© 2002 American Thoracic Society
The Best Peak Expiratory Flow Is Flow-Limited and Effort-Independent in Normal SubjectsClinica di Medicina Interna, Università di Brescia, Brescia, Italy; Laboratoire de Physio-Pathologie Respiratoire et Service de Explorations Fonctionnelles, Groupe Hospitalier Pitié-Salpêtrière, University of Paris VI, Paris, France; and Divisione di Pneumologia, Azienda Ospedaliera di Imola, Bologna, Italy Correspondence and requests for reprints should be addressed to Claudio Tantucci, M.D., Clinica di Medicina Interna I, Università di Brescia, Spedali Civili, 25100 Brescia, Italy. E-mail: clatantu{at}tin.it
Recently, it has been suggested that peak expiratory flow (PEF) may be determined by the wave speed flow-limiting mechanism. In six normal male subjects (age = 33 ± 8 years) performing expiratory forced vital capacity (FVC) maneuvers, a negative expiratory pressure (NEP) of -10 cm H2O was randomly applied at the beginning of maximal expiration to assess changes in PEF as compared with baseline. During FVC maneuvers, the expiratory effort was measured by changes in esophageal pressure (Pes), as either peak expiratory Pes-Pes at end expiratory lung volume (  Pespeak) or maximal rate of rise of Pes (dPes/dtmax). In each experimental condition, at least three FVC maneuvers with comparable expiratory effort were selected for analysis for each subject. With similar Pespeak (107.2 ± 34.9 versus 111.7 ± 40.5 cm H2O) and dPes/dtmax (1181 ± 518 versus 1177 ± 546 cm H2O/second) PEF amounted to 10.84 ± 1.08 L/second and to 10.82 ± 1.03 L/second with and without NEP, respectively. These data show that PEF obtained by normal subjects to the best of their abilities (best PEF) does not increase with NEP and indicate that the best PEF is a flow-limited and effort-independent parameter, reflecting only lung and airways mechanics as the other subsequent maximal expiratory flows achieved during the FVC maneuver.
Key Words: peak expiratory flow • expiratory flow limitation • negative expiratory pressure
Peak expiratory flow (PEF) is the maximum flow that can be generated during a forced expiratory maneuver started from total lung capacity (TLC) and correctly performed. PEF normally occurs at high lung volumes near TLC and is a widely adopted measurement to assess and monitor airway obstruction. According to a common tenet of respiratory physiology, PEF is considered an effort-dependent parameter (1). This is because a plateau of expiratory flow cannot usually be obtained at lung volumes higher than 80% of the vital capacity by increasing pleural (and alveolar) pressure during isovolume flow–pressure curves (2, 3). Hence, PEF is believed to be limited by the force–velocity characteristics of the expiratory muscles instead of the mechanical properties of the lung and airways, as insufficient force would be available to achieve flow limitation near TLC. Thus, after standardization of the preceding inspiration, PEF might be increased by either increasing pleural pressure (i.e., by augmenting somehow the expiratory effort) or decreasing atmospheric pressure. Indeed, both procedures increment the driving pressure that, in the absence of expiratory flow limitation, is the difference in pressure between the alveoli and the mouth.
There is evidence, on the other hand, that PEF may be determined by the wave speed flow-limiting mechanism (4), reflecting the resistance upstream to the flow-limiting segment (Rus), the cross-sectional area here (A), the compliance of the airway wall ( Under these conditions, the actual driving pressure for PEF would be only the lung elastic recoil pressure (Pel) at the corresponding volume. Consequently, a reduction of the atmospheric pressure at the beginning of expiration should not influence PEF. The aim of the present study was to assess the PEF changes occurring by applying negative expiratory pressure at the mouth (NEP) (7), as compared with baseline conditions, during forced expiratory vital capacity maneuver in normal subjects performing similar, maximal expiratory efforts.
