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7(i9C4), j L Cardiopulmonary function studies in workers' dealing with' asbestos and glasswool1 J. BJURE, B. SODERHOLM, AND J. WIDIMSKY" From the Deportment of Clinical Physiology, Sahlgrcnska Sjukliuset, University of Cbtcborg, Coteborg, Sweden Pulmonary fibrosis is thought to be a common complication of exposure to asbestos dust. The inhaled asbestos fibres are supposedly not transported by the pulmonary lymphatics, and thus one single massive exposure might lead to the same stage of fibrosis as a prolonged but less intense exposure. This industrial hazard has led to the search for substitutes for asbestos in insulation work, and at present glasswool and rockwool arc often used. The fragmentation of these materials may give rise to fibre particles which can be inhaled and deposited in the alveoli. The possible effect on cardiopulmonary function in a group of men doing insulation work, with prolonged exposure to glasswool and rockwool dust, is the subject of the present paper, and a similarly exposed group of asbestos workers was studied for comparison. MATERIAL These men have regular routine medical examinations. All the subjects in this study, which formed part of a general survey, were gainfully employed male insu lators who volunteered. Their employment records were carefully studied in an effort to evaluate the kipd of dust to which they had been exposed. Group A consisted of eight subjects whose exposure to asbestos dust comprised at least 50% of their employ ment time. In all subjects the chest radiographs suggested asbestosis, and two patients complained of cough and exertional dyspnoea. Six subjects were selected who had had prolonged exposure to glasswool and rockwool but only minimal exposure to asbestos dust (group B). They had no history of cardiopul monary disease. Physical findings and chest radio graphs were cors'dered normal. Clinical, radiological, and occupational data arc recorded in Table I. 1 Supported br i ifjrt front Sufeni * Revrjr:h fcllo# of Sverjta fSanonjKjrcmnjcn ooi hjiro_a hjfci'jkAdcm jr frc-i-ii idSrtu: lniiiuie tor Cird'ovissuUr DiiriKj, PrsXiKri. Boe.'iorUil 100. CucSo-lorAXil METHODS Dynamic spirometry was performed, as described by Bcrglund, Birath, Bjurc, Grimby, Kjcllmer, Sandqvist, and Soderholm (1963). Functional residual capacity ~(F.R.C.) was deter- mined in the supine position, using an open-circuitnitrogen wasb-out technique (Lundin and Akcsson, 1954), Tne volume required to wash out the nitrogen from 1 litre F.R.C. to an end-tidal concentration of 2%, lung clearance indet (L.C.I.), was calculated from these records (Bccklake, 1952). Electrocardiography was performed using five chest electrodes (CK) and the conventional limb leads as well as aVR, aVL, and aVF. Physical performance was studied on a bicycle ergomclcr as described by Sjostrand (1947). The heaviest work load which could be maintained in a steady state, as judged from the heart rate, was used as an index of the physical performance (Grimby and Soderholm, 1963). Heart catheterization was performed in the morning after a light meal. A doubie-lumen catheter (no. 9) was wedged in a pulmonary artery (P.C.V. position) with the proximal lumen in the pulmonary artery. Brachial artery pressure was recorded from an indwelling polythene tube. Pressures were recorded with strain-gauge manometers on a six-channel directwriting recorder.