The Role of Long-Acting Antimuscarinic Agents in the Treatment of Asthma

The journey of using anticholinergics in the treatment of asthma started with anticholinergic-containing plants such as Datura stramonium and Atropa belladonna, followed by ipratropium bromide and continued with tiotropium, glycopyrronium, and umeclidinium. Although antimuscarinics were used in the maintenance treatment of asthma over a century ago, after a long time (since 2014), it has been recommended to be used as an add-on long-acting antimuscarinic agent (LAMA) therapy in the maintenance treatment of asthma. The airway tone controlled by the vagus nerve is increased in asthma. Allergens, toxins, or viruses cause airway inflammation and inflammation-related epithelial damage, increased sensory nerve stimulation, ganglionic and postganglionic acetylcholine (ACh) release by inflammatory mediators, intensification of ACh signaling at M1 and M3 muscarinic ACh receptors (mAChRs), and dysfunction of M2 mAChR. Optimal anticholinergic drug for asthma should effectively block M3 and M1 receptors, but have minimal effect on M2 receptors. Tiotropium, umeclidinium, and glycopyrronium are anticholinergic agents with this feature. Tiotropium has been used in a separate inhaler as an add-on treatment to inhaled corticosteroid (ICS)/long-acting & beta;2-agonist (LABA), and glycopyrronium and umeclidinium have been used in a single inhaler as a combination of ICS/LABA/LAMA in asthma in recent years. Guidelines recommend this regimen as an optimization step for patients with severe asthma before initiating any biologic or systemic corticosteroid therapy. In this review, the history of antimuscarinic agents, their effectiveness and safety in line with randomized controlled trials, and real-life studies in asthma treatment will be discussed according to the current data

Long-term macrolide therapy in asthma

Macrolides are antibiotics with antiviral, anti-inflammatory and immunomodulatory effects in together with their bacteriostatic effects. In addition to its beneficial effects on chronic respiratory diseases such as COPD, cystic fibrosis, diffuse panbronchiolitis, and bronchiectasis, its effects on uncontrolled severe asthma and asthma exacerbations have been the subject of research in recent years. In randomized controlled trials, azithromycin, a macrolide, has been shown to reduce asthma exacerbations and significantly improve asthma-related quality of life in both eosinophilic and non-eosinophilic asthma phenotypes. However, there are also differences such asdoses, durations and some studies not showing its effectiveness in severe eosinophilic asthma. In the GINA report, azithromycin can be recommended as an add-on therapy in patients with uncontrolled non-T2 severe asthma despite high-dose inhaled corticosteroid/ long-acting beta2-agonist/long-acting antimuscariniric treatments, or in T2 severe asthma patients whose asthma is not under control despite biologic therapy. In this review, the use of macrolides, especially azithromycin, in the treatment of asthma, immunomodulatory activities and safety profiles are discussed on the basis of current studies and guidelines

Doxycycline may be more clinically effective in type 2 chronic rhinosinusitis nasal polyp comorbid with asthma

ObjectiveChronic rhinosinusitis with nasal polyp (CRSwNP) is one of the major phenotypes of chronic rhinosinusitis (CRS) with a high symptom burden. Doxycycline can be used as add-on therapy in CRSwNP. We aimed to evaluate short-term efficacy of oral doxycycline on visual analog scale (VAS) and SNOT-22 (Sino-nasal outcome test) score for CRSwNP.MethodsVisual analog score (VAS) for nasal symptoms and total SNOT-22 scores of 28 patients who applied with the diagnosis of CRSwNP and received 100 mg doxycycline for 21 days were analyzed in this retrospective cohort study. Doxycycline efficacy was also evaluated in subgroups determined according to asthma, presence of atopy, total IgE and eosinophil levels.ResultsAfter 21-day doxycycline treatment, there was a significant improvement in VAS score for post-nasal drip, nasal discharge, nasal congestion, and sneeze, and total SNOT-22 score (p = 0.001, p 300 cell/& mu;L.ConclusionsDoxycycline can be considered as an add-on treatment for symptom control in patients especially with CRSwNP comorbid with asthma