Occupational and Environmental Medicine 1995;52:262-267

Chest radiography and high resolution computedtomography in the evaluation of workers exposedto silica dust: relation with functional findings

D Talini, P L Paggiaro, F Falaschi, L Battolla, M Carrara, M Petrozzino, E Begliomini,C Bartolozzi, C Giuntini

2nd Institute ofInternal Medicine,RespiratoryPathophysiology, CNRInstitute of ClinicalPhysiology, andDepartment ofRadiology, Universityof Pisa, ItalyD TaliniP L PaggiaroF FalaschiL BattollaM CarraraM PetrozzinoE BegliominiC BartolozziC GiuntiniCorrespondence to:Dr Talini Donatella,Fisiopatologia Respiratoria,Ospedale di Cisanello,Monoblocco-Seminterrato,Via Paradisa 2, 56100 Pisa,Italy.Accepted 19 December 1994

AbstractObjectives-To compare the usefulnessof high resolution computed tomography(HRCT) with chest radiography (CR) inthe diagnosis and assessment of severityof silicosis.Methods-27 workers exposed to silicaunderwent CR, HRCT, and pulmonaryfunction tests. Two experienced readersindependently evaluated CR byInternational Labour Office classifica-tion, and grouped the results into fourcategories. HRCT categories of noduleprofusion and the extent of emphysemawere graded on a four point scale; in 20subjects the percentage distribution oflung densities were measured by HRCT.Results-Concordance between readerswas higher for HRCT than for CR (Kstatistic = 0 49 and 0-29 respectively).There was poor concordance between CRand HRCT in the early stages of silicosis.No significant difference in pulmonaryfunction tests was found among differentCR categories, but forced expiratory vol-ume in one second (FEV1), maximalexpiratory flow at 50% and 75% of FVC(MEF5O, MEF7S), and diffusion capacitysignificantly decreased with increasingHRCT categories. Subjects with simplesilicosis detected by HRCT had a lowerFEV1 than subjects without silicosis,whereas subjects with conglomerated sili-cosis showed higher residual volume andfunctional residual capacity than subjectswith simple silicosis. These relations werenot affected by smoking or symptoms ofchronic bronchitis. Different grades ofemphysema detected by HRCT were sig-nificantly different in diffusion capacity.Only the HRCTs of the lowest and thehighest categories of profusion of paren-chymal opacities were significantly differ-ent in their distribution of density classes.Conclusion-HRCT is more reproducibleand accurate than CR, as suggested bythe higher agreement between readersand the better correlation with pul-monary function tests, irrespective ofsmoking and chronic bronchitis; how-ever, these data do not support thehypothesis that HRCT is more sensitivethan CR in the early detection of silicosis.

(Occup Environ Med 1995;52:262-267)

Keywords: silicosis;tomography

chest radiography; computed

Radiographic assessment is paramount in thediagnosis of silicosis,' particularly the stan-dardised chest x ray film classification.2 Thereproducibility and the sensitivity of chestradiography (CR) to diagnose early silicosis isnot very high34 and some alternative methodshave been evaluated. Functional measure-ments have been shown to be of little use inthe diagnosis of silicosis, because they can benormal even in the presence of high profusionof small opacities, and they have been usedmore frequently to assess the severity of func-tional impairment due to the associatedchronic obstructive pulmonary disease(COPD).56 Markers of activity of the intersti-tial disorder (like broncho-alveolar lavage orgallium-67 scan) have been shown to beabnormal in the early stages of silicosis,7 8 buttheir usefulness in the diagnosis of earlysilicosis in individual people has not beenshown.

Since 1983, several reports have shown thatcomputed tomography (CT) and high reso-lution computed tomography (HRCT, thincollimation slices performed with a small fieldof view and targeted by means of high spatialfrequency algorithm) were very informative indetecting silicotic parenchymal abnormalitiesand in quantifying their extent and severity,910as they have been in other diffuse interstitiallung diseases." 13 Several studies have beencarried out to compare the CT findingswith the conventional radiographic patterns.Many authors showed that CT does imagethe parenchimal disease more clearly andidentifies significantly more coalescence orlarge opacities than plain film.9 1014 On thecontrary, other authors reported the relativeinsensitivity of lung CT in detection of mildsilicosis.'5 16 Lung CT was useful in the evalua-tion of changes in emphysema that couldexplain the functional abnormalities found insilicosis. 16-18The aim of this study was to compare CR

and HRCT in a group of subjects exposed tosilica dust and with silicosis of different sever-ity; furthermore, the relation between theradiological assessment and pulmonary func-tion tests was evaluated, taking into accountthe simultaneous presence of the associatedCOPD.