* A point 5 cm. dorsal to the stem.il angle was used as zero reference level. Mean pressures were measured by electrical integration. Cardiac out put was estimated according to Fick's direct principle. Gas analyses and measurements of oxygen satura tion and oxygen capacity were performed as described by Holmgren and Pernow (1959;. The oxygen tension in arterial blood was determined by the potentiorrctric method described by Gleichmann and .Lubbers (I960). The alveolo-arterial difference in oxygen tension was calculated from the alveolar air equation and the arterial oxygen tension. Venous admixture to arterial blood was calculated in per cent of cardiac output, assuming an end-capillary oxygen saturation of 9S%. After introduction of the catheters the subjects were allowed to rest for 30 minutes. Pressures and (lows were then studied in the supine position. All measure- 4 Minjojrjph, Elcm* CONFIDENTIAL-SUBJECT TO COURT ORDER BC '3701 J BB 0005060 i Cardiopulmonary function studies in workers dealing with asbestos and .glasswool 23 TABLE I Sub* {& I 2 3 4 5 6 7` 8 9 10 11 12 13 M Ait 29 37 41 37 45 43 48 50 40 33 51 49 47 46 Height (cm.) Pleural Th-ck* tmr.j 167 - 191 -- 171 -- 177 187 -- 178 ISO 16$ + 183 + 173 4- 172 + * tes + 16$ + ' 164 + Stre.xk* irtr Mottling DyJpnoci Working Cnpjciiy (kpm./mio.) Pulse Rite TUsp'fu'Ory Rile Occupational History - - 600 124 3 11 yr. almost exclusively rockwool and ftasf*ool; minimal exposure to axbes(os *- -- 1,200 157 30 22 yr. exclusively roekwcol and giasswool; no exposure to asbestos -- -- 600 IIS 20 25 yr. almost exclusively rockwool anti glaiS*oo!j minim tl esrosurc to asbestos --** -- 900 150 . 2$ 6 yr, exclusively rockwool and glasswce! -- 1.200 162 ' 28 29 >r. Since 15 >r. no exposure to asbexicj but has earlier been moderately exposed lu asbestos -- 900 172 28 11 yr. almost exclusively rockwool *nd i*iss woe!; minimal exposure to asbestos _4- 900 154 35 30 yr. exposure to b'Mh asbestos and rockwool _4 4- 900 132 40 25 yr. exposure to both asbestos and rockwool 4* 600 120 2$ 10 yr. mostly expoitrre to asbestos bu: has used face muxk -- i,:oo ISO 44 11 yr, mostly exposure to asbestos but has used face mask -- 900 165 2$ 30 yr. mostly exposure to asbestos 4- -- 900 163 30 22 yr.'mcsily exposure to asbestos 4- + 600 130 36 7 yr. mostly exposure to asbestos 4* 600 115 28 9 yr. mostly exposure to asbestos (mattresses) 1 Scoliosis of thoraci: spine. 1 Pleural and,'or diaphragmatic calcification!. Subject No. Group B 1 2 3 4 3 6 Group A 7 8 9 10 Jl 12 13 14 Mean values Group B Group A F-vatues for difference A-B .. V.C. 0.5 Found Predicted 4 63 5-76 4 3? 4'B6 4-76 4-52 4-67 5*64 4-55 4 97 5 29 4'8S 4-42 2-69 4-03 3 08 3 83 3 36 3-44 2-90 4-89 427 5*44 4-84 4-43 4*29 4-31 4-16 4S5 3-47 lOltf 76:: <001 T|A B L E II PULMONARY FUNCTION STUUIES -,F.E.V 0.5 Found Fredicted F.E.V.V, Found Predicted ' N, Difference F.R.C. L.C.I. 3 96. 3 S3 3 44 2 92 3-39 344 3-84 4-37 3 31 3 SS 397 3 69 85 66 76 60 71 76 81 7S 77 78 ' 75 76 09 1-8 09 M 25 1-4 3 o: 1-76 1-98 2 59 2-44 -- 90 78 6-3 90 8 2-92 3-63 66 74 1-8 2-36 10 6 1*96 3*14 73 73 __ __ __ 3 31 417 S'* 77 6-5 3-31 8-3 2-69 3-R< 87 79 0-9 1-69 10 2 y2 22 3 22 SB 73 5 4 3-07 , IIS 2-64 3-18 76 74 0 8 2-76 7-o 2-97 3-21 86 74 1-5 1-8$ 11-3 2-30 3-14 79 75 6*3 2*05 8S 3*50 2 63 90*/* v>% 72 76 78 `1-6 2-36 7-r6 73 3-3 1 2*4$ ,--9-71 <0 01 >0-05 >0*05 >0-05 >005 Di,, 19-6 30 t 21-7 20 2 29 4 2*> ; 9'* ` 13 2 17 3 21-2 M'S 13 C Xn' N 1-9 23-9 i4: <0-01 V.C.vital capacity (I. A.T.P S.) siinrg F,E.VM t~forced expired volume in l s?c. 0- A.T.P.S.) stiiing, F-E-V */t* forced expired voiur.c m 1 tec. in per cent of vita1 capacity. Nj difference `single breath* diflerence in expired N, content between 750 and I ,-30 nil. F. ft.C * fyncd'inil residual capacity (1. B.T.P.S.) supine. L.C-t. ^ lung clearance index (litre? of total ventilation per lure of F.R.C-). Dlco*` pulmonary diffusing capacity Tor carbon monoxide (ml,'min. x mm. Hg). menli were made under steady-state conditions, as judged by pulse rate and pressures. Haemodynamic data were studied during rest only in group B and during rest and exercise in group A. The difTusing capacity of the lung was determined at rest