eMedicine Specialties > Pulmonology > Obstructive Airways Diseases

Chronic Obstructive Pulmonary Disease: Differential Diagnoses & Workup

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: Oct 26, 2009

Differential Diagnoses

Alpha1-Antitrypsin Deficiency
Pneumonia, Bacterial
Asthma
Pneumonia, Community-Acquired
Bronchiectasis
Pneumonia, Viral
Bronchitis
Pneumothorax
Chronic Bronchitis
Pulmonary Embolism
Cyanosis
Pulmonary Fibrosis, Idiopathic
Diaphragmatic Paralysis
Pulmonary Fibrosis, Interstitial (Nonidiopathic)
Emphysema
Respiratory Failure
Farmer's Lung
Restrictive Lung Disease
Hypersensitivity Pneumonitis
Tracheomalacia
Injecting Drug Use
Ventilation, Mechanical
Nicotine Addiction
Ventilation, Noninvasive
Perioperative Pulmonary Management

Other Problems to Be Considered

  • Congestive heart failure is differentiated by the presence of fine basal crackles, by findings on chest radiographs, and by nonobstructed pulmonary function test (PFT) results.
  • In bronchiectasis, patients produce a large amount of purulent sputum, coarse crackles are present, and clubbing occurs; abnormalities appear on chest radiographs.
  • Bronchiolitis obliterans affects younger people with rheumatoid arthritis or with certain fume exposures (but is not associated with cigarette smoke); CT scans may show areas of mosaic perfusion.
  • Chronic asthma is difficult to distinguish in older patients; the important distinction is a large bronchodilator response. Chronic airway inflammation as seen in asthma may lead to airway remodeling and a more fixed obstruction as seen in COPD.

Workup

Laboratory Studies

Secondary polycythemia due to chronic hypoxemia may develop in persons with severe chronic obstructive pulmonary disease (COPD) or in those patients who smoke excessively. A hematocrit value of more than 52% in males and more than 47% in female indicates disease.

Measure the alpha1-antitrypsin (AAT) levels in all patients younger than 40 years or in those with a family history of emphysema at an early age. If the AAT level is low, then phenotyping should be performed.

  • Sputum
    • In persons with stable chronic bronchitis, sputum is mucoid and macrophages are the predominant cell. With an exacerbation, sputum becomes purulent because of the presence of neutrophils. A mixture of organisms often is visible after a Gram stain.
    • The pathogens most frequently cultured during exacerbations are Streptococcus pneumoniae and Haemophilus influenzae. Moraxella catarrhalis is also a common organism, and Pseudomonas aeruginosa can be seen in patients with severe obstruction.

Imaging Studies

  • Chest radiography
    • Frontal and lateral chest radiographs reveal signs of hyperinflation, including a flattening of the diaphragm, increased retrosternal air space, and a long narrow heart shadow. Rapid-tapering vascular shadows accompanied by hyperlucency of the lungs are signs of emphysema.
    • With complicating pulmonary hypertension, the hilar vascular shadows are prominent, with possible right ventricular enlargement and opacity in the lower retrosternal air space.

Posteroanterior (PA) and lateral chest radiograph...

Posteroanterior (PA) and lateral chest radiograph in a patient with severe chronic obstructive pulmonary disease (COPD). Hyperinflation, depressed diaphragms, increased retrosternal space, and hypovascularity of lung parenchyma is demonstrated.

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Posteroanterior (PA) and lateral chest radiograph...

Posteroanterior (PA) and lateral chest radiograph in a patient with severe chronic obstructive pulmonary disease (COPD). Hyperinflation, depressed diaphragms, increased retrosternal space, and hypovascularity of lung parenchyma is demonstrated.



Chronic obstructive pulmonary disease (COPD). A l...

Chronic obstructive pulmonary disease (COPD). A lung with emphysema shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on lateral chest radiograph.

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Chronic obstructive pulmonary disease (COPD). A l...

Chronic obstructive pulmonary disease (COPD). A lung with emphysema shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on lateral chest radiograph.



Chronic obstructive pulmonary disease (COPD). A l...

Chronic obstructive pulmonary disease (COPD). A lung with emphysema shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on posteroanterior chest radiograph.

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Chronic obstructive pulmonary disease (COPD). A l...

Chronic obstructive pulmonary disease (COPD). A lung with emphysema shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on posteroanterior chest radiograph.

 
  • Computed tomography scanning
    • High-resolution CT (HRCT) scanning is more sensitive than standard chest radiography.
    • HRCT scanning is highly specific for diagnosing emphysema, and the outlined bullae are not always visible on a radiograph. HRCT scanning may provide an adjunct to diagnosing various forms of COPD (ie, lower lobe disease may suggest AAT deficiency) and may help determine if surgical intervention would be of benefit to the patient.

