Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Diagnosing COPD Gregory L. Angstman MD To cite this article: Gregory L. Angstman MD (1992) Diagnosing COPD, Postgraduate Medicine, 91:1, 61-67, DOI: 10.1080/00325481.1992.11701165 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701165
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [La Trobe University]
Date: 17 June 2016, At: 01:37
Symposium
First of four articles on COPD
Downloaded by [La Trobe University] at 01:37 17 June 2016
Diagnosing COPD How to identify patients with irreversible obstruction of the airways
Damage to the small airways, usually the result of smoking, cannot be undone. However, if disease is detected early, symptomatic treatment started, and life-style changes undertaken, progression can be arrested and the course of the disease improved. Or Angstman describes patient evaluation and differentiation of chronic obstructive pulmonary disease from asthma and other pulmonary disorders.
•:• Chronic obstructive pulmonary disease (COPD) may affect as manv as 30 million Americans and is th~ fifth most common cause of death in the United States. 1 The main feature ofCOPD is chronic, irreversible obstruction of air flow from the lungs. COPD includes emphysema, chronic bronchitis, and small airways disease. Asthma, which is a reversible airway obstruction characterized by recurrent attacks of dyspnea and wheezing, is not included in this category. COPD is seen often in primary care offices, and commonly available office tests allow detection of airway obstruction. Understanding the pathophysiology ofCOPD,
CHRONIC BRONCHITis--Char-
acterized by chronic cough and sputum production, this disorder causes inflammatory changes on the mucosal surfaces of the larger cartilaginous airways. 5.r' Thus, chronic bronchitis is defined clinically. SMALL AIRWAYS DISEASE-Air-
Preview
Gregory L Angstman, MD
chest radiography. 3 However, computed tomography of the chest can detect and quantitate emphysema.4
risk factors for its development, its natural history and clinical features, and methods of evaluation aids in early recognition and diagnosis.
Types of obstruction End-stage COPD is severely disabling. Thus, diagnosis before airflow obstruction has developed or while it is still minimal is critical. EMPHYSEMA- Pathologically, emphysema is characterized by permanent abnormal airspace enlargement occurring distal to the terminal bronchioles with associated destruction of the airspace walls and no obvious fibrosis. 2 The presence of emphysema does not necessarily correspond to clinical symptoms, and this diagnosis cannot be made by clinical examination or
way obstruction, as measured by peak expiratory flow rate or forced expiratory volume in 1 second (FEY1), results from airway narrowing or collapse and/or loss of elastic recoil of the lungs.- The small noncartilaginous conducting airways are the major site of airflow obstruction in CO PD. These small airways show pathologic changes of inflammation, fibrosis, mucus production, and narrowing. The definite pathologic changes of emphysema and chronic bronchitis are not necessarily related to the airway obstruction ofCOPD. Chronic obstruction is related more closely to disease of the small airways. Unfortunately, early small airways disease is not easily or reliably detected by presently available clinical tests. 7
Diagnostic criteria The criteria for diagnosis ofCOPD in patients with evidence of chronic airway obstruction are as follows: • Obstructive ventilatory impairment is apparent on spirometry, with a low FEY 1 value compared with forced vital capacity (FVC). continued
VOL 91/NO 1/JANUARY 1992/POSTGRADUATE MEDICINE • DIAGNOSING COPD
61
Smoking is the main risk factor for development of COPD.
Downloaded by [La Trobe University] at 01:37 17 June 2016
Table 1. Steps and techniques in evaluation of possible chronic obstructive pulmonary disease History taking and physical examination Spirometry (before and after bronchodilation) Chest radiography Sputum evaluation Complete blood cell count with differential Serum alpha 1-antitrypsin testing Baseline electrocardiography Follow-up spirometry after maximal therapy Arterial blood gas measurement if cor pulmonale. cyanosis, or erythrocytosis present or forced expiratory volume in 1 sec less than 1 L
Adapted from Burrows. ' 8
• Impairment persists despite medical therapy. This fearure distinguishes asthma from COPD. Some COPD patients have significant response to bronchodilators, but airway obstruction does not completely reverse. • Physical examination and chest radiography exclude other causes of airway obstruction. If there is a history of asthma, attacks of wheezing and dyspnea, allergic rhinitis, or atopy, chronic asthma may be the correct diagnosis and should be ruled out.
