Chronic Obstructive Pulmonary Disease: Diagnostic Considerations MARVIN DEWAR, M.D., J.D., and R. WHIT CURRY, JR., M.D. University of Florida College of Medicine, Gainesville, Florida
Chronic obstructive pulmonary disease is characterized by the gradual progression of irrevers- ible airflow obstruction and increased inflammation in the airways and lung parenchyma that is generally distinguishable from the inflammation caused by asthma. Most chronic obstructive pulmonary disease is associated with smoking, but occupational exposure to irritants and air pollution also are important risk factors. Patients with chronic obstructive pulmonary disease typically present with coughing, sputum production, and dyspnea on exertion. However, none of these findings alone is diagnostic. The Global Initiative for Chronic Obstructive Lung Disease diagnostic criterion for chronic obstructive pulmonary disease is a forced expiratory volume in one second/forced vital capacity ratio of less than 70 percent of the predicted value. Severity is further stratified based on forced expiratory volume in one second and symptoms. Chest radiog- raphy may rule out alternative diagnoses and comorbid conditions. Selected patients should be tested for G1-antitrypsin deficiency. Arterial blood gas testing is recommended for patients pre- senting with signs of severe disease, right-sided heart failure, or significant hypoxemia. Chronic obstructive pulmonary disease also is a systemic disorder with weight loss and dysfunction of respiratory and skeletal muscles. (Am Fam Physician 2006;73:669-76, 677-8. Copyright © 2006 American Academy of Family Physicians.) S Patient Information: he global burden of chronic limitation that is not fully reversible and A handout on chronic obstructive pulmonary disease that is associated with an abnormal inflam- obstructive pulmonary disease, written by the (COPD) is increasing; the disease matory response of the lungs to noxious authors of this article, is is projected to be the third leading particles or gases. provided on page 677. causeT of death and fifth leading cause of over- Patients with COPD present with a
S 1 See related editorial all disability worldwide by 2020. Men and variety of clinical findings, including ele- on page 590. women seem to be at an equal risk, and the ments of chronic bronchitis and emphy- death rate attributable to COPD is increasing sema.6-8 Although COPD and asthma are significantly in both sexes.1,2 The economic both associated with airflow obstruction consequences of COPD are substantial. In and inflammation of the lung and airways, 2002, the estimated total societal cost of asthma-related airflow obstruction is more COPD in the United States was $32 billion.2 reversible and the disease course is more variable than with COPD.6,8,9 Definition COPD is a heterogeneous disorder that Risk Factors encompasses traditional clinical entities such Exposure to tobacco smoke is the most as emphysema and chronic bronchitis.3,4 significant risk factor for COPD, with 80 to The Global Initiative for Chronic Obstruc- 90 percent of all cases attributable to smok- tive Lung Disease (GOLD),5 a ing.6 Evidence linking tobacco smoke expo- collaborative effort from the sure and COPD predominantly comes from Smokingcessationcangive National Heart, Lung, and population-based studies that have consis- a former smoker the Blood Institute; the National tently shown that smoking is associated with same average ongoing Institutes of Health; and the diminished lung function, more frequent loss of lung function as World Health Organization, respiratory symptoms, and increased COPD- a never-smoker. defines COPD as a usually pro- related deaths.5,10-13 Pipe and cigar smoking gressive disease with airflow are associated with increased COPD risk,
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Evidence Clinical recommendation rating References
Spirometry should be used as the first-line diagnostic tool when C 5, 6
evaluating patients for COPD. A FEV1/FVC ratio of less than 70 percent of the predicted value suggests COPD. Patients with suspected COPD should receive chest radiography C6, 31 to exclude other diagnoses and comorbidities.
G1-Antitrypsin deficiency testing should be performed in select C15 patients (e.g., COPD in never-smokers, idiopathic cirrhosis,
family history of G1-antitrypsin deficiency, predominantly lower lung emphysema, “premature” COPD, and refractory asthma at a young age). ABG testing should be performed if the patient presents with C 5 right-sided heart failure or has more severe COPD.
COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in one second; FVC = forced vital capacity; ABG = arterial blood gas. A = consistent, good-quality, patient-oriented evidence; B = inconsistent or limited-quality, patient-oriented evi- dence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 573 or http://www.AAFP.org/afpsort.xml.
but at a lesser rate than with cigarette smok- fuels, commonly used for indoor cooking ing.5,6 Although cigarette smoking is a sig- and heating, is a risk factor for COPD, par- nificant risk factor for COPD, only about ticularly in the developing world.5,6,9,19,20 20 percent of cigarette smokers develop clinically significant COPD.6,8,13 Natural History The second most significant documented Patients with COPD may present with loss risk factor for COPD is G1-antitrypsin defi- of lung function beyond normal age-related ciency. Although G1-antitrypsin deficiency decreases. Clinical disease develops fairly increases the risks associated with smok- late in the disease course, after lung function ing, COPD can develop in never-smokers drops below threshold values. with G1-antitrypsin deficiency. One percent After 25 years of age, a nonsmoking adult’s of COPD cases are attributable to severe forced expiratory volume in one second 5,6,14,15 G1-antitrypsin deficiency. (FEV1) decreases by an average of 20 to 40 mL Certain occupational exposures are per year. In some smokers, FEV1 decreases by associated with increased risk of COPD two to five times this amount, making them (Table 116-18). Exposure to solid biomass particularly susceptible to COPD.6,8,12,13,21,22 Smoking cessation may cause slight initial improvement in FEV1 (approximately 50 mL TABLE 1 in the first year).21 More importantly, smok- Occupational Irritants That ing cessation can give a former smoker the IncreasetheRiskofCOPD same average ongoing loss of lung function as a never-smoker.13,21 Figure 113,21 illustrates Occupation Irritant the progressive loss of lung function in a Agricultural worker Endotoxin variety of settings. Coal miner Coal dust Patients with COPD usually have a smok- Concrete worker Mineral dust ing history of at least 20 pack-years. Wheez- Construction worker Dust ing and dyspnea on exertion generally occur Gold miner Silica when the FEV1 is less than 50 percent of the Hard rock miner Mineral dust predicted value, and significant physical Rubber worker Industrial chemicals disability usually occurs when the FEV1 is less than 35 to 40 percent of the predicted COPD = chronic obstructive pulmonary disease. value.4,22,23 Patients who started smoking in Information from references 16 through 18. their 20s and have already sustained appre- ciable FEV1 loss by their 40s are likely to
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develop significant COPD if they continue matous changes are most prominent in the to smoke. Those in their mid-40s who have upper lung fields. Loss of the structural sup- normal FEV1 values, however, probably will ports that keep the airways open allows the not develop symptomatic disease.13 bronchioles to collapse during expiration; the resulting nonfunctioning alveolar units Pathophysiology reduce the amount of lung area available for COPD involves a chronic inflammatory pro- gas exchange.4-6,24 cess, primarily in the peripheral airways and Patients with COPD have high neutro- the lung parenchyma. Airway irritation causes phil, macrophage, and CD8+ T-lymphocyte mucous gland enlargement, hypersecretion, counts in the airways and lung parenchyma. ciliary dysfunction, and squamous metaplasia These cells release inflammatory cytokines early in the disease course. An ongoing cycle and proteases that cause an imbalance of the of inflammation and repair ultimately nar- pro-inflammatory and protective mediators rows the airway lumen and obstructs air- found in healthy lungs.5,8,20,25 flow. Patients with emphysema experience destruction of the structural constituents Diagnosis of the alveolar walls, causing permanent Common differential diagnosis of COPD enlargement of the air spaces distal to the ter- includes asthma, heart failure, bronchiecta- minal bronchioles. In early COPD, emphyse- sis, bronchiolitis obliterans, cystic fibrosis,
Lung Function Decline in Smokers and Nonsmokers
Average nonsmoker 4
Severely susceptible smoker who stops smoking at 40 years 3 of age (L) 1 Clinical symptoms develop
FEV 2 Susceptible smoker Severely susceptible smoker
Severe disability 1
0 25 45 65 85 Age (years)
Figure 1. The natural history of lung function decline. Smokers who are susceptible to lung injury experience an increase in the rate of age-related loss in FEV1 compared with nonsmokers (red, green, and blue lines). After lung function declines to threshold levels, clinical symptoms develop (black dotted lines). When a smoker stops smoking, the rate of FEV1 loss again approximates to that of a nonsmoker (blue dotted line). (FEV1 = forced expiratory volume in one second.)
Information from references 13 and 21.
