Bronchiolitis in Rheumatoid Arthritis

After surgery the patient continued to have mild respiratory distress and right pulmonary hyperinflation. Therefore, his aortic suspension was revised through a median sternotomy one month later. Capillaryblood gas levelsat the time ofdischargeshoweda pH of7.41, a carbon dioxidetension (Pea.) of47 mm Hg, and an oxygen pressure (Po.) of 41 mm Hg. A chest x-ray film at the time of discharge showed return of the mediastinum to the normal position and absence ofhyperinflation(Fig3).The patient has done wellsince his reoperation. Respiratory distress completely resolved, and weight improved. One year following the patient's aortopexy, a left modifiedBlalock-1lwssig shunt was performed uneventfullythrough a left thoracotomy. DISCUSSION

Right aortic arch is widely recognized as a cause of obstruction of the airway when it forms part of a vascular ring around the trachea. U Several isolated aortic arch anomalies in the absence of a vascular ring may also produce obstruction of the airway, including an anomalous origin of the left innominate artery' and a normal left aortic arch displaced rightward secondary to a hypoplastic right lung.' Edwards' has reported postmortem findings in a patient with tetralogy ofFallot, right aortic arch, and aberrant left subclavian artery whose right main-stem bronchus was compressed by a large right aortic arch. In our patient, progressive bronchomalacia and tracheomalacia was caused by a large right aortic arch compressing the right main-stem bronchus and trachea anteriorly. Air could enter the right lung during inspiration but could not be completely expired. This led to progressive hyperinflation of the right lung and severe respiratory decompensation with increasing cyanosis by the age of two months. Suspension of the aorta by apposition to the underside of the sternum has been used to correct both innominate arterial and aortic compression of the trachea in infants with respiratory distress secondary to a crowded mediastinum." Because the planes of tissue surrounding the aorta, trachea, and bronchus are intact, the suspension helps to maintain patency of the structurally weakened airway. Apposition to the sternum is important fur good healing. The first suspension through a right thoracotomy pulled loose. A second suspension with better exposure of the arch through a median sternotomy has remained intact and effective at 16 months of follow-up, Cardiac catheterization will be necessary to outline the anatomy of the great vessels so that future corrective surgery can be carefully planned. In summary, this report documents fur the first time severe obstruction of the airway produced by a dilated right aortic arch in association with tetralogy of Fallot and its successful surgical management. Increasing cyanosis in patients with tetralogy of Fallot may have a respiratory cause which must be differentiated from progressive hypoxemia due to decreasing pulmonary blood flow. REFERENCES

1 Edwards JR. Congenitalcardiovascularcausesoftracheobronchial and/or esophageal obstruction. In: Tucker BL, Lindesmith GG, eds. First clinical conference on congenital heart disease. New York: Grone and Stratton, 1979:49-95 2 Gross RE. Surgical relief fur tracheal obstruction from a vascular ring. N Eng! J Med 1945;233:586-90 3 Gross RE, Neuhauser EB. Compression of the trachea by an anomalousinnominate artery: an operation fur its relief. AmJ Dis

Child 1948;75:570-74 4 VanPraagh Rv, Vlad p. Dextrocardia, mesocardia, and levocardia: the segmental approach to diagnosis in congenital heart disease. In: KeithJO, Rowe RO, Vlad P, eds. Heart disease in infancy and childhood. NewYork: Macmillan PublishingCo, Inc, 1978:638-95 5 Filler RM, Rosello PJ, Lebowitz RL. Life-threatening anoxic spells caused by tracheal compression after repair of esophageal atresia: correction by surgery. J Pediatr Surg 1976;11:739-48

Bronchiolitis In Rheumatoid Arthritis· Aame Lahdenauo, M.D., F.C.C.P.;]OfTI'IIl Mattila, M.D.; and

Annl Vilppula, M.D.

Bronchiolitis in association with rheumatoid arthritis has been reported, to our knowledge, in 18 patients to c1ate. In some cases use of penicillamine has been strongly associated with the development of bronchiolitis. Most of the reported cases are described as having marked irreversible airways obstruction and hyperinflation. We describe a patient with rheumatoid arthritis whose respiratory tract symptoms began during gold therapy. Physiologic studies showed marked lung hyperinftation without pathologic findings in forced dry spirometric study. On open lung biopsy a mild degree of granulomatow bronchiolitis was found. Immun08uorescent microscopy showed IgM- and IgG-containing plasma ceDs in the bronchiolar walls.

