Etiology

1.

Cigarette smoking

The primary cause of COPD is exposure to tobacco smoke. Overall, tobacco smoking
accounts for as much as 90% of COPD risk.
Cigarette smoking induces macrophages to release neutrophil chemotactic factors and
elastases, which lead to tissue destruction. Clinically significant COPD develops in 15%
of cigarette smokers, although this number is believed to be an underestimate. Age of
initiation of smoking, total pack-years, and current smoking status predict COPD
mortality.
People who smoke have an increased annual decline in FEV 1: the physiologic normal
decline in FEV1 is estimated to be 20-30 ml/y, but the rate of decline in COPD patients is
generally 60 ml/y or greater.
Secondhand smoke, or environmental tobacco smoke, increases the risk of respiratory
infections, augments asthma symptoms, and causes a measurable reduction in pulmonary
function.
A study by Nagelmann et al concluded that lung function deviation and lung structural
changes are present in people who smoke cigarettes before the clinical signs of airway
obstruction reveal them.[19] These changes can be detected by body plethysmography and
diffusing capacity measurement with routine spirometry.

2.

Environmental factors

COPD does occur in individuals who have never smoked. [20] Although the role of air
pollution in the etiology of COPD is unclear, the effect is small when compared with that
of cigarette smoking. In developing countries, the use of biomass fuels with indoor
cooking and heating is likely to be a major contributor to the worldwide prevalence of
COPD. Long-term exposure to traffic-related air pollution may be a factor in COPD in
patients with diabetes and asthma.[21]

3.

Airway hyperresponsiveness

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.
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. This may contribute to airway remodeling, leading to a more fixed
obstruction, as is seen in persons with COPD.

4.

Alpha1-antitrypsin deficiency

Alpha1-antitrypsin (AAT) is a glycoprotein member of the serine protease inhibitor

family that is synthesized in the liver and is secreted into the bloodstream. The main
purpose of this 394-amino-acid, single-chain protein is to neutralize neutrophil elastase in

the lung interstitium and to protect the lung parenchyma from elastolytic breakdown.
Severe AAT deficiency predisposes to unopposed elastolysis with the clinical sequela of
an early onset of panacinar emphysema. To see complete information on Alpha1Antitrypsin Deficiency, please go to the main article by clicking here.
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. Severe AAT deficiency leads to
premature emphysema at an average age of 53 years for nonsmokers and 40 years for
smokers.
Nearly 24 variants of the AAT molecule have been identified, and all are inherited as
codominant alleles. The common M allele (PiM) may be found in 90% of people, and
homozygous (PiMM) phenotypes produce serum levels within the reference range. The
homozygous PiZZ state is the most common deficiency state and accounts for 95% of
people in the severely deficient category.

5.

Intravenous drug use

Emphysema occurs in approximately 2% of persons who use intravenous (IV) drugs.

This is attributed to pulmonary vascular damage that results from the insoluble filler (eg,
cornstarch, cotton fibers, cellulose, talc) contained in methadone or methylphenidate.
The bullous cysts found in association with IV use of cocaine or heroin occur
predominantly in the upper lobes. In contrast, methadone and methylphenidate injections
are associated with basilar and panacinar emphysema.

6.

Immunodeficiency syndromes

Human immunodeficiency virus (HIV) infection has been found to be an independent

risk factor for COPD, even after controlling for confounding variables such as smoking,
IV drug use, race, and age.[22]
Apical and cortical bullous lung damage occurs in patients who have autoimmune
deficiency syndrome and Pneumocystis carinii infection. Reversible pneumatoceles are
observed in 10-20% of patients with this infection.

7.

Vasculitis syndrome

Hypocomplementemic vasculitis urticaria syndrome (HVUS) may be associated with

obstructive lung disease. Other manifestations include angioedema, nondeforming
arthritis, sinusitis, conjunctivitis, and pericarditis.

8.

Connective tissue disorders

Cutis laxa is a disorder of elastin that is characterized most prominently by the

appearance of premature aging. The disease usually is congenital, with various forms of
inheritance (ie, dominant, recessive). Precocious emphysema has been described in
association with cutis laxa as early as the neonatal period or infancy. The pathogenesis of
this disorder includes a defect in the synthesis of elastin or tropoelastin.
Marfan syndrome is an autosomal dominant inherited disease of type I collagen
characterized by abnormal length of the extremities, subluxation of the lenses, and

cardiovascular abnormality. Pulmonary abnormalities, including emphysema, have been

described in approximately 10% of patients.
Ehlers-Danlos syndrome refers to a group of inherited connective tissue disorders with
manifestations that include hyperextensibility of the skin and joints, easy bruisability, and
pseudotumors; it has also been associated with a higher prevalence of COPD.

9.

Salla disease

Salla disease is an autosomal recessive storage disorder described in Scandinavia; the

disease is characterized by intralysosomal accumulation of sialic acid in various tissues.
The most important clinical manifestations are severe mental retardation, ataxia, and
nystagmus. Precocious emphysema has been described and likely is secondary to
impaired inhibitory activity of serum trypsin.

Classification
There is a discrepancy between the value VEP1 and symptoms of patients , and therefore
need to be considered other conditions . Shortness of breath may not be predicted with
VEP1
Classification of Diseases
Mild

Moderate

Severe

Symptoms
- No symptoms of a break
or when the exercise
- No symptoms of a break
but mild symptoms in
moderate exercise (eg,
walking fast, climbing
stairs)
- No symptoms of a break
but began to be felt in
training/ work light (eg,
dressing)
- Mild symptoms at rest
- Moderate symptoms at
rest
- Severe symptoms at rest
- Signs of cor pulmonal

Spirometry
VEP > 80%
Prediction of VEP/KVP <
75%

VEP 30 - 80%
Prediction VEP/KVP < 75%