COPD: maximization of bronchodilation

Abstract


 
 
 
 The most recent guidelines define COPD in a multidimensional way, nevertheless the diagnosis is still linked to the limitation of airflow, usually measured by the reduction in the FEV1/FVC ratio below 70%. However, the severity of obstruction is not directly correlated to symptoms or to invalidity determined by COPD. Thus, besides respiratory function, COPD should be evaluated based on symptoms, frequency and severity of exacerbations, patient’s functional status and health related quality of life (HRQoL). Therapy is mainly aimed at increasing exercise tolerance and reducing dyspnea, with improvement of daily activities and HRQoL. This can be accomplished by a drug-induced reduction of pulmonary hyperinflation and exacerbations frequency and severity. All guidelines recommend bronchodilators as baseline therapy for all stages of COPD, and long-acting inhaled bronchodilators, both beta-2 agonist (LABA) and antimuscarinic (LAMA) drugs, are the most effective in regular treatment in the clinically stable phase. The effectiveness of bronchodilators should be evaluated in terms of functional (relief of bronchial obstruction and pulmonary hyperinflation), symptomatic (exercise tolerance and HRQoL), and clinical improvement (reduction in number or severity of exacerbations), while the absence of a spirometric response is not a reason for interrupting treatment, if there is subjective improvement in symptoms. Because LABA and LAMA act via different mechanisms of action, when administered in combination they can exert additional effects, thus optimizing (i.e. maximizing) sustained bronchodilation in COPD patients with severe airflow limitation, who cannot benefit (or can get only partial benefit) by therapy with a single bronchodilator. Recently, a fixed combination of ultra LABA/LAMA (indacaterol/glycopyrronium) has shown that it is possible to get a stable and persistent bronchodilation, which can help in avoiding undesirable fluctuations of bronchial calibre.
 
 
 

Clinical management of chronic obstructive pulmonary disease patients with muscle dysfunction

“…The use of bronchodilators, and probably of double bronchodilation, allows us to obtain different improvements in symptoms and lung function (reductions in airway obstruction, pulmonary hyperinflation and work of breathing) (3,(209)(210)(211)(212)(213). This will facilitate the work of respiratory muscles contributing to a higher level of physical activity, which in turn will have beneficial effects on limb muscles.…”

Pharmacological Profile of AZD8871 (LAS191351), a Novel Inhaled Dual M3 Receptor Antagonist/β2-Adrenoceptor Agonist Molecule with Long-Lasting Effects and Favorable Safety Profile

“…In this sense, AZD8871 showed some selectivity over the b 1 -adrenoceptors, which was in the same range as that of indacaterol. The M 2 receptor is also expressed in heart and regulates chronotropism and inotropism (Brodde and Michel, 1999); however, combination of antimuscarinic and b 2 -adrenoceptor activities has not led to an increase in tachycardia in COPD patients at doses with long-lasting bronchodilation effects (Wielders et al, 2013;Nardini et al, 2014;Calzetta et al, 2016;Matera et al, 2016), suggesting low potential of cardiovascular effects at therapeutic doses. When tested in the dog model, AZD8871 did not increase heart rate at efficacious and long-acting doses, which confirmed the favorable cardiovascular profile of the compound.…”

Sirtuin 1 and Aging Theory for Chronic Obstructive Pulmonary Disease

“…The prevalence is particularly high in the elderly and it is expected to become the third leading cause of death worldwide by 2020 [ 2 , 3 ]. Existing therapies are essentially symptomatic and not able to positively influence the course of the disease [ 4 – 6 ]. Moreover, the guidelines for respiratory disorders, including COPD, are not well clear and thus often disappointing [ 7 , 8 ].…”

“…Nowadays it is evident that COPD represents a syndrome with several phenotypes differentiated by symptoms, number of exacerbations, and therapy response [ 6 , 9 ]. The molecular mechanisms determining COPD are not still clarified because of its complexity and great heterogeneity.…”