Targeting lipid mediators in asthma : time for reappraisal
(2019) In Current Opinion in Pulmonary Medicine 25(1). p.121-127- Abstract
PURPOSE OF REVIEW: In the past decades, cysteinyl leukotrienes (CysLTs) and prostaglandin D2 have been recognized as key mediators of asthma and comorbid conditions for their potent broncho-active and proinflammatory properties. However, both the development and initial positioning of small molecules targeting these lipid mediators [i.e., leukotriene-synthesis inhibitors, CysLT-antagonists, and chemoattractant receptor homologous molecule on T-helper2-cells (CRTH2) antagonists] experienced drawbacks by lacking adequate biomarkers to define potential responders. RECENT FINDINGS: New insights into the mechanisms of airway inflammation in asthma including the interaction of leukotrienes and prostanoids has uncovered potential therapeutic... (More)
PURPOSE OF REVIEW: In the past decades, cysteinyl leukotrienes (CysLTs) and prostaglandin D2 have been recognized as key mediators of asthma and comorbid conditions for their potent broncho-active and proinflammatory properties. However, both the development and initial positioning of small molecules targeting these lipid mediators [i.e., leukotriene-synthesis inhibitors, CysLT-antagonists, and chemoattractant receptor homologous molecule on T-helper2-cells (CRTH2) antagonists] experienced drawbacks by lacking adequate biomarkers to define potential responders. RECENT FINDINGS: New insights into the mechanisms of airway inflammation in asthma including the interaction of leukotrienes and prostanoids has uncovered potential therapeutic targets. Emerging application of biomarkers in more recent clinical studies helped identify responders to therapies targeting lipid mediators and demonstrated their clinical efficacy in distinct asthma phenotypes and endotypes. SUMMARY: Interest in small molecules targeting lipid mediators in asthma and related conditions is emerging. Several clinical trials evaluating the efficacy and safety of CRTH2 (Prostaglandin D2 receptor 2) antagonists are ongoing. There is an urgent need for sensitive biomarkers to identify responders to such therapies and for monitoring of (long-term) effects. Furthermore, evaluation of effectiveness of combining different agents targeting lipid mediators or combining them with available or emerging biologics may uncover other potential benefits in certain asthma populations warranting future research.
(Less)
- author
- Diamant, Zuzana LU ; Aalders, Wytze ; Parulekar, Amit ; Bjermer, Leif LU and Hanania, Nicola A.
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Current Opinion in Pulmonary Medicine
- volume
- 25
- issue
- 1
- pages
- 7 pages
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:30422894
- scopus:85057518710
- ISSN
- 1531-6971
- DOI
- 10.1097/MCP.0000000000000544
- language
- English
- LU publication?
- yes
- id
- ea9d9563-9035-49cc-a51b-6185b3377f25
- date added to LUP
- 2018-12-10 14:19:57
- date last changed
- 2024-10-01 12:17:52
@article{ea9d9563-9035-49cc-a51b-6185b3377f25, abstract = {{<p>PURPOSE OF REVIEW: In the past decades, cysteinyl leukotrienes (CysLTs) and prostaglandin D2 have been recognized as key mediators of asthma and comorbid conditions for their potent broncho-active and proinflammatory properties. However, both the development and initial positioning of small molecules targeting these lipid mediators [i.e., leukotriene-synthesis inhibitors, CysLT-antagonists, and chemoattractant receptor homologous molecule on T-helper2-cells (CRTH2) antagonists] experienced drawbacks by lacking adequate biomarkers to define potential responders. RECENT FINDINGS: New insights into the mechanisms of airway inflammation in asthma including the interaction of leukotrienes and prostanoids has uncovered potential therapeutic targets. Emerging application of biomarkers in more recent clinical studies helped identify responders to therapies targeting lipid mediators and demonstrated their clinical efficacy in distinct asthma phenotypes and endotypes. SUMMARY: Interest in small molecules targeting lipid mediators in asthma and related conditions is emerging. Several clinical trials evaluating the efficacy and safety of CRTH2 (Prostaglandin D2 receptor 2) antagonists are ongoing. There is an urgent need for sensitive biomarkers to identify responders to such therapies and for monitoring of (long-term) effects. Furthermore, evaluation of effectiveness of combining different agents targeting lipid mediators or combining them with available or emerging biologics may uncover other potential benefits in certain asthma populations warranting future research.</p>}}, author = {{Diamant, Zuzana and Aalders, Wytze and Parulekar, Amit and Bjermer, Leif and Hanania, Nicola A.}}, issn = {{1531-6971}}, language = {{eng}}, number = {{1}}, pages = {{121--127}}, publisher = {{Lippincott Williams & Wilkins}}, series = {{Current Opinion in Pulmonary Medicine}}, title = {{Targeting lipid mediators in asthma : time for reappraisal}}, url = {{http://dx.doi.org/10.1097/MCP.0000000000000544}}, doi = {{10.1097/MCP.0000000000000544}}, volume = {{25}}, year = {{2019}}, }