Thorax (i964), 19, 28

Pulmonary function in sclerodermaBLAIR RITCHIE'

From the University of Melbourne Department of Medicine, Royal Melbourne Hospital

Pulmonary manifestations of scleroderma havebeen well documented in terms of the clinical,radiological, and pathological appearances

(Orabona and Albano, 1958). The variability ofthe disease is indicated by case reports of respira-tory manifestations without evidence of radiologi-cal abnormalities in the lung fields (Miller, Fowler,and Helmholtz, 1959a), the presence of radiologi-cal abnormalities without symptoms (Orabona andAlbano, 1958), pulmonary manifestations preced-ing the cutaneous and articular changes (Haymanand Hunt, 1952; Shuford, Seaman, and Goldman,1953), and pathological changes without clinicalevidence (Piper and Helwig, 1955).A more objective assessment of the pulmonary

changes, and their earlier detection even in theabsence of radiological changes, is possible bymeans of tests of pulmonary function. Although,until recently, such studies have been infrequent,the pattern of abnormality of a reduced ventila-tory capacity, a reduction in lung volumes, andevidence of 'alveolar-capillary block' was re-

corded by Baldwin, Cournand, and Richards(1949) and by Spain and Thomas (1950), whileMiller et al. (1959a) reported abnormalities of lungfunction in the absence of radiological changes.

This paper reports more extensive studies ofpulmonary function in 22 patients with sclero-derma and correlates these findings with the clini-cal, radiological, electrocardiographic, and patho-logical findings. Particular attention is paid to therelation of the pulmonary findings to the extent ofthe skin changes. Evidence is presented to supportthe view that scleroderma is essentially a general-ized disease, the extent of the visceral involvementbeing unrelated to the extent of the cutaneousmanifestations.

MATERIAL AND METHODS

Twenty-two patients with seleroderma were studied,17 females (aged 25 to 75, mean 51-2 years) and fivemales (aged 38 to 61, mean 46-4 years). Eighteenpatients had been investigated previously as part ofa larger study of the extra-pulmonary manifestations

I Present address: King's College Hospital, London, S.E.5.

of scleroderma (Lumb, F., to be published); the fourothers were referred from out-patient clinics for lungfunction tests. Raynaud's phenomenon, stiffness of thefingers, or joint pains had been present for two to36 years (mean 10-2 years). Symptoms had beenpresent for over 10 years in six patients. All patientshad characteristic skin changes, which were localizedto the fingers in eight but were more extensive in theremainder; 15 patients had radiological or biochemi-cal evidence of gastro-intestinal involvement.

CLINICAL ASSESSMENT In the assessment of thesymptoms and signs of cardiac and pulmonarydisease, special attention was paid to the definition ofexertional dyspnoea, changes in the skin of thethorax, thoracic mobility, and adventitious sounds.Respiratory symptoms were assessed by the use ofa questionnaire (Fletcher and Tinker, 1961). Chronicbronchitis is defined as the presence of cough orsputum for more than three months of the year.

Exercise tolerance was classified as follows: Grade1: able to keep up with others of the same age onstairs, hills, or heavy work; Grade 2: able to keepup with others of the same age on the flat only;Grade 3: unable to keep up on the flat but able towalk for a mile at own pace; Grade 4: able to walka few yards only without resting; and Grade 5:unable to walk more than 25 yards on the flat, breath-less on dressing, or confined to the house by dyspnoea.The presence and extent of increased thickness and

loss of elasticity of the skin over the chest wall weredetermined by inspection and palpation. The chestexpansion from full expiration to full inspiration wasmeasured at the level of the third costal cartilage,the highest of three readings being accepted. Persistentpulmonary crepitations on deep inspiration, especiallyat the bases, were carefully sought by two observersindependently.

Postero-anterior and lateral chest radiographs wereread independently by three observers who were un-aware of the clinical findings. In particular, they wereasked to record appearances suggestive of cystic orfibrotic changes in the lung parenchyma; the recordedresults reflect the combined judgments. A standard 12-lead electrocardiogram was recorded on each patient.In all cases a barium swallow examination was per-formed to assess the motility and diameter of theoesophagus.