B

ronchiolitis obliterans has been described as a rare pleuropulmonary complication of rheumatoid arthritis.·-5 Most of the reported cases have been found to have marked irreversible airways obstruction and a fulminating course of the disease. Histology of the lung has revealed fibrous narrowing and obliteration of the bronchioles and the smallest bronchi, with infiltration of mononuclear cells. We recently encountered a patient with rheumatoid arthritis who also had granulomatous bronchiolitis in herlungs. Physiologic studies showed marked lung hyperinflation without pathologic findings in furced dry spirometric testing, and the course of the disease showed some reversible features. CASE REPORT

The patient was a 44-year-old, nonsmokingwomanwhose grandmother had rheumatoidarthritis. She had never been exposedto any specificdusts. In 1971 she suffered from recurrent vaginaldischarge, cervicitis, and hematuria due to Escherichiacoli-bacterialcystitits. She had had no other previous diseases. She fell ill in 1974 with recurrence of pain in the shoulders. In 1975 she developed a seropositiverheumatoid arthritis which fulftlled the criteria fur the classicclass of the American Rheumatism Association. 8 Since 1979her arthritis has progressed continuously. During the years 1975-76,the patient was treated with penicillamine, to which her condition seemed to respond. Upon reactivation of the disease, gold therapy was started in June 1979, and she received 1,620mg of gold altogether. In January 1980there was a short pause in the gold therapy because of a rash. In January 1981 the patient noticed *From the Departments of Pulmonary Diseases, Pathology and Internal MedIcine, University Central Hospital, 'Ilunpere, Fin-

land.

Reprint requests: Dr. Lahdenauo, Department ofCUnlcal Sciences, University ofTampere, SF-33lOl Tmnpere. FlnlQnd CHEST I 85 I 5 I MAY, 1984

705

FIGURE 1. Mononuclear cell infiltration in the wall of a respiratory bronchiolus. The lumen contains mucus with polymorphonuclear leukocytes and macrophages (H&:E, x 225). dyspnea and wheezes invariably two days after gold injections. Gold therapy was stopped in June 1981. On physical examination in July 1981, a bibasilar midinspiratory "squeak" was heard in the posterior chest. A palpable lymph node was found in the right axilla, but biopsy examination of the node revealed no pathologic changes. The patient had no dyspnea at rest, but on exertion showed dyspnea and a mild, dry cough. The ESR was 56 mmlhr and hemoglobin was 126,;L. Findings in the bone marrow were normal except for iron deficiency; the RoseWaaler test was strongly positive (512 to 1,(00); and chlamydial isolation and serology tests were negative, as were precipitations against molds. Values of serum angiotensin-eonverting enzyme, total serum protein, electrophoresis and serum immunoglobulins all were normal. The plain chest roentgenogram was normal. Reactions to skin tests with common aeroallergens were negative. Respiratory function studies were performed as follows: forced expiratory flowvolume loops were registered on a dry spirometer. Lung volumes and specific airway conductance (Sgaw)were registered durmg quiet breathing with a constant-volume body plethysmograph;' closing volume (CV) and the slope of phase 3 by the single-breath nitrogen test;" the diffusing capacity for carbon monoxide (Dsb) and the effective alveolar volume (VA) by the single-breath method.' The results of the lung function studies are presented in 1llble I. The methacholine inhalation challenge test using increasing doses of methacholine (up to 15breaths of2.5 percent methacholine solution) did not show bronchial hyperreactivity. After the examination in July 1981, penicillamine therapy was reinstituted, with low-dose corticosteroids because of the activity of rheumatoid arthritis. In February 1982, an open lung biopsy was performed. The walls of several respiratory bronchioli were densely

FIGURE 2. A granulomatous collection ofhistiocytes in the wall of a respiratory bronchiolus. (H&:E, x 360).

