CRITICAL CARE PERSPECTIVE

Transpulmonary Pressure: The Importance of Precise Definitions and

Limiting Assumptions
Stephen H. Loring1, George P. Topulos2, and Rolf D. Hubmayr3
1
Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School,
Boston, Massachusetts; 2Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard
Medical School, Boston, Massachusetts; and 3Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota

Abstract
Recent studies applying the principles of respiratory mechanics to
respiratory disease have used inconsistent and mutually exclusive
definitions of the term “transpulmonary pressure.” By the traditional
definition, transpulmonary pressure is the pressure across the whole
lung, including the intrapulmonary airways, (i.e., the pressure
difference between the opening to the pulmonary airway and the
pleural surface). However, more recently transpulmonary pressure
has also been defined as the pressure across only the lung tissue
(i.e., the pressure difference between the alveolar space and the
pleural surface), traditionally known as the “elastic recoil pressure of
the lung.” Multiple definitions of the same term, and failure to
recognize their underlying assumptions, have led to different
interpretations of lung physiology and conclusions about appropriate
therapy for patients. It is our view that many current controversies in
the physiological interpretation of disease are caused by the lack of
consistency in the definitions of these common physiological terms.
In this article, we discuss the historical uses of these terms and recent
misconceptions that may have resulted when these terms were
confused. These misconceptions include assertions that normal
pleural pressure must be negative (subatmospheric) and that a
pressure in the pleural space may not be substantially positive when a
subject is relaxed with an open airway. We urge specificity and
uniformity when using physiological terms to define the physical
state of the lungs, the chest wall, and the integrated respiratory
system.
Keywords: esophageal pressure; respiratory mechanics;
mechanical ventilation; pleural pressure; breathing

Transpulmonary pressure, the pressure
across the lung that gives rise to pulmonary
ventilation, is central to our understanding
of respiratory mechanics. With the
measurement of esophageal pressure (1),
transpulmonary pressure can be estimated
and used to make clinical decisions. For
example, measuring transpulmonary
pressure in ventilated patients allows
positive end-expiratory pressure (PEEP) to
be adjusted to compensate for chest wall
mechanics. Transpulmonary pressure
indicates potential stress on the lung
parenchyma, stress that can lead to
ventilator-induced lung injury in acute
respiratory disease syndrome (ARDS).
Evaluating transpulmonary pressure in
these patients can reveal the effects of
respiratory efforts on lung stress. Other
clinical uses of esophageal manometry are
described in a recent review (1).
Recent studies applying the principles
of respiratory mechanics to respiratory
disease have revealed differences among
interpretations and uses of physiological
measurements. In particular, the terms
“transpulmonary pressure” and “pleural
pressure” have evolved multiple
definitions and interpretations. Different
interpretations have led logically to
different conclusions about appropriate
therapy for patients. It is our view that
many current controversies in the
physiological interpretation of disease are
due to the lack of consistency in the
definitions of these common physiological
terms as well as an underappreciation of
certain limiting assumptions. In this article,
we describe the traditional and alternate
definitions of these terms, discuss
misconceptions that may have resulted
when these terms were confused, and
highlight some caveats in their applications
in clinical practice.
The Traditional Definition of
Transpulmonary Pressure,
Pao 2 Ppl
Transpulmonary pressure (PL) has
traditionally been used to describe the

( Received in original form December 18, 2015; accepted in final form September 7, 2016 )
Author Contributions: S.H.L., G.P.T., and R.D.H. conceived, drafted, revised, and approved the final version of this manuscript.
Correspondence and requests for reprints should be addressed to Stephen H. Loring, M.D., 330 Brookline Avenue, DA 717, Boston, MA 02115.
E-mail: sloring@bidmc.harvard.edu
Am J Respir Crit Care Med Vol 194, Iss 12, pp 1452–1457, Dec 15, 2016
Copyright © 2016 by the American Thoracic Society
Originally Published in Press as DOI: 10.1164/rccm.201512-2448CP on September 8, 2016
Internet address: www.atsjournals.org

