J Appl Physiol 117: 979–988, 2014.

First published August 28, 2014; doi:10.1152/japplphysiol.00466.2014.

Pendelluft in the bronchial tree

Elliot E. Greenblatt,1,4 James P. Butler,2,3 Jose G. Venegas,4 and Tilo Winkler4
1
Massachusetts Institute of Technology, Cambridge, Massachusetts; 2Molecular and Integrative Physiological Science
Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts; 3Division of Sleep
Medicine, Departments of Medicine and Neurology, Harvard Medical School and Brigham and Women’s Hospital, Boston,
Massachusetts; 4Massachusetts General Hospital and Harvard Medical School, Department of Anesthesia and Critical Care,
Boston, Massachusetts
Submitted 2 June 2014; accepted in final form 25 August 2014

Greenblatt EE, Butler JP, Venegas JG, Winkler T. Pendelluft in sure in the region with higher resistance compared with the
the bronchial tree. J Appl Physiol 117: 979 –988, 2014. First published other region. If the inspiration is followed by a pause, having
August 28, 2014; doi:10.1152/japplphysiol.00466.2014.—Inhomoge- zero flow at the airway opening, the pressure difference will
neous inflation or deflation of the lungs can cause dynamic pressure cause pendelluft flow from one region to the other until the
differences between regions and lead to interregional airflows known pressures are equilibrated. If the region with the higher resis-
as pendelluft. This work first uses analytical tools to clarify the
theoretical limits of pendelluft at a single bifurcation. It then explores
tance also has a greater compliance (i.e., it is less stiff) than the
the global and regional pendelluft that may occur throughout the other region, more pendelluft flow will be needed to balance
bronchial tree in a realistic example using an in silico model of the pressures throughout the lungs. Experimental evidence and
bronchoconstriction. The theoretical limits of pendelluft volume ex- theoretical aspects of pendelluft attributable to varied resis-
changed at a local bifurcation driven by sinusoidal breathing range tance and compliance were first described in a classic paper by
from 15.5% to 41.4% depending on the relative stiffness of the Otis et al. in 1956 (12), which included an excellent analysis of
subtended regions. When nonsinusoidal flows are considered, pendel- frequency dependence of resistance and compliance at a bifur-
luft can be as high as 200% inlet tidal volume (Vin). At frequencies cation as well as a theoretical upper limit for pendelluft.
greater than 10 Hz, the inertia of the air in the airways becomes Clinically, pendelluft can be observed during mechanical
important, and the maximal local pendelluft is theoretically un- ventilation of patients with unilateral chest or lung injury,
bounded, even with sinusoidal breathing. In a single illustrative where the two lungs can sometimes be seen inflating and
numerical simulation of bronchoconstriction with homogenous com-
deflating out of phase with each other (6, 16). More subtle
pliances, the overall magnitude of global pendelluft volume was ⬍2%
of the tidal volume. Despite the small overall magnitude, pendelluft
pendelluft is sometimes observed as a gradual drop in pressure
volume exchange was concentrated in poorly ventilated regions of the during an end-inspiratory pause, which may be caused by
lung, including local pendelluft at bifurcations of up to 13% Vin. This airflow between the different regions of the lungs. There is
example suggests that pendelluft may be an important phenomena emerging evidence of pendelluft in bronchoconstricted asth-
contributing to regional gas exchange, irreversible mixing, and aero- matics (15), in subjects with chronic obstructive pulmonary
sol deposition patterns inside poorly ventilated regions of the lung. disease (20), and during mechanical ventilation under certain
The analytical results support the concept that pendelluft may be more conditions including spontaneous effort (22).
prominent in diseases with significant heterogeneity in both resistance At breathing frequencies much higher than those at rest,
and compliance. differences in how air mass within parallel regions of the lungs
ventilation distribution; ventilation mechanics; gas exchange; asthma; respond to rapid pressure changes (characterized by their
computational modeling inertance, L) can also lead to pendelluft. This kind of pendelluft
has been postulated to aid gas exchange during high-frequency
ventilation (7, 8, 18). Although this effect was not explicitly
INSPIRATORY AND EXPIRATORY AIRFLOWS in healthy lungs are included in the analytical description of pendelluft by Otis et
relatively uniform throughout the bronchial tree. However, in al. (12), their mathematical model would allow adding inertive
pulmonary diseases or under abnormal conditions, this uniform terms. Other investigators included inertance in more compli-
pattern can be disturbed; inhomogeneous inflation or deflation cated analytical descriptions (7, 18), and in a sophisticated
of the lungs can cause dynamic pressure differences between model of airflows in an airway tree (1).
different regions, which in turn lead to interregional airflows. Since the 1956 paper of Otis et al. (12), work on pendelluft
This effect is referred to as pendelluft (“swinging air”) because at a single bifurcation has continued analytically, numerically,
gas is passed back and forth between the different regions of and experimentally. For example, pendelluft can affect gas
the lungs. transport by displacing air in the anatomical dead space within
Pendelluft occurs when regions of the lung have different the volume of the airways (14). It has also been shown that
dynamics of regional inflation and deflation. For example, in a pendelluft can be observed even in symmetrical bifurcations if
lung with two regions of equal compliance, inspiratory airflow instabilities (like those that emerge from nonlinearities in
is diverted away from a region with higher resistance (R), and airway resistance) are considered (9). Additionally, pendelluft
incomplete equilibration leads to lower end-inspiratory pres- may be an important physiological phenomenon for irrevers-
ible particle and gas mixing in the bronchial tree (3, 17).
Pendelluft in a multibranching bronchial tree is more com-
Address for reprint requests and other correspondence: Tilo Winkler, Mas-
sachusetts General Hospital, Dept. of Anesthesia, Critical Care and Pain
plicated than that at a single bifurcation, as it may occur at
Medicine, 55 Fruit St., Boston, MA 02114 (e-mail: twinkler@mgh. several bifurcations. In particular, pendelluft that occurs at
harvard.edu). multiple airway bifurcations between the central airway and
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980 Pendelluft in the Bronchial Tree • Greenblatt EE et al.

