Interstitial Rheumatoid Lung Disease

•

CLINICAL INVESTIGATIONS

Interstitial Rheumatoid Lung Disease*

A Reassessment and Review of the Literature

Michael s. Popper, A-f.D.;t Maurice L. Bogdonoff, M.D.; and Richard L. Hughes, M.D., F.C.C.P.

Thirty rheumatoid arthritic patients (RA) _d 30 osteoarthritic patients (OA) were stadied radioInPlaicaIIy ~ fUDCtiooaly to further evaluate the sig-

nifiamce of dUfuse intentitial pulmonary disease in patients with rheumatoid arthritis. Tea RA patieDts (33 perceIlt) were found to have either radiographic or ditfusion abaormaHties consisteDt with interstitial fibrosis. None of the OA patients were foad to be affected. Except for sips aDd symptoms directly attributable to the paImoDary lesions, hBtoric: aDd diDicai cllancteristics were not found to be of value in defining affected RA patients. Surveys which screea for interstitial disease should utilize both chest ndiograpbs and diffusion capacity measuremeat for adequate evaluation.

I n addition to Caplan's syndrome,' there are three

cial attention was directed to the historic and clinical characteristics of patients found to have indications of pulmonary disease.

forms of pulmonary involvement in systemic rheumatoid disease: pleural effusions, pleuropulmonary granulomas, and diffuse interstitial pneumonitis and pulmonary fibrosis.2,3 The effusions and granulomas have characteristic features that many feel establish a definite rheumatoid patho-

METHODS

Patient Selection From January to August 1970, 32 patients with ARA defined classical or definite rheumatoid arthritis 12 and 33 patients with radiographic evidence of degenerative joint disease were interviewed. All patients were consecutively selected from the outpatient medical clinic and the hospital census of an 860 bed general hospital. The rheumatoid patients interviewed represent all patients with a known diagnosis of rheumatoid arthritis seen during that interval, while the osteoarthritic patients were limited for purposes of comparison, and were not necessarily representative of the osteoarthritic population. Thirty rheumatoid arthritic patients ( RA) and 30 osteoarthritic patients (OA) were accepted and evaluated for indications of interstitial pulmonary disease. Two osteoarthritic patients with histories of chronic bronchitis, one with uremia, and two RA patients unable to perform pulmonary function tests were excluded.

genesis.r"

Consideration of the interstitial lesion as a form of rheumatoid lung disease, however, has been based more on clinical circumstance than on definitive evidence. The pathology of this lesion is nonspecific, and radiographic surveys have failed to demonstrate the lesion to be significantly more prevalent among rheumatoid patients.I" Recently, however, two uncontrolled studies'P:'! using pulmonary function as an adjunct in evaluation, have suggested that interstitial pulmonary disease may occur with greater frequency than previously estimated from radiographic evaluation alone. The following controlled survey was therefore undertaken and used both radiographic and functional criteria to screen for diffuse interstitial pulmonary disease in patients with rheumatoid arthritis. Spe-

Investigative Protocol Complete histories were obtained from all patients and full physical examinations were performed. Tests for vital capacity (VC), maximum voluntary ventilation (MVV) and one second forced expiratory volume (FEV I) were performed with a 13" liter spirometer using standard techniques.P Residual volumes (RV) were calculated by the methods of Meneely and associates 14 and Boren and co-workers.w The Cotes HJ modification of the Krogh single breath carbon

°From the Sections of Cardio-Respiratory Disease and Thoracic Radiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago. tttr:d~~~r c:t~~ in Medicine, Rush-Presbyterian-St. Luke's

243

244

POPPER, BOGDONOFF AND HUGHES

monoxide technique was used for determining total lung diffusion capacity (DL c..~)' RV and OLeo estimates were both made with a commercially available pulmonary function analysis unit .• All participants were tested in the hospital service Iabora-

tory in a seated position and in the postabsorptive state. Patients were req uested not to smoke prior to testing but no other effort was made to regulate their medication. Single RV deterrnrnatrons and duplicate spirometry and diffusion studies wer e performed and compared with predicted normal values .13.n- HI In aU tests. instruments were calibrated prior to each trial, measurements were made by the same technician . and calculations were performed on a programmed caJcuJator. PA and lateral chest films were taken at 70 In 85 kv and standard 125 kv penetrations. Tbe x-ray pictures were random ized and independently read by one of us (~f.L.B.) and a second radio logist without preexisting knowledge of patient disposition. At the lime of testing, Rose-Waaler sheep cell agglutination titers ( SeAT) were determined.

