Everyone uses the FEV1/FVC ratio as the primary factor in determining the presence or absence of airway obstruction but there are differences of opinion about what value of FEV1/FVC should be used for this purpose. Currently there are two main schools of thought; those that advocate the use the GOLD fixed 70% ratio and those that instead advocate the use the lower limit of normal (LLN) for the FEV1/FVC ratio.
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has stated that a post-bronchodilator FEV1/FVC ratio less than 70% should be used to indicate the presence of airway obstruction and this is applied to individuals of all ages, genders, heights and ethnicities. The official GOLD protocol was first released in the early 2000’s and was initially (although not currently) seconded by both the ATS and ERS. The choice of 70% is partly happenstance since it was one of two fixed FEV1/FVC ratio thresholds in common use at the time (the other was 75%) and partly arbitrary (after all why not 69% or 71% or ??).
The limitations of using a fixed 70% ratio were recognized relatively early. In particular it has long been noted that the FEV1/FVC ratio declines normally with increasing age and is also inversely proportional to height. For these reasons the 70% threshold tends to over-diagnose COPD in the tall and elderly and under-diagnose airway obstruction in the short and young. Opponents of the GOLD protocol say that the age-adjusted (and sometimes height-adjusted) LLN for the FEV1/FVC ratio overcomes these obstacles.
Proponents of the GOLD protocol acknowledge the limitation of the 70% ratio when it is applied to individuals of different ages but state that the use of a simple ratio that is easy to remember means that more individuals are assessed for COPD than would be otherwise. They point to other physiological threshold values (such as for blood pressure or blood sugar levels) that are also understood to have limitations, yet remain in widespread use. They also state that it makes it easier to compare results and prevalence statistics from different studies. In addition at least two studies have shown that there is a higher mortality of all individuals with an FEV1/FVC ratio below 70% regardless of whether or not they were below the FEV1/FVC LLN. Another study noted that in a large study population individuals with an FEV1/FVC ratio below 70% but above the LLN had a greater degree of emphysema and more gas trapping (as measured by CT scan), and more follow-up exacerbations than those below the LLN but above the 70% threshold.
Since many of the LLN versus GOLD arguments are based on statistics it would be useful to look at the predicted FEV1/FVC ratios in order to get a sense of how much under- and over-estimation occurs with the 70% ratio. For this reason I graphed the predicted FEV1/FVC ratio from 54 different reference equations for both genders and a variety of ethnicities. Since a number of PFT textbooks have stated that the FEV1/FVC ratio is relatively well preserved across different populations what I initially expected to see was a clustering of the predicted values. What I saw instead was an exceptionally broad spread of values.
Looking closely I am unable to see any particular relationship between ethnicity or geographical location and the FEV1/FVC ratio. This fact is highlighted by the slope (rate of decline) of the FEV1/FVC ratios with age.
Many of the studies that were the source of these reference equations did not include an LLN specifically for the FEV1/FVC ratio. For this reason I used 90% of predicted as a conservative substitute (this decision is based on the NHANESIII FEV1/FVC ratio LLN that is approximately 89%-90% of the predicted across the range of ages for all ethnicities).
When this is done, the limitation of the 70% ratio in relation to increased age becomes more obvious, particularly since the average of all LLN’s (for males) reaches 70% at age 65. This means that approximately half of the reference equation LLN’s show a decrease below 70% before that age, and some as young as age 33. Theoretically at least, using the GOLD criteria by age 65 up to half of the world population could have spirometry that was potentially within normal limits but would be considered to have COPD.
At first glance this is a strong argument in favor of the use of the LLN to determine the presence of airway obstruction, and in general I would agree. However, what it also makes quite clear is that the LLN is highly dependent on which reference equation is chosen and this to some extent bolsters the pro-GOLD argument about its simplicity.
I was surprised at the wide range of values from the different reference equations particularly since the FEV1/FVC ratio is often considered to be a highly conserved value between ethnicities (and notably within the NHANESIII and GLI studies there is little difference between Blacks, Hispanics, Caucasians and Asians). The reasons for this wide range of results are unclear and may be related to differences in the size or makeup of the different study populations, differences in statistical analysis and/or differences in the spirometry equipment. It should also be noted that the criteria used to assess test quality and the acceptability of spirometry results are based on the individual characteristics of the FVC and FEV1, not on the FEV1/FVC ratio.
