Respiration Physiology, 75 (1989) 141-156 141

Elsevier

RSP 01493

Is airway closure caused by a liquid f'flm

instability?
R . D . K a m m I and R . C . Schroter ~
tFluid Mechanics Laboratory, Department of Mechanical Engineering, Massachuse~" Institute of Technology,
Cambridge, MA 02139, U.S.A. and 2Physiological Flow Studies Unit, Imperial College, London SW72AZ,
U.K.
(Accepted for publication 28 October 1988)

Abstract. A physical model for small airway closure is developed, based on the assumption that closure
occurs as a result of a surface tension-induced instability of the thin liquid film lining the airways. To
distinguish this mechanism from others involving airway compliance, experiments were performed in rigid
tubes, I mm in diameter, with length-to-diameter ratios between one and ten. Oil was added to the film in
small increments and photographed at each stage. For total liquid volumes (V) less than some critical value
(Vc) surface tension draws the oil into an axi-symmetric film on the tube walls leaving the lumen relatively
unobstructed. When V exceeds Vc, the film becomes unstable and coll~oses, bridging the lumen and causing
obstruction. The ratio of V¢ to the tube diameter cubed was found to be approximately 0.7 for the entire
range of tube lengths studied. These experimental findings were then used to predict airway closure in a
morphometric model of the bronchial tree. Assuming that the liquid film at TLC is 10 pm and that the
volume of each airway varies in direct proportion to lung volume, the model predicts that airway closure
will first occur in the terminal bronchioles at a lung volume of 23~o TLC, in approximate agreement with
observed values of residual volume.

Airway closure; Bronchial mechanics; Fluid mechanics; Gas trapping; Obstructive disease

Airway closure has long been recognized as one of the major determinants of the
hysteresis seen in the pressure-volume curve of air-fflled lungs (Glaister et al., 1973a,b)
and the main contributing factor in phase IV of the single breath inert gas washout curve
and gas trapping. In addition, it is viewed as one of the primary mechanisms determining
residual volume (RV), especially in elderly subjects and in various obstructive diseases.
Direct evidence for closure has been obtained from several different approaches.
Hughes et aL (1970) were able to identify the site of closure in lungs rapidly frozen at
low lung volumes to be in the vicinity of the terminal bronchioles. In other experiments
performed on cannulated, excised cat lobes, liquid menisci were observed in airways
smaller than about 0.5 mm in diameter (Macldem et al., 1970). These menisci were

Correspondence address: R.D. Kamm, Massachusetts Institute of Technology, Room 3-260, 77 Massa-
chusetts Ave., Cambridge, MA 02139, U.S.A.

0034-56871891503.50 © 1989 Elsevier Science Publishers B.V. (Biomedical Division)

142 R.D. KAMM AND R.C. SCHROTER

observed to move back and forth in the airways when the volume of the lobe was varied.
In experiments using alveolar capsules mounted on exposed dog lungs, alveolar pressure
has been observed to follow tracheal pressure during a slow expiration from high lung
volumes, but to deviate from tracheal pressure at lung volumes approaching RV
(J. Fredberg, personal communication), suggesting closure of some intervening airway.
Davis et al. (1975) compared the slopes of observed pressure-volume curves at low lung
volumes with the predicted values obtained by extrapolation of the experimental
behavior evident above the inflection point to determine the rate of closure of airways.
Their observations indicated that extensive closure occurred at positive transpulmonary
pressures.
Despite the significance of airway closure, the physical phenomena responsible have
not yet been clearly elucidated. Furthermore, closure has received surprisingly tittle
attention in the recent literature. In the early seventies Macklem (1971) reasoned, on
the basis of experimental data, that closure is a result of liquid plugging by a meniscus
that forms in the airway, rather than a result of airway wall collapse. To appreciate the
difference between these two modes of closure, consider the airway as a tube of fmite
length L and diameter D with a uniform thin liquid lining film of thickness h whose
surface diameter is d (fig. 1). Surface tension will cause a reduction in the surface
diameter along the entire length of the tube; the actual diameter attained will depend
upon the balance between the surface tension force and the airway or tube wall stiffness.
At any configuration, we have a pressure Pi in the lumen of the tube and an effective
pressure Pe outside of the tube (including the effect of parenchymal tethering) so that
the total transmural pressure Ptm is Pi - Pc. The pressure inside the liquid film Pr will
be negative relative to Pi.

