* Cigarette smoking
o The primary cause of COPD is exposure to tobacco smoke. Clinically significant COPD develops in 15% of cigarette smokers. Age of initiation of smoking, total pack-years, and current smoking status predict COPD mortality. People who smoke have a greater annual decline in FEV1. Overall, tobacco smoking accounts for as much as 90% of the risk.
o Secondhand smoke, or environmental tobacco smoke, increases the risk of respiratory infections, augments asthma symptoms, and causes a measurable reduction in pulmonary function.
* Air pollution
o Although the role of air pollution in the etiology of COPD is unclear, the effect is small when compared to cigarette smoking.
o The use of solid fuels for cooking and heating may result in high levels of indoor air pollution and the development of COPD.
* Airway hyperresponsiveness
o Airway hyperresponsiveness (ie, Dutch hypothesis) stipulates that patients who have nonspecific airway hyperreactivity and who smoke are at increased risk of developing COPD with an accelerated decline in lung function. Nonspecific airway hyperreactivity is inversely related to FEV1 and may predict a decline in lung function.
o The possible role of airway hyperresponsiveness as a risk factor for the development of COPD in people who smoke is unclear. Moreover, bronchial hyperreactivity may result from airway inflammation observed with the development of smoking-related chronic bronchitis.
* Alpha1-antitrypsin deficiency
o AAT deficiency is the only known genetic risk factor for developing COPD and accounts for less than 1% of all cases in the United States. AAT is a protease inhibitor produced by the liver that acts predominantly by inhibiting neutrophil elastase in the lungs.
o Severe AAT deficiency leads to premature emphysema at the average age of 53 years for nonsmokers and 40 years for smokers.
o PiMM phenotypes occur in 90% of people and produce serum levels within the reference range. PiZZ is the most common deficient state and accounts for 95% of people in the severely deficient category.
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