TY - JOUR
T1 - How Do Dual Long-acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?
AU - Beeh, Kai M
AU - Burgel, Pierre-Regis
AU - Franssen, Frits M E
AU - Lopez-Campos, Jose Luis
AU - Loukides, Stelios
AU - Hurst, John R
AU - Fležar, Matjaž
AU - Ulrik, Charlotte Suppli
AU - Di Marco, Fabiano
AU - Stolz, Daiana
AU - Valipour, Arschang
AU - Casserly, Brian
AU - Ställberg, Björn
AU - Kostikas, Konstantinos
AU - Wedzicha, Jadwiga A
PY - 2017/7/15
Y1 - 2017/7/15
N2 - Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting b2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaledcorticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus productionwith impairedmucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into thismanuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease.
AB - Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting b2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaledcorticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus productionwith impairedmucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into thismanuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease.
U2 - 10.1164/rccm.201609-1794CI
DO - 10.1164/rccm.201609-1794CI
M3 - Review
C2 - 27922741
SN - 1073-449X
VL - 196
SP - 139
EP - 149
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 2
ER -