Summary of current and future treatment strategies for multimorbidity in COPD
| Pulmonary effects | Multimorbid effects | |
| Current strategies | ||
| Smoking cessation | Reduction in airway inflammation Improves respiratory symptoms and bronchial hyperresponsiveness Prevents accelerated lung decline | Reduction of risk of cardiovascular disease and lung cancer [180] |
| Exercise and pulmonary rehabilitation | Delays dynamic hyperinflation Reduces functional breathlessness | Increases exercise capacity Improves quality of life Reduces anxiety and depression [181] Increases BMI, skeletal muscle mass and improves osteoporosis [182] |
| Inhaled corticosteroids | Limited reduction in airway inflammation: decrease in CD8+ T-lymphocytes in airway biopsies [183] Reduction in exacerbations, especially in eosinophilic COPD [131] Increased risk of pneumonia, especially in severe disease [184] | Possible reduction in cardiovascular mortality [185] Possible reduction in systemic inflammation (CRP, TNF-α) [86] Improvement in quality of life (in combination with bronchodilator) |
| Theophylline | Possible increased inspiratory muscle strength [186] Reduction in neutrophilic inflammation [187] | Not known |
| PDE4 inhibitors, e.g. roflumilast | Reduction in exacerbations and improvement in lung function in patients with chronic bronchitis, FEV1 <50% and history of frequent exacerbations | Prevention of bone loss and increase in skeletal muscle mass (in a murine model) [188] |
| Cardiovascular-targeted treatments | ||
| Statins | May reduce exacerbations [189] | Reduction in cardiovascular risk [190] Reduction in oxidative stress and inflammation [191] |
| ACE inhibitors/ARB | Reduction in exacerbations [192] Decrease in hyperinflation [193] | May improve survival (in those with cardiovascular risk) |
| β-Blockers | Reduction in exacerbations [194] | Reduction in mortality after myocardial infarction [195] and in heart failure [196] Reduction in oxidative stress [197] Improved exercise capacity [198] |
| Future strategies | ||
| Metformin (targeting PI3K-AKT-mTOR pathway) | May improve respiratory symptoms and reduce hospitalisations [199] | Possible reduction in mortality in COPD patients with diabetes [200] |
| Resveratrol (plant-based antioxidant) | Anti-inflammatory in lung epithelial cells [201] | Possible cardioprotective effects [202] |
| Losmapimod (p38 MAPK inhibitor) | No effect on respiratory symptoms or lung function, but a trend towards reduction in exacerbations [203] | Not yet determined; possible effect on arterial inflammation |
| NF-κB inhibitors, e.g. IκB kinase inhibitors | Not yet determined; possible effects on exacerbations given role in activating inflammatory signalling in the COPD lung [204] | Not yet determined; possible effects on skeletal muscle wasting [205], cardiovascular disease, lung cancer, osteoporosis and diabetes [206] |
| Antioxidants, e.g. Nrf2 activators, NOX4 inhibitors | Not yet determined; possible reduction in inflammation and reversal of corticosteroid resistance | Not yet determined; issues with side-effect profile |
| Mesenchymal stem cell EVs | Not yet determined; initial trials failed to show benefit [207] | Not yet determined; possibly neuroprotective [208], cardioprotective [209] and anti-inflammatory [210] |
PDE4: phosphodiesterase-4; ACE: angiotensin-converting enzyme; ARB: angiotensin receptor blockers; PI3K: phosphatidylinositol 3-kinase; AKT: also known as protein kinase B; mTOR: mechanistic target of rapamycin; MAPK: p38 mitogen-activated protein kinase; IκB: inhibitor of NF-κB; Nrf2: nuclear factor erythroid 2-related factor 2; NOX: NADPH oxidase; EVs: extracellular vesicles; BMI: body mass index; CRP: C-reactive protein; TNF: tumour necrosis factor; FEV1: forced expiratory volume in 1 s.