(Chest. 2000;117:219S-223S.)
© 2000
American College of Chest Physicians
Expiratory Flow Limitation*
Roger S. Mitchell Lecture
Joseph Milic-Emili, MD
*
From the Meakins-Christie Laboratories, McGill University, Montreal, Canada.
Correspondence to: Joseph Milic-Emili, MD, Meakins-Christie Laboratories, 3626 St. Urbain St, Montreal, Quebec, Canada H2X 2P2; e-mail: milic{at}meakins.lan.mcgill.ca
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Introduction
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Abbreviations: FL = flow limitation; NEP = negative
expiratory pressure; VT = tidal volume;
-V = tidal expiratory flow-volume
The
highest pulmonary ventilation that a subject can achieve is ultimately
limited by the highest flow rates that can be generated. Most normal
subjects do not exhibit expiratory flow limitation (FL) even during
maximal exercise. In contrast, patients with COPD may exhibit FL even
at rest, as first suggested by Hyatt.1
This was based on
his observation that patients with severe COPD often breathe tidally
along their maximal expiratory flow-volume curve. The presence of
expiratory FL during tidal breathing promotes dynamic pulmonary
hyperinflation, with concomitant increase of inspiratory work,
impairment of inspiratory muscle function, and adverse effects on
hemodynamics.2
This, together with flow-limiting dynamic
compression during tidal breathing, may contribute to
dyspnea.3
4
Conventionally, FL is assessed by comparison of the tidal expiratory
flow-volume (-V) curves with the corresponding maximal
expiratory flow-volume curves: patients in whom, at comparable lung
volumes, tidal flows are similar or higher than those obtained during
the FVC maneuver are considered flow limited.1
As
discussed below, this approach has both theoretical and practical
limitations. Nevertheless, this analysis has been the kernel for
understanding respiratory dynamics. Furthermore, it still is commonly
used in clinical practice to assess tidal expiratory FL. Accordingly it
is useful to review it in some detail.
Figure 1
depicts the -V loops at rest and during maximal exercise,
together with the corresponding maximal -V curves of a normal
subject and a patient with severe airway obstruction. In the normal
subject, even during maximal exercise, the flows are less than maximal
(ie, there is no FL). In this case, the increase of tidal
volume (VT) during exercise occurs as a result of
both an increase in end-inspiratory and a decrease in end-expiratory
lung volume, and the work of breathing during exercise is sustained by
activity of both inspiratory and expiratory muscles. In contrast, in
patients with airway obstruction, maximal expiratory flows may be
attained even at rest. Thus, their increase in VT
during exercise can only occur as a result of an increase in
end-inspiratory volume.6
7
However, as a result of
excessive expansion of the chest wall, the inspiratory muscles work
inefficiently. Furthermore, the hyperinflation causes the following:
(1) an increase in inspiratory work through a decrease in static
compliance of the respiratory system, as patients now breathe along a
flatter portion of the static volume-pressure curve; and (2) a high
inspiratory threshold load due to the need to generate additional
pressure before inspiratory flow can begin (this threshold pressure has
been labeled intrinsic positive end-expiratory
pressure).2
With severe dynamic hyperinflation, this
phenomenon becomes self-limiting because the changes in volume and
inspiratory flow require too high force development by the inspiratory
muscles. Thus, in patients with severe airway obstruction, inspiratory
muscle fatigue may limit exercise performance. This explains why
detection of tidal expiratory FL is of great clinical importance.
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Figure 1. Flow-volume curves obtained from a normal subject
and a patient with COPD. Spontaneous flow-volume loops at rest (dashed
lines) and maximum exercise (MAX. EX.; dotted lines) are compared with
maximum flow-volume loops (outer solid lines).5
VC = vital capacity; insp. = inspiration; exp. = expiration;
REST = resting.