PULMONARY FUNCTION STUDIES With the patientseated, vital capacity (V.C.), estimated in the conven-

28

on 7 July 2018 by guest. Protected by copyright.

http://thorax.bmj.com

/T

horax: first published as 10.1136/thx.19.1.28 on 1 January 1964. Dow

nloaded from

Pulmonary function in scleroderma

tional unhurried manner, and a forced expiratoryspirogram were recorded using a low resistance spiro-meter and Palmer kymograph with a paper speed of3 cm./sec. both before and after one and a halfminutes' inhalation of a 1% isoprenaline sulphateaerosol from a Wright nebulizer with compressed air.Normal standards for V.C. and forced expiratoryvolume in 1 second (F.E.V.l.o) were taken from Miller,Johnson, and Wu (1959b). Lung volumes weremeasured by the closed-circuit helium dilution methodand compared with the predicted values by theformulae of Needham, Rogan, and McDonald (1954).Total lung capacity (T.L.C.) was predicted from thesimple regression based on height; 6% was added topredicted values to convert from ambient to bodytemperature (atmospheric pressure, water vapoursaturation). Ventilatory response to exercise at a pre-determined work level was measured in 19 patientsduring a five-minute stepping test previously describedwith normal standards (29±5 1./min.) from thislaboratory (Gandevia, 1962). The result is expressedas a standardized ventilation in litres per minute'adjusted' to a 300 kg. M. per minute work level(S.V.300). The work levels used were adjustedaccording to sex and stated exercise tolerance; unlessexercise tolerance was severely impaired, a 350 kg. M.level was used for males and a 250 kg. M. level forfemales. The diffusing capacity of the lungs for carbonmonoxide (DLzo) was determined in 18 patients by thesingle-breath method of Ogilvie, Forster, Blakemore,and Morton (1957). The mean of duplicate estima-tions, which agreed to within ±2 ml., was accepted.Lung compliance, using a thin-walled oesophagealballoon 11 cm. long containing 2 ml. of air, wasmeasured in 19 patients during spontaneous breathingin the sitting position at respiratory rates between 8and 20/min., and during a slow vital capacitymanoeuvre with breath-holding in the more co-opera-

tive subjects. The pressure difference between themouth and the oesophagus and the tidal volumes wererecorded as a pressure-volume 'loop' with the Godartcompliance apparatus. The results of DLCO, and com-pliance were compared with those obtained by thesame methods in 20 normal subjects of the same ageand sex distribution as the patients with scleroderma;the lowest limits of normal values for these are 14ml./min./mm. Hg and 0-100 litre/cm. water respec-tively. The control subjects had no respiratory symp-toms or signs, a normal chest radiograph, and normalvalues for V.C. and F.E.V.a.o.

RESULTS

CLINICAL ASSESSMENT Table I shows the physicalcharacteristics and symptoms in the 22 patientsstudied. Thirteen patients had some impairment ofexercise tolerance. Ten gave a history of chronicbronchitis; only four of these patients smoked(Nos. 3, 9, 10, and 20) and in five of the non-smokers bronchitic symptoms developed after theonset of symptoms of scleroderma. Three patients(Nos. 10, 16, and 21) had a history of pleurisywhich began after the onset of symptoms ofscleroderma.Table II shows the results of the clinical, radio-

graphic, and electrocardiographic examination.The skin over the chest wall was involved in sevenpatients but lesions extended below the upper one-third of the chest in only one patient (No. 7).Twelve patients had a chest expansion of less than5 cm.; nine of these had no changes in the skinof the chest wall. Crepitations were present in 14subjects but were localized to one side in four.

TABLE IPHYSICAL CHARACTERISTICS AND SYMPTOMS

Duration of ExercisePatient Sex Age Height Weight Symptoms of Respiratory Symptoms Exerce SmoknNo. ~~~~(cm.) I (kg.) Scieroderma ReprtrGyposTlrance Hsmokin

(Years)Grd Hity

I F 37 162-5 510 4 Nil 22 F 45 165-0 56-5 6 Nil 23 M 44 169-5 71-5 3 Bronchitis 5 years I +4 F 47 167-0 56-5 24 Bronchitis 5 years I5 F 67 157-5 55-0 30 Bronchitis 2 years 36 M 61 180-0 57-5 7 Nil 47 M 42 180-0 72-5 4 Nil I8 F 64 162-5 40-5 2 Bronchitis nrany years 29 M 38 175-0 66-5 8 Bronchitis 12 years I -4-10 F 51 167-0 58-5 18 Bronchitis 30 years; pleurisy 12 years previously I +11 F 52 167-0 62-0 4 Nil I12 F 73 157-5 42-0 7 Bronchitis 1 year 413 F 49 147-0 35-5 36 Bronchitis 2 years 414 F 58 165-0 65-0 14 Nil t _15 F 58 157-5 54-5 8 Nil I _16 F 35 152-0 48-0 19 Pleurisy 3 months previously 317 F 25 157-5 60-0 6 Nil I118 F 69 162-5 77-0 4 Bronchitis 5 years 3-419 F 75 167-0 54-0 9 Nil 420 M 47 175-0 76-0 3 Bronchitis 10 years 4 +21 F 34 157-5 51-0 5 Pleurisy 4 years previously 2-422 F 31 160-0 47-0 4 Nil 4-5

29

on 7 July 2018 by guest. Protected by copyright.

