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<p>COPD is a multifaceted and progressive respiratory disorder that comprises emphysema and chronic bronchitis. It is distinguished by chronic inflammation in the airways, with limited airflow, and frequent exacerbations, leading to crucial morbidity and mortality worldwide. Treatment options include bronchodilators and inhaled corticosteroids, in which some individuals often experience resistance, exacerbation, and overall worsening of the condition, which could be difficult to prescribe for a chronic period of time. Consequently, this highlights the need for novel therapeutic strategies to overcome resistance to standard drugs and airway inflammation with minimal side effects. Phosphodiesterase, particularly PDE4, elevates intracellular cyclic adenosine monophosphate (cAMP) and reduces the activity of immune cells and inflammatory cytokines, which modulate transcriptional proteins and cause bronchial relaxation. Thus, targeting PDE4 could benefit anti-inflammatory action with changes in lung architecture, alveolar destruction, airway hyperresponsiveness, and mucus hypersecretion. This review explores how PDE4 plays a part in the pathophysiology of COPD, and molecular mechanisms focusing on existing PDE4 inhibitors and future implications.</p> Graphical Abstract <p></p>

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Phosphodiesterase-4 Inhibitors in Chronic Obstructive Pulmonary Disease: Molecular Mechanisms, Current Therapeutics, and Future Perspectives

  • 期刊论文

  • 发表日期：

    2026年2月25日

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  • Subhajit Dutta,
  • Shanmugam Ramaswamy,
  • L Priyanka Dwarampudi,
  • Aritra Dutta,
  • Mirunalini Gobinath,
  • Parikshit Roychowdhury

摘要

COPD is a multifaceted and progressive respiratory disorder that comprises emphysema and chronic bronchitis. It is distinguished by chronic inflammation in the airways, with limited airflow, and frequent exacerbations, leading to crucial morbidity and mortality worldwide. Treatment options include bronchodilators and inhaled corticosteroids, in which some individuals often experience resistance, exacerbation, and overall worsening of the condition, which could be difficult to prescribe for a chronic period of time. Consequently, this highlights the need for novel therapeutic strategies to overcome resistance to standard drugs and airway inflammation with minimal side effects. Phosphodiesterase, particularly PDE4, elevates intracellular cyclic adenosine monophosphate (cAMP) and reduces the activity of immune cells and inflammatory cytokines, which modulate transcriptional proteins and cause bronchial relaxation. Thus, targeting PDE4 could benefit anti-inflammatory action with changes in lung architecture, alveolar destruction, airway hyperresponsiveness, and mucus hypersecretion. This review explores how PDE4 plays a part in the pathophysiology of COPD, and molecular mechanisms focusing on existing PDE4 inhibitors and future implications.

Graphical Abstract