Peak Expiratory Flow Is Not a Quality Indicator for Spirometry*
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1 Original Research PULMONARY FUNCTION TESTING Peak Expiratory Flow Is Not a Quality Indicator for Spirometry* Peak Expiratory Flow Variability and FEV 1 Are Poorly Correlated in an Elderly Population Matthew J. Hegewald, MD, FCCP; Michael J. Lefor, MD; Robert L. Jensen, PhD; Robert O. Crapo, MD, FCCP; Stephen B. Kritchevsky, PhD; Catherine L. Haggerty, PhD, MPH; Douglas C. Bauer, MD; Suzanne Satterfield, MD; and Tamara Harris, MD; for the Health, Aging, and Body Composition Study Investigators Background: Peak forced expiratory flow (PEF) and FEV 1 are spirometry measures used in diagnosing and monitoring lung diseases. We tested the premise that within-test variability in PEF is associated with corresponding variability in FEV 1 during a single test session. Methods: A total of 2,464 healthy adults from the Health, Aging, and Body Composition Study whose spirometry results met American Thoracic Society acceptability criteria were screened and analyzed. The three best test results (highest sum of FVC and FEV 1 ) were selected for each subject. For those with acceptable spirometry results, two groups were created: group 1, normal FEV 1 /FVC ratio; group 2, reduced FEV 1 /FVC ratio. For each subject, the difference between the highest and lowest PEF ( PEF) and the associated difference between the highest and lowest FEV 1 ( FEV 1 ) were calculated. Regression analysis was performed using the largest PEF and best FEV 1, and the percentage of PEF (% PEF) and percentage of FEV 1 (% FEV 1 ) were calculated in both groups. Results: Regression analysis for group 1 and group 2 showed an insignificant association between % PEF and % FEV 1 (r , p 0.59, and r , p 0.15, respectively). For both groups, a 29% PEF was associated with a 1% FEV 1. Conclusion: Within a single spirometry test session, % PEF and % FEV 1 contain independent information. PEF has a higher degree of intrinsic variability than FEV 1. Changes in PEF do not have a significant effect on FEV 1. Spirometry maneuvers should not be excluded based on peak flow variability. (CHEST 2007; 131: ) Key words: forced expiratory flow rate; forced expiratory volume; peak expiratory flow; respiratory function tests; spirometry Abbreviations: ATS American Thoracic Society; ERS European Respiratory Society; FEV 1 difference between the highest and lowest FEV 1 ;% FEV 1 percentage of FEV 1 ; FEV 1 -A FEV 1 associated with the largest peak expiratory flow; FEV 1 -B FEV 1 associated with the smallest peak expiratory flow; PEF peak expiratory flow; PEF difference between the highest and lowest peak expiratory flow; % PEF percentage of difference in peak expiratory flow; PEF-A largest peak expiratory flow Peak expiratory flow (PEF) is a measure of maximal expiratory flow that is used to assess qualitative and quantitative effort in spirometry maneuvers and is clinically utilized independently for asthma monitoring via handheld devices. 1 5 FEV 1 is a measurement of volume in the first second of a spirometry maneuver that is used for the diagnosis and monitoring of lung disease. 1,6 Both of these measurements have played an important role in the identification and management of lung disease, particularly asthma. Physiologically, flow characteristics influence measurements of both PEF and FEV 1. Although the viscosity and density of the gas measured, and the length and caliber of the airways impact change in PEF and FEV 1 measurements, 7 9 PEF and FEV 1 measure different aspects of flow. PEF is thought to 1494 Original Research
2 be a measurement of large-caliber airway function ( 2 mm diameter) and is very effort dependent. FEV 1, however, is thought to be a reflection of intermediate and smaller airways. This measurement has both effort-dependent and effort-independent components. Effort during spirometry is, in part, judged by the individual s PEF. It directly correlates to maximal work and the initial effort during a spirometry maneuver. 10 It is also easily quantifiable and can be incorporated in automatic defaults on spirometers that use computer-assisted markers for spirometry acceptability standards. Prior guidelines 11 state that individual PEF measurements should be within 10% of the maximal value. Some popular spirometers provide an error code if there are no trials within 10% of the best (largest) trial for PEF. As a result, PEF reproducibility has been used as a measure of quality assurance for spirometry. Despite this, the most recent American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria for standardization of spirometry do not use differences in PEF between maneuvers to assess quality within a single session. 12 PEF and FEV 1 are used to objectively monitor obstructive lung disease and to evaluate occupational asthma, and are often used as primary outcomes in drug studies. 1,13 16 FEV 1 is commonly assumed to be partly dependent on PEF, based on a high correlation between PEF and FEV Hence, PEF has been used as a surrogate for FEV 1, particularly within an individual over time (ie, change in PEF reflects a similar degree of change in FEV 1 ). There is debate about whether or not changes in PEF truly reflect changes in FEV 1 and subsequently correspond to the degree of obstructive disease in an individual. 