Development of a Prediction Score for the Occurrence of Death or Lung Transplantation in Patients With Emphysema Secondary to Alpha-1-anti-tripsin Deficiency (FLARE)
Emphysema linked to alpha-1-antitrypsin deficiency (DAAT): towards a better prediction of risks Emphysema caused by alpha-1-antitrypsin deficiency (DAAT) is a rare genetic disorder that can lead to serious complications, such as the need for a lung transplant or death, affecting up to 15% of patients. The only specific treatment available is a weekly infusion of alpha-1-antitrypsin (IV-AAT), an expensive and burdensome therapy.
Currently, there is no reliable model to predict the course of the disease in these patients. Our study, conducted in several French hospitals, aims to develop a prediction tool combining clinical, biological, functional data and advanced medical image analysis (lung CT). This model will make it possible to identify the most at-risk patients, in order to better adapt their care, anticipate transplant needs and avoid unnecessary treatments for low-risk patients.
Ultimately, this approach could also improve access to care for patients who need it most, while optimizing health system resources.
調査の概要
詳細な説明
Context. Emphysema secondary to alpha-1-anti-trypsin deficiency (AATD) is a genetic rare disease, but with pejorative events such as death or lung transplantation (LT) which affect up to 15% of patients. Aside from standard medical care for COPD management, the only specific treatment as augmentation therapy for severe AATD, is weekly intravenous alpha-1 antitrypsin (IV-AAT) which is still expensive and restrictive. Several prognostic scores for tobacco-related COPD have been developed but, none of them have been validated in AATD, neither have included quantitative chest CT imaging while they have been associated with mortality in emphysema. Therefore, we aim to develop a prediction model combining clinical, biological, functional and quantitative CT data (including radiomics) for mortality or LT to identify at-risk patients with emphysema secondary to AATD.
Methods: From several French hospitals, we'll conduct a multicenter retrospective study based on data collected in usual care among patients over 18-year-old, with an available chest CT. We'll collect clinical data (BMI, mMRC dyspnea scale), respiratory function parameters and quantitative imaging data (including radiomics) from the initial CT from AATD patients secondary to ZZ, Znull, ZMalton, Z and rare mutations. We'll then validate our results on an independent external database from the European AADT cohort (EARCO), with specific dedicated funding.
Perspectives: To develop a prediction model to identify the AATD patients at risk of clinical deterioration, defined by death or LT allowing for personalized care, in order to: 1. anticipate registration on the transplant list, 2. optimize overall management, including pharmacological (IV-AAT) and non-pharmacological management. 3. to avoid cost-prohibitive and constraining IV-AAT infusion for low risk patients For Health policy, finding a way to target high-risk patients may help a better access for IV-AAT to appropriate individuals.
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Maéva ZYSMAN, MD, PhD
- 電話番号：+335 57 65 63 38
- メール：maeva.zysma@chu-bordeaux.fr
研究連絡先のバックアップ
- 名前：Margot GENAUD
- 電話番号：+335 25 35 21 94
- メール：margot.genaud@chu-bordeaux.fr
研究場所
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Bron、フランス、69677
- 募集
- Hospices Civils de Lyon
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コンタクト：
- Jean-Francois MORNEX, MD, PhD
- 電話番号：+334 72 11 80 17
- メール：jean-francois.mornex@univ-lyon1.fr
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主任研究者：
- Jean-Francois MORNEX, MD, PhD
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Lille、フランス、59000
- 募集
- CHU de Lille
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コンタクト：
- Olivier LE ROUZIC, MD, PhD
- 電話番号：+333 20 16 05 30
- メール：Olivier.LEROUZIC@chu-lille.fr
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主任研究者：
- Olivier LE ROUZIC, MD, PhD
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Paris、フランス、75018
- 募集
- Hopital Bichat Claude-Bernard
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コンタクト：
- Vincent BUNEL GOURDY, MD
- 電話番号：+331 40 25 61 01
- メール：vincent.bunel@aphp.fr
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主任研究者：
- Vincent BUNEL GOURDY, MD
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Pessac、フランス、33600
- 募集
- Bordeaux University Hospital
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コンタクト：
- Maéva ZYSMAN, MD, PhD
- 電話番号：+335 57 65 63 38
- メール：maeva.zysma@chu-bordeaux.fr
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コンタクト：
- Margot GENAUD
- 電話番号：+335 25 35 21 94
- メール：margot.genaud@chu-bordeaux.fr
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主任研究者：
- Maéva ZYSMAN, MD,PhD
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
Inclusion criteria:
- diagnosed between 2010 and 2025
- in the pulmonology department
- diagnosis of emphysema and COPD secondary to alpha-1 antitrypsin deficiency ZZ, Znull, ZMalton, Z and rare mutations,
- emphysema according to the initial thoracic CT scan (+/- 12 months after diagnosis).
