CASE REPORT Successful Treatment of a Case with Rapidly Progressive Bronchiolitis Obliterans Organizing Pneumonia (BOOP) using Cyclosporin A and Corticosteroid Daizo Koinuma, Makoto Miki, Masahito Ebina, Minoru Tahara, Koichi Hagiwara, Takashi Kondo*, Yoshio Taguchi** and Toshihiro Nukiwa Abstract therapy, which results in a better prognosis comparedwith id- iopathic pulmonary fibrosis (9, 10). There are reports, how- A60-year-old womanwas suffering from acute onset and ever, of patients with steroid-resistant idiopathic BOOPhav- progressive respiratory distress. Her radiographic findings ing an unfavorable outcome (1 1-15). showed bilateral volume loss in her lower lobes and con- In this report we present a steroid-resistant patient with an solidation predominantly distributed in peribronchovas- acute onset of idiopathic BOOP,showing consolidation dis- cular areas. The biopsied specimens performed by video- tributed in the peribronchovascular regions by chest CT, who assisted thoracoscopic surgery revealed prominent fibro- responded well to the simultaneous administration of myxoidconnective tissue within the terminal respiratory cyclosporin Aand corticosteroid. bronchioles and the alveolar spaces along the airways with- out marked interstitial fibrosis. No relevant cause was deter- Case Report mined, and she was diagnosed as having idiopathic BOOR Although her clinical course was fulminant with a poor A 60-year-old womanwas admitted to our hospital with reaction to steroid therapy, simultaneous administration of dyspneaand bilateral hilar consolidation shownon a chest roent- cyclosporin Aand corticosteroid elicited a rapid improve- genogram. She was a green grocer whohad never smoked. She ment. This case report presents the effectiveness of had been in good health until two months prior to admission, cyclosporin A in the treatment of progressive BOOR whenshe developed dyspnea with effort and a productive cough (Internal Medicine 41 : 26-29, 2002) after cleaning a dusty room that had not been used for years. She consulted a physician whoreferred her to us based on the Key words: cryptogenic organizing pneumonia,therapy roentogenographic findings. On admission, she presented as an obese woman(BH, 156.2 cm; BW, 72.2 kg) without fever or tachypnea (RR, 12/min; BT, 36.8°C). No cyanosis, eruption, or clubbing was noted. Introduction Chest auscultation revealed minimal coarse crackles at the base of each lung posteriorly. Chest roentgenogram and chest CT Bronchiolitis obliterans organizing pneumonia (BOOP)is a showed loss of volume bilaterally in the lower lobes and clinicopathological diagnosis with characteristic pathologic peribronchovascular consolidation in both lungs (Fig. 1A, and features reported first by Epler et al (1). Because organizing B). Her WBCcount was 6.4x109// without eosinophilia. The pneumonia is a non-specific inflammatory process it can be ESR was augmented (58 mrn/h), but the serum CRP level was caused by a number of pathogens (2, 3), and heterogeneity in within normal range (0.22 mg/dl). Neither rheumatoid factor radiographic features and clinical outcome has been reported nor anti-nuclear antibody was detected. Serum KL-6 and SP- (4-6) even in cases with idiopathic BOOPor cryptogenic or- Dlevels, markers for lung epithelial injury, were elevated to ganizing pneumonia (COP) (7). Lee et al characterized CT find- 1,390 U/ml and 341 ng/ml, respectively. ings in 43 patients with COPand categorized the distribution Arterial blood gas analysis under room air showedslight patterns of consolidation (8). As for the clinical course of pa- hypoxemia (PaCO2 of 42.3 Torr, PaO2 of 71.4 Torr). A pulmo- tients with BOOP,they usually respond well to corticosteroid nary function test revealed mild restrictive impairment (1.86 / From the Department of Respiratory Oncology and Molecular Medicine, *the Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai and **Tenri Yorozu Sodansho Hospital, Tend Received for publication February 15, 2001 ; Accepted for publication September 24, 2001 Reprint requests should be addressed to Dr. Masahito Ebina, the Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Sendai, Miyagi 980-8575 26 Internal Medicine Vol. 41, No. 1 (January 2002) Fulminant BOOPResponsive to Cyclosporin A Figure 1. A) Chest roentgenogram on admission. Bihilar consolidation was accompanied by depletion of lung volume. B) Chest CTon admission. Consolidation shows a peribronchovascular distribution. of VC(75.8%)) and deteriorated diffusion capacity (68.5% of %DLC0). Bronchoalveolar lavage fluid (BALF) from the right B5b showed a moderately increased cell count of 22.5x104/ml and minimal granulocytosis without eosinophilia. Immunocyto- metry