The ATS/ERS statement on interpretation recommends the use of the largest vital capacity, regardless of source, when calculating the FEV1/FVC ratio. The effect that this has on the prevalence of airway obstruction by either the LLN or 70% threshold does not appear to have been explored, however. Using the reference equations from Gutierrez et al (chosen because the same population was used to derive reference equations for both spirometry and lung volumes) it appears that the FEV1/SVC ratio is lower than the FEV1/FVC ratio at all ages and that the difference between the two increases as age increases.
Although I fully understand and agree with the point of using the SVC when it is larger than the FVC, this makes it clear that the LLN for the FEV1/FVC ratio does not apply to the FEV1/SVC ratio.
Conversely, the FEV1/FEV6 has less variability than the FEV1/FVC ratio and for this reason has been suggested as a more reliable substitute. FEV6 however, can also be reduced when obstruction is present and for this reason the decrease in the FEV1/FEV6 ratio may not be a reliable indicator of the severity of obstruction.
The GOLD criteria were developed primarily to diagnose the presence of COPD. One of the hallmarks of COPD is that it is only minimally responsive to short-acting bronchodilators. For this reason at least some of the confusion surrounding the GOLD 70% threshold lies in the fact that it should only be applied to the post-bronchodilator FEV1/FVC ratio. It has been shown that the number of individuals considered to have airway obstruction using the GOLD criteria increases by up to 30 percent when only the pre-bronchodilator FEV1/FVC ratio is considered. This doesn’t necessarily make the 70% threshold more correct but it also shouldn’t be applied as a general rule to all spirometry either.
One criticism that I’d level at a number of the papers advocating the use of the LLN over the GOLD 70% threshold is that the authors often begin by defining airway obstruction as an FEV1/FVC ratio below the LLN and then proceed to critique the 70% threshold for mis-categorizing individuals. I don’t necessarily disagree with the underlying premise but this approach is a little specious since at least one study has indicated that the use of the LLN alone tends to under-diagnose COPD. Other studies have indicated that the addition of a reduced FEV1 (either below 80% of predicted or the LLN) and an elevated RV/TLC ratio are needed in addition to an FEV1/FVC below the LLN in order to improve specificity.
There is some evidence that individuals with an FEV1/FVC ratio below 70% tend to have more significant lung disease and a higher mortality. Numerous studies however, have shown that the GOLD threshold overestimates airway obstruction in the elderly and the tall and underestimates it in the young and the short. The predicted FEV1/FVC ratio LLN’s largely agree with this finding. I think that the greatest fault of the GOLD 70% threshold is that for too many individuals it confuses the normal changes that occur as part of aging with a disease process. Since an incorrect diagnosis of COPD can lead to inappropriate care plans, testing and medications for a patient, this alone probably outweighs any advantages the 70% threshold may have.
The preponderance of evidence is in favor of the FEV1/FVC ratio LLN. Moreover it is applicable to all forms of airway obstruction which includes pre-bronchodilator spirometry and this generally makes it more useful than the 70% threshold, particularly for the young. The LLN approach is not without its own problems, however, and any diagnosis of COPD should be multifactorial and rely on more than just the FEV1/FVC ratio. In addition more than one study has noted that which patients are considered to have airway obstruction was dependent on which set of reference equations were used for analysis and as can be seen the differences between reference equations, even within the same ethnicities, can be quite large.
Part of the problem with either approach is that most patients being screened for COPD are often performing spirometry for the first time in their lives. Without any knowledge of an individual’s baseline results the quality of any diagnosis is necissarily going to be limited. A simple answer to this is that spirometry, like blood pressure, needs to become a more commonly performed test, most particularly for patients that for whatever reason (smoking, work exposure, elevated air pollution, genes) have a higher level of risk.
The broad spread in the FEV1/FVC ratio reference equations is a problem for both the 70% threshold and the LLN. For the 70% threshold it puts into question both whether the FEV1/FVC ratio is actually preserved across different population and moreover whether 70% itself is correct. For the LLN, it may well be true that the LLN is more statistically correct, but the selection of the most appropriate reference equations for any one individual remains problematic.
FEV1/FVC Ratio Reference Equations, Study characteristics:
|Ethnicity:||#Female:||Female Ages:||#Male:||Male Ages:|
|[R]||White||97||Not stated||102||Not stated|
|[T]||White||270||25 to >75||373||20 to >75|
|[W]||White||96||18 to >70||83||18 to >70|
FEV1/FVC Ratio Reference Equations, Direct
FEV1/FVC Ratio Reference Equations, Indirect
Aggarwal AN, Gupta DG, Agarwal R, Jindal SK. Comparison of the lower confidence limit to the fixed-percentage method for assessing airway obstruction in routine clinical practice. Resp Care 2011; 56; 56(11): 1778-1774.
