Long-Acting Muscarinic Antagonists for Difficult-to-Treat Asthma: Emerging Evidence and Future Directions.
Asthma is a complex disease where many patients remain symptomatic despite guideline-directed therapy. This suggests an unmet need for alternative treatment approaches. Understanding the physiological role of muscarinic receptors and the parasympathetic nervous system in the respiratory tract will provide a foundation of alternative therapeutics in asthma. Currently, several long-acting muscarinic antagonists (LAMAs) are on the market for the treatment of respiratory diseases. Many studies have shown the effectiveness of tiotropium, a LAMA, as add-on therapy in uncontrolled asthma. These studies led to FDA approval for tiotropium use in asthma. In this review, we discuss how the neurotransmitter acetylcholine itself contributes to inflammation, bronchoconstriction, and remodeling in asthma. We further describe the current clinical studies evaluating LAMAs in adult and adolescent patients with asthma, providing a comprehensive review of the current known physiological benefits of LAMAs in respiratory disease.
Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 19, Tampa, FL, 33612, USA.|Department of Internal Medicine, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Adeeb
A
Bulkhi
Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 19, Tampa, FL, 33612, USA.
Farnaz
F
Tabatabaian
Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 19, Tampa, FL, 33612, USA. tbcasale@health.usf.edu.
Thomas B
TB
Casale
D000109:Acetylcholine / Q000378:metabolism; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D006801:Humans; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010275:Parasympathetic Nervous System / Q000187:drug effects; D020239:Receptor Cross-Talk; D011976:Receptors, Muscarinic / Q000378:metabolism; D000069447:Tiotropium Bromide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D018927:Anti-Asthmatic Agents; D003692:Delayed-Action Preparations; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D000109:Acetylcholine; D000069447:Tiotropium Bromide