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Spirometric Criteria for Airway Obstruction

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James E. Hansen, Xing-Guo Sun and Karlman Wasserman Chest 2007;131;349-355 DOI 10.1378/chest.06-1349 The online version of this article, along with updated information and services can be found online on the World Wide Web at:

CHEST is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright 2007 by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. ( ISSN:0012-3692

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spirometry Abbreviations: ATS ϭ American Thoracic Society. In 1988. however. many recent publications continue to use the Global Initiative for Chronic Obstructive Lung Disease (GOLD) primary criterion that defines obstruction as a FEV1/FVC% < 70%. BA ϭ both abnormal. Department of Medicine. Methods: Using these two guidelines.06-1349 CHEST / 131 / 2 / FEBRUARY. BN ϭ both normal. Miller and Pincock2 emphasized the necessity of using statistically derived lower limits of normal *From the Division of Respiratory and Critical Care Physiology and Medicine. resulting in ongoing confusion regarding the prevalence of airManuscript received May 30. DOI: 10. 2010 © 2007 American College of Chest Physicians . There is no financial support or author involvement with organizations with financial interest in the subject matter. 2007 349 Downloaded from chestjournal. MD. at Hopital St Antoine on September 8. But nearly one half of young adults with FEV1/FVC% below the NHANES-III fifth percentile of normal were misidentified as normal because their FEV1/FVC% was > 70% (abnormals misidentified as normal). individual values of FEV1/FVC% were compared by decades in 5. MD.shtml). LLN ϭ lower limit/limits of normal. (CHEST 2007. GOLD ϭ Global Initiative for Chronic Obstructive Lung Disease. respected organizations of pulmonary specialists have defined spirometric airway obstruction in conflicting ways. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. MD. Box 405.CHEST Original Research LUNG FUNCTION TESTING Spirometric Criteria for Airway Obstruction* Use Percentage of FEV1/FVC Ratio Below the Fifth Percentile. ERS ϭ European Respiratory Society. Hansen. Support was provided by the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. 2006. e-mail: jhansen@labiomed. NHANES-III ϭ Third National Health and Nutritional Examination Survey. help resolve this conflict. The American Thoracic Society/European Respiratory Society Task Force characterizes obstruction as a FEV1/FVC% below the statistically defined fifth percentile of normal.9 years. FCCP. CA 90509. and reduce inappropriate medical and public health decisions resulting from misidentification. org/misc/reprints. Harbor-UCLA Medical Center. FN ϭ false (LLN).1378/chest. and Karlman Wasserman. PhD. FP ϭ false positive. 131:349 –355) Key words: airway obstruction. revision accepted September 20. Conclusions: The GOLD guidelines misidentify nearly one half of abnormal younger adults as normal and misidentify approximately one fifth of normal older adults as abnormal. percentage of predicted FEV1/FVC. FEV1/FEV6% ϭ percentage of FEV1/forced expiratory volume in 6 s. Currently. FEV1/FVC% ϭ percentage of FEV1/FVC. Hispanic (Latin).chestjournal. NPV ϭ negative predictive value. Correspondence to: James E. Not < 70% James E. Results: In the never-smoking population.0 to 79. FCCP Background: Current authoritative spirometry guidelines use conflicting percentage of FEV1/ FVC ratios (FEV1/FVC%) to define airway obstruction. reference values. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www. PPV ϭ positive predictive value. Torrance. However. Data from the Third National Health and Nutrition Examination Survey (NHANES-III) should identify and quantify differences. or white ethnicities aged 20. Hansen. 2006. Xing-Guo Sun. MD. the lower limits of normal used in other reference equations fit reasonably well the NHANES-III statistically defined fifth percentile guidelines. Sobol and Weinheimer pointed out the I error of using fixed percentages of spirometric 1 predicted values to define abnormality.906 healthy never-smoking adults and 3. www. Approximately one fifth of older adults with observed FEV1/FVC% above the NHANES-III fifth percentile had FEV1/FVC% ratios < 70% (normals misidentified as abnormal).chestjournal.chestpubs.497 current-smokers of black (African American). VC ϭ vital capacity n 1966. CA.