Fig. 1. Schematic depicting the liquid film on an airway wall. Pressures are identified that act external to
the vessel (Pc) within the liquid lining film (Pr) and inside the airway (Pi). D is the wall diameter and d is
the inside diameter of the liquid film.
 AIRWAY CLOSURE BY A LIQUID FILM INSTABILITY 143

Pressure Difference (a) Pressure Difference (b)

i,~ Pi -Pf //
~"Pi "Pf .,., //
t

t
Pi "Pe
"'b ' b ' o ~ . ,,. Q m, e , , ,,,,

Diameter

~ "" Pf -Pe

Fig. 2. A qualitative illustration showing how the pressure-diameter relationship for the airway/film combi-
nation depends on the independent characteristics ofthe airway wall and liquid film. The pressure difference
across the gas-liquid interface (Pi-Pf) varies inversely with airway diameter as shown by the dotted line.
The wall stiffness is characterized by the light solid line showing (Pr"Pe) as a function of airway diameter.
The combination (heavy solid line) is obtained by adding (Pi-Pf) to (Pf-Pc) at each diameter to obtain
(Pi-Pe). (a) A case where the airway/film combination is stable for all values of(Pi-Pe). (b) A case in which
the airway collapses due to an instability when the pressure difference is lowered below the value cor-
responding to the diameter d*.

The way in which the tube diameter varies with Ptm in the absence of a liquid fdm
is shown in fig. 2 (light solid line) as is the curve for the surface tension induced pressure
difference across of the liquid lining (dashed fine). The actual resultant diameter of the
tube which balances these forces is also shown (heavy solid line). There are two
principal modes of behavior as indicated. In (a) the liquid surface is stabi~ at all tube
diameters and a monotonic decrease in lumen diameter results. In (b) there comes a tube
diameter at which the surface forces become relatively large compared with the tube
stiffness and the film causes the tube to collapse and close; this occurs at the critical
diameter d* in the figure and is characterized by a sudden co~lapse of the airway wall.
If the tube and fdm were perfectly uniform, all points would tend to collapse
simultaneously; in reality, local non-uniformities cause collapse to occur at isolated
points. This instability is most likely to be observed when the surface tension is large
or when the tube is very compliant. We will refer to this mechanism as 'compliant
collapse'.
Studies of liquid film closure inside long tubes show that compliant collapse is not
the only phenomenon that can cause closure; there is a second mechanism that can also
operate. This is the mode described by Macldem as liquid plugging; an unstable collapse
ofthe liquid film ('film collapse') that bridges across the airway lumen to produce a local
obstruction. Frazer and Khoslmood (1979) likened this process to the instability that
occurs in a thin liquid film on the walls of a cylinder. With this conceptual model, they
144 R.D. KAMM AND R.C. SCHROTER

predicted that closure would occur when two conditions were met: (i)that the airway
length exceeded 2~ times the radius, and (ii)that a sufficient volume of liquid was
present to form a meniscus. The process they described has also been studied by fluid
dynamicists (Goren, 1962; Hammond, 1983), but none have provided a specific criterion
for closure. Furthermore, while film collapse can occur in a rigid tube, it would clearly
be promoted by airway compliance that leads to a further reduction in area. Thus, in
reality, both modes of collapse, 'compliant' and 'film', are present.
The primary objective of the present study is to provide a quantitative description of
film collapse and to use this description to investigate the conditions for airway closure
in the lung. In order to isolate this effect from compliant collapse, experiments were
conducted in rigid tubes as described below.

