Abstract
The airway epithelium stretches and relaxes during the normal respiratory cycle, and hyperventilation exaggerates this effect, resulting in changes in lung physiology. In fact, stretching of the airways influences lung function and the secretion of airway mediators, which in turn may cause a potentially injurious inflammatory response. This aim of the present narrative review was to illustrate the current evidence on the importance of mechanical stress in the pathophysiology of lung diseases with a particular focus on chronic obstructive pulmonary disease (COPD) and to discuss how this may influence pharmacological treatment strategies. Overall, treatment selection should be tailored to counterpart the effects of mechanical stress, which influences inflammation both in asthma and COPD. The most suitable treatment approach between a long-acting β2-agonists/long-acting antimuscarinic-agonist (LABA/LAMA) alone or with the addition of inhaled corticosteroids should be determined based on the underlying mechanism of inflammation. Noteworthy, the anti-inflammatory effects of the glycopyrronium/indacaterol combination on hyperinflation and mucociliary clearance may decrease the rate of COPD exacerbations, and it may synergistically improve bronchodilation with a double action on both the cyclic adenosine monophosphate (cAMP) and the acetylcholine pathways.
Highlights
Treatment selection should be tailored to counterpart the effects of mechanical stress, which influences inflammation both in asthma and chronic obstructive pulmonary disease (COPD). e most suitable treatment approach between a long-acting β2-agonists/long-acting antimuscarinic-agonist (LABA/LAMA) alone or with the addition of inhaled corticosteroids should be determined based on the underlying mechanism of inflammation
The anti-inflammatory effects of the glycopyrronium/indacaterol combination on hyperinflation and mucociliary clearance may decrease the rate of COPD exacerbations, and it may synergistically improve bronchodilation with a double action on both the cyclic adenosine monophosphate and the acetylcholine pathways
The direct evidence of the clinical and pathophysiological effects of ICS withdrawal in patients with COPD is limited but consistent, and this has led to the publication of numerous de-escalating algorithms [26,27,28,29] e indirect proof that ICS withdrawal did not increase the exacerbation rate was shown by the subgroup analysis of a recently published real life, noninterventional, longitudinal prospective cohort study conducted in primary and secondary care patients with COPD [30]; these results were confirmed in a subgroup analysis of the CRYSTAL study, a pragmatic trial that shows that symptomatic patients with moderate COPD switched from a treatment with LABA/ICS to indacaterol/glycopyrronium which demonstrated a significant increase in forced expiratory volume in 1 s (FEV1) (71 mL, p < 0001) and TDI score (+1.10 units, p < 0.0001) [31]
Summary
Small airways play an important role in the pathogenesis of COPD, and their functional evaluation relies on specific lung functional tests, known from many years [7] Taking in account these pathophysiological evidence, it should be underlined that further damage and substantial inflammatory reactions may occur when small airway collapse is enhanced by increased surface tension [8], supporting the hypothesis that the cyclic opening and closing of small airways during tidal breathing causes lung injury in man [9]. Preliminary in vitro findings suggest that the specific LABA/LAMA combination of glycopyrronium/ indacaterol may synergistically improve bronchodilation by increasing cAMP concentrations in both airway smooth muscle and bronchial epithelium and by decreasing acetylcholine release from the epithelium [6]
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