Eur Reaplr J EDITORIAL 1991, 4, 774-775

Obliterative bronchiolitis, cryptogenic organising pneumonitis and bronchiolitis obliterans organizing pneumonia: three names for two different conditions

R.M. du Bois, O.M. Geddes

Over the last five years, increasing confusion has has been applied to conditions in which airflow obstruc­ developed over the use of the terms "bronchiolitis tion is prominent and in which response to treatment is obliterans" and "bronchiolitis obliterans organizing poor. pneumonia". The confusion stems largely from the common use of the term "bronchiolitis obliterans" or "obliterative bronchiolitis" in the diagnostic labels applied "Cryptogenic organizing pneumonitis" or "bronchi· to two entities which are quite distinct clinically but which otitis obliterans organizing pneumonia" (BOOP) bear certain resemblances histologically. Cryptogenic organizing pneumonitis was first described by DAVISON et al. [7] in 1983. The clinical syndrome ObUterative bronchiolitis consisted of breathlessness, malaise, fever, high erythrocyte sedimentation rate (ESR), pneumonic In 1977, GEODES et al. [1] reported the case histories shadowing on chest radiograph with a restrictive of six patients whose clinical condition was characterized pulmonary function defect and low gas transfer coeffi­ by airways obliteration in association with rheumatoid cient. On histological examination of lung biopsy mate· arthritis. The striking clinical features were of rapidly rial, the typical and distinguishing feature was the progressive breathlessness and the fmding on examination presence of connective tissue within the alveoli, alveolar of a high-pitched mid-inspiratory squeak heard over the ducts and, occasionally, in respiratory bronchioles. This lung fields. Chest radiographs showed hyperinflated lungs connective tissue consisted of "loosely woven fibres of but were otherwise normal. Lung function studies revealed collagen and reticulin" but with preservation of the a predominantly obstructive ventilatory defect with normal bronchoalveolar architecture. In some patients, interstitial gas transfer coefficient. The central feature of the involvement in the form of chronic inflammatory cells pathological appearances of the lungs at autopsy ex­ and some fibrosis was also present. Cryptogenic amination was a narrowing or obliteration of the major­ organizing pneumonitis was readily corticosteroid ity of airways measuring 1-6 mm in diameter but the responsive and patients rapidly improved on such therapy alveolar ducts and alveoli were spared. as measured by symptomatic, chest radiographic and Three of the six patients described in this series, had physiological indices. received cl-penicillamine. Subsequent studies have The nomenclature became clouded in 1985 with the described patients with rheumatoid arthritis and publication of an article by EPLER et al. [8] of an entity obliterative bronchiolitis with no history of cl­ which they termed "bronchiolitis obliterans organizing penicillamine ingestion, and obliterative bronchiolitis is pneumonia". They reported a series of patients who were not described in other conditions for which cl­ selected on the basis of pathological reports on biopsy penicillamine has been prescribed. It is concluded, material collected over a 30 yr period between 1950 and therefore, that the entity is associated with rheumatoid 1980. The essential selection criterion for inclusion in arthritis. the study was the mention of the term "bronchiolitis Other reports have described a similar clinical obliterans" in description of open lung biopsies, and this syndrome in association with graft versus host disease in was subsequently correlated with radiographic and bone marrow transplantation [2], rejection in lung trans­ physiological features, and response to treatment. This plantation [3], the response to viral infection [4], the entity, now widely known as BOOP, is identical to response to the ingestion of certain drugs other than cryptogenic organizing pneumonitis. In 57 of this series d-penicillamine [5], and in a group of patients in whom of 67 patients, plugs of granulation tissue was observed, no initiating factor could be identified [6]. In all of predominantly in terminal and respiratory broncbioles, these syndromes, the label obliterative bronchiolitis alveolar ducts and alveoli. Obliteration of airways by mature fibrous tissue is not described. The remaining ten Royal Brompton, National Heart and Lung Hospital, Sydney Street, patients had histological lesions limited to the small London SW3, UK. airways without parenchyma! involvement. EDITORIAL: BOOP 775

Table 1. - Comparison of obliterative bronchiolitis (08) and cryptogenic organizing pneumonitis (COP orBOOP)

Pathology Corticosteroid Clinical Physiological Ahways Alveoli response OB Airways Obstruction Widespread obstruction obliteration Spared Poor Kco normal of bronchioles

COP Pneumonia Obstruction Involvement of Organizing Good uncommon respiratory pneumonia bronchioles (50%) Impaired gas alveolar ducts (67%) exchange Kco: carbon monoxide transfer coefficient; BOOP: bronchiolitis obliterans organizing pneumonia.