18,19 It has also been suggested that there is a negative effort dependence, also referred to as *From the Division of Pulmonary and Critical Care Medicine (Drs. Hegewald, Lefor, Jensen, and Crapo) LDS Hospital and University of Utah, Salt Lake City, UT; Wake Forest University (Dr. Kritchevsky), Winston Salem, NC; Department of Epidemiology (Dr. Haggerty), University of Pittsburgh, Pittsburgh, PA; University of California San Francisco (Dr. Bauer), San Francisco, CA; University of Tennessee Memphis (Dr. Satterfield), Memphis, TN; and National Institutes of Health (Dr. Harris), Bethesda, MD. This study was supported by contracts N01-AG , N01- AG , and N01-AG , and was also supported in part by the Intramural Research program of the National Institutes of Health, National Institute on Aging. The authors have no conflicts of interest to disclose. Manuscript received November 15, 2006; revision accepted January 21, Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( org/misc/reprints.shtml). Correspondence to: Matthew Hegewald, MD, FCCP, Pulmonary Division, LDS Hospital, Eighth Ave & C St, Salt Lake City, UT 84143; matt.hegewald@intermountainmail.org DOI: /chest inverse effort dependence, of the FEV 1. 10,20 This states that maximal effort corresponding to the highest PEF will result in a reduced FEV 1 due to thoracic gas compression. In an attempt to clarify these issues, we tested the premise that difference between the highest and lowest PEF ( PEF) within an individual during a single session is associated with a parallel difference between the highest and lowest FEV 1 ( FEV 1 ). Materials and Methods Participants from the Health, Aging, and Body Composition Study were analyzed. All participants were 70 to 79 years old during recruitment, free of disability in activities of daily living, and free of functional limitations. The institutional review boards at both field centers approved the study, and informed consent was obtained. Subjects performed spirometry and were coached to perform maximal efforts. A National Institute for Occupational Safety and Health volume-based spirometer using a digital shaft encoder to measure volume displacement was used. Three-liter syringe calibrations were done daily. Two of the authors (R.L.J. and R.O.C.) from LDS Hospital in Salt Lake City, UT, scored the quality of the spirograms as A (best) through F (worst) for FEV 1 and FVC based on ATS acceptability and reproducibility standards. Spirograms with FEV 1 and FVC quality scores of C or better were then analyzed. All of these met ATS criteria published in 1995 for reproducibility, with 200 ml between the highest and the next highest FEV Of those that were acceptable, two groups were formed: group 1, normal FEV 1 /FVC ratio; group 2, reduced FEV 1 /FVC ratio, based on the lower limits of normal using prediction equations of Crapo et al. 22 For each group, the three best tests (based on the highest sum of FVC and FEV 1 ) were selected for each subject as recommended by ATS spirometry guidelines. 21 The largest PEF (PEF-A) and the smallest PEF in a single session were chosen from those three best tests. FEV 1 values associated with each PEF were labeled as FEV 1 -A and FEV 1 -B, respectively. Equations associated with these values are as follows: Equation 1: PEF PEF-A PEF-B; all PEF values were positive. Equation 2: FEV 1 FEV 1 -A FEV 1 -B; FEV 1 ; values could be either positive or negative. Equation 3: % PEF ( PEF/PEF-A) 100. Equation 4: % FEV 1 ( FEV 1 /largest FEV 1 ) 100, where PEF-B is the smallest PEF in a single session. Regression analysis was performed on PEF-A and the largest FEV 1, and % PEF and % FEV 1 to look for significant relationships between these variables in both normal and obstructed individuals. The frequency of negative effort dependency was determined by calculating the percentage of subjects in which the largest FEV 1 was associated with a submaximal PEF. Those subjects with acceptable spirometry results based on ATS acceptability and reproducibility criteria, and a 50% PEF were excluded from analysis to reduce the effect of outliers. This resulted in exclusion of 1.9% of subjects. CHEST / 131 / 5/ MAY,
