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Assessment of variable obstruction by forced expiratory
volume in 1 second, forced oscillometry, and interrupter
technique
Alfredo Boccaccino, M.D.,* Diego G. Peroni, M.D.,# Angelo Pietrobelli, M.D.,#Giorgio Piacentini, M.D.,# Alessandro Bodini, M.D.,# Atanasio Chatzimichail, M.D.,§Enrico Spinosa, M.D.,* and Attilio L. Boner, M.D.# (Italy and Greece) ABSTRACT
The aim of this study was to evaluate the presence and the degree of reversible airflow obstruction as detected by forced expiratory volume in 1 second (FEV1), forced oscillometry (FOT), and interrupter technique (resistance measured by theinterrupter technique [Rint]) in mild asthmatic children compared with controls. FOT, Rint, and FEV1 were evaluated beforeand after albuterol (200 ␮g) administered by metered-dose inhaler and spacer in 28 asthmatic children (mean age Ϯ SD, 9.1 Ϯ1.9 years) and in 20 healthy children (mean age Ϯ SD, 8.5 Ϯ 2.1 years). No correlation was found between FEV1, FOT, andRint values either before or after albuterol. FOT and Rint values were highly correlated pre- and postbronchodilatation. Animprovement in FEV Ն 12% after albuterol was observed in 11 (39%) asthmatic subjects. As suggested using the cutoff value at R Ն 29%, significant bronchodilatation was observed in 20 (71%) children with FOT and using a reduction Ն0.20 kPa or 2 cm of H2O, 22 (78%) subjects showed significant bronchodilatation with Rint. No significant changes were observed afteralbuterol in controls. FOT and Rint techniques showed a greater sensitivity in detecting reversibility of bronchoconstriction inmild asthmatic patients. Prospective studies are needed to clarify the possible advantages of these findings in mild–moderateasthmatic children. (Allergy Asthma Proc 28:331–335, 2007; doi: 10.2500/aap.2007.28.2963) Key words: Asthma, children, FEV1, forced expiratory volume, forced oscillometry, interrupter technique, pulmo-
nary function test, spirometry
The detection of reversible airflow limitation is a and interrupter technique (resistance measured by the
major criteria for asthma diagnosis in children.1 interrupter technique [Rint]), may be used to measure In the evaluation of asthmatic children it is inappro- respiratory resistance (Rrs) even in younger and not priate to relate only to clinical perception of airway collaborative children.7,8 Few studies evaluated FOT obstruction because it may persist despite therapy in and Rint as tools in the detection of bronchial obstruc- apparently asymptomatic patients.2,3 Therefore, air- tion and its reversibility in asthmatic children.9–11 Re- way obstruction frequently might go undetected in cently, cutoff values of postbronchodilator changes in apparently healthy children who have a history of rs were defined to discriminate children with a neg- persistent wheezing or asthma if lung function test are ative or positive response to albuterol.9 However, the not performed.4,5 Measurement of forced expiratory concordance in FEV1 and Rrs in establishing reversibil- volume in 1 second (FEV1) and its improvement after ity of airway obstruction is not always present.10 In this ␤2-agonist is considered the “gold standard” for the study we performed lung function tests (FEV1, FOT, assessment of airway obstruction and its reversibili- and Rint) in children with mild asthma and in normal ty.1,6 Other techniques that use the “respiratory tidal children, as controls, to evaluate the presence and the volume” and demand only passive cooperation and no degree of reversible airflow obstruction as detected by forced maneuvers, such as forced oscillometry (FOT) From the Department of Pediatrics, Ospedale “G. Rummo,” Benevento, Italy, #De-partment of Pediatrics, University of Verona, Verona, Italy, and §Clinic of Pediatrics, Subjects
Democrition University, Alexandropolis, GreeceAddress correspondence to Diego Peroni, M.D., Department of Pediatrics, Verona Twenty-eight asthmatic children (13 boys and 15 University, Policlinic GB. Rossi, P.le Scuro 10, 37134 Verona, Italy, girls), 5–13 years old (mean age Ϯ SD, 9.1 Ϯ 1.9 years) E-mail address: peroni.diego@tiscalinet.itAddress reprint requests to Attilio Boner, M.D., Department of Pediatrics, Verona were studied. They were all well-known asthmatic University, Policlinico GB. Rossi, P.le Scuro 10, 37134 Verona, Italy children according to the American Thoracic Society E-mail address: attilio.boner@univr.it (ATS) definition.12 Only children complaining of mild Copyright 2007, OceanSide Publications, Inc., U.S.A. wheeze and/or cough without any other symptoms at the physician’s evaluation were consecutively enrolled available with Pulmowin software. These measure- into the study. Twenty normal subjects (12 boys and 8 ments were recorded and coefficients of variation were girls) 5–14 years old (mean age Ϯ SD, 8.5 Ϯ 2.1) were enrolled as controls. Parents and guardians gave writ-ten inform consent to the study protocol, which was approved by the local Hospital Ethical Committee.