the terminal units results in some form of stacking or propa- VB,j The bulk volume that directly passes through
gation of the effects of pendelluft across airway generations. the jth airway of a bifurcation without expe-
Pendelluft throughout the tree increases the overall tidal ex- riencing pendelluft.
pansion of the acini, albeit with an uncertain combination of ␤ The set of bifurcations in an airway tree or
fresh gas and gas that has already been resident elsewhere in subtree.
the lungs. We reasoned that this additional pendelluft volume T The set of terminal airways in an airway tree
could be explored using a numerical model of the airway tree or subtree.
during bronchoconstriction (19). This model would thus permit
Rj, Cj, Lj, Zj The (frequency-dependent) resistance, compli-
quantitative exploration of the magnitude and effect of pendel-
ance, inertance, and impedance of the jth
luft within a bronchial tree in an illustrative example.
airway of a bifurcation and its subtended
This study has two distinct aims that are mutually support-
region.
ive. The first is to clarify the definition, causes, and magnitude
of pendelluft. To this end, we use analytical tools to define a ␶j Model-dependent nondimensional time con-
generalized quantitative definition of pendelluft, identify its stant of the jth airway of a bifurcation and
limits, and evaluate its magnitude using analytical methods. its subtended region.
We then extend this definition to include pendelluft throughout ␬ Nondimensional compliance or inertance ra-
a bronchial tree. The second aim of the paper is to provide an tio of the daughter airways and their sub-
example of local and regional effects of pendelluft on airflow tended regions.
and ventilation in a realistic context using an in silico model of
METHODS
bronchoconstriction. We then use the numerical simulation to
explore the frequency dependence of global pendelluft volume Pendelluft flow, volume, and ventilation definition. Pendelluft flow,
and the conditions for which the inertance of the airways volume, and ventilation definition at a bifurcation are based on an
becomes important. earlier definition by Otis et al. (12). Despite the complicated dynamics
of airflows during pendelluft, Otis et al. (12) found an analytical
Glossary description of the pendelluft volume at a bifurcation over a breathing
period by using a circuit model of the lungs including resistances and
V̇j, Vj Flow and tidal volumes of the jth daughter compliances (Fig. 1). Otis defined the relative pendelluft volume at a
airway in a bifurcation (j ⫽ 1,2 for all given bifurcation as the excess in the sum of the tidal volumes of two
subscripts j). daughter airways relative to the tidal volume delivered through the
Vk Tidal volume passing through the kth airway. parent airway. This pendelluft volume exchanged between regions
V̇in, Vin Inlet flow and (tidal) volume to a bifurcation; increases the sum of the daughter tidal volumes without affecting the
parent tidal volumes. This ratio quantifies pendelluft at a bifurcation.
depending on the context it may be related We seek to extend this definition to include pendelluft flow over
to the whole airway tree or a subtree. time, understand its limitations, and to ultimately use it to characterize
V̇P,j Pendelluft flow in the jth daughter airway of the intergenerational aggregation of pendelluft throughout the global
a bifurcation. bronchial tree. However, before quantifying this aggregation, it is
V̇PB,k, VPB,k Pendelluft flows and volumes at the kth bi- helpful to first identify the features that characterize pendelluft flow
furcation. In the context of a local bifurca- originating at an individual bifurcation. 1) Pendelluft flow occurs if
tion, the subscript k is omitted. and only if the flows in the daughter branches have opposite sign (Fig.
VP Pendelluft volume in an airway tree (global) 1B). 2) Pendelluft flow passes from one daughter to the next and is
or subtree (regional). therefore equal in magnitude in both daughters. 3) This magnitude is
equal to the smaller flow of the two daughters, which flows in the
VAP,j The aggregate pendelluft volume passing opposite direction as the parent and is entirely pendelluft. If there is no
through the jth daughter airway in a bifur- flow through the parent, then both daughter flows are equal in
cation. magnitude, and both are entirely pendelluft. 4) The direction of the
VAP,in The aggregate pendelluft volume passing pendelluft flow in each of the daughter airways is the same as the
through the parent airway of a bifurcation. direction of the total flow in the airway. These observations lead to

A B Vin
C D
Vin

V1 V2
VP1 VP2
R1 R2 Z1 Z2

C1 C2

Fig. 1. Schematics of single bifurcation models to describe pendelluft. A: definition of local parent flow and daughter flows. B: example of a pendelluft flow
condition at the beginning of inspiration, note the pendelluft flow going from one daughter into the other, combining with parent flow here in the left branch.
Flows in the 2 daughters have opposite signs. C: resistance-compliance model of a bifurcation. D: general complex impedance model of a bifurcation. For
definitions of abbreviations, please refer to the Glossary.