the authors used high-quality spirometric data from nearly 10. the individual subjects in each never-smoking and current-smoking group who had FEV1/FVC% Ͻ 70% were similarly identified.147 153 204 127 69 48 11 612 Hispanic 426 312 201 84 160 58 1. To further explore the potential magnitude of the problem and importance of selecting good criteria of airflow obstruction.9 years (third to eighth decades). and ethnicity. if below.7 Despite this recognition and its lack of statistical justification. .241 91 72 44 28 23 4 262 White 224 274 209 221 201 293 1.15. sex.4 and reinforced in the most current GOLD guidelines5 and the 2004 ATS/ERS standards for diagnosis and treatment of patients with COPD. By decade. Analysis and Statistics First. as summarized in their position statement. Third.497 current-smoking adults from the Third National Health and Nutrition Examination Survey (NHANES-III) database16 from ages 20. by sex and smoking status.794 1.3 with which the authors agree.906 never-smoking adults without recognized respiratory or musculoskeletal disease and 3.” This definition contrasts with that described by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). and ethnicity. the 9. Latin. and derived from healthy NHANES-III never-smokers were used. (2) spirometric values after aerosolized bronchodilators are necessary4. 2010 © 2007 American College of Chest Physicians .chestpubs. even though it is recognized that this fixed ratio identifies an unusually high incidence of obstruction in older never-smoking individuals unexposed to noxious particles or gases. and (3) a reduction in FEV1 is necessary to diagnose airflow obstruction. by decade.000 ethnically defined. or white. healthy never-smokers and current-smokers in the United States15 to quantify the degree of overidentification and underidentification of airway obstruction as related to age.906 948 974 677 425 340 113 3. Each subject selected (Table 1) was classified ethnically as black. since the latter is often larger in those with airway obstruction14. If above. they were considered to have a Ͻ 5% chance of being normal and were therefore identified as abnormal.497 350 Original Research Downloaded from chestjournal. many current reports8 –13 continue to use the fixed limit of FEV1/FVC% Ͻ 70% to identify and define airway obstruction.425 201 172 115 95 59 45 687 Black 289 135 91 44 50 24 633 147 224 155 90 68 21 705 Men Hispanic 303 165 95 46 71 19 699 197 143 102 32 64 12 550 White 181 178 113 86 119 90 764 159 159 134 111 78 40 681 Totals 1.6 These latter publications primarily define airway obstruction as percentage of FEV1/FVC (FEV1/FVC%) Ͻ 70%. Hankinson et al17 LLN equations for FEV1/FVC% specific for sex. a usage that tends to underestimate airway obstruction in the young and overestimate it in older adults.0 to 79.403 individual subjects in each never-smoking and current-smoking group were identified as being above or below the fifth percentile of normal. and had performed repeated spirometric maneuvers meeting ATS standards.16 These data from unidentified subjects had been ethically obtained with informed consent and Institutional Review Board approval. sex.18 Second. states that an “obstructive ventilatory defect . Minor considerations are as follows: (1) the ratio denominator should be FVC or vital capacity (VC).370 900 576 704 562 5. grouping all ethnicities together. such individuals were identified as normal. The most recent guideline of the American Thoracic Society (ATS)/European Respiratory Society (ERS) Task Force interpretative strategies. Materials and Methods Subjects Subjects were 5. we identified the number and percentage of subjects in Table 1—Number of NHANES-III Subjects Included in Study Women Decade of Life Never-smokers Third Fourth Fifth Sixth Seventh Eighth Total Current-smokers Third Fourth Fifth Sixth Seventh Eighth Total Black 371 306 191 98 103 78 1. at Hopital St Antoine on September 8. . is defined as a reduced forced expiratory For editorial comment see page 335 volume in one second/vital capacity ratio (FEV1/VC) below the fifth percentile of the predicted value.way obstruction in a general or specific population. and age.