1452 American Journal of Respiratory and Critical Care Medicine Volume 194 Number 12 | December 15 2016
CRITICAL CARE PERSPECTIVE

pressure difference (or pressure drop)
across the whole lung, including the
airways and lung tissue (2–4), and is thus
defined as the pressure at the airway
opening (Pao) minus the pressure in
the pleural space (Ppl), PL = Pao 2 Ppl
(Figure 1, Table 1). The transpulmonary
pressure can be partitioned into
the pressure drop down the airway
(Pao 2 Palv), where Palv is alveolar
pressure, and the pressure drop across the
lung tissue, known as the elastic recoil
pressure of the lung [Pel(L) = Palv 2 Ppl].
Thus, PL = (Pao 2 Palv) 1 (Palv 2 Ppl).
In subjects breathing without equipment,
Pao is the pressure at the mouth or nose,
whereas in patients who are intubated, Pao
is the pressure in the external port of the
endotracheal tube or ventilator tubing,
which is often called airway pressure (Paw).
All pressures are measured relative to
atmospheric pressure (0 cm H2O).
Closed
alveolus
Flooded
alveolus
Mead (3) used this traditional
definition of transpulmonary pressure in
explaining the equation of motion of the
lung. In Mead’s model, the pressure across
the whole respiratory system is the sum of
PL and the pressure drop across the chest
wall (Pcw = Ppl 2 Pbs), where Pbs is the
pressure at the body surface.
Pressure differences across the lung can
be attributed to several physical phenomena.
Thus, PL includes Pel(L), the elastic recoil
pressure needed to stretch lung tissue and
expand the alveolar surface; Pres(L), the
pressure needed to overcome viscous
resistance (including airflow resistance
and tissue “resistance” to deformation),
and Pin(L), the pressure to overcome
the inertia of tissues and gas, principally
for temporal acceleration of gas in the
airway. The last term, Pin(L), is usually
negligible and omitted in most clinical
applications.
Eq
Equipment
Pao
Airway Opening
Airway AW
Alveolus
Palv Pbs
Esophagus
Lung Tissue
Lt
Pleural Space
Body Surface Ppl or
Pes
Chest Wall
CW
Similarly, Pcw = Ppl 2 Pbs is the
pressure drop across the chest wall (which
includes the diaphragm and belly wall).
Pcw (or Pw) includes the elastic recoil of
the passive chest wall, a small chest wall
resistive pressure, and pressure generated
by respiratory muscle activity that increases
or decreases Ppl. In the discussion that
follows, we will adopt these traditional
definitions and notations for PL and Pel(L).
Inhalations with identical flows and
volumes generate identical time courses of
PL, whether breaths are generated using
respiratory muscles or a mechanical
ventilator that raises Pao (or an iron lung
that lowers Pbs over the whole body).
Although Pao is easily measured
continuously, Ppl is not practical to
measure directly. However, Ppl can be
estimated by measuring esophageal
pressure (Pes), allowing PL to be
continuously estimated as Pao 2 Pes.
The elastic recoil pressure of the lung,
Pel(L) = Palv 2 Ppl, is the relevant pressure
when considering the stress applied to the
lung tissue (5). Determination of Pel(L)
requires estimation of Palv, which is not
easily measured directly. Fortunately, under
static conditions when the intrapulmonary
airways are open and there is no airflow or
temporal acceleration of gas, Pao 2 Palv = 0,
and therefore Pao = Palv and PL = Pel(L).
(This equivalence underlies the
measurements of lung compliance, auto-
PEEP during an end-expiratory hold, and
plateau alveolar pressure during an end-
inspiratory hold.)
These traditional definitions have been
used since the mid-1900s, a time of active
research in pulmonary mechanics (2–6),
and these definitions are still in widespread
use today (1, 7, 8). We recommend the
use of these traditional definitions for
consistency and clarity in future
communications.

Alternate Definitions of
Figure 1. The anatomical drawing (left) shows principal respiratory structures and locations at Transpulmonary Pressure
which key pressures could theoretically be measured. By convention, all pressures at a location are
measured relative to atmospheric (barometric) pressure, which is usually also the pressure at Transpulmonary Pressure Has Been
the body surface (Pbs). Pressure differences cause volume displacements of elastic structures Redefined as the Pressure across
and airflow in airways (see Table 1). Normally, alveoli communicate with the airway opening Lung Tissue, Palv 2 Ppl
through a continuous column of air. Under some conditions (see text), alveoli are filled with liquid or
Numerous relatively recent texts and articles
isolated by closed airways. The schematic diagram (right) shows the respiratory system as a
continuous circuit, illustrating the relations between pressures at a location (ellipses) and
have used the term “transpulmonary
intervening structures (rectangles), with and without respiratory equipment connected to pressure” or “PL” to describe Palv 2 Ppl,
the airway (dashed lines). AW = airway; CW = chest wall; Eq = equipment; Lt = lung tissue; that is, Pel(L), the elastic recoil pressure of
Palv = alveolar pressure; Pao = pressure at the airway opening; Pes = esophageal pressure; the lung tissue (i.e., without considering the
Ppl = pressure in the pleural space. pressure drop down the airway). Among

