Lung Tissue Resistance in Diffuse Interstitial Pulmonary

Fibrosis
H. Bachofen, M. Scherrer
J Clin Invest. 1967;46(1):133-140. https://doi.org/10.1172/JCI105506.

Research Article

1) Measured during spontaneous breathing in ten patients with diffuse interstitial lung disease, total pulmonary resistance
averaged 3.53 ± 1.56 cm H2O per L per second; airway resistance, 1.63 ± 0.79 cm H2O per L per second; and lung
tissue resistance, 1.90 ± 0.95 cm H2O per L per second (range, 0.89 to 3.96). The lung tissue resistance was on an
average about four times higher in patients with lung fibrosis than in ten healthy persons of the same age. No significant
difference in airway resistance was found between healthy subjects and patients.

2) In three patients the lung tissue resistance was measured during spontaneous breathing and during panting. Much
higher values were found during spontaneous breathing.

3) In patients with lung fibrosis and also in healthy subjects, there seems to have been an inverse correlation between the
vital capacity, or the compliance, on the one hand, and the lung tissue resistance on the other. Nevertheless, in patients
with lung fibrosis the lung tissue resistance was more increased than could be attributed to the loss of normally compliant
lung tissue only.

4) No correlation was found between the lung tissue resistance and severity of impairment of pulmonary gas exchange;
especially no relationship appeared to exist between the lung tissue resistance and the alveolar-end capillary PO2
gradient during hypoxia. This result […]

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Journal oClinical Investigation
Vol. 46,ONo. 1, 1967

Lung Tissue Resistance in Diffuse Interstitial Pulmonary

Fibrosis *
H. BACHOFEN t AND M. SCHERRER
(From the Department of Medicine, Inselspital, University of Berne, Berne, Switzerland)

Summary. 1) Measured during spontaneous breathing in ten patients with

diffuse interstitial lung disease, total pulmonary resistance averaged 3.53 ±
1.56 cm H2O per L per second; airway resistance, 1.63 ± 0.79 cm H20 per L
per second; and lung tissue resistance, 1.90 ± 0.95 cm H20 per L per second
(range, 0.89 to 3.96). The lung tissue resistance was on an average about
four times higher in patients with lung fibrosis than in ten healthy persons of
the same age. No significant difference in airway resistance was found be-
tween healthy subjects and patients.
2) In three patients the lung tissue resistance was measured during spon-
taneous breathing and during panting. Much higher values were found dur-
ing spontaneous breathing.
3) In patients with lung fibrosis and also in healthy subjects, there seems to
have been an inverse correlation between the vital capacity, or the compliance,
on the one hand, and the lung tissue resistance on the other. Nevertheless,
in patients with lung fibrosis the lung tissue resistance was more increased
than could be attributed to the loss of normally compliant lung tissue only.
4) No correlation was found between the lung tissue resistance and severity
of impairment of pulmonary gas exchange; especially no relationship appeared
to exist between the lung tissue resistance and the alveolar-end capillary PO2
gradient during hypoxia. This result indicates that the pathological altera-
tions producing a measurable end gradient in hypoxia may be independent of
the augmentation of the fibrous framework responsible for the stiffening of
the lung.

Introduction ber of patients examined (three cases), or to their

The disturbances of the mechanics of breathing experimental procedure (all measurements were
and pulmonary gas exchange have been extensively made in panting subjects), no success was achieved
studied in patients with diffuse interstitial fibrosis in demonstrating any relationship between values
[(1-9) and many other more recent authors]. for lung tissue resistance and other data of lung
Nevertheless, little attention has been paid to the function. This study is a further attempt to il-
viscous properties of lung tissue in this disease. luminate the problem of lung tissue resistance and
Marshall and DuBois (10) observed a slight in- its correlation to other figures of pulmonary func-
crease of lung tissue resistance by a plethysmo- tion tests in diffuse interstitial lung disease. In
graphic method. Possibly owing to the small num- contrast to the method of Marshall and DuBois,
the total pulmonary, airway, and lung tissue re-
* Submitted for publication June 24, 1966; accepted sistance was measured during spontaneous breath-
October 6, 1966. ing in our experiments.
Supported by the Swiss National Science Foundation
and the Science Foundation of the University of Berne. Methods
t Address requests for reprints to Dr. H. Bachofen,
Dept. of Medicine, Inselspital, University of Berne, 3000 Subjects. Ten patients were studied. For the selec-
Berne, Switzerland. tion the following points were decisive:
133
134 H. BACHOFEN AND M. SCHERRER