Methods

Experimental. Experiments were conducted to determine under what conditions a

liquid fdm on the inside wall of a short, rigid tube would collapse due to a surface
tension-induced instability and thereby occlude the lumen. We anticipated that, as lung
volume decreased, the total amount of liquid in each airway would remain nearly
constant. Therefore, the ratio of liquid volume to airway volume would increase with
decreasing lung volume. If there were sufficient liquid in the airway to begin with, then
we expected the film to eventually bridge the lumen and close the tube when the liquid
volume (V) reached some critical limit (Vc). In these experiments, we produced a gradual
increase in V by repeatedly adding small amounts of liquid to the tube. By proceeding
in small steps, and allowing the film to approach an equilibrium state at each step, we
were able to identify the critical volume necessary for closure.
We used three different holes with length-to-diameter ratios (L/D) of 1.2, 3, and 10,
each drilled in a small acrylic block. The hole diameter was I mm in each case. A
countersink was used to flare the ends of each hole, producing a tube as shown in
cross-section in fig. 3. The purpose ofthe countersink was to impose a smooth entrance
to the tube but nevertheless create a defmed tube length. During the experiments, the
acrylic blocks were held with the axis of the tube vertical.
The liquid used was a commercially available baby oil, selected over several alterna-
tives primarily for its wetting characteristics on acrylic. The coefficient of viscosity ~),
density (#), and surface tension (y) of the oil were measured using standard techniques.
The values obtained are given in table 1. In addition we added sugar to the oil until its
refractive index (n = 1.47) was close to that of acrylic (n ffi 1.49), a fact that enabled
us to obtain photographs of the film (see below) with relatively tittle optical distortion.
The procedure ultimately adopted was to incrementally add small amounts of oil to
the film using a syringe placed at the countersink near the mouth of the tube. With each
addition of oil, the combined effects of surface tension and gravity pulled the oil into
the hole and distributed it into an axisyrnmetric configuration on the tube walls,
reaching an apparent steady state in about 1 min.
 AIRWAY CLOSURE BY A LIQUID FILM INSTABILITY 145

Top
view

dio hole

Side
view ///A / / / / /
/
/ /
/
/ /
/ /
/
/ /
/ /

Fig. 3. Test apparatus consisting of a I mm diameter hole drilled into a Plexiglas sheet and countersunk
at both ends, The length L of the hole was either 1.2, 3 or 10 hole diameters.

TABLE 1
Physical parameters relevant to film collapse. Values given for the properties ofthe liquid lining the terminal
bronchioles are only rough estimates. The diameter of the terminal bronchioles is taken from Fredberg and
Hoenig (1978).

Parameter Units Experimental value Terminal bronchioles

p g. cm - 3 0.848 1.0
p g. cm- ~s- s 0.215 0.01
? mN. m - ~ 38 20
D cm 0.1 0.05

Bo - 0.22 0.123
Re - 8.4 100
146 R.D. KAMM AND R.C. SCHROTER

Although the fdm configuration appeared steady, it can be shown, given the surface
contours we observed, that there remained a pressure gradient tending to draw liquid
from the thin fdm on the wall into the main body of oil. Because the time scale of this
residual motion was so long, and the total liquid volume involved so small, the con-
figuration appeared steady, and was so for all practical purposes.
With progressive increments in film volume, a near critical state was eventually
reached corresponding to the maximum amount of liquid the tube could hold and still
remain open. The next volume increment would then set the fdm in motion, causing a
collapse of the fdm so rapid as to appear instantaneous.

t, B C

Fig. 4. A sequence of photographs showing the progression toward closure (A) and (B), and just following
film collapse (C) in the long (L/D = I0) tube. The line down the tube center is a reflection off the back
wall.
 AIRWAY CLOSURE BY A LIQUID FILM INSTABILITY 147

The sequence of equilibrium states leading up to film collapse (fig. 4A,B), and the
state just following collapse (fig. 4C) were photographed with the intent of obtaining a
record of the critical liquid volume needed to produce collapse. The photographs were
obtained using a 35 mm SLR camera with extension bellows and 55 mm lens, thus
producing a magnification of 2.5 times on the negative. The tubes were illuminated by
side rioting with a dark background.
The photographs were printed to a magnification of 20 x and analysed with the aid
of a digitizing pad to obtain the corresponding values of V/D 3. The data for all three
L/D ratios were processed in this manner.

