eMedicine Specialties > Pulmonology > Obstructive Airways Diseases

Chronic Obstructive Pulmonary Disease

Author: Nader Kamangar, MD, FACP, FCCP, FAASM, Associate Professor of Clinical Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Multi-campus Pulmonary and Critical Care Fellowship Program, University of California, Los Angeles, David Geffen School of Medicine; Medical Director, Hospitalist/Intensivist Program, Olive View-UCLA Medical Center; Associate Program Director, Combined Pulmonary and Critical Care Fellowship Program, Cedars-Sinai/Olive View-UCLA Medical Center/West Los Angeles Veterans Affairs Medical Center
Coauthor(s): Nidhi S Nikhanj, MD, Fellow, Department of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles; 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: Feb 19, 2010

Introduction

Background

Chronic obstructive pulmonary disease (COPD) is a disorder that causes a huge degree of human suffering. According to the US Centers for Disease Control and Prevention (CDC), 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-sided 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.

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, on the other hand, is defined pathologically as an abnormal, permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis. Airflow limitation in emphysema is due to loss of elastic recoil and decrease in airway tethering, whereas chronic bronchitis leads to narrowing of airway caliber and increase in airway resistance. Although some patients predominantly display signs of one or the other, most fall somewhere in the middle of the spectrum.

The past definitions of COPD have been pessimistic at best, suggesting that the disease process is irreversible with little therapy to offer. More recently, however, a more optimistic definition has become widely accepted. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines define COPD as a disease state characterized by airflow limitation that is not fully reversible, is usually progressive, and is associated with an abnormal inflammatory response of the lungs to inhaled noxious particles or gases.1 This definition shifts the paradigm of the disease, suggesting that it is both treatable and preventable. For a guideline summary, see Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease.2

Venn diagram of chronic obstructive pulmonary dis...

Venn diagram of chronic obstructive pulmonary disease (COPD). Chronic obstructive lung disease is a disorder in which subsets of patients may have dominant features of chronic bronchitis, emphysema, or asthma. The result is irreversible airflow obstruction.

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Venn diagram of chronic obstructive pulmonary dis...

Venn diagram of chronic obstructive pulmonary disease (COPD). Chronic obstructive lung disease is a disorder in which subsets of patients may have dominant features of chronic bronchitis, emphysema, or asthma. The result is irreversible airflow obstruction.



Additionally, the Medscape COPD Resource Center may be helpful.

Pathophysiology

Pathological changes in chronic obstructive pulmonary disease (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. Accelerated aging and autoimmune mechanisms have also been proposed as having roles in the pathogenesis of COPD.3,4

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, leading to the spectrum that is known as COPD. 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 often irreversible, bronchoconstriction due to inflammation accounts for a limited amount of reversibility.

Furthermore, airflow limitation is not the only pathophysiologic mechanism by which symptoms occur. Lung volumes, particularly dynamic hyperinflation, have also been shown to play a crucial role in the development of dyspnea perceived during exercise. In fact, the improvement in exercise capacity brought about by several treatment modalities, including bronchodilators, oxygen therapy, lung volume reduction surgery (LVRS), and pulmonary rehabilitation, are more likely due to delaying dynamic hyperinflation rather than improving the degree of airflow obstruction.5,6,7,8,9,10,11,12,13 Additionally, hyperinflation (as defined as the ratio of inspiratory capacity to total lung capacity [IC/TLC]) has been shown to predict survival better than forced expiratory volume in 1 second (FEV1 ).14

Role of inflammation in COPD
In contrast to the eosinophil, which is the most prominent inflammatory cell in persons with 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.

Indeed, mounting evidence supports that the dysregulation of apoptosis and defective clearance of apoptotic cells by macrophages play a prominent role in airway inflammation, particularly in emphysema.15 Azithromycin has been shown to improve this macrophage function, providing yet another possible modality of treatment in the future.16

Chronic obstructive pulmonary disease (COPD). Gro...

Chronic obstructive pulmonary disease (COPD). Gross pathology of advanced emphysema. Large bullae are present on the surface of the lung.

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Chronic obstructive pulmonary disease (COPD). Gro...

Chronic obstructive pulmonary disease (COPD). Gross pathology of advanced emphysema. Large bullae are present on the surface of the lung.



Chronic obstructive pulmonary disease (COPD). Gro...

Chronic obstructive pulmonary disease (COPD). Gross pathology of a patient with emphysema showing bullae on the surface.

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Chronic obstructive pulmonary disease (COPD). Gro...

Chronic obstructive pulmonary disease (COPD). Gross pathology of a patient with emphysema showing bullae on the surface.

