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PULMONARY FUNCTION IN ASBESTOSIS: SERIAL TESTS IN A LONG-TERM PROSPECTIVE STUDY Mortimer E. Bader, Richard A. Bader. Alvin S. Tierstein, Irvin? J- Selikoff Cardiopulmonary Laboratory. Department of Medicine Mount Sinai Hospital, Snv York, .V. 1*. Introduction Studies of pulmonary function in asbestosis of the lung have been pre viously reported."* There is good agreement that the principal findings include reduced vital capacity, fairly well preserved maximum breathing capacity, hyperventilation at rest and particularly on exercise,-dccreased diffusing capacity of the lung, impaired oxygenation of the arterial blood, and reduced pulmonary compliance. No significant incidence of pulmonary emphysema has been reported. All who did studies have had the same difficulty assessing the degree of exposure to asbestos dust, and both clinical and physiological data have varied with respect to duration of exposure. There is a lack of serial obser vations in asbestos workers. The present study was undertaken to followseveral parameters of pulmonary function in a group of workers who had been exposed to asbestos dust and then had been withdrawn from further industrial exposure. Data were collected over a ten-year period, during which time clinical and radiological features were also followed. In 1954 1955 1? workers were made the subject of careful pulmonary function studies', and follow-up studies, varying from 1 to 3 subsequent studies, were made it; 13. Additional observations on 21 asbestos workers were made with reference to pulmonary compliance to obtain information rela tive to vital capacity independent of patient performance. These data will be presented also. ' Materials and Methods In 1954*1955 tsee table 1 for date of initial study). 17 workers from asbestos factories were studied.' Clinical symptomatology and lung involve ment un radiographic examination varied. All patients had been exposed to asbestos dust for years (range 4 to 24 years; average ll1^ years at that time). In each case, a detailed history was elicited with particular reference to occupational exposure to asbestos dust or other offending agents which included the intimacy of contact with du^t, duration of contact, degree of exertion <increased ventilation) of the workers, and concentration of oust in the inspired air. Severity of exposure wax graded 1 to 4.* In addition to routine laboratory tests, search was made for asbestos Supported by the Robert S. Clark Foundation, New York, N. Y. 301 Tarlr 1 Serial Orsv.rvations op 1'vlmonary FrNmos Case 1 Cate | .... . ! Maximum 1 . . . , of :! CaViritalty I- ... |c7^yl =ASrateturriaaUl on Study Mo./ Year T ZxT` Air Velocity Index 1. J.P. l 12/54 10/61 l 9/62 1 12/63 2. R.J. 10/56 11/61 3. N.C. 7.^5 2/61| 1/64i 4. R.B. 8/55 2/60 9/621 5. M.C. 12/54 12/59 2/601 11/61 11/62 ]li/63 6. M.JL 12/54 2/60 2/62 7. 2..Me. 12/54 1/60 a. T.H. 10/55 1/60 11/62 9. A.C. 2/55 2/60 11/62 9/G4 10. T.W. 10/56 6/63 12. H.S. 8/55 10/62 13. A.F. 5/55 4/59 2/CO 15. J.P. 10/55 10/62 56 100 46 50 l 88 43 85 65 113 34 62 *53 81 42 63 37 65 88 131 "2 141 117 120 100 94 118 124 104 106 53 112 63 92 77 120 77 100 66 S9 71 113 55 79 97 38 79 93 81 77 98 88 31 124 77 78 70 79 90 106 31 89 65 101 74 88 107 87 61 87 82 81 81 118 72 73 90 93 : 93 j 93 ! 