using the steady-state carbon monoxide method described by Fillcy, Macintosh, and Wright (1954), modified according to Linderholm (1957). Carbon monoxide was analysed in a hopcalite apparatus (Stilex). The carbon monoxide content of arterial blood was determined after release of CO by sulphuric acid in an extraction chamber. RESULTS Table II gives details of the pulmonary function studies. The predicted values have been calculated according to Bcrglund et at. (1963). Group 3 showed completely norma! values in ail respects. In group A the dynamic function tests revealed a marked restriction, and the ditfusmg capacity for carbon monoxide was reduced. However, there were no signs of increased airway resistance, as judged from F.E.V.%, nor any indications of CONFIDENTIAL-SUBJECT TO COURT ORDER BC 3702 I BB 0005061 J 24 }, Bjure, B. Sodsrholm, and ]. V/idimsky impaired distribution of the inspired air, as judged front the lung clearance index and single-breath N' test. Physical performance (Table I) was comparable in the two groups. In only one subject (no, 13) in group A was there any reason to suspect a limitation of the working capacity because of impaired ventilation. However, all subjects in group A had a tendency to use a higher respiratory rate at a given work load than the subjects in group B, Table III shows the haemodynamic data. Also from this table it is evident that the abnormal findings are confined to group A. Even though the average pulmonary artery pressure is not definitely raised for the whole group, the difference between groups is significant, as is the difference in calculated pulmonary vascular resistance. The respiratory data are given in Tabic IV. When comparing the two groups- there is a significant difference only in the arterial ox>gen tension and the alvcolo-arterial oxygen tension difference. However, the lowest oxygen satura tions, as well as the highest VD/VT and Q, /Q,, are found in group A. In both groups some subjects (nos. 4, 6, 7, and 12) had a low arterial Pcos at rest. This has been interpreted as being due to anxiety. The normal value during exercise in subject 12 gives some support to this interpretation. In subject 8 essential hypertension might be suspected because of the increased brachial artery pressure and systemic vascular resistance. Electrocardiography revealed in group B only one subject with signs suggestive of right ventricular hypertrophy (R.V.H.) but here the pulmonary artery (P.A.) pressure was normal. In gi'oup A two subjects had the E.C.G. pattern of R.V.H.; one had a normal P.A. pressure at rest whereas the other had pathologically raised pressures both at rest and on exercise. Three other subjects had signs suggestive only of R.V.H. Of these only one had an abnormally raised P.A. pressure at work. One subject with pulmonary hypertension at rest had a normal E.C.G. In view of the difference between the two groups these findings indicate that electrocardiographic signs of right ventricular hypertrophy in a subject exposed to asbestos dust would indicate the neces sity for further cardiopulmonary function studies. TABLE III HAEMODYNAMIC DATA Subject No. Brachial Artery Systolic Diastolic Mean P.C.V. Pulmonary Artery Systolic Diastolic Mean R.A. ` S.V.R. F.V.R. (-v)o, C.O. H.R. 5.V, Croup & 1 2 3 4 5 b ._* 122 73 92 __ -- __ -- -- -- 69 __ 128 77 lot 13 27 13 18 -- 171 08 51 r s-9 64 92 117 72 93 4 13 7 8 0 20 7 0-9 44 4 3 63 66 no 61 8t 6 13 4 9 -- 13 3 05 43 60 6S 83 130 76 93 3 20 8 13 1 II 1 ! 0 40 8 4 73 113 130 81 104 3 16 4 8 2 13-8 OS 36 6-6 70 94 Croup A 7 133 79 106 6 25 7 13 8 173 104 1)2 J3 38 17 23 9 147 73 90 3 27 3 13 10 R 117 67 93 7 25 6 16 E 141 77 96 3 44 14 23 UR 134 76 100 4 7 13 E 166 91 123 7 35 II 21 12 R I25J 84 103 3 ^2 9 16 E J60 103 123 __ *0 22 33 13 R 129 76 96 3 ^v 7 13 F. M3 8 1 105 10 32 10 19 HR 14] 84 113 12 32 II 21 E 190 103 1IQ 17 60 23 33 1 , 15 6 4 29-3 1 77 0 14 8 S9 0 n3 14 3 2 IS 1 1) 5 0 16 3 95 4 2I'6 14 3 ;-3 41 6 8 34 125 27 47 4 3 63 66 0 7 23 11*7 93 119 1`4 37 6 3 sn 79 1-7 79 :o a I0i 100 2 0 44 1 ? 