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Subjects and methodsSUBJECTSWe studied 27 subjects (26 men, one woman;eight smokers, six non-smokers, 13 ex-smokers) with mean (SD) age of 57 (8 8)(range 44-76) years. All of them had beenexposed to silica dust in mines, in glass andpottery industries, and in the building indus-try. Most of them had been diagnosed as hav-ing silicosis, based on a history of exposure tosilica and radiographic changes consistentwith silicosis (presence of rounded or irregularsmall opacities with profusion > 1/0 on theInternational Labour Office (ILO) classifica-tion).

CHEST RADIOGRAPHYStandard high kilovoltage posteroanterior andlateral CR was carried out at maximal inspira-tion. The posteroanterior view of each filmwas graded for the profusion of opacities bytwo experienced observers separately (oneradiologist and one pulmonary specialist)according to the ILO 1980 classification.2 Togroup patients with similar profusions of dis-ease, four categories were defined on the basisof the same ILO profusion grades: category0 = profusion grades 0/-, 0/0, 0/1; category1 = profusion grades 1/0, 1/1, 1/2; category2 = profusion grades 2/1, 2/2, 2/3; category3 = profusion grades 3/2, 3/3, 3/ + , associ-ated or not with coalescence. In the presence ofa discrepancy between the two readers (differ-ence in the CR categories > 1), the CR filmswere read by the two readers together and afinal evaluation was reached.

HIGH RESOLUTION COMPUTED TOMOGRAPHYHigh resolution computed tomography scanswere obtained in the supine position by meansof a third generation tomograph (GE CT/T9800, GE Sytec 3000) with a two to three sec-ond scanning time and a 512 x 512 matrix.The HRCT was performed with breath heldafter deep inspiration and a 1-1 5 mm sectionthickness at 10 mm intervals from the apex tothe base of the lungs. The scans were per-formed with a small field of view (from 26 to30 cm) and targeted by means of a bonealgorithm. All images were photographed atwindow levels and widths appropriate forlung parenchyma (level = -500-600, width =

1200-1500) and for the mediastinum (level =10-50, width = 250-350).

All HRCT images were graded by the sametwo readers separately, according to the criteriaof Bergin et al for the profusion of theparenchymal opacities.'8 Briefly, they wereclassified in five categories as follows: category0 = no definite nodules; category 1 = smallnumber of nodules without disruption of vas-cular markings; category 2 = many definitenodules, but with no confluence; category 3 =

confluence of nodules with disruption of vas-cular markings; category 4 = confluence ofnodules extending over two or more slices.The HRCT scans were also scored for theextent of nodules or emphysema with a visualscoring system; this four point system wasbased on estimation of the percentage of the

overall area that showed emphysematous ornodular changes: grade 1 = involvement oflung parenchyma < 25%; grade 2 =

involvement of 25%-50% of the parenchyma;grade 3 = involvement of 50%-75% of theparenchyma; grade 4 = involvement of lungparenchyma > 75%. Discordant resultsbetween the two readers were resolved as forCR.

Density measurements of lung parenchymawere performed in 20 patients. Densities byHRCT were expressed in HUs (HounsfieldUnits). A mean value of density was com-puted separately for a right and left section ofthe lung parenchyma, taken in the top (at theaortic knob level) and in the middle (at thelevel of the right middle lobar bronchus) ofthe field. The distribution of different densityclasses at the above mentioned levels, werevisualised by means of histograms.

PULMONARY FUNCTION TESTSEach subject completed the following mea-surements: static lung volumes (vital capacityand its division by spirometry; functionalresidual capacity by multiple nitrogenwashout technique), forced vital capacity(FVC) and derived indices (by Fleisher No 3pneumotacograph), diffusion capacity of car-bon monoxide (TLCo) using the single breath(TLCOSB), and steady state (TLCOSS) tech-nique; arterial oxygen and carbon dioxide tension(Pao2 and Paco2). Lung volume and flowswere measured by means of an HP PulmonaryDesk System 47804/A; reference values wereobtained by Paoletti et al for the flow volumecurve,'9 and from Quanjer for static lung vol-umes.20 Diffusion capacity was obtained bymeans of a Morgan Resparameter MK4; ref-erence values were derived from Cotes for thesingle breath technique2' and from Bates et alfor the steady state technique.22

