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Is there a rationale and role for long-acting anticholinergic bronchodilators in asthma?

Price D, Fromer L, Kaplan A, van der Molen T, Román-Rodríguez M - NPJ Prim Care Respir Med (2014)

Bottom Line: Patients with asthma have increased bronchial smooth muscle tone and mucus hypersecretion, possibly as a result of elevated cholinergic activity, which anticholinergic compounds are known to reduce.Further, anticholinergic compounds may also have anti-inflammatory properties.Thus, evidence suggests that long-acting anticholinergic bronchodilators might offer benefits for the maintenance of asthma control, such as in patients failing to gain control on ICS and a LABA, or those with frequent exacerbations.

View Article: PubMed Central - PubMed

Affiliation: 1] Centre of Academic Primary Care, University of Aberdeen, Aberdeen, UK [2] Research in Real Life Ltd, Cambridge, UK.

ABSTRACT
Despite current guidelines and the range of available treatments, over a half of patients with asthma continue to suffer from poor symptomatic control and remain at risk of future worsening. Although a number of non-pharmacological measures are crucial for good clinical management of asthma, new therapeutic controller medications will have a role in the future management of the disease. Several long-acting anticholinergic bronchodilators are under investigation or are available for the treatment of respiratory diseases, including tiotropium bromide, aclidinium bromide, glycopyrronium bromide, glycopyrrolate and umeclidinium bromide, although none is yet licensed for the treatment of asthma. A recent Phase III investigation demonstrated that the once-daily long-acting anticholinergic bronchodilator tiotropium bromide improves lung function and reduces the risk of exacerbation in patients with symptomatic asthma, despite the use of inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs). This has prompted the question of what the rationale is for long-acting anticholinergic bronchodilators in asthma. Bronchial smooth muscle contraction is the primary cause of reversible airway narrowing in asthma, and the baseline level of contraction is predominantly set by the level of 'cholinergic tone'. Patients with asthma have increased bronchial smooth muscle tone and mucus hypersecretion, possibly as a result of elevated cholinergic activity, which anticholinergic compounds are known to reduce. Further, anticholinergic compounds may also have anti-inflammatory properties. Thus, evidence suggests that long-acting anticholinergic bronchodilators might offer benefits for the maintenance of asthma control, such as in patients failing to gain control on ICS and a LABA, or those with frequent exacerbations.

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Combined approaches for the management of control in asthma.2,5,10–16 FLAP, 5-lipoxygenase-activating protein; ICS, inhaled corticosteroids; IL, interleukin; LABA, long-acting β2-agonist; PDE4, phosphodiesterase-4; SABA, short-acting β2-agonist.
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fig1: Combined approaches for the management of control in asthma.2,5,10–16 FLAP, 5-lipoxygenase-activating protein; ICS, inhaled corticosteroids; IL, interleukin; LABA, long-acting β2-agonist; PDE4, phosphodiesterase-4; SABA, short-acting β2-agonist.

Mentions: For those receiving low-dose inhaled corticosteroids (ICS), current step-up treatment involves the addition of a long-acting β2-agonist (LABA) or leukotriene receptor antagonist as controller therapy. In patients unable to attain or maintain control with ICS and LABA—those in Global Initiative for Asthma treatment steps 3–5 (Figure 1)—upward titration of ICS dose, leukotriene modifiers, sustained-release theophylline, oral glucocorticosteroids and anti-immunoglobulin E (omalizumab) are all further or alternative treatment options.2


Is there a rationale and role for long-acting anticholinergic bronchodilators in asthma?

Price D, Fromer L, Kaplan A, van der Molen T, Román-Rodríguez M - NPJ Prim Care Respir Med (2014)

Combined approaches for the management of control in asthma.2,5,10–16 FLAP, 5-lipoxygenase-activating protein; ICS, inhaled corticosteroids; IL, interleukin; LABA, long-acting β2-agonist; PDE4, phosphodiesterase-4; SABA, short-acting β2-agonist.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4373380&req=5

fig1: Combined approaches for the management of control in asthma.2,5,10–16 FLAP, 5-lipoxygenase-activating protein; ICS, inhaled corticosteroids; IL, interleukin; LABA, long-acting β2-agonist; PDE4, phosphodiesterase-4; SABA, short-acting β2-agonist.
Mentions: For those receiving low-dose inhaled corticosteroids (ICS), current step-up treatment involves the addition of a long-acting β2-agonist (LABA) or leukotriene receptor antagonist as controller therapy. In patients unable to attain or maintain control with ICS and LABA—those in Global Initiative for Asthma treatment steps 3–5 (Figure 1)—upward titration of ICS dose, leukotriene modifiers, sustained-release theophylline, oral glucocorticosteroids and anti-immunoglobulin E (omalizumab) are all further or alternative treatment options.2

Bottom Line: Patients with asthma have increased bronchial smooth muscle tone and mucus hypersecretion, possibly as a result of elevated cholinergic activity, which anticholinergic compounds are known to reduce.Further, anticholinergic compounds may also have anti-inflammatory properties.Thus, evidence suggests that long-acting anticholinergic bronchodilators might offer benefits for the maintenance of asthma control, such as in patients failing to gain control on ICS and a LABA, or those with frequent exacerbations.

View Article: PubMed Central - PubMed

Affiliation: 1] Centre of Academic Primary Care, University of Aberdeen, Aberdeen, UK [2] Research in Real Life Ltd, Cambridge, UK.

ABSTRACT
Despite current guidelines and the range of available treatments, over a half of patients with asthma continue to suffer from poor symptomatic control and remain at risk of future worsening. Although a number of non-pharmacological measures are crucial for good clinical management of asthma, new therapeutic controller medications will have a role in the future management of the disease. Several long-acting anticholinergic bronchodilators are under investigation or are available for the treatment of respiratory diseases, including tiotropium bromide, aclidinium bromide, glycopyrronium bromide, glycopyrrolate and umeclidinium bromide, although none is yet licensed for the treatment of asthma. A recent Phase III investigation demonstrated that the once-daily long-acting anticholinergic bronchodilator tiotropium bromide improves lung function and reduces the risk of exacerbation in patients with symptomatic asthma, despite the use of inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs). This has prompted the question of what the rationale is for long-acting anticholinergic bronchodilators in asthma. Bronchial smooth muscle contraction is the primary cause of reversible airway narrowing in asthma, and the baseline level of contraction is predominantly set by the level of 'cholinergic tone'. Patients with asthma have increased bronchial smooth muscle tone and mucus hypersecretion, possibly as a result of elevated cholinergic activity, which anticholinergic compounds are known to reduce. Further, anticholinergic compounds may also have anti-inflammatory properties. Thus, evidence suggests that long-acting anticholinergic bronchodilators might offer benefits for the maintenance of asthma control, such as in patients failing to gain control on ICS and a LABA, or those with frequent exacerbations.

Show MeSH
Related in: MedlinePlus