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318 Thorax 2000;55:318–328 Rare diseases c 8 Thorax: first published as 10.1136/thorax.55.4.318 on 1 April 2000. Downloaded from Series editors: A E Tattersfield, R M du Bois Organising pneumonia Jean-François Cordier Organising pneumonia is defined pathologi- infectious pneumonia, lung abscess, empyema, cally by the presence in the distal air spaces of lung cancer, bronchiectasis, broncholithiasis, buds of granulation tissue progressing from chronic pulmonary fibrosis, aspiration pneu- fibrin exudates to loose collagen containing monia (giant cells and foreign bodies usually fibroblasts (fig 1).12 The lesions occur pre- are present), adult respiratory distress syn- dominantly within the alveolar spaces but are drome, pulmonary infarction, and middle lobe often associated with buds of granulation tissue syndrome.34 occupying the bronchiolar lumen (bronchioli- Organising pneumonia may be classified into tis obliterans). This pathological pattern is not three categories according to its cause: organis- specific for any disorder or cause, but reflects ing pneumonia of determined cause; organis- one type of inflammatory process resulting ing pneumonia of undetermined cause but from lung injury. It may also be a feature of the occurring in a specific and relevant context; organising stage of adult respiratory distress and cryptogenic (idiopathic) organising pneu- syndrome and may be an accessory finding in monia. Several possible causes and/or associ- other inflammatory disorders such as vasculi- ated disorders may coexist in the same patient. tis. However, organising pneumonia is the par- There are no clear distinguishing clinical and ticular pathological hallmark of a characteristic radiological features between cryptogenic and clinicoradiological entity called cryptogenic secondary organising pneumonia.5 organising pneumonia. This terminology is preferred to the other name used for this ORGANISING PNEUMONIA OF DETERMINED CAUSE condition—namely, idiopathic bronchiolitis Infection is a common cause of organising http://thorax.bmj.com/ obliterans with organising pneumonia pneumonia. Indeed, the concept of organising (BOOP)—which may be confused with other pneumonia as a distinct pathological entity types of bronchiolar disorders, particularly emerged at the beginning of the 20th century constrictive bronchiolitis obliterans which is with its recognition at necropsy in patients Service de mainly characterised by airflow obstruction. dying from bacterial pneumonia, especially Pneumologie, Hôpital pneumococcal pneumonia.6–10 It was inter- Louis Pradel, preted as the failure of the usual resolution of Université Claude Aetiology of organising pneumonia Bernard, 69394 Lyon Because organising pneumonia is a non- pneumonia. Organising pneumonia has since Cedex, France specific inflammatory pulmonary process, it been found in association with many other on September 26, 2021 by guest. Protected copyright. J-F Cordier may result from a number of causes. Patholo- infections, mainly bacterial, but also in viral, gists may report features of organising pneu- parasitic and fungal infections (table 1). In Correspondence to: bacterial infections organising pneumonia oc- Professor J-F Cordier monia in association with conditions such as Table 1 Infectious causes of organising pneumonia Reference Bacteria Chlamydia pneumoniae 169, 170 Coxiella burnetii 171 Legionella pneumophila 86, 125, 172–176 Mycoplasma pneumoniae 86, 125, 177 Nocardia asteroides 178, 179 Pseudomonas aeruginosa 62 Serratia marcescens 62, 180 Staphylococcus aureus 62 Streptococcus group B (newborn treated by extracorporeal oxygenation) 181 Streptococcus pneumoniae 6, 7, 182 Viruses Herpes virus 62 Human immunodeficiency virus 183–185 Influenza virus 125, 186 Parainfluenza virus 187 Parasites Plasmodium vivax 188 Fungi Cryptococcus neoformans 189 Penicillium janthinellum 190 Figure 1 Buds of granulation tissue in the distal air spaces defining organising pneumonia Pneumocystis carinii (in AIDS) 62, 191, 192 at histopathology. Organising pneumonia 319 Table 2 Drugs identified as causing organising treatment. The pathological findings are typi- pneumonia cal of organising pneumonia. Bronchoalveolar Thorax: first published as 10.1136/thorax.55.4.318 on 1 April 2000. Downloaded from lavage (BAL) fluid di erential cell counts show Reference V an increase in lymphocytes in particular, but 5-aminosalicylic acid* 69, 70 also in neutrophils, eosinophils, and mast cells. Acebutolol 193 Acramin FWN 194–196 Although corticosteroid treatment is usually Amiodarone 5, 193, 197–202 necessary, spontaneous improvement may Amphotericin 203 occur.20 Interestingly, unilateral breast irradia- Bleomycin 83, 137, 204–212 Busulphan 213, 214 tion, whether or not it results in pneumonitis, Carbamazepine† 215 