Orthopnea and Tidal Expiratory Flow
Limitation in Patients With Stable
COPD*
Loubna Eltayara, MD; Heberto Ghezzo, PhD; and Joseph Milic-Emili, MD
Background: Orthopnea is a common feature in COPD patients, although its nature is poorly
understood.
Objective: To study the role of tidal expiratory flow limitation (FL) in the genesis of orthopnea in
patients with stable COPD.
Measurements: Tidal FL was assessed in 117 ambulatory COPD patients in sitting and supine
positions using the negative expiratory pressure method. The presence or absence of orthopnea
was also noted.
Results and conclusions: In patients with stable COPD with tidal expiratory FL in seated and/or
supine position, there is a high prevalence of orthopnea, which probably results in part from
increased inspiratory efforts due to dynamic pulmonary hyperinflation and the concomitant
increase in inspiratory threshold load due to intrinsic positive end-expiratory pressure. Increased
airway resistance in supine position due to lower end-expiratory lung volume probably also plays
a role in the genesis of orthopnea.
(CHEST 2001; 119:99 –104)
Key words: inspiratory work; intrinsic positive end-expiratory pressure; negative expiratory pressure method to detect
flow limitation; posture; routine lung function
Abbreviations: ATS ⫽ American Thoracic Society; BMI ⫽ body mass index; EELV ⫽ end-expiratory lung volume;
FL ⫽ flow limitation; FRC ⫽ functional residual capacity; HD ⫽ heart disease; LHF ⫽ left heart failure;
NEP ⫽ negative expiratory pressure; NFL ⫽ not flow limited; PEEPi ⫽ intrinsic positive end-expiratory pressure;
RHD ⫽ right heart disease; RV ⫽ residual volume; TLC ⫽ total lung capacity; Vr ⫽ relaxation volume;
WPEEPi ⫽ inspiratory work due to PEEPi
atients with severe COPD often exhibit expiraP tory
flow limitation (FL) during resting breathing, ie, their tidal expiratory flows are maximal under
the prevailing conditions.1–3 While the maximal expiratory flow volume curve is essentially independent
of body position,4 the functional residual capacity
(FRC) in patients with mild-to-moderate COPD is
smaller when in the supine position than when
sitting.5 As a result, tidal expiratory FL is an earlier
manifestation of COPD in the supine than in the
sitting position.2,3 At a later stage, however, COPD
patients eventually exhibit tidal expiratory FL both
seated and supine.2,3 The presence of expiratory FL
promotes dynamic pulmonary hyperinflation, a con*From the Meakins-Christie Laboratories, and Montreal Chest
Institute Research Centre, McGill University, Montreal, Quebec,
Canada.
This study was supported by the J. Costello Memorial Research
Fund, Royal Victoria Foundation, and the Montreal Chest
Institute Research Center.
Manuscript received February 10, 2000; revision accepted August 2, 2000.
Correspondence to: Joseph Milic-Emili, MD, Meakins-Christie
Laboratories, McGill University, 3626 St. Urbain St, Montreal,
Quebec H2X 2P2, Canada; e-mail: [email protected]
dition in which the FRC is higher than the elastic
equilibrium volume (the relaxation volume [Vr]) of
the respiratory system, the difference between the
FRC and Vr being termed ⌬FRC.6,7 As a result of
dynamic hyperinflation, there is a positive endexpiratory elastic recoil pressure, which has been
labeled intrinsic positive end-expiratory pressure
(PEEPi), which acts as an inspiratory threshold
load.6,7 Dynamic hyperinflation is associated with
increased inspiratory work due to PEEPi6,7 and
impaired inspiratory muscle function.8 These are
probably the main causes of chronic dyspnea in
COPD patients.2
Patients with COPD often experience more severe
dyspnea in supine than in sitting positions, ie, orthopnea.9,10 The nature of this phenomenon is not
clear. Since in COPD patients diaphragmatic function is probably not impaired in supine position
compared to sitting position, this cannot explain
orthopnea.11,12 In contrast, increased inspiratory
work due to PEEPi (WPEEPi) and airway resistance
in supine position is a more likely explanation. Since
airway resistance increases with decreasing lung
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99
volume,13 the lower FRC in supine position5 should
be associated with an augmented inspiratory resistive
work. Furthermore, in patients with mild-to-moderate COPD, who during resting breathing exhibit
expiratory FL only in the supine position, the presence of WPEEPi in the supine position should
promote orthopnea. The same should also occur in
patients with severe COPD who exhibit tidal expiratory FL both seated and supine. Indeed, while in
such patients the end-expiratory lung volume
(EELV) during resting breathing is essentially the
same in seated and supine position,14 –16 as a result of
gravitational factors the Vr is lower supine than
sitting.17 As a result, in COPD patients who are flow
limited both seated and supine, the ⌬FRC and the
WPEEPi should also be greater in supine position,
promoting orthopnea.