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 Pendelluft in the Bronchial Tree • Greenblatt EE et al. 981
the following definition of pendelluft flow emerging at an individual volume gives the result shown in Eq. 7. Note the terminal airways
bifurcation: used in Eq. 7 are those at the end of any defined portion of the airway

再
tree with a single inlet and need not be those airways that directly feed
sgn (V̇ j) min(|V̇1|,|V̇2| ); sgn (V̇1) ⫽ sgn (V̇2) the compliances. Therefore, the regional relative pendelluft definition
V̇P,j ⫽ (1) in Eq. 7 reduces to the bifurcation definition in Eq. 6 because a single
0; sgn (V̇1) ⫽ sgn (V̇2)
bifurcation may be considered as a subtree with two terminal airways.
The subscript j indicates either of the two daughter airways in a While the regional pendelluft volume is a quantification including
bifurcation (j ⫽ 1,2 for all subscripts in this paper). V̇1, V̇2 are the all local pendelluft volumes in a region, it does not show how the local
overall flows, and V̇P,1, V̇P,2 are the pendelluft flows. The total pendelluft generated at bifurcations propagates through the airway
bifurcation pendelluft flow V̇PB is the sum of the magnitude of the tree. To quantify how pendelluft is distributed throughout the bron-
daughter pendelluft flows and is signed (arbitrarily) with V̇1: chial tree, we define the aggregate pendelluft volume VAP,j as the
volume through the jth daughter airway of a given bifurcation, which
共 兲共 兲
V̇PB ⫽ sgn V̇1 | V̇p,1|⫹|V̇p,2| ⫽ V̇p,1 ⫺ V̇p,2 ⫽ 2V̇p,1 ⫽ ⫺2V̇p,2 has accumulated from pendelluft in that or more proximal bifurca-
(2) tions. This volume combines with bulk flow VB,j that has never
experienced pendelluft in the total flow through the airway Vj:
An equivalent definition to the one presented in Eqs. 1 and 2, but
without the piecewise character of Eq. 1 and the minimum function is: V j ⫽ VAP,j ⫹ VB,j (8)
共 兲共
V̇PB ⫽ sgn V̇1 |V̇1| ⫹ |V̇2|⫺|V̇in| 兲 (3) Recall that the subscript j indicates either of the two daughter airways
in a bifurcation (j ⫽ 1,2 for all subscripts in this study).
where V̇in is the parent flow, which by conservation of mass satisfies The aggregate pendelluft itself is a combination of the local
V̇in ⫽ V̇1 ⫹ V̇2. Integration of the absolute amount of pendelluft flow pendelluft VP,j and a fraction of the aggregate pendelluft of the parent
over the breathing period T yields the local pendelluft volume at a
airway VAP,in. Because the daughter airways cannot distinguish bulk
bifurcation:
volume from aggregate pendelluft volume, this fraction is the same as

ⱍV̇ ⱍdt ⫽ 21 共兰 ⱍV̇ (t)ⱍdt ⫹ 兰 ⱍV̇ (t)ⱍdt

1 the fraction of ventilation that goes to that airway.
兰
T T T
VPB ⫽ PB 1 2
2 0 0 0
Vj
⫺ 兰 ⱍ V̇ (t)ⱍ dt兲 ⫽ V ⫹ V ⫺ V VAP,j ⫽ VAP,in ⫹ VP,j
T (9)
0 in 1 2 in (4) V1 ⫹ V2
where the volumes VPB, V1, V2, Vin are defined as: Note that the earlier definition of local and regional pendelluft
considered pendelluft that emerges in a bifurcation or subtree,
Vx ⫽
1
2
兰0
T
ⱍV̇ ⱍdt
x (5) without considering pendelluft from more proximal bifurcations in
the bronchial tree that can arrive through the parent airway. In
contrast, the aggregate pendelluft deals with this issue directly and
for any subscript x.
considers the total pendelluft driven volume that passes through a
Note that Vin at the carina is the conventional tidal volume VT of
given airway.
the whole lung, and the factor of ½ converts the integral of the
This concludes our definitions of pendelluft flow and the volume of
absolute airflow over the breathing cycle to VT; this is equivalent to
an integral over inspiration or expiration only, provided there are no local, regional, and aggregate pendelluft. We next use analytical
breath-to-breath changes in end-expiratory lung volume, which would methods to evaluate the magnitude of pendelluft volume at a single
require an average over multiple breathing cycles. The relative pen- bifurcation.
delluft volume at a bifurcation is defined as the pendelluft volume Analytical characterization of pendelluft. Analytical characteriza-
normalized by the local tidal volume delivered through the parent tion of pendelluft in a model with linear elements can be illustrated
airway, which matches the description of Otis et al. (12): using the electrical analogs of resistance and compliance (Fig. 1C) or
more generally with impedance elements (Fig. 1D). The components
VPB V1 ⫹ V2 ⫺ Vin represent two daughter branches and subtended regions at any bifur-
⫽ (6) cation in the tree. The amplitude of a sinusoidal flow through an
Vin Vin
impedance is given by the amplitude of the driving pressure divided
Pendelluft can occur at many bifurcations throughout a given by the magnitude of the impedance.
region of the bronchial tree, and its aggregation over the generations When such a system is driven with a single sinusoidal frequency
of the airway tree determines the overall increase in ventilation of the the pendelluft volume over a breathing period can be expressed
region. The regional pendelluft volume (denoted VP) is normalized to directly in terms of these impedances:
the tidal volume feeding the region (denoted Vin) to yield the nor-
malized regional pendelluft volume VP/Vin. For the set of bifurcations VPB
⫽
ⱍZ ⱍ ⫹ ⱍZ ⱍ ⫺ 1
1 2
(10)
␤ within the tree or subtree, and the set of terminal airways of the tree
or subtree ⌻:
Vin ⱍZ ⫹ Z ⱍ
1 2