101 5 7 76 S 3 no 73 *7 2 3 45 -- 102 3-7 82 9 5 114 70 83 1-4 37 3 9 66 6) 0 8 7S 11 1 102 1C*| 18 42 5 2 64 l 2 0 92 10 3 10: toi Mean \a!uti 1 revi Group D .. A . ;:i U3 73 >1 94 104 6 19 7 !! 7 11 8 r< 6 17 6 , 0 s 43 2 6 3 61 17 40 1 6 3 74 S3 P-olue for , deference >0 03 >0 03 . 0A 0 All pfc*<u"j ere gjvsr. m mm. II4. P.C. V. * pi; Or. unary artery '*:]je prison. R-A. JTlIir:: P.V.R. -- pulmomry vascular rsrsunct ^fA` C.O -cirjue ojtpul (1,,'min.), H.P.*hejrt riu. S.V.-jiraite volume (mi.). >0 03 <0 05 >003 i>on: >0 05 >0 03 1 n;hl atrium p: U^O * arieno-ienous oiyjen difference (mS./j.). CONFIDENTIAL-SU: XT TO COURT ORDER BC 3703 / '____ 00 05 06 2~7  - Cardiopulmonary function studies in workers dealing with asbestos and glasswool 5 SuSlKI No. Qrcdp B I 2 } 4 ,. 5 '6 O'dtp A 8 9 10 R E 1! P. E 12 R E 13 R E 14 R E Mean valves at rui Croup 0 A P-val.ics for difTercnce A-S 97 9? 97 98 96 98 93 98 97 . 96 nc 92 94 97 97 93 94 96 96 97`0 9? 9 >003 0,-cip. 17 8 19 8 18-7 17 5 18 5 JS-2 17 3 19 4 iTt 17 7 18 b 19 8 IQ.9 20 2 19-5 17-2 17-6 18 I 19 8 18-4 18-4 >0 03 240 300 199 270 334 239 275 215 293 24J 852 252 tzo 272 97( 219 867 220 964 264 249 >0 03 TABLE IV RrSniRATOXY DATA VD VT Vo, 6S 79 64 M3 10 1 80 35 40 33 39 25 32 i * 24 5: 36 27 30 n-7 69 90 7-5 171 9: 25*1 13 1 22 9 63 23 8 77 . 31-4 34 27 ' 46 /,< 22 43 21 23 IS 31 27 40 24 30 35 39 41 42 3fi 36 19 2! 34 36 35 33 *-9 90 * 30-7 36 1 33 3 33 6 >0 03 >0-05 >0-05 p>. 96 97 97 121 . 8* 10S 91 85 79 83 92 72 89 104 83 83 83 82 79 (A~a)o, 8 4 16 5 23 6 27 27 19 (9) (10) lx 20 20 21 22 24 26 34 QsQi ' 3 S' ' 5`I 36 0 83 2-3 0 i-2 ; 66 ' 7*5 43 21-3 6-6 2*9 2*4 19 2 75 68 4*7 101*3 85 5 10*3 23 1 46 82 <002 <C*01 >0 03 * ^H'erense uvjtfed io be 4r30 vol,%. Figures in parentheses indicate Fi() calculated from Dill curve. S3(i ''arterial o*j;*n saturation (') Oj-c.^p.oaysen capacity (ml.,MOO ml ) V0 - ox>een consumption (ml 'min. 5.T.P.D.). S'r^tolal vcnu'jtion (l./min. B.T.P.5.). VD/VT = dead spjee ventilation in per cent of total ventilation. arterial carbon dtoxidc tension (mm Hg). (A-aJoj "Ivtoloortcrial on>gen tension difTerer.ee (mm. He). F#0 ip arterial o>cen ten won (mm. Hj). Q^ Oi - >cnous admixture in per cent of cardiac output. DISCUSSION The subjects studied were selected from a larger group of insulation workers. They all had similar working conditions and employment times, the main difference being the insulating material used. A positive diagnosis of asbestosis was made in the presence of prolonged exposure to asbestos dust or radiological findings suggestive of asbestosis. To exclude any exposure to asbestos dust in' the group of glasswool workers proved impossible. However, the time of exposure to asbestos was much shorter, and no one had been employed in the production of mattresses etc., where the exposure to dust is known to be severe. The absence of radiological findings was considered confirmative. Nevertheless any patho-physiological findings in group B should be judged with caution since asbestosis might occur even without radio logical changes (Williams and Hugh-Jones, I960; Leathart, I960). In spite of prolonged exposure to glasswool and rockwool dust no subjects in group B \have shown impairment of those cardio pulmonary functions studied. Thus it seems rate to conclude that prolonged exposure to this type of dust does not initiate any fibrosis of the lungs. This is in agreement with studies performed on different animal species by Schcpcrs, Durkan, Dclahant, Rcdlin, Schmidt, Crcedon, Jacobson, and Bailey (195S) and by Schcpers (1959). They found