Analytical. As a basis for interpreting the experimental results, consider two dependent
variables that relate to the process of airway closure: the minimum volume (V~) ofliquid
needed to produce closure, and the time (t¢) required for closure to occur once a
sufficient volume is present. These two would, in general, depend upon the liquid
properties (a, /t, Y), the geometry of the airway or tube (as characterized by its
diameter D and length L), and may be influenced by gravity (g). Two approaches will
be used to describe the dependence of V¢ and t¢ on the independent parameters.
The first approach is to examine the force and momentum balance that governs the
motion of liquid within the fdm. Liquid flow is driven by a pressure gradient, the
magnitude of which depends on surface tension and the geometry of the interface. The
pressure gradient (denoted here by P) is balanced by a collection of terms representing
gravity (G), viscous shear stress (V), temporal acceleration (T) and convective accelera-
tion (C). In symbolic form, we can write:

P-G+V+T+C (l)

To a first approximation, P scales as a characteristic pressure difference across the

gas-liquid interface (y/D)divided by a characteristic length (D), giving P ~ y/D2. U sing
similar reasoning, order-of-magnitude estimates can be obtained for each of the terms
on the riOt-hand side of eq. (1): G ~ pg; V ~/~/tcD where D/to is taken to be a
characteristic liquid velocity within the fdm; T ~ pD/t~; and C ~ pD/t~.
In static equilibrium, the weight of the fdm is supported by the pressure gradient
associated with surface tension while all other effects associated with fluid motion are
identically zero. The relative importance of gravity is represented in this situation by the
Bond number

Be - pgD2/~ (2)

which, using the symbolism just introduced, is simply the ratio G/P.
Generally speaking, when the Bond number is small compared to unity, the effects
ofgravity can be neglected. For our experiments, Be = 0.22 while for the small airways
of the lung, Be = 0.12. Therefore, while our experiments may be influenced slightly by
gravity (as evidenced by the lack of vertical symmetry in the photos of the fdm shown
148 R.D. KAMM AND R.C. SCHROTER

in fig. 4) these effects should be of even lesser importance in the lung. In the following,
the influence of gravity will be assumed small.
Consider now the dynamic process. With regard to the force balance arguments given
above, and assuming gravity can be neglected, three possibilities arise: (l)that the
pressure gradient is balanced by the two inertial terms (P ~ T + C), (2) that the pressure
gradient is balanced by viscous effects (P ~ V), or (3)that both inertial and viscous
effects are important. Case (1) yields the following relationship:
pD/(tc) 2 ~ 3'/D2

which leads to the following estimate:

(to) I ,~ (pD3]3') ./2 (3)

where (t¢)t is the time scale for closure when inertia dominates. Case (2) implies that
closure occurs on a viscous time scale, given by

(to),, ~ D /v (4)

Case (3) is more difficult to analyse but will presumably apply only in the transition
between cases (1) and (2). From the estimates above, we can form a ratio of inertial to
viscous time scales which we identify as the appropriate Reynolds number for the
closure process.
(to)m pD3' '/2
~~ = Re (5)
(to)v V21

Accordingly, either inertia or viscosity dominate when Re is large or small, respectively,

compared to unity. Using the numerical values given in table 1, we find that the
Reynolds number is 8 for our experiments while in the terminal bronchioles it is
approximately 100, suggesting that inertial effects dominate in both cases during
unstable film closure. As noted below, however, the viscous time scale may also be
relevant.
We now examine the general relationships for Vo and to by means of a standard
dimensional analysis. The foregoing statements suggest that, in the most general case,
V¢ and t¢ are functions ofgeometry, liquid properties, and gravity. This can be expressed
as"

Vc = fnc (L, D, ,o, ,u, 3', g) (6a)

tc = fnc (L, D, p,/~, 3', g) (6b)

or, in dimensionless form it can be shown that:

