Cigarette SmokeIts Effect on Pulmonary Function Measurements

HURLEY L. MOTLEY, M.D., and WILLIAM J. KUZMAN, M.D., Los Angeles

THE RELATIONSHIP of chronic pulmonary disease,such as emphysema, and smoking is of particularinterest in the Cardio-Respiratory Laboratory ofthe University of Southern California School ofMedicine. A very high incidence of cigarette smok-ing has been noted commonly in the history of pa-tients with severe emphysema when there was noapparent cause for the emphysema, such as a his-tory of exposure to silica, asbestos, diatomaceousearth or other known irritating dusts, or a historyof having had tuberculosis, asthma or some otherchronic pulmonary disease.Some physicians have arbitrarily ordered patients

to stop smoking as part of the management ofpulmonary emphysema. On the other hand, otherphysicians do not even advise patients with emphy-sema to stop smoking.The Cardio-Respiratory Laboratory is frequently

asked for an opinion as to whether or not a patientshould stop smoking, and if so, what is the objec-tive evidence. If pulmonary function measurementswere to show definite and significant changes im-pairing lung function as the result of smoking, thenit would be much easier to convince patients withemphysema that they should give up smoking.

Pulmonary emphysema may be the result of sev-eral factors and the evaluation of the importanceof each one may be quite difficult. The present studywas set up to explore the practical tests of pulmo-nary function which might be used to assess acutechanges which could be induced by smoking one ortwo cigarettes, and thus permitting each subjectto serve as his own control. The subjects studiedwere all smokers and the group included personswithout disease and patients with chronic pulmonarydisease of varying degrees of severity, especiallypulmonary emphysema and pulmonary fibrosis. Thesubjects were advised to abstain from smoking fromfour to six hours before the tests of function wereto be done, and in a few cases for as long as twenty-four hours. A longer time interval without smokingwould be desirable; and it would also be helpful to

From the Cardio-Respiratory Laboratory, University of SouthernCalifornia School of Medicine, Los Angeles.

Supported by a research grant from Tobacco Industry ResearchCommsttee, 150 East Forty-Second Street, New York 17, N. Y.

Presented before the Section on Allergy at the 86th Annual Sessionof the California Medical Association, Los Angeles, April 28 to May1, 1957.

* Inhaling cigarette smoke with each breath,with the subject at rest, by use of a smoking de-vice that brought more smoke into the lungsthan would be the case in ordinary smoking,produced consistent significant decreases in ar-terial blood oxygen saturation and in arterialPO2 in most subjects who had severe or verysevere pulmonary emphysema. In normal sub-jects and in those with a moderate degree ofemphysema no significant changes in blood gasexchange resulted.No consistent significant changes in blood gas

exchange were noted after the smoking of twocigarettes, either with the subject at rest or aftera one-minute step-up exercise.A decrease in oxygen uptake occurred when

treadmill exercise was done after smoking twocigarettes, and the ventilation volume was alsodecreased, probably accounting for part of theoxygen decrease.

Pulmonary compliance measurements aftersmoking one cigarette were consistently and sig-nificantly decreased in most subjects-normal aswell as those with pulmonary emphysema. Theelastic work of breathing was increased in themajority of cases.

In two cases in which studies were done afterthe subjects stopped smoking, one for threemonths and one for two years, significant reduc-tions in residual air were noted.The results indicated that persons with severe

or very severe emphysema would be better offto stop smoking.

obtain studies before and during the period of ab-stinence, and after resuming smoking. However,obtaining volunteers for such restrictions would bedifficult. In two cases, follow-up studies were ob-tained after longer time intervals, as the patientsdecided to stop smoking; and as far as could bedetermined, no medication had been taken duringthis time which might be a factor in altering thepulmonary function measurements.

METHODS

All the subjects-125 men and 16 women-were fasting and in an essentially basal state at thetime of the studies. The ages ranged from 24 to 70years. Each of the subjects had a complete pulmo-nary function evaluation including lung volume de-

VOL. 88, NO. 3 * MARCH 1958 I211

terminations and blood gas exchange measurementswhile at rest and after exercise (except for threesubjects who had heart disease and one normalsubject) .

Spirogram recordings on the 13.5 liter respirom-eter were made to determine the total vital capacity,the timed vital capacity for three seconds and themaximal breathing capacity, before and after ad-ministration of a bronchodilator drug.12 Residualair was measured by the oxygen open circuit methodand the helium closed circuit method.13 The residualmeasurements were made with the subject supine ina fasting and resting state. The alveolar nitrogensample was taken just above the mouthpiece afterseven minutes of oxygen breathing. In a few cases,the nitrogen curve was obtained after a single deepbreath of oxygen, using the nitrogen meter. Thenitrogen wash-out was also obtained in a few ofthese subjects with the nitrogen meter with con-tinuous recordings. All lung volume measurementswere expressed at body temperature, pressure satu-rated (BTPS).