1) The histories (progressive exertional dyspnea, non- Total pulmonary resistance (R,) and airway resistance
productive cough), clinical signs (persistent moist rales (Ra) were measured with subjects sitting and breathing
over both lungs), and radiological appearances were char- spontaneously [a moderate hyperventilation could not be
acteristic. There was no evidence of bronchopulmonary avoided because of the rebreathing system used (15) ].
infection. Ra was determined with a volume displacement body
2) The clinical status showed relative stability; for plethysmograph of the type designed by Mead (16) and
several weeks at least there were no noticeable changes modified by Jaeger and Otis (15, 17-19). The changes of
of signs, symptoms, or X-ray findings. temperature and water content of respiratory gases dur-
3) Lung volume measurements by spirometry gave a ing spontaneous breathing were eliminated by having the
purely restrictive pattern; in all patients who were co- subjects rebreathe from a bag containing gas at BTPS
operating well, the forced expiratory volume over sec- (body temperature and pressure, saturated with water)
ond was 75%o or more of the vital capacity. conditions. R, was obtained by simultaneous recordings
4) The alveolar-arterial Po2 difference during hypoxia of intraesophageal pressure and rate of air flow. Intra-
(fractional concentration of 02 in inspired air, FIO2, = esophageal pressure was measured with a thin-walled
0.154), from which the components induced by shunts and rubber balloon (length, 10 cm; perimeter, 3.5 cm) simi-
distribution inequalities were subtracted, was remarkably lar to that described by Schilder, Hyatt, and Fry (20).
increased. This alveolar-end capillary gradient seemed to With a polyethylene tube (length, 65 cm; i.d., 0.1 cm)
us to be more reliable a criterion for the degree of im- the balloon was connected to a Statham pressure trans-
pairment of diffusion than the 02 or CO diffusing ca- ducer (model PM 131 TC 5-350) equipped with a special
pacity, considering the various hypotheses involved in the pressure adapter having a small chamber volume on the
Bohr integration and trial and error procedure for cal- positive side of the gauge. The balloon-tubing-gauge
culating the 02 diffusing capacity (11) on the one side, system had a natural frequency of 30 cycles per second.
the difficulties in estimating the CO diffusing capacity All variables (intraesophageal pressure, volume fluctu-
in patients with unequal distribution (12, 13) on the ations of the plethysmograph, rate of air flow, tidal vol-
other side. ume, and mouth pressure) were plotted simultaneously
Of course, the clinical, roentgenological, and physio- on photographic paper by an Electronics for Medicine
logical alterations mentioned above are not specific signs multichannel recorder. After the balloon was passed by
of "fibrosis," but may also include interstitial pneumonitis the nasal route into the esophagus until the tip of the tube
(14) and granulomatosis. However, the prolonged his- was lying about 40 cm from the nares, the balloon sys-
tories (2 months to 15 years), the marked decrease of tem was emptied, then filled again with 6 ml air. Fi-
lung volumes, and the stability of the clinical status point nally enough air was extracted that only 0.8 ml remained
to rather fibrotic and advanced forms of diffuse inter- in the system (between tube and transducer a three-way
stitial pulmonary disease designated in this paper as "dif- stopcock was connected). The computation of R, was
fuse interstitial pulmonary fibrosis." based upon pressure volume loops that were plotted from
Physical data, duration of symptoms, and results of the photograph recordings, each loop determined by 14
lung volume measurements are given in Table I. points. For each of these points the corresponding al-
Technics. The lung volumes were determined by veolar pressure was calculated from the photograph and
spirometry, and the functional residual capacity was cal- added to (inspiration) or subtracted from (expiration)
culated with a helium dilution technic. the proper value of intraesophageal pressure. Thus, by

TABLE I
Physical data, duration of symptoms, and lung volumes in ten patients with diffuse
interstitial pulmonary fibrosis (mean age, 55 years)*