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and tuberculosis (Table 2). Clinical history; failure, in whom orthopnea typically occurs physical examination; and diagnostic test- hours after reclining, when fluid mobilizes ing, such as lung function measurements, from the lower extremities. COPD-associ- can help diagnose COPD. Chest radiogra- ated hemoptysis often is caused by airway phy may rule out alternative diagnoses and mucosal erosion from coughing, but a coex- comorbid conditions. isting cancer or underlying infection (e.g., tuberculosis) should be considered. Severe CLINICAL HISTORY nocturnal hypoxia or hypercapnia should be Patients with COPD typically present with considered if a patient with COPD presents cough, sputum production, and dyspnea with a persistent morning headache. on exertion. A COPD diagnosis is likely if a patient with a significant history of tobacco PHYSICAL EXAMINATION smoke exposure has these symptoms. Patients Patients with COPD often present with with COPD also may experience orthopnea diminished breath sounds, prolonged expi- soon after reclining, unlike patients with heart ratory time, and expiratory wheezing that
TABLE 2 COPD and Common Differential Diagnosis
Diagnosis Characteristics Clinical presentation Pulmonary function test findings
COPD Midlife to late-life onset; steadily Chronic productive cough, Predominantly fixed airflow progressive with exacerbations; dyspnea, and wheezing obstruction, decreased DLCO associated with smoking history
Asthma Usually early-life onset; episodic; Episodic wheezing, cough, Predominantly reversible airflow associated with other allergic disorders and dyspnea obstruction, normal DLCO and family history
Bronchiectasis Usually midlife onset; progressive with Productive cough with thick, Obstructive airflow limitation, exacerbations purulent sputum; dypsnea; both fixed and reversible and wheezing
Bronchiolitis Onset at any age; may be associated Often subacute presentation Decreased vital capacity, obliterans with history of flu-like illness, collagen with dyspnea, cough, and decreased DLCO, usually no vascular disease, or toxic exposure fever obstructive component
Congestive Midlife to late-life onset; associated with Fatigue, exertional and Decreased DLCO, predominantly heart failure risk factors such as hypertension and paroxysmal nocturnal used to exclude other diagnoses coronary artery disease dyspnea, and peripheral edema
Tuberculosis Onset at any age; associated with history Productive cough, hemoptysis, Not used for diagnosis of exposure fever, and weight loss
Cystic fibrosis Usually early-life onset; progressive with Predictive cough with purulent Predominantly fixed airflow exacerbations; associated with pancreatic sputum, dyspnea, and obstruction disease, failure to thrive, intestinal wheezing obstruction, cirrhosis, and steatorrhea
COPD = chronic obstructive pulmonary disease; DLCO = carbon monoxide diffusion in the lung; ABG = arterial blood gas; CT = computed tomography; ESR = erythrocyte sedimentation rate; BNP = brain natriuretic peptide; AFB = acid-fast bacillus.
672 American Family Physician www.aafp.org/afp Volume 73, Number 4 U February 15, 2006 COPD TABLE 3 Signs and Symptoms to Predict Airflow Limitation in Selected Patients with Suspected COPD*
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initially may occur only on forced expiration. Additional findings on physical examina- tion include hyperinflation of the lungs with an increased anteroposterior chest diameter Chest radiography Other recommended (“barrel chest”); use of accessory muscles of findings testing respiration; and distant heart sounds, some-
Hyperinflation, G1-Antitrypsin testing, times best heard in the epigastrium. Patients increased basilar ABG testing, and with more advanced disease may have pursed markings, bronchial chest CT in selected lip breathing or postures that relieve dyspnea thickening patients (e.g., leaning forward against outstretched Normal between Allergy testing, peak- palms). The presence of significant edema episodes flow monitoring may indicate right-sided heart failure and cor pulmonale in patients with pulmonary hyper- Focal pneumonia, Bacterial, microbacterial, tension from severe long-standing COPD. atelectasis; dilated, and fungal sputum The literature on the effectiveness of thickened airways culture, chest CT specific components of the patient history (ring shadow) and physical examination as predictors Multifocal, bilateral ESR, high-resolution of obstructive airway disease is of limited alveolar infiltrates CT, lung biopsy value. A history of COPD and a significant smoking history generally are strong predic- Increased heart size, Echocardiography, tors of airway obstruction, and the clinical pulmonary vascular BNP measurement, likelihood of COPD is greater when mul- congestion, pleural electrocardiography; tiple symptoms or signs suggesting COPD effusions cardiac catheterization are present.24-28 Table 324 lists the predictive in selected patients values of common physical symptoms and Infiltrate, nodular Sputum AFB culture signs for detecting airflow obstruction. lesions, hilar adenopathy DIAGNOSTIC TESTING
