Department of Medicine, North District Hospital
Whether a subject has airflow obstruction or not is a common question to be answered by lung function testing A number of spirometric indices are used in the assessment of airflow limitation.
Forced expiratory volume in one second/ (forced) vital capacity (FEV1/VC or FEV1/FVC)
The standard index to diagnose airflow obstruction by the American Thoracic Society (ATS), European Respiratory Society (ERS)1 and Global Initiative of Obstructive Lung Diseases (GOLD)2. GOLD and the ATS/ERS standards for the diagnosis and management of patients with COPD3 recommend a fixed FEV1/FVC ratio of 0.7 as the cut-off. A post-bronchodilator FEV1/FVC ≤ 0.7 confirms presence of airflow limitation that is not fully reversible.
FEV1/FVC decreases with increasing age and height in normal subjects, therefore an over-diagnosis of airflow obstruction will occur in elderly and tall subjects when a fixed cut-off value is used4,5,6. A fixed cut-off ratio is recommended in GOLD and the ATS/ERS guidelines on COPD3 because not many population has a prediction equation for the FEV1/FVC. The ATS official statement in 19917 and the ATS/ERS task force on standardization of lung function testing in 20051 recommend the use of a statistically derived lower limit of normal (LLN) if prediction equations are available. The LLN is typically the 5th percentile value, which can be roughly estimated by the predicted value - 1.645*standard error of the estimate (SEE). Airflow obstruction is diagnosed if FEV1/FVC is lower than the LLN. An example in shown (Figure 1).
Should we use FVC or VC in the ratio? The ATS/ERS task force prefers using VC instead of FVC. This is because the unforced slow VC usually exceeds FVC in the presence of airflow obstruction and FEV1/VC can identify more obstructive patterns than FEV1/FVC1. In the ATS/ERS task force document VC refers to the maximal volume that can be displaced from the lung, that is the largest value among inspiratory VC (IVC), expiratory VC (EVC) and FVC when it is applied to calculate the FEV1/VC ratio.
A normal FEV1/FVC does not exclude airflow obstruction8. A pattern of “pseudo-restriction” (FEV1 and FVC concomitantly decreased, FEV1/FVC ratio is normal) can occurs if the subject cannot exhale long enough to empty the lungs to the residual volume. Patchy peripheral airway collapse can also results in this pattern. On spirometry the expiratory flow-volume curve will appear concave at the end of the maneuver. In this case one should still suspect the presence of an underlying airflow obstruction, especially if a significant post-bronchodilator response is observed in the FEV1 or FVC. The diagnosis of airflow obstruction is then need to be confirmed by excluding true restriction on a lung volume study. When FEV1/VC or FEV1/FVC is normal but VC or FVC is decreased, airflow obstruction should still be diagnosed if the total lung capacity is normal or high1.
FEV1/ Forced expiratory volume in six seconds (FEV6)
In performing the FVC maneuver the total exhalation time can be prolonged and technically demanding in patients with severe airflow limitation. FEV6 is suggested as a surrogate of FVC. It has been demonstrated that 99 % of the FVC can be obtained in the first 6.64 seconds for patients with an FEV1/FVC ratio as low as 50 %9. The FEV1/FEV6 ratio below LLN has a positive and negative predictive value of 97 % for spirometric diagnosis of airway obstruction10. Data from the Lung Health Study also showed that FEV1/FEV6 is as good as the FEV1/FVC ratio in predicting the decline in lung function in adult smokers11. Population prediction equations for FEV1/FEV6 have been determined in the U.S. and Europe5,12. The ATS/ERS task force statement1 formally accepted the use of FEV6 as a substitute of VC if LLN is available. When using fixed cut-offs, although not recommended, one may refers to the conclusion by two large population studies that FEV1/FEV6 < 0.73 is an valid alternative to the FEV1/FVC < 0.70 to diagnose airflow obstruction13,14.
Mean forced expiratory flow between 25 % and 75 % of FVC (FEF25-75)
In the presence of borderline value of FEV1/VC a reduced FEF25-75 may suggests airflow limitation. When the FEV1 and FEV1/VC are within the normal range, the clinical significance of an abnormal FEF25-75 is however limited. The ATS/ERS task force has cautioned the wide variability of FEF25-75 in healthy subjects on interpretation of an abnormal FEF25-75, and recommend to limited primary interpretation of spirograms to VC, FEV1 and FEV1/VC to avoid the problem of simultaneously examining a multitude of parameters to see if any abnormalities are present1. The percentage of subjects with at least one abnormal lung function parameter can rise substantially if a complete battery of lung function tests is performed15.
Forced expiratory volume in three seconds (FEV3)/FVC and 1-FEV3/FVC
FEV3/FVC is proposed to be a sensitive and more reliable index to identify early expiratory flow limitation when compared to FEF25-75. While a decrease in FEV1/FVC reflects reduction in short-time-constant lung units, a decrease in FEV3/FVC or increase in the fraction that had not been expired during the first 3 seconds (1-FEV3/FVC) represents an increase in long-time-constant lung units. Therefore these indices should be sensitive in detecting early airflow limitation. In contrast to FEF25-75, FEV3/FVC is similar to FEV1/FVC in that the LLN of both indices are relatively stable at a fixed percentage of the predicted mean value regardless of advancement of age. The variability of FEV3/FVC is much lower than FEF25-75 and also lower than that of FEV1/FVC in a large population16. Prediction equations for FEV3 and FEV3/FVC have been published16,17,18. FEV3 and FEV3/FVC however are not yet included as a standard parameter by the ATS/ERS1.