http://thorax.bmj.com

/T

horax: first published as 10.1136/thx.19.1.28 on 1 January 1964. Dow

nloaded from

Blair Ritchie

TABLE IIRESULTS OF CLINICAL, RADIOGRAPHIC, AND E.C.G. EXAMINATIONS

Skin Changes Chest Pulmonary CetBlood BruPatient CetBruNo. Hands Chest Other Expansion Crepita- Radiograph Pressure E.C.G. Swallow2

Only Wall Sites (CM.) tions1 sga (mm. Hg)

I _ + + 6 5 - Normal 120/70 Normal2 - + + 4 0 + + Normal 140190 Normal + +3 +± _ 10-0 + Normal 120/75 Normal4 _ + + 4 0 + + Normal 140/90 Normal + +5 +± _ 2 0 + Normal 160/90 Normal6 _ + + 5-0 + Increased heart size 130'80 Right bundle branch block + + +7 _ + + 7-0 _ Normal 180/105 Normal +8 _ + + 5*0 _ Normal 120/65 Normal9 _ _ + 4-5 ++ Normal 210/130 Normal + +10 + _ _ 5 5 + + Normal 110150 Normal +1 1 +± _ 7-5 _ Normal 130/80 Transient T wave inversion V1-3 +12 _ _ + 3-5 _ Normal 120'65 Normal +13 _ _ + 4-0 + + Bilateral basal reticular and 165/90 Normal + + +

nodular shadows14 _ _ + 3*5 _ Normal 160 100 Normal +15 +± _ 5*5 _ Normal 160 90 Normal16 + _ _ 8-0 + Cysts right base 130190 Normal17 _ + + 2-0 _ Normal 100'70 Normal18 _ _ + 1-0 + + Normal 130/80 Normal +19 - _ + 4 0 + + Bilateral fine reticular and 220 110 Right bundle branch block

nodular shadows overlower half of lung fields

20 + 6-0 +++ Bilateral coarse reticulation 110 90 Right ventricular hypertrophy +over lower two-thirds oflung fields

21 +_- 40 +++ Bilateral basal coarse reti- 105,75 Right ventricular hypertrophy + +culation

22 + 4 0 + + + Increased basal broncho- 180,'80 Right ventricular hypertrophyvascular markings; dilatedmain pulmonary artery

1 + Localized to one side; + + at both bases; + + + extending above inferior angle of scapula.2 + Loss of motility of oesophagus; + + loss of motility and dilatation of oesophagus; + + + loss of motility, dilatation and mucosa

ulceration of oesophagus.

Radiological abnormalities in the lung paren-chyma attributable to scleroderma were presentin six subjects. Two patients (Nos. 20 and 21)showed a coarse reticular pattern which extendedover the lower two-thirds of the lung fields in one(No. 20, Fig. 1). Two (Nos. 13 and 19) showedcombined reticular and nodular shadows at thebases. One subject (No. 22, Fig. 2) showedmarked dilatation of the pulmonary artery with aminimal increase in the basal broncho-vascularmarkings, and another (No. 16) showed large'emphysematous' cysts at the right base. With oneexception (No. 17), all patients with radiologicalchanges had basal crepitations, but three patientswith basal crepitations had a normal chest radio-graph. Radiological abnormalities in the lungswere present in three patients who had no respira-tory symptoms. Four patients had casual bloodpressure recordings above 160/90 mm. Hg withoutclinical or electrocardiographic evidence of leftventricular hypertrophy or retinal changes; basalcrepitations were present in two of these (Nos. 9and 19), and one (No. 19) had a radiographicabnormality. Radiological evidence of cardiacenlargement was present in two other patients(Nos. 6 and 11); in one (No. 11) this was atransient finding a year before the present study.

Electrocardiographic abnormalities were presentin five patients, two having right bundle branchblock (Nos. 6 and 19), three right ventricularhypertrophy (Nos. 20, 21, and 22), and a sixth(No. 11) one year previously had temporary Twave inversion over leads V1I3 which was notpresent at the time of the study. Four of thesepatients (Nos. 19, 20, 21, and 22) had radiologicalabnormalities in the lung fields and five (Nos. 6,19, 20, 21, and 22) had basal crepitations. Thepresence of pulmonary hypertension was con-firmed in one patient (No. 22) by right heartcatheterization, the main pulmonary artery pres-sure being 65 mm. Hg systolic and 30 mm. Hgdiastolic.The barium swallow examination was abnormal

in 13 patients. Two patients (Nos. 6 and 13) hadgross stasis with dilatation and ulceration of theoesophageal mucosa. Nine of these patients hadnormal lungs radiologically.

PULMONARY FUNCTION Table III shows the resultsof the pulmonary function studies expressed inabsolute values. All but one of the 22 patientstested showed some abnormality; the exception(No. 16) was not fully studied. Seven patientsshowed single defects in pulmonary function, four

30

on 7 July 2018 by guest. Protected by copyright.

http://thorax.bmj.com

/T

horax: first published as 10.1136/thx.19.1.28 on 1 January 1964. Dow

nloaded from

FIG. 1. Patient 20. Chest radiograph showing reticular and nodular shadowsover lower two-thirds oflungfields.