The present study was undertaken on 117 COPD
patients to (1) assess if the prevalence of orthopnea
is related to the presence of tidal expiratory FL in
sitting and supine positions, and (2) to further characterize the relationship of orthopnea with other
physiologic and clinical findings, in particular routine
spirometric variables and heart disease (HD).
Materials and Methods
Subjects
A cross-sectional study was carried out on 117 consecutive
ambulatory COPD patients (75 men and 42 women). All patients
were suffering from COPD according to the American Thoracic
Society (ATS) guidelines,18 and were studied in a stable clinical
and functional state. Their anthropometric characteristics and
lung function data are given in Table 1. Thirty-six of the patients
had clinical evidence of chronic right heart failure. Each patient
gave informed consent and the study protocol was approved by
the Institutional Ethics Committee. The present investigation
was carried out concurrently with a study on the relationship
between chronic dyspnea and tidal expiratory FL in the same 117
COPD patients.2
Pulmonary Function Tests
The FVC and FEV1 were measured with the patient in sitting
position using a spirometer (Spiro Analyzer ST-250R; Fukuda
Sangyo; Tokyo, Japan). This system, which meets the ATS
standards, was calibrated every day with standardized techniques
according to the guidelines of the ATS.19 In 83 patients, thoracic
gas volumes obtained with a pressure/flow whole body plethysmograph (Autobox 2800; SensorMedics; Yorba Linda, CA) were
also available. The predicted values for routine spirometry and
thoracic gas volumes were those of Morris and coworkers.20 In 27
patients, Pao2 and Paco2 measured with a blood gas analyzer (ABL
330; Radiometer; Copenhagen, Denmark) were also available.
Expiratory FL
The experimental set-up used to assess tidal FL by negative
expiratory pressure (NEP) was similar to that described in detail
Table 1—Anthropometric and Lung Function Data of
COPD Patients With and Without Orthopnea*
Variables
No Orthopnea
Orthopnea
Subjects, No.
Gender, male/female
Age, yr
Height, cm
Weight, kg
BMI, kg/m2
FEV1, % predicted
FVC, % predicted
FEV1/FVC, % predicted
3-point FL score (0, 1, and 2)
Subjects, No.
TLC, % predicted
FRC, % predicted
RV, % predicted
RV/TLC, % predicted
Subjects, No.
Pao2, mm Hg
Paco2, mm Hg
24
9/15
71 ⫾ 8
164 ⫾ 10
63 ⫾ 11
24 ⫾ 6
43 ⫾ 18
66 ⫾ 18
63 ⫾ 18
0.4 ⫾ 0.7
17
122 ⫾ 19
138 ⫾ 24
157 ⫾ 32
130 ⫾ 20
4
85 ⫾ 5
41 ⫾ 1
93
33/60
69 ⫾ 8
163 ⫾ 8
70 ⫾ 17
27 ⫾ 4†
34 ⫾ 13†
61 ⫾ 17
55 ⫾ 17
1.6 ⫾ 0.7†
66
131 ⫾ 20
158 ⫾ 38†
189 ⫾ 45†
150 ⫾ 20†
23
66 ⫾ 9†
47 ⫾ 4†
*Values are presented as means ⫾ SD unless otherwise indicated.