Observed FEV1/FVC% Ͻ 70%. thereafter. 14. is the primary GOLD spirometric criterion used to screen for airway obstruction. it increased to 6 to 14% for the sixth decade. respectively. Fourth.9 years is only 41% (bottom of Table 3). but FP-observed FEV1/FVC% values continue to increase. with observed FEV1/FVC% Ͻ 70%. positive predictive value (PPV). FP/ (FP ϩ BN). all of those above the expected fifth percentile dashed line will be improperly identified as “airway obstruction” using the GOLD FEV1/FVC% Ͻ 70% criterion. Figure 1. top. Fifth.906 NHANES-III neversmokers (top.9%. and negative predictive value (NPV) were calculated for each decade by gender and smoking status (Table 2). These values contrast with an optimal 5% during each decade. 14.2%. ethnicity. Percentages of healthy 5.6%. 42. rather than the statistically valid fifth percentile. considering the Hankinson et al17 fifth percentile as the “correct” and “gold standard.chestpubs.3%. and 19 to 33% for the eighth decade.1%. Sensitivity.1%. Table 2—Summary of Abbreviations and Formulae Used Groupings BA ϭ FEV1/FVC Ͻ 5th percentile and FEV1/FVC Ͻ 70% BN ϭ FEV1/FVC Ն 5th percentile and FEV1/FVC Ն 70% FN ϭ FEV1/FVC Ͻ 5th percentile and FEV1/FVC Ն 70% FP ϭ FEV1/FVC Ն 5th percentile and FEV1/FVC Ͻ 70% Formulae Sensitivity. mean values for the third through eighth decades. specificity (correct diagnosis of nonobstruction) has declined from 100 to 81% while the PPV (percentage of reliability of positive test results) has declined from 100 to 55%. After the fifth decade. and 25. were 2. sex. With equal weighting. If ethnic.4%.chestjournal. (2) normal by both guidelines (both normal [BN]).6%. the percentages of FN cases are negligible. 1 – sensitivity. % ϭ 100 ϫ BA/(BA ϩ FP) NPV. % ϭ 100 ϫ FP/(FP ϩ BN) Figure 1. 31. B. to further assess the validity of the formulae used by Hankinson et al. For each group.20 for never-smokers with well-defined fifth percentile limits to see if the number per decade of the “abnormal” 2. respectively. ie. so that overall sensitivity from 20 to 39. ie.0%. Table 3 gives details of the third analysis. the percentages for men exceeded those of women.2%. some of those above the expected fifth percentile dashed line will be improperly identified as “airway obstruction” using the GOLD FEV1/FVC% Ͻ 70% criterion. For 11 of the 12 group/decade comparisons. and 54.189 white neversmoking individuals from the NHANES-III database16 approximated 5%. Results The percentage of NHANES-III never-smokers with FEV1/FVC% Ͻ 70% are shown by decade of age.and sex-specific groups were weighted equally. the prevalence was Ͻ 5% for the third and fourth decades.17 we compared two other frequently used American FEV1/FVC% formulae19.3%. and ethnicity in Figure 1. and decade. or (4) above or equal to the fifth percentile but FEV1/FVC% ratio Ͻ 70% (false positive [FP]).each decade with the following characteristics: (1) obstruction as per both guidelines (both abnormal [BA]). 1 Ϫ specificity. shows similar values for the current-smoking population. CHEST / 131 / 2 / FEBRUARY. Sensitivities were low in all groups in the third and fourth decades. (3) below the fifth percentile but with FEV1/FVC% ratio Ն 70% (false negative [FN]). Among current-smokers. % ϭ 100 ϫ BA/(BA ϩ FN) Specificity. specificity. For the seventh and eighth decades. and normals misidentified as at Hopital St Antoine on September 8.7%.” we calculated for each decade and smoking status the normal and abnormal subjects misidentified by substituting the FEV1/FVC% Ͻ 70% or Ն 70% standard: abnormals misidentified as normals. 4. % ϭ 100 ϫ BN/(BN ϩ FP) 351 Downloaded from chestjournal. % ϭ 100 ϫ BN/(BN ϩ FN) Abnormals misidentified as normals. likely because men normally have lower FEV1/FVC% values than women of the same age. A) and 3. 2010 © 2007 American College of Chest Physicians . B). A. Among never-smokers. 8. by sex. FN/(FN ϩBA). mean values for the third through eighth decades. 5. 11 to 18% for the seventh decade. were 3. 2007 www. 2. % ϭ 100 ϫ FN/(FN ϩ BA) Normals misidentified as abnormals.497 current-smokers (bottom. bottom.