93 87 ' 95 92 92 93 92 91 95 94 97 57 94 93 94 54 95 S3 94 94 97 94 97 95 94 95 96 93 96 36 71 83 81 73 65 83 SO 84 36 81 8G 83 92 91 86 82 88 90 91 91 91 92 92 92 91 92 94 95 94 95 95 92 1.79 1.76 1.33 1.74 0.94 1.53 1.50 1.76 1.49 1.96 1.03 0.94 1.C3 1.22 1.79 1.47 1.56 1.30 1.35 1.59 1.41 0.91 1.18 0.95 0.90 1.53 1.01 1.13 1.18 1.11 1.55 1.08 0.81 1.43 0.69 1.46 L02 Arterial 40 7.40 40 7.41 41 7.42 42 7.40 41 7.40 36 7.40 41 7.40 45 7.39 41 7.39 42 7.40 40 7.41 42 7.40 37 7.39 43 7.39 35 7.43 26 7.43 39 7.42 43 7.41 33 7.42 41 7.41 39 7.40 43 7.39 41 7.40 39 7.42 23 7.41 36 7.42 36 7.42 40 7.39 40 7.40 40 7.40 40 7.40 40 7.38 42 7.41 37 7.42 Barter ct ai\ Pulmonary Function in Asbostosis Tamjr 2 Cunical Status. X-ray Fhati-res, and Cm-itsc is IT ratients with 1'rLMONARY AStlKSTOSIS . "* " SUtus 19S4-19S5 1964 Patient 1. J.P. Years onset Age X-ray DOE* ClubT X-ray PROG1 DOE PROG Club PROG Comment 14 41 3 ' 2 ' ***3*' *' 1 ' -1 - 0 Working regularly 1964 (1959) no significant change 1959-1964 2. RJ. 12 43 4 33 2 2 0 Died cor pulmonale 1962 3. N.C. 11 35 3 33 0 0 - Not able to work row (1963) 4. R.B. 10 66 3 00 1 0 0 Died 1963; Carcinoma of stomach S. M.C. 13 42 1 23 2 2 0 Carcinoma of lung* (1964) segmental resection; recent progression other side with tncrease DOE. 6. MJL 11 67 2 20 0 0 0 Died Carcinoma of lung 1963 T. S. Me. 3. T.fl. 9. A.C. 10. T.W. U.fi.R. 10 24 13 13 62 1 46 1 36 n SI 46 A 42 1 01 0 3 2 0 Died Asbestos!* 1961 0 0 0 Working regularly 0 0 0 Working regularly 0 0 Working regularly -- Died 1958 Carcinoma of lung 12. H.S. 13 63 1 00 0 0 0 Coronary; DOE now 2* 13. A.F. 11 37 3 00 0 2 0 Died coronary 1962 14. W.S. 37 0-1 1 0 -0 Not seen since 1959 So change to 1959 but known to bs well uj X-ray IS. J.P. 16. CA * 38 0-1 0 62 1 4 0 2 00 21 0 Worttng regularly 0 Died Mesothelioma (Carcinoma 1959) 17. J. P*t- 12 58 0-1 0 0# Deceased Died 1956 of carcinoma of stomach DOE * Dyspnea of Eaertiaa. TCLUB Cluhfting. 1PR0G Progression. Numbers la the column* labeled X-ray and DOE art CasJ on a grading at l 10 4.1 30-1 Annals Vcw York Academy of Sciences bodies in 14 of the 17. at least once, ami ail sputa were cultured for tubercle bacilli. A routine electrocardiogram and PA chest film were obtained. The latter were graded from 1 to 4- based on criteria previously reported.1 Measurement of lung volumes, maximum breathing capacity, index of intrnpulmonary mixing, arterial oxygen saturation, ar.d carbon dioxide con tent were carried out according to the methods of Baldwin. Cournand. and Richards.1' The partial pressure of oxygen in the arterial blood was meas ured by the direct technique of Riley, Froemmcl, and Franke,'" and the ventilation perfusion relations am! diffusing capacity of the lung were determined by the method of Riley and Cournand.n-,J From the analysis, data for physiological dead space, venous admixture, and diffusing capacity nf the lung were obtained. Of these 17 men, follow-up studies were obtained on 13. listed by number in table 1. The status in terms of X-ray, dyspnea on exertion and clubbing arc listed in table 2, with any changes between 1054-1055 and 1064 noted. The clinical fate and reason for loss to follow-up are shown in the righthand column of the Table. As may b< seen, eight are now dead -- one of cor pulmonale, two of carcinoma of the lung, two of carcinoma of the stom ach, one of asbestosis, one of coronary occlusion, and one of pleural meso thelioma. Of the living, six are working, one had surgery for carcinoma of the lung, one had a coronary occlusion, and one is unable to work. It was decided to follow these patients with ventiiometric measurements and .arterial blood gas studies. In 1 of the 13 cases followed, residual vol ume measurements were repeated. Data on the 13 patients are listed in TABLE 1. In 21 cases of asbestosis dynamic pulmonary compliance was measured 32 times by the method of Mead and Whittenberger.** No serial data are presented on those parameters. Results Initial Observation* Initial observations carried out in 1954-1255 on the 17 patients have been reported in detail.' For convenience the data are shown in figures i and 2. These results may be summarized as follows: Vital capacity was well preserved in half the patients and moderately reduced in the remain der. Residual volume was not significantly altered except for a .