Duration of
Name Sex Age Height Weight symptoms Vital capacity Residual volume FEVi.o/VC
years cm kg years ml % ml % %
pre- of TC
dicted
1. C.E. 9 71 160 67 5 2,130 69 910 30 66t
2. S.A. 9 34 148 65 2 1,500 53 630 30 55t
3. B.G. 28 163 57 18 months 3,180 68 790 20 82
4. H.G. ci 56 176 65 4 2,680 60 990 27 82
5. Z.R. 9 56 165 63 15 1,130 32 850 43 88
6. R.D. 58 161 63 5 months 2,200 59 560 20 76
7. L.R. 48 173 75 10 months 2,900 62 780 21 83
8. M.M. 9 58 151 59 2 months 1,570 56 960 38 66t
9. R.W. 72 172 71 15 months 2,860 69 1,720 38 76
10. G.J. 72 172 60 3 months 3,150 75 1,370 30 82
* TC = total capacity; FEVI.o/VC = timed vital capacity.
t The poor cooperation of the three patients accounts for these low values.
 LUNG TISSUE RESISTANCE IN PULMONARY FIBROSIS 135
connecting these 14 new points, a smaller loop could be r-- L ter ---
drawn in the center of the intra'esophageal pressure-vol-
ume loop (Figure 1). Whereas the area of the latter
corresponded with the work done against the total vis-
cous resistance of the lung, the area of the former (small)
loop was proportional to the work done against the vis-
cous lung tissue resistance. The areas of both loops
I
were measured with a planimeter, and R,, as well as Rt, E
was computed with the area formulas indicated by Nisell U

and Ehrner (21). Dynamic lung compliance was obtained

by dividing the tidal volume by the change in the esopha-
geal pressure between points of zero flow. The values B C
of Rp, R., and Rt are averages of at least three measure-
ments, that of the dynamic compliance of at least five Ii
measurements. For calculating these mean values only
those cycles of respiration were evaluated during which
the functional residual capacity and the tidal volume re- a,
mained nearly constant. _0b
In all subjects the gas exchange was analyzed with the
subjects supine and breathing spontaneously. The alveolar-
arterial Po2 difference (A-aDO2) was determined at normal FIG. 1. VOLUME-PRESSURE LOOPS A) IN A HEALTHY
oxygen (FI02 =0.21), hypoxia (Fio2= 0.154), and hyper- ADULT, B) IN A HEALTHY CHILD (11 YEARS OLD), AND C)
oxia (FIO2 = 0.95) under steady state conditions. The pa- IN A PATIENT WITH DIFFUSE INTERSTITIAL PULMONARY
tients breathed each gas mixture during 15 to 20 minutes FIBROSIS. The stippled areas correspond with the work
from the closed circuit of the metabographe designed by done against the viscous lung tissue resistance.
Fleisch (22). The FIN2 was continuously measured and
held constant by Lundin and Akeson's (23) nitrogen meter as an alveolar-end capillary Po2 gradient, i.e., a gradient
(24). The deflections of the nitrogen meter were cali- mainly due to diffusion (25-27). It should be empha-
brated by analyzing samples of inspired air for 02 by a sized that the most questionable assumption made by
Haldane apparatus. Ventilation, 02 uptake, C02 output, Riley and Lilienthal-constant 02 diffusing capacity in
and respiratory quotients were measured with the meta- normal oxygen and hypoxia-was not involved in these
bographe. The arterial Pco2 was calculated by the for- calculations. Our new assumption that there is no dif-
mula of Henderson-Hasselbalch, with the pH and the fusion gradient at normal oxygen may be incorrect in pa-
plasma C02 content of the arterial blood obtained by an tients with severe "alveolar-capillary block." However,
indwelling needle. The arterial 02 content and capacity the only consequence of neglecting this possibility is that
were determined by the Van Slyke technique, and the the end gradients obtained by this method must be con-
arterial Po, was determined by an 02 electrode of the sidered as minimal values, i.e., that a much increased end
Clark type immediately after sampling the blood in gradient could possibly be larger, but in no case smaller.
syringes warmed up to 370 C. The electrode was cali- Normal values. Normal values were obtained with the
brated in each case with the patients' blood equilibrated technics described above and have been published in part
at three different levels of Po2 (50, 100, and 600 mm Hg) elsewhere (19, 28). The mechanics of breathing were
at 37° C. With an assumed arteriovenous 02 difference also studied in five healthy children. They were asked to
of 5 ml per 100 ml, the anatomical shunt was calculated hyperventilate to reach breathing patterns similar to those
by the A-aDO2 during hyperoxia (the absence of any signs registered on adults during plethysmographic measure-
of heart disease suggested that there was no important in- ments. The mean values found in the different age groups
crease or decrease of pulmonary blood flow or arterio- of healthy subjects are plotted at the bottom of Table II.
venous 02 difference). On the assumption that there was
no gradient due to diffusion at normal oxygen, the ve-
nous admixture due to ventilation-perfusion or other Results
distribution inequalities was calculated with the A-aDo, at Measured during spontaneous breathing in ten
normal oxygen, from which the true shunt component
had already been subtracted. Then, the A-aDo, in hypoxia patients with diffuse interstitial lung fibrosis, total
was corrected also by subtracting the anatomical shunt pulmonary resistance (Rp) averaged 3.53 ± 1.56
and distribution component, assuming that there was no cm H20 per L per second, the mean airway re-
change in venous admixture during the whole procedure. sistance (Ra), 1.63 ± 0.79 cm H2O per L per
The correction of the A-aDo2 from true shunt and distri- second, and the lung tissue resistance (Rt), 1.90 ±
bution effects was performed with individual in vivo 02
dissociation curves extrapolated from the two arterial 0.95 cm H20 per L per second, or 54%1o of Rp.
points measured during normal oxygen and hypoxia. Compared with values in a group of healthy persons
The remaining Po2 gradient in hypoxia was considered showing a similar age and sex distribution (Table
136 H. BACHOFEN AND M. SCHERRER