Chronic obstructive pulmonary disease (COPD). A C...

Chronic obstructive pulmonary disease (COPD). A CT scan shows hyperlucency due to hypovascularity and bullae formation diffusely, predominantly in upper lobes.

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Chronic obstructive pulmonary disease (COPD). A C...

Chronic obstructive pulmonary disease (COPD). A CT scan shows hyperlucency due to hypovascularity and bullae formation diffusely, predominantly in upper lobes.



Severe bullous disease observed on CT scan in a p...

Severe bullous disease observed on CT scan in a patient with chronic obstructive pulmonary disease (COPD).

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Severe bullous disease observed on CT scan in a p...

Severe bullous disease observed on CT scan in a patient with chronic obstructive pulmonary disease (COPD).


  • Two-dimensional echocardiography
    • Many patients with long-standing COPD develop secondary pulmonary hypertension from chronic hypoxemia and vascular remodeling. This may result in eventual right-sided heart failure (cor pulmonale).
    • Two-dimensional echocardiography may be helpful as a screening tool to estimate pulmonary arterial systolic pressure and right ventricular systolic function.

Other Tests

  • Pulmonary function tests
    • These measurements are essential for the diagnosis and assessment of the severity of disease, and they are helpful in following its progress.
    • Forced expiratory volume in 1 second (FEV1) is a reproducible test and is the most commonly used index of airflow obstruction.
    • Lung volume measurements  often show an increase in total lung capacity, functional residual capacity, and residual volume. The vital capacity often decreases. Dynamic hyperinflation during exercise is now thought be a greater contributor to the sensation of dyspnea than airflow obstruction alone (as measured by FEV1).
    • Carbon monoxide diffusing capacity is decreased in proportion to the severity of emphysema.
    • Arterial blood gas analysis reveals mild-to-moderate hypoxemia without hypercapnia in the early stages. As the disease progresses, hypoxemia becomes more severe and hypercapnia supervenes. Hypercapnia commonly is observed as the FEV1 falls below 1 L/s or 30% of the predicted value. The lung mechanics and gas exchange worsen during acute exacerbations.
    • As many as 30% of patients have an increase in FEV1 by 15% or more after inhalation of a bronchodilator. However, the absence of bronchodilator response does not justify withholding therapy.

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

Chronic obstructive pulmonary disease (COPD). Pressure volume curve comparing lungs with emphysema lungs and restrictive lungs to normal lungs.

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

Chronic obstructive pulmonary disease (COPD). Pressure volume curve comparing lungs with emphysema lungs and restrictive lungs to normal lungs.



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

Chronic obstructive pulmonary disease (COPD). Flow volume curve of lungs in emphysema shows marked decrease in expiratory flows, hyperinflation, and air trapping (patient B) compared to a patient with restrictive lung disease, who has reduced lung volumes and preserved flows (patient A).

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

Chronic obstructive pulmonary disease (COPD). Flow volume curve of lungs in emphysema shows marked decrease in expiratory flows, hyperinflation, and air trapping (patient B) compared to a patient with restrictive lung disease, who has reduced lung volumes and preserved flows (patient A).



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

Chronic obstructive pulmonary disease (COPD). Forced expiratory volume in 1 second (FEV1) can be used to evaluate the prognosis in patients with emphysema. The benefit of smoking cessation is shown here because the deterioration in lung function parallels that of a nonsmoker, even in late stages of the disease. Redrawn from Fletcher C, Peato R. The natural history of chronic airflow obstruction. Br Med J 1977; 1: 1645-1648.

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

Chronic obstructive pulmonary disease (COPD). Forced expiratory volume in 1 second (FEV1) can be used to evaluate the prognosis in patients with emphysema. The benefit of smoking cessation is shown here because the deterioration in lung function parallels that of a nonsmoker, even in late stages of the disease. Redrawn from Fletcher C, Peato R. The natural history of chronic airflow obstruction. Br Med J 1977; 1: 1645-1648.

  
  • Six-minute walking distance
    • The distance walked in 6 minutes is a good predictor of all-cause and respiratory mortality in patients with moderate COPD.13,19
    • Patients with COPD who desaturate during the 6-minute walking distance (6MWD) have a higher mortality rate than those who do not desaturate.
    • Consequently, this test is used as a part of the multidimensional BODE index (body mass index, obstruction [FEV1], dyspnea [ie, Medical Research Council Dyspnea Scale], and exercise capacity [ie, 6MWD]) designed to help predict mortality in COPD patients (see Staging).

Procedures

  • Right-sided heart catheterization: If pulmonary hypertension is suggested based on the clinical examination findings or on estimates from a 2-dimensional echocardiogram, then a right-sided heart catheterization may be preformed to directly measure the pulmonary artery pressures and their responsiveness to vasodilators.