-flight in crease in six patients. The ratio of residual volume to total capacity was normal in all but two patients. Maximum breathing capacity was well preserved in all cases. Analysis of ventilation-perfusion relationships re vealed normal intrapulmonary mixing of gases thy the residual nitrogen technique > in all but throe subjects, in whom it was reduced. Hyperventila tion was present at rest and exercise in the majority of patients. Arterial Daclur (7 a/.: Pulmonary Function in Aslvslosis 30n uxygcn saturation was slightly reduced in G patients at rest amt lower than 92 per cent on exercise in JO patients. While dead space ventilation (ex pressed as per cent of minute ventilation) exceeded the upper limits of normal in 22 patients, alveolar ventilation was increased in absolute terms, and in no case was it decreased. The diffusing capacity of the lung for oxygen was measured in live patients at rest. In four of these, it was reduced. In addition, in four.ofJhe>e five subjects venous admixture was increased. The abnormalities correlated poorly with intimacy and duration of exposure. A better correlation was found when compared with radiolog ical findings. Vital Capaoit Dsr*d b^imootry Compliant* ' 0, OiUuimt C*mcu)> ' Oirftn mi. imil Normal Oi?fcui. Ittnntl Dccrtaaad pCOi Normal Mat. breath caff. ftv.TC hilm air. ram. jj 1 io.o: f9 1Q 1?l r* t 70 I 2r i M 1 n t o!of l IT r "*2 7 T7T 411* i:a 0 14 IS .n 147 y>i yi_____________________ is: 44 il FIGURE 1. Summary of initial observations of pulmonary function in IT cases oi asbestosis. - Folloir-up Studies Those are observations made after withdrawal of the patient from indus trial exposure, and reflect the natural history of the asbestosis of the lung already present. Vital Capacity Vital capacity data expressed as per cent of predicted are presented for Figure 2. Clinical features in IT patients with pulmonary ash*'stn5is. the 13 patients available to follow-up in TABLE 1. and in figure 3. In 12 of the 13 there was a fall in vital capacity ranging from 9 to 31 per cent ex pressed as per cent of predicted. In one case, it rose 9 per cent. The aver age fall was 18 per cent, which is in excess of what may be expected from aging alone. In the original study, nine patients had a vital capacity above 80 i>er cent of predicted (.maximum 1 IT ;er cent), six ranged between 60 and 30 per cent, and two had less than 60 per cent. In the last follow-up studies, only three had volumes in excess of 80 per cent, and four below 60 per cent. Maximum Breathing Capacity Maximum breathing capacity data expressed as per cent predicted are presented in table 1 and figure 4. Of the 13 patients followed, the maxi mum breathing capacity fell in 12. The fall ranged 6 to 51 per cent (aver age 21 per cent) with a rise in one patient of 10 per cent. In the original 17 patients, the maximum breathing capacity exceeded predicted figures in 10. and ranged between 88 and 130 j>er cent in the remaining 7 cases. In the last obtained serial studies, maximum breathing capacity exceeded predicted in only one. ranged between 80 and 99 per cent in six. between GO and 80 per cent in another six. Air Velocity Index Because of the fall in maximum breathing capacity (sec tabi.f. 1 and FIGURE 5); calculation was made of the air velocity index (2EMBC' V'T V( to deter mine if there was evidence of a fall in this index, and in how many cases Linder ct at.: Pulmonary Function in Asbostosis 397 it Ml bi*lnv <*m\ In the 13 pal ients .serially studied, the original air velocity index was greater than one in ten patients, and less than