FIG. 2. Patient 22. Chest radiograph showing dilated main pulmonary artery withsome increase in the basal broncho-vascular markings.

on 7 July 2018 by guest. Protected by copyright.

http://thorax.bmj.com

/T

horax: first published as 10.1136/thx.19.1.28 on 1 January 1964. Dow

nloaded from

Blair Ritchie

TABLE IIIPULMONARY FUNCTION STUDIES

4 61 (98) 32(36)6-51 (134) 51 (38)7 63 (118) 35( 34)5-28 (10o) 28 (39)3-02 (67) 33 (46)6-26 (87) 35 (48)o-81 (95) 30(35)4-09 (99) 43 (47)5 64 (83) 21 (34)3 79 (76) 40 (40)5 26 (105) 28 (40)3-66 (90) 44 (50)4-54 (87) 62 (43)3-42 (71) 45 (41)5-15 (115) 54(43)4-84 (108) 35 (36)3-61 (80) 28 (31)3-47 (74) 47 (43)4-38 (88) 48 (49)4 80 (70) 47 (35)2 82 (63) 39 (36)3 04(66) 31 (35)

F.R.C.(%~) I~*0 (in.c DLCO Complianc(SV3 min 5A (10.cm.I... (1Im. mm.Hg) H210)58 (55) 40 366 (55) 39-645 (52) 39.749 (55) 33-750 (59) 69-959 (68) 46-563 (56) 37-469 (64) 55 658 (55) 34-160 (55) 28-654 (53) 31-067 (65) 17 877 (64) 51-355 (53) 21-066 (58) 31-459 (56) 28-344( 50) 29-256 (50) 30-261 (61) 40 266 (52) -63 (55) 64 161 (56) -

20 2 13 2 0-136

24-512 48-3

21t523-117-528-717 312 811 214 317-322-4

14 620 514 79 06-32 3

13 47-65.4

12 112 012 515t910 47.58 1

11 710.1

14-5

9.111 29-24.74-216

0 1760 2140-0940 2500-300

0 0650 0880-0940 2800 1500 0740 0880 133

0-1430-0860 1000-083

e Com-plianceF.R.C.

0 051

0 0520-0840-0620.0(80 0700-0200 0270 0410 0700-0610 0210 0470 039

0-0890 0440-0370-026

1 Figures in brackets express result as percentage of predicted value. 2 Predicted values in brackets. 3 Body surface area.CGreater than 10 increase in F.E.V.I., after bronchodilator aerosol.

an increased ventilatory response to exercise, twoa reduced DLc,3 and one a lowered compliance.

In 12 patients the V.C. was reduced below 80%of the predicted values. The F.E.V.1 n was reducedbelow 70% of the V.C. in two patients (Nos. 7and 15), and in three (Nos. 7, 17, and 20) a 10%increase in F.E.V.1.0 was found after broncho-dilator aerosol. The total lung capacity was below80% of the predicted value in seven subjects, allof whom had a reduced V.C., residual volume(R.V.), and functional residual capacity (F.R.C.).Three others (Nos. 2, 13, and 15) had a significantincrease (above 120% predicted) in F.R.C. andR.V.; in one (No. 15) there was evidence of air-ways obstruction. Eleven of the 20 subjects testedhad an abnormally high ventilatory response toexercise (above 34 litres/min.). Three patients(Nos. 12, 16, and 18) showed a normal ventilatoryresponse but complained of severe impairment ofexercise tolerance; the very low value of 17 8litres/min. (No. 12) is probably a technical error.

Figure 3 is a plot of DLCO in 20 of the patientswith scleroderma and 20 control subjects pairedfor age and sex. The range of results in thepatients with scleroderma was from 2-3 to 28-7ml./min./mm. Hg (mean 16 0+666) and in thecontrol group from 14-0 to 27-8 ml./min./mm. Hg(mean 21-2+4-5). The range of the ratio of DLcJ/body surface area for the control group was 8 8 to17 8 and for the scleroderma patients from 16 to15 9. Seven of the patients with sclerodermashowed DLc, values below the lowest of the control

30T

20

DLcOmnl/nfn/mm Hg.

lot

*

*.0

I

a.0

I

16.

SCLERODERMA. CONTROLS.

FIG. 3. Plot of DLcO in patients with scleroderma andcontrol subjects. The bars represent the means for eachgroup.

group; five of these had a reduced V.C. and lungvolumes.Lung compliance was measured in 18 patients.

