Assessing the Reversibility of Airway Obstruction Riccardo Pellegrino, Joseph R. Rodarte and Vito Brusasco Chest 1998;114;1607-1612 DOI 10.1378/chest.114.6.1607 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/114/6/1607
Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright1998by 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. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692
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Assessing the Reversibility of Airway Obstruction*
Riccardo Pellegrino, MD; Joseph R. Rodarte, MD; and Vito Brusasco, MD whether changes of partial expiratory flow-volume curve (PEFV) Study objective: To determinedetect functional responses to bronchodilator in patients who do not and inspiratory capacity (IC) for meet the FEV! criteria reversibility of airway obstruction. of salbutamol (200 u,g by metered-dose inhaler) on lung function The effects Design/methods: were examined in 50 patients with asthma and 28 patients with COPD. Measurements evaluated were FEVl5 forced expiratory flow at 30% of control FVC from maximal expiratory flow-volume curve (Vm30), forced expiratory flow at 30% of control FVC from PEFV (Vp30), and IC. On a separate occasion, a representative sample of 26 subjects inhaled placebo to determine the 95%
confidence limits (CLs) of each of the parameters. Results: A percent and absolute increment of FEVX above the upper CL was recorded in 28 increase of Vp30, 21 of Vm30, 9 of FVC, and 11 patients. Of these, 26 had a percent and absolute of IC above the 95% CL. Of the 50 patients who did not have an increase in FEVX above the 95% CL, 25 had a percent and absolute increase in Vp30, 15 of Vm30, 3 of FVC, and 13 of IC above the 95% CL. On average, the percent and absolute increase Vp30 above the 95% CL significantly identified more responders than every other parameter. Conclusion: Increases in maximal flow detected by PEFV and/or changes in IC may be substantially obscured by the effects of inspiration to total lung capacity required for the measurement of FEVX in patients with chronic bronchoconstriction. Decreases in functional residual capacity (FRC) manifested by an increase of IC occur because, in patients whose FRC is bronchodilatation that increases maximal flow in the tidal breathing dynamically determined, at lower lung volumes. Changes of FEVX frequently fail to detect breathe to allows range patients to functional response bronchodilators in patients with chronic airflow obstruction. significant
(CHEST 1998; 114:1607-1612)
words: asthma; COPD; FEVX; functional residual capacity; inspiratory capacity; partial and maximal flow-volume Key curves Abbreviations: CL confidence limit; FRC functional residual capacity; IC inspiratory capacity; MDI metered-dose inhaler; MEFV maximal expiratory flow-volume curve; PEFV partial expiratory flow-volume curve; RV residual volume; sGaw specific airway conductance; TLC total lung capacity; Vm30 forced expiratory flow at 30% of control FVC from MEFV; Vp30 forced expiratory flow at 30% of control FVC from PEFV =
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/^ urrent guidelines of the American Thoracic So^^ ciety Committee of Lung Function Testing rec¬ ommend bronchodilator responsiveness be evalu¬ ated by change in FEVX greater than the short-term between-test variability.1 Measurement of FEVt re¬ quires a deep inhalation maneuver, which may alter airway caliber.2 Flow measured during a forced expiration started from total lung capacity (TLC), or
Respiratoria (Dr. Pelle¬ Fisiopatologia S. Croce e Carle, Cuneo, Italy; Ospedaliera grino), Azienda (Dr. Rodarte), Baylor College of Medicine, Pulmonary Section Houston, TX; and the Dipartimento di Scienze Motorie e Riabilitative (Dr. Brusasco), Universita di Genova, Genoa, Italy. received December 12, 1997; revision accepted June Manuscript 16, 1998. Correspondence to: Vito Brusasco, MD, Dipartimento di Scienze Motorie e Riabilitative, Facolta di Medicina e Chinirgia, Largo R. Benzi, 10, 16132 Genova, Italy; e-mail:
[email protected] *From the Servizio di
