improve patient outcomes.

From the FDA Drug Label

Alpha1-PI deficiency is a chronic, autosomal, co-dominant hereditary disorder characterized by reduced levels of Alpha1-PI in the blood and lungs1, 2 Smoking is an important risk factor for the development of emphysema in patients with Alpha1-PI deficiency3 Augmenting the levels of functional protease inhibitor by intravenous infusion is an approach to therapy for patients with Alpha1-PI deficiency.

The best management approach for alpha 1 anti-trypsin disease patients who smoke is to stop smoking as it is an important risk factor for the development of emphysema in these patients.

• Augmentation therapy with alpha 1 anti-trypsin protein (IV) may be considered for patients with severe Alpha1-PI deficiency who have clinically evident emphysema.
• However, the efficacy of augmentation therapy in affecting the progression of emphysema has not been demonstrated in randomized, controlled clinical trials 2.

From the Research

Management Approach for Alpha 1 Anti-Trypsin Disease Patients Who Smoke

• The management of lung disease in patients with alpha-1 antitrypsin deficiency (AATD) includes both non-pharmacological and pharmacological approaches 3.
• Lifestyle changes, such as avoidance of environmental pollutants, including tobacco smoke, improving exercise levels, and nutritional status, are crucial pillars of AATD management 3.
• Non-pharmacological therapies follow conventional treatment guidelines for chronic obstructive pulmonary disease (COPD) 3.
• Specific pharmacological treatment consists of administering exogenous alpha-1 antitrypsin (AAT) protein intravenously (augmentation therapy) 3, 4.
• Augmentation therapy raises AAT levels in serum and lung epithelial lining fluid, increases anti-elastase capacity, and decreases several inflammatory mediators in the lung 3.
• Smoking has a significant impact on the decline in lung function in AATD patients, with past or present smoking history having the strongest relationship to reduction in forced expiratory volume in 1 s (FEV1) 5.
• The effect of smoking on lung function decline is more pronounced in current smokers than in ex-smokers, and greatest in patients with initial FEV1 in the range 30-65% predicted 5.

Diagnosis and Treatment of Lung Disease Associated with Alpha 1 Anti-Trypsin Deficiency

• AATD is a common inherited disorder associated with an increased risk of developing pulmonary emphysema and liver disease 6.
• Many people with AATD-associated pulmonary emphysema remain undiagnosed and therefore without access to care and counselling specific to the disease 6.
• AAT augmentation therapy is available and consists of i.v. infusions of exogenous AAT protein harvested from pooled blood products 6.
• The clinical efficacy of AAT augmentation therapy has been the subject of some debate, and its use was recently permitted by regulators in Australia and New Zealand 6.
• The diagnosis and management of AATD-related lung disease should include testing for AATD in all adults with symptomatic fixed airflow obstruction, whether clinically labeled as COPD or asthma 4.
• Individuals with unexplained bronchiectasis or liver disease should also be tested for AATD 4.
• Family testing of first-degree relatives is currently the most efficient detection technique for AATD 4.