Arterial blood samples were obtained through anindwelling needle from the brachial artery, at restand immediately after exercise. Oxygen content andcapacity and carbon dioxide content determinationswere made in duplicate by two trained techniciansusing different manometric Van Slyke analyzers andwere repeated unless the results were close together.The arterial blood oxygen saturation (as per cent)was also determined on the Water's oximeter, doublescale cuvette with the use of whole blood. The cu-vette was calibrated daily against the Van Slykeanalyzers, and in this laboratory it has been foundvery satisfactory, the results consistently stayingwithin one per cent of the Van Slyke measurementswhen properly calibrated. The pH was measured ona Cambridge glass electrode. The arterial partialpressure oxygen (pO2) and partial pressure carbondioxide (pCO2) were determined by the direct bub-ble tension met-hod described by Riley.15Oxygen uptake and carbon dioxide output were

calculated from the percentage of oxygen and car-bon dioxide in the expired air, as determined in aScholander gas analyzer. The step-up exercise con-sisted of stepping up and down on a stool, 20 cm.high, 30 times in one minute; and the treadmillexercise was walking, level, at a rate of two milesper hour. The minute ventilation volume was meas-ured during the basal rest period and during theone minute of step-up exercise, or during the sam-pling period on the treadmill after five minutes ormore of walking. The minute ventilation and theoxygen uptake were expressed at standard tempera-ture and pressure as liters per minute, or millilitersper minute per square meter of body surface area(ml./min./M2, BSA). The alveolar P02 was calcu-

lated from the values obtained for arterial pO2, thearterial pCO2 and the respiratory quotient. The ef-fective tidal air was calculated from the expiredpCO2 and the arterial pCO2 using the average tidalvolume. Hemoglobin was determined both by theoxygen capacity method and by converting all thehemoglobin to cyanmethemoglobin8 and measuringlight absorption at 540 mu. on the Beckman DUspectrophotometer.Measurements of pulmonary compliance were de-

termined by the continuous cycling method withmodifications.9 The recording device consisted of a6-liter Benedict-Roth metabolism apparatus equippedwith a helipot for volume changes. A blower wasprovided in the circuit to circulate the air, and allvalves were removed to reduce breathing resistance.Oxygen was added to the system and the CO2 wasabsorbed. Volume and pressure changes were re-corded on a DuMont cathode ray oscilloscopethrough a compliance control apparatus employinga capacity transducer in a radio frequency circuit.The loop was interrupted by means of a blankinggenerator which allowed time measurements of 5,10, 15 and 20 cycles per second intervals. In addi-tion, the points at which there was no flow were de-termined by a flow-sensitive zero pressure devicewhich produced blips on the oscilloscope at the endof expiration and inspiration. A balloon as de-scribed by Crane7 was used to measure the intra-esophageal pressure at its mid-position. The loopwas then photographed with a polaroid Land cam-era. The patients were studied in the sitting positionduring spontaneous quiet breathing before and im.mediately after smoking one cigarette.

PROCEDURE AND SUBJECT MATERIAL

Studies were obtained on nine patients, all excepttwo with severe pulmonary emphysema, in the su-pine position after smoking two cigarettes' Theamount of smoke inhaled varied widely betweendifferent subjects during the smoking of two ciga-rettes; some inhaled deeply, others hardly at all.

It was felt that the acute effects of cigarette smokeon the lung could be intensified by the use of asmoking device so that with each breath some smokewould be inhaled in the lung with the respiratorygases. The subject was connected by a mouthpieceto a two-way directional valve which was connectedon the intake side to a Douglas bag containing airon one side of a "Y" tube and on the other- sidecontaining a cigarette holder with a lighted ciga-rette. By the use of a three-way valve attached to theDouglas bag, the resistance could be varied so thata small amount of air with each breath was directedthrough the cigarette, with a resulting glow during

2CALIFORNIA MEDICINE212

inspiration. The expired air was collected in a Tis-sot gasometer and the smoke was quite visible inthe expired air from the subject.

In some subjects the inhaled smoke produced asensation of burning, particularly on the posteriorpharynx, and in a few it caused cough. Other sub-jects, most commonly heavy smokers with a historyof smoking for many years, said that they were notaware that they were even getting smoke with thedevice. The use of the smoking device in the closedcircuit insured that the smoke was distributed inthe lung, so that the effect of smoke on the lungwith respect to blood gas exchange could be studied.In all instances, the patients were allowed to smokethe cigarette of choice if they had their own. Therate of smoking was set so that usually it took aboutthree to five minutes to completely smoke one ciga-rette, and in most instances at least 90 per cent of thecigarette was smoked. Fifty subjects were studiedduring the smoking of one cigarette, and these sub-jects were divided into three groups according to theseverity of the pulmonary emphysema present. Therewere 23 cases in which the emphysema was insignifi-cant, eight in which there was a moderate degree ofemphysema and 19 in which it was severe or verysevere (residual air greater than 45 per cent of totallung capacity).Pulmonary compliance measurements were ob-

tained on 41 subjects. In these subjects the residualper cent of total lung capacity had been determined(with the exception of three subjects who had car-diac disease and one who was normal). The vitalcapacity was determined in most of the subjects be-fore and after smoking, utilizing the usual volumerecording apparatus, but with the subjects in thesitting position. Compliance and the elastic work ofbreathing were the two specific measurements ob-tained at this study, and these data were correlatedwith the severity of the emphysema as measured bythe residual per cent of total lung capacity, the ven-tilation factor, the resting arterial pO2 and the vitalcapacity, before and after smoking.A group of fifty subjects had blood gas exchange