3 Results Of the 3,075 participants in the Health, Aging, and Body Composition Study, 2,863 subjects performed the spirometric evaluation; 352 subjects were excluded because they did not meet ATS acceptability and reproducibility criteria (12.3% of total). Fortyseven subjects were excluded based on a 50% PEF (1.9% of total). Data from 2,464 subjects were analyzed. The mean age of participants was years ( SD). Gender distribution was 49% male and 51% female. Fifty-nine percent of the subjects were white, and the remainder were African American (41%); 10.4% of participants reported being active smokers, 45.7% reported being former smokers, and 43.9% indicated that they never smoked. Group 1 comprised 2,064 subjects with a normal FEV 1 /FVC ratio. Group 2 had 400 subjects with a reduced FEV 1 /FVC ratio. Mean ages of group 1 and group 2 subjects were similar: years and years, respectively. Mean values of each group for best PEF, best FEV 1, best FVC, PEF, FEV 1, % PEF, and % FEV 1 are contained in Table 1. All data appear to be distributed normally. Correlations between PEF and FEV 1 are shown in Figures 1 4. In both groups, the PEF-A and the largest FEV 1 were statistically significantly correlated (group 1: r , p [Fig 1]; group 2: r , p [Fig 3]). % PEF and % FEV 1 were not correlated in either group (group 1: r , p 0.59 [Fig 2]; group 2: r , p 0.15 [Fig 4]). In group 1, the % PEF explains 0.3% of the variability in % FEV 1 in normal patients with acceptable spirometry results (Fig 2). Among all participants, we calculated that on the average a 29% PEF was associated with a 1% FEV 1. Mean % PEF was 14.3, and mean % FEV 1 was In 39.4% of all subjects, the PEF-A was associated with a less than maximal FEV 1. This relationship did not change when the % PEF was limited to 10% (those with the most reproducible PEF values). Table 1 Demographic and Spirometry Values by Group* Variables Group 1 (n 2,291) Group 2 (n 410) Age, yr Best PEF, ml/s 5,666 1,850 4,183 1,703 Best FEV 1,mL 2, , Best FVC, ml 2, , PEF, ml/s FEV 1,mL % PEF % FEV *Data are presented as mean 1 SD. Discussion Our study demonstrates that in healthy older subjects within a single test session, there is a poor correlation between PEF variability and FEV 1 variability. An average 29% PEF has an associated average FEV 1 of 1%. FEV 1 is a stable measurement even with large changes in PEF. This suggests that FEV 1 and PEF measure different aspects of lung function. This is not unexpected because PEF occurs in the first 100 to 200 ms of an expiratory effort and is considered a measure of large airway function, whereas FEV 1 measures the entire first second of exhalation and is influenced by both large and small airways function. These data suggest that current ATS/ERS acceptability criteria that emphasize reproducibility of FEV 1 and FVC for determining acceptable spirometric results, and do not include PEF reproducibility, are appropriate. 12 These findings challenge the utility of using PEF as a measure of quality in spirometry and suggest that spirometry maneuvers should not be excluded based on PEF variability. The primary limitation of this study is that it included only elderly adults and therefore may not be applicable to the general population. The value of using PEF to assess quality in spirometry has been debated. Several studies have tried to address this issue in various ways. Krowka et al 10 examined PEF and its effect on FEV 1 with maximal and submaximal effort. After demonstrating that maximal work was related to the highest PEF, they discovered that the highest PEF was not associated with the largest FEV 1. This concept, called negative effort dependence, was attributed to thoracic gas compression. Krowka et al 10 proposed that PEF should be used as an objective, reproducible parameter for individual effort during spirometry maneuvers because this will result in less variability in FEV 1. Our results question the importance of negative effort dependence of FEV 1. In our data, increasing PEF (and thus increasing effort) resulted in an increase in FEV 1 in 60% of subjects. The majority of subjects exhibited positive effort dependence for FEV 1. Regardless, PEF and thus initial effort results in minimal FEV 1. Park 23 examined spirometry results from 10 normal and 12 obstructed patients. The study compared acceptable tracings with the highest PEF (largest effort) vs those with the highest FVC (largest lung volume). In tracings with the largest sum of FEV 1 and FVC, the FEV 1 was little affected by PEF variability. Park concluded that the ATS guidelines 21 for acceptability and reproducibility were appropriate and should not include PEF variability. Our data confirm the conclusions of Park. 23 FEV 1 has small intraindividual change during a particular session, whereas PEF variability is significantly 1496 Original Research
4 Figure 1. Regression analysis between best FEV 1 and best PEF in normal subjects with acceptable curves. greater. For all individuals studied, there is an average PEF of 14.3%. with a 0.50% average FEV 1. Other researchers 24 have confirmed the significantly greater variability in PEF compared with FEV 1 in a single session. Hence, PEF may be unreliable to accurately assess the quality of a spirometry maneuver despite the fact that it is the most appropriate way to assess initial effort. This suggests that FEV 1 is not very dependent on the initial effort. Our finding that PEF and FEV 1 are significantly and strongly correlated is in agreement with prior work. 17 However, our study uniquely examined the relationship between PEF and FEV 1 measurements within a single session, and it was the first to demonstrate that differences in these parameters in repeated measurements during the same testing sessions were not significantly correlated. However, maximal initial efforts should be encouraged because current reference standards were obtained using maximal efforts and all sources of increased variability should be minimized. Figure 2. Regression analysis of % FEV 1 against % PEF for normal subjects with acceptable curves. CHEST / 131 / 5/ MAY,
