Anticholinergics Information

You are here

Anticholinergics in asthma e-learning module

Introduction to asthma

  • Asthma is a heterogeneous disease, characterised by chronic airway inflammation and a history of respiratory symptoms, including:1

  • wheeze

  • breathlessness

  • chest tightness

  • cough, varying over time and in intensity

  • expiratory airflow variation greater than that seen in healthy people

  • Bronchial hyper-responsiveness, inflammation, and airway remodelling are key features of asthma, leading to a decline in lung function and increased severity of disease2

Introduction to asthma therapy

  • The current standard of care is initial treatment with low-dose ICS, with SABA as needed, followed by increasing ICS dose or ICS+LABA therapy1

  • Referral to the secondary care setting for investigation and consideration for add-on therapy is recommended in patients with more severe or difficult-to-control asthma1

  • A high proportion of patients with asthma do not achieve control despite receiving standard-of-care asthma therapy, thus highlighting the need for different strategies to address this issue1

  • The importance of acetylcholine in the pathophysiology of asthma and also as a potential treatment target is now widely recognised1

Role of acetylcholine in asthma

When symbol appears
click for more information

Acetylcholine plays a significant role
in the pathophysiology of asthma1-4

Click here to see
the effect on the airways

When symbol appears
click for more information

Anticholinergics in asthma: background

  • Bronchoconstriction is the primary cause of airway obstruction in patients with asthma, predominately owing to the downstream effects of acetylcholine1

  • Anticholinergics target the muscarinic receptors within the airway, reducing the downstream effects of acetylcholine2,3

Short-acting anticholinergics Long-acting anticholinergics
Ipratropium bromide Tiotropium bromide
Oxitropium bromide Aclidinium bromide
  Glycopyrronium bromide
  Umeclidinium bromide

When symbol appears
click for more information

Tiotropium Respimat®
mechanism of action1-3

Click here to see
the effect on the airways

Anticholinergics in asthma:
tiotropium Respimat®

  • Add-on therapy to ICS+LABA with tiotropium Respimat® may have additional benefits (e.g. greater bronchodilation) compared with ICS+LABA alone in patients with asthma1,2

  • Anticholinergics block acetylcholine-induced smooth muscle contraction whereas LABAs stimulate adrenergic smooth muscle relaxation1

  • Preclinical studies in animal models, have shown that tiotropium partly prevents airway remodelling and eosinophilic inflammation3

  • Tiotropium Respimat® shows a slower dissociation from the M3 receptor compared with the other anticholinergics

  • The longer duration of action allows for a once-daily dosing pattern3

Click here for more information on tiotropium Respimat®

When symbol appears
click for more information

Anticholinergics in asthma:
clinical data

  • The first clinical trial of tiotropium Respimat® was in 12 adult male patients with mild allergic asthma

  • Tiotropium Respimat® was associated with prolonged bronchodilator response and protection from methacholine challenge1

  • The early proof-of-concept studies further supported these findings, including in patients with severe asthma2,3

  • The tiotropium Respimat® clinical trial programme in asthma, with Phase II and III trials assessing patients with mild-to-severe and poorly controlled asthma, has been completed4

  • This clinical trial programme included 18 trials with over 6000 patients5

  • This also includes several recently completed clinical trials of tiotropium Respimat® in children and adolescents6–8

A closer look at the studies for
tiotropium Respimat® in asthma

PrimoTinA-asthma®1 MezzoTinA-asthma®2 GraziaTinA-asthma®3
Population Adults, uncontrolled asthma,
despite high-dose ICS
(≥800 µg budesonide
or equivalent) + LABA
Adults, moderated uncontrolled asthma, despite medium-dose
ICS (400-800 µg budesonide or
equivalent)
Adults, uncontrolled asthma,
despite low-to-medium dose
ICS (200-400 µg budesonide or
equivalent)
Randomized
patients
Trial 1: N = 459
Trial 2: N = 453
Trial 1: N = 1070
Trial 2: N = 1032
N = 465
Comparators 5 µg tiotropium Respimat® qd vs. placebo 5 or 2.5 µg tiotropium Respimat® qd or salmeterol 50 µg bid vs. placebo 5 or 2.5 µg tiotropium Respimat®
 qd vs. placebo
Primary
endpoints
Lung function
Exacerbations
Lung function
Asthma control
Lung function
Outcomes
  • Significant lung function improvement

  • Exacerbation reduction

  • Asthma control improvement

  • Comparable safety profile
    with placebo

  • Significant lung function improvement

  • Asthma control improvement (ACQ-7 responder rate)

  • Comparable safety profile with placebo

  • Significant lung function improvement

  • Comparable safety profile with placebo

When symbol appears
click for more information

Summary

  • Acetylcholine binds to muscarinic receptors to trigger airway
    inflammation and hyper-responsiveness seen in patients with asthma

  • Anticholinergics target the M3 muscarinic receptors within the airway to
    reduce the downstream effects of acetylcholine

  • Long-acting anticholinergics have demonstrated benefits in asthma

  • Clinical data suggest that add-on anticholinergics are an option for the treatment and management of patients with asthma

  • Tiotropium Respimat® is the only long-acting anticholinergic approved for the treatment of asthma as an add-on treatment and has demonstrated:

  • Improvements in lung function

  • Reductions in the risk of severe exacerbations and asthma worsening

  • Improvements in asthma control

  • These effects were demonstrated independently of the patient´s baseline characteristics (phenotype)

  • Tiotropium Respimat® is the only long-acting anticholinergic recommended in Steps 4 and 5 of the international GINA strategy

Explore patient profiles for
anticholinergic treatment

Karen

James

Samantha

When symbol appears
click for more information

Sorry, case studies are not available on this device. Please use a computer or a tablet on landscape mode.