Exclusion criteria:
- Age <18 years
- Patient opposed to the use of their data for research purposes
- Patient deprived of liberty by judicial decision
- Patient not affiliated with a social security scheme
- no CT scan available
- no lung function test available the year around CT scan
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
|---|
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Emphysema secondary to alpha-1-anti-trypsin deficiency (AATD)
The subjects included will be any patients followed and diagnosed between 2010 and 2025 in the pulmonology department for emphysema and COPD secondary to alpha-1 antitrypsin deficiency ZZ, Znull, ZMalton, Z and rare mutations, based on the diagnosis of emphysema made from an initial thoracic CT scan (+/- 12 months after diagnosis).
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Evaluation of vital status
時間枠：5 years
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Death within 5 years of emphysema diagnosis.
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5 years
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Evaluation of transplantation status
時間枠：5 years
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Lung transplantation within 5 years of emphysema diagnosis.
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5 years
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協力者と研究者
出版物と役立つリンク
一般刊行物
- McElvaney NG, Burdon J, Holmes M, Glanville A, Wark PA, Thompson PJ, Hernandez P, Chlumsky J, Teschler H, Ficker JH, Seersholm N, Altraja A, Makitaro R, Chorostowska-Wynimko J, Sanak M, Stoicescu PI, Piitulainen E, Vit O, Wencker M, Tortorici MA, Fries M, Edelman JM, Chapman KR; RAPID Extension Trial Group. Long-term efficacy and safety of alpha1 proteinase inhibitor treatment for emphysema caused by severe alpha1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir Med. 2017 Jan;5(1):51-60. doi: 10.1016/S2213-2600(16)30430-1. Epub 2016 Dec 2.
- Ho ESY, Ellis PR, Kavanagh D, Subramanian D, Stockley RA, Turner AM. Proposal and Validation of the Minimum Clinically Important Difference in Emphysema Progression. Chronic Obstr Pulm Dis. 2025 Mar 27;12(2):109-116. doi: 10.15326/jcopdf.2024.0511.
- Stolk J, Stockley RA, Piitulainen E, Stoel BC. Relationship between Change in Lung Density and Long-Term Progression of Lung Function. Am J Respir Crit Care Med. 2015 Jul 1;192(1):114-6. doi: 10.1164/rccm.201502-0370LE. No abstract available.
- Sieluk J, Levy J, Sandhaus RA, Silverman H, Holm KE, Mullins CD. Costs of Medical Care Among Augmentation Therapy Users and Non-Users with Alpha-1 Antitrypsin Deficiency in the United States. Chronic Obstr Pulm Dis. 2018 Nov 8;6(1):6-16. doi: 10.15326/jcopdf.6.1.2017.0187.
- Gildea TR, Shermock KM, Singer ME, Stoller JK. Cost-effectiveness analysis of augmentation therapy for severe alpha1-antitrypsin deficiency. Am J Respir Crit Care Med. 2003 May 15;167(10):1387-92. doi: 10.1164/rccm.200209-1035OC. Epub 2003 Feb 5.
- Fraughen DD, Ghosh AJ, Hobbs BD, Funk GC, Meischl T, Clarenbach CF, Sievi NA, Schmid-Scherzer K, McElvaney OJ, Murphy MP, Roche AD, Clarke L, Strand M, Vafai-Tabrizi F, Kelly G, Gunaratnam C, Carroll TP, McElvaney NG. Augmentation Therapy for Severe Alpha-1 Antitrypsin Deficiency Improves Survival and Is Decoupled from Spirometric Decline-A Multinational Registry Analysis. Am J Respir Crit Care Med. 2023 Nov 1;208(9):964-974. doi: 10.1164/rccm.202305-0863OC.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CHUBX 2024/85
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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