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 CRITICAL CARE PERSPECTIVE

Table 1. Pressures Measured at a Location and Pressure Differences across PL = Pel(L). However, the measurement of
Intervening Respiratory Structures PL under such static conditions does not
guarantee that the pressure measured will
Definition
be representative of Pel(L). For example,
when the intrapulmonary airways are
obstructed or closed, as is often the case at
Pressures at a location
Pao or Paw Pressure at the airway opening very low lung volumes or in severe lung
Palv Alveolar pressure disease, or the alveoli are filled with liquid
Ppl Pleural pressure or foam (Figure 1), Pao differs from
Pbs Body surface pressure the local Palv, and the measurement of
Pressure differences across
structures
static PL may include a large pressure drop
Pel(L) Elastic recoil pressure of the lung (pressure across down the (occluded) airway. Under these
the lung tissue, transalveolar pressure), Palv 2 Ppl conditions, Palv and thus Pel(L) of the
PL Transpulmonary pressure, Pao 2 Ppl affected lung regions may not be uniform
Pcw or Pw Pressure across the chest wall, Ppl 2 Pbs or measurable.
Prs Transrespiratory system pressure, Pao 2 Pbs
Pleural Pressure Need Not Be Lower
than Atmospheric Pressure during
these are John West’s Respiratory compliance (or 1/elastance). On the other Normal Breathing
Physiology, the Essentials, Weinberger’s hand, Pel(L) is the pressure exerted across We agree with the widely held assumption,
Principles of Pulmonary Medicine, the lung tissue only, and depends on lung that the lung tissue cannot substantially
Schwartzstein’s Respiratory Physiology, a volume and elastance (the inverse of resist compressive forces [i.e., that, locally,
Clinical Approach, and other current compliance) only; it is independent of Palv is never substantially less than Ppl and
reviews and journal articles (9–13). In these respiratory airflow and resistance. If we thus Palv 2 Ppl = Pel(L) > 0]. However,
examples, PL and transpulmonary pressure use transpulmonary pressure to denote when this assumption about Pel(L) is
were used to describe the forces distending Pel(L), it is not clear what term should be incorrectly applied to PL, estimates of
lung tissue and/or the mechanical stresses used for the pressure across the entire lung positive pleural pressures or negative
applied to the lung tissue during (Pao 2 Ppl) or the pressure drop down transpulmonary pressure (Pao 2 Ppl) are
mechanical ventilation, uses that are the airway (Pao 2 Palv). There is no assumed to be in error. For example,
conceptually consistent with the traditional term commonly in use for the concept of Wikipedia defines transpulmonary pressure
approach, albeit using different terms. Is PL (Pao 2 Palv) when transpulmonary as Palv 2 Ppl and states, “Normally, the
this alternate definition of transpulmonary pressure is assigned to the elastic recoil pressure within the pleural cavity is slightly
pressure, then, simply a minor difference pressure of the lung, Pel(L), and both terms less than the atmospheric pressure...”
in the use of terms without significant are needed. (https://en.wikipedia.org/wiki/Intrapleural_
consequence, or does it lead to pressure). However, during normal passive
miscommunication and confusion about PL Is Continuously Measurable; exhalation, Ppl is positive at all volumes
the interpretation of measurements and the Pel(L) Is Not above the chest wall relaxation volume,
meaning of PL and Pel(L)? PL and Pel(L) both vary continuously in and Ppl is often positive during supine
In the traditional approach, both time. However, Pel(L) cannot be measured expiration, during active expiration
transpulmonary pressure and elastic recoil continuously, because it requires such as with high minute ventilation, or
pressure are useful concepts that have determination of Palv, which can only be when expiratory airway resistance is
distinctly different meanings. We believe measured when there is no pressure drop increased.
that the use of “transpulmonary pressure” down the airway (i.e., when flow is zero and
to denote both Pao 2 Ppl and Palv 2 Ppl the intrapulmonary airways are open, Esophageal Pressure Need Not Equal
has resulted in confusion. Here, we first assuring that Pao = Palv). If the term Average Pleural Pressure
present arguments for using the traditional transpulmonary pressure was defined as Most evidence suggests that in the upright
definitions of “transpulmonary pressure” Palv 2 Ppl there would be no label for posture the pressure in the distal third of the
and “elastic recoil pressure of the lung,” Pao 2 Ppl when it is measured esophagus approximates average pleural
then present published ideas apparently continuously as Pao 2 Pes. pressure. (Here, the “average” pleural
based on misunderstandings of limiting pressure is taken to mean that pressure
assumptions underlying these definitions. which, if applied to the whole pleural
Limiting Assumptions That surface, would result in the same observed
Two Concepts Need Two Names Apply to Both PL and Pel(L) lung volume and total flow.) However, it is
As noted above, PL and Pel(L) are both known that esophageal pressure exceeds
useful concepts that need clear and distinct Airway Pressure during Airway average Ppl in the supine posture by 3 to
definitions. PL is the pressure exerted across Occlusion Need Not Equal Average 7 cm H2O (14), an artifact attributed to
the entire lung, including the airways, and Alveolar Pressure the weight of the mediastinal contents
depends on both respiratory airflow It is often assumed that when respiratory that biases PL estimates toward lower
and resistance, and lung volume and airflow is zero, Pao = Palv and therefore values. This bias is the reason some

