Safety of inhaled long-acting anti-muscarinic agents in COPD

Hanania, Nicola A.; Lareau, Suzanne C.; Yawn, Barbara P.

doi:10.1080/00325481.2017.1317575

Cited by 3 publications

(2 citation statements)

References 110 publications

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“…Neutrophilic inflammation, a central feature of COPD, is closely associated with the severity of peripheral airway dysfunction in COPD [ 22 ]. Long-acting antimuscarinics or long-acting β 2 -adrenoceptor agonists, with or without inhaled glucocorticoids, are suggested by the COPD guidelines [ 23 ]. Clinical studies indicate that inhaled budesonide can be a good alternative for patients with acute exacerbation of chronic obstructive pulmonary disease [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure

Wang

Pelgrim

Swart³

et al. 2021

IJMS

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Chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) is featured by oxidative stress and chronic inflammation. Due to the poor efficacy of standard glucocorticoid therapy, new treatments are required. Here, we investigated whether the novel compound SUL-151 with mitoprotective properties can be used as a prophylactic and therapeutic treatment in a murine CS-induced inflammation model. SUL-151 (4 mg/kg), budesonide (500 μg/kg), or vehicle were administered via oropharyngeal instillation in this prophylactic and therapeutic treatment setting. The number of immune cells was determined in the bronchoalveolar lavage fluid (BALF). Oxidative stress response, mitochondrial adenosine triphosphate (ATP) production, and mitophagy-related proteins were measured in lung homogenates. SUL-151 significantly decreased more than 70% and 50% of CS-induced neutrophils in BALF after prophylactic and therapeutic administration, while budesonide showed no significant reduction in neutrophils. Moreover, SUL-151 prevented the CS-induced decrease in ATP and mitochondrial mtDNA and an increase in putative protein kinase 1 expression in the lung homogenates. The concentration of SUL-151 was significantly correlated with malondialdehyde level and radical scavenging activity in the lungs. SUL-151 inhibited the increased pulmonary inflammation and mitochondrial dysfunction in this CS-induced inflammation model, which implied that SUL-151 might be a promising candidate for COPD treatment.

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Section: Discussionmentioning

confidence: 99%

SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure

Wang

Pelgrim

Swart³

et al. 2021

IJMS

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“…Side effects associated with the use of β 2 -agonists increase dose-proportionally and may increase with advancing age, particularly with the concomitant use of other drugs in patients with comorbidities, such as the elderly. The most common side effect associated with the use of anticholinergics is dry mouth 38 , which in elderly patients can impact the ability to communicate, and may lead to secondary events such as predisposing to malnutrition and increasing the risk of respiratory infections. Nevertheless, in the present analysis, no increase in the proportion of patients experiencing dry mouth was observed with tiotropium/olodaterol compared with the monocomponents.…”

Section: Discussionmentioning

confidence: 99%

Long-term safety of tiotropium/olodaterol in older patients with moderate-to-very-severe COPD in the TONADO® studies

Ferguson¹,

Maltais

Karpel³

et al. 2020

npj Prim. Care Respir. Med.

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Older patients with chronic obstructive pulmonary disease (COPD) may be at increased risk of adverse events (AEs) due to decreased protective organ function and increased comorbidities. TONADO® 1 + 2 were replicate, randomized, double-blind, parallel-group, 52-week, Phase III trials comparing the efficacy and safety of tiotropium/olodaterol (5/5 µg) versus the monocomponents via the Respimat® inhaler in patients with moderate-to-very-severe COPD. In this prespecified safety analysis, patients were grouped by age. Of 3100 patients, 1585 (51.1%) were aged <65 years, 1198 (38.7%) 65–<75 years, 309 (10.0%) 75–<85 years, and eight (0.3%) ≥85 years. At baseline, 23.4% had a pre-existing cardiac disorder, 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diagnosed diabetes. Overall, there was no increase in major adverse cardiac events, other AEs, or serious AEs with tiotropium/olodaterol versus the monocomponents in any age group, supporting the safety of tiotropium/olodaterol in older patients with COPD.

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The discovery and development of aclidinium bromide for the treatment of chronic obstructive pulmonary disease

Malerba

Radaeli

Santini

et al. 2018

Expert Opinion on Drug Discovery

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Bronchodilators, including long-acting muscarinic receptor antagonists (LAMAs), are a mainstay of the pharmacological treatment of chronic obstructive pulmonary disease (COPD). LAMAs act as bronchodilators principally by antagonizing airway smooth muscle cells M muscarinic receptors. Aclidinium bromide is a twice-daily LAMA which was developed to improve on the efficacy and/or safety of previous LAMAs. Area covered: Herein, the authors present the pharmacotherapeutic role of aclidinium in COPD and point out unmet need in this research area. The following aspects are covered: a) the discovery and medicinal chemistry of aclidinium bromide; b) an overview of the market; c) its mechanism of action; d) its pharmacokinetic/pharmacodynamic profile derived from pre-clinical studies; e) the clinical studies which led to its licensing; f) the evidence from meta-analyses; g) the aclidinium/formoterol fixed dose combination for COPD and h) priorities in this area of research. Expert opinion: Aclidinium bromide has the pharmacological properties, safety and efficacy profile and inhaler characteristics which makes it a valuable therapeutic option for pharmacological management of patients with COPD. Due to its rapid biotransformation into inactive metabolites, aclidinium is potentially one of the safest LAMAs. Further head-to-head randomized clinical trials are required to define efficacy and safety of aclidinium when compared to once-daily LAMAs. The clinical relevance of airway anti-remodeling effects of aclidinium has to be defined.

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Safety of inhaled long-acting anti-muscarinic agents in COPD

Cited by 3 publications

References 110 publications

SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure

SUL-151 Decreases Airway Neutrophilia as a Prophylactic and Therapeutic Treatment in Mice after Cigarette Smoke Exposure

Long-term safety of tiotropium/olodaterol in older patients with moderate-to-very-severe COPD in the TONADO® studies

The discovery and development of aclidinium bromide for the treatment of chronic obstructive pulmonary disease

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