Evaluation Criteria Pat ients were considered to have interstitial pulmonary disease if either their chest x-ray films were interpreted as being compatible with diffwe interstitial 8brosis or if testing ind icated a decrease in carbon monoxide diffusion. Bediclogists were instructed to grade x-ray films in accordance with the UICC/Cincinnati c1assi6cation.20 Diffuse disease was defined as involvement in three or more noncontiguous zones. Chest x-ray pictures were considered abnonnal only if both radiologists reported findings of dilluse disease. Normal OLeo values were predicted on the basis of sex, age, and body surface area as proposed by Burrows and colleagues.ts Values less than 80 percent of the predicted value were

the RA and OA populations examined were distinct . Patients with RA were found to be affected by interstitial pulmonary disease; patients with OA were not.·· Of the ten RA patients found to have indications of interstitial disease, four had only radiographic abnormalities, three had only diHusion defects , and three had both . Combinations of diHuse, fine and coarse, reticular and linear opacities were described by radiography (Fig 1 and 2) . No distinction could be made between active infiltration and old fibrosis. Abnonnalities were present on both low and high kv films, and divergent radiographic interpretations were not encountered in this series of 120 films. Six RA pat ients had diffusion abnormalities (Fig 3) . Three were found to have diffusion defects even though their chest x-ray 6!ms gave no indication of disease. Of these three, one patient also had a decreased VC and MVV. There were four men and six women in the abnormal RA population, ages 43 to 70. Their salient historic and clinical characteristics are listed in Table 2. Four patients related histories of mild periodic dyspnea associated with ep isodes of articu•• 1£ the 60 patients tested comprised a homogenous popula-

tion, the expected freq uencies for the given marglnal totals in a 2 X 2 conttngency table would be 5 of 30 patients affected in both the RA and OA samples.

considered abnormal.

RESULTS

Ten of the 30 RA patients (33 percent) were found to have either radiographic abnonnalities or diffusion defects suggestive of diffuse interstitial pulmonary disease (Appendix, Tables A and B) . None of the 30 OA patients was found to have radiographic abnonnalities or diffusion deficits (Appendix, Table C) . TIle probability of the observed deviation (Table 1) occurring in a single homogeneous population is 0.0008. This probability is sufficiently smaU to conclude that the entire population under study was not homogeneous and that with respect to interstitial pulmonary disease, "Coll ins lung analyzer, model P·I260 with Liston-Beeker infrared analyzer, model LB 15A. Table 1-R"ftun_U>id ArtIariIU _." l_iIW

""'..." """,m-. Interstitia) Pulmonary Disease

Vnaff... ted

Totala

RA·

10 0

20 30

30 30

Totals

10

50

60

0"··

·RA = Rheumatoid arthritic population. uOA - OMteoarthritie population.

FICURE 1. Chest x-ray 81m of case 20. a 58-year-old whit e woman with a Bve-year history of rheumatoid arthritis. Th e radiograph was taken during a period of articular exacerbation . The patient complained of mild exertional dyspnea and the 0 ....... wa.. greatly reduced. Note the reticular interstitial opacities (125 kv} .

CHEST, VOL. 62, NO.3, SEPTEMBER, 1972

245

INTERSTITIAL RHEUMATOID LUNG DISEASE

FIGURE 2. Chest x-ray 6lm of case 5, a 68-year-
where (J25Icv) .

lar exacerbat ion. A\I four were found to have det ectable diffusion defect s. The remaining six gave no bistory of past or present pulmonary symptoms. Patient 20 was evaluated during a period of articular exacerbat ion and dry crackling rales were heard throu ghout both lung fields. Thoracic examinations were otherwise unremarkable. No distinction could be made between the normal RA patients and those patients found to have indications of interstitial pulmonary disease (Table 3 ). Both sexes were affected in approximate proportion to their appearance in the total RA population studied. In this series, allergic histories, histories of occupational hazard and histories of past or present smoking habits did not suggest a predispos ition to tbe development of interstitial pulmonary complications. Likewise, neither the duration, severity, or therapy of the arthritis, nor the presence of subcutaneous nodules or elevated SCAT were found to be of value in ca\ling attention to pulmonary involve-

