COPD, by definition, involves irreversible damage to lung parenchyma and airways. Such damage only accumulates over time, and there is not a mode of treatment currently available to “cure” COPD and regain normal lung function. There a few methods to slow the progression of COPD, however.
The cessation of smoking is the single most potent “therapy” for COPD. Cigarette smoking accounts for more than 95% of the clinical cases of COPD. The ROS formed by cigarette smoking recruit inflammatory cells, increasing the risk of lung tissue damage. Cessation of smoking avoids further risk of lung tissue damage. The interrelationships involved in COPD are outlined in Figure 8. It should be noted that cigarette smoking is not especially highlighted in this figure; in reality, it is the most prevalent and most preventable cause of COPD.
Dual PDE3/PDE4 Inhibitors
Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) regulate many cellular processes. One such regulatory role of cAMP and cGMP is the inhibition of inflammatory mediator release. Phosphodiesterase (PDE) enzymes hydrolyze cAMP and cGMP to the inactive forms 5’AMP and 5’GMP respectively. The use of phosphodiesterase inhibitors as possible therapies for inflammatory diseases, such as COPD, has been proposed. A summary of the effects of these inhibitors is shown in Figure 9.
PDE4 is a phosphodiesterase that favors cAMP, while PDE3 hydrolyses both cAMP and cGMP with high affinities. PDE4 inhibitors have been found to be efficacious at inhibiting the activation and release of inflammatory mediators from certain cells, such as neutrophils and eosinophils. However, there is little evidence that suggests the inhibition of PDE3 inhibits inflammation. The dual inhibition of PDE3 and PDE4 was found to be synergistic at suppressing inflammatory mediator release, however. Therefore, this dual inhibition is a possible management option for COPD patients.
Cilomilast and roflumilast-n-oxide are two examples of PDE4 inhibitors, while SDZ ISQ 844 is an inhalable PDE3/4 inhibitor. Combinations of PDE4 and dual PDE3/4 inhibitors was found to cause bronchodilation and decreased inflammation in mice, which is potentially promising news in terms of the development of an efficacious COPD management option (Abbot-Banner 2014).
Alpha-1-Antitrypsin Deficiency Treatment
Concentrates of the functional enzyme can be provided to those with A1AT deficiency. It is generally taken intravenously on a weekly basis. Prolastin-C is the most commonly-used augmentation therapy currently. The NIH reports a 1.5x increased overall death rate for those who did not receive this augmentation therapy than those who did – which is promising. Again, this treatment option is only for those whose genetics yields a deficiency in A1AT, and may not have significant effects in smokers who are not deficient in this enzyme.
Lung Transplantation and Stem Cell Therapy
Lung transplantation is currently an option for patients with COPD. Generally, the two main factors that determine whether or not a patient is eligible for a transplant is (a) the severity of the COPD symptoms, and (b) age under 65. Often, only one lobe is replaced by transplant, but has been shown to be at least mildly effective in patients with advanced COPD.
Stem cell therapy, which could potentially yield new lung tissue (that is not damaged), is not currently an approved mode of treatment, but is undergoing several clinical trials, and may in fact be an option in the near future. Besides lung transplantation, this may be one of the only methods of truly treating the irreversible nature of COPD.
Besides true “treatment” of COPD, there are methods of symptomatic management. Bronchodilators are one of the most common and effective methods to improve airway movement in acute exacerbations of COPD. Steroids, while not effective in COPD treatment as they are in asthma treatment, can have mildly beneficial effects, and are often used as well. Oxygen treatment is often used in severe cases that require hospitalization. Lastly, if the acute exacerbation is caused by a bacterial infection, antibiotics are provided and can prevent fatality.