one in three. Of the three with air velocity indices of less than one, all rose--- two to greater than one. and one remained below one with an insignificant rise. Of the 10 patients with air velocity indices greater than 1 it rose in 4, and fell In (5 vonly in tme ease did it fall below 1JI._. ,, Arterial Blond Cases 1. Arterial oxygen saturation at rest (see TABLE 1. FIGURE 6). There was no significant trend in oxygen saturation at rest. Of the 13 patients, 8 had an initial value of 93 per cent or greater, one of 94 per cent, three of 93 per cent, and one of 90 per cent. On follow.up study, there was a fall in seven, but the only noteworthy ones were 93 to 37 per cent (patient died of cor pulmonale i. 93 to 91 per cent, and 95 to 92 per cent. All others wen* insignificant. In the remaining six, arterial oxygen saturation at rest cither Eict RK :i. Changes in vital cap--?y of in year period. 308 Annals Xew \ ork Academy of Sciences k. <o 5 Sg is k. yj i ? i Fiut KK4. Clian-jes in maximum capacity over 10 year period. I 1934 1936 1936 i960 1962 '964 YEAR OF STUDY Fi:ri::: Flmnucs :n air \*ity inn\ v*r id yi*nr ponM. Dalur W id.: Pulmonary Function in AsU-stosis SOD rose or remained unchanged, the only noteworthy ris>- being DO to 93 per cent. 2. Artirinl orygai sn(nrafum > exercise. Of the* original I? patients, in 10 the arterial oxygen saturation on exercise was 02 per vent or less. At the conclusion of the initial study,', it was thought that this would be perhaps a valuable anti sensitive thriex of progression of the disease. In TahLE 1 and yiCu'UE 7 one can see that 7 (.of 13' had no significant change, three foil i 8S to 82 per cent. So to 81 per cent, and 78 to 6" per cent, the last dying of cor pulmonale shortly nf*er the study i. In one there was a significant rise from 71 per cent to a still quite abnormal 81 per cent. In the time period of the study there was no distinct downward trend of the arterial oxygen saturation on exercise. 3. Arterial carbon dioxide tension ( >-v TAHLK I). There was no signifi cant hypercapnia in these pnta-..s originally nr in final study. pr07 values did not change significantly in the initial and final studies. 4. Arterial pH txec takk 1*. Arterial pH remained essentially un changed throughout the study. . Residual V<d'onc_ In the original studies on 17 patients, the residual volume did not differ &.-V4W- **& &X&&?* ^*3rS5fe57.fi" 400 Annals New York Academv of Sciences Vi 1 s I 1 k. 5 o* <* 1954 1956 <958 i960 1902 YAft OF STUOY 1964 Figure 7. Changes in arterial oxygen saturation on exercise over 10 year period. significantly /rum the predicted figure in 10 cases. In six. it exceeded the predicted figure by 20 per cent or more. The ratio of residual volume to total capacity, however, was within normal limits in all but two patients. In four cases i fs 1. #5. 7, j?9l studied serially, residual volume increased in two. The ratio RV TC. increased in ail four. Indeed in only one was it within normal limits on the final follow-up study. It should be noted that in only one (case xl) was there a marked increase in residual volume to account for the increase in RV TC ratio. The changes in P.V-TC ratio were markedly influenced by the fall in VC. rather than by a rise in resi dual volume. Pulnmuanj Compliance In 21 asbestos workers, measurements were made of pulmonary compli ance 30 times. On the same visit, vital capacity was measured. Compliance , Bader ct til. : Pulmonary Function in Asboslosis 101 j is compared with vital capacity in Kh;t:ui: b. Inspirliun of fkwkk S rewals ; a linear relation between vital capacity and pulmonary compliance. I . Discussion I Pathologically,'4 asbestos panicles lodge particularly in the vestibular , area of the lobules ami elicit a fairly uniformly distributed diffuse (non* I nodular) fibrosis. ,_I_t js not surprising, therefore, that previous investigaj tion has established that the physiological changes encountered are those | of the alveolar-capillary block syndrome.' 