an essentially cellular reaction to glasswool particles while the deposition of collagen in the lungs is very slight compared to that in asbestosis. The main patho-anatomica] findings have been peribronchioiar and perivascular infiltrations sometimes combined with proliferative cell masses obliterating the alveolar lumen. No signs of fibrosis have beer, observed and all the changes described have been reversible on cessation of exposure. There are few palho-anatomical studies performed on human lungs, but Kahlau (1947) reports on a patient who died with pneumonia after a relatively short period of exposure to glasswool. Microscopy revealed foreign bodies, supposedly glasswool particles, but no fibrotic reaction. Murphy (1961) describes multiple local abscesses arising from terminal bronchi and bronchioles containing glass fibres and only slight fibrosis. Pjtho-analomical studies'of the lungs in cases of asbestosis' have shown dense fibrosis of the * I CONFIDENTIAL -SUBJECT TO COURT ORDER BC 3T04 _if_0005063~7 26 /. fljnre, IS. Sodcrhohn, end J. Widimsky pleura, often with calcifications and a more or less generalized ri tirosis of the lung parenchyma (Vorwald, Durban, and Pratt, 1931 ; Heard and Williams, 1961). These patho-anatomical findings should be compared with the physiological altera tions observed. There arc several findings in asbestosis which have been attributed to the induced fibrosis. dlckeascd vital catacitv This is a common finding (Leathart, I960 ; Easterner, Denoiin, dc Coster, and Englert, 1955; Williams and HughJones, 1960) and in our subjects the V.C. averaged 76% of predicted normal. There' was a poor correlation between the radiological findings and a decrease in V.C. Calcifications were found both in cases with a markedly reduced and an almost normal V.C. On the other hand, those subjects with the lowest V.C. also had an elevated pulmonary artery pressure at rest or during exercise. Similar observations have been made by Soderholm (1957) in patients with pulmonary tuberculosis where a good correlation was found between a reduced maximum voluntary,ventilation and increased pulmonary artery pressure during standardized exercise. This observation might bo of importance as a simple screening test. LOW compliance of the LUNG Leathart (1960) found a markedly reduced dynamic compliance which was closely correlated to the reduction in vital capacity. Similar findings have been reported by Rubino, Garbagni, Scansetti, and Carelli (1961). Thisdecreased pulmonary diffusing capacity has been found by several authors (Leathart, 1960 ; Williams and Hugh-Joncs, I960 ; Thomson, McGrath, Smithcr, and Shepherd, 1961). In our group A six of eight subjects had both a reduced diffusing capacity and an increased pulmonary vascular resistance (Fig. 1). Such an increased vascular resistance in the absence of any indications of obstructive lung disease fits well with the concept of a reduced pulmonary vascular bed due to pulmonary fibrosis. There is no direct relation between vascular resistance and diffusing capacity even if an increased resistance is usually found in cases with a reduced diffusing capacity. Thus the impairment of diffusing capacity might be due to both a reduction in the pulmonary' capillary bed and alterations in the alveolar membrane and/or uneven distribution of the diffusion to parfusion_ratios.. Measurement of the end-capillary oxygen tension is not possible, but some deductions can be made since the mean FIG, 1. Pulmonary diffusing capacity per litre functional residual capacity (DiI0ji. F.R.C.) in comparison Kith the pulmonary \asatlar resistance (P.V.R.) at rest. The normal limits ere derived from subject's studied with the Satne techniques in this laboratory: DLcoj!. F.R.C.: 12 subjects 20-25 years ofage. P. V.R.: 12 subjects 21-50 