pulmonary disease." This was soon fo\lowed by a number of case reports!2-34 which defined a fairly characteristic clinical picture. In a1I but one instance , arthritis preceded the pulmonary disease." Cough , dyspnea or chest pain usually brought attention to the pulmonary lesion. On occasion, however, asymptomatic lesions were discovered on routine chest 6Ims.".32 Chest x-ray pictures showed variable degrees of mottling, reticulation or honeycombing . Once established, the pulmonary lesions were stable or slowly progressive, with only rare instances of remission or complete consolidation occurring."''' On biopsy the lung findings ranged from nonspecific interstitial inf1ammation to frank 6brosis...... As additional cases were reported,37'" the repeated occurrence of simultaneous articular and pulmonary exacerbations suggested a close clinical association.17-30..3I.3I ..... However, some observers were reluctant to relate the two except where interstitial lesions were round in association with characteristic pleuropulmonary rheumatoid granulomas...·.. Three large radiographic surveys by Aronoff and eo-workers," Talbot and Calkins,' and Walker and Wright" all failed to demonstrate a significant differences in the incidence of interstitial disease in rheumatoid and control populations. Others suggested that an association could never be established because interstitial disease was only an infrequent manifestation of rheumatoid lung disease.....7 Subsequently, Brannan and associates," Stack and Grant,'· and Martel and co-workers" 14

:

120

OLeo %

PREDICTED

ment .

DISCUSSION

Previous Studies

In 1948, E\lman provided the first description of a patient with rheumatoid arthritis and interstitial CHEST, VOL. 62, NO.3, SEPTEMBER, 1972

RA

OA

FIGURE 3. Pulmonary diffusion capacities in rheumatoid arthritic and osteoarthritic patients. Patienls with delectable diffusion abnonnalities appear in the shaded area. Three had normal x·ray films. Note alsothat four patients had abnormal x-ray pictures but DO functional impairment.

246

Case No.

POPPER, BOGDONOFF AND HUGHES

Pulmonary Symptoms

Thoracic Examination

Subcutaneous Nodules

Abnormal X-ray Films and Abnormal Diffusion. None 5 Unremark Yes

Elevated SCAT-

Duration of Arthritis, yr

History of Steroid Therapy

Allergic History

Industrial Smoking Exposure History

Yes

No

~o

~o

Yes

20

Dyspnea

Diffuse Rales

No

Yes

No

No

No

Yes

24

Dyspnea

Unremark

No

No

Yes

No

No

Yes ~o

Abnormal X-ray Films and Normal Diffusion. 18 None Unremark

No

No

28

No

No

No

21

None

Unremark

Yes

No

10

Yes

No

No

No

23

None

Unremark

No

No

No

No

steel mills

Yes

25

None

Unremark

Yes

No

Yes

No

No

Yes

No

No

No

Yes

No

No

No

No

Yes

No

No

No

Abnormal Diffusion and Normal X-ray Films. Dyspnea Unremark 12

8~

No

No

22

None

Unremark

Yes

No

29

Dyspnea

Unremark

No

Yes

·SCAT - Sheep cell

~lutination

1~

12

titers.

reported a total of 56 rheumatoid patients with radiographic evidence of interstitial disease, but they could not estimate what proportion of the rheumatoid population was represented in their cases. It was only with the additional measurement of diffusion capacity that a potentially higher incidence was suggested. In the past, little attention was given to physiologic assessment of patients with interstitial rheumatoid lesions, and the data presented were often limited. However, when pulmonary function was reported in individual cases, abnormalities consistent with interstitial pneumonitis and pulmonary fibrosis were detected. _.43.44.48051,52 Frank and co-workers!" studied an unmatched series of 41 rheumatoid arthritis patients and found 17 to have abnormal diHusion studies compatible with diHuse interstitial disease. Biopsy or autopsy material confirmed this diagnosis in ten, although only eight of the patients had abnormal x-ray 6lms. This study was noteworthy in two respects. First, indications of interstitial disease were found in a large percentage (40 percent) of the population studied and were documented by biopsy in 25 percent. Second, the single breath diHusion capacity was shown to be capable of detecting interstitial lesions in RA patients even when chest x-ray pictures gave no indication of disease. More recently, in a similar unmatched study of RA patients, Cugell'" encountered a 10 percent incidence of

diHusion abnormality. but suggested that industrial exposure may have been a factor in lowering the diHusion capacity. In an effort to isolate some of these differences, we included a control group of osteoarthritic patients in our survey. Present Study In this study, both radiographic and diHusion abnormalities were accepted as criteria in screening for diHuse interstitial pulmonary disease. The diagnostic accuracy of the chest x-ray film and the merits and limitations of the single breath diHusion study have been extensively discussed elsewhere. S4-6O Table

I' aelor. arad Clinical ClutraeterUlU:. of Rheumatoid Arthritic Pop,"atimu.