1454 American Journal of Respiratory and Critical Care Medicine Volume 194 Number 12 | December 15 2016
CRITICAL CARE PERSPECTIVE

experts disregard absolute esophageal
pressure measured in supine patients with
injured lungs (15).
The lung is an elastic network structure,
which is deformed by surface tension,
gravity, and shape constraints imposed by
the thorax. Therefore, pleural pressure
(i.e., pressure on the visceral surface of the
lung) is nonuniformly distributed and may
vary considerably over different regions of
the lung. Because the lung parenchyma
resists deformation, vigorous respiratory
efforts that are associated with large changes
in thoracic shape cause different changes
in Ppl and PL in different regions. This
causes a partial redistribution of gas
between lung regions (pendelluft), which
has been recently observed in experimental
animals and some patients with respiratory
failure (16).
Elastance and Elastic Recoil Pressure
Are Not Interchangeable Estimates of
Lung Parenchymal Stress
In characterizing the lung and chest wall,
it is important to distinguish between
elastance (reciprocal of the slope of P–V
curve) and the recoil pressure (the position
of P–V curve) at a specified volume
(Figure 2). For example, in the clinical
literature it is often implied that recumbent
obese patients have a high chest wall
0.5
0.4
Ppl-elast
Volume above FRC (L)
elastance (low chest wall compliance)
simply because they have greater-than-
expected end-inspiratory plateau airway
pressures during mechanical ventilation.
The high end-inspiratory plateau pressures
of the relaxed respiratory system are the
sum of the elastic recoil pressures of the
lung [Pel(L)] and chest wall [Pel(cw)].
Because in recumbent obese patients the
chest wall is loaded by the increased mass
of the abdomen, abdominal and pleural
pressures are elevated, while elastic recoil
pressure of the lung [Pel(L)] is often
normal. It takes added pressure to displace
the diaphragm/abdomen during inflation,
because the chest wall P–V curve is
shifted to higher pressures, not because
the slope is decreased. As a result, in
recumbent patients with increased
abdominal mass, absolute lung volumes
and Pel(L) at end-inspiration and at end-
expiration are both lower than in normal
individuals, irrespective of chest wall
elastance, which is often normal even in
severely obese subjects (18–20). In this
case, the position of the P–V curve is
shifted to higher pressures, but its slope
may be unchanged and normal (Figure 2).
Importantly, the application of PEEP to
counterbalance the high intrinsic PEEP
(21) may benefit obese patients by
reducing their work of breathing and
Pao
Pes
preventing atelectasis and atelectrauma.
Therefore, it would be inappropriate to
rely simply on elastance measurements,
be it lung, chest wall, or respiratory
system, when individualizing PEEP
management. A further example is that
in patients with ARDS, there is no
correlation between the end-expiratory
esophageal pressure, which is often
very high, and chest wall elastance, which
is often normal ([17] and unpublished
data).
Perhaps the most important
controversy involving PL and Pel(L) is the
emergence of a practice of estimating PL
or Ppl from airway pressure and the
ratio of chest wall (or lung) elastance to
total respiratory elastance. This practice
was introduced by Gattinoni and
colleagues to estimate transpulmonary
pressure in critically ill patients (12) to
account for restriction of the lungs by
the chest wall. Gattinoni and colleagues
write,
The distending force of the lung per unit
area, i.e., the pressure, is that applied
to the visceral pleura. This is the
transpulmonary pressure (PL), which is
the difference between the pressure inside
the alveoli and the pleural pressure (Ppl).
Unfortunately, in normal clinical
practice, it is usual to consider the
plateau or airway pressure (Paw) as the
distending force of the lung. Under static
conditions, Paw closely reflects the intra-
alveolar pressure, which, in part, is spent
to inflate the lung, and, in part, to inflate
the chest wall. (12)