Rint was measured as previously described.7,23 Briefly, children were instructed to sit upright, while Study Design
breathing quietly, and a minimum number of 6 correct Baseline measurements were obtained in all children.
tracings (maximum number 10) were obtained in all FOT (Oscilink V; SensorMedics, Yorba Linda, CA) and children by the same operator. Shutter closure was Rint (MicroRint; Micromedical, Rochester, U.K.) mea- programmed at maximal inspiration of tidal flow to surements were performed before flow volume curves avoid problems related with airway collapse during to avoid the influence of deep inspiration.13 Albuterol expiration.24 Thus, Rint values were obtained at or (200 ␮g) was administrated via metered-dose inhaler close to midinspiration, minimizing the breath-to- and spacer 20 minutes before all postbronchodilator breath variation in inflation level and, hence, on Raw.
Timing of the shutter closure was shown on the dis- were withheld for at least 8 and 24 hours, respectively, play. The mean value of six consecutive, technically before the reversibility tests were performed.
satisfactory measurements (identical pressure and flowcurves) was saved as the results. Tracings were in- Spirometry
spected immediately after the measurement and ac- Forced expiratory flow–volume curves were re- cepted or rejected according to Bridge et al.7 corded using Oscilink and Pulmowin software (Sen-sorMedics). Spirometric tests were done according to Statistical Analyses
ATS criteria: at least three acceptable forced expiratory All analyses were performed using the statistical curves were recorded and the curve with the highest program SAS release 6.10 (SAS Institute, Inc., Cary, NC). Descriptive analyses are presented as mean Ϯ SD.
1 and forced vital capacity was selected.14 Reference values were used according to Quanjer.15 Pre- and postbronchodilator administration values andasthmatic versus control data were analyzed using Stu- dent’s t-test. Pearson’s coefficients of correlation wereused to compare parametric variables. To test the FOT impedance measurements (Zrs) were performed agreement between methods of clinical measurements, by Oscilink spirometer impedancemeter using Pul- a Bland and Altman analysis was performed.25 Signif- mowin software as previously described.16,17 Pressure icance levels were based on two-tail tests and ␣ was set and flow calibrations were done before each new pa- tient. Children’s positions were monitored carefully.
Briefly, the FOT method used in our study used the frequency range of 4 –32. The signals were filtered for low- (Ͻ3 Hz) and high-frequency components to elim- Pulmonary function tests at baseline and postbron- inate errors caused by the presence of breathing noise18 chodilator for asthmatic children and controls are re- and processed by computer using Fourier analysis.
Low frequencies are suited most for studying vis-coelastic respiratory properties after bronchoconstric- Asthmatic Children
tion/bronchodilatation.19 We selected the low frequen- Evaluation of baseline lung function showed high cies (R6 and R12) according to previous studies, which significant differences between asthmatic subjects and indicated high sensitivity in distinguishing normal ver- controls in FEV1 (p Ͻ 0.0001), in FOT values (R6 and sus asthmatic children.20 Furthermore, Rrs use at low R12, all p Ͻ 0.0001; R16, p ϭ 0.001; and R24, p ϭ 0.02, frequencies (i.e., 6 –10) rather than high frequencies respectively), and in Rint values (p Ͻ 0.0001).
(i.e., 24 –32) is accepted widely in the evaluation of the FEV1 significantly increased, whereas Rrs (R6, R12, effect of bronchoconstricting agents.18,21 Particular at- R16, and R24) and Rint showed a highly significant tention was given to monitor resting ventilation, ex- reduction postbronchodilator in asthmatic children cluding data with coughing, hyperventilation, irregu- (for all, p Ͻ 0.0001). At baseline Pearson’s correlation lar breathing, apnea, or leaks through mouthpiece.
test showed no correlation between FEV1 and Rrs at R6, Measurements were repeated on an average of three to R12, R16, and R24 as expected by the slope of the FOT five times until three consecutive tests gave adequate curve. Furthermore, no correlation was found between reproducibility.22 This was done based on the two FEV1 and Rint. Prebronchodilatator Rint and Rrs at low graphs (Rrs versus frequency and Xrs versus frequency) frequencies were highly correlated (R6, r ϭ 0.67, p Ͻ Table 1 Pulmonary function test results
Asthmatic Subjects
Normal Subjects
Prebroncho-
Postbroncho-
p*
Prebroncho-
Postbroncho-
p*
Data are shown as mean Ϯ SD.