VoID3 = fnc (L/D, pgD2/3', ~ / P ~ / P ) (Ta)

 AIRWAY CLOSURE BY A LIQUID FILM INSTABILITY 149

tc7//~D = fnc ( L / D , pgD217,v/'P~I/1) (?b)

where the second and third parameters inside the parentheses are recognized as the
Bond number and Reynolds number defmed above.
Consider first the relationship for V¢/D3. At each stable equilibrium volume (V < V¢)
the shape taken by the fdm is one that minimiTes the surface area, and hence the surface
energy of the film. The underlying cause of the instability is that, when V = V¢, a small
perturbation of the open equilibrium state can produce a surface with lower energy
leading to closure. The critical feature of this process, for our purposes, is that the
stability ofany equilibrium state is simply a matter ofgeometry. If, for a given equilibrium
shape at a particular liquid volume, a small perturbation from equilibrium produces a
smaller total surface area, then the f~n will undergo an unstable transition to the new,
stable state. On the strength of these physical arguments, we reason that the critical
volume for collapse is simply determined by the geometry of the fdm and should
therefore be independent ofthe fluid properties 7, tt and p. If, in addition, we omit g while
recognizing that it may have a small but non-negligible effect, a dimensional analysis
leads to the following, much simplified form:

V©/Ds = fnc (L/D) (8a)

Our experimental results suggest further that for L/D >~3, Vc/D 3 - constant as dis-
cussed below.
It is somewhat more difficult to reduce eq. (7b) for t© since the time it takes for
dynamic collapse will certainly depend on the properties of the liquid film. Recognizing,
however, that the Bond number is typically less than one and the Reynolds number is
large compared to one, we have some justification for a s s u ~ g that tc is relatively
independent of gravity and viscosity. Omitting/t and g from eq. (6b) and proceeding
as before, we obtain

t©(7/pD3) '/2 = fnc ( L / D ) (8b)

If, as in the case of Vc/D 3, the dependence on L/D is weak, then the following expression
is obtained:

tc -~ const. (pD3/7) '/" (9)

Values for (,oD3/7)'/2 are 5 msec for our experiments and 25 msec for the terminal
bronchioles using the data in table 1. These values represent an order-of-magnitude
estimate for to.
The utility of eqs. (7) (or (8)), aside from the physical insight they provide, is that they
constitute a way of relating our experimental results to conditions in the lung.
150 R.D. KAMM AND R.C. SCHROTER

Results

Measurement of critical values. Guided by the similitude arguments of the last section,
we plot our results in the dimensionless form V / D 3 as a function of L/D (fig. 5). Values
of V/D 3 corresponding to an unobstructed tube (open circles) and those corresponding
to an obstructed tube (closed circles) are shown and give a critical value for instability
of 0.61 for L/D = 1.2, and rising to an approximately constant value of 0.7 for L/D in
excess of three. When cast in this form, we see that the critical value V¢/D 3 is nearly
independent of L/D within the range of these experiments, and for the purpose of
discussion we will take the critical value to be constant and approximately equal to 0.7.
For liquid volumes less than the critical value a stable film could be maintained
indefinitely. If a small amount of liquid remained in the flanged end regions, surface
tension forces would tend to draw the liquid into the tube. If sufficient liquid were
available to achieve critical volume, the meniscus would close. The time scale for
drawing liquid in from the end regions was typically very long, taking on the order of
minutes. In contrast, the instability that produced closure proceeded too rapidly to be
discerned by eye once a sufficient volume was present. Lacking the equipment for high
speed photography, we can only say that collapse took place on a time scale less than
about 0.1 sec. This observation provides very rough confu'mation of the time scale for
collapse from the estimates of the previous section.

Application to the lung• On the basis of the model experiments and the dimensional
analysis we can predict the onset ofclosure in a human lung. For this purpose, we make
several assumptions.