0.3 In the second sentence (our italics) they

define “transpulmonary pressure” as
0.2 Palv 2 Ppl [i.e., what is traditionally Pel(L)].
The following sentences state that airway
0.1 pressure (Paw or Pao) measured statically is
equivalent to alveolar pressure, implying
that without airflow, PL = Pel(L). This
0
ignores the possibility that Pao can differ
from Palv even statically when the small
–0.1 airways of the lung are closed or flooded.
0 10 20 30
Gattinoni and colleagues (12) continue,
Pressure (cmH2O)
Figure 2. Pressure–volume plots connecting static end-expiratory volume (FRC) and end-inspiratory The elastance of the respiratory system
volumes in a patient with acute respiratory distress syndrome. Pao reflects the pressure across the (Ers) is the Paw required to inflate the
entire respiratory system; Pes is the measured pressure across the chest wall, and Ppl-elast is the respiratory system to 1 L above its resting
elastance-derived estimate of the pressure across the chest wall based on the assumption that position under static conditions. Indeed,
Ppl = 0 when Pao = 0 (see text). The slopes of the lines represent the compliances of the respective Paw equals the sum of the pressure used to
structures. Note that the compliance is not sufficient to specify the pressure at any volume. The inflate the lung (PL) and the one used to
measured and elastance-derived estimates of pleural pressure differ by 11 cm H2O (arrow). inflate the chest wall (Ppl):

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 CRITICAL CARE PERSPECTIVE

Paw ¼ PL 1 Ppl; (1)
and
Ers ¼ EL 1 Ew; (2)
where EL and Ew are the elastances of the
lung and chest wall.
Accordingly,
PL ¼ Paw$EL=Ers: (3) (12)
This conclusion is inconsistent with
respiratory mechanics. Elastance is the
reciprocal of the slope of the P–V relationship;
therefore, it cannot by itself specify the elastic
recoil pressure at any volume (Figure 2).
However, Equation 3 states that the value
of PL can be determined without knowing the
value of Pes at any volume merely by
measuring Pao and the changes in pressures
with tidal volume. The equations
erroneously imply that when Pao = 0,
PL = 0, and by extension, when airway
pressure is atmospheric, pleural pressure
must also be atmospheric (22, 23).
Since its introduction, the elastance-
derived estimation of PL and Ppl has been
applied in numerous studies (12, 15, 24–31).
Its appeal seems to be that it avoids having to
make sense of the substantially positive
baseline values of Pes (and negative values of
PL) that are common in the supine position,
especially in critical illness (15). The
elastance-based estimation of Ppl leaves
unexamined the possibility that in a large
part of the lung, both Palv and Ppl are
substantially greater than atmospheric
pressure because the alveoli do not contain
air in equilibrium with air in the central
airway. This might occur with small airway
closure due to severe obesity (18) or alveolar
flooding in ARDS (32). In patients with
ARDS, the elastance-derived values of PL are
substantially different from directly measured
values, leading to different recommendations
for appropriate PEEP settings (22, 26).
In a recent post hoc analysis of several
clinical trials in ARDS, driving pressure,
which was defined as the tidal excursion in
airway pressure measured at points without
airflow, was shown to predict mortality
(33). The rationale for this study was that
driving pressure of the respiratory system is
an easily measured surrogate for cyclic
stress applied to the lung. We suggest
that the transpulmonary driving pressure
[i.e., the tidal excursions in Pel(L) measured
during end-expiratory and end-inspiratory
airway occlusions] would be a better
surrogate to assess the stress applied to
the lung tissue, as it would exclude any
contribution from the chest wall.
In summary, we urge specificity
when using the terms transpulmonary
pressure and elastic recoil pressure to
define the physical state of the lungs, the chest
wall, and the integrated respiratory system.
We have provided several examples that
underscore the potential for erroneous
conclusions when terms such as stress, strain,
and transpulmonary pressure are used in an
ambiguous manner. We contend that our
concern does not simply address a semantic
nuance in a debate among physiologists but
that it is central to the care of patients with
respiratory failure. n
Author disclosures are available with the text
of this article at www.atsjournals.org.

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