411 Almost all reports have dem` onstrnted decreased vital capacity.'** fairly well preserved maximum breath : ing capacity,,:i impaired oxygenation of the blood'4 due to decreased , diffusing capacity,'-4 and increased rigidity of the lung as measured by ; decreased, pulmonary' compliance.1 ,-,4` What have been lacking are data i on patients followed over a several year period in which there was no lnJ dustrial exposure. :r period. ded the :e to patients, acreased e was it ied that volume TC ratio in resi- compli. r.pliance 0 22 0 2* 0 20 0. i 0.l> o O.J 7 1 : 01* \5u Oil 0.1* S3 Oil . 3* 0.> 2 * Oil * L> 9 10 _ <o 0.0 1 o.oe -a 0 07 ` oo 0.09 0 0 0 01 0.02 OOi 0 10 20 30 *0 90 tO 70 *0 90 -00 nO VITAL CAPOGTY - RCN7 Of PfiEDiC'SO FtGURE 8. Correlation of vital capacsty and pulmonary compliance in patients with asbestosis of the lung. 1ISPMP r Bar The principal change encountered in the present stuffy whs the* uniform finding of ;i significant reduction in vital capacity compared with initial studio* in l'i"' 1-1053. It was previously demonstrated that the reduction in vital capacity correlated poorly with intimacy of exposure.' Ketler cr* relation existed with regard to radiological findings.' Analysis of the data in Tahlks 1 and 2. comparing the mlnrtiini in vital capacity in the initial and final studies with X-ray prnfjrcs/iirm. reveals good correlation in six. fair in two. and poor in five. Poor correlation in almost ever;.' case meant a reduction in vital capacity without evidence of X-ray progression. Simi larly, about half of the patients had good correlation with progression of dyspnea on exertion but fair or poor correlation in the remainder, vital capacity again living reduced without significant progression of dyspnea. Then- arc two jxjssible explanations of the fall in vital capacity without significant change in the radiological or clinical picture in half these cases of asbestosis of the lungs: (1) It is a more sensitive index of pulmonary involvement than cither, the X-ray or clinical symptoms and (2; the data may refieeb poor patient cooperation. Taking the first fusibility, it has been previously shown thr.t correlation of reduced vital capacity with X-ray is only fair.' Furthermore, significant pathological alteration may exist without evident radiological changes.1* Indeed roentgenographic diagnosis and differential diagnosis can he very difficult.1* With regard to the second (tossibility, the data on the 21 patients in whom pulmonary compliance data are available demonstrate a good cor- lehition between vital capacity and dynamic pulmonary compliance. The Jntter test duos nut involve patient performance cooperation, other than breathing differing tidal volumes. This lends great weight to the validity of the vital capacity measurements and suggests the view that it i an ^accurate and move iw imh-x of pulmonary involvement than the clini cal or radiographic features. Arterial oxygen saturation on exercise in the original studies on IT pa- tients.1 although found to l>c a sensitive index of impairment, did not >how a uniform pattern of change in follow-up studies despite fair correlation with X-ny and dyspnea on exertion in about half the patients. Further more. vital capacity fell much more often than the oxygen saturation on exercise. Xvcdloss i* say the vital capacity is a simpler and more convenient test to perform. With Tegard to the question of the development of ventilatory changes, it is clear that the maximum breathing capacity values, while reduced voni- pared to the initial observation* in llio4-lp.jo, are in the range expected in alveolar-capillary bl<ek cases. Other studies have also stressed the main tenance of the maximum breathing capacity. In our series the only marked fall was in one patient who died of cor pulmonale shortly after the study. Analysis of the air velocity index (AVI, reveals that the majority msc th ci a* T` ul d: be uniform with initial riinlion i t*r cur* i>f the uata ;lu- initial inn in six. ;sm* meant -ion. Simi* , l.