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However, the conventional approach for detecting expiratory FL, which
is illustrated in Figure 1
, has an important practical limitation
because, as a result of thoracic gas compression during the FVC
maneuver, the tidal and maximal -V curves have to be measured
with a body plethysmograph.8
This implies that such
measurements are usually confined to resting breathing in sitting
position. Apart from this, there are several other factors that make
assessment of FL based on comparison of tidal and maximal -V
curves problematic: (1) volume-dependent changes in airway resistance
and lung recoil during the maximal inspiration prior to the FVC
maneuver; and (2) time-dependent viscoelastic behavior of pulmonary
tissues and time-dependent lung emptying due to time constant
inequality.9
10
11
These mechanisms imply that the maximal
flows that can be reached during expiration depend on the volume and
time history of the preceding inspiration. Furthermore, since
axiomatically the previous volume and time history vary between tidal
and maximal inspiration, assessment of FL based on comparison of tidal
and maximal -V curves often leads to erroneous conclusions, even
if the measurements are made with body
plethysmography.12
13
Recently, however, an alternate
technique, the negative expiratory pressure (NEP) method, has been
introduced to detect expiratory FL during tidal breathing, which does
not require either performance of FVC maneuvers on the part of the
patient or a body plethysmograph.14
15
This method has can
also been applied to patients receiving mechanical
ventilation.14
The NEP method has been validated by
concomitant determination of isovolume flow-pressure
relationships.14
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NEP Method for Detection of Expiratory FL
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Figure 2
illustrates the experimental setup used to detect expiratory FL with
the NEP method. It consists of a pneumotachograph and a Venturi device
capable of generating a negative pressure when connected to a source of
compressed air. The Venturi device is activated by opening a rapid
solenoid valve. The NEP method consists in applying negative pressure
at the mouth during a tidal expiration and comparing the ensuing
-V curve with that of the previous control expiration.
Therefore, with this technique, the volume and time history, as well as
the intrathoracic pressures, during the expiration with NEP are the
same as in the preceding control breath. If application of NEP elicits
increased flow over the entire range of the control VT, the
patient is not flow limited (Fig 3
, left panel). In contrast, if with NEP the subject exhales
along part or the entire control -V curve, FL is present (Fig 3 ,
middle and right panels). The FL portion of the
tidal expiration can be expressed as percentage fraction of the control
VT (percent VT). In the two
FL subjects in Figure 3
, FL amounted to 45% and 68% of
VT, respectively. If expiratory FL is present
when NEP is applied, there is a transient increase of flow (spike in
Fig 3
, right panel), which mainly reflects enhanced dynamic
airway compression and sudden reduction in volume of the compliant oral
and neck structures.14
15
Such spikes are useful markers
of FL.
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Figure 2. Schematic diagram of equipment setup for NEP test.
Pao = pressure at airway opening; = flow. Volume is
obtained by numerical integration of signal. During the study, the time
course of flow, volume, and pressure are continuously monitored on the
screen of the computer, together with the corresponding flow-volume
curve.4
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Figure 3. Flow-volume loops of NEP test breaths and
preceding control breaths in three representative COPD patients sitting
at rest: no FL (left panel), FL over last 45% of
control expired VT (middle panel), and FL
over 68% VT (right panel). Long arrows
indicate onset of NEP. Short arrows indicate onset of FL. Zero volume
is end-expiratory lung volume of control breaths.4
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Relationship of FEV1 to FL
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Figure 4
depicts the relationship between FEV1 percent
predicted and FL in 117 stable COPD patients. Expiratory FL was
determined during resting breathing in sitting and supine positions.
Although, on average, the patients who were experiencing FL when both
seated and supine had a significantly lower FEV1
percent predicted than those who were not experiencing FL
(p < 0.001), there was marked scatter of the data. Indeed, 60% of
the non-FL group had an FEV1 < 49% predicted,
and would be classified as having severe to very-severe airway
obstruction.16
Thus, FEV1 is not a
good predictor of tidal expiratory FL.
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Figure 4. Individual values of FEV1 percent
predicted (%pred) and tidal FL of 117 COPD patients while seated and
supine at rest. Twenty-six patients were not experiencing FL when both
seated and supine, 22 had FL only supine, and 69 had FL when both
seated and supine; p value refers to difference between non-FL and FL
both seated and supine.4
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FL and Chronic Dyspnea
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Intuitively, one would expect patients with the most severe airway
obstruction, as assessed with routine lung function measurements, to be
the most dyspneic. However, some patients with severe airway
obstruction are minimally symptomatic, whereas others with little
objective dysfunction appear to be very dyspneic.17
In
fact, many studies have shown that the correlation between chronic
dyspnea and FEV1 is weak.4
In
contrast, FL as measured with the NEP technique is a much better
predictor of chronic dyspnea then
FEV1.4
12
13
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FL and Exercise Capacity
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Since in COPD the reduced exercise capacity shows only a weak
relation to FEV1 and FVC,18
it has
been concluded that other factors, such as peripheral muscle weakness,
deconditioning, and impaired gas exchange, play a predominant role to
reduced exercise tolerance.19
A recent study, however, has
shown that in COPD there is a strong correlation (r = 0.81) between
the resting inspiratory capacity and the exercise
capacity.20
Accordingly, lung function impairment is
probably an important cause of decreased exercise tolerance in many
COPD patients. Indeed, because of expiratory FL, the maximal
VT (and hence ventilation) is closely related to resting
inspiratory capacity.21
In conclusion, the NEP technique provides a simple and reliable
tool for detecting expiratory FL both at rest and during exercise. The
method does not require a body plethysmograph, does not depend on
patient cooperation and coordination, and can be applied in any desired
body posture.