measurements made before and after smoking, usingthe one minute step-up exercise test. This group offifty subjects was divided into three classes, depend-ing on the severity of the emphysema. There were19 with an insignificant degree of emphysema, 16with a moderate degree of emphysema and 15 witha severe or very severe degree of pulmonary em-physema. The second exercise test was performedimmediately after smoking two cigarettes and themeasurements were compared to those of the firsttest. In 21 cases, treadmill exercise was used insteadof step-up exercise, and the blood gas exchangemeasurements before and after smoking two ciga-rettes were compared.

EFFECT SMOKI N CIGARETTE O RTEiAL BLOO.DHU70C H802 0P02 pC022

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Chart 1.-Correlation of the residual per cent of totallung capacity with the change during the smoking of onecigarette with the smoking device, at rest, on: (1) Ar-terial blood oxygen saturation (HbO2 saturation, per cent,(2) arterial pO2, and (3) pCO2 in mm. Hg., both by directtension measurement. TLC (total lung capacity), HbO2per cent (arterial oxygen saturation, per cent), PO2 (par-tial pressure oxygen), pCO2 (partial pressure carbondioxide). Measurements on 50 cases.

RESULTS

Blood gas studies in the supine position beforeand after smoking two cigarettes were obtained innine subjects, seven of whom had severe emphy-sema. There was no significant average differenceafter smoking in the group, as shown by the arterialblood or the pulmonary ventilation measurements.*There was a slight increase in the pulse rate, but nosignificant change in the respiratory rate. In onesubject at rest there was a significant decrease(-6.5 per cent) in the arterial blood oxygen satu-ration after smoking. This subject had a very severedegree of emphysema, and following the smokingthe pulse rate, respiration rate and minute ventila-tion were significantly increased, but the arterialpO° was decreased from 73.5 to 56.1 mm. of mer-cury.The smoking device with the closed circuit was

next used in the supine position to insure that thesmoke from the cigarette got into the lung. The datausing the smoking device were compared in sum-mary form by three groups based on the severity ofthe emphysema. There was no significant change inthe arterial blood oxygen saturations before andafter smoking either in the nonemphysema group orin the group with a moderate degree of emphysema.However, in the severe emphysema group there wasan average decrease in the arterial blood oxygensaturation from 90.7 per cent at rest to 88.6 per centafter smoking. The changes in the arterial bloodsaturation before and after smoking have beenplotted for each case on a basis of the severity of the

More detailed data in tabular form will be published in the reprintof this paper.

VOL. 88, NO. 3 * MARCH 1958 213

emphysema as measured by the residual per centof total lung capacity (Chart 1). It can be notedthat none of the subjects with a residual per centof total lung capacity below 45 per cent had signifi-cant change. In some the saturation was increased alittle and in others it was decreased. However, inthis group of 19 subjects with severe or very severepulmonary emphysema there was definitely a de-crease in the saturation after smoking, a decreaseoccurring in 14 and an increase in four, with nochange in one. The standard deviation for the 19subjects was ±1.96 per cent with a standard errorof 0.45 per cent. In a similar manner, the arterialpO2, as determined by direct tension measurement,was correlated with the severity of the pulmonaryemphysema (Chart 1), and a consistent decreasewas present only in subjects with a residual ratiogreater than 45 per cent of total lung capacity (de-creased in all except four). The standard deviationof the arterial P°2 was +7.6 mm. of mercury witha standard error of 1.7 mm. of mercury. When thearterial pC02 was correlated with the residual percent of total lung capacity, it was noted that in theemphysema group in all except four cases there wasan increase after smoking. The standard deviationof the arterial pC02 was +2.0 mm. of mercurywith a standard error of 0.9 mm. There was no sig-nificant change in the arterial C02 content or pHafter smoking with the smoking device. Also thealveolar-arterial P02 difference was not significantlychanged after smoking. The mean alveolar pO2 wascalculated from the arterial pC02, the arterial PO2and the respiratory quotient. There was no signifi-cant change in the tidal volume or the effectivetidal air with smoking, or in the oxygen uptake,the C02 output or the per cent of oxygen extractedfrom the inspired air breathed, using the smokingdevice.The blood gas measurements with step-up exer-

cises before and after smoking two cigarettes werestudied in 50 cases. The changes, after smoking, inthe arterial blood oxygen saturation, in the C02content in volumes per cent and in the minute ven-tilation (in liters per minute per square meter ofbody surface area) are correlated with the residualper cent of total lung capacity in Chart 2. The sub-jects smoked two cigarettes while in the sitting posi-tion following the first step-up exercise. A few hadreactions, possibly related to the fasting state. Thesereactions consisted of feeling dizzy or weak, and afew subjects had headache, sweating and tachy-cardia. If the subject had a reaction following thesmoking, a rest period of a few minutes was givenand then the second exercise was started. In prac-tically all cases, the subjects felt better after theexercise. A few of the subjects complained that thecigarette did not taste good. In none of the three

CHANGE AFTER SMOKING WITH STEP-UP EXERCISE65- ART CO02SAT9 C°2 CONT VL.% VENT. L./MIN" M.