Subjects Six healthy male subjects (age = 33 ± 8 years; range 26–46 years) with body mass index less than 25 kg/m2 were investigated in a prospective open study. All subjects were non-smokers. The subjects were well motivated and familiar with respiratory maneuvers. All had normal pulmonary function tests. None of them had acute or chronic cardiopulmonary or neuromuscular diseases. No electrolytic or metabolic abnormalities were found in the routine laboratory evaluation. All subjects had a normal chest radiograph. The experimental protocol was approved by the local Ethics Committee and informed consent was obtained from all subjects.
Measurements
A Venturi device capable of rapidly generating a negative pressure (Aeromech Devices Ltd., Almonte, ON, Canada) was connected in series with the cone of the pneumotachograph. The dead space of the assembly was about 150 ml and its resistance amounted to 0.5 cm H2O/L/second at a flow of 1 L/second. A side orifice on the Venturi device was attached via an electrically operated solenoid valve (Asco electrical valve, model 8262G208; Ascolectric, ON, Canada) to a tank of compressed air. A pressure regulator between the tank and the valve was used to obtain the desired level of negative pressure at the mouth. The valve was driven by a computer (Direc Physiologic Recording System; Raytech Instruments, Vancouver, BC, Canada) and had an opening time of 28 milliseconds. The opening valve was activated when the expiratory flow reached a threshold level of 150 ml/second (Figure 1). All signals (V·, Pes, and Pm) were amplified (AC Bridge Amplifier-ABC module; Raytech Instruments), low pass filtered at 100 Hz, sent to a 16-bit A/D converter (Direc Physiologic Recording System; Raytech Instruments) connected to an IBM compatible computer (486DX, 66 MHz; Hewlett-Packard, Cupertino, CA), and sampled at 200 Hz. All digitized signals were displayed in real time on the computer screen together with the volume signal obtained by the numerical integration of the flow signal. The tracings were continuously monitored both with respect to time and as flow–volume curves. The recordings were stored on hard disk in Direc format for subsequent analysis. Data analysis was performed using either the Direc (version 3.1; Direc NEP software, Raytech Instruments) or the Anadat (version 5.2; RHT-InfoDat, Montreal, QC, Canada) data analysis software.
Procedure and Data Analysis
To evaluate and match expiratory effort, the following indices were taken both in control condition and during the NEP application: (1) peak expiratory esophageal pressure (Pespeak) - Pes at end-expiratory lung volume (EELV) ( Pespeak); (2) Pes at PEF (PesPEF) - Pes at end-expiratory lung volume (PesPEF); (3) maximal rate of rise of Pes by differentiating the pressure waveform (dPes/dt,max); and (4) the rate of rise of Pes from Pes at TLC immediately before the FVC maneuver to Pes either at time of PEF (dPes/dtPEF) or at time of peak (dPes/dtpeak) (Figure 2A). Moreover, the time required to reach PEF (PFT), from the flow/time curve, and the expired volume at PEF as % FVC (% PEFVOL), from the flow–volume curve, were also computed. Approximately 5 minutes of rest were allowed between each maneuver. Among FVC maneuvers with similar expiratory effort, at least three acceptable and reproducible FVC maneuvers (12) for each experimental condition (control and during NEP) were averaged for analysis. For each acceptable maneuver, FVC and FEV1 could not differ more than 5% from the respective maximum value. Although each previous maximal inspiration was initiated from the EELV after a period of quiet and regular tidal breathing, the FVC maneuver was discarded if the preceding inspiratory capacity was less than 90% of the maximum recorded value. Paired Student's t tests were used to compare the parameters obtained in each maneuver performed with and without NEP. Data were expressed as means ± SD. A p level less than 5% was considered significant.
