Document MoyQJya8M47NKk0vMNGGQZ82a

PLAINTIFF'S EXHIBIT DUP-69 Thorax (1964), 19, 22 ^Cardiopulmonary function studies in workers i dealing with asbestos and glasswool' _I J- B J U RE, B. S0DERHO1.M, AND J. WiDIMSKY51 From the Department o/ Clinical Physiology, Sohlgrenska Sjukhusct, 2^: University of Cdteborg, Gdteborg, Sweden Pulmonary fibrosis is thought to be a common complication of exposure to asbestos dust. The inhaled, asbestos fibres arc 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 are often used. The fragmentation of these materials may give rise fojjibre 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. sft MATEKUL 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. Tbcir employment records were carefully studied in an effort to evaluate the kind ofdust to which they had been exposed. Croup A consisted of eight subjects whose exposure to asbestos dust comprised at least 50% of their employ ment tee. In all subjects the chest radiographs suggested asbestosis. sod 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 BV They had no history of cardiopul monary disease, physical findings and ehest radio graphs were considered normal. Clinical, ndioiogieat, and occupational data are recorded in Table I. kto**uorn*S br * matatSfrorow*fcaStIwWn<ulMS*lUcdiWidmnfwcaanFenk*aiaaeuirriodc* hum aSiliTM * IihHuic tar CaTOieMievlar Dbcaan. Fna>. Xti. BiM'wrtrtl am. CadnMU METHODS Dynamic spirometry was performed, is described by Berglund, Birath, Bjurc, Grimby, Kjcllmcr, Sandqwst, and Sddcrholm (1962). Functional residual capacity (F.R.C.) was deter mined in the supine position, using an open-circuit nitrogen wash-out technique (Lundin and Akcsson, 1954). The volume required to wash oui the nitrogen from 1 litre F.K.C to an end-tidal concentration of 2%, lung clearance index (L.C.I.), was calculated from these reeords (Bceklake, 1952). Electrocardiography was performed using five chest electrodes (CR) and the conventional limb leads as well as aVR, aVL, and aVF. Physical performance was studied on a bicycle ergometer as described by Sjbstrand (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 Suderbolm. 1963). Heart catheterization was performed in the morning after a light meal. A double-lumen catheter (no. 9) was wedged in a pulmonary artery (P.C.V. position) with the proximal iumcn in the puimonary artery. Brad ial artery pressure was recorded from an iodwe'iing polythene tube. Pressures were recorded with strain-gauge manometers on a six-channel directwriting recorder.* A point 5 cm. dorsal to the sternal angle was used as zero reference level. Mean pressures were measured by eleetneal integration. Cardiac out put was estimated according to Fiek's direct principle Gas analyses and measurements of oxygen satura tion and oxygen eepeeity were performed as described by Holmgren and Pernow (1959). The oxygen tension in arterial blood was determined by the potentiometnc method described by Gleichmann and Lubbers (I960) The alvcolo-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 98%. After introduction of the catheters the subjects were atiowed to rest for 30 minutes. Pressures and (lows were then studied in the supine position. All mcasurc- * Mweuerapk. Ekau DUP 1141966 Im Cardiopultnonary function shtdics in workers dealing with asbestos and glasswooi 23 TABLE l No. AC Height (era.) Pleural Thick* cniAg Sunk- m,,. I Wertin* int MouTins | CxpKity j (team.,wwl) Puto* JUl Ro~ pintoty Ru Ortvgiils--I Hjawr 1 29 147 2 37 191 ) 41 171 4 37 177 5 4S 147 - Btoo t^w 124 90 II rr. afcoou ndwhxb wrtiVMl ad gaiml; awtaaal n,iiei l, tsSana, - 90 111 r***1,n*1 d--wd; -- arain -- 124 20 ** P- tlmwm irtdn^ wawd and #--s'til: mmmmI mum n mOobm 100 IJM NO M2 If 21 J Jjrr. gM*l> wtwl art (kwaari StjmgkBMSruw^aataMhasMs art* 43 171 see 172 29 7* I ** 50 9 40 10 33 11 St 12 49 U 47 14 44 140 144 US 173 172 144 144 144 + + f 900 + M0 <00 1,200 900 900 4* 400 400 i Scoitottt of thoracic kpin*. fteura) *Ad 'or diaphn 154 14 192 40 IM 24 too 44 Ml 2t 90 yr. mmttrmpemn m Mtara 143 90 22 yt. Mh n>nw m iOmw 190 34 Hi 24 ~ - 7JABLE U PULMONARY FUNCTION STUDHt Subject No. Croup S X 2 3 Croup A 7 S 9 10 II 12 13 Mean value* rfi)up b Group A P*>alun for Uiflctcnca A-B .. v.C.