eMedicine Specialties > Pulmonology > Obstructive Airways Diseases

Chronic Obstructive Pulmonary Disease

Author: Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St. Boniface General Hospital
Contributor Information and Disclosures

Updated: Jun 14, 2006

Introduction

Background

Chronic obstructive pulmonary disease (COPD) is a devastating disorder that causes a huge degree of human suffering. COPD is currently the fourth leading cause of death in the United States.

In Western Europe, Badham (1808) and Laennec (1827) made the classic description of chronic bronchitis and emphysema in the early 19th century. A British medical textbook of the 1860s described the familiar clinical picture of chronic bronchitis as an advanced disease with repeated bronchial infections that ended in right heart failure. Overall, this malady caused more than 5% of all deaths in the Middle Ages and earlier. The condition was the most common among the poor; therefore, it was attributed to "bad" living.

Developments in the 20th century include the widespread use of spirometry, recognition of airflow obstruction as a key factor in determining disability, and the improvement of pathological methods to assess emphysema. Participants of the Ciba symposium of 1958 proposed definitions of chronic bronchitis and emphysema, incorporating the concept of airflow obstruction.

COPD is defined as a disease state characterized by the presence of airflow obstruction due to chronic bronchitis or emphysema. The airflow obstruction generally is progressive, may be accompanied by airway hyperreactivity, and may be partially reversible. Chronic bronchitis is defined clinically as the presence of a chronic productive cough for 3 months during each of 2 consecutive years (other causes of cough being excluded). Emphysema is defined as an abnormal, permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis. Chronic bronchitis is defined in clinical terms and emphysema in terms of anatomic pathology.

Pathophysiology

Pathological changes in COPD occur in the large (central) airways, the small (peripheral) bronchioles, and the lung parenchyma. The pathogenic mechanisms are not clear but most likely involve diverse mechanisms. The increased number of activated polymorphonuclear leukocytes and macrophages release elastases in a manner that cannot be counteracted effectively by antiproteases, resulting in lung destruction. The primary offender has been human leukocyte elastase, with a possible synergistic role suggested for proteinase 3 and macrophage-derived matrix proteinases, cysteine proteinases, and a plasminogen activator. Additionally, increased oxidative stress caused by free radicals in cigarette smoke, the oxidants released by phagocytes, and polymorphonuclear leukocytes all may lead to apoptosis or necrosis of exposed cells.

Chronic bronchitis

Mucous gland enlargement is the histologic hallmark of chronic bronchitis. The structural changes described in the airways include atrophy, focal squamous metaplasia, ciliary abnormalities, variable amounts of airway smooth muscle hyperplasia, inflammation, and bronchial wall thickening. Neutrophilia develops in the airway lumen, and neutrophilic infiltrates accumulate in the submucosa. The respiratory bronchioles display a mononuclear inflammatory process, lumen occlusion by mucous plugging, goblet cell metaplasia, smooth muscle hyperplasia, and distortion due to fibrosis. These changes, combined with loss of supporting alveolar attachments, cause airflow limitation by allowing airway walls to deform and narrow the airway lumen.

Emphysema

Emphysema has 3 morphologic patterns. The first type, centriacinar emphysema, is characterized by focal destruction limited to the respiratory bronchioles and the central portions of acinus. This form of emphysema is associated with cigarette smoking and is most severe in the upper lobes. The second type, panacinar emphysema, involves the entire alveolus distal to the terminal bronchiole. The panacinar type is most severe in the lower lung zones and generally develops in patients with homozygous alpha1-antitrypsin (AAT) deficiency. The third type, distal acinar emphysema or paraseptal emphysema, is the least common form and involves distal airway structures, alveolar ducts, and sacs. This form of emphysema is localized to fibrous septa or to the pleura and leads to formation of bullae. The apical bullae may cause pneumothorax. Paraseptal emphysema is not associated with airflow obstruction.

Chronic obstructive pulmonary disease

Both emphysematous destruction and small airway inflammation often are found in combination in individual patients. When emphysema is moderate or severe, loss of elastic recoil, rather than bronchiolar disease, is the mechanism of airflow limitation. By contrast, when emphysema is mild, bronchiolar abnormalities are most responsible for the deficit in lung function. Although airflow obstruction in emphysema is virtually irreversible, bronchoconstriction due to inflammation accounts for a limited amount of reversibility.