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Chart 2.-Correlation of the residual per cent of totallung capacity with the change after smoking two cigarettesin the usual manner on the one minute step-up exercisemeasurements of: (1) Arterial blood oxygen saturation,(2) arterial CO2 content and (3) the volume of pul-monary ventilation (liters per minute per square meter ofbody surface area). Measurements on 50 cases.

CHANGE AFTER SMOKING WITH TREADMILL EXERCISE

ART. H002 SAT. % OXYGEN UPTAKE ML,141N/M VENT. L/MIN/M?

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Chart 3.-Correlation of the residual per cent of totallung capacity with the change after smoking two cigarettesin the usual manner on treadmill exercise measurementsof: (1) Arterial blood oxygen saturation, (2) oxygen up-take, and (3) the volume of pulmonary ventilation (litersper minute per square meter, body surface area). Meas-urements on 21 cases.

groups of subjects with varying degrees of emphy-sema was there significant change in the arterialblood oxygen saturation (Chart 2). Nor was therecorrelation between the change in arterial bloodoxygen saturation after smoking and the residualper cent of total lung capacity. There was no signifi-cant change in the arterial CO2 content and pH, be-fore and after smoking with step-up exercise. Thearterial pulse was consistently increased after smok-ing and the respiratory rate was increased slightly.A slight increase was noted in the average minuteventilation and oxygen uptake after smoking withstep-up exercise. The data on individual subjects asto the C02 content change after smoking with step-up exercise revealed a tendency toward a decrease

CALIFORNIA MEDICINE214

Chart 4.-The nitrogen curve (labeled N2) and the corresponding volume (V) and flow during exhalation (totalrecorded as ml.) in a patient with severe emphysema, obtained by taking a single deep breath of oxygen and thenblowing out as far as possible. The nitrogen was recorded from a nitrogen meter and the volume from the 13.5-literCollins respirometer with a helipot to convert volume to electrical output. Impaired intrapulmonary mixing gives aprolonged sloping curve upward as shown in N2 curve before smoking. After smoking the N2 mixing curve was slightlyimproved (middle tracing) although the volume of the deep breath was reduced (vital capacity). After bronchodi-lator isuprel the vital capacity was significantly increased (V from 1425 to 2377 ml.) although the N2 curve was notimproved. Lung volume measurements are expressed at body temperature, pressure saturated (BTPS).

in CO2. However, this was probably correlated witha slight increase noted in the minute ventilation(Chart 2). The average tidal volume was increasedslightly after smoking.

Blood gas studies were obtained before and aftersmoking and treadmill exercise in 21 cases. Thearterial blood oxygen saturation, the oxygen up-take in ml./min./M2 BSA, and the ventilation asL./min./M2 BSA are correlated with the residual percent of total lung capacity for the 21 cases (Chart3). There was no significant change in the arterialblood oxygen saturation after smoking. However,the oxygen uptake on exercise was decreased anaverage of from 565 to 516 ml./min./M2 BSA aftersmoking. The standard deviation for the change inoxygen uptake on exercise was +53 ml. with astandard error of 11.5 ml. There was also an averageventilation change after smoking (Chart 3). Theaverage minute ventilation was decreased from13.05 to 11.62 L./min./M2 BSA. The decrease in theoxygen uptake on exercise may be related in partto the decrease in the minute ventilation. However,no such decrease in minute ventilation was notedduring step-up exercise after smoking two ciga-rettes. Direct tension measurements of arterial pO2and pCO2 in the group of cases with-treadmill exer-cises revealed no significant changes. The effective

tidal air, computed on the basis of the expired pCO2and the arterial pCO2, was not significantly changedin this group.

In several cases of severe emphysema, the singledeep breath technique of oxygen with continuousrecording of nitrogen on the nitrogen meter wasemployed and the volume of exhalation measuredby electrical recording (Chart 4). No significantchange in the air distribution as judged from theshape of the nitrogen curve was noted after smoking,even though the vital capacity usually showed somereduction. Although treatment with bronchodilatordrugs after the smoking test increased the vitalcapacity significantly, the shape of the nitrogencurve was not improved.

In 41 subjects who smoked regularly the effectof one cigarette on pulmonary compliance was de-termined. The group consisted of eight normal per-sons and 33 patients with varying degrees of cardio-respiratory insufficiency as determined by completepulmonary function studies. The pulmonary com-pliance was determined by a modification of thecontinuous cycling method, and timed pressure-volume loops were obtained over the range of quietrespiration. Pressure determinations were obtainedby means of an esophageal balloon placed in themid-esophagus. The resting compliance determina-

VOL. 88, NO. 3 * MARCH 1958 215

tion was obtained after the patient smoked a ciga-rette of his choice. There were no variations in thelevel of the balloon, the amount of air in the bal-loon or the position of the patient (variables thatare known to affect the results in determining pul-monary compliance).