*s''nn of vital f d\.pnea. y without :hesc cases .Hiimonary . the data . onviation .significant changes.'* :.r. lie very ! patients good cor ; iitri*. The rher than .0 validity t it is an * -Uni on 1? panut show orrdation Furtherration on pavement change?, ured <vmcxpi-cied . ae raainv marxed he .'tody. .;;y rote t I Baricr ft of.: 1'ulmotmry Function in Asbestosix l`i:> t i during the follow-up period and that -miy o:n- patient had an AVI of less i than one in the final studies. Further evidence against emphysematous } changes is available in the large mimbvr of studied cases in whom evidence i against an emphysematous pattern of pulmonary function is presented.'-*-*" The only significant exception is the report of Hastenier ft nl.,,v hut five of these nine patients had chronic bronchitis. Finally in none of our cases did any significant hypercapnia-or acidosis appear. No serial measurements were made of the diffusing capacity of the lung in our series, and it is impossible for us to conclude that the vital capacity is superior to the diffusing capacity as an index of progression of ashes* tosix of the lung. The finding, however, that the arterial oxygen saturation \ on exercise showed no significant downward trend would support the view that if changes in diffusing capacity did occur as frequently as the reduc tions in vital capacity, they were not sufficient to be reflected in oxygenation of the arterial blood on exercise. We can conclude that the vital capacity is the most sensitive index of progression of the parameters we studied. Needless to say. the vital capacity is the most accessible, easily applied, and repeatable technique available. Summary and Conclusions 1. In l&o4-1955. pulmonary physiological ?uidi**s in iT asbestos workers revealed the characteristic pattern of alveolar-capillary block syndrome. These patients were withdrawn from industrial exposure. 2. Of these IT patients, K were available to follow-up study up to 10 years after the initial observation. Eight are now J.-sul --one of cor pul monale. two of carcinoma of th<*lung, two of carcinoma of the stomach, one of asbestusis, one of coronary occlusion, and one of mesothelioma. Of the living, six are working, one had surgery for carcinoma of the lung, one had a coronary occlusion and is unable to work. 3. Follow-up measurements were made in 13 patients. These included vital capacity, maximum breathing capacity, arterial oxygen saturation at rest and with exercise, and arterial pCOr and pH. 4. During the period of the study, vital capacity was found to be reduced significantly in 12 of the 13 patients. There was also a fall in maximum breathing capacity, but in general they remained relatively well preserved. Air velocity indices showed an upward trend in more than half, and in only one was the air velocity index slightly less than one. 5. There wjts no significant trend in the arterial oxygen saturation at rest or on exercise. -Arterial pCO-.- and pH remamexl (,'*eniially unchanged. o. The rail in vital capacity correlated well in about half of the cases with proj/ft.of X-ray findings and progression ..f dyspnea on exertion, in the remainder, vital capacity fell in almost all. without `igniricaju pro gression of radiological features or clinical symptoms. 