†p ⬍ 0.05 between the two groups (unpaired t test).
previously.2 All patients were studied both seated upright in a
comfortable chair and lying supine on a comfortable couch, in
random order. The pattern of breathing was continuously monitored on a computer screen. After reaching steady-state breathing, we performed a series of three to five test breaths in which
NEP of ⫺ 5 cm H2O was applied at the beginning of expiration
and maintained throughout expiration. These expiratory flowvolume loops were compared by superimposition with those
obtained during the immediately preceding breaths. The volume
signal was corrected for any offset based on the assumption that
inspired and expired volumes of the preceding breath were
identical.2 In the absence of preexisting FL, the increase in
pressure gradient between the alveoli and the airway opening
caused by NEP should result in increased expiratory flow,
whereas in flow-limited subjects, NEP should enhance dynamic
airway compression downstream from the flow-limiting segments, without substantial effect on pressure or flow upstream.
Accordingly, in flow-limited subjects, expiratory flow does not
change with NEP, except for a brief flow transient (spike), which
is thought to mainly reflect sudden reduction in volume of the
compliant oral and neck structures. To a lesser extent, however,
enhanced dynamic airway compression and a small artifact
caused by the common-mode rejection ratio of the system for
measuring flow also contributed to such flow transients. In line
with previous studies,2,4 after the application of NEP, the
expiratory flow either increased (reflecting absence of FL) or did
not change (reflecting presence of FL). There was no instance in
which application of NEP resulted in a sustained decrease of
expiratory flow below the corresponding control values as a
consequence of upper-airway collapse.
Subjects in whom the application of NEP did not elicit an
increase of flow over all or part of the control tidal expiration
were considered flow limited. By contrast, subjects in whom flow
increased with NEP over the entire range of the control tidal
expiration were considered as not flow limited (NFL). The
degree of expiratory FL was assessed in terms of a 3-point FL
score2: score 0 ⫽ NFL both supine and seated; score 1 ⫽ FL
when supine but not seated; and score 2 ⫽ FL both supine and
seated. As previously described,2,3 we found that all COPD
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Clinical Investigations
patients who had FL when seated also had FL when supine,
while many COPD patients who had FL when supine were NFL
when seated. With patients both seated and supine, the NEP
tests were reproducible in the sense that each patient was
classified as either FL or NFL on all three to five NEP tests
performed in any given position.
During the application of NEP, air may leak around the lips
into the expired line and contribute to the expiratory flow. Such
leaks, however, are easily detected because they result in a
sustained decrease of the EELV during the tidal breaths following NEP application. Accordingly, great care was taken to avoid
such leaks by proper positioning of the mouthpiece and by asking
the subjects to hold their lips tight.
Multiple logistic regression analysis was carried out to evaluate
the strength and significance of the 3-point FL score as potential
risk factor for orthopnea. Age, gender, body mass index (BMI),
FEV1 (percent predicted), and presence of right heart disease
(RHD) according to clinical history were taken as possible
confounders. Age, BMI, and FEV1 (percent predicted) were
treated as continuous covariables, while gender, RHD, and the
3-point FL score were expressed as categorical covariables. The
logistic regression analysis was performed using statistical software (SPSS Statistical Package; SPSS; Chicago, IL). With this
package, the first category is taken as a reference category for
each categorical independent variable.
Results
Orthopnea
During the above session, the occurrence and the severity of
orthopnea were assessed by the following two questions: (1) “Do
you feel more breathless when you are lying on your back than
when you are seated?” Based on this question, the patients were
classified into two groups: group 0, patients who did not report
orthopnea (by answering No to the question); and group 1,
patients who reported orthopnea (by answering Yes to the
question), (2) “How many pillows do you use when sleeping?”