Vital capacity was also determined on most of thepatients before and after smoking, utilizing the

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Chart 5(c).-Same as in Chart 5(a) except in a patientwith fibrosis and emphysema and left thoracoplasty witha residual 57.0 per cent of total lung capacity, total vitalcapacity 32.0 per cent of normal predicted and a ventila-tion factor of 35 per cent. Compliance 47 ml./cm. H20before smoking and 41 after.

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Chart 5(a).-Pulmonary compliance measurements be-fore and after smoking one cigarette in the sitting posi-tion in a patient with severe emphysema (residual 61.0per cent of total lung capacity (R), total vital capacity(VC) 72.0 per cent of normal, predicted and ventilationfactor (VF) 42.0 per cent). Volume is recorded on thevertical axis and pressure on the horizontal axis. The in-terruption of the tracing permits timing, as the oscillo-scope beam moves around counter clockwise, describinga complete loop for each respiratory cycle. The blip atthe bottom is the no flow point at the end of expirationand the blip at the top the no flow point at the end ofinspiration. The sloping line connects the points of noflow at the end of inspiration and expiration. Compliance(C) 150 ml./cm. H20 before smoking and 73 ml/cm. H20after smoking.

~~~~~~~~~~~~~~~~~~~~~~~~~P. _ _

C-1l2 BEFIORE SMOKING -C-149 AFTFTRXX.L / CMcm , vc/91

Chart 5(d).-Same as in Chart 5(a) except in a patientwith fibrosis (x-ray) and polycythemia, with a residualof 28.0 per cent of total lung capacity, total vital capacity91.0 per cent of normal predicted and ventilation factor73.0 per cent. Compliance 112 ml./cm. H20 before smok-ing and 149 after.

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Chart 5(b) .--Same as in Chart 5(a) except in a patientwith a residual of 58.0 per cent of total lung capacity,total vital capacity 74.0 per cent of normal predicted andventilation factor 52 per cent. Compliance 169 ml./cnm.H20 before smoking and 95 after.

Chart 5((e) -Same as in Chart 5(a) except in a diato-

mite worker with a residual of 20.0 per cent of total lungcapacity, total vital capacity 116.0 per cent of normal pre-dicted and ventilation factor 109 per cent. Compliance227 ml./cm. H20 before smoking and 191 after.

CALIFORNIA MEDICINE

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TABLE 1.-Effect of Cigarette Smoking on PuImonary Compliance Measurements

Residual Elastic Work BreathingPer Cent Sitting Vital Capacity Compliance, ml./cm. H,O ggm. M/liter of Ventilationof Total Ventilation Resting Per Cent Per Cent Change Change

Case Lung Factor Arterial Normal Change with with Observed withNo. Capacity Per Cent pO2 mm. Hg. Predicted Smoking Observed Smoking Rest Smoking

1 612 563 364* 315 406 537 578 359 2310 4811 4312 6713 6214 6415* 1916 2517 3318 5319* 1620 572122* 1823 5924 4825* 2326 2827* 2028 5829 29303132 3233 6634 3135 3636* 2237* 2438 .

39 4440 6841 24Normal subjects.

42406588645343641005569613231111877346. ..

44

114315595731092271

72298692109

663289

75.674.582.587.280.7

81.092.197.587.381.885.6

49.1108.173.694.056.1

63.0

90.266.491.3

90.8102.083.3

59.988.588.278.9

75.684.6

73 -577 -1679 -496 -791 + 161 + 87541 -1192 -126095605450100599864 ..

98 -530 -1495 -2116 -162 -2083 +199782 + 4110 387 -567 + 563 + 387 - 6

102 .

66 -880 +23125 - 6110 38975 - 586 -1429 -2092 +10

same volume recording apparatus with the patientin the sitting position. The elastic work of breathingwas determined from the pressure-volume loop ob-tained at rest and again after smoking. Utilizingthis method of determining pulmonary compliancein a group of normals, the mean pulmonary com-

pliance was found to be 166 ml./cm. H20, with a

range from 75 to 304 ml./cm. H20.The results of the compliance studies shown in

Table 1 and typical recordings are shown in Chart5, a, b, c, d and e. There was a significant drop inpulmonary compliance in six of eight normal sub-jects in the study after smoking, with a mean de-crease of 52 ml./cm. H20. In one subject no changewas noted, while another had an increase of 21ml./cm. H20. In the 33 patients with cardio-respira-tory disease, 17 had a significant decrease in com-

pliance after smoking. The maximum decrease was

109 ml./cm. H20 with a mean of 57 ml./cm. H20.In ten patients no significant difference was notedbetween compliance while resting and while smok-ing. Six patients had a significant increase in com-

pliance on smoking, with a maximum increase of56 ml./cm. H20 and a mean of 32 ml./cm. H20.There was no correlation of compliance change withthe residual per cent of total lung capacity (Chart6), as there were significant decreases in the group

of normal subjects as well as in the emphysemagroup. On the whole, smoking tended to decreasecompliance in the normal as well as in the emphy-sema group. The sitting vital capacity was decreasedon an average 8.4 per cent in 20 cases after smok-ing one cigarette, and was increased 9.1 per centin eight cases (Table 1).The elastic work of breathing expressed, as gram