Since this report, there have been a number of versus host disease after bone marrow transplantation. Thorax, publications describing the association of various 1984, 39, 887-894. diseases and drug therapies with the finding on patho­ 3. Burke CM, Theodore J, Dawkins KD, Yousem SA, Blank logical evaluation of intra-alveolar connective tissue N, Billingham ME, van Kessel A, Jamieson SW, Dyer PE, Baldwin JC, Stinson EB, Shumway NE, Robi11 ED. - similar to that described by DAVJSON et al. These include Post-transplant obliterative bronchiolitis and other late ulcerative colitis [9], primary biliary cirrhosis [10], sequelae in human heart-lung transplantation. Chest, 1984, 86, amiodarone [11], acebutolol [12) and gold therapy [13]. 824-829. More recently the clinical pattern of cryptogenic 4. Ham JC. - Acute infectious obstructing bronchiolitis. A organizing pneumonitis and the appropriate histological potentially fatal disease in the adult. Ann Intern Med, 1964, 60, features have been described in three patients with 47-00. rheumatoid arthritis in whom the response to 5. Cooper JAD, White DA, Matthay RA. - Drug-induced corticosteroid& was good [14]. DAVIDSON et al. there was pulmonary disease. Part 2. Noncytotoxic drugs. Am Rev Respir no association with rheumatoid arthritis but in a report Dis, 1986, 133, 488-505. by YousEM et al. [15], in which 40 open Jung biopsies 6. Turton CW, Williams G, Green M. - Cryptogenic from patients with rheumatoid arthritis were assessed, obUterative bronchiolitis in adults. Thorax, 1981, 36, 805-810. the presence of intra-alveolar connective tissue deposition 7. Davison AG, Heard BE, McAllister WAC, Turner­ was described in six patients although the clinical fea­ Warwick MEH. - Cryptogenic organising pneumonitis. Q J tures of these are not described in detail. In the present Med, 1983, 207, 382-494. issue another case of BOOP in a patient with rheumatoid 8. Epler GR, Colby TV, McLoud TC, Carrington CB, arthritis is presented [16). BOOP must, therefore, also Gaensler EA. - Bronchiolitis obliterans organising pneumo­ be included in the spectrum of pulmonary disorders which nia. N Engl J Med, 1985, 312, 152-158. may be found in association with rheumatoid arthritis. 9. Swinbum CR, Jackson GJ, Cobden I, Ashcroft T, Morritt There are a number of good reasons for making a clear GN, Corris PA. - Bronchiolitis obliterans organising distinction between obliterative bronchiolitis and BOOP pneumonia in a patients with ulcerative colitis. Thorax, 1988, as indicated in table 1. 43, 735-736. 10. Davison AG, Epstein 0. - Relapsing organising Since the small airways are often involved in a wide pneumonitis in a man with primary biliary cirrhosis, CREST range of diseases, such as chronic bronchitis and syndrome, and chronic pancreatitis. Thorax, 1983, 38, 316-317. extrinsic allergic alveolitis (hypersensitivity pneumoni­ 11. Kennedy n Jr. - Clinical aspects of arniodarone pulmo­ tis), a condition in which bucs of intra-airway organizing nary toxicity. Clin Chest Med, 1990, 11, 119-129. connective tissue are also seen, we believe that the use 12. Camus P, Lombard J-N, Perrichon M, Piard F, Guerin of a pathological descriptive term to define a clinical 1-C, Thivolet FB, Jeannin L. - Bronchiolitis obliterans condition has caused confusion. We suggest that organising pneumonia in patients taking acebutolol or these two quite distinct clinical entities are called amiodarone. Thorax, 1989, 44, 711-715. obliterative bronchiolitis and cryptogenic organizin~ 13. McCormick J, Cole S, Lahirir B, Knauft F, Cohen pneumonitis. S, Yoshida T. - Pneumonitis caused by gold salt therapy: evidence for the role of ceU-mediated immunity in its pathogenesis. Am Rev Respir Dis, 1980, 122, 145-152. 14. Rees JH, Woodhead MA, Shcppard MN, du Bois RM.­ Rerereoces Rheumatoid arthritis and cryptogenic organising pneumonitis. Respir Med, 1991, 85, 243-246. 1. Geddes DM, Cortin B, Brewerton DA, Davies RJ, 15. Yousem SA, Colby TV, Carrington CB. - Lung biopsy Turner-Warwick M. - Progressive ai.rway obliteration in adull$ in rheumatoid arthritis. Am Rev Respir Dis, 1985, 131, and its association with rheumatoid disease. Q J Med, 19n, 770-777. 184, 427-444. 16. van Thiel, Robert J, van der Burg, Sicco, Groote, 2. Wyatt SE, Nunn P, Hows JM, Yin JAL, Hages MC, Alexander D, Nossent, George D , Willis, Stuart H. - Bronchi· Catovsky D, Gordon-Smith EC. Hughes JMB, Goldman JM, olitis obliterans organizing pneumonja and rheumatoid Gallon DAG. - Airways obstruction associated with graft arthritis. Eur Respir J, 1991, 4, 905-911.