0 0.7 88.9 58.9 14. among never-smokers and probably among current-smokers.Table 3—Comparison of Observed FEV1/FVC% < 70% or Greater Than or Equal to the Fifth Percentile LLN with Observed FEV1/FVC% < 70% or > 70%* FEV1/FVC% FEV1/FVC% FEV1/FVC% Sensitivity: Specificity: PPV: NPV: FEV1/FVC% Ͻ 5% LLN and Ն 5% LLN and Ͻ 5% LLN and Ն 5% LLN and BA/ BN/ BA/ BN/ Ͻ 70% (BA) Ն 70% (BN) Ն 70% (FN) Ͻ 70% (FP) (BA ϩ FN) (BN ϩ FP) (BA ϩ FP) (BN ϩ FN) 2.0 0.6 6.2 64.5 0.2 6.6 2.3 0.7 4.3 0.1 68. The latter indicate that approximately one seventh of never-smokers and one fifth of current-smokers in these decades with FEV1/FVC% above the fifth percentile LLN Original Research Downloaded from chestjournal. FP/ (FP ϩ BN).0 0.8 0.7 95.8 94.0 4. FN/ (FN ϩ BA).5 92.3 12.1 89.7 2.0 0.0 4.7 5. Thus.5 85.2 85.5 94. Table 4 shows that.2 9.0 11. using data from Table 3.5 92.9 2. whether the Hankinson et al.4 20.9 6.8 1.2 6.0 0.0 4.3 90. Confirmatory evidences in these decades are the relatively low specificity and very low PPV (Table 3) and high ratios of normals misidentified as abnormals (Fig 2).2 0.7 95.9 73.0 0.0 95.3 0.0 0.0 0.3 30.0 73.0 1.0 0.0 4.0 1.4 31.9 89.8 9.0 92.0 3.0 10.5 0.0 5. Further.7 82.0 16.0 18. and normals were misidentified.7 0.2 19.5 at Hopital St Antoine on September 8.2 0.3 2. Figure 2 shows the results of the fourth analysis. Use of the GOLD criterion to identify obstruction as an FEV1/FVC% Ͻ 70% results in finding an inappropriately high prevalence of obstruction in adults in seventh and eighth decades.5 4.3 10.4 2. approximately 5% of the NHANES-III never-smokers had ob352 served FEV1/FVC% values below the fifth percentile.7 90. approximately one fourth of current-smokers and one eighth of never-smokers in the seventh and eighth decades who had observed FEV1/FVC% above the fifth percentile were wrongly identified (normals misidentified) as having airway obstruction because their observed FEV1/FVC% was Ͻ 70%.17 Crapo et al.1 32.7 14.6 2.8 49.3 42.2 5.0 0.chestpubs.0 0. More than one half of those in the third and fourth decades and one fifth in the fifth decade with an observed FEV1/ FVC% below the fifth percentile for their age were wrongly identified (abnormals misidentified) as not having airway obstruction because their observed FEV1/FVC% was Ն 70%. in which abnormals were misidentified.1 4.2 34.5 3.6 50.7 25. for each decade.0 0.5 0.3 43 64 90 100 100 100 19 32 48 93 98 100 46 57 86 100 100 100 23 44 76 100 100 100 41 99 100 100 99 95 89 78 100 100 100 99 94 87 100 100 99 87 75 66 100 100 100 98 87 73 100 81 100 100 86 56 31 23 100 100 100 89 65 52 100 100 95 78 68 69 100 100 100 97 72 63 100 55 97 98 99 100 100 100 97 96 98 99 100 100 95 95 97 100 100 100 91 94 95 100 100 100 95 100 Decade of Life Male never-smokers Third Fourth Fifth Sixth Seventh Eighth Female never-smokers Third Fourth Fifth Sixth Seventh Eighth Male current-smokers Third Fourth Fifth Sixth Seventh Eighth Female current-smokers Third Fourth Fifth Sixth Seventh Eighth All adults Third and fourth Seventh and eighth *Data are presented as %. 2010 © 2007 American College of Chest Physicians .0 0.3 0.3 81. and overidentifies airway obstruction in older adults.0 0.0 11.0 0. Discussion This study illustrates the importance of using statistically valid spirometric criteria to identify the prevalence of airway obstruction.0 5.0 0.0 9. the standard of FEV1/FVC% Ͻ 70% or Ն 70% underidentifies airway obstruction in the younger adults.8 15.4 1.5 37.19 or Knudson et al20 reference equations were used.2 3.6 0.