years ofage. diffusion gradient for oxygen is readily calculated from the Dl;o. In the two groups the average ,, mean diffusion gradient was 15 mm. Hg in group A and 9 mm. Hg in group B, when the toial alvcolo-artcrial O, difference was 23 and 10 mm. Hg, respectively. As the average arterial O, tension W'as 86 and 102 mm. Hi; in the two groups, the end-capillary oxygen tension must have exceeded 95 mm. Hg. ]t is thus reasonable to assume an end-capillary oxygen saturation of 98% and an end-capillary 0, gradient of less than 5 mm. Hg. The contribution of venous admixture to the over-all alvcolo-artcrial oxygen difference * approximates 5 and IS mm. Hg in groups B and A respectively. These figures agree closely with the Q> / Qt of 5% and 3?o calculated otherwise. It is a matter of conjecture whether this admixture of poorly oxygenated blood is considered a result of perfusion of poorly ventilated alveoli or the interposition of an enormously thickened alveolar wall between normally ventilated and perfused alveoli (c/., Piiper, 1961). When calculating the effect of increasing alvcolo-capillary membrane thickness on the O. diffusing capacity, Finley, Swenson, and Comroe (1962) found that a six- to eight-fold increase of the membrane must occur before the alveolo-arterial 02 tension difference is measurable (1 mm, Hg). Thus uneven distribu tion of ventiiation in relation to blood r.osv is a more probable cause of hypoxaemia even in cases with advanced impairment of diffusion. i I I I- i CONFIDENTIAL -C J3JECT TO COURT ORDER BC 3F05 I BB 0005064 J Cardiopulmonary function studies ir. workers dealing with asbestos and glasswool 27 Thus our data indicate a mixed impairment of the fas transport mechanisms where both an impaired diffusion and a disturbance of the ventiiation-perfusion ratio coexist. This is in agreement with the observations of Williams and Huyh-Joncs (1960) and of Bader, Bader, and SclikofT (1961). No relation was found between physical performance or radiological findings and diffusing capacity. This might indicate that an impaired diffusing capacity is a sensitive index of asbestosis, which Williams and Hugh-Joncs have already stated. Lcathart showed that among asbestos workers those with radiological changes had a significantly lower diffusing capacity. In three of eight subjects a pathologically increased pulmonary artery pressure at rest and/or during light exercise was found. Bearing in mind that all subjects were gainfully employed and symptom-free and that the investigation was performed as part of a routine health check up, this is a surprisingly high incidence. Presumably they represent moderately advanced cases of asbestosis and yet their cardiopulmonary function studies have shown marked deviations from . normal. These findings put further emphasis on the importance of preventive medical supervision of 'workers exposed to asbestos dust. It is concluded that even prolonged exposure to glasswoo! and rockwool does not cause any significant impairment of cardiopulmonary function. On the other hand, similar exposure to asbestos does cause such impairment even if the subjects are symptom-free and fit for work, SUMMARY Cardiopulmonary function studies have been' performed in insulators exposed to glasswool or asbestos. With a similar time of exposure glasswool did not cause any detectable functional impairment. Exposure to asbestos gave rise to a marked restriction in dynamic lung function, a reduced diffusing capacity, and, in three out of eight subjects, a pathologically raised pulmonary artery- pressure at rest or during exercise. , V/c would life io tiiark Dr. G. Ahlbory. without whnic hi.Ip much of tins study would have been impossible. We arc indebted in Dr. L.