Abstract
Bibek Gooptu, Division of Asthma, Allergy and Lung Biology, King’s College London, 5th Floor, Tower Wing, Guy’s Hospital, Great Maze Pond, London, SE1 9RT, UK. E-mail: [email protected]
Case history: Routine screening of a newly referred COPD patient reveals a low serum level of α1-AT, and subsequent tests confirm that the patient is homozygous for the Z α1-ATD allele. What is the current evidence for the use of α1-AT augmentation therapy? What is the significance for family members and should they be screened for α1-ATD? How would you explain why the disease can cause both lung and liver disease? What other diseases are linked with this condition?
Chapter summary: The emphysema of α1-ATD is the best understood subphenotype of COPD in terms of its genetic basis, disease behaviour and major pathogenic mechanisms. However, this level of insight has not yet translated to a definitive cure, or even a tailored treatment that has proven robustly effective, for α1-ATD. This apparent paradox drives controversy, by implying an urgent need to identify where knowledge is incomplete or existing data are misunderstood. From another perspective, it highlights how subphenotyping is a necessary element but is not sufficient for development of specific treatments to provide the best possible patient-centred care. In this review of ongoing debates in α1-ATD we address, in turn, the involvement of different cell types, the extent of associated clinical phenotypes, the need to identify the optimal role of existing therapeutic options and how to develop new treatments. In doing so, we define important areas that are the subject of further active research, or that in our view require it.
Case history: Routine screening of a newly referred COPD patient reveals a low serum level of α1-AT, and subsequent tests confirm that the patient is homozygous for the Z α1-ATD allele. What is the current evidence for the use of α1-AT augmentation therapy? What is the significance for family members and should they be screened for α1-ATD? How would you explain why the disease can cause both lung and liver disease? What other diseases are linked with this condition?
Chapter summary: The emphysema of α1-ATD is the best understood subphenotype of COPD in terms of its genetic basis, disease behaviour and major pathogenic mechanisms. However, this level of insight has not yet translated to a definitive cure, or even a tailored treatment that has proven robustly effective, for α1-ATD. This apparent paradox drives controversy, by implying an urgent need to identify where knowledge is incomplete or existing data are misunderstood. From another perspective, it highlights how subphenotyping is a necessary element but is not sufficient for development of specific treatments to provide the best possible patient-centred care. In this review of ongoing debates in α1-ATD we address, in turn, the involvement of different cell types, the extent of associated clinical phenotypes, the need to identify the optimal role of existing therapeutic options and how to develop new treatments. In doing so, we define important areas that are the subject of further active research, or that in our view require it.
| Original language | English |
|---|---|
| Journal | European Respiratory Monograph |
| DOIs | |
| Publication status | Published - 2015 |