Susceptibility to asthma and COPD seems to be associated with microbial colonization of the respiratory tract. In the lower airways of COPD patients, bacterial colonization is found in at least 50% of patients, especially in severe and exacerbating COPD patients. Regular antibiotic therapy would seem an ideal therapeutic strategy; however, antibiotic resistance cautions against this. Furthermore, in a clinical study, a 5-day treatment with moxifloxacin every 8 weeks had no effect on exacerbation rates and lung function; however, a benefit was observed in patients with purulent sputum. Inhaled liposomal formulations of antibiotics are also being developed to minimize adverse effects. Moreover, the effects of liposomal formulations on drug deposition in the lung are currently being explored. Inhaled ciprofloxacin is currently under clinical development. Long-term use of antibiotic therapy, macrolides, has shown to significantly reduce exacerbation rates in COPD patients, particularly in patients with purulent sputum. In addition to their antibiotic effects, macrolides have also shown to have anti-inflammatory effects. In hypoxia and oxidative stress-induced reduction in HDAC-2 activity, EM-703, a nonantibacterial erythromycin derivative, restored HDAC-2 activity. This resulted in reduced NF-KB-driven inflammation [69]. Several macrolides are currently under development as anti-inflammatory drugs [70].

Antiageing Molecules

COPD is an age-related disease that shows evidence of accelerated lung ageing [3,71]. It is believed to be due to defective function of endogenous antiageing molecules, such as sirtuins and forkhead box proteins [72]. Oxidative stress has been shown to directly reduce sirtuin 1 activity and expression [72]. In rodent models, resveratrol, a weak sirtuin activator, has been shown to prolong the life span of mice [73]. In macrophages from COPD patients and healthy epithelial cells, resveratrol suppressed the inflammatory response [74]. A more potent sirtuin activator SRT2172 reversed the effects of cigarette smoke on MMP-9 activity in mice [71]. Sirtuin activators are currently in preclinical development for COPD.

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