Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

Applying Pharmacogenomics in the Therapeutics of Pulmonary Diseases
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leading to various symptoms such as coughing that produces large amounts of
mucus, wheezing, shortness of breath, and chest tightness among other symptoms. 14
The prevalence of COPD is substantial with >300 millions of estimated patients
in 2010 worldwide. 15 Overall, the number of deaths from COPD has decreased
slightly from 3.1 million to 2.9 million between 1990 and 2010, 16 making it the
fourth leading cause of death globally. 17 COPD is also a major cause of disability
and the third leading cause of death in the United States. The total number of global
COPD is expected to continually increasing, as the population continues to get older.
The World Health Organization (WHO) predicts that COPD will become the third
leading cause of death worldwide by 2030. 18
Independently of other risk factors, regular cigarette smoking is the leading cause
of COPD, accounting for approximately 80% of cases. 19 Most COPD cases are those
who used to smoke or are current smokers. In multivariate analysis, cigarette smokers,
as compared with nonsmokers, were at higher risk for developing COPD with
dose–response effects. 19 Total deaths from COPD are projected to increase by more
than 30% in the next 10 years unless urgent actions are taken to reduce the underlying
risk factors, especially tobacco use. 18 Long-term exposure to other lung irritants
in the environment, 20,21 such as indoor and outdoor air pollution, occupational dusts
and chemicals (vapors, irritants, and fumes), and frequent lower respiratory infections
during childhood are also risk factors that contribute to the pathogenesis and
development of COPD. In addition, genetic susceptibility of individuals could be
used to explain why not all smokers would develop COPD. 22 For example, a small
proportion of COPD cases (about 1–5%) have been known to have α1-antitrypsin
deficiency. 23,24 This risk is even higher if an individual who is α1-antitrypsin deficient
also smokes regularly. 23
Therapy for COPD
Although COPD cannot be cured completely, drug treatment for COPD and subsequent
exacerbations of respiratory symptoms must be included in an effective strategy
for COPD management, in which the major therapeutic approaches include risk
factor reduction, such as smoking cessation and treatment with bronchodilators and
corticosteroid therapy. When selecting a treatment plan, the benefits and risks to the
individual and to the community must be taken into account. To date, none of the
existing medications for COPD have been shown to modify the long-term decline in
lung function, which is the hallmark of this syndrome. Therefore, pharmacotherapy
for COPD is primarily meant to decrease symptoms and complications. In particular,
bronchodilator medications, which include β-agonists, anticholinergics, theophylline,
25–27 and a combination of one or more of these drugs, as well as glucocorticosteroids,
28 are central to the symptomatic management of stable COPD and control
of exacerbations.
Bronchodilators
Bronchodilators help open the airways in the lungs by relaxing smooth muscle around
the airways. Bronchodilators can be classified as short or long acting. The short- acting
bronchodilators, sometimes called “quick-reliever” can quickly decrease shortness of
breath for about 4 to 6 hours. Common short-acting bronchodilators include β-agonists,