STATISTICAL ANALYSISThe concordance in the CR and HRCT inter-pretations between two readers, and betweenCR and HRCT was evaluated by the Cohen'sK statistic. Analysis of variance was used tocompare mean values of pulmonary indices(in percentages of the predicted value) amongdifferent classes of radiological involvement,and multiple logistic regression analysis wasused when the influence of smoking andchronic bronchitis on the relation betweenHRCT categories and spirometric impair-ment was considered. The distribution of thedifferent classes of lung density in groups ofsubjects with different degrees of silicosis byHRCT was analysed with the Kolmogorov-Smirnov non-parametric test. A level of prob-ability < 5% was considered as significant.23

ResultsThe agreement between two readers aboutthe categories of parenchymal opacities onCR and HRCT was better for HRCT than forCT (Cohen's K statistic: 0-49 v 0-29 respec-tively). The largest discrepancy occurred inthe 0 and 1 categories.

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a)._

0

0)

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0

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0 0 c

0 00

0 00 0 0

0 00 0 0

0 0

0 0

0 1

0 0

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2CR categories

Table 1 Clinical data of27 subjects exposed to silica dust, with different categprofusion ofsmall opacities by CR

0 1 2

Subjects (n) 8 10 7Mean (SD) age (y) 57-8 (5-9) 55-6 (9-2) 57-7 (12)Smoking (n):

Current smokers 2 5 1Ex-smokers 4 4 5Non-smokers 1 2 1

Mean (SD) Wack/y) 187 (14 3) 14 3 (13) 15-2 (13-9,Mean (SD) silica exposure (y) 35-2 (8) 29-2 (13-2) 31 2 (12 3;Chronic bronchitis (%) 71-4 54-5 71-4

Table 2 Mean (SD) values ofpulmonaryfunction tests (% ofpredicted valublood gas concentrations in CR categories of different profusion of the parenchyiopacities (categories 2 and 3 were pooled because oflow numbers ofsubjects)

0 12

Subjects (n) 8 10FVC 96-6(17 6) 99 3(212)FEV, 89-7 (19 7) 94 (14-7)MEF5(, 73-8 (27 4) 87.9 (27 0)MEF7, 57-6 (21-2) 65 (29-0)FEV,/FVC 66-2 (9-0) 69-9 (7 7)VC 107-8 (14-7) 109 (20 0) 1RV 82-3 (12-5) 84 (20 8)FRC 93-7 (17-1) 94-9 (18-7) 1TLC 97-9 (10-8) 99-2 (15-1)TLCOSB 113-5 (11-4) 107-1 (43-0)TLCOSS 90-9 (26-8) 87-8 (35 7)Paco2 (mm Hg) 38-1 (4 5) 39-2 (3-6)Pao2 (mm Hg) 101 0 (15-7) 94-3 (12-7)

*P < 0-05 v category 1.

Table 3 Mean (SD) values ofpulmonary function tests (% ofpredicted valueblood gas concentrations in HRCT categories ofprofusion ofparenchymal opac(categories 2, 3, and 4 were pooled, because of low numbers of subjects)

0 1 2

Subjects (n) 7 13FVC 103 (15-3) 92 (19-4) 9FEV, 102-2 (11-9) 85-1 (15-4)* 8MEF5O 98 6 (12-9) 73-6 (28.1)* 5MEF7, 81-4 (24-7) 57.5 (28-4)* 4FEV,/FVC 72-4 (5 7) 66-4 (10-2) 6VC 113-7 (13 1) 102-5 (19-1) 1CRV 79-1 (18-8) 77 (22-5) 9FRC 91 9 (204) 92-8 (18-5) 10TLC 100-5 (13 6) 91-8 (14 7) 10TLCOSB 116-5 (30-4) 105-2 (30-7)TLCOSS 91 (20-9) 96-7 (28-6)Paco2 (mm Hg) 39-5 (3-2) 38-9 (4-3) 3Pao2 (mm Hg) 95-1 (12 7) 98 (14-6) 9

*P < 0-05 v category 0; tP < 0-05 v category 1.

Table 1 shows the distribution of the sub-jects in the different CR categories. There wasno significant difference in the mean age,

Do smoking, or duration of work between the CRcategories, although subjects with higherprofusion of small opacities were mainlyex-smokers or non-smokers. Symptoms ofchronic bronchitis (according to the CIBAGuest Symposium criteria) were reported by17 out of 27 subjects (63%), without any sig-nificant difference between the different cate-gories.

