The lungs need to be deflated: effects of glycopyrronium on lung hyperinflation in COPD patients

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation caused by bronchial alterations, small airways disease and parenchymal destruction. In patients with COPD the structural and functional lung alterations can progress more or less rapidly from the initial small airways disease to an overt COPD where a severe expiratory flow limitation takes place. In these conditions, lung hyperinflation develops characterized by increase in functional residual capacity (FRC) and decrease in inspiratory capacity (IC). Thus, IC is an easy and reliable index to monitor lung hyperinflation and to assess the efficacy of bronchodilator drugs. When FRC increases, tidal volume (VT) is located in a more flatted upper part of the P –V curve of the respiratory system and respiratory muscles must sustain a greater elastic workload. Furthermore, due to inadequate time for expiration, there is a positive alveolar pressure at the end of expiration (PEEPi). This represents a further elastic workload for the inspiratory muscles. This impairment of ventilatory mechanics generates dyspnea that in most severely compromised patients occurs also for small efforts causing activity limitation and worst health-related quality of life (HRQoL). Due

to these respiratory alterations, bronchodilators are the cornerstone of the long-term treatment of COPD in order to decrease airways resistances, lung hyperinflation and exacerbation rate, and improve patient’s symptoms, exercise tolerance and health status. Long-acting antimuscarinic bronchodilators (LAMAs) have proven to be very useful in terms of lung deflation and exercise tolerance. Recently, new LAMAs with several positive characteristics have been introduced into clinical use among which glycopyrronium bromide has shown to be particularly effective. Glycopyrronium has a longer-lasting effect compared to other anticholinergic drugs, therefore it allows a single daily administration and facilitates the therapy of a disease that needs a chronic bronchodilation by decreasing the mechanic stress of the airways determined by repeated bronchoconstriction and increasing patient’s adherence to treatment plan with better clinical results. Several studies demonstrated that glycopyrronium is able to positively and significantly decrease lung hyperinflation, symptoms, and improve psycho-physical status of COPD patients, with a low rate of adverse events, similar to that of placebo.