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FIGURE 3. The interstitium contains focal infiltrates of mononuclear cells. A granulomatous focus is also seen. (H&:E, x 90). infiltrated with lymphocytes and histiocytes, with a small number of plasma cells and afeweosinophils (Fig 1).In the bronchiolar wall there were collections ofhistiocytes forming small granulomatous foci (Fig2 and 3). The bronchiolar lumen contained mucus with polymorphonuclear leukocytes and macrophages. There wasno evidence of more bronchiolar scarring, obliteration, or intraluminal polyps. In patches in the interstitium there were foci of inflammatory cells composed of lymphocytes and histiocytes. A few plasma cells were also seen. Sometimes the infiltrate was seen to extend into adjacent alveoli. Most of the alveolar spaces were, however, normal. The histiocytes formed granulomatous areas with multinucleated giant cells. Occasionally in peripheral alveolar spaces and in the adjacent interstitium there were small collections offOamyhistiocytes. Foci of developing interstitial fibrosis were also seen; in these areas the alveolar lining cells were cuboidal with prominent nuclei. The pulmonary vessels were normal. For immunofluorescent microscopy, the lung biopsy was stained by the direct technique with eommerciallyprepared fluorescein isothiocyanate-conjugatedantiserato IgA, IgG, IgM, andC3. IgM-and IgG-eontainingplasmacellswere seen in the bronchiolar walls (Fig 4). Additionally, a weak focal fluorescence of IgM was seen in some alveolar walls. In April 1982, 30 mgfday of prednisolone was given for one month with no significant changes in respiratory symptoms or lung function results. In the middle of November 1982,the penicillamine treatment was stopped, and the patients symptoms diminished. The lung function parameters improved in December 1982. DISCUSSION

Bronchiolitis in association with rheumatoid arthritis has been reported in 18 cases to date. In 1977, Geddes and co-

FIGURE 4. IgM-eontaining plasma cells in a bronchiolar wall. In the left upper comer a mucous plug in the bronchiolar lumen can be seen. Brollctiolllllln RI1lUnIIIDId ArthrllIlI (1..IJIIdenauo. MlII/Ia, VlppuIe)

Table l-Ruulta ofLung I1Inction Studiea Test FVC, 1 (BTPS) FEV 1, 1 (BTPS) FEV, % FEF25-75%, 1/s MEF25,1/s Sgaw, 1IkPa x s FRC, 1 (BTPS) Rv, 1 (BTPS) TLC, 1 (BTPS) RVffLC ratio, % Slope of phase 3, %/1 CVNC,% Dsb, mmoV60 s x kPa DsbNA, mmoV60 s x kPa x i

July 1981 3.40 3.00 88 3.40 1.69 3.94 4.42* 2.92* 6.42* 45* 1.3 10.7 6.60 1.37*

January 1982

3.82 5.53* 4.08* 7.58*

54*

April 1982

May 1982

December 1982

3.25 2.90 89 3.24

3.30 2.90 88 2.92

3.50 2.80 80 2.69

5.19 3.78* 2.23* 5.58 40*

2.35 4.21* 2.81* 6.26 45*

2.36 3.49 1.79 5.39 33

6.03* 1.26*

6.09* 1.39*

5.77* 1.25*

Predicted 3.50 2.80 80 3.36 1.47 2:1.27 2.66 1.34 4.84 28 1.4 15.7 7.93 1.76

*Pathologic findings.

workers' described five patients with signs of rapidly progressive bronchiolitis obliterans and rheumatoid arthritis, three of whom had received penicillamine therapy. After excluding all recognized causes of chronic airflow obstruction in 2,094 patients, Turton and eo-workers" detected ten patients with cryptogenic bronchiolitis obliterans, five of whom also had rheumatoid arthritis. Three of these had received penicillamine. In addition, there are reports of five rheumatoid patients in whom penicillamine has been strongly associated with the development ofacute bronchiolitis.t" as well as some occasional cases in earlier studies. IO-U In lung function studies, almost all patients have shown profound airway obstruction, with highly diminished FEV 1 and hyperinflation. The course of the disease has been fulminating in about one half of the cases described, and deaths due to bronchiolitis are not unusual. Further, a patient with a benign course was recently described by Herzog et al." The symptoms of our patient were typical of bronchiolitis , as were the auscultatory findings. Marked hyperinflation was the prominent feature in her lung function studies, while the results from dry spirometer tests were completely normal. The course of her disease seems to be benign. In these respects she resembles a patient recently described by Herzog et al." The intraluminal granulation polyps at the bronchiolus level seen in bronchiolitis of various etiologies" are not seen in patients with rheumatoid arthritis. The granulomatous narrowing of bronchioles seen in our patient is very rare. Granulomas may reflect a cell-mediated immune response to antigen. Common granulomatous diseases of the lungs (tuberculosis, sarcoidosis, hypersensitivity pneumonias) can be excluded on clinical grounds in this case. Interestingly, granulomas have also been observed following injections of immune complexes. 13 The demonstration of IgM- and IgG-eontaining plasma cells in the bronchiolar walls of our patient suggests direct immune-mediated lung injury. Herzog et al" reported in their patient with bronchiolitis and rheumatoid arthritis linear deposition of IgG in alveolar walls. Extensive IgM deposition in pulmonary arterioles, alveolar walls, and adjacent to the cavitary pulmonary rheumatoid nodules has been reported along with faint linear IgG alveolar wall staining in rheumatoid lungs. 14