meter per liter (gm. M/L) of ventilation, was de-

VOL. 88. NO. 3 * MARCH 1958

10831092411691681472391874896179153249180

224109152471432977819713211523916877

1112262677713016711075

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- 73- 22-8-131-- 15- 26- 79- 83- 72+ 2- 11

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42.0027.5031.0036.5023.5036.0039.0045.0023.5021.5034.5018.0035.5038.0035.5050.5086.509.00

18.00

+ 9.50+16.00+21.50+15.50+ 5.00+ 8.00+ 13.50+ 5.50+ 7.50+ 12.50

0- 5.00+12.00- 1.50- 4.50-13.00+24.00- 3.50+ 19.50+ 5.00+21.00- 2.00+ 10.50- 5.00- 1.50- 3.50+ 1.50+ 18.00+ 1.50-14.50

0- 5.50- 7.00+ 2.00-10.50- 7.50+ 9.00

0- 7.50+ 2.00+23.50

217

termined before and after smoking in the group of41 subjects who were regular smokers. The eightnormal subjects in the group had a mean value of42.5 gm. M/L ventilation at rest. The 33 patientswith cardio-respiratory impairment had a mean of33.3 gm. M/L ventilation with a range from 9.0gm. M/L ventilation to 86.5 gm. M/L ventilation.The values obtained for the elastic work of breathingby this method compare favorably with those re-ported elsewhere.2'5'6'11,14

After smoking, four of the normal subjects hadan average increase of 15.0 gm. M/L ventilation intheir elastic work of breathing while four had adecrease, the average for the group being 3.9 gm.M/L ventilation (Table 1 and Chart 7). In thegroup with cardio-respiratory impairment, 19 sub-jects had an increase, the average increase for thegroup being 11.5 gm. M/L ventilation. Eleven hada decrease, the average for the group being 6.95 gm.M/L ventilation. In three cases there was no change.The change in the elastic work of breathing aftersmoking was correlated with the residual per centof total lung capacity (Chart 7). An increase in theelastic work of breathing after smoking was notedas often in the normal subjects as in those withsevere emphysema. Similar changes were notedwith regard to correlation with the ventilation fac-tor. The elastic work of breathing is a static meas-urement, reflecting the elastic properties of the lungrecorded at the instant of zero air-flow, and is there-fore independent of time, but directly correlated tovolume changes and rate of breathing. The elasticwork of breathing was determined only at rest dur-ing normal tidal volume exchange.No direct correlation was noted between the ar-

terial P02 by direct tension measurements andchanges in pulmonary compliance that were broughtabout by smoking. In 14 cases the arterial PO2 aftersmoking showed a decrease; in four of them thecompliance was increased, in two was unchangedand in eight was decreased (Table 1). In five sub-jects there was an increase in the arterial P°2 aftersmoking; compliance was increased in two of themand decreased in three. In most of the subjects witha low compliance, there was a low arterial P02 also,although in some cases a low arterial P°2 was asso-ciated with a normal compliance value.

There was a significant decrease in complianceafter smoking in 56 per cent of the group, while 27per cent showed no change and 17 per cent had anincrease in compliance. Further studies of the effectof cigarette smoking on pulmonary compliance ap-pear indicated in order to delineate the changes dueto vascular effect, both in the greater and lesser cir-culation, and distinguish them from the direct effecton the respiratory mechanism.

In two cases follow-up studies of lung volume

COMPLIANCE CHANGE AFTER SMOKING. ML./ CM. Hp.

70-

65 -- -

60- _

5 0-

50.

Ij4- 040 0 *

~35- -- - -

20

i I-120 -lOS -90 -75 -60 -45 -30 -IS +15 +30 +45 +60

Chart 6.-Correlation of the residual per cent of totallung capacity with the change after smoking one cigarettein the usual manner on the pulmonary compliance meas-urement (milliliter volume change per centimeter H20pressure change). Pulmonary compliance change, ml./cm.H20, average mean -25, standard deviation 4 39 andstandard error 6.3.

70

55.

J SO'

ELASTIC WORK OF BREATHING -GM. MILITER VENTILATIONCHANGE AFTER SMOKING

@00

*000 0

0

0- --

1- ~~~~~0S0S

-0

J4o

510

jows 30- .

25 *- .

-1 -0

Chart 7.-Correlation of the residual per cent of totallung capacity with the change after smoking one cigarettein the usual manner on the elastic work of breathing (ex-pressed as gram-meter per liter of ventilation).

were obtained after smoking of cigarettes had beenstopped voluntarily by the subjects-for threemonths by one and two years by the other (Table2). In both cases the residual air was decreased andthe vital capacity increased after smoking wasstopped. The timed vital capacity for three secondsand the maximal breathing capacity increasedslightly in one case and decreased in the other. Thesubject in whom the decreases were shown com-plained of having had, for several weeks, a bad coldwhich had subsided very slowly. Bronchospasm wasdemonstrated in both cases before and after smok-ing was stopped (Table 2).

DISCUSSION