*p for student’s unpaired t-test prebronchodilator versus postbronchodilator administration. 0.0001; R12 r ϭ 0.53, p ϭ 0.004, respectively), while at given frequencies (R6, r ϭ 0.62 and p ϭ 0.005; R12, r ϭ high frequencies (R16 and R24) we did not find any 0.56 and p ϭ 0.01; R16, r ϭ 0.61 and p ϭ 0.006; and R24, r ϭ 0.64 and p ϭ 0.003).
cutoff value suggested by ATS for a significant bron- DISCUSSION
chodilatation,14 was observed in only 11 (39%) asth- The gold standard for the diagnosis of airway ob- matic subjects. Using the cutoff of Ն29% at R6,26 sig- struction is represented by evaluation of lung function nificant bronchodilatation was observed in 20 (71%) with forced expiratory maneuvers performed before children. Twenty-two (78%) subjects showed signifi- and after bronchodilator administration.1,6,14 No single cant bronchodilatation with Rint, using the cutoff re- test by itself can be considered completely adequate for duction of Ն0.20 kPa or 2 cm of H2O.27 Postbronchodi- assessing variable obstruction associated with persis- latator data showed no correlation between FEV1and tent asthma.4 Furthermore, previous studies have Rrs at any given frequencies (R6, R12, R16, and R24). The shown a difficult relationship between asthma symp- correlations between Rint and Rrs were instead highly toms and objective measures of airway obstruction significant (R6, r ϭ 0.76, p Ͻ 0.0001; R12, r ϭ 0.65, p Ͻ 0.0001; R16, r ϭ 0.45; p ϭ 0.01; and R24, r ϭ 0.69, p Ͻ In this study, the patients, despite complaining of only minimal symptoms (cough and/or mild wheeze), The Delta (⌬), i.e., the difference between post- and presented with reduced FEV1 and significantly in- prebroncodilator values, was also evaluated. The creased FOT and Rint values. This is in agreement with ⌬FEV1 and ⌬Rrs at any given frequency (R6, R12, R16, previous findings suggesting that asthma disease ac- and R24) were not correlated. We found a significant tivity can not always be completely revealed by history ⌬Rint and ⌬Rrs at R6 (r ϭ 0.56 and clinical examination alone both in populations and and p ϭ 0.002) and R12, (r ϭ 0.42 and p ϭ 0.02), but in clinical studies.29,30 Failure to perform lung function not at R16 and R24. The Bland-Altman analysis tests in asthmatic children, even when they are asymp- showed no significant correlation between the ana- tomatic, may result in underdiagnosis of airflow ob- struction5 with consequent loss of elastic recoil andchronic hyperinflation if obstruction is prolonged.31 In Controls
our study FOT and Rint evaluation detected reversibil- Prebronchodilator data showed no correlation be- ity of airflow limitations in a greater number of mild tween FEV1, Rint, and Rrs at any given frequency.
asthmatic children than that depicted by FEV1. Using Instead, Rint was highly correlated with R6 (r ϭ 0.85 established cutoff values,14,23,24 a significant bron- and p Ͻ 0.0001), R12 (r ϭ 0.80 and p Ͻ 0.0001), R16 (r ϭ chodilatation was documented only in 39% of our sub- 0.79 and p Ͻ 0.0001), and R24 (r ϭ 0.77 and p Ͻ 0.0001).
jects with FEV1 but in 71% using FOT and in 78% with Postbronchodilator analysis showed no correlation be- tween FEV1 and Rint. FEV1 presented a negative cor- Discrepancies between FEV1 and FOT results were relation with Rrs at low frequencies R6 (r ϭ Ϫ0.54 and found in other studies,10,32 showing that FOT and Rint p ϭ 0.01) and R12 (r ϭ Ϫ0.48 and p ϭ 0.03), whereas no were not significantly correlated to FEV1 in detecting correlation was found at high frequencies (R16 and bronchodilatation after albuterol use in children. Our R24). Rint was significantly correlated with Rrs at any results are according to previous studies in adults showing that Rint and FOT have higher capacity than 5. Bye MR, Kerstein D, and Barsh E. The importance of spirometry spirometry in detecting reversible bronchial obstruc- in the assessment of childhood asthma. Am J Dis Child 146:977– tion.33,34 The reduced sensitivity of FEV 6. Dickman ML, Schmidt CD, and Gardner RM. Spirometric stan- plained by the fact that forced expiratory maneuvers dards for normal children and adolescents (ages 5 years are effort dependent and require a deep inhalation that through 18 years). Am Rev Respir Dis 104:680 – 687, 1971.