Frequency

United States

The exact prevalence of COPD in the United States, as in the rest of the world, is unknown. This is largely due to the fact that it is an underdiagnosed (and undertreated) disease. The most recent study estimates a prevalence of 10.1% in the United States.17

International

The exact prevalence worldwide is largely unknown, but estimates have varied from 7-19%. The most recent study suggests a global prevalence of 10.1% (the same as in the United States alone).18 Men were found to have a prevalence of 11.8% and women 8.5%. The numbers vary in different regions of the world. Capetown, South Africa has the highest prevalence, affecting 22.2% of men and 16.7% of women. Hannover, Germany, on the other hand, has the lowest prevalence of 8.6% for men and 3.7% for women.

As noted above, whatever estimates are reported are widely believed to be underestimates because COPD is known to be an underdiagnosed and undertreated disease. Additionally, the prevalence in women is believed to be increasing.

Mortality/Morbidity

Absolute mortality rates for US patients aged 55-84 years (1985) were 200 deaths per 100,000 males and 80 deaths per 100,000 females. Internationally, a marked variation exists in overall mortality rates from COPD. 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 population in Japan.

COPD is the fourth leading cause of death in the United States.

Sex

Although currently the rates in men are higher than the rates in women, the rates in women have been increasing.

Clinical

History

Most patients with chronic obstructive pulmonary disease (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 (although it may occur much earlier). By the time the FEV1 has fallen to 30% of predicted, the patient is usually breathless after minimal exertion. In fact, the FEV1 is the most common variable used to grade the severity of COPD, although it is not the best predictor of mortality (see Staging).
  • Wheezing may occur in some patients, particularly during exertion and exacerbations.
  • With disease progression, intervals between acute exacerbations become shorter, and each exacerbation may be more severe.
  • COPD is now known to be a disease with systemic manifestations, and the quantification of these manifestations has proved to be a better predictor of mortality than lung function alone. Many patients with COPD may have decreased fat-free mass, impaired systemic muscle function, osteoporosis, anemia, depression, pulmonary hypertension, cor pulmonale, and even left-sided heart failure (see Staging).

Physical

The sensitivity of a physical evaluation for detecting mild-to-moderate chronic obstructive pulmonary disease (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 (known as the Hoover sign). In advanced disease, cyanosis, elevated jugular venous pulse (JVP), and peripheral edema are observed.
  • Measurement of forced expiratory time maneuver is a simple bedside test; a forced expiratory time of more than 6 seconds indicates considerable expiratory flow obstruction. Bedside spirometry is another test that can be used, which can actually help quantify the severity of obstruction by virtue of the FEV1 .
  • 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 chronic obstructive pulmonary disease (COPD) is exposure to tobacco smoke. 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 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 with 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. This may contribute to airway remodeling, leading to a more fixed obstruction as is seen in persons with COPD.
  • 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.

More on Chronic Obstructive Pulmonary Disease

Overview: Chronic Obstructive Pulmonary Disease
Differential Diagnoses & Workup: Chronic Obstructive Pulmonary Disease
Treatment & Medication: Chronic Obstructive Pulmonary Disease
Follow-up: Chronic Obstructive Pulmonary Disease
Multimedia: Chronic Obstructive Pulmonary Disease
References
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Further Reading

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Keywords

chronic obstructive pulmonary disease, COPD, chronic bronchitis, emphysema, chronic obstructive airway disease, COAD, airflow obstruction, centriacinar emphysema, panacinar emphysema, distal acinar emphysema, paraseptal emphysema

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Contributor Information and Disclosures

Author

Nader Kamangar, MD, FACP, FCCP, FAASM, Associate Professor of Clinical Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Multi-campus Pulmonary and Critical Care Fellowship Program, University of California, Los Angeles, David Geffen School of Medicine; Medical Director, Hospitalist/Intensivist Program, Olive View-UCLA Medical Center; Associate Program Director, Combined Pulmonary and Critical Care Fellowship Program, Cedars-Sinai/Olive View-UCLA Medical Center/West Los Angeles Veterans Affairs Medical Center
Nader Kamangar, MD, FACP, FCCP, FAASM is a member of the following medical societies: American Academy of Sleep Medicine, American Association of Bronchology, American College of Chest Physicians, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, California Thoracic Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Nidhi S Nikhanj, MD, Fellow, Department of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles
Nidhi S Nikhanj, MD is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

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
Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Ryland P Byrd Jr, MD, Professor, Department of Internal Medicine, Division of Pulmonary Medicine and Critical Care Medicine, Program Director of Pulmonary Diseases and Critical Care Medicine Fellowship, James H Quillen College of Medicine, East Tennessee State University; Medical Director of Respiratory Therapy, James H Quillen Veterans Affairs Medical Center
Ryland P Byrd Jr, MD is a member of the following medical societies: American College of Chest Physicians and American Thoracic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Gregg T Anders, DO, Medical Director, Great Plains Regional Medical Command , Brooke Army Medical Center; Clinical Associate Professor, Department of Internal Medicine, Division of Pulmonary Disease, University of Texas Health Science Center at San Antonio
Gregg T Anders, DO is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

 
 
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