where Z1 and Z2 are the complex impedances of the daughters (Fig. 1D).
VP 兺 VPB,k k僆T
k僆␤
兺 Vk ⫺Vin This equation is equivalent to the one found originally by Otis et al.
⫽ ⫽ (7) (12). It is limited to a single bifurcation driven with a single frequency
Vin Vin Vin
and is evaluated over a complete period. Note that the impedances are
Note that when the set includes the entire tree, VP/Vin is the global complex, and the absolute value operator is that defined for complex
pendelluft. Also, note that the regional pendelluft is evident from the numbers. Given that the initial definition of pendelluft flow (Eq. 1)
sum of tidal volumes of the terminal airways compared with the inlet includes a piecewise definition, a minimum function, and absolute
tidal volume. As proof of this, consider a tree with two generations value operators, it is remarkable that the pendelluft volume of the
and three bifurcations. Summing the pendelluft of these bifurcations breathing cycle can be expressed in this simpler form. This form
(each given by Eq. 4) results in an algebraic combination of the airway permits calculations in networks of impedances such as the airway
tidal volumes that simplifies to the sum of tidal volumes of terminal tree. However, note that Eq. 10 remains nonanalytical because of the
units minus the inlet tidal volume. Normalizing by the inlet tidal absolute value operators; meaning that it is not additive, and harmonic

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982 Pendelluft in the Bronchial Tree • Greenblatt EE et al.

decomposition cannot be used to evaluate nonsinusoidal driving 0.5

pressures.
Equation 10 can be derived directly from Eq. 4, but some obser-
vations simplify this considerably. The local pendelluft volumes can 0.4

Relative Airway Radius

be evaluated using only the amplitudes of the input flow and the flow
through the daughters without directly considering the phase differ-
ence between the flows. This is because integrating over a complete 0.3
cycle to identify the tidal volume of each of the daughters’ subtended
regions is independent of the phase difference (even though the phase
difference between the daughters is important, indeed key to the 0.2
existence of pendelluft). These subtended volumes are determined by
the magnitude of the daughter impedances, and, after normalizing to
the input flow, Eq. 10 is reached. See also the geometric construction 0.1
in Fig. 4.
The pendelluft equation (Eq. 10), although only valid at a single
sinusoidal frequency, permits any linear element to be included in the 0
0 4 8 12
circuit. This can include conditions at very high breathing frequencies,
where the effect of inertance on airflows and pressures becomes Airway Generation
important. At normal breathing frequencies, however, the airway tree Fig. 2. Example of self-organized bronchoconstriction used to explore pendel-
can be modeled as a combination of resistances and compliances. Otis luft in a realistic context. Note that the constricted airways group together,
et al. (12) pointed out that any bifurcation within such a tree might be leading to regionally clustered ventilation defects, and that there are substantial
modeled using a single frequency-dependent effective resistance and differences in constriction among daughter airways. The airways are shown as
compliance for each daughter branch. We therefore expressed Eq. 10 points and the connectivity among the airways as lines; darker areas illustrate
explicitly for any RC circuit in Eq. 11 and in doing so describe higher local density.
pendelluft volume at any bifurcation of the airway tree during normal
breathing. The resulting equations were used to find the analytical
limits of relative pendelluft for a range of circuits and conditions (Eqs. and global pendelluft volumes. An example of pendelluft flow at a
12–14). bifurcation is presented in Fig. 6 for both the sinusoid and mechanical
In the next section, we describe the methodology of the second aim ventilation breathing simulations. In addition, the global relative
in this paper: to use an in silico model of bronchoconstriction to pendelluft volume of the bronchial tree, the maximum and average
illustrate both local and global effects of pendelluft on airflow and local relative pendelluft volume at a bifurcation, the average fraction
ventilation in a realistic context and nonsinusoidal input. of the breathing cycle a bifurcation exhibited pendelluft flow, and the
Numerical simulation of pendelluft. Numerical simulation of pen- fraction of the breathing cycle that pendelluft occurred somewhere in
delluft was used to illustrate the pendelluft that can occur during the bronchial tree were tabulated. Finally, the frequency dependence
heterogeneous bronchoconstriction observed in asthma. An integra- of global pendelluft volume in the numerical example was explored
tive model of bronchoconstriction including an airway tree with 12 using this same steady-state solution for the airway diameters.
generations was used to simulate a pattern of the self-organized
airway constriction that emerges during an asthma attack, as previ- RESULTS
ously described in detail (19). Briefly, our computational model
involves solving the distribution of airflow, pressure, and volume Theoretical limits for pendelluft. Theoretical limits for pen-
within a bronchial tree with 12 generations of branching using Euler’s delluft with sinusoidal airflow and at a single bifurcation were
method for numerical integration and time steps of 10 ms. The derived from the analytical evaluation of Eq. 10. Despite the
dynamics of airflow distribution in the model are determined by five parameters in the physical circuit (two resistances, two
the input at the central airway opening and recursive equations for the compliances, and the frequency) shown in Fig. 1C, the pen-
network of resistances connected to the compliances of the terminal delluft depends only on three independent parameters ␶*1, ␶*2,
units. Airway radii were updated breath by breath according to the and ␬:
relative airway smooth muscle tone (Tr) and the peak transmural
pressure of the airway during the breathing cycle, taking into account VPB 共␶*2
1 ⫹ 1兲
1⁄2
⫹ 共␶*2
1 ⫹ 1兲 ␬
1⁄2
⫽ ⫺1 (11)
the transmural pressure and parenchymal forces. The simulation using
Tr ⫽ 90%, a mechanical ventilation profile with a volume-controlled
Vin 共共␶*1 ⫹ ␶*2␬兲2 ⫹ (1 ⫹ ␬)2兲1⁄2
mode, constant inspiratory flow, a tidal volume of 650 ml, positive where ␶*1 and ␶*2 are the time constants, nondimensionalized
end-expiratory pressure of 5 cmH2O, and 12 breaths per minute for a
period of 600 breaths resulted in the emergence a typical steady-state by frequency, ␶*1 ⫽ ␻␶1, ␶1 ⫽ R1C1; ␶*2 ⫽ ␻␶2, ␶2 ⫽ R2C2; and
pattern of heterogeneous airway constriction (Fig. 2) (19). This ␬ ⫽ C1/C2. Importantly, note that ␶*1 and ␶*2 can also be read as
pattern of bronchoconstriction within the airway tree is consistent the frequency, nondimensionalized by the respective time con-
with the emergence of ventilation defects (regions of gas trapping or stants. This function is explored in Fig. 3 for ␬ ⫽ 1. As ␬
very poor ventilation) in asthma (21). The fraction of closed or increases from unity, the maximum on the horizontal axis
hypoventilated terminal units receiving less than 15% of the average increases and moves to the right.
ventilation was 16.7%, indicating substantial ventilation defects. We The impedances in Eq. 10 can be represented with vectors in
used that pattern of heterogeneous airway constriction including the the complex plane. The specific elements in the circuit deter-
8,191 airways of the model and simulated the airflows in all of the
airways of the model over a complete breathing cycle. These airflows
mine the quadrant(s) of this plane from which the daughter
were used to calculate the pendelluft flow and volumes using Eqs. 3 impedances can be chosen. A circuit without inertance (i.e., an
and 4, respectively. RC circuit) can only have impedances in the lower right
To explore the effect of breathing waveform on pendelluft, we used quadrant, whereas a circuit without compliance effects (i.e., an
the pattern of airway constriction and applied a sinusoidal breathing RL circuit) can only have impedances in the upper right
pattern. The airflows throughout the tree were used to calculate local quadrant. When all effects are considered (i.e., an RLC circuit)