[A] Al Ghobain MO, Ahamad EH, Alorainy HS, Hazmi MA, Al Moamary MS, Al-Hajjaj MS, Idress M, Al-Jahdali H, Zeitouni M. Spirometric reference standards for healthy nonsmoking Saudi adults. Clinical Respir J 2014; 8: 72-78.
Bhatt SP, Sieren JC, Dransfield MT, Washko GR, Newell JD, Stinson DS, Zamba GKD, Hoffman EA. Comparison of spirometric thresholds in diagnosing smoking-related airflow obstruction. Thorax 2014; 69: 409-414.
[B] Bibi H, Goldsmith JR, Vardi H. Racial or ethnic variations in spirometric lung function norms. Recommendations based on study of Ethiopian Jews. Chest 1988; 93(5): 1026-1030.
Celli BR, Halbert RJ, Isonaka S, Schau B. Population impact of different definitions of airway obstruction. Eur Respir J 2003; 22(2): 268-273
Celli BR, Halbert RJ. Point: Should we abandon FEV1/FVC < 70% to detect airway obstruction? No. Chest 2010; 135(5): 1037-1040.
Celli BR, Halbert RJ. Rebuttal from Drs Celli and Halbert. Chest 2010; 138(5): 1042-1043
Cerveri I, et al. Underestimation of airflow obstruction among young adults using FEV1/FVC <70% as a fixed cutoff: a longitudinal evaluation of clinical and functional outcomes. Thorax 2008; 63: 1040-1060.
[C] Crapo RO, Jensen RL, Lockey JA, Aldrich V, Elliott CG. Normal spirometric values in healthy Hispanic Americans. Chest 1990; 98(6):1435-1439.
Enright PL, Brusasco V. Counterpoint: Should we abandon FEV1/FVC < 70% to detect airway obstruction? Yes. Chest 2010; 138(5): 1040-1042
Enright PL, Brusasco V. Rebuttal from Drs Enright and Brusasco. Chest 2010; 138(5): 1043-1044.
[D] Fulambarker A, Copur AS, Javen A, Jere S, Cohen ME. Reference values for pulmonary function in Asian Indians living in the United States. Chest 2004; 126: 1225-1233
Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Updated 2016.
[E] Golshan M, Nematbakhsh M, Amra B, Crapo RO. Spirometric reference values for a large Middle Eastern population. Eur Respir J 2003; 22: 529-534.
Goossens LMA, Leimer I, Metzdorf N, Becker K, Rutten-van Molken MPMH. Does the 2013 GOLD classification improve the ability to predict lung function decline, exacerbations and mortality: A post-hoc analysis of the 5-year UPLIFT trial. BMC Pulm Med 2010; 14:163.
Guder F, Brenner S, Angermann CE, Ertl G, Held M, Sachs AP, Lammers JW, Zanen P, Hoes AW, Stork S, Rutten FH. Gold of lower limit of normal definition? A comparison of with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohort-study”. Respir Research 2012; 13:13.
[F] Gutierrez C, et al. Reference values of pulmonary function tests for Canadian caucasians. Can Respir J 2004; 6: 414-424.
[G] Hankinson JL, Odencrantz JR, Fedan, KB. Spirometric reference values from a sample of the general U.S. Population. Amer J Resp Crit Care 1999; 159: 179-187
Hansen JE, Sun XG, Wasserman K. Spirometric criteria for airway obstruction: Use percentage of FEV1/FVC tatio below the fifth percentile, not <70%. Chest 2007; 131: 349-355.
[H] Ip MS, Ko FW, Lau AC, Yu W, Tang K, Choo K, MM Chan-Yeung. Updated spirometric reference values for Adult Chinese in Hong Kong and implications on clinical utilization. Chest 2006; 129: 384-392.
[I] Jindal SK, Wahi PL. Pulmonary function laboratory in the tropics: needs, problems and solutions. In: Sharma OP, editor. Lung disease in the tropics. New York: Marcel Dekker; 1991: 523–542.
[J] Johannessen A, Lehmann S, Omenaas ER, Side GE, Bakke PS, Gulsvik A. Post-bronchodilator spirometry reference values in Adults and implications for disease mangement. Amer J Resp Crit Care Med 2006; 173(12): 1316-1325
[K] Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow volume curve with growth and aging. Am Rev Resp Dis 1983; 127: 725-734
[L] Kuster SP, Kuster D, Schindler C, Rochat MK, Braun J, Held L, Brandli O. Reference equations for lung function screening of healthy never-smoking adults aged 18-80 years. Eur Respir J 2008; 31: 860-868.