0.8-
Airway closed

0.7 "
0

V :0.67
m

D3
Airway open
0.6-

0.5
1.2 3. O
L/D
Fig. 5. Experimentally determined liquid volumes corresponding to closed (•) and open (o) states, for each
of the three L/D values tested.
 AIRWAY CLOSURE BY A LIQUID FILM INSTABILITY 151

1. That airway closure occurs when the volume ofliquid contained in a single airway exceeds the critical
limit VJD 3 = 0.7. Since a similar process occurs in each airway, the competition for liquid between adjacent
airway segments will preclude much transfer of liquid across branch points. Furthermore, the time scales
for transfer through a thin connecting film would likely be long compared to the normal breathing period.
Consequently, closure will occur as a result ofthe liquid film volume in a single airway eventually becoming
greater than 0.7 D 3 as the airway radius decreases with decreasing lung volume. In algebraic terms this
implies that closure will occur when

V__ =.~Lo (Doho - h~) TLC

--~0.7 (10)
D3 Do3 VL

where VL is lung volume and Lo, Do and I1o are the airway length and diameter and the film thickness,
respectively, all measured at TLC.

2. That the thickness of the liquid film at TLC is either 10 #m or 5/4m.

3. That all linear dimensions of the airways change as V~ 3 but that the airways are stiff at each lung
volume.

4. That airway morphology is adequately represented by the model of Fredberg and Hoenig (1978). In
that model, the trachea is order 35; the terminal bronchioles are order 8.

Using eq. (10) we have computed the lung volumes at which closure would occur,
for all generations from the terminal bronchioles mouthward. The results shown in fig. 6

0.24
0.22-
Closure ~'~ 2:5 % TLC
(lOp. film )
0.2-
O.18
VL
TLC 0.14-
12% TLC
O.t (5V film)
0.08
0.06-
0,O4-
0.02-
0 I

8 t2 16 ' 20 ' 52 56
Order #
Fig. 6. Values for normalized lung volume (VL/TLC) at which airway closure would occur by film collapse,
using the experimental results of this study and the morphometric model of the human lung of Fredberg
and Hoenig (1978). If the film is 10/Jm thick at TLC, then closure will occur first in the order 9 airways
at a lung volume of 23% TLC. Changes in liquid film thickness at TLC produce inversely proportional
changes in the lung volume corresponding to closure but do not alter the site of closure.
152 R.D. KAMM AND R.C. SCHROTER

suggest that, for a film thickness of 10 #m at TLC, the airways of order nine (which have
an internal diameter of 0.53 mm at TLC) would be first to close, and that closure would
occur at a lung volume corresponding to 23 % TLC. Note that the lung volume at which
closure occurs in a given airway scales linearly with the film thickness, but that the
location of the critical airway is unaltered.

Discussion

Closure in a rigid tube. In these experiments we have characterized the process by

which a liquid film in a short, rigid tube becomes unstable and collapses to obstruct the
tube lumen. We observed that when liquid is first added to the tube, surface tension
distributes it into an axi-symmetric film, slightly reducing the open lumen diameter
locally. For liquid volumes less than some critical value, the film is stable. As the critical
volume is approached, however, the film protrudes progessively further inward. When
the critical volume is reached, the film undergoes a rapid transition to closure. This is
presumably initiated when a small perturbation from the open equilibrium configuration
produces a reduction in total inteffacial area and hence, in inteffacial energy as well.
The ratio Vc/D 3, found to be approximately 0.7, is independent ofthe physical properties
of the film and varies only slightly when L/D ranges from 1.2 to 10. The time for closure
t¢ is very small, and is likely to be governed by inertial effects in the film.

Closure in an airway. In the lung, we anticipate that the total volume of liquid lining
the airways remains essentially constant during the course of a breathing cycle. Further-
more, on the basis of our observations it is unlikely that enough liquid can be transferred
between neighboring generations in one breath to significantly alter the distribution of
liquid volume from that which is found at TLC. Consequently, as lung volume and local
airway volume fall during expiration, the ratio of liquid-to-airway volume increases.
Based on our observations in rigid tubes, we expect the film lining the airway to distort
in the manner shown in fig. 4, then abruptly close as the critical ratio Vc/D 3 -~ 0.7 is
reached. According to our predictions based on a morphometric model of the human
lung, closure would first occur in the tern~Jnal bronchioles at a lung volume of about
20% TLC. Subsequent movement of the meniscus has been considered by Frazer and
Khoshnood (1979).
The process would reverse as lung volume is increased. The meniscus would
presumably thin and propagate peripherally as the open regions of the lung expand and
the pressure peripheral to the site of closure falls, but we have no data to use to quantify
this process.