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 Pendelluft in the Bronchial Tree • Greenblatt EE et al. 983

V
• •
/ V (%) vs. * and * for =1 Maximum Bifurcation Relative Pendelluft Volume Vs.κ
PB in 1 2
50
7
Maxima (15.5%)
Minima (0%) 40
6

30

/Vin
5

•
PB
max(V
•
20
4
2
*

10
3

0
2 10
0
10
1 2
10
3
10
1
κ

1 Fig. 5. The maximum possible relative pendelluft varies with the ratio of the
effective compliances of the 2 daughter pathways. A bifurcation with matched
7 stiffness (␬ ⫽ 1) gives the lower limit, whereas the upper limit is reached when
0 the path with lower resistance (always subscript 1) has a higher stiffness.
0 1 2 3 4 5 6 7
*
1 The relationship between the maximum relative pendelluft
Fig. 3. Isocontours marking 3% increments in local relative pendelluft volume volume and ␬ is plotted in Fig. 5. The maximum with respect
as a function of the nondimensional time constants, for ␬ ⫽ 1. The shape of the to 共␶1*, ␶2*兲 for any fixed ␬ occurs when one daughter has
isocontours shows the steep transition from the maximum at the { (15.5%) to
the minimum (0) on the line of symmetry. vanishingly low compliance or resistance 共␶*2 ¡ 0). These
maxima over 共␶1*, ␶2*兲 increase with ␬ and have an asymptotic
limit as ␬ ¡ ⬁, given by:

冏 冉 冊
the daughter impedances can be anywhere in the right half of
VPB
the complex plane. Equation 10 is maximized when the sum max ␶*1,␶*2,␬
⫽ 兹2 ⫺ 1 ⫽ 0.4142 ⫽ 41.4% (13)
of the impedance magnitudes are large and when the magni- Vin
tude of the sum of the impedances are small (i.e., the vectors
This overall maximum matches Otis et al. (12) and is
tend to cancel each other out). Geometrical proofs that find the
approached as one daughter resistance decreases and the
combination of impedance vectors that maximize pendelluft
other daughter compliance increases, such that the magni-
(similar to what is illustrated in Fig. 4) result in the following
tudes of the impedances in the two branches are equal (as in
limits for relative pendelluft volume at a bifurcation.
First, for an RC circuit with a fixed ratio of terminal Fig. 4, high pendelluft). In this case ␶*1 ⫽ 1 (R1 ⫽ 1/C2␻),
compliances ␬ ⫽ C1/C2, where C1 ⱖ C2, the maximum ␶*2 ¡ 0, and ␬ ¡ ⬁. If the compliances are equal (␬ ⫽ 1),
pendelluft is achieved when ␶*1 ⫽[(␬ ⫹ 1)(␬ ⫹ 3)]1/2 and ␶*2 ⫽ the maximum over 共␶1*, ␶2*兲 is:
0. At this point we have:

max 冏 冉 冊 冑
␶*1,␶*2
VPB
⫽ 2
(␬ ⫹ 1)
⫺1 (12)
max 冉 冊冏
VPB
Vin ␶*1,␶*2,␬⫽1
⫽
2兹3
3
⫺ 1 ⫽ 0.1548 ⫽ 15.5%

Vin (␬ ⫹ 2) (14)
In this case ␶*2 ¡ 0 and ␶*1 ⫽ 2公2. This 15.5% maximum is
different than the 5.5% maximum presented in Otis et al. (12),
but, as the fundamental formulas in that paper are correct, this
Im Im is most likely a typographical error in Otis et al. (12), rather
Re
Z1 Re than an error of substance.
Second, RL circuits with resistance and inertance (without
capacitance) are not typically relevant for the bronchial tree but
Z1 can give insight into the conditions that lead to pendelluft in
Z2 circuits during high-frequency ventilation. These circuits have
the same limits as RC circuits presented in the equations and
Z2 figures above, where the dimensionless variables are redefined
Z1 + Z 2 Z1 + Z 2 as ␶*1 ⫽ R1/L1␻, ␶*2 ⫽ R2/L2␻, and ␬ ⫽ L2/L1. Maxima are
found when the daughter with high inertance has low resis-
Fig. 4. A geometrical description of the combinations of daughter impedances tance.
(Z1 and Z2) that lead to low and high pendelluft. For RC models of the lung,
these vectors are confined to the lower right quadrant of the complex plane.
Third, RLC circuits with resistances, inductances, and ca-
Higher pendelluft happens when the impedances diverge and the sum of the pacitances can have unbounded pendelluft. In these cases,
daughter magnitudes is considerably larger than the magnitude of their sum. pendelluft may oscillate back and forth between the daughters

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984 Pendelluft in the Bronchial Tree • Greenblatt EE et al.