Our patient had received penicillamine five years before her bronchiolitis was detected, so it may not have been the initial stimulus for the disease process. Her respiratory symptoms always developed two days after gold injections at the beginning of the pulmonary disease. When the resumed penicillamine therapy was stopped, her respiratory symptoms diminished and disappeared, and her lung function improved ('Thble 1). Probably patients with rheumatoid arthritis are more prone to develop bronchitis and bronchiolitis," and in such cases penicillamine may interfere with the usual healing process. 3 The effect of gold in the development of bronchiolitis is completely unknown, although notably gold can cause nonspecific interstitial inflammation with fibrosis. 111 Although bronchiolitis in rheumatoid patients may be a rare condition, we advocate extreme care with rheumatoid patients receiving antirheumatic drugs who develop respiratory symptoms. Their lungs must be thoroughly examined, and the ausculatory findings themselves may be important for diagnosis. In our opinion, the measurement of lung volumes is the most sensitive lung function parameter in early bronchiolitis. REFERENCES

1 Geddes DM, Corrin B, Brewerton DA, Davies RJ, TurnerWarwick M. Progressive airway obliteration in adults and its association with rheumatoid disease. Q J Med 1977; 46:427-44 2 Turton CW, Williams G, Green M. Cryptogenic obliterative bronchiolitis in adults. Thorax 1981; 36:805-10 3 Epler GR, Snider GL, Gaensler EA, Cathcart ES, FitzGerald MX, Carrington CB. Bronchiolitis and bronchitis in connective tissue disease. JAMA 1979; 242:528-32 4 Murphy KC, Atkins CJ, OIJer RC, Hogg JC, Stein HB. Obliterative bronchiolitis in two rheumatoid arthritis patients treated with penicillamine. Arthritis Rheum 1981; 24:557-60 5 Cordier JF, Falconnet M, Moulin J, Brune J, Touraine R. Bronchiolite severe et polyarthrite rheumatoide: role tres probable de la d-penicillamine dans deux observations. Lyon Medi-

cal 1980; 224:113-14

6 Ropes M, Bennet G, Cobb S, JacoxR, Jessar R. 1958 revision of diagnostic criteria lOr rheumatoid arthritis. Arthritis Rheum 1959; 2:16-20 7 Woitowitz HJ, Buchheim FW, Woitowitz R. Zur Theorie und Praxis der Oanzkorperplethysmographte in der LungenCHEST I 85 I 5 I MAY, 1984

707

funktionsanalyse. Praxis Klin Pneumoll967; 21:449-71 8 Buist AS, Ross BB. Quantitative analysis of the alveolar plateau in the diagnosis of early airway obstruction. Am Rev Bespir Dis 1973; 108:1078-87 9 Ogilvie CM, Forster RE, Blakemore WS, Morton JW A standardized breath holding technique fOrthe clinical measurement of the diffusing of the lung fOr carbon monoxide. J Coo Invest 1957; 36:1-17 10 Price TML, Skelton MD. Rheumatoid arthritis with lung lesions. Thorax 1956; 11:234-40 11 Gosink BB, Friedman PJ, Uebow AA. Bronchiolitis obliterans; roentgenologic-pathologic correlation. AJR 1973; 117:816-32 12 Herzog CA, Miller RR, Hoidal JR. Bronchiolitis and rheumatoid arthritis. Am Rev Respir Dis 1961; 124:636-9 13 Spector WG, Heesom N. The production of granulomata by antigen-antibody complexes. J Patholl969; 98:31-39 14 DeHoratins RJ, Abruzzo JL, Williams RC. Immunofluorescent and immunologic studies of rheumatoid lung. Arch Intern Med 1972; 129:441-6 15 Collins RL, Thrner RA, Johnson AM, Whitley NO. McLean RL. Obstructive pulmonary disease in rheumatoid arthritis. Arthritis Rheum 1976; 19:623-8 16 Winterbauer RH, Wilske KR, Wheelis RF. Diffuse pulmonary injury associated with gold treatment. N Engl J Med 1976; 294:919-21

Dissolution of Pulmonary carcinoma via Argon-Laser Bronchoscopy* First Clinical Use of FlberoptIc Metal cautery Cap Heated by Laser Radiation Garrett Le«, M.D.; Rlclua,.dRulnll8Oll, M.D., F.C.C.P.; Mjng C. Cluan, M.D.; Damel Stobbe; Robert L. lIeU, M.D., F.C.C.P.; and Don T. MflIOfI, M.D., F.C.C.P.

