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Although the airway conductance1 increases at were studied in patients who had emphysema or
larger lung volumes in normal subjects (1), it bronchitis of toxic etiology.
is reduced in patients with asthma or emphysema
who are breathing with a large functional residual METHODS
capacity (FRC) (2). We have therefore tried to Airway resistance and thoracic gas volume were meas-
assess the influence of other factors which might ured during panting2 using an upright body plethysmo-
affect the airway conductance in both normal sub- graph (2). The methods hinge on Boyle's law for com-
jects and in patients with asthma, bronchitis and pression of gases. Volume change owing to compres-
emphysema. These include the interrelationship sion of gas inside the thorax is measured by -the equal
and opposite small displacement of gas around the body.
of lung volume, lung elastic pressure and airway After appropriate calibrations, the intrathoracic gas vol-
conductance, the effect of exercise, forced breath- ume changes found when rebreathing the air of the
ing and normal aging, and the composition of the chamber through a heated flowmeter are converted
respired gas and bronchomotor drugs. We in- mathematically to alveolar pressure changes, thence to
vestigated the balance of forces regulating the di- airway resistance and airway conductance; or, when
ameter of the airway lumen, i.e., the tone of the breathing against a closed shutter and manometer, to
thoracic gas volume. In practice, these values are read
airway wall, directed inward, opposed by the directly from a precalibrated scale and protractor on
traction of the lung tissues, directed outward. the face of an oscilloscope, thus reducing labor. Esopha-
We studied whether, in normal subjects, this geal pressure and mouth pressures were measured al-
balance was altered by bronchmotor drugs or by ternately using a capacitance manometer and Brush re-
corder. Lung elastic pressure (3) at each lung volume
a change in lung elastic pressure following chest was measured as mean esophageal pressure, while pant-
strapping, and whether in patients with asthma, ing (4). Chest constriction was accomplished by bind-
the airway conductance/lung volume relationship ing the subj ect's chest or abdomen, in the expiratory
was altered after forced breathing or exercise. position, with adhesive tape or a long strip of rubber
Patterns of disturbance leading to air trapping (4). Other tests of pulmonary function were performed
according to generally accepted methods. All meas-
* Supported in part by a contract between the Uni- urements were made with the subj ect in the sitting
versity of Pennsylvania and the Army Chemical Center position. Lung volumes are expressed at BTPS.
Medical Laboratories.
t Rockefeller Traveling Fellow in Medicine. Present RESULTS ON HEALTHY SUBJECTS
address: Department of Medicine, University of Man-
chester, Manchester, England. Spontaneous variation of airway resistance with
tFellow of the Doherty Charitable Foundation, New time. The airway resistance of six healthy sub-
York, N. Y. Present address: Clinica de la Concepcion, jects was studied at 20 minute intervals over a
Madrid, Spain. 2 hour period. Measurements were made during
§ Established Investigator of the American Heart
Association. 2 The larynx was maintained wide open while panting
1 Airway conductance, the reciprocal of airway re- at different lung volumes as was seen in two normal
sistance, is defined as the rate of airflow at the mouth subjects who were investigated by indirect laryngoscopy.
for unit pressure difference between alveolus and mouth. 3 Lung elastic pressure is equivalent to static intra-
It was measured over the range of 0 to 0.5 L per second pleural pressure and represents the pressure derived from
of inspiratory airflow. the elastic properties of the lung.
584
PHYSIOLOGICAL FACTORS AFFECTING AIRWAY RESISTANCE 585
NORMAL SUBJECTS
AIRWAY
RESISTANCE
2
(CM WATER
L/AEC Y-
.\*
. . . .
O 1 2 3 4 5 6 10 5 + 0-5 10 15 20 25
THORACIC VOLUME ESOPHAGEAL PRESSURE
(L) (CM WATER)
0 20 40 60 80 too 120 FIG. 2. RELATIONSHIP OF AIRWAY CONDUCTANCE TO
TIME (MIN) THORACIC GAS VOLUME AND ESOPHAGEAL PRESSURE.
FIG. 1. VARIATION OF AIRWAY RESISTANCE WITH TIME.
similar to that of younger people. These sub-
panting at about the FRC. The mean value at jects had a reduction of maximal breathing ca-
each sitting was calculated from five consecutive pacity, similar to that found by others, and of
readings. The airway resistance changed but maximal flow rates. Reduction in the maximum
little during the two hours (Figure 1). pressure generated by the respiratory muscles and
Values for airway resistance in old age. Air- increased lung tissue resistance probably con-
way resistance measured in ten healthy colored tributed to the diminution of maximal flow rates.
subjects, ranging in age from 75 to 90 years, was Values are listed in Table I.