The reproducibility of the above two questions was assessed on
a pilot study on 10 subjects. These subjects were chosen from the
outpatient clinics of the Saint-Luc Hospital, Montreal, Canada.
Five of them were selected based on a physician’s diagnosis of
stable COPD. The five other subjects chosen from the list of
nonrespiratory outpatient clinics did not have any respiratory
disease and did not complain of dyspnea. They were scheduled
for two visits, 2 weeks apart.
They completed the FL measurements in seated and supine
position and answered the above orthopnea questions. The
reproducibility in this sample was 95%. The reproducibility of
assessment of FL was also high, as previously reported.2
Statistical Analysis
Values reported in the text are means ⫾ SD. Statistical analysis
was made using the unpaired t test, with the level of significance
set at p ⬍ 0.05. In addition, multiple logistic regression analysis
was used, as explained below.
There were 24 patients (20.5%) who did not report
orthopnea and 93 patients (79.5%) who did. None of
the 24 patients who did not report orthopnea used
two or more pillows. Among the 93 patients who
reported orthopnea, 40 patients (43%) used two
pillows, 35 patients (38%) used three pillows, and 18
patients (19%) used four or more pillows.
The anthropometric and lung function data of the
117 COPD patients stratified according to presence
or absence of orthopnea are shown in Table 1. While
age, height, and weight did not differ significantly
between the two groups, the average BMI of the
group without orthopnea was slightly though significantly different from that with orthopnea. The
FEV1 percent of predicted was significantly lower in
the patients with orthopnea, while no significant
differences were found in either FVC or FEV1/FVC
(percent predicted). The 3-point FL score was significantly higher in the orthopnea group.
Figure 1A depicts the individual values of the
3-point FL score stratified according to the two
orthopnea groups. Although most of the patients
who reported orthopnea had FL when seated and/or
Figure 1. Left, A: Individual values of 3-point FL score of all 117 COPD patients studied stratified
according to the two orthopnea groups. Right, B: Same as left, A, but without the 36 patients with RHD.
All p values (unpaired t test) refer to significant differences between the two groups.
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101
supine (scores 1 or 2), there were nine patients who
reported orthopnea in spite of the fact that they were
NFL both seated and supine. Figure 1, right, B
depicts the individual values of the 3-point FL score
after exclusion of the patients who had RHD. In this
case, there were only four NFL patients left in the
orthopnea group.
As shown in Table 1, in the subset of COPD
patients in whom thoracic gas volume was measured
(n ⫽ 83), those who reported orthopnea exhibited a
significantly higher residual volume (RV), FRC, and
RV/total lung capacity (TLC) (percent predicted)
than those who did not. In the subset of COPD
patients in whom arterial blood gases were analyzed
(n ⫽ 27), those with orthopnea had a significantly
lower Pao2 and higher Paco2.
According to the multiple logistic regression analysis in Table 2, the only variables significantly related
to orthopnea were the 3-point FL score and HD,
while FEV1 (percent predicted), age, gender, and
BMI were found to carry no significant risk. However, when the logistic regression analysis was carried out by omitting the 3-point FL score, the FEV1
(percent predicted) was found to be significantly
related to orthopnea, though the significance level
was lower than that for the 3-point FL score
(p ⬍ 0.05 vs 0.01). To the extent that FEV1 (percent
predicted) is an indirect index of FL,2 after omission
of the 3-point FL score a significant correlation was
necessarily found between orthopnea and FEV1
(percent predicted).
Discussion
In this study, we have examined the association of
orthopnea with the 3-point FL score and routine
Table 2—Multiple Logistic Regression Equations of
Reported Orthopnea With Various Covariables
Covariables/Categories
3-point FL score
NFL
FL when supine
FL when seated and supine
FEV1, % predicted
Age, yr
Gender
Male
Female
BMI, kg/m2
HD
No
Yes
Constant
*p ⬍ 0.01.
†p ⬍ 0.05.