in asthmatic patients may be associated with broncho- 7. Bridge PD, Rangantathan S, and McKenzie SA. Measurement of constriction.13,35 This could limit the effect of broncho- airway resistance using the interrupter technique in preschool dilator, and, on the other hand, FOT and Rint are children in the ambulatory setting. Eur Respir J 13:792–796,1999.
performed during tidal volume breathing and are ef- 8. Nielsen KG, and Bisgaard H. Lung function response to cold air fort independent. These techniques at low frequencies challenge in asthmatic and healthy children of 2–5 years of age.
measure resistance mainly determined by the patency Am J Respir Crit Care Med 161:1805–1809, 2000.
of the peripheral airways,11,36 where obstruction could 9. Delacourt C, Lorino H, Herve-Guillot M, et al. Use of forced oscillation technique to assess airway obstruction and revers- be even less related to symptoms’ perception.37 ibility in children. Am J Respir Crit Care Med 161:730 –736, Therefore, FOT and Rint seem to be particularly promising in clinical pediatric practice.7–11 They 10. Lebecque P, and Stanescu D. Respiratory resistance by the present the advantages of being rapid to perform and forced oscillation technique in asthmatic children and cystic require minimal cooperation. For these reasons they fibrosis patients. Eur Respir J 10:891– 895, 1997.
11. Delacourt C, Lorino H, Fuhrman C, et al. Comparison of the can be performed in preschool children7,38,39 and in forced oscillation technique and the interrupter technique for infants,40 in whom detection of airflow limitation may assessing airway obstruction and its reversibility in children.
be more difficult. Obviously, evaluation of Am J Respir Crit Care Med 164:965–972, 2001.
struction and its reversibility are central keys for early 12. American Thoracic Society Committee on Diagnostic Standards diagnosis and early treatment of children with asth- for Non-tuberculosis Respiratory Diseases. Definition and clas-sifications of chronic bronchitis, asthma, and pulmonary em- ma.41 Moreover, Rint has been found useful in detect- physema. Am Rev Respir Dis 85:762–768, 1962.
ing airways responsiveness to methacholine42 and cold 13. Pellegrino R, Sterk PJ, Sont JK, and Brusasco V. Assessing the air43 in young children, further increasing the applica- effect of deep inhalation on airway caliber: A novel approach to tion of the method in the evaluation of young asth- lung function in bronchial asthma and COPD. Eur Respir J 14. American Thoracic Society. Standardization of spirometry— In conclusion, our results confirm and further expand 1994 update. Am J Respir Crit Care Med 152:1107–1136, 1995.
the concept that FOT and Rint, particularly with the 15. Quanjer P, Borsboom GJ, Brunekreef B, et al. Spirometric refer- evaluation of the bronchodilator response, should be en- ence values for withe European children and adolescents: Pol- couraged in asthmatic patiens. FOT and Rint should be gar revisited. Pediatr Pulmonol 19:135–142, 1995.
used to add sensitivity to classic lung function measure- 16. Van de Woestijne KP, Desager KN, Duiverman EJ, and Marchal F. Recommendations for measurement of respiratory input im- ments particularly in asthmatic children with normal or pedance by means of the forced oscillation method. Eur Respir near normal FEV1. The good correlation between FOT and Rint suggests that both techniques offer useful infor- 17. Lorino A, Atlan G, Lorino H, et al. Influence of posture on mechanical parameters derived from respiratory impedance.
asthmatic children. The clinical meaning of changes in 18. Duiverman EJ, Neijens HJ, Van der Snee-van Smaalen M, and Kerrebijn KF. Comparison of forced oscillometry and forced spective studies performed in patients with low correla- expirations for measuring dose-related responses to inhaled tion between symptoms severity and traditional lung histamine in asthmatic children. Bull Eur Physiopathol Respir 19. Klug B, and Bisgaard H. Specific airway resistance, interrupter resistance, and respiratory impedance in healthy children aged2–7 years. Pediatr Pulmonol 25:322–331, 1998.
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