The results ranged from 0065 to 0300 litre/cm.water (mean 0137 + 0-067) and from 0-107 to0 360 litre/cm. water (mean 0 203 + 0 072) in thecontrol group. Eight patients with scleroderma hadcompliance levels below those of the controls andbelow the lower limit of normal (0 100 litre/cm.

32

F.E.V.lC.(%) T.L.C. R.V.(%)2V.C:. (I.) T.L.C.

Patient!No.

2345678910tl121 3141516171819202122

VitalCapacity'

(1.)

313 (89)3 17 (90)4 99 (117)376 (102)2 04 (67)4 08 (96)4 74 (98)2 67 (81)4.44 (95)2 29 (63)3 78 (104)2 05 (68)173 (56)1-88 (54)2 38 (77)3-15 (105)2 59 (78)1 84 (56)2-29 (71)2 54 (58)1t72 (72)2 10(66)

F.E.V.1*,(I.)

2-492 654.552 961453-883-41 41993 602 0430091741t47X *721 452 502 5841671932.4641 501660

80889179708864787983797894876890909082858280

on 7 July 2018 by guest. Protected by copyright.

http://thorax.bmj.com

/T

horax: first published as 10.1136/thx.19.1.28 on 1 January 1964. Dow

nloaded from

Puilmotnary function in scleroderma

o-o4

COCIUANCEFR.C. o-oa3

0064

0

* 0

S

II

*004j

0028t

SCLERODERMA. CONTROLS.

FIG. 4. Plot ofratio ofCFomliance in scleroderma patients

and control subjects. The bars represent the meansfor eachgroup.

water) accepted by this laboratory. Figure 4 showsa plot of the ratio of compliance to F.R.C. Fivepatients had values below those of the controlgroup and below the normal range for this ratioof 0-038 given by Marshall (1957). Three of thefive also had a reduced V.C., but only one showeda defect in DLCO.

RELATION BETWEEN CLINICAL AND FUNCTIONALABNORMALITIES There was no direct relation be-tween the duration of symptoms attributable toscleroderma and the degree of pulmonary involve-ment. Three of the seven patients with multipleabnormalities in pulmonary function (Nos. 5, 13,14, 18, 20, 21, and 22) had symptoms extendingover 10 years, and the remaining four (Nos. 18,20, 21, and 22) had had symptoms for only fiveyears or less. A complaint of shortness of breathdid not imply severe impairment in pulmonaryfunction nor an increased ventilatory response toexercise (Nos. 12, 16, and 18), although those withsevere grades of exercise tolerance (grades IVand V) usually showed multiple functionalabnormalities.

Localization of the skin changes to the fingersdid not necessarily imply absence of severe pul-monary involvement (Nos. 3, 5, and 21). Similarly,there was no correlation between chest wall or

oesophageal involvement and impaired pulmonaryfunction. None of the seven patients with func-tional abnormality in several tests had lesions overthe chest wall, and three had a normal barium

swallow. Of the 12 patients with a chest expansionbelow 5 cm., nine had a reduced vital capacity. Thepresence of basal crepitations did not necessarilyimply severe impairment in pulmonary function,although the patients with crepitations over mostof the chest (Nos. 20, 21, and 22) were severelyaffected. By contrast, the presence of abnormali-ties in the chest radiograph could be related tosevere impairment of pulmonary function (Nos.13, 18, 20, 21, and 22). Only one of four patientswith systemic hypertension showed more than oneabnormality in pulmonary function. Thc threepatients with cardiographic evidence of pulmonaryhypertension had multiple abnormalities with, inparticular, a marked reduction in diffusingcapacity; compliance was not measured in two.

In general, the seven patients with multipledefects in pulmonary function had the mostsevere impairment of exercise tolerance, basalcrepitations, and abnormal chest radiographs, butthere were notable exceptions. One patient (No.14) claimed no impairment of exercise toleranceand had no basal crepitations, and two patients(Nos. 5 and 14) had normal chest radiographs.

HISTOLOGY Specimens of lung were examined intwo subjects. One patient (No. 2) died after therapid development of malignant hypertension withrenal failure. Macroscopically, the pleural and cutsurface of the lungs appeared normal. Micro-scopically (Fig. 5), cystic spaces, some of whichwere lined with bronchiolar epithelium, replacedthe normal alveolar architecture. The interstitialtissue contained increased amounts of fibroustissue. Patchy myocardial fibrosis with normalcoronary vessels was an additional feature.A lung biopsy (Fig. 6) in a second subject (No.

13) showed replacement of normal lung architec-ture by cysts lined with a columnar epithelium.The interstitial tissue showed a marked increasein smooth muscle, fibrous tissue, and hyalinematerial. Peribronchial giant cell systems withvacuolated cytoplasm were scattered throughout.Some pulmonary vessels showed proliferation ofthe media and intima but no evidence of fibrinoidnecrosis.

