Alpha-1 antitrypsin deficiency and replacement therapy - Current developments and clinical significance

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.

Inhaltsverzeichnis:

1. Introduction 16
1.1. Basics 16
1.2. Alpha-1 antitrypsin 16
1.3. Alpha-1 antitrypsin deficiency 16
1.4. Genetics 16
1.5. Epidemiology 17
1.6. Course of disease 17
1.7. References 17
2. (Genetic) diagnostics and testing/screening for AATD 20
2.1. Clinical picture 20
2.2. (Genetic) diagnostics 20
2.2.1. Determination of A1AT serum level 21
2.2.2. Moleculargenetic analysis 21
2.3. References 23
3. Clinical course in patients with AATD 26
3.1. Genotype 26
3.2. Exposure to inhalative or nutritional noxae 26
3.3. (Infectious) exacerbations 26
3.4. Follow-up diagnostics 27
3.4.1. Measurement of body pletysmography and diffusion capacity 27
3.4.2. Imaging 27
3.5. AATD and liver disease 27
3.6. Annual follow-up examinations 27
3.7. References 28
4. Imaging in AATD 32
4.1. CT protocols 32
4.2. Emphysema diagnostics 32
4.3. Lung density measurement 32
4.4. Radiation dose 34
4.5. MRT of the thorax 34
4 .6. Summary 34
4.7. References 34
5. Treatment of lung disease in AATD 38
5.1. Introduction 38
5.2. Scientific background 38
5.3. Indications for substitution therapy 40
5.4. Contraindications for substitution therapy 40
5.5. Safety 41
5.6. Summary and outlook 41
5.7. References 41
6. Comorbidities in AATD 44
6.1. Liver disease in AATD 44
6.1.1. Diagnostics 44
6.1.2. Treatment 44
6.2. Further comorbidities 44
6.2.1. Bronchiectasis in AATD 45
6.2.2. Anxiety and depression in patients with AATD 45
6.2.3. Vasculitis and AATD 46
6.3. Conclusion 46
6.4. References 46
7. Liver involvement in AATD 50
7.1. Introduction 50
7.2. Clinical picture 50
7.3. Recording of liver involvement in everyday clinical practice 51
7.4. Treatment of liver involvement in AATD 52
7.5. References 53
8. Vaccinations in AATD 56
8.1. Relevance of vaccine-preventable diseases and vaccination recommendation in AATD 56
8.2. Pneumoco ccal vaccination 57
8.3. Influenza vaccination 58
8.4. Pertussis vaccination 58
8.5. Zoster vaccination 58
8.6. Vaccination before a planned organ transplant 58
8.7. Vaccinations in children with AATD 58
8.8. Vaccination against SARS-CoV-2 59
8.8. References 59
9. Sports and exercise in patients with AATD 62
9.1. Evidence for physical training 62
9.2. Effects of physical training 62
9.3. Adaptation of training in AATD vs. COPD 63
9.4. Practical aspects of training 63
9.5. Outlook 64
9.6. References 66
10. Lung transplantation in AATD 70
10.1. Indications and contraindications 70
10.2. Lung transplantation in COPD vs. AATD 70
10.3. Survival rate and QoL after LTX 71
10.4. A1AT substitution therapy after lung transplantation - pro and contra 72
10.4.1. Pro 72
10.4.2. Contra 73
10.5. Summary 74
10.6. References 74
11. Appendix 78
11.1. Abbreviations 78
11.2. Alpha1 Deutschland e.V. 78
Index 79