Risk factors Smoking is the main risk factor for development of COPD. Burrows and associates8 showed a close relationship between increased airway obstruction (reduced FEY 1) and a high number of pack-years of smoking. Numerous srudies have looked at populations with obstructive disease of the airways. In srudies
62
where known asthmatics were deleted, there was no relationship of atopy, eosinophilia, or serum IgE levels to respiratory impairment9; that is, by deleting asthmatics from the srudy, all ventilatory impairment seen in nonsmokers disappeared. Other factors play varying roles. Increased age, male sex, and reduced lung function seem to have an effect in development ofCOPD. Air pollution and certain occupational exposures are also risk factors,10 and persons with alpha 1antitrypsin deficiency are at risk for emphysema. 11 There is evidence that childhood respiratory problems may predispose to COPD in adulthood. Martinez and associates 12 reported that poor lung function soon after birth precedes and predicts subsequent childhood wheezing illnesses. This decreased pulmonary function may lead to persistent childhood respira-
tory problems and then COPD later in life. 13 Burrows 14 proposed a hypothesis for development ofCOPD that indudes a combination of factors, such as alpha 1-antitrypsin deficiency, other antitrypsin deficiencies, childhood respiratory trouble, and smoking.
Natural history The preclinical course of smokingrelated COPD varies. Patients with childhood respiratory trouble may begin adulthood with reduced pulmonary function, and smoking then leads to a progressive decline in lung function. Other patients who smoke probably begin adult life with normal pulmonary function. One srudy11 showed that some smokers retain a basically normal FEY1 until middle age, and then a rapid decline in pulmonary function begins. This decline stops in patients who quit smoking, 16 but clinical symptoms ofCOPD appear in patients who continue to smoke.
Clinical presentation COPD patients present with dyspnea, often with coughing and wheezing. Coughing usually indicates mucus production, typically due to airway inflammation. Wheezing is secondary to airway narrowing, mucosal edema, and retained secretions. Dyspnea results from the increased work of breathing through obstructed airways. Initially, dyscontinued
DIAGNOSING COPD • VOL 91/NO 1/JANUARY 1992/POSTGRADUATE MEDICINE
Downloaded by [La Trobe University] at 01:37 17 June 2016
In COPD, dyspnea is constant. lt does not vary as it does in asthma.
pnea occurs with exenion or exercise. Later in the course of the disease, dyspnea occurs with less exertion until it is present at rest. In COPD, dyspnea does not vary as it does in asthma. COPD patients at the two ends of a continuum of characteristics have been described as "blue bloaters" or "pink puffers." Most patients fall somewhere between and have a combination of signs and symptoms. Blue bloaters have central cyanosis with secondary polycythemia and edema. Anerial blood gases reflect hypoxemia (Po2 , 45 to 55 mm Hg), carbon dioxide retention (Pco2 , 50 to 60 mm Hg), and compensated respiratory acidosis (pH, 7.38 to 7.42). The ventilatory drive of hypoxia and raised Pco2 is reduced. 17 Pink puffers do not have secondary polycythemia or cor pulmonale, so edema is not present. They have less hypoxemia (Po2, 60 to 80 mm Hg) and no carbon dioxide retention (Pco 2, 30 to 40 mm Hg). The ventilatory drive of hypoxia and raised Pco2 is maintained. Patients with emphysema are not necessarily pink puffers and those with chronic bronchitis are not necessarily blue bloaters. In all of these patients, pulmonary function tests show airway obstruction and inflated lung volumes. Degrees ofhypoxemia, carbon dioxide retention, and polycythemia vary with the individual.
