Do patients with Alpha-1 (A1) antitrypsin deficiency live normal lifespans with or without augmentation therapy?

From the Guidelines

Patients with Pizz alpha-1 antitrypsin deficiency can achieve near-normal life expectancy with appropriate replacement therapy, but typically do not live normal lifespans without it. The most recent and highest quality study, 1, suggests that augmentation therapy can slow the progression of emphysema and improve survival rates in affected individuals. This study found that intravenous administration of purified human AAT concentrate increased lung levels of AAT in AAT-deficient individuals, and that weekly infusions of AAT at a dose of 60 mg/kg body weight can slow the annual decline in FEV1.

Key Findings

• The study 1 demonstrated that augmentation therapy can reduce mortality and slow disease progress in moderately advanced emphysema due to severe alpha-1 antitrypsin deficiency.
• Another study, 1, found that FEV1 is the most important predictor of survival of patients with emphysema due to AAT deficiency, and that life expectancy is less than 20 years after diagnosis in smokers who cannot stop smoking.
• The decline in FEV1 is most rapid when this value is between 30 and 65% of the predicted value, as reported in study 1.
• Comprehensive management, including smoking cessation, prompt treatment of respiratory infections, bronchodilators, and pulmonary rehabilitation, is crucial in addition to replacement therapy, as noted in study 1.

Treatment Recommendations

• Alpha-1 antitrypsin augmentation therapy, administered as weekly intravenous infusions of purified human alpha-1 antitrypsin (typically 60 mg/kg), is recommended to slow the progression of emphysema and improve survival rates.
• Early diagnosis and treatment initiation are crucial, as replacement therapy cannot reverse existing lung damage but aims to prevent further deterioration, as highlighted in study 1.
• Smoking cessation is essential, as smoking can significantly reduce life expectancy in patients with AAT deficiency, as reported in study 1.

From the Research

Patient Lifespans with Alpha-1 Antitrypsin Deficiency

• Patients with Alpha-1 antitrypsin deficiency (AATD) may experience reduced lifespans due to the development of chronic obstructive pulmonary disease and liver disease 2, 3.
• The severity of the disease and the presence of other comorbidities or risk factors can affect disease progression and lifespan 2, 4.
• Replacement therapy, such as weekly intravenous administration of purified AAT, may help to slow disease progression and improve lung function in some patients 5, 6.

Effectiveness of Replacement Therapy

• Studies have shown that replacement therapy can reduce the decline in forced expiratory volume in 1 second (FEV1) in patients with moderate lung disease or accelerated FEV1 decline 4, 6.
• However, the effectiveness of replacement therapy in improving overall lifespan and quality of life is still being researched and debated 4, 6.
• Other treatments, such as liver replacement therapy and lung transplantation, may be necessary for severe cases of liver or lung disease 3.

Disease Progression and Lifespan

• The natural history of AATD is highly heterogeneous, and disease progression can vary significantly between individuals 2, 3.
• Screening studies have shown that only 10-15% of individuals with the Pi*ZZ genotype develop clinically significant liver disease over the first 20 years of life 3.
• Further research is needed to understand the factors that affect disease progression and lifespan in patients with AATD 2, 4, 6, 3.