Drug-Gene Risk Stratification in Patients with Suspected Drug-Induced Interstitial Lung Disease.
Drug Saf
; 47(4): 355-363, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38460070
ABSTRACT
BACKGROUND:
Pulmonary toxicity has been associated with drug use. This is often not recognized in clinical practice, and underestimated.OBJECTIVE:
We aimed to establish whether polymorphisms in certain genes corresponding with a metabolic pathway of drug(s) used are associated with pulmonary toxicity in patients with suspected drug-induced interstitial lung disease (DI-ILD).METHODS:
This retrospective observational study explored genetic variations in three clinically relevant cytochrome P450 (CYP) iso-enzymes (i.e., CYP2D6, CYP2C9, and CYP2C19) in a group of patients with a fibroticinterstitial lung disease, either non-specific interstitial pneumonia (n = 211) or idiopathic pulmonary fibrosis (n = 256), with a suspected drug-induced origin.RESULTS:
Of the 467 patients, 79.0% showed one or more polymorphisms in the tested genes accompanied by the use of drug(s) metabolized by a corresponding affected metabolic pathway (60.0% poor metabolizers and/or using two or more drugs [likely DI-ILD], 37.5% using three or more [highly likely DI-ILD]). Most commonly used drugs were statins (63.1%) with a predominance among men (69.4 vs 47.1%, p < 0.0001). Nitrofurantoin, not metabolized by the tested pathways, was prescribed more frequently among women (51.9 vs 4.5%, p < 0.00001).CONCLUSIONS:
In our cohort with suspected DI-ILD, 79% carried one or more genetic variants accompanied by the use of drugs metabolized by a corresponding affected pathway. In 60%, the diagnosis of DI-ILD was likely, whereas in 37.5%, it was highly likely, based on CYP analyses. This study underlines the importance of considering both drug use and genetic make-up as a possible cause, or at least a contributing factor, in the development and/or progression of fibrotic lung diseases. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov identifier NCT00267800, registered in 2005.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Pulmonares Intersticiais
/
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
/
Fibrose Pulmonar Idiopática
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article