There was a mild concordance betweenCR and HRCT categories of parenchymalopacities. Only 10 out of 27 subjects were

3 4 classified in the same category for CR andHRCT (fig 1), and the largest discrepancywas found in the categories 0 and 1. Eightsubjects were classified in the category 0by CR; only two of these eight were classifiedin the category 0 by HRCT. Similar findings

tonies of existed for the subjects classified in thecategory 0 by HRCT. The concordance

3 between CR and HRCT was not influenced2 by smoking or symptoms of chronic bron-

60 (8-5) chitis; in particular chronic bronchitis was- reported in a similar percentage of subjects-2 with category 0 by HRCT or CR (five out of

)- eight subjects with category 0 by CR, and in20 (21-2) four out of seven subjects with category 0 by50

HRCT).No relation was found between pulmonary

function tests and profusion of parenchymalopacities as assessed by CR, except for areduction of maximal expiratory flow at 50%

te) andof FVC (MEF5O) in the highest CR category

Pmal (table 2). On the contrary, the profusion ofopacities detected by HRCT was associated

+ 3 with an impairment of the indices of airwayobstruction (FEVI, MEFO, MEF75) and diffu-

96-4 (9) sion capacity (table 3); in particular, subjects82-6 (9-5) with the highest category by HRCT showed57.9 (18(7)* lower values of FEVI, expiratory flows, and56 (33-7)63-6 (9) diffusion capacity than subjects with category 0[04-6 (9) or 1. Subjects with simple silicosis by HRCT86.2 (45-5)1033 (404) (categories 1 and 2) and subjects with con-97 5 (23-5) glomerated silicosis (categories 3 and 4)84 (33-8)73-8 (24 9) showed lower FEV1 and expiratory flows40 (2°5) compared with subjects without silicosis92.5 (13-6)

(category 0), but subjects with conglomeratedsilicosis had higher values of RV and FRCthan subjects with simple silicosis (fig 2).Evaluation of cigarette smoking in these sub-jects identified a significant relation withimpairment of FRC and total lung capacity,

-es) and but not with other spirometric indices.Stoles Multiple logistic regression analyses between

pulmonary function tests and HRCT cate-+ 3 + 4 gories showed that the relation was not7 explained by smoking or symptoms of chronic39-6 (12) bronchitis.315 (8)*51 (116)*t The HRCT evaluation of emphysema12(4 (17.4)* showed a significant reduction of TLCOSB52 (6.3)*)7 2 (9 7) (percentage of the predicted value) in subjects)9 (41) with the highest grades of emphysema (113)9 (39-5))5 (21) (28-8)% in grade 0, 103-3 (39 9)% in grade 1,7898 (40)* and 63-9 (24-1)% in grade 2, P < 0-05).59.3 (27)-t59 6 (2-8) There was also a significant correlation)22 (14-5) between the grades of emphysema and the

HRCT categories of profusion (r = 0-75, P <

Figure 1 Concordancebetween CR andHRCTcategories (Cohen's Kstatistic: 0 49).

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m0= 1 + 2M 3 + 4* P<0.05; **P<0.01forO v(1 +2)

Figure 2 Mean values ofpulmonary function tests in pooled HRCT categories ofprofusion ofparenchymal opacities.

0O001) or of extent (r = 0A43, P < 0-05) ofparenchymal opacities; in fact, subjects withthe higher categories of nodule profusion byHRCT also had higher grades of extent ofemphysema.

In 20 patients histograms of lung densitywere obtained from two slices of the HRCTscans, and their mean values were comparedbetween the different HRCT categories.There was a significant difference in the distri-bution of classes of lung density between cate-gory 1, and categories 3 + 4 (X2 = 6, P <005, fig 3).

DiscussionIn recent publications there is some disagree-ment on the concordance between CR andCT in the evaluation of the profusion of lungparenchymal opacities in silicosis, especiallyin the initial stages.' 48 This discrepancy canbe partially explained by the lack of a "goldstandard" for the diagnosis of silicosis, tosome methodological problems related to thetechnique of analysis, and to interpretation bythe readers. A true gold standard for interpre-tation of x ray films should be the morphologyof the lung parenchyma obtained by necropsy

Figure 3 Percentagedistribution ofdensityclasses in a section of theupper lungfield in differentHRCT categories.Distribution ofcategory 1is significantly differentfrom that of category 3 + 4(x2 = 6, by Kolmogorov-Smirnov test, P < 005).

