Regulation of Airway Smooth Muscle Contraction in Health and Disease

Maggie Lam, Emma Lamanna, Jane E. Bourke

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review

4 Citations (Scopus)

Abstract

Airway smooth muscle (ASM) extends from the trachea throughout the bronchial tree to the terminal bronchioles. In utero, spontaneous phasic contraction of fetal ASM is critical for normal lung development by regulating intraluminal fluid movement, ASM differentiation, and release of key growth factors. In contrast, phasic contraction appears to be absent in the adult lung, and regulation of tonic contraction and airflow is under neuronal and humoral control. Accumulating evidence suggests that changes in ASM responsiveness contribute to the pathophysiology of lung diseases with lifelong health impacts. Functional assessments of fetal and adult ASM and airways have defined pharmacological responses and signaling pathways that drive airway contraction and relaxation. Studies using precision-cut lung slices, in which contraction of intrapulmonary airways and ASM calcium signaling can be assessed simultaneously in situ, have been particularly informative. These combined approaches have defined the relative importance of calcium entry into ASM and calcium release from intracellular stores as drivers of spontaneous phasic contraction in utero and excitation-contraction coupling. Increased contractility of ASM in asthma contributes to airway hyperresponsiveness. Studies using animal models and human ASM and airways have characterized inflammatory and other mechanisms underlying increased reactivity to contractile agonists and reduced bronchodilator efficacy of β2-adrenoceptor agonists in severe diseases. Novel bronchodilators and the application of bronchial thermoplasty to ablate increased ASM within asthmatic airways have the potential to overcome limitations of current therapies. These approaches may directly limit excessive airway contraction to improve outcomes for difficult-to-control asthma and other chronic lung diseases.

Original languageEnglish
Title of host publicationSmooth Muscle Spontaneous Activity
Subtitle of host publicationPhysiological and Pathological Modulation
EditorsHikaru Hashitani, Richard J. Lang
Place of PublicationSingapore
PublisherSpringer
Chapter16
Pages381-422
Number of pages42
ISBN (Electronic)9789811358951
ISBN (Print)9789811358944
DOIs
Publication statusPublished - 24 Jun 2019

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1124
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Airway smooth muscle
  • Asthma
  • Bronchodilator
  • Calcium
  • Contraction
  • Phasic
  • Tonic

Cite this

Lam, M., Lamanna, E., & Bourke, J. E. (2019). Regulation of Airway Smooth Muscle Contraction in Health and Disease. In H. Hashitani, & R. J. Lang (Eds.), Smooth Muscle Spontaneous Activity: Physiological and Pathological Modulation (pp. 381-422). (Advances in Experimental Medicine and Biology; Vol. 1124). Springer. https://doi.org/10.1007/978-981-13-5895-1_16