<p>Future perspectives of anticholinergics for the treatment of asthma in adults and children</p>

Abstract

Despite major advances in therapeutic interventions and the availability of detailed treatment guidelines, a high proportion of patients with symptomatic asthma remain uncontrolled. Asthma management is largely guided by the Global Initiative for Asthma (GINA) strategy and is based on a backbone of inhaled corticosteroid (ICS) therapy with the use of additional therapies to achieve disease control. Inhaled long-acting bronchodilators alone and in combination are the preferred add-on treatment options. Although long-acting muscarinic antagonists (LAMAs) are a relatively recent addition to disease management recommendations for asthma, tiotropium has been extensively studied in a large clinical trial program. In Europe and the United States, tiotropium is approved for patients aged ≥6 years and uncontrolled on medium- to high-dose ICS/long-acting β2-agonists at GINA Steps 4 and 5 with a history of exacerbations. Evidence supports the efficacy of tiotropium Respimat® in adults in terms of lung function and asthma control, with a safety profile comparable with that of placebo across a range of asthma severities. Similarly, clinical trials in patients aged 1–17 years have shown improvements in lung function and trends toward improved asthma control. Furthermore, its efficacy makes tiotropium relatively easy to incorporate into routine clinical practice, irrespective of allergic status and without the need for patient phenotyping. Tiotropium is a cost-effective treatment that may offer an important alternative to other, more expensive add-on therapies. This review discusses the potential future position of LAMAs in clinical practice by considering the continuously evolving evidence. Prominence is given to tiotropium, the only LAMA supported by a structured clinical trial program in asthma to date, while also considering other recommended treatment options for patients with uncontrolled asthma. The importance of effective patient/caregiver–clinician communication and shared decision-making in enhancing treatment adherence is also highlighted.

Comparing LAMA with LABA and LTRA as add-on therapies in primary care asthma management

“…The long-term aims of asthma management are symptom control, reduction of the future risk of exacerbations and airflow limitation, while at the same time minimising treatment side effects 9 . Although major advances have been made in asthma treatment and management, there still remain many patients who have poor asthma control and maintain the potential risk of worsening of their symptoms, as well as an increased risk of exacerbations, and unscheduled urgent and emergency care visits and hospitalisations 46 , 47 . For adults, adolescents and children, there is a need for effective add-on treatments as an alternative to increasing the ICS dose alone, as long-term, high-dose ICS use is associated with an increased risk of side effects 9 .…”

“…When stepping up asthma therapy and considering add-on therapy, it is important to review the options available, to involve patients in decisions about their treatment and to keep a dialogue between patients and HCPs 46 . An up-to-date individualised asthma action plan can help to keep a record of any attempted treatment approaches and help the patient to self-manage 54 .…”

An Algorithm for Strategic Continuation or Restriction of Asthma Medication Prior to Exercise Challenge Testing in Childhood Exercise Induced Bronchoconstriction

“…LAMA's are included in the GINA 2021 guidelines as optional add-on maintenance therapy in both children and adolescents whose asthma remains uncontrolled despite treatment with ICS-LABA ( 32 ). LAMA's act by blocking muscarinic acetylcholine receptors on the airway smooth muscle cells, causing airway relaxation ( 56 , 57 ). Inhibition of these muscarinic receptors may also play a role in reducing mucus secretion, inflammation and airway remodeling, thereby leading to reduced airway hyperresponsiveness ( 56 , 58 ).…”

Rosuvastatin blocks allergic airway vagal hypertonia via reversed central CD73 downregulation in rats

“…Increased airway vagal activity is well known to play important roles in the asthmatic constriction, mucous secretion, inflammation and remodeling of the airway (2)(3)(4)(5). Accordingly, inhaled muscarinic antagonists, alone or in combination with glucocorticoids and/or β 2adrenergic agonists, have become the common therapy for asthma clinically, especially in its severe attacks (6). In patients with obstinate severe asthma symptoms, high selective vagotomy of hilus pulmonis has become a choice of treatment (7).…”