60

50 -

40 -

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20 -

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or transbronchial or open biopsy. The fewdata published on this point concern mainlyother interstitial lung diseases and only occa-sional cases of silicosis are reported24; further-more, the relation between CT andmorphology was only qualitative, and no com-parison was attempted between the profusionof small opacities detected by HRCT and amorphological score of interstitial involve-ment. Other authors used the mineral contentof bronchoalveolar lavage cells as a surrogateof the total lung burden of dust25; unfortu-nately, the technique of this analysis is notcompletely standardised, and a clear cut offpoint between normal and exposed subjectshas not been reported. This technique, how-ever, could identify the severity of the expo-sure to dust, but not the degree of the reactionof the lung parenchyma to silica dust.Our data confirm the poor concordance

between CR and HRCT in the early stages ofthe disease. In the absence of a gold standardfor the diagnosis of silicosis, it is difficult todecide which technique is more accurate todetect early parenchymal involvement in sili-cosis. The better concordance between thereaders for HRCT than for CR, similar to thatreported'4 despite the absence of ILO typefilms for the CT images, and the presence of asignificant correlation between HRCT cate-gories and pulmonary function tests seem toindicate a better accuracy for HRCT than forCR.The presence of a significant relation

between the profusion of the parenchymalopacities evaluated by HRCT, and the pul-monary function tests has not been exten-sively reported in previous studies. Begin andcoworkers showed that lung volumes, diffu-sion capacity, and expiratory flow rates weresignificantly reduced in the presence of com-plicated silicosis (coalescence or conglomera-tion of nodules on chest x ray films or CT),but that there was a significant correlationbetween expiratory flow rates and profusioncategories in subjects with simple silicosis.17Some authors think that the functional abnor-malities are almost completely explained bythe presence of pulmonary emphysema, which

- Category 0L Category 1M Category 2m Category3+4

u0 Mt CV)

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Density classes

mm-V, r- t

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is mainly related to smoking.'618 Our studyshows that the increasing severity in HRCTcategories is associated with progressive deteri-oration in expiratory flows and diffusioncapacity, whereas no relation could be foundbetween CR categories and lung function.This finding has not been previously reported,and supports the argument that HRCT ismore accurate in detection of functionally sig-nificant pulmonary changes. In particular,category 0 by HRCT selected subjects withnormal lung function better than category 0 ofCR, whereas higher categories of HRCT areassociated with higher abnormalities in lungvolumes, expiratory flows, and diffusioncapacity. A recent study shows that the degreeof silicosis but not of emphysema at necropsy,was associated with a significant impairmentof lung function in non-smoking gold min-ers,26 which suggests that silicosis can causechanges in pulmonary function without thecontribution of smoking and emphysema. Soas HRCT correlates better than CR with pul-monary function tests it can be argued thatHRCT is more accurate than CR. Previousresults had suggested that parenchymal nod-ules can also be found in symptomatic smokerswithout relevant airway obstruction.27 Thuswe could argue that parenchymal opacitiesfound by HRCT are mainly due to smokingand to the concomitant chronic bronchitis,which then explains the association withabnormal pulmonary function tests. The pres-ence of similar percentages of smokers in ourHRCT categories does not support thishypothesis, although the limitation of oursample does not allow a separate analysis ofsmokers and non-smokers. The results of themultiple logistic regression analysis betweenpulmonary function tests and HRCT cate-gories, taking into account smoking andchronic bronchitis, showed that the relationfound was not explained by these confound-ing factors.As reported by other authors,'7 HRCT

detected the presence of the coalescenceor conglomeration in silicosis better thanCR, and subjects with conglomerated silicosisby HRCT showed more impairment inpulmonary function than did subjects withsimple silicosis. This fact was not found withCR, which again supports HRCT as beingmore accurate in grading the severity ofsilicosis.The extent of emphysema as detected by

HRCT was in general mild in our subjects(all of them had a category < 2); nevertheless,a significant difference in diffusion capacitywas found between the different categories ofthe extent of emphysema, which confirmedprevious results.'6 18 Recent data have con-firmed a significant correlation betweendiffusion capacity and emphysema detectedby CT in subjects with mild to moderateCOPD.28 A significant correlation was foundin our subjects between the severity ofemphysema and the severity of nodularparenchymal opacities, which suggests thatemphysema could be related to the silicosisand not only to associated smoking or

chronic bronchitis. With the present data wecannot definitively assess the relative impor-tance of silica exposure and smoking in thedevelopment of emphysema; more extensiveevaluation on a larger number of subjectscould allow a separate analysis of thesefeatures.