(M Found Predicted 4-44 374 4-55 449 474 4-32 4-42 2*49 403 3-04 3 43 3-34 3-44 2-90 4*47 3*44 4 33 497 5-29 4-41 4 49 4-27 5*44 4*44 4-43 4-29 4-31 4 14 444 3-47 ioi*: <0*01 F.E.V i-.n> Found PradictML 3*94 3 43 3*44 2*92 3-39 3*44 3*04 4*37 JSI 3*44 3*97 3*49 2-92 1*94 2*31 2*49 2 22 2-44 2-97 2 30 3*0 3*14 4*17 3*94 3*22 3*19 3*21 3 14 823 30 243 <o*t MpKiir <i. M.i.r.a.) iminr r.c.t * ire. m per cent tu vtui capacity. N, timcrcer*'>u*i 'vudual capacity (l. K.T.P.S.) tupmc. UC.I- -- hint cto capacity for carbon inotitjrit (ai.uLXo. Hi). F.IV.X Pauad Pradiwd ss <4 70 40 71 70 ~ 77 R 74 <4 74 73 79 92 77 97 79 99 73 3 74 74 79 79 72 71 7< .79 N. p.ax. 49 1*9 942 00 1*79 2*1 149 21**54 2*50 2*44 19 H *9 5-4 0*0 _ 1*5 0*9 2*99 9*21 1*99 -347 149 243 1*4 2 99 2*J 2*40 - R % 7*9 9*9 94 7*9 104 1*3 10*2 114 74 11*3 94 7*T9 9*71 794 , 39-1 21*7 _ 29-2 - 29-4 22*2 * 9*4 19*2 17*3 21*2 114 i - (|*S ii* TC-- 239 14*2 >MS >H) >H5 >M1 <Mt n to I HNB. Ab...T....P...4..> ii npMt(MUM *1**. F.E.VL..*.2. 3i0Onrfd.. lEPcKS i of--q< vuWftna par Utra of FJUC.3. Ob menu were made under steady-state conditions, at ludjjed by pulse rale and pressures. Haemodynamic >l.i la were studied during rest only in group B and during rest and exercise in (roup A. The diffusing capacity of the lung was determined ii rest using the steady-state carbon monoxide method d.strihed by Fillcy, Macintosh, and Wright 0954), modified according to Underholm (1957). Carbon monoxide was analysed in a hopealite apparatus i.Sulcx). The carbon monoxide content of arterial blood was determined after release of CO by sulphuric acid in an extraction chamber. WSULTS Table II gives details of the pulmonary function studies. Tbe predicted values have been calculated according to Bcrglund et al. (1963). Croup B showed completely normal values in all respects. In group A the dynamic function tests revealed a marked restriction, and the diffusing 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 3? Cardiopulmonary function studies in workers deaUnj> with asbestos and ulasswool 2S Sa*jw No. l.rnstf 9 l 2 3 4 5 6 Qr&*p A 7 9 10R E 11 * E 12 R E 13 ft E 14 R E , i 1 Mean value* at rot Group 8 A P*vuluo for difference A-9 S*o, 07 87 7 n81 H 88 87 94 82 84 97 87 93 94 96 96 97-6 95*9 >0 05 0,-fcip. 17 1 II 7 17 5 US 11-2 ITS 19*4 17 6 17 7 11 k 19 1 19-9 20 2 19-5 17 2 176 It 1 19-t 1*4 II 4 ` >003 TABLE IV RESPIRATORY DATA Vo, f 7 V, Vo/VT 240 * 300 7-9 i 6-4 270 14 3 334 10 t U> . 17* 11-7 215 6*9 283 *0 24i 7-5 152 19*1 252 9*5 to 231 272 -13 1 7! 22S 219 65 67 25*1 220 7-7 864 __31-4 S3 is 25 32 32 27 24 27 44 43 22 43 21 23 is 31 27 40 24 2*4 ** 249 to 307 3.| >0 05 >005 >0*05 "O. 40 | s* ! 32 24 s* . ! 30 { 1 30 34 41 41 3* H 19 37 34 m 35 33 33-3 33* I . ; 1 . !1 ; 96 99 99 121 4 101 91 . 15 79 II 92 72 19 104 13 13 13 12 79 101-5 ISS >0-05 ! <0-02 (A-4tt, , 16 23 27 27 19 (9) (10) 35 20 20 21 22 24 26 34 10-3 13 1 <C*0l 0,/Q, 3,. 52 34 0 IS IS 0 i: 6-6 7*5 4-3 213 64 2-9 2-4 19 2 75 61 47 46 ri >005 1 <a~v>ot difference assumed to be 4 30 *&.%. Figures tn perentheso indicate calculated from Dill curve. * arterial oxygen uturation (%). 0,-cap.-oxjrgefl capecuy (ml.'100 ml.). V0|oaygcn comumptton (ml. min. S.T.F.D.). Vt toul lation(I. min. B.T.F.S.). Vq^ *dced space we.ttilataonia per earn of total vefttiiation. Fac0 arterial cartoon dioxide tenuon (mm. llg)* jiut aivcolo-arterial oxygen tension difference (mm. of cardiac output. - arterial oxygen tension (mm. Hg). Q* 'Q\* venous admixture in per cent DISCUSSION The subjects studied were selected from a larger group of insulation workers. They all had similar working conditions and employment times, the mum 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 ih: 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 .ilrscnc: of radiological findings was considered eonfirniaiive. Nevertheless any patho-physiologicai louiings in group B should be judged with caution mikc asbestosis might occur even without radio logical changes (Williams and Hugh-Joncs. 