BLE I
Mechanics of breathing in ten normal subjects 75 to 90 years of age *
vals during an exposure of 5 to 6 hours' duration airway conductance was measured at different
(Table II). Four to 10 per cent carbon dioxide lung volumes in healthy subjects, in symptomatic
administered in the respired air over periods of and asymptomatic asthmatic patients, and in pa-
time lasting up to 10 minutes gave variable results, tients with emphysema. Airway conductance was
but there was no change in the average airway plotted against lung volume and the curve of best
resistance of the group (Table II). fit was drawn by inspection. From the curve,
the volume at which airway conductance appeared
RESULTS ON PATIENTS
to approach zero (1) and the airway conductance
The relationship between airway conductance at the FRC were read. The average slope of the
and lung volume in asthma and emphysema. The curve of airway conductance versus volume was
TABLE III
Characteristic alterations in the interrelation of airway conductance and lung volume in patients with asthma
and emphysema, and values (in parentheses) following isoproterenol aerosol, 1 :200 solution *
Lung gas volume
Airway conduc- Conduct. change at zero con-
Subjects tance at FRC FRC + volume change ductance
CONDUCTANCE
AGAI NST
CONDUCTANCE
AGAINST
in the patients with emphysema, the FRC (5)
VOLUME P. ESOPH. was increased and the airway conductance, meas-
I I AT06ImII5 I I
Industrial
Youth bronchitist Old age
Age 32 43 82
Maximal breathing capacity 150 (8) 84 (9) 38 (5)
Maximal expiratory flow rate 476 (19) 213 (36) 132 (25)
Maximal inspiratory flow rate 390 (40) 226 (18) 135 (25)
Airway resistance and % change after bronchodilator 1.37 (0.26) 2.94 (0.25) 1.30 (0.21)
-29% -44%
* Mean values, and standard error (in parentheses).
t Eleven patients were studied. Of these, 6 had accidentally inhaled toxic vapors, and 5 had undergone lengthy
industrial exposure to particulate matter (carbon, silica, and iron particles). Other findings in these patients were in-
creased residual volume, uneven ventilation, slight hypoxemia, and gas trapping.
conductance was plotted against esophageal pres- forced expiration the airways may be widely di-
sure. Figure 6 shows the effect of bronchodilator lated owing to lung elastic pressure; during forced
drugs in the normal and in the asthmatic state. expiration they tend to collapse from positive in-
Airway resistance and other tests of pulmonary trapleural pressure. We concluded that changes
function in patients with chronic bronchitis. We in the state of the airways, while adequately re-
studied several patients who had been exposed flected in measurements of airway resistance, were
to chemical vapors or particulate matter in the sometimes obscured or erroneously interpreted
inspired air and who subsequently developed clini- when forced voluntary ventilation was being used.
cal evidence of chronic bronchitis (Table V).
These patients had no prior history suggestive of DISCUSSION
asthma or emphysema. The airway resistance
was elevated in most. However, there was an The airway conductance, measured in the body
appreciable response to bronchodilator drugs. plethysmograph by relating alveolar pressure to
Values for airflow obtained from tests of forced airflow at the mouth, presumably depends upon
voluntary ventilation, although depressed, were the patency, number and length of the conducting
not so low as is usual in fully developed emphy- airways. It remained relatively constant over
sema. By contrast, normal elderly people had im- several hours in normal subjects. Others have
pairment of forced voluntary ventilation but nor- shown that the airway conductance increased at
mal airway resistance. larger lung volumes (1); the present results in-
An acute exposure of normal subjects to carba- dicate that it varies directly with lung elastic
chol aerosol or inert particles dispersed in the in- pressures and that its relationship to lung volume
spired air had resulted in an elevation of airway is determined by the pressure-volume behavior of
resistance with little or no change in maximal ex- the lung. Thus, at the same lung volume there
piratory flow rate (Table VI). At the onset of was a rise in airway conductance when the lung
elastic pressure was increased following chest
TABLE VI constriction. This was presumably due to an en-
Response of normal subjects to carbachol largement of the airways as a result of the greater
aerosol or inert particles * pull on their walls and not to a relaxation of the
Before After
tone in the walls. There was no evidence that the
number of patent airways was increased under
Airway resistancet 1.37 (0.26) 2.63 (0.49) these conditions; in fact it was more likely that
Maximal expiratory flow rate 476 (19) 464 (28)
there were fewer, since there was some evidence
*
Mean values, and standard error (in parentheses). of gas trapping (7). This effect of lung elastic
t These airway resistance values were reported previ- pressure on airway conductance had been sug-
ously in this journal (6). Values for maximal expiratory
flow rate reveal that a moderate degree of bronchocon- gested before (8-11) but had not been established
striction may be overlooked unless suitable methods are experimentally.
used for its measurement.