the maximal expiratory flow-volume curve (MEFV), increases after bronchodilatation less than flow mea¬ sured during a forced expiratory maneuver started from near end-tidal inspiration (partial expiratory flow-volume curve, or PEFV).3"5 Therefore, the bronchodilator response would be underestimated such as FEVjl, instan¬ by MEFV-derived parameters, taneous flow at a given absolute lung volume or FVC. In patients with reversible airflow limitation, bronchodilators may improve lung function by in¬ creasing airway conductance during tidal breathing and reducing dynamic hyperinflation.6 These effects cannot be evaluated by FEV1? but can be simply inferred from changes in PEFV67 and inspiratoiy capacity (IC),6 as TLC does not change substantially after inhaling small doses of P2-agonists.6-8 This study was conducted to determine whether
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1607
and IC occur beyond the short changes in PEFV in variability response to bronchodilator admin¬ istration, even in patients who do not meet the FEVX criteria for reversibility of ainvay obstruction. term
integrator drift. No breath hold was allowed before starting forced expirations. The maneuvers were judged acceptable if PEFV and MEFV showed sharp peak flows and the best of three technically acceptable FEV1 readings did not exceed the next
highest one by more than 5% or 0.1 L. All measurements were repeated 20 min after 200 jxg of salbutamol (n 78) or placebo (n 26) was given by a metered=
Materials
and
Methods
Subjects The study participants were 78 outpatients with chronic airflow obstruction who were referred to a pulmonary function labora¬ tory by their family physician. Fifty patients (37 men) met the American Thoracic Society criteria for bronchial asthma and 28 patients (27 men) met the criteria for COPD.9 To enter the study, the patients were required to have an FEV/FVC below the lower normal limit,10 not to have suffered from exacerbations in the previous month, and to be able to abstain from bronchodilators for 24 h before the study. A subgroup of 26 patients was used to
determine the expected variability of lung function tests. This subgroup did not differ from the group as a whole in terms of anthropometric data or pulmonary function tests (conducted in a separate test session comparing spirometry before and after inhalation of a placebo). All individuals were informed of the scientific aim of the study and gave informed consent.
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dose inhaler connected to a spacer. Statistics
The unpaired Student's t test and x2 test with Yates' correction used for comparisons of means and frequencies, respec¬ tively. The distribution of changes induced by salbutamol or placebo was tested for normality by the Kolmogorov-Smirnov method. The 95% confidence interval of both percent and absolute changes of each pulmonary function variable after placebo was calculated by using mean values, standard deviations, and t values for 25 degrees of freedom.11 The upper 95% confidence limit (CL) was taken as the expected variability to which changes after salbutamol treatment were compared. Thus, a response to salbutamol was labeled as positive when both the percent and absolute increments of a variable over the control value were above the relative 95% CLs. Correlations were tested by Pearson's test. A p value of < 0.05 was considered statistically were
significant.
Lung Function Measurements measured at the mouth through a heated-screen pneumotachograph linear up to 16 L/s, coupled to a differential pressure transducer (Jaeger; Wiirzburg, Germany). Volume was obtained by electrical integration of the flow signal, after drift was corrected by adjusting a potentiometer. Flow-volume curves were displayed on an oscilloscope and then plotted on an X-Y recorder (LY 1400; Linseis; Selb, Germany). Forced expiratory flows were measured at 30% of control FVC on both PEFV (Vp30) and MEFV (Vm30). Pre- and postbronchodilator flowvolume curves were compared by superimposing them at TLC, which can be reasonably assumed to be constant.68 FEV] was calculated from the spirographic tracing according to the guide¬ lines of the American Thoracic Society. The IC was calculated as the difference between FRC, determined over the course of 8 to 10 breaths, and TLC, measured during a slow inspirator}7 ma¬ Flow
Results
was
neuver.
body plethysmograph (Jaeger) was used the control during portion of the study to measure thoracic gas volume at FRC while the patients were panting against a closed shutter at a frequency of < 1 Hz. Residual volume (RV) was calculated by subtracting the expiratory reserve volume, mea¬ sured immediately after the opening of the shutter, from FRC. The TLC was obtained by adding slow inspiratory vital capacity to A constant-volume
RV.
