Muscarinic receptor antagonists and airway inflammation: A systematic review on pharmacological models

Use of human airway smooth muscle in vitro and ex vivo to investigate drugs for the treatment of chronic obstructive respiratory disorders

“…Indeed, this is a condition characterised by several features associated with asthma and several features associated with COPD, suggestive of asthma–COPD overlap (ACO) as already reported in humans (Miravitlles, 2017). Despite the anatomical, pathophysiological, and mechanistic differences with human airways, isolated equine bronchi may represent an alternative, although not a specific, model of human chronic obstructive respiratory disorders (Calzetta, Pistocchini, Ritondo, Cavalli, et al, 2022d; Calzetta, Rogliani, et al, 2019c; Calzetta, Rogliani, Pistocchini, et al, 2018d, 2018e).…”

“…Challenging isolated human airways, bronchial epithelial cells, alveolar macrophages and lung fibroblasts with LPS is a technique extensively used to reproduce in vitro and ex vivo the detrimental conditions detectable in the airways of patients with stable COPD that are at higher risk of exacerbation due to the of the respiratory tract by Gram‐negative bacteria (Beasley et al, 2012; Calzetta, Aiello, Frizzelli, Pistocchini, et al, 2022b; Calzetta, Luongo, et al, 2015b; Calzetta, Matera, & Cazzola, 2018a; Cazzola et al, 2011; Cazzola et al, 2017; Papi et al, 2006; Wedzicha & Seemungal, 2007). More specifically, the incubation of bronchial tissue with LPS significantly alters ASM contractility (Calzetta, Luongo, et al, 2015b; Calzetta, Pistocchini, Ritondo, Cavalli, et al, 2022d; Calzetta, Rogliani, Pistocchini, et al, 2018e; Cazzola et al, 2011; Cazzola et al, 2017), induces neutrophilic inflammation (Calzetta, Matera, & Cazzola, 2018a; Calzetta, Pistocchini, Ritondo, Cavalli, et al, 2022d; Cazzola et al, 2017) and NKA‐driven neurogenic inflammation (Calzetta, Luongo, et al, 2015b; Calzetta, Matera, & Cazzola, 2018a; Calzetta, Pistocchini, Ritondo, Cavalli, et al, 2022d; Calzetta, Rogliani, et al, 2017b; Calzetta, Rogliani, Pistocchini, et al, 2018e) by activating capsaicin‐sensitive sensory nerves (Calzetta, Luongo, et al, 2015b; Calzetta, Pistocchini, Ritondo, Cavalli, et al, 2022d; Calzetta, Rogliani, Pistocchini, et al, 2018e), affects the oxidant/antioxidant profile (Calzetta, Matera, & Cazzola, 2018a; Cazzola et al, 2017) and triggers protein prenylation (Cazzola et al, 2011). Certainly, these conditions are difficult to be standardised and to be detected primarily in isolated airways from COPD donors not challenged by specific stimuli such as LPS.…”