Loomis10 carried out studies that led to a conclu-sion that there is a bronchoconstrictor factor otherthan nicotine in cigarette smoke. Bickerman and

0

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.-- ___

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0 +5 +19 tl* a

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Tw w w~~~~~~~~~~~~~~~~~~.t4 41in 4n15 4- 20 +25

218

TABLE 2.-Lung Volume Changes After Cigare*te Smoking Stopped

A Woman, Age 42 Years, Body Surface A Man, Age 67 Years, Body Surface AreaArea 1.67 Square Meters 1.90 Square Meters

Observed Observed Observed ObservedTest Predicted June 25, 1953 April 2, 1956* Predicted Jan. 1, 1956 March 12, 1957*

Total vital capacity, ml.............................. 3453 2540 (74%o) 3320 (96%o) 4165 2899 (70%) 3642 (87%)Timed vital capacity, 3 sec. ml...................... 3453 1650 (48%) 1929 (56%) 4165 1739 (42%o) 1293 (31%)Maximal breathing capacity, L./min.:

Initial.............................. 104 26.2 (26%) 32.2 (31%) 121 35.0 (29%o) 27.1 (23%)After isuprel.............................. 104 48.0 (47%) 47.0 (46%) 121 51.0 (42%) 42.1 (35%)

Alveolar N2, per cent.............................. <1.5 6.895.05 <1.5 11.3 13.6Residual air, ml.............................. 1190 2736 (227%) 2296 (193%) 1785 5263 (295%) 3382 (190%)Total lung capacity, ml.............................. 4760 5276 (113%) 5616 (118%) 5960 8162 (137%) 7024 (118%)Residual per cent of total lung capacity 25.0 51.9 40.9 30.0 64.5 48.1Ventilation factor, per cent............................ 100 41.049.0 100 39.0 39.0Duration smoking stopped. ........................... ........ 2 years 3months

Study after smoking stopped.

Barach,3 in a study of vital capacity and maximalbreathing capacity in 122 subjects-91 with bron-chial asthma and pulmonary emphysema and 21normal persons-found no evidence of increasedbronchospasm or impaired ventilatory functioncapacity in 108 of the subjects. There was a reduc-tion of vital capacity and maximal breathing ca-pacity in ten cases although unaccompanied by clin-ically perceptible increase in severity of asthma. Anincrease in vital capacity and maximal breathingcapacity after smoking three cigarettes occurred innine patients in whom coughing provoked by smok-ing resulted in expectoration of mucoid or muco-purulent sputum. A number of investigators havenoted a decrease in vital capacity associated withlong continued use of cigarettes.4 16'18 Turley17 notedno effect on vital capacity. Some of the observerswho noted a decrease in vital capacity were of theopinion it may be associated with bronchospasm asa result of smoking, but the individual responseswere quite varied. In some instances even an in-crease was noted. The decrease noted in pulmonaryventilation in some patients after smoking has beenexplained on a basis of the expectoration of muco-purulent secretions.3 In some patients carbon mo-noxide may be a factor in stimulating pulmonaryventilation with smoking. However, Asmussen andChiodi1 carried out a study in which it was notedthat the pulmonary ventilation was not stimulatedby carbon monoxide poisoning as it was in hy-poxemia due to breathing a low oxygen mixture.The problem of allergic sensitivity to tobacco

smoke has to be considered in studies like the pres-ent one. Some investigators regard allergic reactionto cigarettes as rather infrequent, although therecan be little question that smoking or exposure tosmoke from tobacco can aggravate asthma in somepersons. The number of reported cases with detailedevidence of sensitivity to tobacco as a cause ofrespiratory manifestations is surprisingly small in

view of the widely quoted statement that in one percent of patients with asthma, tobacco is a factor.19

In a review of the literature very little informa-tion was found on changes in the blood associatedwith smoking, and not much more on gas exchange;what there was of the latter was principally onresting oxygen uptake. In the present study, whencigarette smoke was inhaled with the smoking de-vice, there was a significant lowering in the restingarterial blood oxygen saturation in the majority ofpatients who had severe or very severe pulmonaryemphysema. Direct tension measurements of arterialpO2, using the bubble technique of Riley, alsodemonstrated a significant decrease in this groupof subjects. However, the average pCO2 was in-creased slightly but not to a statistically significantdegree. There was no significant change in the ven-tilation volumes at rest when tests using the smokingdevice were carried out. Tests that were done in 50cases before and immediately after smoking, withstep-up exercise, showed no consistent significantchanges in the blood gas exchange. Studies of 21subjects before and after smoking, with treadmillexercise, did show a significant decrease in the ex-ercise oxygen uptake after smoking. However, therewas also a significant decrease in the minute ven-tilation, and this may have been the cause of thereduced oxygen uptake on exercise. One has to con-sider, however, that the reduced exercise oxygenuptake may possibly reflect some change in pul-monary vascular resistance, which could result froman increase in pulmonary blood volume or frombronchospasm.When a very sensitive test such as pulmonary