3-Hwori~al

RAPatients with Indications of Pulmonary Disease Population size Allergic histories Industrial exposure Smoking histories Duration of the arthritis (avg, History of steroid therapy Subcutaneous nodules Elevated SCAT

to

o

yrs)

1" 6 8.3 4 4

3

Normal RAPatients 20 5

8

13.9 9 11 16

-RA - Rheumatoid arthritic. --Steel mills.

CHEST, VOL. 62, NO.3, SEPTEMBER, 1972

247

INTERSTITIAL RHEUMATOID LUNG DISEASE

and will only be summarized here. With either technique, a normal study does not preclude the existence of interstitial pathology. Each, or both, may appear normal when histologically confirmed interstitial lesions are presenty·54-56 The single breath estimate of diHusing capacity may be low in states of altered ventilation-perfusion, diminished lung volumes, decreased pulmonary blood flow and increased intracapillary diffusion resistance, as well as in conditions characterized by interstitial tissue pathology.57-60 Not uncommonly, patients with severe dyspnea or markedly restricted lung volumes cannot adequately perform the single breath holding technique. In screening for potential impairment of diffusing capacity however, it is an accepted test. 58 •59 All patients performed technically adequate studies and none had evidence of compromised cardiac function or anemia. Except for one patient (No. 24), none had evidence of obstructive airway disease. In this series all chest films were independently interpreted with complete unanimity between the two radiologists. Using these two parameters, ten of the 30 RA patients (33 percent) had evidence for interstitial lung disease, while none of the 30 OA patients was found to be affected. Although these findings suggest that the occurrence of interstitial pulmonary disease in patients with rheumatoid arthritis is more than chance association, this small series cannot be extrapolated to the RA population at large without much larger and detailed studies being conducted. We regard the variation in the previous literature and in our own findings as a reflection of the methods of screening and of biases created by small sample populations selected from large referral institutions. In our patient series, historic and clinical findings did not appear to be of value in calling attention to pulmonary involvement. Histories of allergy, occupational hazard or smoking habit did not suggest a predisposition to the development of interstitial rheumatoid complications. The presence of pulmonary disease was not found to be related to the duration, severity or therapy of the arthritis. Subcutaneous nodules were found in comparable proportion in both affected and unaHected populations. At one time, autoimmune globulins detected by the seAT were thought to be instrumental in the development of pulmonary lesions. 61-64 Tomasf" suggested that the precipitation of immunocomplexes in the pulmonary capillaries initiated the pathologic changes described. However, fixed antibodies have not been demonstrated in immunoflourescent tissue preparations and the hypothesis has not been confirmed.66-67 Only three patients in CHEST, VOL. 62, NO.3, SEPTEMBER, 1972

this series had both indications of pulmonary disease and an elevated SCAT. In conclusion, this study has demonstrated that interstitial pulmonary lesions in patients with rheumatoid arthritis may be more common than previously suspected and may be detected in asymptomatic patients with normal x-ray films by the addition of pulmonary function screening procedures. H indeed, the statistical association of RA and interstitial pulmonary disease is confirmed, the relationship does not define a common pathogensis.68 To establish the exact nature of the association, the primary cause of rheumatoid disease must be more clearly understood and the factors influencing pulmonary reactivity need to be dearly defined. 3.46 ACKNOWLEDGMENTS: We wish to express our appreciation to Dr. Guy Matthew, Dr. Evan Barton, and Mr. Mitchell Passovoy for their assistance and encouragement. We art> also indebted to Miss Jacqueline Humphreys, Miss Kathryn Wakeman, Mrs. Ursie Wallcer and Mr. John Erotas for their technical assistance and manuscript preparation. REFERENCES