TABLE II
Dynamic compliance of the lung and total pulmonary, airway, and lung tissue resistance in ten patients
with diffuse interstitial pulmonary fibrosis and in 34 healthy subjects*
Resistance
Total Lung
Respiratory . pulmonary Airway tissue Lung tissue Rt - Cdyn (1)
Name rate V Cdyn(l) Rp Ra Rt as % Rp (time-constant)
rpm Llsec ml/cm H20 cm H20/L/sec % Sec
1. C.E. 21 0.70 58 3.61 2.15 1.46 40 0.085
2. S.A. 21 0.40 37 4.15 2.16 1.99 48 0.073
3. B.G. 25 0.65 90 2.40 1.51 0.89 37 0.080
4. H.G. 19 0.51 36 3.06 0.66 2.40 78 0.086
5. Z.R. 30 0.69 18 7.23 3.27 3.96 55 0.071
6. R.D. 18 0.41 50 3.64 1.84 1.80 50 0.090
7. L.R. 23 0.67 66 2.71 1.31 1.40 52 0.092
8. M.M. 26 0.55 37 4.54 1.71 2.83 62 0.105
9. R.W. 35 0.84 61 1.89 0.81 1.08 57 0.066
10. G.J. 30 0.70 56 2.10 0.87 1.23 59 0.069
Mean 24.8 0.61 50.9 3.53 1.63 1.90 54 0.097
±20.0t ±t1.56 i0.79 ±40.95
Healthy subjects
5 children
(mean age 10 years) 0.64 83 3.57 2.26 1.31 37 0.108
i10.2 t 0.98 ±0.73 ±0.37
7 females
(mean age, 25 years) 0.64 160 1.96 1.46 0.50 26 0.080
±50 ±t0.45 ±0.47 ±0.15
12 males
(mean age, 32 years) 0.65 260 1.25 0.96 0.29 23 0.076
±60 ±t0.28 ±t0.27 ±0.12
10 elderly persons
(4 females, 6 males; 0.60 226 1.62 1.20 0.42 26 0.096
mean age, 52 years) ±91 ±0.47 ±0.38 ±:0.14

*V = mean flow rate; Cdyn(l) = dynamic compliance of the lung. Sequence of the patients analogous to Table I.
t Standard deviation.