specificity. The 2005 ATS/ERS definition of airway obstruction. In cross-sectional studies. seems both unfortunate and unnecessary. www.9) 27 (7.0) 126 (5. although the FEV1 begins to decline earlier than the FVC CHEST / 131 / 2 / FEBRUARY. would be misidentified as having airway obstruction using the GOLD FEV1/FVC% criterion (Fig 2).1) 17 (5.1) 26 ( at Hopital St Antoine on September 8.4) Knudson et al20 26 (6. 2007 353 Downloaded from chestjournal. and one fifth in the fifth decade (Fig 2).1) 162 (7.5) 12 (3. plus the high frequency of misidentified normal subjects (approximately two thirds in the third decade. The latter indicates that in these decades. Underidentification and overidentification of airway obstruction. 2010 © 2007 American College of Chest Physicians .7) 16 (5.4) 22 (4.8) Crapo et al19 31 (7.4) 28 (8.0) 57 (14. is statistically valid.4) 31 (8. (%). and PPV.9) 24 (7. only an interpretation based on a fixed standard for all adults.3 ie. For each decade.9) 181 (8. Also importantly. The columns below the zero line are abnormals misidentified as normals.chestjournal. one half in the fourth decade. This criterion causes underidentification of airway obstruction in the younger subjects.chestpubs. 405 452 322 307 320 383 2. No.3) *Data are presented as No. a FEV1/FVC% below the fifth percentile of a normal never-smoking population of similar age.4) 23 (5.5) 32 (10. We do not question the numeric value of the observed FEV1/FVC%.906 never-smokers and 3. with inherent lowered sensitivity. The continuing use of the GOLD 70% criterion. the observed GOLD FEV1/ FVC% criterion fails to identify airway obstruction in many in the third to fifth decades of life. and overidentification in the older subjects. the columns above zero line are normals misidentified as abnormals. the left of the paired columns are never-smokers (N-S) and the right of the paired columns are current smokers (C-S). nearly half of those with observed FEV1/FVC% values below fifth percentile LLN values would not be considered to have airway obstruction by the GOLD criterion because their observed FEV1/FVC% Ն 70%.189 Hankinson et al17 22 (5. by decade. in 5.9) 19 ( decade and the 32 to 64% sensitivity in the fourth decade (Table 3).497 current-smokers using the GOLD 70% of FEV1/FVC% as a criterion.Figure 2. reasonable identification in early middle age.2) 27 (8. Confirming this finding are the 19 to 46% sensitivity in the third Table 4 —NHANES-III Never-Smoking White Adults With FEV1/FVC% Below the Fifth Percentile LLN Using Three Sets of Reference Values* Abnormal Values Decade of Life Third Fourth Fifth Sixth Seventh Eighth Total Patients.7) 29 (6.

4 To the authors.19.20 A proper concern is whether the FVC alone. Lundback et al. have lower coefficients of variation than those of individual lung volumes17. at least in American and European never-smoking populations. peak oxygen uptake. suffices as a denominator in ascertaining the presence of airway obstruction. concluded that 26% of Korean men and 10% of Korean women Ͼ 45 years old have COPD. values below fifth percentile have been recommended for use in identifying abnormality since 1991.with increasing age in never-smoking populations after maturity. Following are some examples in which use of GOLD criteria could lead to ill-advised actions. and FEV1. many of these individuals have FEV1/FVC% that are well within normal limits for their age and should not be identified or treated as having airways obstruction. and height are approximately 1. the VC may be considerably larger. The planning for and necessity of preventative or therapeutic interventions and their cost/benefit ratio should be based on the best available spirometric criteria. However. or acute or chronic inhalant exposure. such as forced expiratory flow. The high prevalence in both latter studies11.12 is undoubtedly due to not using appropriate age-specific fifth percentile values.chestpubs.8 Wilson et al. yet they failed to advocate using fifth percentile values. FEV1/FVC% declines linearly with age.12 on the basis of FEV1/FVC% Ͻ70%. when evaluating a general population. 