1 Caplan A: Certain unusual radiological appearances in the chest of coal-miners suHering from rheumatoid arthritis. Thorax 8:29-35, 1953 2 Walker WC, Wright V: Pulmonary lesions and rheumatoid arthritis. Medicine 47:501-520, 1968 3 Ferguson RH, Worthington JW: Recent advances in rheumatic diseases: 1967 through 1969. Ann Intern Med 73:109-124, 1970 4 Carr DT, Power MH: Pleural fluid glucose with special reference to its concentration in rheumatoid pleurisy with effusion. Dis Chest 37 :321-323, 1960 5 Carr DT, Mayne JG: Pleurisy with effusion in rheumatoid arthritis, with reference to the low concentration of glucose in pleural fluid. Amer Rev Resp Dis 85:345-346, 1962 6 Rubin EH, Gordon M, Thelmo WL: Nodular pleuropulmonary rheumatoid disease. Amer J Med 42:567-581,

1961

7 Aronoff A, Bywaters EGL, Fearnley GR: Lung lesions in rheumatoid arthritis. Brit Moo J 2:228-232,1955 8 Talbott J~ Calkins E: Pulmonary involvement in rheumatoid arthritis. JAMA 189:911-913, 1964 9 Walker WC, Wright V: Diffuse interstitial pulmonary 6brosis and rheumatoid arthritis. Ann Rheum Dis 28:252258,1969 10 Frank ST, Weg JG, Walsh RE, et al: Pulmonary dysfunction in rheumatoid disease. Ann Intern Med 68:11941195,1968 11 LoddenkemperR, Bach GL, Carton RW: Diffusion defects in rheumatoid arthritis and systemic lupus erythematosis. .Beitr Klin Tuberk 141 :230-241, 1970 12 Ropes MW, Bennet G~ Cobb S, et al: 1958 revision of diagnostic criteria for rheumatoid arthritis. Arthritis and Rheum 2: 16-20, 1959 13 Kory RC, Callahan R, Boren HG, et al: The Veterans Administration-Army cooperative study of pulmonary function. I. Clinical spirometry in normal men. Amer J Med 30:243-258, 1961

POPPER, BOGDONOFF AND HUGHES

248 14 Meneely GR. Ball COT. Kory RC. et al: A simplified closed circuit helium dilution method for the determination of the residual volume of the lungs. Amer J Med 28:825-831. 1960 15 Boren HG. Kory RC. Syner JC: The Veterans Administration-Army cooperative study of pulmonary function. U. The lung volumes and its subdivisions in normal men. Amer J Med41:96-114.1966 16 Cotes JE: Lung Function: Assessment and Application in Medicine. Oxford. Blackwell Scienti6c Publications. 1968. pp245-259 17 Goldman HI. Beeklake MR: Respiratory function tests. Normal values at median altitudes and the prediction of normal results. Amer Rev Resp Dis 79:457-467.1959 18 Baldwin EF, Coumand A, Richards OW: Puhnonary insufficiency. I. Physical classification, clinical methods of analysis. standard values in normal subjects. Medicine 27 :243-278, 1948 19 Burrows B. Kasik JE. Niden AH. et al: Clinical usefulness of the single-breath pulmonary diffusing capacity test. Amer Rev Resp Dis 84:789-806.1961 20 Bohlig H. Bristol LJ. Cartier PH. et al: UICC/Cincinnati classification of the radiographic appearances of pneumoconioses. Chest 58:57-67.1970 21 Ellman P: The etiology of rheumatism. Proc Roy Soc Med 40:332-336. 1947 22 Ellman P, Ball RE: "Rheumatoid disease" with joint and pulmonary manifestations. Brit Med J 2:816-820.1948 23 Hart FD: Pulmonary rheumatoid disease. Brit Med J 2:996-997.1948 24 Leys DG. Swift PN: Pulmonary lesions in rheumatoid arthritis. Brit Med J 1:434-435. 1949 25 Bloom J. Rubin JH: Transient pulmonary manifestations in rheumatoid arthritis. Canad Med Assoc J 63: 355-357, 1950 26 Ellman P, Cud1cowicz L: Pulmonary manifestations in the diHuse collagen disease. Thorax 9:46-57, 1954 27 Harris LH: Pulmonary manifestations of "rheumatoid disease:' Lancet 2:119-120,1954 28 Rubin EH: Pulmonary lesions in "rheumatoid disease" with remarks on diHuse interstitial 6brosis. Amer J Med 19:569-582,1955 29 Spence MP: Rheumatoid disease of the lungs and pleura. Arch Middlesex Hosp 5:95-106, 1955 30 Price TML, Skelton MO: Rheumatoid arthritis with lung lesions. Thorax 11 :234-240. 1956 31 Ellman P: Pulmonary manifestations in the systemic collagen diseases. Postgrad Med J 32:370-387,1956 32 Edge Jft, Rickards AG: Rheumatoid arthritis with lung lesions. Thorax 12:352-357, 1957 33 Smith WW, Rothermich NO: Diffuse interstitial fibrosis complicating rheumatoid arthritis. Ohio Med J 55:773776,1957 34 Dixon AStJ, Ball J: Honeycomb lung and chronic rheumatoid arthritis. Ann Rheum Dis 16:241-245, 1957 35 Christie GS: Pulmonary lesions in rheumatoid arthritis. Aust Ann Med 3:49-58, 1954 36 Cruickshanlc B: Interstitial pneumonia and its consequences in rheumatoid disease. Brit J Dis Chest 53:226236,1959 37 Ellman P: Discussion on the lungs as an index of systemic disease. Proc Roy Soc Med 51 :649-661, 1958 38 Lee FI, Brain AT: Chronic diHuse interstitial pulmonary fibrosis and rheumatoid arthritis. Lancet 2:693-695, 1962 39 Doctor L, Snider GL: DiHuse interstitial pulmonary fibrosis associated with arthritis. With comments on the

