Additional Question: What contributes to mortality and morbidity from this disease? Once again, COPD is the third leading cause of death in the US. Chronic/acute respiratory failure and has been found to be the primary contributor to deaths in COPD patients (mortality), though in the past researchers have also blamed coexisting/associated lung cancer. However, people can live and have been living long(ish) with this condition. In 2011, 12.7 million U.S. adults (aged 18 and over) were estimated to have COPD. However, close to 24 million U.S. adults have evidence of impaired lung function, indicating an under diagnosis of COPD. An estimated 715,000 hospital discharges were reported in 2010; a discharge rate of 23.2 per 100,000 population. COPD is an important cause of hospitalization in our aged population. Approximately 65% of discharges were in the 65 years and older population in 2010. The cause of these morbidity rates is due to the gradual/ongoing manifestation of COPD.

Etiology: Causes

Long-term exposure to lung irritants that damage the lungs and the airways usually is the cause of COPD. In the US, the most common irritant that causes COPD is cigarette smoke. Pipe, cigar, and other types of tobacco smoke also can cause COPD, especially if the smoke is inhaled.

Breathing in secondhand smoke, air pollution, or chemical fumes or dust from the environment or workplace also can contribute to COPD. (Secondhand smoke is smoke in the air from other people smoking.)

Rarely, a genetic condition called alpha trypsin 1 deficiency may play a role in causing COPD. People who have this condition have low levels of alpha-1 antitrypsin (AAT)—a protein made in the liver.

Having a low level of the AAT protein can lead to lung damage and COPD if you're exposed to smoke or other lung irritants. If you have this condition and smoke, COPD can worsen very quickly.

Although uncommon, some people who have asthma can develop COPD. Asthma is a chronic (long-term) lung disease that inflames and narrows the airways. Treatment usually can reverse the inflammation and narrowing. However, if not, COPD can develop.

Pathophysiology: How COPD manifests

Inhaled irritants cause inflammatory cells such as neutrophils, CD8⁺ T-lymphocytes, B cells and macrophages to accumulate.² When activated, these cells initiate an inflammatory cascade that triggers the release of inflammatory mediators such as tumour necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), matrix-metalloproteinases (MMP-6, MMP-9), C-reactive protein (CRP), interleukins (IL-1, IL-6, IL-8) and fibrinogen. These inflammatory mediators sustain the inflammatory process and lead to tissue damage as well as a range of systemic effects. Chronic inflammation is present from the outset of the disease and leads to structural changes in the lung which further perpetuate airflow limitation. This chronic inflammatory cascade is illustrated at left. 

COPD is characterized by chronic inflammation of the airways, lung tissue and pulmonary blood vessels as a result of exposure to inhaled irritants such as tobacco smoke. 

Airway remodeling in COPD is a direct result of the inflammatory response associated with COPD and leads to narrowing of the airways. Three main factors contribute to this: peribronchial fibrosis, build-up of scar tissue from damage to the airways and over-multiplication of the epithelial cells lining the airways.

Parenchymal destruction is associated with loss of lung tissue elasticity, which occurs as a result of destruction of the structures supporting and feeding the alveoli (emphysema). This means that the small airways collapse during exhalation, impeding airflow, trapping air in the lungs and reducing lung capacity 

Smoking and inflammation enlarge the mucous glands that line airway walls in the lungs, causing goblet cell metaplasia and leading to healthy cells being replaced by more mucus-secreting cells. Additionally, inflammation associated with COPD causes damage to the mucociliary transport system which is responsible for clearing mucus from the airways. Both these factors contribute to excess mucus in the airways which eventually accumulates, blocking them and worsening airflow.

Key References:

-Saqib A. Gowani, Sana S. Memon, and Javaid A. Khan "A Major Cause of Death in COPD and Risk Factors for Lung Cancer—a Dilemma or a Mistake?" American Journal of Respiratory and Critical Care Medicine, Vol. 176, No. 6 (2007), pp. 624-625.
-Centers for Disease Control and Prevention. National Center for Health Statistics. National Hospital Discharge Survey raw data, 2010. Analysis performed by the American Lung Association Research and Health Education Division using SPSS software.
-Centers for Disease Control and Prevention. National Center for Health Statistics. National Health Interview Survey Raw Data, 2011. Analysis performed by the American Lung Association Research and Health Education Division using SPSS and SUDAAN software. 
-Chung KF. The role of airway smooth muscle in the pathogenesis of airway remodelling in COPD. Proc Am Thorac Soc 2005;2:347-54. 
-Laperre TS, Sont JK, van Schadewijk A, et al. Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study. Respir Res 2007;8:85-93.
-Danahay H & Jackson AD. Epithelial mucus-hypersecretion and respiratory disease. Curr Drug Targets Inflamm Allergy 2005;4:651-64
-National Institute of Health: National Heart, Lung, and Blood Institute: http://www.nhlbi.nih.gov/health/health-topics/topics/copd/causes