100

Fig. 6. Example of flows at the bifurcation

with the highest pendelluft volume (both are
at generation 10). Inset: flow profile into the
airway tree. The flows within the daughters 0
sum to the parent flow. Pendelluft flow be-
gins and ends when one of the flows crosses Vin

Flow
0 and changes sign. V1
V2
VP1
−100
0 1 2 3 4 5 0 1 2 3 4 5
Time [s] Time [s]

if the resistances are sufficiently small that the system is profile applied to the airway tree during mechanical ventilation
underdamped. The characteristic frequency as R1 ⫹ R2 ¡ 0 is is changed to the input ventilation profile of the bifurcation by
given by ␻2 ⫽ [1/(L1 ⫹ L2)] * [(C1 ⫹ C2)/(C1C2)] (series the frequency-dependent dynamics of the airway tree. Table 1
inductance, series capacitance). shows metrics of pendelluft for the two simulations.
The limits presented above apply, like the results in the Otis Figure 7 shows the distribution of ventilation, relative pen-
paper (12), only to pressure or flow-driven inputs at a single delluft, and aggregate pendelluft volumes throughout the bron-
frequency. For other waveforms, the pendelluft volume may chial tree for the sinusoidal and ventilator waveforms. The
exceed these values. For example, consider a circuit compris- distribution at each generation of the tree is visualized with a
ing vanishing resistance in one branch and unbounded com- number of boxes matching the number of airways at that
pliance in the other (the case above, for which relative pendel- generation. The color profile along a vertical line from the top
luft may reach 41% if driven at the appropriate single fre- to the bottom represents theoretical streamtubes that go from
quency). Driving this with a step change in pressure would the most central airway generation of the model to the terminal
instantaneously fill the compliance with the tidal volume fol- airways like a bundle of virtual paths. The Fig. 7, top, shows
lowed by the discharge of the compliance through the resistor. the ventilation pattern during steady-state bronchoconstriction
During the instantaneous filling, no volume is passed through for each waveform as a percent of the ventilation the airway
the resistive branch. Subsequently, if an exponential pressure would experience in a perfectly symmetric tree (% Uniform
drop matching the pressure inside the compliance is applied to Vin). Using this normalization allows us to see the smaller
the parent, the capacitance will discharge entirely through the volumes in the higher generations. The dark regions indicate
parallel resistance. Reversing the input pressure would reverse poorly ventilated regions that are similar for the two ventilation
the process. Here the normalized tidal volumes for the com- profiles. Figure 7, middle, shows the magnitude of relative
pliance daughter, resistance daughter, and the whole circuit are pendelluft volume at each bifurcation. Observe that regions of
2, 1, and 1, respectively. On the basis of Eq. 6, this yields a high relative pendelluft volume (yellow and red lines) are
relative pendelluft volume of 200%. In contrast, we will shortly almost always within the ventilation defects in Fig. 7, top. This
show that other nonsinusoidal flows such as the one used in the is where substantial differences in constriction between neigh-
mechanical ventilation simulation can lead to lower pendelluft boring pathways exist (Fig. 2). Also, there was pendelluft in
than a sinusoidal flow at the same frequency. more central airways for sinusoidal waveform (dark red areas)
Illustrative example of pendelluft in the bronchial tree. An but not for mechanical ventilation. Figure 7, bottom, shows the
illustrative example of pendelluft in the bronchial tree was distribution and buildup of aggregate pendelluft volume (%
explored using numerical simulations. Both sinusoidal and Uniform Vin). These panels illustrate how pendelluft generated
mechanical ventilation profiles were applied to a simulation of at a bifurcation is redirected to better ventilated regions within
self-organized bronchoconstriction in an airway tree. Pendel- the ventilation defect.
luft flow was observed in both the sinusoidal and mechanical The frequency dependence of global pendelluft volume in
profiles at bifurcations within poorly ventilated regions of the the bronchial tree as a function of the frequency of the driving
lung (Fig. 6). Note that the originally constant flow inhalation signal is shown in Fig. 8. The maximum total global pendelluft

Table 1. Pendelluft simulation results for the two simulations

Sinusoidal Ventilation Mechanical Ventilation

Global relative pendelluft volume, % VT 1.57 0.13

Maximum local relative pendelluft volume, % Vin 12.67 13.45
Average local relative pendelluft volume, % Vin 0.25 0.10
Average fraction of breathing cycle in local pendelluft, % Total 3.12 1.80
Fraction of breathing cycle with any pendelluft, % Total 78.8 100
See Glossary for definition of terms.