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Acknowledgements
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We thank Ms. Angie Bentivegna for typing this
manuscript.
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References
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Hyatt, RE (1961) The interrelationship of pressure, flow and volume during various respiratory maneuvers in normal and emphysematous patients. Am Rev Respir Dis 83,676-683[ISI][Medline]
-
Gottfried SB. The role of PEEP in the mechanically ventilated COPD patient. In: Roussos C, Marini JJ, eds. Ventilatory failure. Berlin, Germany: Springer-Verlag 1991:392–418
-
O’Donnell, DE, Sanii, R, Anthonisen, NR, et al (1987) Effect of dynamic airway compression on breathing pattern and respiratory sensation in severe chronic obstructive pulmonary disease. Am Rev Respir Dis 135,912-918[ISI][Medline]
-
Eltayara, L, Becklake, MR, Volta, CA, et al (1995) Relationship of chronic dyspnea and flow limitation in COPD patients. Am J Respir Crit Care Med 154,1726-1734[Abstract]
-
Leaver, DG, Pride, NB (1971) Flow-volume curves and expiratory pressures during exercise in patients with chronic airways obstruction. Scand J Respir Dis Suppl 77,23-27[Medline]
-
Stubbing, DG, Penegelly, LD, Morse, JLC, et al (1980) Pulmonary mechanics during exercise in subjects with chronic air-flow obstruction. J Appl Physiol 49,511-515[Abstract/Free Full Text]
-
Grimby, G, Stiksa, J (1970) Flow-volume curves and breathing patterns during exercise in patients with obstructive lung disease. Scan J Clin Lab Invest 25,303-313[ISI][Medline]
-
Ingram, RH, Jr, Schilder, DP (1966) Effect of gas compression on pulmonary pressure, flow and volume relationship. J Appl Physiol 47,1043-1050
-
Koulouris, NG, Rapakoulias, P, Rassidakis, A, et al (1995) Dependence of FVC maneuver on time course of preceding inspiration in patients with restrictive lung disease. Eur Respir J 8,306-313[Abstract]
-
D’Angelo, E, Robatto, E, Calderini, M, et al (1991) Pulmonary and chest wall mechanics in anesthetized paralysed humans. J Appl Physiol 70,2602-2610[Abstract/Free Full Text]
-
Melissinos, CG, Webster, P, Tien, YK, et al (1979) Time dependence of maximum flow as an index of nonuniform emptying. J Appl Physiol 47,1043-1050[Abstract/Free Full Text]
-
Murciano, D, Pichot, M-H, Boczkowski, J, et al (1997) Expiratory flow limitation in COPD patients after single lung transplantation. Am J Respir Crit Care Med 155,1036-1041[Abstract]
-
Boczkowski, J, Murciano, D, Pichot, M-H, et al (1997) Expiratory flow limitation in stable asthmatic patients during resting breathing. Am J Respir Crit Care Med 156,752-757[Abstract/Free Full Text]
-
Valta, P, Corbeil, C, Lavoie, A, et al (1994) Detection of expiratory flow limitation during mechanical ventilation. Am J Respir Crit Care Med 150,1311-1317[Abstract]
-
Koulouris, NG, Valta, P, Lavoie, A, et al (1995) A simple method to detect expiratory flow limitation during spontaneous breathing. Eur Respir J 8,306-313
-
Burrows, B, Lebowitz, MD (1975) Characteristics of chronic bronchitis in a warm, dry region. Am Rev Respir Dis 112,365-370[ISI][Medline]
-
Fletcher CM. Bronchitis: an international symposium. Assen, The Netherlands Discussion. Springfield, IL: Charles C. Thomas, 1961; 212–214
-
Jones, NG, Jones, G, Edwards, RHT (1971) Exercise tolerance in chronic airway obstruction. Am Rev Respir Dis 103,477-494[ISI][Medline]
-
Gosselink, R, Troosters, T, Decramer, M (1997) Exercise training in COPD patients: the basic questions. Eur Respir J 10,2884-2891[Abstract]
-
Murariu, C, Ghezzo, H, Milic-Emili, J, et al (1998) Exercise limitation in obstructive lung disease. Chest 114,965-968[Abstract/Free Full Text]
-
Koulouris, NG, Dimopoulou, I, Valta, P, et al (1996) Detection of expiratory flow limitation during exercise in COPD patients. J Appl Physiol 82,723-731[Abstract/Free Full Text]
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Introduction
NEP Method for Detection...