Experimental Protocol After the initial visit, 52 of the 78
patients attended the
laboratory on a second occasion for the bronchodilator test; the remaining 26 patients, who agreed to attend the laboratory twice after the initial visit, underwent both bronchodilator and placebo tests in random order. All tests were performed in the midafternoon, after a light meal. The protocol consisted of three sets of maneuvers separated by 2 to 3 min. After stable end-expiratory volume was established over the course of 8 to 10 tidal breaths, the patients expired forcefully from near end-tidal inspiration to RV (to obtain PEFV) and then from TLC to RV (to obtain MEFV). A final inspiration to TLC was performed to check for
Under control conditions (Table 1), all patients were a mean (±SD) FEV! 63 ± 19% of 86 ± 18% of predicted, and mod¬ and FVC predicted erately hyperinflated (FRC 136 ± 29% of predicted). The FEVX was slighdy but significantly less in COPD patients than in asthma patients (58 ± 20% vs 67 ± 18%; p < 0.05). Vm30 was on average similar to Vp30, though their ratio (M/P) was slightly greater in asthma patients than in COPD patients (1.05 ± 0.42 vs 0.88 ± 0.24; p < 0.06). The mean intraindividual coef¬ ficients of variation for Vp30 and for IC were 15 ± 13% and 5 ± 3%, respectively.
obstructed, with
Table
and Pulmonary Function 1.Anthropometric Data at
Baseline*
Sex, M/Ff Asthma/COPD
64/14 50/28 48/30
Smoke, yes/no Age, yr
49 ± 16 169 ± 8 2.07 ± 0.82 63 ± 19 3.53 ± 1.02 86 ± 18 165 ± 43 136 ± 29 114 ± 14 0.52 ± 0.36 0.52 ± 0.30 2.59 ± 0.63
Height, cm FEV,., L % predicted FVC, L % predicted RV, % predicted FRC, % predicted TLC, % predicted Vm30, L/s Vp30, L/s IC, *
L
Values
fM
are mean
± SD.
male; F female. =
1608
Clinical
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Investigations
Table
After Placebo 2.Spirometric Changes in 26 Patients Administration
Mean
FEV1; % of control FVC, % of control
Vm30, % of control
Vp30, % of control IC, % of control
7 15 1 L0.01 -0.16 L-0.03 36 4 L/s0.01 36 4 L/s0.01 49 0 L0.01
SD
Upper 95% CL
0.12 14 6.95 0.26 15 1.00 15 0.08
0.25 0.51 0.20 0.16 0.22
0.11
Spirometric changes after placebo were normally distributed. Mean values, SDs, and upper 95% CLs are given in Table 2. After inhaling salbutamol, a percent and absolute increment of FEVX above the 95% CL was recorded in 28 patients (36%). Of these patients, a percent and absolute increase above the upper 95% CL was noted for Vp30 in 26, Vm30 in 21, FVC in 9, and IC in 11 patients. Two patients had an increment of Vp30 slightly below the upper 95% CL (about 28%) of control). Of the remaining 50 patients in whom FEVX remained within the 95% confidence interval after salbutamol inhalation, percent and absolute increase above the upper 95% CL was observed for Vp30 in 25, Vm30 in 15, FVC in 3, and IC in 13 patients. Figure 1 shows the changes of Vp30 and IC FEVX in all subjects. changesandofabsolute plotted against increments of Overall, the percent Vp30 above the upper 95% CL after salbutamol
inhalation identified a substantially greater percent¬ age of responders (65%) than did increments of Vm30 (46%; p