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 Pendelluft in the Bronchial Tree • Greenblatt EE et al. 985

Sinusoidal Ventilation Mechanical Ventilation

Ventilation (%)

2
4 100
Generation

6
8
50
10
12
0
• •
Local Relative Pendelluft V /V (%)
PB in
>5
2
4
4
Generation

3
6
8 2

10 1
12 0
•
Aggregate Pendelluft VAP (%)
>3
2
4
Generation

2
6
8
1
10
12
0
1000 2000 3000 4000 1000 2000 3000 4000
Virtual Path Virtual Path
Fig. 7. Top: bronchoconstricted ventilation pattern with darkly colored regions of reduced ventilation as a percent Uniform Vin. Middle: high relative pendelluft
emerging within ventilation defects is shown with bright colors. Bottom: regional aggregate pendelluft volume illustrating the diversion to better ventilated
regions as a percent Uniform Vin.

volume for a single frequency sinusoid was 1.75% of the input that pendelluft may be higher in diseases causing heteroge-
volume (VT) at 0.02 Hz. Gas inertia becomes important above neous changes in compliance such as emphysema. When the
about 10 Hz and creates the second peak with a maximum of effects of inertance are also considered, it is theoretically
1% at 400 Hz. possible to have any amount of pendelluft. We also introduced
a nonsinusoidal waveform that could result in pendelluft vol-
DISCUSSION

Key findings. The key findings in this work can be separated

into analytical and numerical results. In the first portion of this Global Relative Pendelluft Volume s. Frequency
2
work, we clarified the definition of pendelluft and generalized No Inert.
this definition to include nonsinusoidal flows as well as to a Inertance
multigenerational tree. This allowed us to explore local pen- 1.5
delluft at bifurcations, aggregate pendelluft volume that builds
up over the bronchial tree, and the global pendelluft volume
1
VP/Vin

over the entire tree. We then used analytical tools to identify

•

the limits of pendelluft at a bifurcation for a range of airway

•

models. For a conventional resistance and compliance model 0.5

of the airway tree driven by a single frequency sinusoid, we
found that the limits of possible pendelluft depend on the ratio 0
of compliances of the daughter pathways. When these compli- −5 0 5
ances were equal, the maximum possible pendelluft volume 10 10 10
Frequency [Hz]
was 15.5% of the tidal volume of the bifurcation. [As noted in
RESULTS, this is different from the 5.5% presented by Otis et al. Fig. 8. Frequency dependence of global pendelluft volume in a bronchial tree
(12), which is most likely a typographical error]. When these for the example of heterogeneous bronchoconstriction showing the effect of
sinusoidal input at different frequencies. Both models of the tree that exclude
compliances are dissimilar, the maximum pendelluft for a (No Inert.) or include (Inertance) the effects of the air mass are shown. The
sinusoidal breathing pattern rises to 41%. The difference in the physiologically relevant ranges for normal and high-frequency ventilation are
upper limit of pendelluft between the two conditions suggests indicated with vertical gray lines.

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986 Pendelluft in the Bronchial Tree • Greenblatt EE et al.