Direct and indirect indices of expiratory effort measured during an FVC maneuver, together with the PEF, FVC, and FEV1 values, are reported for the six subjects in Table 1, both in control condition and with NEP. In addition, the time taken to reach the complete application of NEP from the beginning of expiratory flow is also indicated (Table 1). Accordingly, NEP was fully operating 0.019 ± 0.004 seconds before PEF (i.e., on average, throughout the last 36% of the time required to each PEF) and during each occasion at PEF (Figure 2B).
As an example, two FVC maneuvers performed by a representative subject (Subject 2) and presented as maximal expiratory flow–volume curve, were compared in control condition (Figure 3A) and during the NEP application lasting 1.5 seconds (Figure 3B). The expiratory curves appeared virtually identical. In particular, PEF and the following maximal expiratory flows were similar in either condition. Nine maximal expiratory flow–volume curves, four with and five without NEP, meeting the acceptability and reproducibility criteria and performed with comparable, maximal expiratory efforts, were superimposed, starting from TLC in the same subject (Subject 1). All these curves perfectly overlapped and no appreciable difference could be detected in the PEF achieved in either condition (Figure 4) .
The same results were obtained in all six subjects.
The main finding of this study was the inability of a negative pressure of -10 cm H2O to increase PEF when administered at the beginning of an FVC maneuver performed by normal subjects to the best of their abilities. This proves that PEF occurs in the presence of expiratory flow limitation and strongly supports the theory that PEF is limited by the wave speed mechanism, as suggested by other authors (4–6). In addition, our data indicate that the "best" PEF (that is, the PEF that does not increase with NEP) and the subsequent maximal expiratory flows are actually effort-independent parameters. Hence, given an adequate effort, PEF and the following maximal expiratory flows should reflect only the mechanical properties of the lung parenchyma and airways, as believed for maximal expiratory flows corresponding to lung volumes lower than 80% of FVC. The results of this study contrast with data obtained previously generated isovolume pressure–flow curves, from which the investigators were not able to find flow limitation at PEF (1–3). It is difficult, however, to construct isovolume pressure–flow curves showing a plateau of flow at different pleural pressure values near TLC. Therefore, intrinsic difficulties with this method may prevent a clear demonstration of flow limitation at PEF (12). Following a different approach, Pedersen and coworkers elegantly showed that the flow at wave speed, computed in the large airways in normal subjects, was similar to PEF (13). They concluded that PEF can be determined from the wave speed flow-limiting mechanism in central airways. This may apply to several values of PEF obtained even during submaximal expiratory efforts, providing that PEF is reached at the perimeter of the maximal expiratory flow–volume curve (5). Under these circumstances, however, PEF is still effort-dependent, because with increasing effort, wave speed is reached at a higher lung volume, where the presence of higher elastic recoil pressure and lower upstream frictional pressure loss cause a further increase in PEF. It follows that in cases of submaximal efforts, the early application of the NEP at the onset of expiration should shorten the rise time of the expiratory flow. As a consequence, PEF would be reached at a greater lung volume and would be necessarily higher. In contrast, in our experiments, performed asking the subjects to exhale "as quickly and forcefully as possible" according to American Thoracic Society recommendations (14), PEF did not change during the NEP application. This finding clearly indicates both the occurrence of flow limitation at PEF and, indirectly, the impossibility of increasing PEF with a further effort, suggesting that during a well-performed FVC maneuver, normal subjects develop the "best" PEF that can be considered effort independent.