DISCUSSION

The interpretation of correlations between theclinical features and the functional findings in thepatients studied is of necessity limited to specificcases; generalizations based on the whole groupare not only biased according to the selection ofthe patients in the series but also fail to reflect thevariation in the clinical, radiological, electro-cardiographic, and functional findings.

33

I.-

on 7 July 2018 by guest. Protected by copyright.

http://thorax.bmj.com

/T

horax: first published as 10.1136/thx.19.1.28 on 1 January 1964. Dow

nloaded from

Blair Ritchie

*}". .: * A:., §^t"} . \ :~~~~~~

),'' <~~

4v0W

FIG. 5. Patient 2. Photomicrograph ofnecropsy specimenof lung showing replacement of normal alveolar architec-ture by cystic spaces and compact areas offibrous tissue.(Haematoxylin and eosin, x 50).

The variability of the respiratory symptomsparalleled the functional findings. The absence ofshortness of breath in half of the patients studieddid not necessarily imply normal lung function, afinding common to other diffuse lung diseases. Thepresence of chronic bronchitis in non-smokers,beginning after the onset of symptoms ofscleroderma, suggests the possibility of bronchialinvolvement, as indicated by the pathologicalstudies of Getzowa (1945) and of Talbott andFerrandis (1956), who commented on fibrinoidchanges in the bronchial mucosa. Similarly, thepresence of bronchiectasis has been emphasized bySpain and Thomas (1950), but other workers (Hay-man and Hunt, 1952; Murphy, Krainin, and Ger-son, 1941) report bronchograms as being usuallynormal. Descriptions of pleural lesions in necrop-sied patients have not been infrequent (Getzowa,1945; Orabona and Albano, 1958) but the rarityof symptoms of pleurisy emphasized by Opie(1955) has been notable. Four patients in thisstudy gave a history of pleurisy but with no

i<V S..e V9.

4t4

jA~~~~~~~~~~~A

FIG. 6. Patient 13. Photomicrograph of lung biopsyshowing cystic spaces lined with ciliated columnar epithe-lium and increased interstitial fibrous tissue and smoothmuscle. (Haematoxylin and eosin, x 31).

clinical or radiological evidence of residualabnormality.The radiological appearances of pulmonary

scleroderma have been classified by Garland andSisson (1954) into (i) diffuse or localized fibrosis,(ii) diffuse or localized nodulation, (iii) subpleural'cystic disease' (basal), and (iv) calcification. Theearlier claim by Pugh (1948) that the appearanceswere diagnostic appears difficult to substantiate.In this study radiological abnormalities in thelungs were present in approximately a quarter ofthe series and the changes were not specific toscleroderma. Most of the patients with radio-graphic changes had severe defects in pulmonaryfunction, suggesting that the radiograph detectsonly the more severe pathological changes.

Systemic hypertension was present in fourpatients and may have been related to sclerodermalesions in the kidney (confirmed by biopsy in oneinstance, No. 9). The presence of hypertensive leftventricular failure might simulate the clinical andfunctional aspects of scleroderma of the lung,

34

'4

on 7 July 2018 by guest. Protected by copyright.

http://thorax.bmj.com

/T

horax: first published as 10.1136/thx.19.1.28 on 1 January 1964. Dow

nloaded from

Pulmonary function in scieroderma

but this does not explain the abnormalities in thepresent series. Recently Oram and Stokes (1961)have indicated the frequency of myocardial in-volvement in scleroderma. Of interest in this studywere electrocardiographic findings of non-specificT wave changes in one patient, radiological evi-dence of cardiac enlargement in another, and, ina third subject, patchy myocardial fibrosis atnecropsy.Pulmonary hypertension in scleroderma has

been discussed by Opie (1955), who described itsoccurrence with minimal radiological abnormali-ties in the lung fields. The pathological studies ofMatsui (1924) and of Weiss, Stead, Warren, andBailey (1943), demonstrating the marked intimalproliferation of the pulmonary arterioles, point tovascular obstruction as probably the most signifi-cant factor in the rise of pressure. Sackner, Akgun,Kimbel, and Lewis (1962) note a high incidence ofpulmonary hypertension in scleroderma and con-sider that this is not necessarily correlated with theclinical, radiological, or electrocardiographicsigns. In the present study patients with clinicaland electrocardiographic evidence of pulmonaryhypertension all had gross functional defects witha low diffusing capacity, although the develop-ment of severe pulmonary hypertension withminimal radiological changes in the lung fields inone patient was notable.Some authors (Finlay, 1889; Dinkler, 1891