The effect of airway compliance. The scenario just described presumes that a unique
relationship exists between lung volume and airway size. As discussed in the intro-
duction of this article, however, airway size is intrinsically linked to the properties of
the airway wall and the nature ofthe lining film. Moreover, a second mode of instability
 AIRWAY CLOSURE BY A LIQUID FILM INSTABILITY 153

can occur as a result of the interaction between these two factors. To examine the
competition between these two instability modes, consider the example illustrated in
fig. 7. Given the airway wall and surface film behavior depicted in fig. 7a, the 'compfiant
collapse' mode will occur when the vessel diameter reaches d= (corresponding to a
transpulmonary pressure P=), while 'film closure', as observed in the present experi-
ments, occurs at dr (Pr). Depending on the airway stiffness, film surface tension, and
total fiquid volume contained in the airway, d= may be either larger or smaller than de

Pressure Baseline Prl s s u r e Surface t e n s i o n i n c r e a s e d

5 0 ~ I 200 ....... 0 ......... n -- v W.......
lal (b)

4011 J - 150

/ I00

'°1 //
/ "-

/ dc (If

0 0.02 0.04 0.06 0 . 0 8 0.1 0.12 0 0.02 0.04 0.06 0.08 0.1 0.12
0iometer Diameter

Pressure Airway stiffness increased Pressure Diameter r e d u c e d

200 "----'-T----'---~--:--T--~-X"~" 100 r - - ~ ' - r - - ' - - ~ - - - , , , ........
(C) (d)

80
IS0 -

60
100

4O

so.~

0
0

Id c (If l dc d
-5q -20 n n ..... J , n
0 0.02 0.04 006 0.08 0. I 0.12 0 0.01 0.02 0 . 0 3 O. 0 4 0.05 0.06
Diameter Diameter
Fig. 7. Schematic showing the pressure difference across the film (dashed line) airway (light solid line) and
airway/film combination (heavy solid line) as a function ofalrway diameter for different values of the critical
parameters (arbitrary units). Conditions at film instability are denoted by diameter dr and transmural
pressure Pr while compliant collapse occurs at the minimum in the airway/film curve at dc and P=.
(a) Baseline; (b)with an increase in surface tension; (c)with an increase in airway stiffness; (d)with a
reduction in the rest diameter of the airway. See text for full description.
154 R.D. KAMM AND R.C. SCHROTER

The mode of instability corresponding to the larger diameter will be responsible for
closure in any particular instance. In the example of fig. 7a, df > dc so closure occurs
as a result of a localized film instability.
We can now qualitatively examine the effects of a variety of perturbations from the
'typical' state pictured in fig. 7a. For example, if surface tension is increased (fig. 7b)
the airway stiffness curve remains the same while the surface tension curve is shifted
upward. Consequently, the value of do increases. But since df is unaffected, airway
closure is less likely to be due to a loc~ized collapse of the film. An increase in airway
stiffness is represented by a steepening of the airway curve (fig. 7c). This produces a
downward shift in the value of do while df remains constant, making fdm collapse more
likely. Note that in the limit of a very stiff airway, the compliant collapse mode may no
longer be possible, leaving only film collapse as a potential mechanism for closure.
Finally, if the rest diameter (that corresponding to a state of zero transmural pressure)
of the airway is reduced (fig. 7d) do is once again reduced, tending to favor closure by
a localized film instability.
All the perturbations just mentioned only affect the airway diameter for compliant
collapse. The diameter for film closure is influenced primarily by the amount of liquid
lining the airways which was assumed to remain constant. If, however, the liquid volume
were increased, df would increase since the critical ratio V¢/D 3 would be reached sooner.
These effects can also be considered in terms of the transpulmonary pressure or lung
volume at which airway closure occurs. If we assume that instability first occurs as a
result of film collapse as in all the cases of fig. 7, then we can see that an increase in
airway surface tension produ¢:es closure at a higher value of PL and a higher lung
volume. This is because an increase in ~ causes a reduction in airway diameter at any
given state of lung inflation due to the negative pressure produced in the liquid film.
Therefore, while we reasoned previously that ~ played no significant role in determining
Vo/D 3 in the rigid tube experiments, it does indirectly affect the lung volume correspond-
ing to airway closure. Similar reasoning can be used to demonstrate that airway
stiffening reduces the lung volume at closure while a reduction in rest diameter or an
increase in film volume both cause it to increase.