compliance was employed, significant changes in thepressure volume relationship were obtained in sub-jects who were essentially normal and also in thosewith various degrees of pulmonary insufficiency.When the elastic work of breathing was calculated,it was noted that smoking increased the work of

VOL. 88. NO. 3 * MARCH 1958 219

breathing in most subjects. There was no significantcorrelation of the change noted in complia:.ce withsmoking and the severity of the pulmonary emphy-sema or fibrosis.

In practically every case of severe emphysemawhich has been studied in this laboratory, whenthere was no other apparent cause for emphysema,there was a history of heavy cigarette smoking formany years. Significant changes in the arterial bloodoxygen saturation were found only in the subjectswith severe or very severe pulmonary emphysemawhen they inhaled the smoke with the smoking de-vice, which delivered smoke in greater concentrationsthan was obtained by ordinary cigarette smoking.The experiment with the smoking apparatus wasdesigned to try to intensify the effects of smokingas far as possible to see if blood gas exchange couldbe affected.

The data of this study in general indicated thatpatients with severe emphysema would be better offif they stopped smoking. No apparent differencewas noted regarding the brand of cigarette smoked,or the presence of the filter tip. In normal personsthe pulmonary compliance changes in some subjectswere the only constant abnormality noted; this maybe an undesirable change and may be a factor pro-ducing changes later on in some but not in all sub-jects, with respect to the development of a signifi-cant degree of emphysema.

1212 Shatto Street, Los Angeles 17 (Motley).

REFERENCES

1. Asmussen, E., and Chiodi, H.: The effect of hypoxemiaon ventilation and circulation in man, Am. J. Physiol.,132:426, 1941.

2. Attinger, E. O., Goldstein, M. M., and Segal, M. S.:Ventilation in chronic pulmonary emphysema: II. Correla-tion of compliance and mechanical resistance with routinepulmonary function tests, Am. Rev. of Tuberc. and Pul-monary Dis., 74:220, 1956.

3. Bickerman, H. A., and Barach, A. L: The effect ofcigarette smoking on ventilatory function in patients with

bronchial asthma and obstructive pulmonary emphysema,J. Lab. and Clin. Med., 43:455, 1954.

4. Bogen, E.: Tobacco and tuberculosis, Dis. of Chest,3:22, 1937.

5. Cherniack, R. N.: The physical properties of the lungin chronic obstructive pulmonary emphysema, J. Clin.Invest., 35:394, 1956.

6. Comroe, J. H. Jr., Forster, R. E., DuBois, H. R., Bris-coe, W. A., and Carlsen, E.:. The Lung. Clinical Physiologyand Pulmonary Function Tests. Year Book Publishing Co.,Chicago, 111., 1955.

7. Crane, M. G., Hamilton, D. A., and Affeldt, J. E.: Aplastic balloon for recording intraesophageal pressures, J.Applied Physiol., 8:585, 1956.

8. Evelyn, K. A., and Malloy, H. T.: Modified microdeter-mination of oxyhemoglobin, methemoglobin and sulfhemo-globin in a single sample of blood, J. Biol. Chem., 126:655,1933.

9. Kuzman, W. J., Froeb, H. F., and Motley, H. L.: Modi-fications of the continuous cycling method for recordingpulmonary compliance, Clinical Research Proceedings,5:224, 1957.

10. Loomis, T. A.: A bronchoconstrictor factor in ciga-rette smoke, Proc. Soc. Exper. Biol. and Med., 92:337, 1956.

11. Mead, J., and Whittenberger, J. L.: Physical proper-ties of human lungs measured during spontaneous respira-tion, J. Applied Physiol., 5:779, 1953.

12. Motley, H. L.: The use of pulmonary function testsfor disability appraisal: Including evaluation standards inchronic pulmonary disease, Dis. of Chest, 24:378, 1953.

13. Motley, H. L.: Comparison of a simple helium closedwith the oxygen open circuit method for measuring residualair, Am. Rev. of Tuberc. and Pulmonary Dis., 76:601, 1957.

14. Rahn, H., Otis, A. B., Chadwick, L. E., and Fenn,W. O.: The Pressure-Volume Diagram of the Thorax andLung, A. F. Technical Report No. 6528, Aug. 1951.

15. Riley, R. L., Proemmel, D. D., and Franke, R. E.:A direct method for determination of oxygen and carbondioxide tensions in blood, J. Biol. Chem., 161:121, 1945.

16. Short, J. D., Johnson, H. J., and Leg, H. A.: Effectof tobacco smoking in health: Study of 2,031 medical rec-ords, J. Lab. and Clin. Med., 24:586, 1939.

17. Turley, F. C., and Harrison, T. R.: Respiratory meas-urements as affected by smoking in athletics, Am. J. Med.Sc., 183:702, 1932.

18. Whitfield, A. G. W., Arnott, W. M., and Waterhouse,J. A. H.: Effect of tobacco on lung volume, Quart. J. Med.,20:141, 1951.

19. Wynder, E. L.: The Biologic Effects of Tobacco.Little, Brown and Co., Toronto, 1955.

Social Security FootnotesTHE "SOUNDNESS" of Social Security depends on compulsion, high employment.and no wars.

-From the Department of Public Relations, American Medical Association

220 CALIFORNIA MEDICINE