2010 © 2007 American College of Chest Physicians .17 decline in FEV1/FVC% appears to be quite linear within each gender and ethnic group.22. sex. spirometry can help identify lung injury due to exposure to occupational hazards.25 Of the several measurements advocated to identify airway obstruction.20 –22 Confirmatory is the finding in three commonly used reference groups that approximately 5% of healthy never-smoking adults have FEV1/FVC% below the 95% confidence limits. response to inhaled bronchodilators. Behrendt. Clearly. these reasons seem unimportant compared to the objective of being able to properly detect airway obstruction in the young or prevent the overdiagnosis and treatment of older individuals who do not have airway obstruction. at least in survivors to age 70 or 80 years. concluded that 16 to 18% of those never-smokers aged 60 to 69 years and 25 to 30% of those aged 70 to 79 years had COPD. gender. unnecessary costs.19. Clinical findings including history.11 using the NHANES-III data for 7. but the prebron354 chodilator spirometric values are key in identifying whether or not baseline airway obstruction is present. and individual and societal harm. the primary measurement of airway obstruction.23 and Celli et al al13 correctly noted that the prevalence of airway obstruction in their studies depended on what spirometric criteria were used. Using poor spirometric criteria may lead to misdirection of resources.17. the GOLD criterion4 that concerns response to bronchodilators should be helpful in differential diagnosis.24 and much lower coefficients of variation than measures of flow dependent on volume.20 coefficients of variation for volume measures such as FEV1 and FVC for a given age. acute or chronic infection. chronic bronchitis. Original Research Downloaded from chestjournal. Of those Ͼ 45 years. As also found.17. and measurement of gas transfer index are useful in recognizing if airway obstruction may be due to asthma. in this era. The additional GOLD criterion4 requiring a reduction in the absolute value of FEV1 to identify airway obstruction can be questioned because in three commonly used reference groups. and percentage of predicted FEV1/ forced expiratory volume in 6 s (FEV1/FEV6%).14 In the our experience. emphysema. the percentage of forced expiratory volume in 3 s/FVC. The high percentage of older never. For example.24 Only when these normal declines are exceeded should the spirometric finding of airway obstruction be made. the VC and FVC are usually quite similar.19. and other noxious inhalants. all ratios of volume/volume.17. As previously noted. the use of the body mass index to define obesity is not discarded because the formula uses the square of height. VC. and ethnicity.5 to 3 times those for the FEV1/FVC ratio. Kim et al.and currentsmoking adults with observed FEV1/FVC% Ͻ 70% noted in Figure 1 deserves comment. minimized by reference to age.526 never-smokers and a cut-off for FEV1/FVC% of 70%. 20% of men and 91% of women were never-smokers. height. Because of the variability of spirometric values within the general population. the FEV1/ FVC%. or forced expiratory flow at 50% of VC. Normal aging changes should not be considered disease or abnormal. Nevertheless.17. many current-smoking adults in their third and fourth decades with FEV1/FVC% below the LLN should not be dismissed as normal because their FEV1/FVC% is Ͼ 70% (Fig 2). Spirometric surveys do not identify the specific cause of airway obstruction or the presence or absence of disease. physical examination.20. but with moderate-to-severe obstructive disease. GOLD defends its definition of airway obstruction as an FEV1/FVC% Ͻ 70% on the basis of its simplicity and ease of remembrance. strengthening the evidence of airway obstruction. tobacco at Hopital St Antoine on September 8.19 –22. without obtaining the slow or unforced VC for expressing the percentage of FEV1/VC. Other examples of aging-related physiologic changes in which age is factored into predicted values are peak heart rate. mid-expiratory range.

org CHEST / 131 / 2 / FEBRUARY. Chest 2005. 129:369 –377 23 Wilson D. Am Rev Respir Dis 1985. 144:1201–1218 26 Ferguson GT. Vital capacities in acute and chronic airway obstruction: dependence on flow and volume histories. Rodarte JR. Jensen RL. Eur Respir J 2004. Am J Med 2005. et al. Viegi G. Odencrantz JR. 118:1364 – 1372 14 Brusasco V. Prevalence of chronic obstructive pulmonary disease in Korea. Difficulties identifying and targeting COPD and population-attributable risk of smoking for COPD. 2007 355 Downloaded from chestjournal. MD: Centers for Disease Control and Prevention. Am J Respir Crit Care Med 2005. Gardner RM. 1994 update. Adams R. References 1 Sobol BJ. et al. COPD in Japan: the Nippon COPD Epidemiology study. Crichton DA. Heaney L. Brusasco V. 2007 6 Celli BR. Pincock AC. FEV1/ FEV6 and FEV6 as an alternative for FEV1/FVC and FVC in the spirometric detection of airway obstruction and restriction. 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