[M] Lam DCL, Fong DYT, Yu WC, Ko FWS, Lau ACW, Chan JWM, Choo KL, Mok TYW, Tam CY, Ip MSM, Chan-Yeung MMW. FEV3, FEV6 and their derivatives for detecting airflow obstruction in adult Chinese. Int J Tuberc Lung Dis 2012; 16(5): 681-686.
Mannino DM, Buist AS, Vollmer WM. Chronic obstructive pulmonary disease in the older adult: what defines abnormal lung function. Thorax 2007; 62(3): 237-241.
[N] Marion MS, Leonardson GR, Rhoades ER, Welty TK, Enright PL. Spirometry reference values for American Indian adults. Chest 2001; 120: 489-495
[O] Marsh S, Aldington S, Williams M, Weatherall M, Shirtcliffe P, McNaughton A, Pritchard A, Beaseley R. Complete reference ranges for pulmonary function tests from a single New Zealand population. New Zealand Med J 2006; 119: N1244.
Medbo A, Melbye H. Lung function testing in the elderly – Can we still use FEV1/FVC < 70% as a criterion of COPD. Respir Med 2007; 101: 1097-1105.
[P] Mengesha YA, Mekonnen Y. Spirometric lung function tests in normal non-smoking Ethiopian men and women. Thorax 1985; 465-468.
[Q] Morris JF, Koski A, Johnson LC. Spirometric standards for healthy nonsmoking adults. Am Rev Resp Dis 1971; 103: 57-67.
[R] Morris JF, Koski A, Temple WP, Claremont A, Thomas DR. Fifteen-year interval spirometric evaluation of the Oregon Predictive equations. Chest 1988; 93: 123-27
[S] Oh YM, Hong SB, Shim TS, Lim CM, Koh Y, Kim WS, Kim DS, Kim WD, Kim YS, Lee SD. Effect of a new spirometric reference equation on the interpretation of spirometric patterns and disease severity. Tuber Respir Dis 2006; 60: 215-220.
[T] Pereira CADC, Sato T, Rodrigues SC. New Reference Values for forced spirometry in white adults in Brazil. J Bras Pneumol 2007; 33: 397-406.
Quanjer PH et al. ERS Task Force. Multi-ethnic reference values for spirometry for the 3-95-yr range: The global lung funtion 2012 equations. Eur Respir J 2012: 40: 1324-1343.
[U] Razi E, Moosavi GHA, Akbari H. Spirometric standards for healthy Iranians dwelling in the centre of Iran. Tanoffos 2005; 4(15): 19-26.
[V] Roa CC, Zaldivar CA, Salonga RC, Bobadilla J, Lansang MA, Reodica R, Balgos A, Blanco J, Tanchuco JQ. Normal standards for ventilatory function in adult Filipinos. Phillipine J Internal Med, 2013; 51(1): 1-6.
[W] Roberts CM, MacRae KD, Winning AJ, Adams L, Seed WA. Reference values and prediction equations for normal lung function in a non-smoking white urban population. Thorax 1991; 46: 643-650.
Roberts SD, Farber MO, Knox KS, Phillips GS, Bhatt NY, Mastronarde JG, Wood KL. FEV1/FVC ratio of 70% misclassifies patients with obstruction at the extremes of age. Chest 2006; 130: 200-206.
[X] Singh R, Singh HJ, Sirisinghe RG. Spirometric studies in Malayasian between 13 and 69 years of age. Med J Malaysia 1993; 48: 175-184
[Y] Steinvil A, Fireman E, Wolach O, Rebhun U, Cohen M, Shapira I, Berliner S, Rogowski O. The effect of ethnic origin on pumonary prediction equations in a Jewish immigrant population. Respiratory Medicine 2008; 102: 919-926.
Swanney MP, Ruppel G, Enright PL, Pederson OF, Crapo RO, Miller MR, Jensen RL, Falashetti E, Schouten JP, Hankinson JL, Stocks J, Quanjer PH. Using the lower limit of normal for the FEV1/FVC ratio reduces misclassification of airway obstruction. Thorax 2008; 63: 1046-1051.
Vaz Fragoso CA, Concato J, McAvay G, Van Ness PH, Rochester CL, Yaggi HK, Gill TM. The ratio of FEV1 to FVC as a basis for establishing chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010; 181(5): 446-451.
Vollmer WM, Gislason p, Burney P, Enright PL, Gulsvik A, Kocabas A, Buist AS. Comparison of spirometry criteria for the diagnosis of COPD: Results from the BOLD study. Eur Respir J 2009; 34(3): 588-597.
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