Assessment of severity of airflow obstruction
Readers may have noticed there are apparent discrepancies in the severity classifications of airflow limitation. In the ATS/ERS task force statement1 severity of airflow obstruction is assessed by FEV1 as a percentage of the predicted. The severity classification applies to both the pre- and post-bronchodilator test. On the other hand it is a requirement of GOLD and ATS/ERS guidelines on COPD that severity is based on the post-bronchodilator FEV1 (Table 1).
Why is the post-bronchodilator FEV1 used in the diagnosis and classification of the severity of COPD? The post-bronchodilator parameter is used because of the intention to remove the reversible component. Any airflow obstruction left after maximal bronchodilatation is the fixed “chronic” component. It therefore refers to the severity of the “disease”. The severity of an airflow obstruction per se should naturally be determined by the pre-bronchodilator FEV1.
Classifications of severity are just “schemas”7. In practice, I usually avoid applying different schemas at the same time to avoid confusion (e.g. a spirometry report stating patient has “moderately severe airflow obstruction, compatible with Moderate COPD (GOLD stage II) - although the statement can be the most correct description).
The difference in severity of airflow obstruction and severity of the disease can also be understood by the fact that assessment of COPD and asthma severity is not based on spirometric values alone. Symptoms and other clinical parameters (e.g. presence of chronic respiratory failure in COPD2, the frequency of symptoms and peak flow variability in asthma) are required in assessing disease severity. Therefore, it is recommended to always insert a disclaimer “… as assessed by spirometry” or “Physiologic assessments of severity may differ from clinical assessments” in the spirometry report7. In practice, I insert the disclaimer whenever the severity of the disease is commented.
Local reference equations
In Hong Kong spirometry prediction equations for FEV1, FVC, FEV1/FVC, FEF25-75, FEF50, and the corresponding prediction equation for the 5th percentile LLN (or instead, the residue standard deviation allowing estimation of the LLN) in paediatric and adult population has been published19,20. Local prediction equations are also available for carbon monoxide diffusing capacity and plethysmographic lung volumes and they are listed as well in the reference21,22.
Reference
1. Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function test. Eur Respir J 2005; 26:948-968
2. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2006. Available at: http://www.goldcopd.org. Accessed August 29, 2007.
3. Celli BR, MacNee WM and committee members. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004; 23:932-946
4. Roberts SD, Farber MO, Knox KS, et al. FEV1/FVC ratio of 70 % misclassifies patients with obstruction at the extreme of age. Chest 2006; 130: 200-206
5. Hankinson JL, Odencratz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med 1999; 159:179–187
6. Hardie JA, Buist AS, Vollmer WM, et al. Risk of over-diagnosis of COPD in asymptomatic elderly never-smokers. Eur Respir J 2002; 20:1117–1122
7. American Thoracic Society. Lung function testing: Selection of reference values and interpretative strategies. Am Rev Respir Dis 1991; 144:1202-1218
8. Stănescu D, Veriter C. A normal FEV1/VC ratio does not exclude airway obstruction. Respiration 2004; 71:348-352
9. Pederson OF. FEV6: a shortcut in spirometry?. Eur Respir J 2006; 27:245-247
10. Vandevoorde J, Verbanck S, Schuermans D, et al. FEV1/FEV6 and FEV6 as an alternative for FEV1/FVC and FVC in the spirometric detection of airflow obstruction and restriction. Chest 2005; 127:1560-1564
11. Enright PL, Connett JE, Bailey WC. The FEV1/FEV6 predicted lung function decline in adult smokers. Respir Med 2002; 96: 444-449
12. Garcia-Rio F, Pino JM, Dorgham A, et al. Spirometric reference equations for European females and males aged 65–85 years. Eur Respir J 2004; 24: 397–405.
13. Vandevoorde J, Verbanck S, Schuermans D, et al. Obstructive and restrictive spirometric patterns: fixed cut-offs for FEV1/FEV6 and FEV6. Eur Respir J 2006; 27:378-383
14. Melbye H, Medbøa A, Crockett A. The FEV1/FEV6 ratio is a good substitute for the FEV1/FVC ratio in the elderly. Prim Care Respir J 2006; 15:294-298
15. Vedal S, Crapo RO. False positive rates of multiple pulmonary function tests in healthy subjects.Bull Eur Physiopathol Respir 1983; 19:263-266
16. Hansen JE, Sun XG, Wasserman K. Discriminating measures and normal values for expiratory obstruction. Chest 2006; 129: 369-377
17. Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis 1981; 123:659-664
18. Miller MR, Grove DM, Pincock AC. Time domain spirogram indices: their variability and reference values in nonsmokers. Am Rev Respir Dis 1985; 132:1041-1048
19. Ip MS, Ko FW, Lau AC, et al. Updated spirometric reference values for adult Chinese in Hong Kong and implications on clinical utilization. Chest 2006; 129:384-392
20. Ip MS, Karlberg EM, Karlberg JP, et al. Lung function reference values in Chinese children and adolescence in Hong Kong. I. Spirometric values and comparison with other populations. Am J Respir Crit Care Med 2000; 162:424-429
21. Ip MS, Lam WK, Lai AY, et al. Reference values of diffusing capacity of non-smoking Chinese in Hong Kong. Respirology 2007; 12:599-606
22. Ip MS, Karlberg EM, Chan KN, et al. Lung function reference values in Chinese children and adolescence in Hong Kong. II. Prediction equations for plethysmographic lung volumes. Am J respire Crit Care Med 2000; 162:430-435
