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Antioxidants in lung disease: Failures and pathways for success

Brian J Day1

  • 1Department of Medicine, National Jewish Health, Denver, CO, USA.

Free Radical Biology & Medicine
|March 27, 2026
PubMed

Insights

Decades of failed antioxidant trials for lung disease stem from flawed drug design, not invalid redox biology. A precision approach targeting specific reactive oxygen species (ROS) is needed for effective therapies.

Area of Science:

  • Pulmonary Medicine
  • Redox Biology
  • Pharmacology

Background:

  • Oxidative stress is implicated in lung disease pathogenesis.
  • Numerous clinical trials of antioxidants have yielded disappointing results.
  • This failure highlights conceptual and design issues in antioxidant drug development.

Purpose of the Study:

  • To address the translational gap in antioxidant therapy for lung diseases.
  • To propose a new framework for antioxidant drug development.
  • To reframe antioxidants as targeted, mechanism-based therapeutics.

Main Methods:

  • Critique of current antioxidant drug development strategies.
  • Analysis of reactive oxygen species (ROS) roles in physiology and pathology.
  • Proposal of a precision redox medicine framework.

Main Results:

  • Indiscriminate ROS suppression overlooks their crucial signaling functions.
  • ROS are compartmentalized and heterogeneous across different lung diseases.
  • A precision medicine approach requires mechanistic specificity and biomarker stratification.

Conclusions:

  • Current antioxidant strategies are too broad and ineffective.
  • Precision redox medicine offers a path forward by targeting specific ROS.
  • Developing catalytic antioxidants tailored to disease mechanisms may unlock therapeutic potential.
Keywords:
Lung injuryPulmonary oxidative stressRedox signalingTherapeuticsTranslational failure

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