590 BUTLER, CARO, ALCALA AND DuBOIS
Atropine subcutaneously, and isoproterenol by were found in certain cases of bronchitis of toxic
aerosol, increased airway conductance in normal etiology. Maximum flow rates were not so re-
subjects in the absence of any alteration in lung duced as in emphysema. By contrast, in healthy
elastic pressure. This suggested that these drugs, old age there was a reduction in the maximum flow
by their action in reducing active (tonic) effects rates which was not associated with any increase
in the airway wall, had allowed a greater distention in airway resistance. It appeared to be due to a
of the airway from the passive (mechanical) ef- reduction in the power of the respiratory muscles,
fects of the existing lung elastic pressure. How- the maximum pressure generated at the mouth be-
ever, mucosal shrinkage as well as decrease of ing reduced in most subjects. There was an in-
tone may be concerned in this rise of airway con- crease in the lung tissue resistance of some of
ductance and our studies do not distinguish be- these older subjects. Our results may be com-
tween them. Breathing oxygen, carbon dioxide pared with and extend those of other workers
or water aerosol produced no significant change (12, 13).
in the airway conductance. We have isolated and described some of the
When the airway conductance was reduced by factors that affect the balance which we believe to
disease (asthma, bronchitis, emphysema) there exist between the tension of the airway wall and
was less than the normal change in airway con- the transmural pressure gradient imposed by the
ductance from alterations of lung elastic pressure. elastic pull of the lung. However, assuming some
The distensibility of the airways appeared to be degree of regulation of airway patency, we have
decreased. Furthermore, both the lung elastic shown little about the control system. Among
pressure and the lung volume at which the airway other factors still to be explored are the effects of
conductance approached zero, obtained by extra- diminished oxygen and CO2 tension, altered pH,
polation, were increased in these patients. This lesions of the nervous system, and psychogenic
suggested that gas trapping occurred at greater and endocrine factors. Our methods appear to be
than normal transpulmonary pressures and lung satisfactory for this type of observation in man.
volumes.
Bronchodilator drugs produced striking re- SUMMARY
sults in asthma, a greater-than-expected response
in bronchitis of toxic etiology, and some response The effects on airway conductance (the recipro-
in emphysema. The relationship of airway con- cal of airway resistance) of chest strapping, bron-
ductance to both esophageal pressure and lung chomotor drugs, exercise, forced breathing, oxy-
volume was altered toward normal by these drugs. gen, carbon dioxide, and old age, were measured
They appeared to improve airway distensibility in normal subjects and compared with similar ob-
and to reduce the lung volume at which the air- servations in patients with asthma, bronchitis and
way conductance approached zero. However, it emphysema. Airway conductance was found to
is often impossible to distinguish between asthma be dependent upon lung elastic pressure rather
and emphysema by a therapeutic test with these than on lung volume. This relationship was al-
drugs, since both may respond or be refractory to tered by bronchomotor drugs. Breathing oxygen
isoproterenol. and different concentrations of carbon dioxide did
We found that forced breathing or exercise in not alter the airway resistance. In several pa-
asthmatic patients may decrease the airway con- tients with mild asthma, airway resistance in-
ductance while tending to increase the FRC. This creased after forced breathing or exercise. In
has been suspected clinically but experimental normal subjects, airway conductance appeared to
confirmation was lacking. The mechanism of this depend upon a balance of forces between the ten-
response is unknown, but it is presumably de- sion in the airway walls and the opposing trans-
pendent upon changes in the airway wall, the lung mural pressure gradient due to the elastic trac-
elastic pressure at different volumes being un- tion of the lung. The airway conductance was
changed or increased. found to be reduced and the balance of forces was
Unsuspected degrees of airway obstruction, un- altered in patients who had lower airway ob-
even ventilation, and arterial oxygen desaturation struction.
PHYSIOLOGICAL FACTORS AFFECTING AIRWAY RESISTANCE 591
ACKNOWLEDGMENTS volume: A comparison with a nitrogen washout
method for measuring functional residual capacity
The authors are grateful to Dr. Julius H. Comroe, Jr., in normal subjects. J. clin. Invest. 1956, 35, 322.
for helpful advice. We acknowledge the collaboration 6. DuBois, A. B., and Dautrebande, L. Acute effects
of Comdr. Robert L. Burdick, MC, USN, of the Air Crew of breathing inert dust particles and of carbachol
Equipment Laboratory, Philadelphia, in the evaluation aerosol on the mechanical characteristics of the
of the effects of breathing oxygen, and of Drs. W. A. lungs in man. Changes in response after inhaling
Briscoe and J. Zabara in other parts of this work. We sympathomimetic aerosols. J. clin. Invest. 1958,
appreciate the cooperation of the ten older normal sub- 37, 1746.
jects and the officers of the Stephen Smith Home for 7. Caro, C. G. Lung compliance, hysteresis and clos-
the Aged. ure of lung units in man. Fed. Proc. 1959, 18, 23.
8. Fry, D. L., Ebert, R. V., Stead, W. W., and Brown,
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