Bronchodilators, receptors and cross-talk: Together is better?

Abstract

The most widely used maintenance therapies in chronic obstructive pulmonary disease (COPD) are long-acting muscarinic antagonists (LAMAs), and a number of these drugs are now available in combination with long-acting β₂-agonists (LABAs). LAMAs inhibit the parasympathetic muscarinic pathway, while LABAs, as sympathomimetics, reduce airway smooth muscle (ASM) tone. As well as directly controlling the constriction and relaxation of ASM, muscarinic and adrenergic receptors are found on inflammatory cells, and drugs that target these receptors may also reduce inflammation in COPD. Evidence suggests that the muscarinic and adrenergic pathways cross-talk at the level of neuronal input to the ASM via second-messenger pathways within ASM cells. Although the cross-talk is not completely understood, pharmacologically targeting both pathways in COPD can maximize bronchodilation. Combining LAMAs and LABAs demonstrated improved efficacy compared with the individual therapies and so, for greater convenience, several fixed-dose combinations for once-daily use have been developed. These fixed-dose combinations demonstrate improvements in both lung-function and patient-reported outcomes compared with well-established monotherapies, with similar tolerability profiles to the individual agents.

Keywords:

• Chronic obstructive pulmonary disease
• bronchodilation
• β₂-agonist
• antimuscarinic
• combination therapy

Acknowledgments

The author meets criteria for authorship as recommended by the International Committee of Medical Journal Editors and takes full responsibility for the scope, direction, content of, and editorial decisions relating to, the manuscript, was involved at all stages of development, and has approved the submitted manuscript. Medical writing assistance was provided by Claire Scofield, MRes, of Complete HealthVizion, which was contracted and compensated by Boehringer Ingelheim Pharma Inc. Boehringer Ingelheim personnel were given the opportunity (by the author prior to submission) to check the data used in the review for factual accuracy only.

Declaration of interest

Medical writing assistance, in the form of literature searches and preparation and revision of the draft manuscript, was provided by Claire Scofield of Complete HealthVizion and funded by Boehringer Ingelheim Pharma Inc. RA Panettieri Jr declares grants and personal fees from AstraZeneca, Johnson & Johnson, Merck and Teva, and grants from National Institute of Health, Gilead, Roche and Sanofi. The author received no compensation related to the development of the manuscript. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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