Lewin and Heller, 1895) recorded the presence ofrespiratory symptoms and necropsy evidence ofabnormal pulmonary fibrosis, but they attributedthese changes to a reduction in mobility of thechest wall by the skin changes. The results of thisstudy and those of others (Adhikari, Bianchi,Boushy, Sakamoto, and Lewis, 1962) indicate thelack of correlation between changes in the chestwall and impairment of pulmonary function.Harper (1953) related the pathological findings offibrosis to 'spill over' from oesophageal stasis, butMahrer, Evans, and Steinberg (1954) indicated thefrequent absence of oesophageal changes inpatients with pulmonary involvement. In thisstudy only 13 of the 22 patients had evidence ofoesophageal involvement, although most of thepatients with severe impairment of pulmonaryfunction had oesophageal lesions.The results of pulmonary function studies in

general confirm the finding of previous workers ofa reduction in vital capacity, and its frequencystresses the usefulness of this measurement inpatients with scleroderma. Evidence of mild air-ways obstruction in four patients suggested thepossibility of bronchial involvement. The presenceof an increased residual volume and functional

D,

tesidual capacity in two patients in the absence ofairways obstruction supports similar observationsby Salomon, Appel, Dougherty, Herschfus, andSegal (1955), although their findings were attri-buted to bronchial obstruction. The presence ofventilated cystic spaces in the absence of airwaysobstruction could explain these results but bron-chographic (Hayman and Hunt, 1952) and patho-logical (Church and Ellis, 1950) evidence suggeststhat the cysts do not communicate directly with thebronchial tree.A notable feature of the functional studies was

the poor correlation between different tests, sothat even in patients with severe defects all para-meters of lung function were not necessarilyaffected. In patients with a single functional abnor-mality there was no one test consistently abnormal,although an increased ventilatory response toexercise was the most frequently found singledefect. Wilson, Rodnan, and Robin (1962), andCatterall and Rowell (1963) suggested that a fallin diffusing capacity was possibly the earliestabnormality detectable, but this is not confirmedin the present study.

Classifications of scleroderma into local andgeneral types based on the distribution of thecutaneous manifestations have received attention(Leading Article, 1961), and, in particular, skinchanges localized to the fingers have beenregarded by some authors (O'Leary and Waisman,1943; Brunsting, 1959) as indicating a good prog-nosis. The present study suggests that neither theduration of the cutaneous symptoms nor thelocalization of the skin lesions allows predictionof the extent or severity of pulmonary involve-ment. It remains to be seen to what extent theaccuracy of prognosis can be improved by thequantitative functional assessment of pulmonaryinvolvement.

SUMMARY

A study of pulmonary function was made in 22patients with scleroderma. Particular attention waspaid to the relation between the clinical, radio-graphic, electrocardiographic, and functionalfindings. In general, a reduction in ventilatorycapacity, lung volumes, compliance, and diffusingcapacity with an increased ventilatory response toexercise was found, but individual variation in thefunctional defects was striking. The lack of corre-lation between the extent of the cutaneous lesionsand the radiological changes in the lungs withfunctional impairment was a notable finding.There was no evidence that cutaneous lesions ofthe chest wall were responsible for the pulmonarychanges.

35

on 7 July 2018 by guest. Protected by copyright.

http://thorax.bmj.com

/T

horax: first published as 10.1136/thx.19.1.28 on 1 January 1964. Dow

nloaded from

36 Blair Ritchie

I am indebted particularly to Dr. F. H. Lumb for hisinvaluable assistance and to Dr. A. J. Barnett (BakerInstitute) for permission to study the patients underhis care. Thanks are due to Miss Nancy Rogers fortechnical assistance and to Mr. K. Inglis for the photo-graphic plates. I wish to thank Professor R. R. H.Lovell and Dr. Bryan Gandevia for their encourage-ment and helpful criticism.

REFERENCES

Adhikari, P. K., Bianchi, F. A., Boushy, S. F., Sakamoto, A., andLewis, B. M. (1962). Pulmonary function in scleroderma. Amer.Rev. resp. Dis., 86, 823.

Baldwin, E. deF., Cournand, A., and Richards, D. W., Jr. (1949).Pulmonary insufficiency: 1I. A study of 39 cases of pulmonaryfibrosis. Medicine (Baltimore), 28, 1.

Brunsting, L. A. (1959). Scleroderma. Introduction and cutaneousaspects. In symposium on manifestations of scleroderma. Proc.Mayo Clin., 34, 53.

Catterall, M., and Rowell, N. R. (1963). Respiratory function inprogressive systemic sclerosis. Thorax, 18, 10.

Church, R. E. and Ellis, A. R. P. (1950). Cystic pulmonary fibrosisin generalised scleroderma: report of two cases. Lancet, 1 392.

Dinkler, M. (1891). Zur Lehre von der Sklerodermie. Dtsch. .4rch.klin. Mfed., 48, 514.

Finlay, D. W. (1889). Scleroderma. Middlesex Hosp. Rep., p. 29.Fletcher, C. M., and Tinker, C. M. (1961). Chronic bronchitis: A

further study of simple diagnostic methods in a working popula-tion. Brit. med. J., 1, 1491.