umes that were twice the tidal volume of the bifurcation, even out the generations of the tree. However, comparison with
without inertive effects. experimental data focusing on the larger airways and proximal
In the second portion of this work, an illustrative example of bifurcations is possible. Shinozuka et al. (16) measured pen-
pendelluft in the bronchial tree was explored using numerical delluft at the carina in an animal model of flail chest. They
simulations. Both sinusoid and typical mechanical ventilation measured the magnitude of pendelluft volume transferred be-
profiles were applied to an instance of self-organized broncho- tween the two lungs to be ⬍2% of the tidal volume. In flail
constriction in an airway tree. The main quantitative findings chest, we expect the collapsed lung to be both stiffer (as the
were as follows: 1) a small amount of pendelluft occurs at chest wall is no longer supporting the lung) and have higher
bifurcations in a realistic model of bronchoconstriction; 2) resistance (attributable to reduced size of the lung). Pendelluft
local pendelluft can be as high as 13% relative to tidal volume is highest when the stiffer lung has lower resistance, and the
flowing through the parent airway and is most commonly findings of a small local pendelluft volume at the carina in flail
found in poorly ventilated regions of the lung attributable to the chest are consistent with the results presented here.
increased heterogeneity between parallel pathways (Fig. 2) that In another experimental study of pendelluft in dogs with flail
occurs within ventilation defects during bronchoconstriction chest, Harada et. al. (6) found pendelluft volumes exchanged
(21); and 3) pendelluft volume created at any given bifurcation by one of the daughters to be as high as 12.5% of the total
level is distributed to the better ventilated distal regions. volume passing through that branch. This is similar in magni-
Lastly, we characterized the frequency dependence of pen- tude to the maximum relative pendelluft observed in the
delluft in the example and found two separate regions where simulations at low frequency (12.6% and 13.5%). It should be
global pendelluft emerged. The first region happens at lower noted that Harada et al. (6) defined pendelluft volume as the
frequencies and is driven by heterogeneous resistance and total, rather than excess, volume passing through the daughter
compliance. The maximum for this type of pendelluft was airways when the flows between two connected segments of
⬍2% of the tidal volume and occurs at near normal breathing the lung are in opposing direction. This is potentially con-
frequencies. Above 10 Hz, a second mode of pendelluft founding, insofar as anything beyond twice the minimum of
emerges for models that include inertance. The maximum for the absolute values of flow in the daughter branches is passed
this kind of pendelluft was 1% of the tidal volume and emerged to or from the parent airway (14).
at frequencies much larger than those used for high-frequency In a mechanical model of the respiratory system, High et al.
ventilation. (3) found that the largest pendelluft was 275% of the tidal
Sinusoidal input resulted in greater pendelluft than mechan-
volume; when the model was driven with a high frequency,
ical ventilation (Fig. 7, middle). The particular frequency
resistances were low, inertances were high, and the compli-
chosen for the simulations (12 breaths/min) may have also
ances were very different. The analytical results for RLC
contributed to higher pendelluft with the sinusoidal waveform
circuit limits presented here match the “cross-over frequency”
because the frequency dependence of global pendelluft volume
at which the highest pendelluft was observed.
(Fig. 8) showed a maximum near 12 breaths/min. Pendelluft
occurred somewhere in the tree during 78.8% (sinusoidal Clear asynchronies in parallel filling were apparent when an
input) or 100% (mechanical ventilation) of the breathing cycle excised dog lung was driven at high frequencies by Lehr et al.
despite its small overall magnitude. (the “Disco Lung”) (10). One interpretation of these results
Contribution of pendelluft to overall gas transport. The rests on the idea of wave propagation, where the gas inertance
contribution of pendelluft to overall gas transport depends on is coupled to local compliance, resulting in a type of pendelluft
its magnitude and the composition of the added pendelluft closer to underdamped high-frequency RLC circuits. These
volume. In the bronchoconstriction example, the magnitude of phenomena nevertheless conform to our general description
the global pendelluft volume was ⬍2% relative to the tidal within the context of inertance-dominated branches, with the
volume that passed through the central airways. To determine resulting spatial patterns reflecting the structure of the tree at
the gas composition of pendelluft flow throughout the airway the segmental or subsegmental bronchial level. Amini and
tree would require modeling the gas transport through the Kaczka (1) included impedances, gas compression, and airway
actual volume of the airways for dynamic flow conditions. For wall distention in a computational model of the bronchial tree
example, the gas composition of pendelluft flow at one point of and found frequency-dependent asynchrony among acinar
the airway tree could be fresh gas that would have otherwise flows, indicating that pendelluft was present.
ended up in the anatomical deadspace, or it could be gas The pendelluft explored in this study does not consider
coming from neighboring alveolar units. The small magnitude pendelluft that may emerge as the consequence of an unevenly
of the pendelluft volume suggests that, even if it were fresh distributed plural pressure. There is recent evidence supporting
gas, it is unlikely to be an important phenomenon for overall that this latter form of pendelluft may emerge during mechan-
gas exchange. On the other hand, pendelluft that occurs at ical ventilation in the presence of spontaneous effort (22).
bifurcations within ventilation defects (Fig. 7) may be impor- Similarly, the beating heart can create local pressure differ-
tant for gas exchange if it could, for example, increase oxygen ences that result in pendelluft (17). In addition, nonlinear
delivery in hypoventilated terminal units. phenomenon, such as recruitment and derecruitment of alveoli
Comparisons with experimental studies. Comparisons with and airways, can also lead to pressure differences throughout
experimental studies are limited because it is challenging to the lung that may lead to pendelluft. For example, the sudden
experimentally approximate the flow patterns throughout the opening of an alveolus will most likely demand air from both
bronchial tree; our example of bronchoconstriction in asthma parallel pathways (i.e., pendelluft) as well as the serial path
clearly showed the complexity of local pendelluft at the distal from the mouth. Although the balance of these volumes might
bifurcations of the bronchial tree and its propagation through- be determined from the mechanical properties of the airway

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 Pendelluft in the Bronchial Tree • Greenblatt EE et al. 987
network, these nonlinear sources of pendelluft are not charac- tified the limits of pendelluft volume at a single bifurcation.
terized by the present work. Using a numerical example of bronchoconstriction, we illus-
Limitations. Limitations of the simulation are related to the trated that small-magnitude pendelluft can emerge in asthma
model simplifications. The model that we used for our simu- and that pendelluft depends on the breathing profile. Although
lation example includes a bronchial tree based on generation 4 the overall magnitude of pendelluft was small in the example
to 16 of Weibel’s morphometric data for airway length and we explored, it was concentrated in poorly ventilated regions
diameter. It is possible that the four more proximal airway of the lung. This preferential site of pendelluft may contribute
generations could influence the pendelluft at certain frequen- to local gas exchange, irreversible mixing (3), and aerosol
cies and waveforms, but this remains quantitatively unknown. deposition patterns in poorly ventilated regions of the lung.
In addition, we have shown analytically (Fig. 5) that hetero-
geneous compliances can nearly triple the relative pendelluft. GRANTS
However, the challenge for numerical simulations is that the
results depend on the interplay between the pattern of bron- This work was supported by National Heart, Lung, and Blood Institute of
the National Institutes of Health grant R01HL087281.
choconstriction in the airway tree and the pattern of heteroge-
neity in compliance of the terminal units. For example, a tree
could theoretically have a heterogeneity in resistances that DISCLOSURES
spatially matches the heterogeneity in compliances, leading to No conflicts of interest, financial or otherwise, are declared by the authors.
a uniform distribution of time constants and little pendelluft.
The diameters and lengths of the airways were derived from AUTHOR CONTRIBUTIONS
an integrative simulation of bronchoconstriction that has been Author contributions: E.E.G. and T.W. conception and design of research;
demonstrated to generate ventilation defects similar to those E.E.G. and T.W. performed experiments; E.E.G., J.P.B., and T.W. analyzed
observed in Positron Emission Tomography imaging (19). It data; E.E.G., J.P.B., and T.W. interpreted results of experiments; E.E.G. and
can be assumed that the patterns of clustered constriction of T.W. prepared figures; E.E.G. and T.W. drafted manuscript; E.E.G., J.P.B.,
airways that cause the ventilation defects are a reasonable J.G.V., and T.W. edited and revised manuscript; E.E.G., J.P.B., J.G.V., and
T.W. approved final version of manuscript.
approximation of airway behavior in humans. However, asym-
metry in branching of airways within the bronchial tree was not
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