Treatment of disorders characterized by reversible airway obstruction in childhood

Are anti-cholinergic agents the answer?

Annabelle Quizon, Andrew Colin, Umberto Pelosi, Giovanni A. Rossi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Release of acetylcholine from parasympathetic nerves in the airways activates postjunctional muscarinic receptors present on smooth muscle, submucosal glands and blood vessels. This triggers bronchoconstriction, muscle hypertrophy, mucus secretion, and vasodilatation, respectively. The release of acetylcholine from parasympathetic nerves in lungs is induced by a variety of stimuli and downregulated by the inhibitory activity of neuronal M2 muscarinic receptors via a feedback mechanism. Increased parasympathetic nerve activity occurs in a variety of airway diseases in childhood, including viral-induced wheeze and asthma. Common to these conditions are reversible airway obstruction, mucus hypersecretion, vasodilation and enhanced vascular permeability. In animal models of airway hyperreactivity similar findings of increased acetylcholine release resulting in enhanced supply of this neurotransmitter to the postjunctional smooth muscles, submucosal glands and airway vessels, were demonstrated. While the number and function of postjunctional muscarinic receptors in the airways are unchanged in such airway disorders, inhibitory activity on the parasympathetic nerves appears to be impaired. Specifically, M2 muscarinic receptor dysfunction has been demonstrated in models of bronchial hyperreactivity induced by a variety of triggers, including viruses, atmospheric pollutants and allergens. The mechanisms leading to impairment of neuronal M2 muscarinic receptor function and their putative relevance to the pathogenesis and the treatment of airway disease in childhood are described. Finally, the available data on the activity of ipratropium bromide, a short-acting anticholinergic drug, in the most common pediatric airway disease are reported and the possible therapeutic efficacy of tiotropium bromide, a more recently introduced long-acting, selective anticholinergic compound, is discussed.

Original languageEnglish
Pages (from-to)3061-3085
Number of pages25
JournalCurrent Pharmaceutical Design
Volume18
Issue number21
StatePublished - Aug 1 2012

Fingerprint

Muscarinic M2 Receptors
Cholinergic Antagonists
Airway Obstruction
Cholinergic Agents
Acetylcholine
Muscarinic Receptors
Mucus
Vasodilation
Smooth Muscle
Ipratropium
Bronchial Hyperreactivity
Bronchoconstriction
Capillary Permeability
Allergens
Hypertrophy
Neurotransmitter Agents
Blood Vessels
Down-Regulation
Asthma
Animal Models

Keywords

  • Acetylcholine
  • Asthma
  • Bronchiolitis
  • Chronic lung disease of prematurity
  • Cystic fibrosis
  • Muscarinic receptors
  • Pre-school wheezing

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

Cite this

Treatment of disorders characterized by reversible airway obstruction in childhood : Are anti-cholinergic agents the answer? / Quizon, Annabelle; Colin, Andrew; Pelosi, Umberto; Rossi, Giovanni A.

In: Current Pharmaceutical Design, Vol. 18, No. 21, 01.08.2012, p. 3061-3085.

Research output: Contribution to journalArticle

Quizon, Annabelle ; Colin, Andrew ; Pelosi, Umberto ; Rossi, Giovanni A. / Treatment of disorders characterized by reversible airway obstruction in childhood : Are anti-cholinergic agents the answer?. In: Current Pharmaceutical Design. 2012 ; Vol. 18, No. 21. pp. 3061-3085.
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