Role of inflammation in COPD

In contrast to the eosinophil, which is the most prominent inflammatory cell in asthma, the cellular composition of the airway inflammation in COPD is predominantly mediated by the neutrophils. Cigarette smoking induces macrophages to release neutrophil chemotactic factors and elastases, thus unleashing tissue destruction. Severity of airflow obstruction has correlated with greater induced sputum neutrophilia that is also more prevalent in patients with chronic cough and sputum production and is associated with an accelerated decline in lung function.

Macrophages also play an important role through macrophage-derived matrix metalloproteinases (MMPs). Cigarette smoke causes neutrophil influx and is required for the secretion of MMPs, therefore suggesting that both neutrophils and macrophages are required for the development of emphysema. Studies have also shown that T lymphocytes, particularly CD8+, in addition to the macrophages, play an important role in the pathogenesis of smoking-induced airflow limitation. To support the inflammation hypothesis further, a stepwise increase in alveolar inflammation occurs in surgical specimens from patients without COPD versus patients with mild or severe emphysema.

Frequency

United States

Approximately 14.2 million people have COPD, approximately 12.5 million have chronic bronchitis, and 1.7 million have emphysema. Since 1982, the patients diagnosed with COPD increased by 41.5%. Researchers estimate the prevalence of chronic airflow obstruction in the United States as 8-17% for men and 10-19% for women. The prevalence rates increased in women by 30% in the last decade.

International

Worldwide data are sparse, but the rates likely are higher because more than 1.2 billion humans are exposed to the ravages of smoking. A population-based epidemiologic study from Spain determined the prevalence of COPD in individuals aged 40-69 years at 9.1% (78% were men).

Based on pooled data from a number of studies, global prevalence of COPD was 7.5%, chronic bronchitis alone was 6.4%, and emphysema alone was 1.8%. The prevalence from 26 spirometric estimates was 8.9%. The most common spirometric definitions were those of the Global Initiative for Obstructive Lung Disease (GOLD). Thus, the prevalence of physiologically defined COPD in adults aged 40 years and older is approximately 9-10%.

Mortality/Morbidity

Absolute mortality rates for US patients aged 55-84 years (1985) were 200 per 100,000 males and 80 per 100,000 females. Internationally, a marked variation in overall mortality rates from COPD exists. The extremes are the more than 400 deaths per 100,000 males aged 65-74 years in Romania and the fewer than 100 deaths per 100,000 in Japan.

Sex

Researchers estimate that 4-6% of white male adults and 1-3% of white female adults have emphysema or COPD. Men have a higher mortality rate than women, but mortality due to COPD in women is expected to increase.

Clinical

History

Most patients with COPD have smoked at least 20 cigarettes per day for 20 or more years before the onset of the common symptoms of cough, sputum, and dyspnea. Presentation commonly occurs in the fifth decade of life.

• A productive cough or an acute chest illness is common. The cough usually is worse in the mornings and produces a small amount of colorless sputum.
• Breathlessness is the most significant symptom, but it usually does not occur until the sixth decade of life. By the time the forced expiratory volume in 1 second FEV₁ has fallen to 30% of predicted, the patient is breathless after minimal exertion.
• Wheezing may occur in some patients, particularly during exertion and exacerbations.
• With disease progression, intervals between acute exacerbations become shorter; cyanosis and right heart failure may occur. Anorexia and weight loss often develop and suggest a worse prognosis.

Physical

The sensitivity of a physical evaluation for detecting mild-to-moderate COPD is relatively poor; however, the physical signs are quite specific and sensitive for severe disease. Patients with severe disease experience tachypnea and respiratory distress with simple activities.

• The respiratory rate increases proportionally to disease severity. Use of accessory respiratory muscles and paradoxical indrawing of lower intercostal spaces is evident. In advanced disease, cyanosis, elevated jugular venous pulse (JVP), and peripheral edema are observed.
• Measurement of forced expiratory time (FET) maneuver is a simple bedside test; FET of more than 6 seconds indicates considerable expiratory flow obstruction (ie, FEV₁/forced vital capacity (FVC) <50%).
• Thoracic examination reveals hyperinflation (barrel chest), wheezing, diffusely decreased breath sounds, hyperresonance on percussion, and prolonged expiration. Coarse crackles beginning with inspiration may be heard, and wheezes frequently are heard on forced and unforced expiration.

Causes

• Cigarette smoking
  • 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.
  • 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
  • Although the role of air pollution in the etiology of COPD is unclear, the effect is small when compared to cigarette smoking.
  • 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
  • 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.
• Alpha1-antitrypsin deficiency
  • 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.
  • Severe AAT deficiency leads to premature emphysema at the average age of 53 years for nonsmokers and 40 years for smokers.
  • 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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