1 -104 Annnls New York* Academy of Sciences 7. The reduction in vital capacity correlated well with reduction in pul monary compliance in 30 observations on 21 patients with asbestosis. This would indicate that the reduction in vital capacity is not a consequence of poor patient performance. 8. While diffusing capacity was not mensural, the arterial Os satura tion on exercise did not demonstrate changes parallel to the fall in vital capacity observed. 9. It is concluded that of the parameters here studied, vital capacity was the most sensitive index of progression of the disease. Its ease of application, availability, and repeatability all recommend it for use in the frequent assessment of workers exposed to asbestos dust. References i. Baulk, 51. E., R. A. Bauer & 1. J. Selikoft. 1001. Pulmonary function in usbestosis of the lung; an ulveolar-capillarv block svndrone. Am. J. Med. 30: 233. . ' Wrkjht, G. \V. 1953. Functional abnormalities of industrial pulmonary fi brosis. A. M. A. Arch. Inu. Health. 11: 10(5. 3. GEftNEZ-RlEt'X, C., E. RaLGAIRES <fc C. Cr.ALVS. 10"*4. Consideration ,ur les troubles ruspiratoin-.-. rie I'asbcstose. J. Franc. Med. Chir. Thor. 8: 193. 4. Williams, IL & P. Hygii-Jones. I960. The significance of lung function changes in asbestos:*. Yhorax 15: 109. 5. Leatijart, G. L. P*,;" Clinical, bronchographie. radiological and physio logical observations* ten cases of asbostosis. Frit. J. I:ul. Med. IT: 213. 6. Bjvre. J-, B. SdOKRlica:; & J. WipimsKY. 1964. Cardiopulmonary' function studios m worker? dealing with asi*stos and giasswoo). Thorax 19: 22. Ri'pino, G. F., R. Gah::.'.uni, G. Scansetti & E. Carelli. 19*1. Aspett: <ti fismpatologia respir^-^ia e eircolatoria nell' asbestos: polnionare. Med. Lavoro 32: 513. Rokmkld, H. Kempf 'H. Welpk. 1240. L'ntersuchungen uber die I.un- gunfunktion bci die Asl**slosc. Arch. Kim. Med 186: 33. Fuuiwin. E. de F., A. C'WRNAsn & O. \V. Rp*m tans. Jr. i:'48. Pulmonary insufficiency: I. physiological classification, clinical methods of analysis, standard values m normal subjects. Medicine 2T: 243. 10. Riley, IL L.. D. L>. Prokmmel & R. E. Franks. 1943. A dir*ct method for determination of oxygen ami carbon dioxide tension in blood. J. Biol. Chem. 161:621. ' 11. RILEY. Tw L. & A. Cot'RNAND. 1951. Analysis of factors artecting the con centration of oxygen and carbon dioxide in the gas and blood of the lur.gs. I. Theory. J. Appl. Physiol. 2: T7. 12. Riley, 11. 1^ K. W, 1>un.\m> 4 A. CurttNANP. 1*031. Analysis { factors affecting the concentration of oxygen and carbon dioxide in the gas and blood of the lungs. II Methods. J. Appl. Physiol. 2: 102. 13. Mead, J. 4 J. L. Whittknrkrgkr. 1953. Physical properties of human lungs measured during Sf>ontan*ous respiration. J. Appl. Physiol. 5: 779. 14. Lynch. K. M. 1955. The pathology of asbestosis. A. M. A. Arch. Inri. Health. 11: 155. 15. Austrian. R~ J. H. McClemknt. A. D. Rknietti. Jr.. R. L. Riley. X. W. Donalu & A. CottxA.vn. 1931. The clinical and physiological features of some types of pulmonary diseases with impairment of alveolar-capillary diffusion. Am. J. Mud. 11:667T tl. Tkirstein, A. S., A. GoTTLiia. M. E. Radix. K. A. Rader & I. Skukokf. lfif*o. Pulmonary mechanics in uslacstosis of the lungs. Clin. Hi**. 8: 2.56. 17 13. 19 Bader rt (ii : Pulmonary Function in AsUestosis 405 17. Heard, B. L. <1 It. Williams. liKil. The pathology of ashvstnsis with refer ence to lung function. Thorax. 16: 2G4. 18. ILUAMS. R. <& P. Hlch-Jones. I960. The radiological diagnosis of asbestosis. Thorax. 1.1: 1<>3. 19. Bastenjer, H,, H. Denolin, A. De Coster Si M. Enclert. 19.*.*.. Etude de la fonction respiratoire dans 1'asbestose pulmonaire. Arch. Mcl Profess. 16: 540.