Patient evaluation Evaluation of patients with suspected COPD includes several steps and techniques (table 1). History taking and physical examination provide evidence of the presence of other diseases that cause chronic airway obstruction. Specifically, asthma, with its attacks of dyspnea, wheezing, and cough, must be excluded. Also bronchiectasis, idiopathic pulmonary fibrosis, pulmonary sarcoidosis, pneumoconiosis, and pulmonary tuberculosis must be considered. A history of smoking should be elicited, and a baseline electrocardiogram is useful. Spirometry is a simple office procedure that can be used to assess FEV1 and FVC. The FEV1:FVC ratio, which is most useful in identifying mild disease, can then be calculated.18 Typically, FEV1 is reduced and FVC is normal or increased. The ratio should be esrablished before and after bronchodilator use. Once maximal medical therapy has been initiated, follow-up spirometry should be done. In COPD, there is little or no reversibility of obstruction, and with disease progression, FEV1 worsens. In endsrage COPD, FVC may decrease, leading to a false normalization of the FEV1:FVC ratio. Serum alpha 1-antitrypsin testing is recommended, and phenotyping should be done if the level is low. A complete blood cell count with differential may show evidence of erythrocytes or eosinophilia. The latter raises the possibility of asth-
Gregory L. Angstman, MD Dr Angstman is an instructor in family medicine, Mayo Medical School, Rochester, and practices at Kasson-Mayo Family Practice Clinic, Kasson, Minnesota.
ma as the cause of airway obstruction. Anerial blood gases should be measured if there is evidence of cor pulmonale, cyanosis, or erythrocytosis or ifFEV1 is less than 1 L. Chest radiography rules out other causes of chronic airway obstruction but does not diagnose CO PD. Sputum examination may uncover evidence of asthma or infection. Summary
Chronic obstructive pulmonary disease (COPD) is seen often in primary care offices. Its hallcontinued
VOL 91/NO 1/JANUARY 1992/POSTGRADUATE MEDICINE • DIAGNOSING COPD
65
Downloaded by [La Trobe University] at 01:37 17 June 2016
mark is dyspnea with obstrucfuund and spirometric abnortion. Smoking is the leading risk mality persists after therapy, factor. Smokers should be coun- COPD is present. Treatment seled at every encounter to quit early in the clinical course can smoking to prevent development markedly improve COPD and of COPD and lower the rate avoid the severe disability of of decline of pulmonary funcend-stage disease. PCI't'l tion. Office spirometry detects the Earn credit on this article. early changes of small airways See CME Quiz. obstruction. All patients with symptoms should receive baseline spirometry and fullow-up Address for correspondence: Gregory L. spirometry once they have reAngsrman, MD, Kasson-Mayo Family ceived maximal medical therapy. Practice Clinic, 411 W Main, Kasson, If evidence of obstruction is MN55944.
--®
References
1. Petty TL. Chronic obstructive pulmonary disease: can we do better? Chest 1990;97(2 Suppl): 2-55
2. Snider GL, Kleinennan J, Thurlbeck WM,
et al. The definition of emphysema: report of a National Heart, Lung, and Blood Institute, Division of Lung Diseases Workshop. Am Rev Respir Dis 1985;132:182-5 3. Flenley DC. Chronic obstructive pulmonary disease. Dis Mon 1988;34(9):537-99 4. Gould GA, MacNee W, McLean A, et al. CT measurements oflung density in life can quantirate distal airspace enlargement: an essential defining feature of human emphysema. Am Rev Respir Dis 1988;137(2):380-92 5. Mullen JB, Wright JL, Wlf!l}' BR, et al. Reassessment of inflammation of aiiWays in chronic bronchitis. BMJ (Ciin Res) 1985;291(6504): 1235-9 6. Mnllen JB, Wright JL, Wlf!l}' BR, et al. Structure of central airways in current smokers and ex-smokers with and without mucus hypersecretion: relationship to lung function. Thorax 1987;42(11):843-8 7. Thurlbeck WM. Pathophysiology of chronic obstructive pulmonary disease. Clin Chest Med 1990;11(3):389-403 8. Burrows B, Knudson RJ, Cline MG, et al. Quantitative relationships between cigarette smoking and ventilatory function. Am Rev Respir Dis 1977: 115(2): 195-205 9. Burrows B, Knudson RJ, Cline MG, et al. A reexamination of risk factors for ventilatory impairment. Am Rev Respir Dis 1988;138(4):829-36