40 41 42 43

44

45 46 47 48 49 50

51 52

53

54 55 56 57

58 59

60 61

definition of rheumatoid lung disease. Amer Rev Resp Dis 85:413-422, 1962 Sullivan MA, Miller OK: Pulmonary manifestations in collagen diseases. Arch Intern Moo 110:769-781, 1962 Divertie MB: Lung involvement in the connective tissue disorders. Med Clin N Amer 48: 1015-1030, 1964 Brinkman GL, Chaikoff L: Rheumatoid lung disease: report of a case which developed in childhood. Amer Rev Resp Dis 80:732-737, 1959 Ognibene AJ: Systemic "rheumatoid disease" with interstitial pulmonary fibrosis. Arch Intern Moo 105:762769,1960 Cud1cowicz L, Madoff 1M, Ahelman WH: Rheumatoid lung disease. A case report which includes respiratory function studies and a lung biopsy. Brit J Dis Chest 55:3540,1961 Horler AR, Thompson M: The pleural and pulmonary complications of rheumatoid arthritis. Ann Intern Med 51: 1179-1203, 1959 Patterson CD, Harville WE, Pierce JA: Rheumatoid lung disease. Ann Intern Med 62:685-697,1965 Cruickshanlc B: Discussion on rheumatoid disease. Proc Roy Soc Moo 50:461-465, 1957 Brannan HM, Good CA, Divertie MB, et al: Pulmonary disease associated with rheumatoid arthritis. JAMA 189:914-918, 1964 Stack BHR, Grant IWB: Rheumatoid interstitial lung disease. Brit J Dis Chest 59:202-211, 1965 Martel W, Abell MR, Mikkelsen WM, et al: Pulmonary and pleural lesions in rheumatoid disease. Radiology 90:641-653, 1968 Newcomer AD, Miller RD, Hepper NCG, et al: Pulmonary dysfunction in rheumatoid arthritis and systemic lupus erythematosus. Dis Chest 46:562-570, 1964 Austrian R, McClement JH, Renzetti AD, et al: Clinical and physiologic features of some types of pulmonary diseases with impairment of alveolar-capillary diffusion. The syndrome of "alveolar-capillary block." Amer J Moo 11:667-685, 1951 Cugell OW, Callaway 11, Golden HE, et al: Lung mechanics, diHusing capacity, and roentgenologic changes in rheumatoid arthritis. Amer CoIl Chest Phys Bul19:17,1970 Adhikari PK, Bianchi FA, Boushy SF, et al: Pulmonary function in scleroderma. Amer Rev Resp Dis 86:823-831, 1962 Boushy SF, Kurtzman RS, Martin NO, et al: The course of pulmonary function in sarcoidosis. Ann Intern Moo 62:939-955, 1965 Fraser RG, Pare JAP: Diagnosis of Diseases of the Chest. An Integrated Study Based on Abnormal Roentgenograms. Philadelphia, Saunders, 1970, pp 482-483, 882 Forster RE: Exchange of gases between alveolar air and pulmonary capillary blood: pulmonary diffusing capacity. Physiol Rev 37 :391-452, 1957 Marks A, Cugell OW, Cadigan JB, et al: Clinical determination of the diHusion capacity of the lungs. Amer J Moo 22:51-73, 1957 Marshall R: A·comparison of methods for measuring the diHusing capacity of the lungs for carbon monoxide. Investigation by fractional analysis of the alveolar air. J Clin Invest 37 :394-408, 1958 Bates DV, Macklem PT, Christie RV: Respiratory Function in Disease. Philadelphia, Saunders, 1971, pp 75-92 Franklin E, Zucker-Franklin 0, McEwen C: Some observations on patients with interstitial pulmonary fibrosis.