has been shown to induce bilateral lymphocytic Cephalosporin (cefradin) 216 23 24 Cocaine 217 alveolitis with activated CD4+ T cells ; Gold salts¶ 218, 219 however, this does not result in organising Hexamethonium 220 pneumonia in the majority of patients. An Interferon alpha 220 L-tryptophan 221 additional genetically determined host factor Mesalazine 222 and/or trigger acting on radiation “primed” Minocycline 223 lymphocytes may be necessary to induce the Nilutamide 224 15 19 Paraquat 225 organising pneumonia syndrome. Phenytoin 226 Sotalol 227 Sulfasalazine* 69, 228–230 ORGANISING PNEUMONIA OF UNKNOWN CAUSE Tacrolimus 231 Ticlopidine** 232 OCCURRING IN A SPECIFIC CONTEXT Vinabarbital-aprobarbital 233 The connective tissue disorders often involve the pulmonary parenchyma. Infiltrative lung *In patients treated with this drug for ulcerative colitis or Crohn’s disease which may themselves be associated with disease in this context varies and may include organising pneumonia. †In the course of lupus syndrome usual interstitial pneumonia, non-specific in- induced by the drug. ¶In patients with rheumatoid arthritis terstitial pneumonia, or organising pneumonia. which may itself be associated with organising pneumonia. **In a patient with temporal arteritis. The idiopathic inflammatory myopathies may cause a characteristic organising pneumonia curs mostly in non-resolving pneumonia syndrome.25–36 Organising pneumonia also where, despite control of the infectious organ- occurs in rheumatoid arthritis5 22 37–43 and ism by antibiotics, the inflammatory reaction Sjögren’s syndrome44 45 but, in contrast, is un- remains active with further organisation of the common in systemic lupus erythematosus40 46–49 intra-alveolar fibrinous exudate. Rheumatic and systemic sclerosis.55051 In addition to pneumonia occurring during the course of organising pneumonia, bronchiolitis obliterans rheumatic fever was recognised as a typical may occur in connective tissue disorders (par- organising pneumonia with intra-alveolar buds ticularly in rheumatoid arthritis).52 described as “bourgeons conjonctifs” or Mas- Pathological features of organising pneumo- http://thorax.bmj.com/ son’s bodies.11 12 nia may occur with Wegener’s granulomatosis. With drug induced organising pneumonia it These usually consist of small foci of organising is sometimes diYcult to determine causality pneumonia at the periphery of otherwise since organising pneumonia may also be asso- typical granulomatous lesions, but in some ciated with the underlying disease (a connec- cases they are the major histological finding tive tissue disease, for example). Resolution of although the patients do not diVer clinically or organising pneumonia after stopping the drug radiologically from those with classical Wegen- is obviously the best clue to establish causality. er’s granulomatosis.53 Organising pneumonia In many cases, however, it is not possible to has been reported occasionally in polyarteritis on September 26, 2021 by guest. Protected copyright. determine whether the drug is responsible or nodosa.54 not—for example, in patients with cancer or It is well established that both lung trans- haematological malignancies who may be plantation and bone marrow grafting may be treated with several drugs that are able to complicated by constrictive mural bronchiolitis induce organising pneumonia.5 Serious diag- with airflow obstruction. This is generally nostic pitfalls may occur with drug induced interpreted as a manifestation of chronic rejec- organising pneumonia—for example, bleomy- tion and graft versus host disease, respectively, cin induced organising pneumonia which may and it often results in severe chronic obstruc- present as pulmonary nodules resembling tive respiratory failure. Less commonly, organ- metastases in patients treated for aggressive ising pneumonia occurs in transplanted and potentially metastatic cancers (table 2). lungs.55–61 Organising pneumonia in this setting It has long been known that radiation may result from preservation injury, infection therapy to the chest may induce radiation or aspiration, or it may be a manifestation of pneumonitis, an inflammatory reaction within lung rejection57 61 62 and it may be associated the radiation field with some pathological with chronic rejection associated bronchiolitis features of organising pneumonia.13 14 How- obliterans.57 In lung transplant patients the ever, a syndrome similar to cryptogenic organ- combination of constrictive obliterative bron- ising pneumonia has been identified recently in chiolitis and organising pneumonia appears to women receiving radiation therapy to the be associated with a poorer prognosis than breast after removal of a malignant tumour.15–22 constrictive obliterative bronchiolitis alone.59 It diVers
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