10. Sherrill DL, Lebowitz MD, Burrows B. Epidemiology of chronic obstructive pulmonary disease. Clin Chest Med 1990;11(3):375-87 11. Hutchison DC. Natural history of alpha-1protease inhibitor deficiency. Am J Med 1988; 84(6A):3-12 12. Martinez FD, Morgan WJ, WrightAL, et al. Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. N EnglJ Med 1988;319(17):1112-7 13. Burrows B, Bloom Jw; 'fraver GA, et al. The course and prognosis of different forms of chronic airways obstruction in a sample from the general population. N EnglJ Med 1987;317(21): 1309-14 14. Burrows B. Airways obstructive diseases: pathogenetic mechanisms and natural histories of the disorders. Med Clin North Am 1990;74(3): 547-59 15. Burrows B, Knudson RJ, Camilli AE, et al. The "horse-racing effect" and predicting decline in forced expiratory volume in one second from screening spirometry. Am Rev Respir Dis 1987; 135(4):788-93 16. Burrows B, Hasan FM, Barbee RA, et al. Epidemiologic observations on eosinophilia and its relation to respiratory disorders. Am Rev Respir Dis 1980;122(5):709-19 17. Flenley DC, Franklin DH, Millar JS. The hypoxic drive to breathing in chronic bronchitis and emphysema. Clin Sci 1970;38(4):503-18 18. Burrows B. Differential diagnosis of chronic obstructive pulmonary disease. Chest 1990;97 (2 Suppi):16-8S
VOL 91/NO 1/JANUARY 1992/POSTGRADUATE MEDICINE • DIAGNOSING COPD
67
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Diagnosing COPD Gregory L. Angstman MD To cite this article: Gregory L. Angstman MD (1992) Diagnosing COPD, Postgraduate Medicine, 91:1, 61-67, DOI: 10.1080/00325481.1992.11701165 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701165
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [La Trobe University]
Date: 17 June 2016, At: 01:37
Symposium
First of four articles on COPD
Downloaded by [La Trobe University] at 01:37 17 June 2016
Diagnosing COPD How to identify patients with irreversible obstruction of the airways
Damage to the small airways, usually the result of smoking, cannot be undone. However, if disease is detected early, symptomatic treatment started, and life-style changes undertaken, progression can be arrested and the course of the disease improved. Or Angstman describes patient evaluation and differentiation of chronic obstructive pulmonary disease from asthma and other pulmonary disorders.
•:• Chronic obstructive pulmonary disease (COPD) may affect as manv as 30 million Americans and is th~ fifth most common cause of death in the United States. 1 The main feature ofCOPD is chronic, irreversible obstruction of air flow from the lungs. COPD includes emphysema, chronic bronchitis, and small airways disease. Asthma, which is a reversible airway obstruction characterized by recurrent attacks of dyspnea and wheezing, is not included in this category. COPD is seen often in primary care offices, and commonly available office tests allow detection of airway obstruction. Understanding the pathophysiology ofCOPD,
CHRONIC BRONCHITis--Char-
acterized by chronic cough and sputum production, this disorder causes inflammatory changes on the mucosal surfaces of the larger cartilaginous airways. 5.r' Thus, chronic bronchitis is defined clinically. SMALL AIRWAYS DISEASE-Air-
Preview
Gregory L Angstman, MD
chest radiography. 3 However, computed tomography of the chest can detect and quantitate emphysema.4
risk factors for its development, its natural history and clinical features, and methods of evaluation aids in early recognition and diagnosis.