Odds Ratio
SE
Reference category
6.55*
0.70
32.41*
0.77
0.99
0.02
0.99
0.04
Reference category
1.52
0.67
1.03
0.03
Reference category
2.50†
0.35
1.15
lung function data in 117 patients with stable COPD.
The main finding is that FL is the strongest risk
factor for reported orthopnea.
The fact that patients with severe COPD may be
FL during resting breathing is well recognized, and
the consequences in terms of dynamic pulmonary
hyperinflation, increased work of breathing, and
impaired inspiratory muscle function and hemodynamics have been well documented.6,7,21 In a previous study, we have shown that chronic dyspnea, as
assessed with the modified Medical Research Council scale, is more closely correlated with the degree of
FL than with routine lung function data.2 In the
present study, we found that orthopnea is more
prevalent in patients with tidal FL (Fig 1). In COPD
patients who are FL only in the supine position, the
inspiratory work of breathing would be expected to
be higher when supine than seated because of the
additional WPEEPi and increased airway resistance
in the supine position.7 Accordingly, the degree of
dyspnea should be greater in the supine position. In
this connection, it should be noted that in some
COPD patients receiving mechanical ventilation, the
degree of expiratory FL is reduced or abolished by
shifting from the supine to the semirecumbent position, presumably because of increased EELV.22 In
patients who are FL in the sitting position, WPEEPi
should also be greater in supine than in the sitting
position because of greater WPEEPi.2,3 In fact, in
patients with severe COPD who presumably were
FL both seated and supine, the changes in FRC
when shifting from seated to supine position have
been found to be either very small or absent.5,14
Since, as a result of gravitational factors, Vr is
expected to be higher seated than supine,17 it follows
that the degree of dynamic pulmonary hyperinflation
(⌬FRC) and, hence, WPEEPi should be greater in
the supine position. The possible role of tidal FL in
the genesis of orthopnea is supported by two recent
studies. Duguet and coworkers23 studied patients
with acute left heart failure (LHF), in whom orthopnea is a clinical hallmark.9 As airway obstruction is
common in LHF, they hypothesized that postural
aggravation of tidal FL could contribute to LHFrelated orthopnea. In 9 of 12 of their patients with
LHF, they observed that tidal FL was induced or
aggravated by the supine position and that this
coincided with orthopnea. They concluded that, in
acute LHF, tidal FL is more frequent or prominent
in the supine position with a concomitant increase in
PEEPi and hence in load on the inspiratory muscles,
contributing to orthopnea. Pankow and coworkers24
assessed tidal FL and PEEPi in eight healthy obese
subjects in both sitting and supine position. In seven
of these subjects, they found that tidal FL and
PEEPi were either induced or aggravated by the
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Clinical Investigations
supine position, with a concomitant increased load
on the diaphragm. Unfortunately, they did not assess
orthopnea. Similar to patients with acute LHF23 and
obese subjects,24 in many COPD patients tidal FL is
either induced or aggravated by the supine position,2,3 and may contribute to orthopnea. However,
other factors could contribute to orthopnea.
O’Donnell and coworkers25 suggested that flowlimiting dynamic airway compression may per se
elicit dyspnea. However, a recent study26 on normal
subjects with methacholine-induced tidal expiratory
FL does not support this hypothesis. On the other
hand, there is evidence that expiratory FL just
precedes dependent airway closure (closing volume)
at low flow rates.27 This should lead to abnormal
distribution of ventilation within the lung with concomitant hypoxemia.28 While hypoxia per se may not
cause dyspnea, it does increase ventilation. This
would increase the degree of expiratory FL, with a
concomitant increase in dynamic hyperinflation and
PEEPi, enhancing dyspnea in the supine position.
