COPD is a common chronic respiratory disease with high mortality rate. Chronic bronchitis, emphysema, and chronic asthma are three of the major diseases that are grouped together as COPD.

Long-term exposure to harmful gas or particles, especially smoking, can induce chronic inflammation of the respiratory tract and sustained airflow limitation which gradually deteriorates to obstructive lung diseases. Early symptoms of COPD lacks specificity, so it is likely to be confused with asthma. Since COPD mainly affects people over the age of 40, it is often misattributed to aging and delay in treatments. Furthermore, early symptoms of COPD is hard to diagnose, because symptoms can creep up gradually or be mistaken for cold or other less serious ailments. When symptoms get worse, patients start to feel the shortness of breath (SOB) which may cause physical inactivity and exacerbate the activities of daily life.

Sources: Meridigen Biotech. Co., Ltd.

The causes of COPD is long-term inhalation exposure to organic or inorganic dust or chemical stimulants such as cigarettes, biofuels, fumes, and air pollutants. These chemicals would activate the pattern recognition receptors, or PRR, such as Toll-like receptors, and activate the innate immune system. The epithelial cells and the macrophages inside alveoli are stimulated to produce chemokines, attracting inflammatory cells such as monocytes, neutrophils and lymphocyte to the site of a lung. Those immune cells and epithelial cells cause emphysema and fibrosis in small airways by secreting matrix metallopeptidase 9 (MMP-9) and TGF-β.

At later stages, these chemicals activate the acquired immune system. Both of T cells and B cells will activate and proliferation which may cause lymphoid follicles. The amount of killer T cells and helper T cells also increase. Moreover, Th17 may enlarge the immune responses induced by neutrophils. Eventually, these factors drive the development of a chronic inflammatory and airway obstructive disease that affects lung function.

Sources: Meridigen Biotech. Co., Ltd.

According to the World Health Statistics 2012 of WHO, there had been 3 million people died from COPD, accounting for 6% of the death worldwide. In China, approximately 100 million people suffer from COPD with the highest death rate among other countries. According to the report released from Europe, around 75% of COPD patients were not diagnosed. Likewise, in our nation, only one-third of COPD patients would receive medical treatments. It has been estimated that by 2020, COPD will be one of the top 3 causes of death in the world. Another report, the 2014 market analysis and clinical testing platform of COPD drugs, also indicates that the market size of COPD drugs will arise with a CAGR at 7.8%, from 15 billion in 2016 to 20 billion in 2020. The potential growth is due to the emergence of more efficient and more convenient drugs.

Currently, there is no cure for COPD, but treatment can help slow the progression of the condition and control the symptoms. The testament include bronchodilators, anti-inflammatory drugs, antioxidants, protease inhibitors, antibiotics, or mucus regulators. All of these testament can reduce the mortality rate and improve patients’ quality of life. However, it cannot cure the disease completely.

Small molecule drugs are major way to treat COPD symptoms. However, small molecule drugs can only mitigate the symptoms but are unable to improve the pathogenic changes in lung tissues. Most of the improvements of drugs are merely change route of administration or prolong their half time for patients’ convenience. Mild and moderate COPD patients are treated with bronchodilators, while severe patients or those who with exacerbations are treated with corticosteroids.

Whereas those drugs have potential risks. Corticosteroids have excellent anti-inflammatory and immunomodulatory effects, but long-term use of them may enhance the risk of infections. On the other hand, despite that protein-based drugs are effective, they become useless once being subject to attacks from reactive oxygen species. Along with the exacerbations of COPD patients, clinical therapies may combine multiple drugs for them depending on their severity and their responses to drugs. Lung surgery is able to improve the patient's condition while it is a burden on the elderly.

The stem cell therapy however prove the traditional treatment for COPD and minimize the burden of the patient. Besides, stem cells have self-renewal ability that makes them advantageous in clinical use because they do not require frequent injections. Research has shown that cytokines released by stem cells can effectively improve the smoking-induced COPD symptoms in animal models. Therefore, stem cell therapy is being seen as a promising new option for COPD.

Comparison between MSC drugs and small molecular drugs

Sources: Meridigen Biotech. Co., Ltd.