Types of obstruction End-stage COPD is severely disabling. Thus, diagnosis before airflow obstruction has developed or while it is still minimal is critical. EMPHYSEMA- Pathologically, emphysema is characterized by permanent abnormal airspace enlargement occurring distal to the terminal bronchioles with associated destruction of the airspace walls and no obvious fibrosis. 2 The presence of emphysema does not necessarily correspond to clinical symptoms, and this diagnosis cannot be made by clinical examination or
way obstruction, as measured by peak expiratory flow rate or forced expiratory volume in 1 second (FEY1), results from airway narrowing or collapse and/or loss of elastic recoil of the lungs.- The small noncartilaginous conducting airways are the major site of airflow obstruction in CO PD. These small airways show pathologic changes of inflammation, fibrosis, mucus production, and narrowing. The definite pathologic changes of emphysema and chronic bronchitis are not necessarily related to the airway obstruction ofCOPD. Chronic obstruction is related more closely to disease of the small airways. Unfortunately, early small airways disease is not easily or reliably detected by presently available clinical tests. 7
Diagnostic criteria The criteria for diagnosis ofCOPD in patients with evidence of chronic airway obstruction are as follows: • Obstructive ventilatory impairment is apparent on spirometry, with a low FEY 1 value compared with forced vital capacity (FVC). continued
VOL 91/NO 1/JANUARY 1992/POSTGRADUATE MEDICINE • DIAGNOSING COPD
61
Smoking is the main risk factor for development of COPD.
Downloaded by [La Trobe University] at 01:37 17 June 2016
Table 1. Steps and techniques in evaluation of possible chronic obstructive pulmonary disease History taking and physical examination Spirometry (before and after bronchodilation) Chest radiography Sputum evaluation Complete blood cell count with differential Serum alpha 1-antitrypsin testing Baseline electrocardiography Follow-up spirometry after maximal therapy Arterial blood gas measurement if cor pulmonale. cyanosis, or erythrocytosis present or forced expiratory volume in 1 sec less than 1 L
Adapted from Burrows. ' 8
• Impairment persists despite medical therapy. This fearure distinguishes asthma from COPD. Some COPD patients have significant response to bronchodilators, but airway obstruction does not completely reverse. • Physical examination and chest radiography exclude other causes of airway obstruction. If there is a history of asthma, attacks of wheezing and dyspnea, allergic rhinitis, or atopy, chronic asthma may be the correct diagnosis and should be ruled out.
Risk factors Smoking is the main risk factor for development of COPD. Burrows and associates8 showed a close relationship between increased airway obstruction (reduced FEY 1) and a high number of pack-years of smoking. Numerous srudies have looked at populations with obstructive disease of the airways. In srudies
62
where known asthmatics were deleted, there was no relationship of atopy, eosinophilia, or serum IgE levels to respiratory impairment9; that is, by deleting asthmatics from the srudy, all ventilatory impairment seen in nonsmokers disappeared. Other factors play varying roles. Increased age, male sex, and reduced lung function seem to have an effect in development ofCOPD. Air pollution and certain occupational exposures are also risk factors,10 and persons with alpha 1antitrypsin deficiency are at risk for emphysema. 11 There is evidence that childhood respiratory problems may predispose to COPD in adulthood. Martinez and associates 12 reported that poor lung function soon after birth precedes and predicts subsequent childhood wheezing illnesses. This decreased pulmonary function may lead to persistent childhood respira-
tory problems and then COPD later in life. 13 Burrows 14 proposed a hypothesis for development ofCOPD that indudes a combination of factors, such as alpha 1-antitrypsin deficiency, other antitrypsin deficiencies, childhood respiratory trouble, and smoking.
Natural history The preclinical course of smokingrelated COPD varies. Patients with childhood respiratory trouble may begin adulthood with reduced pulmonary function, and smoking then leads to a progressive decline in lung function. Other patients who smoke probably begin adult life with normal pulmonary function. One srudy11 showed that some smokers retain a basically normal FEY1 until middle age, and then a rapid decline in pulmonary function begins. This decline stops in patients who quit smoking, 16 but clinical symptoms ofCOPD appear in patients who continue to smoke.