Histologic Findings


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

Chronic obstructive pulmonary disease (COPD). Histopathology of chronic bronchitis showing hyperplasia of mucous glands and infiltration of the airway wall with inflammatory cells.

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

Chronic obstructive pulmonary disease (COPD). Histopathology of chronic bronchitis showing hyperplasia of mucous glands and infiltration of the airway wall with inflammatory cells.



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

Chronic obstructive pulmonary disease (COPD). Histopathology of chronic bronchitis showing hyperplasia of mucous glands and infiltration of the airway wall with inflammatory cells (high-powered view).

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

Chronic obstructive pulmonary disease (COPD). Histopathology of chronic bronchitis showing hyperplasia of mucous glands and infiltration of the airway wall with inflammatory cells (high-powered view).



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

Chronic obstructive pulmonary disease (COPD). At high magnification, in emphysema, loss of alveolar walls and dilatation of airspaces occurs.

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

Chronic obstructive pulmonary disease (COPD). At high magnification, in emphysema, loss of alveolar walls and dilatation of airspaces occurs.

Staging

Until recently, the severity of airflow obstruction has been the mainstay of staging chronic obstructive pulmonary disease (COPD). The American Thoracic Society (ATS) has provided criteria for staging COPD based on the presence of obstruction (ratio of FEV1 to forced vital capacity [FEV1/FVC] <70%) and its severity as measured by percent of predicted FEV1. The GOLD guidelines have taken staging one step further by incorporating the presence or absence of signs/symptoms in its most severe stage. Furthermore, they have provided guidelines for therapy based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. These staging systems, however, have limited utility in trying to predict mortality.

For a guideline summary, see Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonarydisease.2

The recognition that COPD is a systemic disease has helped develop criteria that are better at predicting mortality than airway obstruction alone. The most widely used staging system in this regard is the BODE index. The multidimensional nature of this index helps physicians determine a more comprehensive assessment of the severity of disease.

  • ATS criteria for assessing the severity of airflow obstruction (based on the percent predicted postbronchodilator FEV1 when the FEV1/FVC is <70%)
    • Stage I (mild) - FEV1 greater than or equal to 80% of predicted.
    • Stage II (moderate) - FEV1 less than 80% and greater than or equal to 50% of predicted
    • Stage III (severe) - FEV1 less than 50% and greater than or equal to 30% of predicted
    • Stage IV (very severe) - FEV1 less than 30% of predicted or FEV1 less than 50% and chronic respiratory failure
  • GOLD guidelines
    • Stage I (mild obstruction) - Reduction of risk factors (influenza vaccine) plus short-acting bronchodilator as needed
    • Stage II (moderate obstruction) - Reduction of risk factors (influenza vaccine) plus short-acting bronchodilator as needed plus long-acting bronchodilator(s) plus cardiopulmonary rehabilitation
    • Stage III (severe obstruction) - Reduction of risk factors (influenza vaccine) plus short-acting bronchodilator as needed plus long-acting bronchodilator(s) plus cardiopulmonary rehabilitation plus inhaled glucocorticoids if repeated exacerbations
    • Stage IV (very severe obstruction or moderate obstruction with evidence of chronic respiratory failure) - Reduction of risk factors (influenza vaccine) plus short-acting bronchodilator as needed plus long-acting bronchodilator(s) plus cardiopulmonary rehabilitation plus inhaled glucocorticoids if repeated exacerbations plus long-term oxygen therapy (if criteria met); also consider surgical options
  • BODE index
    • Body mass index
      • Greater than 21 = 0 points
      • Less than 21 = 1 point
    • FEV1 (postbronchodilator percent predicted)
      • Greater than 65% = 0 points
      • 50-64% = 1 point
      • 36-49% = 2 points
      • Less than 35% = 3 points
    • MMRC dyspnea scale
      • MMRC 0 = Dyspneic on strenuous exercise (0 points)
      • MMRC 1 = Dyspneic on walking a slight hill (0 points)
      • MMRC 2 = Dyspneic on walking level ground; must stop occasionally due to breathlessness (1 point)
      • MMRC 3 = Dyspneic after walking 100 yards or a few minutes (2 points)
      • MMRC 4 = Cannot leave house; dyspneic doing activities of daily living (3 points)
    • Six-minute walking distance
      • Greater than 350 meters = 0 points
      • 250-349 meters = 1 point
      • 150-249 meters = 2 points
      • Less than 149 meters = 3 points
    • Approximate 4-year survival
      • 0-2 points = 80%
      • 3-4 points = 67%
      • 5-6 points = 57%
      • 7-10 points = 18%
The Medscape COPD Resource Center may be helpful.

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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