II), total pulmonary and lung tissue resistances of such a shape be found during spontaneous
were significantly increased (p < 0.001). On the breathing.
other hand, no significant difference of airway The figures characterizing the gas exchange are
resistance (p > 0.05) between patients with lung plotted in Table III. The A-aDo2 in hypoxia was
fibrosis and normal persons was found. Consider- clearly above the normal limits. The alveolar-end
ing these results, the increase of total pulmonary capillary Po2 gradient in hypoxia amounted to
resistance in lung fibrosis is mainly due to the 13.3 ± 9.2 mm Hg, significantly higher (p < 0.02)
marked increase of lung tissue resistance. In Fig- than that determined in healthy 70-year-old men
ure 1 the volume-pressure relationship of a healthy [1.6 ± 1.3 mm Hg (28)].
adult, of a child (11 years old), and of a patient
with interstitial lung disease (HG, Table I) is Discussion
plotted. The ratio of the dotted area (correspond-
ing with the work done against lung tissue resist- In ten patients with diffuse interstitial pulmo-
ance) to the whole area of the volume-pressure nary fibrosis the lung tissue resistance varied be-
loop is much larger in patients with lung fibrosis tween 0.89 and 3.96 cm H2O per L per second
than in the healthy subjects. Furthermore, the (mean value, 1.90 + 0.95); on an average it was
horn-like configuration of the volume-pressure loop even higher than the airway resistance. However,
is a typical finding in lung fibrosis; neither in although a major part of total pulmonary resist-
healthy adults nor in children with a vital capacity ance, the lung tissue resistance is of minor impor-
of the same order as that measured in patients with tance in the total (viscous and elastic) work of
lung fibrosis could a pressure-volume relationship breathing.
 LUNG TISSUE RESISTANCE IN PULMONARY FIBROSIS 137
TABLE III
Ventilation, arterial blood gases, alveolar-arterial Po2 differences, and alveolar-end capillary Po2 difference
during hypoxia in ten patients with diffuse interstitial pulmonary fibrosis
Arterial oxygen Arterial Alveolar-arterial P02 difference
saturation carbon
dioxide Normal Alveolar-end
Minute Respi- At At tension oxygen Hypoxia Hyperoxia capillary Pos
venti- ratory normal hypoxia (at normal (Fio2 = (Fio2 = (F02 = difference
Name lation rate oxygen (FIO2 =0.154)* oxygen) 0.21) 0.154) 0.95) (hypoxia)
L/min rpm % % mm Hg mm Hg mm Hg mm Hg mm Hg
1. C.E. 17.2 22 93.1 89.4 24.5 21 24 46 21
2. S.A. 11.7 28 91.6 87.6 29.4 11 13 24 9
3. B.G. 7.4 15 94.6 87.2 46.9 2 2 26 it
4. H.G. 13.7 18 90.8 54.5 38.6 46 34 11 29
5. Z.R. 10.2 25 91.9 84.5 40.5 27 15 37 11
6. R.D. 13.2 16 86.2 76.4 48.4 19 17 -16 13
7. L.R. 8.7 15 95.8 80.5 37.5 31 18 33 14
8. M.M. 6.8 28 90.5 79.6 39.9 36 17 55 6
9. R.W. 13.3 28 69.2 42.8 43.6 52 41 357 25
10. G.J. 12.6 19 94.9 89.8 31.9 21 13 44 4
Mean 11.5 21.4 89.9 77.2 38.1 27 19.4 61.7 13.3
SD ±15 4±11.2 4105.7 ±9.2
*
F102 = fractional concentration of 02 in inspired air.
t In this patient no disturbance of the pulmonary gas exchange could be detected at rest, but a marked arterial
normocapnic hypoxemia was present at exercise (02 saturation, 84.2%).

Studying panting subjects with lung fibrosis, the original method developed by DuBois, Botelho,
Marshall and DuBois (10) found the values of and Comroe (29), i.e., our high values of lung
lung tissue resistance to be much lower (0.32, tissue resistance are hardly ascribable to incorrect
0.42, and 0.83 cm H20 per L per second) than our measurements of airway resistance. Furthermore,
results. The question may arise whether this dis- it would seem unlikely that the reason for this con-
crepancy has to be attributed to a methodological siderable difference is due only to the individual
error involved in the plethysmographic technique variations of lung tissue resistance in the patients
used. We measured airway resistances with the examined. More probably, the discrepancy is re-
volume displacement plethysmograph of Mead lated to the different breathing patterns. To con-
(16), ingeniously modified by Jaeger and Otis firm this hypothesis, we made repeated parallel
(15) so that one can determine the airway re- measurements on three patients during spontane-
sistance at any breathing pattern. Considering the ous breathing and during panting. The results
theoretical basis (15) and the results of the ex- are given in Table IV. In all cases much higher
tensive preliminary studies (15, 19), there seems values of lung tissue resistance were obtained dur-
to be no reason to assume that this new technique ing spontaneous breathing, whereas there was only
gives less accurate values of alveolar pressure than a slight change in airway resistance. The explana-