Although the 3-point FL score was significantly
higher in the orthopnea group (Table 1), 8% of the
patients reported orthopnea in absence of FL (Fig 1,
left, A). This was due in part to the fact that our
COPD population included patients with concurrent
RHD. After exclusion of the HD patients (30%),
only four of the COPD patients who were NFL did
report orthopnea (Fig 1, right, B). An association of
orthopnea and tidal expiratory FL has been recently
demonstrated in patients with acute LHF.23 None of
our COPD patients, however, exhibited left ventricular dysfunction, which is a rare occurrence even in
patients with severe airway obstruction.29
There was a significant difference in Pao2 and
Paco2 between the two orthopnea groups, which
could be attributed in part to the fact that the
patients with orthopnea had more severe COPD
than the patients without orthopnea (Table 1). The
decreased Pao2 in the orthopnea group is predictable in view of the fact that these patients exhibited
a more severe degree of FL than the nonorthopnea
groups (Fig 1, Table 1). Indeed, the onset of expiratory FL heralds peripheral airway closure in dependent lung zones27 with concomitant abnormality in
ventilation distribution and gas exchange.28 An increased Paco2 (p ⬍ 0.05) has been previously found
in COPD patients with tidal FL both seated and
supine.2 We also found a significant difference in
BMI and FEV1 (percent predicted) between the two
orthopnea groups (Table 1). However, neither represented a significant risk for orthopnea according to
the multiple logistic regression analysis in Table 2.
According to Table 2, the 3-point FL score and HD
were the only significant risk factors for orthopnea,
with the former playing the main role. Indeed, the
COPD patients who were FL both sitting and supine
had a 32-fold greater risk of reporting orthopnea
than the patients who were NFL. Though the HD
covariable was not as strong and significant as the
3-point FL score, the COPD patients with right
heart dysfunction had an almost threefold higher risk
of reporting orthopnea than those without RHD.
When the 3-point FL score was omitted from the
multiple logistic regression analysis, FEV1 (percent
predicted) became a statistically significant risk factor
for orthopnea, although at a lower level of significance
than the 3-point FL score. This probably merely reflects the fact that FEV1 (percent predicted) is a poor,
though significant, indirect index of FL.2
In conclusion, in patients with stable COPD with
tidal expiratory FL in seated and/or supine position,
there is a high prevalence of orthopnea, which may
be due to increased inspiratory effort due to PEEPi
and increased airway resistance in supine position.
Further studies, including measurements of inspiratory work and its components, are required to explain orthopnea.
ACKNOWLEDGMENT: The authors thank Ms. Maria Makroyanni and Ms. Angie Bentivegna for secretarial work.
References
1 Hyatt RE. The interrelationship of pressure, flow and volume
during various respiratory maneuvers in normal and emphysematous patients. Am Rev Respir Dis 1961; 83:676 – 683
2 Eltayara L, Becklake MR, Volta CA, et al. Relationship of
chronic dyspnea and flow limitation in COPD patients. Am J
Respir Crit Care Med 1996; 154:1726 –1734
3 Koulouris NG, Valta P, Lavoie A, et al. A simple method to
detect expiratory flow limitation during spontaneous breathing. Eur Respir J 1995; 8:306 –313