CHEST, VOL. 62, NO.3, SEPTEMBER, 1972

249

INTERSTITIAL RHEUMATOID LUNG DISEASE Arch Interamer Rheum 2:250,1959 62 Sievers K, Aho K, Hurri L, et a1: Studies of rheumatoid pulmonary disease. Acta Tuberc Scan 35:21-34, 1964 63 Stretton TB, Leeming JT: Diffuse interstitial pulmonary fibrosis in patients with a positive sheep cell agglutination test. Thorax 19:79-84, 1964 64 Ward R, Stalker R: Sheep cell agglutination test in chronic interstitial pulmonary fibrosis. Ann Rheum Dis 24 :246-256, 1965 65 Tomasi TB, Fudenberg HH, Finby N: Possible relation-

ship of rheumatoid factors and pulmonary disease. Amer J Moo 33:243-248,1962 66 Turner-Warwick M, Doniach D: Auto-antibody studies in interstitial pulmonary 8brosis. Brit Moo J 1:886-891, 1965 67 Gottlieb AJ, Spiera H, Teirstein AS, et al: Serologic factors in idiopathic diffuse interstitial pulmonary fibrosis. Amer J 39:405-410,1965 68 Scadding JG: The lungs in rheumatoid arthritis. Proc Roy Soc Moo 62:227-238,1969

Moo

ADDENDA

Tali,.. fDUIPertinent RfUliocr.pIUe Fealara 0/ NorJlUllRMaIfUllOid ~"""'iIie

Table A-Pu.lmoruzry Fa~tioJl Case No.

Age, Sex

Ht (in)

Wt(lb)

1 2 3

23F 52M 50F 50M 64F 51F 43M 46F 62F 53F 68F 41M 70F 60F 62M 46M 53F 58F 77F 64F

62.0 73.0 64.0 71.0 65.0 60.0 72.0 59.0 71.0 61.0 61.3 72.3 59.5 61.5 64.5 69.3 66.0 60.7 62.5 65.5

117 165 131 119 175 118 188 135 195 128 135 199 93 135 128 155 98 151 102 127

4

6 7 8 9

10

11 13 14 15 16 17 19 26

27 28 30

Population analysis: Mean 95% Limits of confidence

% Pred VC

%Pred MVV

113 117

168 109 105 37 97 102 129 129 119 107 106 117 87 57 75 129 132 138 129 185

99

77

120 122 157 99 75 92

109 121 84

115 102 88 73 104 121 113 105.0 95.5& 114.6

% Pred FEV. 93 99

77 59 102 94 111 69 65 74 104 101 85 111 72 86 82

93 111 114

112.85 97.0&: 128.7 14 F, 6 M, mean

90.1 82.3 & 97.9 age 54

% Pred DLe

% RVjTLC

124 85 125 95 106 104 152 88

22.0 33.5 22.4 54.8 35.0 29.0 37.0 31.6 44.7 34.2 33.4 28.4 47.0 33.8 43.1 21.3 37.7 31.3 42.3 29.6

106.68 98.79 & 114.57

34.6 30.6& 38.6

119 84

87 102 97 113 118 113 93 112 110 96

Popedation. X-ray·

KEY: VC-vital capacity, MVV-maximum voluntary ventilation, FEV.-one second forced expiratory volume, DLc.o-totaJ lung diffusion capacity, RV -residual volume, TLC-totallung capacity. ·No indications of interstitial pulmonary disease.

CHEST, VOL. 62, NO.3, SEPTEMBER, 1972

250

POPPER, BOGDONOFF AND HUGHES Table

,.......".,,..,.,,..,,.

1'...... .." P. . . . . . . . . . . .",. ,..,.,. .1

~,..,...

'~.f

Cue No.

AJ1Aride P.".,... .....

~

DUea&

Ap, Sex

(Ht (in)

Wt(1b)

% Pred VC

% Pred MVV

%Pred FEV.