Bronchiectasis Sweat chloride test The best diagnostic test for evaluating patients frequent in upper (diagnostic), with suspected COPD is lung function mea- lobes Bacterial sputum sured with spirometry. The GOLD guidelines5 culture characterize the severity of COPD according to clinical and spirometric measures (Table 45). Key spirometric measures may be obtained with a portable office spirometer and should
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include forced vital capacity (FVC) and FEV1. total lung capacity, functional residual capac- Patients with COPD typically present with ity, and residual volume. A substantial loss obstructive airflow. According to the GOLD of lung surface area available for effective criteria, a FEV1/FVC ratio of less than 70 per- oxygen exchange causes diminished carbon cent in a patient with a postbronchodilator monoxide diffusion in the lung (DLCO) FEV1 of less than 80 percent of the predicted in patients with emphysema. This finding value is diagnostic for COPD.5 Severity is fur- may help distinguish COPD from asthma, ther stratified based on symptoms and FEV1 because patients with asthma typically have values. A patient with severe disease has a normal DLCO values.5,6,30 FEV1 of less than 50 percent of the predicted Chest radiography usually is abnormal in value; values below 30 percent of the pre- patients with severe COPD but may not show dicted value represent very severe disease.5,6,29 changes in up to one half of patients with Although some experts have proposed peri- moderate disease.6,31 Chest radiography in odic FEV1 testing for high-risk patients older patients with COPD may show hyperinfla- than 45 years to facilitate risk factor reduction tion of the lungs, flattening of the domes of counseling, no evidence exists to support this the diaphragm, and tapering of the pulmo- recommendation.22 nary vessels as they move to the periphery of Beyond office spirometry, complete pul- the lung fields. Increased basilar markings monary function testing may show increased (“dirty lungs”) sometimes are visible on chest radiographs in patients with chronic bronchitis, and isolated bullae may be seen TABLE 4 in patients with emphysema. A computed GOLD Staging System for COPD Severity tomography (CT) scan of the chest should not be used routinely to diagnose COPD, Stage Description Findings* but it may show findings that are highly 0 At risk Risk factors and chronic symptoms but normal correlated with the degree of COPD changes spirometry found on pathologic examination.31 I Mild FEV1/FVC ratio less than 70 percent Testing for G1-antitrypsin deficiency FEV1 at least 80 percent of predicted value is appropriate in selected patients; testing May have symptoms involves measuring circulating G1-anti- II Moderate FEV1/FVC ratio less than 70 percent trypsin levels followed by phenotype testing FEV1 50 percent to less than 80 percent if levels are abnormal. Patients with severe of predicted value G1-antitrypsin deficiency usually are of Euro- May have chronic symptoms pean descent and develop clinical evidence III Severe FEV1/FVC ratio less than 70 percent of COPD approximately 10 years earlier than FEV1 30 percent to less than 50 percent 6 patients who are not G1-antitrypsin deficient. of predicted value Lung changes associated with severe G1-anti- May have chronic symptoms trypsin deficiency usually include lower lung IV Very severe FEV1/FVC ratio less than 70 percent field predilection. G1-Antitrypsin deficiency FEV1 less than 30 percent of predicted value also may cause otherwise unexplained cirrho- or sis of the liver.6,14,15,19 Clinical circumstances FEV1 less than 50 percent of predicted value in which testing for -antitrypsin deficiency plus severe chronic symptoms G1 should be considered include COPD in never- GOLD = Global Initiative for Chronic Obstructive Lung Disease; COPD = chronic smokers, idiopathic cirrhosis, family history obstructive pulmonary disease; FEV = forced expiratory volume in one second; 1 of G1-antitrypsin deficiency, predominantly FVC = forced vital capacity. lower lung emphysema, “premature” COPD, *—Classifications based on postbronchodilator FEV1. and refractory asthma at a young age.6,15 Adapted from Global Initiative for Chronic Obstructive Lung Disease. Global strategy Arterial blood gas measurement is recom- for the diagnosis, management, and prevention of chronic obstructive pulmonary disease [executive summary]. Updated 2005. Accessed online January 17, 2006, at: mended to rule out significant hypox- http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=996. emia (partial pressure of oxygen less than 60 mm Hg) or hypercapnia in patients with
