HMG-CoA reductase inhibitors
HMG-CoA reductase inhibitors are emerging medications in COPD that have been shown to improve some outcomes, with some improvement in lung function of patients with moderate to severe COPD. Although retrospective studies showed decreased rate and severity of exacerbations, hospitalization, and mortality in patients using statin therapy, especially in patients with coexisting cardiovascular disease (CVD) or hyperlipidemia, a prospective study failed to prove this benefit. In a meta-analysis of randomized controlled trials of patients with COPD taking statins, clinical outcomes were better in patients with coexisting CVD, elevated baseline C-reactive protein (CRP), or a high cholesterol level. Another meta-analysis compared patients with COPD taking high-intensity statins with patients with COPD taking placebo. Use of statins resulted in a reduction in CRP and interleukin-6, but did not lead to significant difference in exercise capacity or quality of life.
Other medical therapies
The increasing awareness of the role of inflammation in COPD has led to consideration of drugs that attack various targets in the inflammatory cascade. Many broad-spectrum anti-inflammatory drugs are now in phase 3 development for COPD and may enter the COPD market within the next decade. Nitric oxide inhibitors, leukotriene modifiers, and tumor necrosis factor antagonists are among these novel therapies. Long-term (≥6 months) treatment with acetylcysteine may decrease exacerbation prevalence but does not appear to affect exacerbation rate, lung volumes, or FEV1. Antiplatelet therapy is associated with decreased all-cause mortality in patients with COPD, independent of cardiovascular risk. Epidermal growth factor receptor kinase has potential to combat mucus overproduction. Therapy to inhibit fibrosis is being developed. There is also a search for serine protease and matrix metalloprotease inhibitors to prevent lung destruction and the subsequent development of emphysema, as well as drugs such as retinoid that may even reverse this process. Efficacy and safety of synthetic ghrelin hormone therapy in COPD patients with severely decreased physical performance and cachexia is under investigation with some promising initial results. Palovarotene is a selective retinoic acid receptor gamma agonist that is under investigation for the treatment of emphysema. It is hypothesized that retinoic acid signaling affects alveologenesis. There have been promising results in animal studies. Many combinations of inhaler therapies are being introduced for COPD treatment. Aclidinium/formoterol is a long-acting muscarinic antagonist and long-acting beta-2 agonist (LABA/LAMA) combination therapy that is available in some countries, but is awaiting approval by the Food and Drug Administration (FDA) in the US. [ ]
Target lobe volume reduction, a novel technique for selective bronchoscopic lung volume resection, has now become available. In this technique, a one-way valve is inserted into the hyperinflated and emphysematous segment, leading to the collapse of the nonfunctional lung segment. Promising reports have been released from case series of patients undergoing this therapy. This approach is an alternative to surgical lung volume reduction in patients with COPD who are likely to require surgery. [ ]
Pharmacogenomic therapy may be important in COPD. It is important to identify the genetic factors that determine why certain heavy smokers develop COPD and others do not. Identification of genes that predispose to the development of COPD may provide novel therapeutic targets.
Club cell protein 16 augmentation
Club cell protein 16 (CC16) is mainly produced by the Club cells (formerly known as Clara cells) in the respiratory tract epithelium. CC16 has anti-inflammatory properties in smoke-exposed lungs, and COPD is associated with CC16 deficiency. Experimental augmentation of CC16 levels reduces inflammation and cellular injury, and so CC16 augmentation may be a new disease-modifying treatment for COPD.
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