Looking at In the absence of expiratory flow limitation, the administration of the NEP could potentially have not improved PEF if it were accompanied by a concurrent increase in the airway resistance due to partial collapse of the compliant upper airways. In healthy young subjects, however, NEP does not increase the respiratory system resistance until -7 cm H2O when applied during quiet tidal expiration, indicating no effect on upper airway resistance (15). Thus, it seems highly improbable that NEP of -10 cm H2O might cause even a slight narrowing of upper airways during a FVC maneuver, when the upper airway muscles are strongly activated to sustain maximal expiratory efforts. Volta and coworkers (11) used essentially the same approach to show the usefulness of the NEP method for online assessment of the FVC performance in the classic effort-independent portion. These authors chose to perform the FVC maneuver after an end-inspiratory breath hold of about 4 seconds, to eliminate the contribution of the lung tissue viscoelasticity. Nevertheless, they observed that PEF did not change significantly in normal subjects who made a maximal effort during the NEP application (from -5 to -10 cm H2O), suggesting the presence of expiratory flow limitation at the lung volume near PEF. However, the time at which NEP was entirely developed (104 ± 7 milliseconds) was very close to the time required to reach PEF by those subjects (116 ± 30 milliseconds), raising doubts about the systematic presence of a fully operating NEP when PEF occurred. Moreover, although PEFtime and PEFVOL appeared similar in the two experimental conditions, the expiratory effort was not directly controlled because esophageal pressure was not measured during the FVC maneuvers with and without NEP. In our opinion, this is a crucial point because one must compare PEF obtained with equivalent expiratory effort to be sure of the ineffectiveness of the NEP to raise it. In our study NEP was always fully applied before PEF, and expiratory effort was assessed by measuring changes in esophageal pressure during FVC maneuvers. This allowed us to control the performance in either condition, and to compare FVC maneuvers with similar, maximal muscular effort. Furthermore, a full inspiration with no breath hold must be required before the maximal expiration to obtain the greatest activation of the expiratory muscles (16) and highest lung elastic recoil pressure (17, 18) for assessing effectively "flow limitation" and "effort independence" of PEF with the NEP method during an FVC maneuver. It is interesting to note, however, that flow limitation appears to occur at PEF during an FVC maneuver, performed either with or without preceding postinspiratory pause, although at different absolute values of PEF. In the present study, among the different parameters measured, only PEFVOL was significantly different in the two experimental conditions, being slightly lower during the NEP application (Table 1). If the NEP is applied in the presence of increasing expiratory flow, when, by definition, expiratory flow limitation is absent, the expiratory flow must further increase and, thus, the expired volume in a given time will likewise increase. This should happen when NEP is operating during the ascending part of the expiratory maximal flow–volume curve before PEF, as in our experiments. Looking at the flow–volume relationship, however, a shorter rise time of the flow induced by the NEP would allow the PEF to be reached at higher lung volume, thus decreasing the PEFVOL, as in this case. As the lung volume at PEF was greater with NEP, the elastic recoil pressure driving expiratory flow should have been greater, with NEP inducing a higher PEF value. Nevertheless, the difference was minimal, amounting in absolute value to about 30 ml (0.6% of a mean FVC equal to 5.38 L), and thus unable to influence the PEF value. Interestingly, a similar result was reported by Volta and colleagues (11). In both cases, however, the difference of PEFVOL with and without NEP was minimal and physiologically irrelevant. Such a very small change in PEFVOL with NEP means that the required expiratory effort was achieved by our subjects, because otherwise, PEF during NEP would have occurred at a much greater lung volume and would have been markedly higher. The absence of any change in PEF during NEP suggests that further effort would have been ineffective in increasing PEF, as the level of NEP was equivalent to a 15–55% increase in the pleural pressure developed by these subjects for generating PEF. Finally, it should be noted that the results of this study were obtained in a small group of normal subjects, and should be substantiated by studying a larger group of healthy subjects as well as patients suffering from obstructive pulmonary diseases.
In conclusion, when normal subjects correctly perform an FVC maneuver, PEF does not increase by increasing the driving pressure between alveoli and mouth through the NEP application. This finding indicates that expiratory flow limitation occurs even at PEF, supporting the theory that PEF is determined by the wave speed flow-limiting mechanism. Our results also suggest that the "best" PEF, which represents the maximal flow rate available because it cannot be increased by NEP, is an effort-independent parameter, thus depending only on Pel, Rus, A, and Received in original form December 4, 2000; accepted in final form February 12, 2002
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