Evaluating the role of leukotriene-modifying drugs in asthma management: Are their benefits 'losing in translation'?

Pulm Pharmacol Ther. 2016 Dec:41:52-59. doi: 10.1016/j.pupt.2016.09.006. Epub 2016 Sep 17.

Abstract

Leukotrienes (LTs) initiate a cascade of reactions that cause bronchoconstriction and inflammation in asthma. LT-modifying drugs have been proved very effective to reduce inflammation and associated exacerbation however despite some illustrious clinical trials the usage of these drugs remains overlooked because the evidence to support their utility in asthma management has been mixed and varied between studies. Although, there are plenty of evidences which suggest that the leukotriene-modifying drugs provide consistent improvement even after just the first oral dose and reduce asthma exacerbations, the beneficial effect of these drugs has remained sparse and widely debated. And these beneficial effects are often overlooked because most of the clinical studies include a mixed population of asthmatics who do not respond to LT-modifiers equally. Therefore, in the present era of personalized medicine, it is important to properly stratify the patients and non-invasive measurements of biomarkers may warrant the possibility to characterize biological/pathological pathway to direct treatment to those who will benefit from it. Endotyping based on individual's leukotriene levels should probably ascertain a subgroup of patients that would clearly benefit from the treatment even though the trial fails to show overall significance. In this article, we have methodically evaluated contemporary literature describing the efficacy of LT-modifying drugs in the management of asthma and highlighted the importance of phenotyping the asthmatics for better treatment outcomes.

Keywords: Asthma; Bronchoconstriction; Eicosanoids; Leukotriene; Montelukast.

Publication types

  • Review

MeSH terms

  • Anti-Asthmatic Agents / pharmacology
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Biomarkers / metabolism
  • Bronchoconstriction / drug effects
  • Humans
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Leukotriene Antagonists / pharmacology
  • Leukotriene Antagonists / therapeutic use
  • Leukotrienes / metabolism*
  • Precision Medicine / methods

Substances

  • Anti-Asthmatic Agents
  • Biomarkers
  • Leukotriene Antagonists
  • Leukotrienes