of BALFcells showed a decreased CD4+/CD8+ratio of 0.14. No pathogen was cultured. A pathologic diagnosis of BOOP,depended on video-assisted lung-biopsy specimens from apical (SI), inferior lingular (S5) and anterior-basal (S8) seg- ments of her right lung, which showed patchy intraluminal or- ganization and proteinaceous exudates within the terminal and respiratory bronchioles. Granulation tissue was distributed in the alveolar spaces around the bronchioles without remarkable interstitial fibrosis (Fig. 2). Although she was first treated with 1 g/day of intravenous methylprednisolone for three days, followed by 30 mg/day (0.42 mg/kg) of oral prednisolone, her dyspnea was exacerbated and her arterial PaO2 declined to 58 mniHg. Adjunctive cyclosporin A therapy was initiated at 75 mg/day, which was later increased Figure 2. Elastica-Masson staining of a lung biopsied specimen to 150 mg/day. The serum trough levels of cyclosporin Awere obtained by video-assisted thoracoscopic surgery (original mag- 47 ng/ml at 75 mg/day and 160 ng/ml at 150 mg/day. As a nification at x40). Intraluminal organization within a terminal bronchiole (an arrow head) and a respiratory bronchiole (an ar- result, her dyspnea diminished and her laboratory data improved row), as well as within alveolar spaces along the bronchioles was to 82.1 TorrofPaO2, 2.25 /of VC (91.8%), and 85.8% of%DLC0. revealed without remarkable interstitial fibrosis. Serum markers also decreased to 646 U/ml of KL-6, and 55.4 ng/ml of SP-D. Peribronchovascular consolidation on chest radiography resolved steadily. After prednisolone was tapered to 25 mg/day, she was discharged on her 91st hospital day. Discussion Cyclosporin A was discontinued after four months of treat- ment without serious side effects. The patient had no signs of BOOPis a heterogeneous disease with a clinicopathologi- recurrence on 12.5 mg/day of prednisolone (213 U/ml of KL- cal definition, caused by various pathogens (2, 3). The typical 6) for eight months following discharge. Linear scars accom- presenting clinical symptomof BOOPstarts with a subacute panied by volumedepletion as seen on chest roentgenogram onset with patchy consolidation on the chest X-ray (2, 3, 16). have persisted (Fig. 3). A definitive diagnosis of BOOPrequires characteristic patho- Internal Medicine Vol. 41, No. 1 (January 2002) 27 Koinumaet al uted predominantly in both of the lower lobes is also an atypi- cal finding for BOOR Corticosteroid-resistance in patients with BOOPis reported to be rare (1 1-15, 21). Cyclophosphamide or azathioprine has been administered simultaneously with a corticosteroid as an alternative therapy with (21-23) or without (13, 15) underly- ing diseases, though their utility has not been established. To et al reported a 27-year-old man with BOOPwho recurred de- spite corticosteroid therapy but whoresponded to cyclosporin A and Pirfenidone, without corticosteroids (24). Wehave suc- cessfully treated a patient with fulminant BOOPusing cyclosporin A combined with corticosteroid. This case indi- cates that cyclosporin A can be useful for corticosteroid-resis- tant BOOP.Further study is warranted to define the utility of this treatment. References Figure 3. Chest CTsix months post treatment. Resolution of 1) Epler GR, Colby TV, McLoud TC, Carrington CB, Gaensler EA. Bron- consolidation was seen, but the bilateral volume loss in the lower chiolitis obliterans organizing pneumonia. N Engl J Med 312: 152-158, lobes persisted. 1985. 2) Epler GR. Bronchiolitis obliterans organizing pneumonia: definition and clinical features. Chest 102: 2s-6s, 1992. 3) Cordier JF. Organizing pneumonia. Thorax 55: 318-328, 2000. logic findings that demonstrate granulation tissue distributed 4) Cordier JF, Loire R, Brune J. Idiopathic bronchiolitis obliterans organiz- within the bronchioles into the distal air space, progressing from ing pneumonia, definition of characteristic clinical profiles in a series of 16 patients. Chest 96: 999-1004, 1989. fibrin exudates to loose collagen-containing fibroblasts ( 17, 1 8). 5) Yamamoto M, Ina Y, Kitaichi M, Harasawa M, Tamura M. Bronchiolitis The patient presented in this report started with acute onset obliterans organizing pneumonia (BOOP) in Japan. Nihon Kyobu Shikkan and progressive respiratory distress. It is plausible that her on- Gakkai Zasshi 28: 1164-1173, 1990 (in Japanese, Abstract in English). set was due to lung injury caused by the substances she in- 6) Nishimura K, Itoh H. High-resolution computed tomographic features of haled when cleaning the dusty roomone month before the bronchiolitis obliterans organizing pneumonia. Chest 102: 26s-3 1 s, 1992. 7) Davison AG, Heard BE, McAllister WA, Turner-Warwick