A 6O-)'NN)Id man with nonresectable lung canc:er underwent broncholcopy which reveaIecI a large squamow cell tumor mass narrowing the free airway to the left lung. A 8esible quartz 8ber connected to an argon ion laser was then inserted through a hollow channel of the 6beroptic bronchoscope. lbe laser was activated to heat the metal cap on the distal tip of the 6ber to thermally dissolve the mass and relieve airway obstruction.

T aser therapy has recently been utilized in clinical pulmo-

L

nary oncology for relief of tracheobronchial stenosis. I The available laser systems for such application have employed a bare-tipped 6ber with recognized inherent hazards related to free-beam photoradiation.1,1 In our laboratories, we have previowly devised a 6beroptic laser-heated metal cautery cap for dissolution of atherosclerotic lesions which also protects against vascular damage. U The present report describes the extension of this new development of a metallic *From the Cedars Medical Center, Cardiovascular Laser Research Laboratory, Miami, and the Western Heart Institute, St. Mary's Hospital and Medical Center, San Francisco. Reprint ,."quem: Dr: Lee, Weltern Hearl IMfflute, 450 Stanyan St,."Bt, San Francllco 94n7

708

cap mounted at the distal end of a flexible quartz laser 6ber for the controlled thermal vaporization of life-threatening nonresectable tumor producing airway obstruction. CASE REPORI'

A 6O-yeaM)ld white man who underwent right upper lobectomy one year previously fOrsquamous ceD lung carcinoma was admitted fOr recurrence of pulmonary cancer. His chief symptoms were shortness of breath and hemoptysis. The patient underwent bronchoscopy using topical tetracaine (Pontocaine) anesthesia. The proximal trachea was benign, but in the distal trachea, just cephalad to the carina, there was a large tumor mass obliterating the right mainstem bronchus and narrowing the free airway to the left lung. 1b relieve the obstruction without thoracotomy, a flexible 400 jI.IJI central core quartz fiber with a metal cautery cap at its distalend was inserted into the flushing channel of a fiberoptic bronchoscope. The proximal end of the fiber was connected to an argon-ion laser source and using fiberoptic visual guidance, the distal tip was positioned in direct contact with the surface of the tumor. In Figure I, the endobronchial tumor mass can be visualizedalong with the cautery cap protruding out the tip of the bronchoscope (top panel). 1b plIJ'o tially dissolve the mass, several bursts of 5-W laser energy were delivered to heat the cautery cap fOr10 to 20 seconds. The middle and bottom panels of Figure 1 demonstrate the result of a single laser burst. Burned pieces of debrided tumor tissue adhered to the surface of the metal cap which were then removed (middle panel). In this way, the central portion of the tumor in the distal trachea was objectively cannali7.ecl allowing considerable enhancement of air passage to the left lung. The bronchoscope was withdrawn, and the patient tolerated the procedure extremely weD without complications. Immediately upon completion ofthisnew treatment modality, his dyspnea was abated concomitantly with the observed improvement of aeration to the left lung. DISCUSSION

The use of lasers in the treatment of endotracheal lesions offers rapid tissue vaporization with little bleeding, edema, and scar formation. However; present carbon dioxide laser systems wuaUy necessitate general anesthesia and direct vision through a rigid bronchoscope. I There are also the inherent dangers of retinal damage to the bronchoscopist and intratracheal 6re hazards to the patient during the administration of oxygen and general anesthetics for laser surgery in the tracheobronchial tree. In addition, the administration of tumor-loealizmg hematoporphyrin to enhance argon laser photoradiation of endobronchial malignancies currently lacks the ability to penetrate deep into the tumor mass. I The application of a metal cautery cap connected to the distal tip of a flexible quartz 6ber provides a number of advantages. It can be easily inserted through a flexible 6beroptic bronchoscope and positioned onto the tumor by 6beroptic visual guidance. The heated metal cap minimizes the risk of damaging surrounding normal tissue due to stray laser beams and eliminates the chance of retinal damage. Furthermore, it can be precisely directed and the vaporization process can occur deep into the tumor mass. This represents the first report of the clinical use of a 6beroptic metal cautery cap heated by laser conduction. The original idea was based on our initial laboratory experiments in 1m wing an electrically heated metal cap device which was successful in dissolving atherosclerotic fatty-fibrous plaques. The vaporization of plaques by this improved metal