Finally, the study of the distribution of theclasses of different density of the lungparenchyma detected by HRCT showed sig-nificant distinctions only between the extremecategories of HRCT. In asbestosis otherauthors showed a very high sensitivity of thistechnique of objective assessment of HRCTto select subjects with early asbestosis fromnormal subjects.29 The lower sensitivity of thistechnique in our experience could beexplained by the simultaneous presence ofemphysema and nodular parenchymalopacities in the different categories ofHRCT, with conflicting influences on thedistribution of the lung density classes.Although the weak significant differenceamong the different HRCT categories sup-ports the validity of our HRCT classification,this technique seems not to have relevantusefulness in the clinical evaluation ofsilicosis.

In conclusion, our study suggests thatHRCT is more reproducible and accuratethan CR in the assessment of the severity ofpulmonary involvement in silicosis, and inthe selection of subjects with different pul-monary functional impairment, althoughthere is no evidence that the sensitivity ofHRCT is better than CR in the earlydetection of silicosis.

1 Graham WG. Silicosis. Clin Chest Med 1992;13:253-67.

2 International Labour Office. Guidelines for the use of ILOinternational classification of radiographs of pneumo-coniosis; revised ed. Geneva: ILO, 1980. (OccupationalSafety and Health Series No 22.)

3 Muir DCF, Bernholz CD, Morgan WKC, Roos JO, Chan J,Maehle W, et al. Classification of chest radiography forpneumoconiosis: a comparison of two methods of read-ing. BrJ Ind Med 1992;49:869-71.

4 Musch DC, Landis JR, Higging ITT, Gilson JC, JoneseRN. An application of Kappa-type analysis to inter-observer variation in classifying chest radiographs forpneumoconiosis. StatMed 1984;3:73-93.

5 Nemery B, Veriter C, Brasseur L, Frans A. Impairment ofventilatory function and pulmonary gas exchange in nonsmoking coal miners. Lancet 1987;ii: 1427-30.

6 Ng TP, Tsin TW, O'Kelly FJ, Chan SL. A survey ofthe respiratory health of silica exposed gemstoneworkers in Hong Kong. Am Rev Respir Dis 1987;135:1249-54.

7 Rom WN, Bitterman PB, Rennard SI, Cantin A, CrystalR. Characterization of the lower respiratory tract inflam-mation of non smoking individuals with interstitial lungdisease associated with chronic inhalation of inorganicdusts. Am Rev RespirDis 1987;136:1429-34.

8 Bisson G, Lamoreux G, Begin R. Quantitative gallium-67lung scan to assess the inflammatory activity in thepneumoconiosis. Semin Nuc Med 1987;17:72-80.

9 Mc Loud T. Occupational lung disease. Radiol Clin NorthAm 1991;29:931-41.

10 Remy-Jardin M, Remy J, Farre I, Marquette CH.Computed tomographic evaluation of silicosis and coalworker's pneumoconiosis. Radiol Clin North Am 1992;30:1155-76.

11 Mathieson JR, Mayo JR, Staples CA, Muller NL. Chronicdiffuse infiltrative lung disease: comparison of diagnosticaccuracy of CT and chest radiography. Radiology1989;171:111-6.

12 Muller NL, Miller NN. State of the art: computed tomo-graphy of chronic diffuse infiltrative lung disease. AmRev Respir Dis 1990;142:1440-8.

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19 Paoletti P, Pistelli G, Fazzi P, Viegi G, Di Pede F,Giuliano G, et al. Reference values for vital capacity andflow-volume curves from a general population study.Bulletin of European Physiopathology and Respiration1986;22:451-9.

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23 Armitage P. Statistica medica. Milano: Feltrinelli, 1981.24 Mathieson JR, Mayo JR, Staples CA, Muller NL. Chronic

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25 Lusuardi M, Capelli A, Donner CF, Capelli 0, Velluti G.Semi-quantitative x ray microanalysis of bronchoalveolarlavage samples from silica-exposed and non-exposedsubjects. Eur RespirJ 1992;5:798-803.

26 Hnizdo E, Sluis-Cremer GK, Baskind E, Murray J.Emphysema and airway obstruction in non-smokingSouth African gold miners with long exposure to silicadust. Occup Environ Med 1994;51:557-63.

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