% Pred DL.

% RV/TLC

88M

86.0

114

81

131

75

79

39.9

X-ray· DiJfuae fine and linear and reticular opacities

COIU'Ile

12 18

66F

46F

66.7 59.5

1M 144

110

89

91 86

89 88

72 92

27.8 47.8

20

MF

59.0

UH

131

109

98

22

27.3

Dift'uae fine reticular opacities

21

66F

81.0

118

70

72

101

88

39.0

22 23

43F

20M

81.0 82.0

148 118

107 110

151 110

98

71

76 100

30.7 36.7

Dift'uaefine and coane reticular opadties

24

84M

87.5

190

65

87

59

53

50.0

25

82M

69.0

109

75

100

58

134

51.0

29

52F

60.0

178

65

48

81

63

35.2

71.0 65.1 & 88.9 age 54

78.28 57.15& 99.42

38.54 32.3& 44.8

Dift'uaefine linear opacities

DiJfuae fine and

00lU'1le reticular and linear opacities

Diffuae fine and coane linear opacities

Population analysis:

Mean

00.3 101.9 73.9& 83.4& 120.4 106.7 6 F, 4 M, mean

95% Limits of confidence

DiJfuae fine linear opacities

KEY: VC-Yital eapacity, MVV-maximum voluntary ventilation, FEV1-ooe seeond forced expiratory volume, DI,.-total lUDK diffUllioD capacity, RV-reBidual volume, TLC-total IUDK capacity. ·No radiographic indicaUoD8 of intentitial ctieeue uoJe. epecified.

1'. .... ..",........ RfNIIopepIaie'....,..oIO.~Po

T.... ~,......

Cue No. C 1 C2 C3 C4 C5 C8 C7 C8 C9 CI0 C11 C12 C13 C14 C15 C16 C17 C18 C19

Ap, Sex MF 60F 58F

69F

71F &SF 78F MF eoM

58M

61F 81F 10M 73F

82M

C20

63F 51M 62M MF 63F

C24

74F 72F 74F

C21 C22 C23

C25 C26

C27

C28 C29

cao

MM

72F

87F

53F 62M 41F 64.M

PopuIatioD . . .,..: Mean

Bt (in)

Wt(lb)

65.5 59.5 62.7 62.0 62.0 eo.5 eo.O 58.0 62.2 70.7 62.0 61.5 66.7 62.5 62.0 60.7 11.3 86.0 60.7 84.5 72.0 59.7 86.0 66.3 61.5 60.7 58.0 70.5 62.3 72.0

151 210 182 13'1 1M 132 122 117 135 217 183 124 139 170 1_ 198

96%Limitaolcon&deDce

235 137 106 105 212 116 129 178 150 138 140

204 141 186

%Pred VC

% Pred MVV

% Pred FEV.

72 91 108 133 115 83 91 151 147 108 103 103 106 117 117 102 99 M 115 104 M 134 93 135 119 113 107 109 110 147

83 76

80

110.6 103.5& 117.7

~

129 172 99 M 153 109 187 M 142 88 118 UH 96 74 110 88 108 104

'JI11

141 15& 164 159 147 88 136 163

65

95 110 105 82 71 122 129 98 103 M 100 103 81 M 89

89 94 107 88 135 90 113 119 86 101 102 104 136

98.9 121.2 92.4& 107.9& 105.4 134.4 21 F, 9 M, meaD age 63

.......... % Pred DL.

% RV/TLC

88 163 132 103 122 138 98 136 101 80 129 117 95 90 101 110 120 107 121 102 107 88 95

42.1 32.9 30.1 38.7 34.1 46.4 43.4 33.9 48.2 33.1 32.3 42.3 44.2 29.9 43.1 38.1 33.1 41.3 39.5 38.6 31.9 36.9 37.5 32.5 35.1 31.3 33.5 44.0 36.2 26.7

107.73 100.28 & 115.17

37.(, 35.0& 39.1

99

92

91 135 91 82 ~

X-ray·

KEY: VC-Yital eapecity, MVV-JDUimum voluntary ventilatioa. FEV.-ooe aecood forced expiratory volume. DL.-total hma cWrWlion eapaei\y, RV -ftIIIidua1 volume, TLC- total hm& eapacity. ·No indicatioDII of iDfa'8titial pulmonary di8eue.

CHEST, VOL. 62, NO.3, SEPTEMBER, 1972