Clinical presentation COPD patients present with dyspnea, often with coughing and wheezing. Coughing usually indicates mucus production, typically due to airway inflammation. Wheezing is secondary to airway narrowing, mucosal edema, and retained secretions. Dyspnea results from the increased work of breathing through obstructed airways. Initially, dyscontinued
DIAGNOSING COPD • VOL 91/NO 1/JANUARY 1992/POSTGRADUATE MEDICINE
Downloaded by [La Trobe University] at 01:37 17 June 2016
In COPD, dyspnea is constant. lt does not vary as it does in asthma.
pnea occurs with exenion or exercise. Later in the course of the disease, dyspnea occurs with less exertion until it is present at rest. In COPD, dyspnea does not vary as it does in asthma. COPD patients at the two ends of a continuum of characteristics have been described as "blue bloaters" or "pink puffers." Most patients fall somewhere between and have a combination of signs and symptoms. Blue bloaters have central cyanosis with secondary polycythemia and edema. Anerial blood gases reflect hypoxemia (Po2 , 45 to 55 mm Hg), carbon dioxide retention (Pco2 , 50 to 60 mm Hg), and compensated respiratory acidosis (pH, 7.38 to 7.42). The ventilatory drive of hypoxia and raised Pco2 is reduced. 17 Pink puffers do not have secondary polycythemia or cor pulmonale, so edema is not present. They have less hypoxemia (Po2, 60 to 80 mm Hg) and no carbon dioxide retention (Pco 2, 30 to 40 mm Hg). The ventilatory drive of hypoxia and raised Pco2 is maintained. Patients with emphysema are not necessarily pink puffers and those with chronic bronchitis are not necessarily blue bloaters. In all of these patients, pulmonary function tests show airway obstruction and inflated lung volumes. Degrees ofhypoxemia, carbon dioxide retention, and polycythemia vary with the individual.
Patient evaluation Evaluation of patients with suspected COPD includes several steps and techniques (table 1). History taking and physical examination provide evidence of the presence of other diseases that cause chronic airway obstruction. Specifically, asthma, with its attacks of dyspnea, wheezing, and cough, must be excluded. Also bronchiectasis, idiopathic pulmonary fibrosis, pulmonary sarcoidosis, pneumoconiosis, and pulmonary tuberculosis must be considered. A history of smoking should be elicited, and a baseline electrocardiogram is useful. Spirometry is a simple office procedure that can be used to assess FEV1 and FVC. The FEV1:FVC ratio, which is most useful in identifying mild disease, can then be calculated.18 Typically, FEV1 is reduced and FVC is normal or increased. The ratio should be esrablished before and after bronchodilator use. Once maximal medical therapy has been initiated, follow-up spirometry should be done. In COPD, there is little or no reversibility of obstruction, and with disease progression, FEV1 worsens. In endsrage COPD, FVC may decrease, leading to a false normalization of the FEV1:FVC ratio. Serum alpha 1-antitrypsin testing is recommended, and phenotyping should be done if the level is low. A complete blood cell count with differential may show evidence of erythrocytes or eosinophilia. The latter raises the possibility of asth-
Gregory L. Angstman, MD Dr Angstman is an instructor in family medicine, Mayo Medical School, Rochester, and practices at Kasson-Mayo Family Practice Clinic, Kasson, Minnesota.
