Drug-induced interstitial lung disease: role of pharmacogenetics in predicting cytotoxic mechanisms and risks of side effects

Naomi T. Jessurun, Marjolein Drent, Eugene P. van Puijenbroek, Otto Bekers, Petal A. Wijnen, Aalt Bast*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

8 Citations (Web of Science)
36 Downloads (Pure)

Abstract

Purpose of review The diagnosis of drug-induced interstitial lung disease (DI-ILD) is challenging and mainly made by exclusion of other possible causes. Toxicity can occur as a cause of drug(s) or drug-drug interactions. In this review, we summarize the possible role of pharmacogenetics of metabolizing enzymes in DI-ILD. Recent findings Knowledge of the genetic predispositions of enzymes involved in drug metabolization and their relation with proposed cytotoxic mechanisms of DI-ILD, in particular direct cell toxicity and free oxygen radical production is increasing. The cytochrome P450 enzyme family and other enzymes play an important role in the metabolism of all sorts of ingested, injected, or inhaled xenobiotic substances. The liver is the major site for metabolism. Metabolic cytotoxic mechanisms have however also been detected in lung tissue. Polymorphisms in genes coding for enzymes that influence metabolic activity may lead to localized (toxic) reactions and tissue damage. This knowledge may be helpful in preventing the risk of DI-ILD. Drug toxicity can be the consequence of absence or very poor enzyme activity, especially if no other metabolic route is available. In the case of reduced enzyme activity, it is recommended to reduce the dose or to prescribe an alternative drug, which is metabolized by a different, unaffected enzyme system to prevent toxic side effects. However, enhanced enzyme activity may lead to excessive formation of toxic and sometimes reactive metabolites. Therefore, knowing a patient's drug-metabolizing profile before drug prescription is a promising way to prevent or explain DI-ILD.

Original languageEnglish
Pages (from-to)468-477
Number of pages10
JournalCurrent Opinion in Pulmonary Medicine
Volume25
Issue number5
DOIs
Publication statusPublished - Sep 2019

Keywords

  • adverse drug reactions
  • cytochrome P450
  • cytotoxic mechanisms
  • drug metabolizing enzymes
  • drug-induced pneumonitis
  • glucose-6-phosphate dehydrogenase
  • polymorphisms
  • thiopurine S-methyltransferase
  • xenobiotics
  • THIOPURINE METHYLTRANSFERASE
  • GENETIC-POLYMORPHISM
  • ACETAMINOPHEN
  • METABOLISM
  • INJURY
  • BIOACTIVATION
  • 4-IPOMEANOL
  • OXIDATION
  • TOXICITY
  • PROTEINS

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