Physiological implications. Consider now the effect on airway closure of pulmonary

edema. An accumulation of fluid within the lumen of the airway will increase the lung
volume at which closure occurs by a fdm instability. Interstitial edema produces a
reduction in the resting diameter of the airway, which also increases the closing volume.
The associated reduction in airway compliance, however, may negate some of this
increase. All these effects tend to favor film rather than compliant collapse.
Smooth muscle contraction has the effect of reducing the resting airway diameter and
also making the airway less compliant (Lai Fook, 1978). As these factors have opposite
effects on closing volume, the net effect would depend on their relative magnitudes.
However, both would favor a film instability as the mechanism for closure.
In cases in which the surface tension of the lining fdm is increased as, for example,
due to a deficiency in the production of surfactant, closing volume would increase and
 AIRWAY CLOSURE BY A HQUID FILM INSTABILITY 155

the mechanism of closure is more likely to be a compliant collapse of the film. An

interesting related point concerns the role of surface tension hysteresis. If surface
tension hysteresis is matched between the airways and the parenchyma, then surface
tensionper se should not lead to large, disproportionate changes in parenchymal volume
relative to small airway volume. On the other hand, if the surface tension of the alveolar
film were to fall more rapidly than that of the airway film there would be a drop in
parenchymal tethering forces relative to airway film forces that would lead to a smaller
airway cross-section at any given lung volume. The airways might therefore close more
readily since the external tethering force due to the parenchyma would be reduced.

Time scalesfor airway closure. In discussing the experimental results, two different time
scales were mentioned as being relevant to the process of closure: the time required for
the film to adjust to an equilibrium distribution as the f'dm volume increased for volumes
less th~a the critical volume Vc, and the time tc for the instability to occur once the
critical volume was reached. The adjustment time can vary considerably depending on
the initial geometry of the fdm relative to the fmal equih'brium state. In the lung, two
situations are pertinent. We might expect the film to be uniformly distributed over the
airway wall at high lung volumes. As lung volume falls and the critical state is
approached, the film will tend to form into a bead as described above. If the linear
dimensions of the film (thickness and length) are not too discrepant, then the scaling
derived in the section Analysis would pertain, suggesting that the adjustment time is
dominated by inertial effects and that it is typically small compared to the time for a
single breath. If the fdm is very thin, however, viscous effects will become more
important and the characteristic time for readjustment will scale as 0 t L / y ) ( L / h ) 3
(Hammond, 1983) which is larger than our previous estimate (eq. (4)) by a factor of
(L/h) 3 if we take L/D to be of order one.
A particular example concerns the competition for liquid between neighboring
airways. As the volume of each airway falls, neighboring airways with similar dimensions
will approach the critical state at roughly similar lung volumes. As they do, each is likely
to draw the contained volume into a bead, thereby extracting liquid from the intervening
bifurcation reducing the fdm thickness there and thereby slowing the rate at which liquid
can be exchanged. Thus the time scale for intra-airway liquid flow may ultimately be
viscous dominated and probably long compared to the breathing period.

Aelmowledgements.We gratefully acknowledge the financial support of the U.S. National Heart, Lung and
Blood Institute (HL-33009) and the U.K. Science and Engineering Research Council (GR/D/76639).

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