ma as the cause of airway obstruction. Anerial blood gases should be measured if there is evidence of cor pulmonale, cyanosis, or erythrocytosis or ifFEV1 is less than 1 L. Chest radiography rules out other causes of chronic airway obstruction but does not diagnose CO PD. Sputum examination may uncover evidence of asthma or infection. Summary
Chronic obstructive pulmonary disease (COPD) is seen often in primary care offices. Its hallcontinued
VOL 91/NO 1/JANUARY 1992/POSTGRADUATE MEDICINE • DIAGNOSING COPD
65
Downloaded by [La Trobe University] at 01:37 17 June 2016
mark is dyspnea with obstrucfuund and spirometric abnortion. Smoking is the leading risk mality persists after therapy, factor. Smokers should be coun- COPD is present. Treatment seled at every encounter to quit early in the clinical course can smoking to prevent development markedly improve COPD and of COPD and lower the rate avoid the severe disability of of decline of pulmonary funcend-stage disease. PCI't'l tion. Office spirometry detects the Earn credit on this article. early changes of small airways See CME Quiz. obstruction. All patients with symptoms should receive baseline spirometry and fullow-up Address for correspondence: Gregory L. spirometry once they have reAngsrman, MD, Kasson-Mayo Family ceived maximal medical therapy. Practice Clinic, 411 W Main, Kasson, If evidence of obstruction is MN55944.
--®
References
1. Petty TL. Chronic obstructive pulmonary disease: can we do better? Chest 1990;97(2 Suppl): 2-55
2. Snider GL, Kleinennan J, Thurlbeck WM,
et al. The definition of emphysema: report of a National Heart, Lung, and Blood Institute, Division of Lung Diseases Workshop. Am Rev Respir Dis 1985;132:182-5 3. Flenley DC. Chronic obstructive pulmonary disease. Dis Mon 1988;34(9):537-99 4. Gould GA, MacNee W, McLean A, et al. CT measurements oflung density in life can quantirate distal airspace enlargement: an essential defining feature of human emphysema. Am Rev Respir Dis 1988;137(2):380-92 5. Mullen JB, Wright JL, Wlf!l}' BR, et al. Reassessment of inflammation of aiiWays in chronic bronchitis. BMJ (Ciin Res) 1985;291(6504): 1235-9 6. Mnllen JB, Wright JL, Wlf!l}' BR, et al. Structure of central airways in current smokers and ex-smokers with and without mucus hypersecretion: relationship to lung function. Thorax 1987;42(11):843-8 7. Thurlbeck WM. Pathophysiology of chronic obstructive pulmonary disease. Clin Chest Med 1990;11(3):389-403 8. Burrows B, Knudson RJ, Cline MG, et al. Quantitative relationships between cigarette smoking and ventilatory function. Am Rev Respir Dis 1977: 115(2): 195-205 9. Burrows B, Knudson RJ, Cline MG, et al. A reexamination of risk factors for ventilatory impairment. Am Rev Respir Dis 1988;138(4):829-36
10. Sherrill DL, Lebowitz MD, Burrows B. Epidemiology of chronic obstructive pulmonary disease. Clin Chest Med 1990;11(3):375-87 11. Hutchison DC. Natural history of alpha-1protease inhibitor deficiency. Am J Med 1988; 84(6A):3-12 12. Martinez FD, Morgan WJ, WrightAL, et al. Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. N EnglJ Med 1988;319(17):1112-7 13. Burrows B, Bloom Jw; 'fraver GA, et al. The course and prognosis of different forms of chronic airways obstruction in a sample from the general population. N EnglJ Med 1987;317(21): 1309-14 14. Burrows B. Airways obstructive diseases: pathogenetic mechanisms and natural histories of the disorders. Med Clin North Am 1990;74(3): 547-59 15. Burrows B, Knudson RJ, Camilli AE, et al. The "horse-racing effect" and predicting decline in forced expiratory volume in one second from screening spirometry. Am Rev Respir Dis 1987; 135(4):788-93 16. Burrows B, Hasan FM, Barbee RA, et al. Epidemiologic observations on eosinophilia and its relation to respiratory disorders. Am Rev Respir Dis 1980;122(5):709-19 17. Flenley DC, Franklin DH, Millar JS. The hypoxic drive to breathing in chronic bronchitis and emphysema. Clin Sci 1970;38(4):503-18 18. Burrows B. Differential diagnosis of chronic obstructive pulmonary disease. Chest 1990;97 (2 Suppi):16-8S
VOL 91/NO 1/JANUARY 1992/POSTGRADUATE MEDICINE • DIAGNOSING COPD
67