TABLE IV
Influence of the breathing pattern on the lung tissue resistance in three patients
with diffuse interstitial pulmonary fibrosis*
Spontaneous breathing Panting
Name FRC f V Cdyn (l) Rp Ra Rt FRC f V Cdyn (l) Rp Ra Rt
ml rpm L/sec mi/cm cm s20L/sec ml rpm L/sec mi/cm cm H20/LIsec
H20 H20
6. R.D.t 1,900 15 0.5 63 3.09 1.37 1.72 2,100 90 0.9 2.33 1.68 0.65
7. L.R. 2,100 23 0.67 66 2.71 1.31 1.40 2,100 100 0.75 2.10 1.24 0.86
Z.RU.4 3,000 21 0.57 101 1.69 1.02 0.67 3,100 86 0.68 1.12 0.85 0.27
* Same symbols as in Table I1; also FRC = functional residual capacity, and f = respiratory rate.
t These results were obtained by a re-examination about 3 months after the first measurements shown in Tables
I-III (after corticosteroid treatment).
t Z.RU. was not listed in Tables I-III.
138 H. BACHOFEN AND M. SCHERRER

tion of this phenomenon can only be a hypothetical 6- Vital Capacity

(Liters)
one. On the one hand, it is possible that, by the
procedure of panting, only those parts of the 5-
fibrotic lung with a low tissue resistance, probably
identical with the most compliant parts, are venti-
lated. On the other hand, keeping in mind the 4-
phenomenon of static hysteresis shown by Mead,
Whittenberger, and Radford (30) to be dependent
on the size of volume change, similar factors may be 3- \o o

