Alpha-1 antitrypsin deficiency and replacement therapy - Current developments and clinical significance () von Andreas Rembert Koczulla

1. Introduction 161.1. Basics 161.2. Alpha-1 antitrypsin 161.3. Alpha-1 antitrypsin deficiency 161.4. Genetics 161.5. Epidemiology 171.6. Course of disease 171.7. References 172. (Genetic) diagnostics and testing/screening for AATD 202.1. Clinical picture 202.2. (Genetic) diagnostics 202.2.1. Determination of A1AT serum level 212.2.2. Moleculargenetic analysis 212.3. References 233. Clinical course in patients with AATD 263.1. Genotype 263.2. Exposure to inhalative or nutritional noxae 263.3. (Infectious) exacerbations 263.4. Follow-up diagnostics 273.4.1. Measurement of body pletysmography and diffusion capacity 273.4.2. Imaging 273.5. AATD and liver disease 273.6. Annual follow-up examinations 273.7. References 284. Imaging in AATD 324.1. CT protocols 324.2. Emphysema diagnostics 324.3. Lung density measurement 324.4. Radiation dose 344.5. MRT of the thorax 344.6. Summary 344.7. References 345. Treatment of lung disease in AATD 385.1. Introduction 385.2. Scientific background 385.3. Indications for substitution therapy 405.4. Contraindications for substitution therapy 405.5. Safety 415.6. Summary and outlook 415.7. References 416. Comorbidities in AATD 446.1. Liver disease in AATD 446.1.1. Diagnostics 446.1.2. Treatment 446.2. Further comorbidities 446.2.1. Bronchiectasis in AATD 456.2.2. Anxiety and depression in patients with AATD 456.2.3. Vasculitis and AATD 466.3. Conclusion 466.4. References 467. Liver involvement in AATD 507.1. Introduction 507.2. Clinical picture 507.3. Recording of liver involvement in everyday clinical practice 517.4. Treatment of liver involvement in AATD 527.5. References 538. Vaccinations in AATD 568.1. Relevance of vaccine-preventable diseases and vaccination recommendation in AATD 568.2. Pneumococcal vaccination 578.3. Influenza vaccination 588.4. Pertussis vaccination 588.5. Zoster vaccination 588.6. Vaccination before a planned organ transplant 588.7. Vaccinations in children with AATD 588.8. Vaccination against SARS-CoV-2 598.8. References 599. Sports and exercise in patients with AATD 629.1. Evidence for physical training 629.2. Effects of physical training 629.3. Adaptation of training in AATD vs. COPD 639.4. Practical aspects of training 639.5. Outlook 649.6. References 6610. Lung transplantation in AATD 7010.1. Indications and contraindications 7010.2. Lung transplantation in COPD vs. AATD 7010.3. Survival rate and QoL after LTX 7110.4. A1AT substitution therapy after lung transplantation pro and contra 7210.4.1. Pro 7210.4.2. Contra 7310.5. Summary 7410.6. References 7411. Appendix 7811.1. Abbreviations 7811.2. Alpha1 Deutschland e.V. 78Index 79

Alpha-1 antitrypsin deficiency (AATD) is one of the most common genetic defects in Europe. As a consequence of the lowered A1AT serum level, the protease-antiprotease balance is disturbed, which among others can lead to an early development of emphysema. The underdiagnosis of AATD is another problematic aspect because it is suspected that only about 5 to 15% of all homozygous patients are currently identified. Usually there is also a diagnostic delay, which can be 5 years or more.This textbook provides an overview of AATD with causes and genetics, diagnosis and therapy, the role of comorbidities and further topics such as vaccinations, sport and physical activities as well as the very complex aspects of a lung transplant. The increasing importance of imaging is addressed as well as the overall clinical evaluation and the need for follow-up examinations. The result is a very practice-oriented volume that will be very helpful in everyday clinical practice in the care of patients with AATD.