1960 ; I cuthart, 1960). In spite of prolonged exposure to i l.ixswool and rockwool dust no subjects in group li have shown impairment of those cardio pulmonary functions studied. Thus it seems safe <o conclude that prolonged exposure to this type of dust does not initiate any fibrosis of the lungs. This is in agreement with studies performtd on different animal species by Schepcrs, Durkan, Deiaham, Rcdlin, Schmidt, Crcedon, Jacobson, and Bailey (1958) and by Schepcrs (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-anatomical findings have been peribronchiolar and perivascular infiltrations sometimes combined with proliferative cell masses obliterating the alveolar lumen. No signs of fibrosis have been observed and all the changes described have been reversible on cessation of exposure. There are few patho-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 librotic reaction. Murphy (1961) describes multiple focal abscesses arising from terminal bronchi and bronchioles containing glass fibres and only slight fibrosis. P<>tho-anatomicai studies of the lungs in cases of asbestosis hate shown dense Gbrosis of the 26 J. Iljtirc, B. Soderltolin, ami J. Widhusky pleura, often with calcifications and a more of less generalized fibrosis of the lung parenchyma (Vorwald, Durkan, and Pratt, 1951 ; Heard and Williams, 1961). These patho-anatomical findings should be compared with the physiological alterationfobserved. There arc several findings in asbestosis which have been attributed to the induced fibrosis. DECREASED VITAL CAPACITY This is a cotRitton finding (Lcathart, 1960; Bastemer, Denolin, dc Coster, and Englcrl, 1955; Williams and HughJones, 1960) and in our subjects the V.C. averaged 96% of predicted normal. There was a poor correlation between the radiological findings and a decrease in V.C. Calcifications were found both in oases with a markedly reduced and an almost normal^ V.C. On the other hand, those subjects with the lowest V.C. also bad an elevated pulmonary artery pressure at rest or during exercise. Similar observations have been made by Sddcrholm (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 be of importance as a simple screening lest. low compliance of the lung Leathart (1960) founds a markedly reduced dynamic compliance which was closely correlated to the reduction in vital capacity. Similar findings have been reported by Rubino, Garbagni, Scansctti, and Carelli (1961). DECREASED PULMONARY DIFFUSING CAPACITY This has been found by several authors (Leathart, 1960 ; Williams and Hugh-Jones, I960 ; Thomson, McGrath, Smither, 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 perfusion ratios. Measurement of the end-capillary oxygen tension is not possible, but some deductions can be made since the mean SO- a-s- |,0. I-S Otftt l--Jt `St HTMl * 1-0 , | Aifccstot Gtwoo* o-s l--------------- ) Di_ tmLlom. i -- Hj? fJl.C. (O P10. I. Pulmonary diffusing rapacity per litre functional residual capacity (Di-t,/!. F.R.C.) in comparison with the pulmonary rascular resistance (P.y.R.) at rest. The normal limits are derived from subjects studied with the same techniques in this laboratory: Di-coll- F.R.C.: 12 subjects 20-25 years ofape. P. V.R.: 12 subjects 21-50 years ofape. diffusion gradient for oxygen is readily calculated from the Dl,,. 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 total alveolo-arterial O, difference was 23 and 10 mm. Hg, respectively. As the average arterial O, tension was 86 and 102 mm. Hg in the two groups, the end-capillary oxygen tension must have exceeded 95 mm. Hg. It 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 alveolo-arterial oxygen difference approximates 5 and 18 mm. Hg in groups B and A respectively. These figures agree closely with the 0, / Q, of 5% and 8% 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/.. Piipcr, 1961). When calculating the effect of increasing alveolo-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 O, tension difference is measurable (1 mm. Hg). Thus uneven distribu tion of ventilation in relation to blood flow is a more probable cause of hypoxaemia even in cases with advanced impairment of diffusion. DUP I Ml970