involved in decreasing lung tissue resistance when *% 0 0

subjects pant or breathe with small tidal volumes. 2-

%, 0 °
It might be possible that with increased stretching 0
0
of the compliant elements the viscous tissue resist-
0
ance increases, i.e., that the lung tissue resistance 1-
is also a function of the degree of elongation of the
Lung Tissue
compliant elements. This hypothesis would agree Resistance (cm H20/l/sec)
with the observation that in persons having small 1
I
2
|
3 4
I
5 6
lung volumes (females, children), higher tissue
resistances were found than in subjects with large FIG. 3. RELATIONSHIP BETWEEN THE VITAL CAPACITY
AND THE LUNG TISSUE RESISTANCE IN HEALTHY SUBJECTS
lung volumes (males), although the tidal volumes AND IN PATIENTS WITH LUNG FIBROSIS. The lung tissue
in all three groups were of the same order. resistance increases with decreasing vital capacity. 0, pa-
Reduced lung volumes and a decreased compli- tients with lung fibrosis. e, mean value of 18 healthy
ance on the one side and a much increased lung males; ?, of 11 females; and (3, of 5 normal children.
tissue resistance on the other are the typical altera-
tions of lung mechanics in our cases of advanced of Rt and Cdyn(l) [i.e., the time constant (10)]
interstitial lung disease; a close interrelationship being of the same order in all cases, points out a
between the two former and the latter figures seems reciprocity between Rt and Cdyn(l). By a graph-
to exist. The result given in Table II, the product ical analysis wherein the elastance substituted for
the compliance in order to obtain linearity, a very
Elastance
(cm H20/Liter)
good correlation between elastance and Rt can be
0 shown (Figure 2). Likewise, an inverse non-
linear relationship was found between the lung tis-
sue resistance and the vital capacity, showing an
increase of Rt with decreasing vital capacity.
These observations suggest the interpretation that
the increase of Rt as well as the decrease of
Cdyn (1) is mainly due to the same cause, the
diminution of compliant lung tissue, as mentioned
0
by Marshall and DuBois (10). Moreover, this in-
terpretation is also in good agreement with the ob-
servations made in healthy subjects; by likewise
plotting the mean values of vital capacity and lung
tissue resistance obtained in 18 healthy males, 11
females, and 5 children, we found a vital capacity-
rissue
Rt relationship quite similar to that obtained in
1 2 3 4 5
patients with lung fibrosis (Figure 3). Neverthe-
FIG. 2. RELATIONSHIP BETWEEN THE ELASTANCE AND
less, although we have taken into account the in-
THE LUNG TISSUE RESISTANCE (RT) IN TEN PATIENTS fluence of decreased lung volumes, the lung tissue
WITH LUNG FIBROSIS. The regression line is elastance = - resistance in pulmonary fibrosis appears to be
1.15 + 12.7 Rt; r= 0.95. higher than in healthy subjects with small lung
 LUNG TISSUE RESISTANCE IN PULMONARY FIBROSIS 139
volumes (children). This result becomes apparent 60 Alveolar- Endcapillary
1 Po2- Gradient (mm Hg)
in Figure 3 if the vital capacity-Rt relationship of
patients is compared with that of normal persons;
50-
the lung tissue resistance obtained in children is
significantly lower (p < 0.01) than that in patients
having a vital capacity of the same order (CE, HG, 40-
RD, and MM in Table I). Therefore, the follow-
ing conclusions seem to be justified: The increase
of lung tissue resistance is mainly due to a diminu- 30- 0
tion of compliant lung tissue, but in addition, other 0
factors, such as the pathological alteration of tis- 0
20-
sue viscosity caused by the augmentation of con-
nective tissue and the infiltration of cells, seem to 0 0
have a part in increasing lung tissue resistance in 10- 0
0
diffuse interstitial pulmonary fibrosis. 0
On the assumption that the increase of Rt was 0 Lung Tissue
0o Resistance (cm H20/l/sec)
due to a diminution of normally functioning lung 1 2 3 4 5
tissue, an augmentation of interstitial tissue, and FIG. 4. LUNG TISSUE RESISTANCES AND ALVEOLAR-END
thickening of the alveolar membranes, one would CAPILLARY Po2 DIFFERENCES DURING HYPOXIA IN TEN PA-
expect a relationship between the lung tissue re- TIENTS WITH DIFFUSE INTERSTITIAL PULMONARY FIBROSIS.
sistance and the impairment of 02 diffusion (due No close correlation was found between these two figures.
to the decrease of the capillary blood volume and to Stippled area = normal subjects.
the membrane thickening). By a statistical com-
parison, however, no correlation was found be- siderable pulmonary hypertension, which would
tween Rt and the alveolar-end capillary Po2 be present in cases with a marked decrease of
gradient in hypoxia nor between other figures char- capillary volume. Therefore, based upon the re-
acterizing the disturbances of pulmonary gas ex- sults of Figure 4 and provided that the alveolar-
change. With regard to the parallel variations of end capillary Po2 gradient in hypoxia reflects es-
Rt and the elastance shown in Figure 2, our re- sentially the membrane component limiting the 02
sults are in accord with previous studies in which diffusion, the hypothesis suggested by West and
no close correlation, either between the compliance Alexander (2) seems to be reasonable, namely,
of the lung and the arterial desaturation (2) or that the pathological changes influencing the me-
between the compliance and the diffusing capacity chanical properties and the pulmonary gas ex-
measured by the single breath CO method, could change may act at different planes, i.e., the thick-
be obtained (31). On the one hand, we have ening of the blood-gas barrier may be independent
shown patients (ZR, MM in Tables II and III) of the increase and thickening of the fibrous frame-
with most severe disturbances of the mechanical work responsible for the stiffening of the lung.
properties of the lung accompanied by an only
slightly increased end capillary gradient; on the References
other hand, moderate mechanical disorders may be
combined with a severe impairment of diffusion 1. Austrian, R., J. H. McClement, A. D. Renzetti, Jr.,
(CE), as can be seen in Figure 4. Although it is K. W. Donald, R. L. Riley, and A. Cournand.
possible that the end gradient may be due in part Clinical and physiologic features of some types of
pulmonary disease with impairment of alveolo-capil-
to a decrease of capillary volume, the membrane lary diffusion. The syndrome of "alveolar-capil-
thickening appears to be a more important factor, lary block." Amer. J. Med. 1951, 11, 667.
for, in our experiments, the influences of the pos- 2. West, J. R., and J. K. Alexander. Studies on respira-
sibly altered circulatory dynamics are probably of tory mechanics and the work of breathing in pulmo-
little importance considering the methodological nary fibrosis. Amer. J. Med. 1959, 27, 529.
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