5 Figure 3. Regression analysis between best FEV 1 and best PEF in obstructed subjects with acceptable curves. In conclusion, both laboratory and clinical decisions are being made based on spirometry measurements using PEF and FEV 1. The changes in these two parameters give different information. Variability in PEF measurements during a single session does not have a significant effect on FEV 1. Spirometry data may be discarded erroneously based on PEF variability that has minimal overall effect on other results of the test, specifically FEV 1. Using PEF variability as a test quality criterion could increase the number of tests required in a single testing session, unnecessarily increasing the test burden for the patient and laboratory. These results are in agreement with the most recent ATS/ERS standardization of spirometry guidelines, 12 published in 2005, that state that the two largest FEV 1 and FVC values must be within L of each other and make no mention of PEF reproducibility. Also, given that PEF has a higher degree of intrinsic variability than FEV 1, Figure 4. Regression analysis of % FEV 1 against % PEF for obstructed subjects with acceptable curves Original Research
6 one must be more cautious in making clinical changes in management based on PEF. References 1 Expert Panel Report 2: guidelines for the diagnosis and management of asthma. Bethesda, MD: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute, Practice parameters for the diagnosis and treatment of asthma. American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology/Joint Council of Allergy, Asthma, and Immunology. J Allergy Clin Immunol 1995; 96: Boulet LP, Becker A, Berube D, et al. Canadian asthma consensus report, 1999: Canadian Asthma Consensus Group. Can Med Assoc J 1999; 161:S1 S61 4 British Thoracic Society. The British guidelines on asthma management: 1995 review and position statement. Thorax 1997; 52:S Gibson PG. Monitoring the patient with asthma: an evidencebased approach. J Allergy Clin Immunol 2000; 106: Pauwels RA, Buist AS, Calverley PM, et al. The GOLD Scientific Committee global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO: Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001; 163: Crit Care Med 2001; 163: Robinson DR, Chaudhary BA, Speir WA. Expiratory flow limitation in large and small airways. Arch Intern Med 1984; 144: Dolyniuk MV, Fahey PJ. Relationship of tracheal size to maximal expiratory airflow and density dependence. J Appl Physiol 1986; 60: Osmanliev D, Bowley N, Hunter DM, et al. Relation between tracheal size and forced expiratory volume in 1 second in young men. Am Rev Respir Dis 1982; 126: Krowka MJ, Enright PL, Rodarte JR, et al. Effect of effort on measurement of forced expiratory volume in one second. Am Rev Respir Dis 1987; 136: Quanjer P, Tammeling G, Cotes J, et al. Lung volumes and forced ventilatory flows: report Working Party Standardization of Lung Function Tests European Community for Steel and Coal. Eur Respir J 1993; 16(suppl): Miller M, Hanjinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J 2005; 26: McFadden ER, elsanadi N, Strauss L, et al. The influence of parasympatholytics on the resolution of acute attacks of asthma. Am J Med 1997; 102: Casaburi R, Briggs DD Jr, Donohue JF, et al. The spirometric efficacy of once-daily dosing with tiotropium in stable COPD: a 13-week multicenter trial; the US Tiotropium Study Group. Chest 2000; 118: Burge PS, Pantin CF, Newton DT, et al. Development of an expert system for the interpretation of serial peak expiratory flow measurements in the diagnosis of occupational asthma: Midlands Thoracic Society Research Group. Occup Environ Med 1999; 56: Tan RA, Spector SL. Diagnostic testing in occupational asthma. Ann Allergy Asthma Immunol 1999; 83: Rosenblatt G, Alkalay I, McCann PD, et al. The correlation of peak flow rate with maximal expiratory flow rate, one-second forced expiratory volume, and maximal breathing capacity. Am Rev Respir Dis 1963; 87: Meltzer AA, Smolensky MH, D Alonzo GE, et al. An assessment of peak expiratory flow as a surrogate measurement of FEV 1 in stable asthmatic children. Chest 1989; 96: Gautrin D, D Aquino LC, Gagnon G, et al. Comparison between peak expiratory flow rates (PEFR) and FEV 1 in the monitoring of asthmatic subjects at an outpatient clinic. Chest 1994; 106: Coates A, Desmond K, Demizio D, et al. Sources of variability in FEV 1. Am J Respir Crit Care Med 1994; 149: American Thoracic Society. Standardization of spirometry, 1994 update. Am J Respir Crit Care Med 1995; 152: Crapo R, Morris A, Gardner R. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis 1981; 123: Park SS. Effect of effort versus volume on forced expiratory flow measurement. Am Rev Respir Dis : Enright P, Beck K, Sherrrill D. Repeatability of spirometry in 18,000 adult patients. Am J Respir Crit Care Med 2004; 169: CHEST / 131 / 5/ MAY,
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