Gandevia, B. (1962).Pulmonary ventilation on exercise and the factorsaffecting a simple standardized exercise test. Amer. Rev. resp.Dis., 85, 378.

Garland, L. H., and Sisson, M. A. (1954). Roentgen findings in the'collagen' diseases. Amer. J. Roentgenol., 71, 581.

Getzowa, S. (1945). Cystic and compact pulmonary sclerosis inprogressive scleroderma. Arch. Path., 40, 99.

Harper, R. A. K. (1953). The radiological manifestations of diffusesystemic sclerosis (scleroderma). Proc. roy. Soc. Med., 46, 512.

Hayman, L. D., and Hunt, R. E. (1952). Pulmonary fibrosis ingeneralized scleroderma. Dis. Chest, 21, 691.

Leading Article (1961). Brit. med. J., 2, 1412.Lewin, G., and Heller, J. (1895). Die Scierodermie. Hirschwald, Berlin.Mahrer, P. R., Evans, J. A., and Steinberg, I. (1954). Scleroderma:

Relation of pulmonary changes to esophageal disease. Ann.intern. Med., 40, 92.

Marshall, R. (1957). The physical properties of the lungs in relationto the subdivisions of lung volume. Clin. Sci., 16, 507.

Matsui, S. (1924). Vber die Pathologie und Pathogenese von Sclero-dermia universalis. Mitt. med. Fak. Tokyo, 31, 55.

Miller, R. D., Fowler, W. S., and Helmholtz, F. H., Jr. (1959a).Scleroderma of the lungs. Proc. Mayo Clin., 34, 66.

Miller, W. F., Johnson, R. L., Jr., and Wu, N. (1959b). Relationshipsbetween fast vital capacity and various timed expiratory capa-cities. J. appl. Physiol., 14, 157.

Murphy, J. R., Krainin, P., and Gerson, M. J. (1941). Sclerodermawith pulmonary fibrosis. J. Amer. med. Ass., 116, 499.

Needham, C. D., Rogan, M. C., and McDonald, 1. (1954). Normalstandards for lung volumes, intrapulmonary gas-mixing andmaximum breathing capacity. Thorax, 9, 313.

Ogilvie, C. M., Forster, R. E., Blakemore, W. S., and Morton, J. W.(1957). A standardized breath holding technique for the clinicalmeasurement of the diffusing capacity of the lung for carbonmonoxide. J. clin. Invest., 36, 1.

O'Leary, P. A., and Waisman, M. (1943). Acrosclerosis. Arch. Dermi.Syph. (Chic.), 47, 382.

Opie, L. H. (1955). The pulmonary manifestations of generalizedscleroderma. Dis. Chest, 28, 665.

Orabona, M. L., and Albano, 0. (1958). Progressive systemic sclerosis.Acta med. scand., 160, Suppl. 333.

Oram, S., and Stokes, W. (1961). The heart in scleroderma. Brit. HeawtJ., 23, 243.

Piper, W. N., and Helwig, E. B. (1955). Progressive systemic sclerosis;visceral manifestations in generalized scleroderma. A.M.A. Arrh.Derm., 72, 535.

Ptigh, D. G. (1948). Roentgenologic manifestations of scleroderma.Amer. J. med. Sci., 216, 571.

Sackner, M. A., Akgun, N., Kimbel, P., and Lewis, D. H. (1962).Pulmonary hypertension; a surprisingly common finding inscleroderma. Clin. Res., 10, 242.

Salomon, A., Appel, B., Dougherty, E. F., Herschfus, J. A., andSegal, M. S. (1955). Scleroderma; pulmonary and skin studiesbefore and after treatment with cortisone. A.M.A. Arch. irtern.Med., 95, 103.

Shuford, W. H., Seaman, W. B., and Goldman, A. (1953). Pulmonarymanifestations of scleroderma. Ibid., 92, 85.

Spain, D. M., and Thomas, A. G. (1950). The pulmonary manifesta-tions of scleroderma; an anatomic physiological correlation.Ann. intern. Med., 32, 152.

Talbott, J. H., and Ferrandis, R. M. (1956). Collagen Diseases.Grune and Stratton, New York.

Weiss, S., Stead, E. A., Warren, J. V., and Bailey, 0. T. (1943).Scleroderma heart disease, with a consideration of certain othervisceral manifestations ofscleroderma. Arch. intern. Med., 71, 749.

Wilson, R. J., Rodnan, G. P., and Robin, E. D. (1962). An earlypulmonary physiologic abnormality in progressive systemicsclerosis (diffuse scleroderma). Clin. Res., 10, 244.

on 7 July 2018 by guest. Protected by copyright.

http://thorax.bmj.com

/T

horax: first published as 10.1136/thx.19.1.28 on 1 January 1964. Dow

nloaded from