4 Castile R, Mead J, Jackson A, et al. Effects of posture on
flow-volume curve configuration in normal humans. J Appl
Physiol 1982; 53:1175–1183
5 Erwin WS, Zolov D, Bickerman HA. The effect of posture on
respiratory function in patients with obstructive pulmonary
emphysema. Am Rev Respir Dis 1966; 94:865– 871
6 Coussa ML, Guérin C, Eissa NT, et al. Partitioning of work of
breathing in mechanically ventilated COPD patients. J Appl
Physiol 1993; 75:1711–1719
7 Roussos C, Marini JJ. Ventilatory failure. Berlin, Germany:
Springer-Verlag, 1991; 396 – 418
8 Bellemare F, Grassino A. Force reserve of the diaphragm in
patients with chronic obstructive pulmonary disease. J Appl
Physiol 1983; 55:8 –15
9 Mahler DA. Dyspnea. Basel, Switzerland: Marcel Dekker,
1998; 243–246
10 O’Neill S, McCarthy DS. Postural relief of dyspnea in severe
chronic airflow limitation: relationship to respiratory muscle
strength. Thorax 1983; 38:595– 600
11 Sharp JT. The chest wall and respiratory muscles in airflow
limitation. In: Roussos C, Macklem PT, eds. The thorax. New
York, NY: Marcel Dekker, 1985; 1155–1202
12 Hejidra YF, Dekhuijzen PNR, van Herwaarden CLA, et al.
Effects of body position, hyperinflation, and blood gas tensions
on maximal respiratory pressures in patients with chronic obCHEST / 119 / 1 / JANUARY, 2001
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21956/ on 06/16/2017
103
structive pulmonary disease. Thorax 1994; 49:452– 458
13 Briscoe WA, DuBois AB. The relationship between airway
resistance, airway conductance and lung volume in subjects of
different age and body size. J Clin Invest 1958; 37:1279 –1285
14 Marini JJ, Tyler ML, Hudson LD, et al. Influence of headdependent positions on lung volume and oxygen saturation in
chronic airflow obstruction. Am Rev Respir Dis 1984; 129:
101–105
15 Tucker DH, Sieker HA. The effects of change of body
position on lung volumes and intrapulmonary gas mixing in
patients with obesity, heart failure, and emphysema. Am Rev
Respir Dis 1960; 82:787–790
16 Vellody VP, Nassery M, Druz WS, et al. Effects of body
position change on thoracoabdominal motion. J Appl Physiol
1978; 45:581–589
17 Agostoni E, Mead J. Statics of the respiratory system. In:
Fenn WO, Rahn H, eds. Handbook of physiology, respiration.
(vol 1). Washington, DC: American Physiological Society,
1964; 387– 409
18 American Thoracic Society. Standards for the diagnosis and
care of patients with chronic obstructive pulmonary disease
(COPD) and asthma. Am Rev Respir Dis 1987; 136:225–244
19 American Thoracic Society. Standardization of spirometry.
Am Rev Respir Dis 1987; 136:1285–1298
20 Morris JF, Koski A, Johnson LC. Spirometric standards for
healthy nonsmoking adults. Am Rev Respir Dis 1971; 103:
57– 67
21 Pepe AE, Marini JJ. Occult positive end-expiratory pressure
22
23
24
25
26
27
28
29
in mechanically ventilated patients with airflow obstruction:
the auto-PEEP effect. Am Rev Respir Dis 1982; 126:166 –170
Valta P, Corbeil C, Lavoie A, et al. Detection of expiratory
flow limitation during mechanical ventilation. Am J Respir
Crit Care Med 1994; 150:1311–1317
Duguet A, Tantucci C, Lozinguez O, et al. Expiratory flow
limitation as a determinant of orthopnea in acute left heart
failure. J Am Coll Cardiol 2000; 35:690 –700
Pankow W, Podszus T, Gutheil T, et al. Expiratory flow
limitation and intrinsic positive end-expiratory pressure in
obesity. J Appl Physiol 1998; 85:1236 –1243
O’Donnell DE, Sanii R, Anthonisen NR, et al. Effect of
dynamic airway compression in breathing pattern respiratory
sensation in severe chronic obstruction pulmonary disease.
Am Rev Respir Dis 1987; 135:912–918
Sulc J, Volta CA, Ploysongsang Y, et al. Flow limitation and
dyspnea in normal supine subjects during methacholine
challenge. Eur Respir J 1999; 14:1326 –1331
Hyatt RE, Okeson AC, Rodarte JR. Influence of expiratory
flow limitation on the pattern of lung emptying in normal
man. J Appl Physiol 1973; 35:411– 419
Alexander J, Spence AA, Parikh RK, et al. The role of airway
closure in post-operative hypoxemia. Br J Anesth 1973;
45:34 – 40
Vizza CD, Lynch JP, Ochoa LL, et al. Right and left
ventilation dysfunction in patients with severe pulmonary
disease. Chest 1998; 113:576 –583
104
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21956/ on 06/16/2017
Clinical Investigations