-0. Lanner for an interpretation of the chest radiographs. RET LRENCLS Bader. M E,. Bader, R, A., and SrliVofT, I. J. (I9GI). Pulmonary function in of ihe lunj, an alveoljr*cpillary block s> n-Jrrmc. Ar-c. j. ,\fcil,, 30, 233. Basi?nier. M-, Dcnolm. H., dp Coster, A., and Fnglcri, M, (1955), Liude dc la (Vn:iton revpiratotri: dans I'.ubrstose pulmon.nre, A-ch, SicL 16, 54G Bcckbke, M. P,. (195 2) A n = w Indci of the inirapulmonary mixture of inspired ajr. Trim'. 7, III, Bcrrlu-id, C., Bir.nh. O., fyerc. J . C* rim by, G-. Kjcllmer, Sand- qvi-xt. L., and Soderhotm, H. (1963). Spirornctric studies In normal subjects. 1. forced c program* in subjects between 7 and 70 years of age. At*a tnrd. nnud.. 173, IR5. FilJr/. G. F.. Macintosh. D. J.. and Wrichi. G W, (1954). Carbon monoxide uptake and pulmonary diffuyng capaciiy in romal sublets at rest and during eternise. J, dm. Invest33, 530. Finlc>, T, N., Swenson, F.. W., and Cnmroe, J. H. (1562). Th? c.mse r of arterial h>poicmia at rest in patients *ith `alvtolar-capill.iry block syndrome1, fnui.. 41, 613. Gleiehmann, U,. and Lubbers, D. W. (fp60). Die Messunp des SauerstoH'drueVes in Ga'cn und Flussigksnen mil def rt-LIck- tProfiducgcursnAterrchte, ^yoeos.derhrcvrsEtrclru, e2V71*,<4ch)lItg, ung dcr Messung im Blul Grimby, G-, and S.'iderholm, D, (1963). Spiromstric studies in normal subjects. III. Stans lung volumes and maximum voluntary, ver.ulaiton tn adults smh a note on physical fitness. Aeto mcd. sto',3., 173, 159 Heard. R. E., and Williams, R. (196(7. The pathology of asbestosis with reference lo lung function ThnrCx, 10, 264. Holmgren, A,, and Ferno-v, II. (1959), Spectrorhoiomctric measure ment of ovypcn saturation of blood in the determination of cardiac output. A comparison with the Van 5J>/.e method. SeenJ. J. elm. Lr*1'. Invest.. 11, M3, Knhinu, G (I917j. Todhche Pneumonic meh Glasstaubinhalation durch Verarbstfung ernes KunstjtofTcs 3uS Gl.nwoUc. Frenifurl, Z. Path., 9.145 Leathart. G, L. (i960). Clinical, bronchoerapbic, radiological and ph><iolo?icpl observations in ten eases of asbestosis, Unt, J. l ndr/ s / r A fnf , 17. 2 I 3. Lindcrholm, 11.(1957). On the sicnificancc of CO tension in pulmonary capillary blood for d-glt* mmatinn of Pulmonary diffusing capacity with the stead) state CO method, Aem mcd, frond., 113, 413 Lund*", G*. and Akcsvnn. L. (1954) A new nitrogen meter model. Scend. J. elin. Lnh. fmrjt,, $, 250. Murphy.G 0*. Jr, (1961). Fiber glass pneumoconiosis. Arch, envtmnrti. filth, 3. 704, PiipC', J. (I9M). Variations of ventilation and diffusing capacity to perfusion determining the alveolar-arterial Oj difference: theory. /, epr>(. PhystnL, 15, 507. Rubino, G. F., Garbaeni. R . Scansetti, G., and CareW- (1961) Aspetti di fijioratolojia respiratona e circclatoria ne^,a5be5t05^ pnlmonare. AIrd d 52. 515. Schepers. G. W, M (1959), Pulmonary histo'ogic reactions to inhaled fiberelass plastic dust. An-.er. J. Path , 33, JJ69. . Durkan, j. M., Ddahant, A. D.. Rejlm, A. 3-. Schmidt, 3. O-* Creedon, F, T., Jacobson, J. W., and Baifcy, D. A. (1935). The biolog'cal action of fiberglas-plastic dust, A-M*A- Arch. tndustr. Hlth, IB, J4 Sjostrand, T. (1947). Changes in the respiratory organs of workmen at an ore smelting works, Acta mc<I. un-ui., Suppl, 196. p. 6S7. SdtJerholm, B. (1937). The hemodynamics oT the lesser circulation In pulmonary tuberculosis, Srand, J, rtl r. Lab- Invest,, 9, s.'ppl, *5. Thomson, M, L., NfeGrath, M. W,. Smuher, W. }., and Shepherd. J. M. (1961). Some anomr.ties in the measurement of pulmonary diTusion in ashcjiosu ind chronic bronchitis with emphysema, C7/". 1. Vorwald. A. J., Durkan, T. M*. and ?f alt, T. C. (1951). E^treritritnlal studies of asbettoi-s. A.SI.A. Arch. Ind^ur. Hyg3, I. Williams, Rit and Hu^h-Jeres, F. (I9C0). Tbs snnifjconcu or lung funclioo changes in asbestoses. Thvrax, 11 JC7. \ CONFIDENTIAL-SUBJECT TO COURT ORDER 3706 | BB 00 0506 5 7