The map that leads to COPD is as follows:

1. Inflammation of airway epithelium. Causes of airway inflammation will be discussed in detail below, however in general airway irritants, such as smoke and particulate matter, lead to an inflammatory response in the tissues of the lungs, which will be discussed in detail below (Huether & McCance, p692).
2. Inflammatory response. The body’s inflammatory response includes the release of neutrophils, CD8 T lymphocytes, B cells, and macrophages (Takeda Pharmaceuticals, 2012). These cells trigger an inflammatory cascade which causes the release of inflammatory mediators such as tumor necrosis factor-alpha, interferon gamma, matrix metalloproteinases -6 and -9, C-reactive protein, interleukin -1, -6, and -8, fibrinogen (Takeda Pharmaceuticals) and leukotriene B4 (MacNee, 2006). Chronic Immune stimulation found in COPD patients may be a cause of COPD itself, or a result of chronic colonization of lower respiratory tract by pathogens due to underlying disease states such as chronic bronchitis or emphysema (MacNee, 2005). The aforementioned inflammatory response causes changes in the tissue and tissue damage specifically that result in the symptoms associated with COPD (Takeda Pharmaceuticals, 2012). In addition to the above pathway, an alternate inflammatory pathway involves an imbalance of proteases and anti-proteases. Neutrophils at the sites of inflammation cause the release of serum proteases such as neutrophil elastase, cathepsin G and protease 3 (MacNee, 2005), which may contribute to destruction of alveoli discussed below. Oxidative stress may also cause inactivation of anti-protease (MacNee, 2006), disrupting the protease/anti-protease balance. Individuals with COPD may also have an inherited alpha1-antitrypsin deficiency which results in the inhibition of normal endogenous antiproteases, ultimately increasing the breakdown of elastin in lung tissues and causing tissue damage discussed below (Huether & McCance, 2012, p692).
3. Continued inflammation, irritation, and tissue damage. Alveoli, the air sacs in the lungs, are supposed to be elastic or stretchy. These sacs act like small balloons when they are inflated and deflated (National Institutes of Health, 2013), however inflammatory changes noted above cause the alveoli and airways to lose their elasticity. The walls between the small alveoli may also be destroyed, making larger “balloons” that are less elastic and have less surface area for gas exchange (National Institutes of Health). The walls of the airways also become thick and inflamed due to the inflammatory processes at work (National Institutes of Health, 2013). Inflammation causes enlargement of the mucous glands that line the walls of the airways within the lung, resulting in normal healthy cells being replaced by more mucous secreting goblet cells (Takeda Pharmaceuticals, 2012) and increased size of bronchial submucosal glands (MacNee, 2006), though mucous hypersecretion is not always present. There is also concurrent damage to the cilia of the mucociliary transport system, causing a deficit in the ability of the body to clear mucous from airways (Takeda Pharmaceuticals, 2012).
4. Airway obstruction, air trapping, and decreased gas exchange. As the cells of the airways make more mucous they have more difficulty clearing it, due to volume and failed ciliary function, ultimately clogging the airways (National Institutes of Health, 2013). Combined with physically inflamed and thickened airway walls, mucous hyper secretion and decreased clearance results in airflow obstruction and increased resistance in the small airways (MacNee, 2006). Decreased surface area of alveolar walls results in decreased gas exchange of CO2 and O2 (National Institutes of Health, 2013). Resulting in abnormal acid-base balance and abnormal ventilation:perfusion ratios. Due to the development of mucous plugs and decrease in airway recoil, air becomes trapped in the alveoli during expiration (Huether & McCance, 2012, p692). The air trapped during expiration,” results in hyperinflation at rest, and dynamic hyperinflation during exercise (MacNee, 2006).”
5. Breathing difficulties, dyspnea, cough, hypoxemia, hypercapnia, cor pulmonale. The progression of COPD is usually slow, with symptoms developing gradually and worsening over time (National Institutes of Health, 2013). Exacerbations are associated with increased neutrophils and increased eosinophils in the lung tissue. Exacerbations may be caused by infection, air pollution or changes in ambient temperature (MacNee, 2006). Extreme exertion is required to inhale and exhale due to both air trapping and reduced lung compliance. This exertion leads to fatigue which leads to hypoxemia, hypercapnia, respiratory acidosis, severe respiratory failure and possibly even death. Pulmonary vasoconstriction also increases the load on right ventrical leading to peripheral edema (MacNee, 2006). Pulmonary hypertension develops late in COPD as a result of multiple processes interacting. Contributing factors are pulmonary arterial constriction, endothelial dysfunction, remodeling of the pulmonary arteries, and destruction of the pulmonary capillary bed. Structural changes of the pulmonary arterioles leads to persistent pulmonary hypertension which leads to right ventricular hypertrophy, enlargement and dysfunction (MacNee, 2006).

However, the development of COPD follows a slightly different pathways depending on the particular disease underlying it (emphysema, chronic bronchitis, asthma).

Signs and Symptoms of Emphysema

• wheezing
• dyspnea with exertion (SOB)
• pursed lips (assists breathing)
• use of accessory respiratory muscles (for breathing)
• tripod sitting position for breathing (as seen in background picture)
• hyperinflation (barrel chest)
• chest is hyperresonant
• distant heart sounds
• increased CO2 retention ("pink puffer")
• increased respiratory rate
• anxious
• speaks in short jerky sentences
• lack of energy
• unintended weight loss
• peripheral edema
• tachypnea (rapid respiration)

COPD's number one risk factor is cigarette smoking (up to 90% of cases). 15-20% of one-pack-a-day smokers and 25% of two-pack smokers will develop COPD in their lifetime (COPD risk factors, 2015). A person's risk is determined by their age of initiating smoking, total pack-years, and current smoking status. Lung function changes usually occur long before they are clinically detected. Smoking cigarettes, as well as cigars and pipe smoke, impairs cilia, inhibits macrophages, and leads to excessive mucus production. Second-hand smoke increases the risk of respiratory infections, can worsen or perpetuate asthma symptoms, and reduces pulmonary function.

Smaller percentages of COPD cases can be attributed to occupational and environmental factors and are often associated with co-morbid diabetes and asthma. Common work exposures are coal, manufactured fibers, cement, welding fumes, organic dusts, engine exhaust, fire smoke, and second-hand cigarette smoke (Chronic Obstructive, 2015).

Genetic predispositions to developing COPD may exist. Alpha1-antitrypsin (AAT) deficiency is the only known genetic link to COPD and accounts for <1% of cases.

HIV-positive patients have been shown to have an increased risk after control tests for other variables.

Airway hyper-responsiveness may have correlation for smokers.

Connective tissue disorders present as risk factors, specifically Marfan's syndrome (pulmonary abnormalities, especially emphysema, in 10% of affected individuals), Ehlers-Danlos syndrome, and Cutis Laxa (Chronic obstructive-medscape, 2015).

Specific risk factors for chronic bronchitis are smoking cigarettes, cigars, pipes, and marijuana (85-90% of cases) (Bronchitis, 2015). Acute bronchitis leads to chronic bronchitis over time with continued exposure to cigarettes and other irritants.

Specific risk factors for emphysema are cigarette smoking; asthma with persistent, fixed airway obstruction regardless of therapy; 2% of IV drug users (direct correlation between pulmonary vascular damage from methamphetamine and development of bullous cysts in the upper lobes of lungs from cocaine or heroin); and severe AAT deficiency (has been linked to premature emphysema around age 53 for non-smokers and age 40 for smokers) (Emphysema, 2015).