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more severe disease. This is based on FEV1 components. Weight loss in patients with (less than 40 percent of predicted value), COPD may be related to increased circulating signs of right-sided heart failure, and signs levels of inflammatory mediators (e.g., tumor of hypoxemia.5 necrosis factor alpha, inflammatory cyto- kines). Pulmonary cachexia associated with Clinical Subtypes severe COPD also causes profound weight Patients with COPD also may be grouped loss, which is a predictor of increased mortality into clinical subtypes based on clinical find- risk independent of lung function.5,6,8,25,33,34 ings. The most common clinical subtypes are Respiratory and skeletal muscle abnor- chronic bronchitis and emphysema. malities accompany COPD. The respiratory muscles of patients with COPD are chroni- CHRONIC BRONCHITIS WITH AIRFLOW cally overworked and fatigued, whereas the OBSTRUCTION extremity muscles tend to be underworked Pure chronic bronchitis is clinically defined as and atrophied. an otherwise unexplained chronic, productive Members of various family medicine departments develop cough for at least three months in each of two articles for “Problem-Oriented Diagnosis.” This is one in successive years. If fixed airway obstruction is a series from the Department of Family Medicine at the present in a patient with chronic bronchitis, University of Florida College of Medicine, Gainesville. the patient also has COPD. Eighty-five percent Coordinator of the series is R. Whit Curry, Jr., M.D. of patients with COPD have chronic bronchi- tis.5 These patients experience prominent The Authors cough and sputum production and frequently MARVIN DEWAR, M.D., J.D., is associate professor in the develop hypoxia and hypercarbia at rest and Department of Community Health and Family Medicine significant oxygen desaturation during sleep. and associate dean for continuing education at the Patients with chronic bronchitis and COPD University of Florida College of Medicine, Gainesville. He also is vice president for affiliations and medical affairs often develop pulmonary hypertension, caus- at Shands HealthCare, Gainesville. Dr. Dewar received ing right-sided heart failure and cor pulmo- his medical degree from the University of South Florida nale with marked peripheral edema.5-8 College of Medicine, Tampa, and completed a family medicine residency at Halifax Hospital Medical Center, EMPHYSEMA Daytona Beach, Fla. Dyspnea is the most prominent symptom R. WHIT CURRY, JR., M.D., is professor and chair of the Department of Community Health and Family Medicine at associated with emphysema-related COPD. the University of Florida College of Medicine. He received his Hypoxia is less marked than in the bron- medical degree from Duke University School of Medicine, chitic form of COPD, and hypercarbia is Durham, N.C., and completed an internal medicine resi- relatively uncommon until very late in the dency at Stanford University Medical Center, Calif. disease course. Address correspondence to Marvin Dewar, M.D., Tidal breathing occurs at high lung vol- University of Florida College of Medicine, Health and Science Center, 720 SW Second Ave., Suite 575, umes in patients with emphysema-related Gainesville, FL 32601 (e-mail: [email protected]. COPD to compensate for high pulmonary edu). Reprints are not available from the authors. residual volumes and to open collapsed Author disclosure: Nothing to disclose. airways. This produces hyperinflation of the lungs and thorax, greatly increasing the REFERENCES total work required to breathe. Patients with emphysema-related COPD are less likely to 1. Mannino DM, Homa DM, Akinbami LJ, Ford ES, have right-sided heart failure and cor pul- Redd SC. Chronic obstructive pulmonary disease surveillance—United States, 1971-2000. Respir Care monale than patients with chronic bronchi- 2002;47:1184-99. tis and COPD.5-7,30,32 2. American Lung Association. Trends in chronic bronchi- tis and emphysema: morbidity and mortality. Accessed COPD as a Systemic Disease online May 18, 2005, at: http://www.lungusa.org/ site/pp.asp?c=dvLUK900E&b=3334. COPD increasingly is considered a systemic 3. Petty TL, Weinmann GG. Building a national strategy disorder with important nonpulmonary for the prevention and management of and research
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