common than generally considered. COP occurs with equal frequency in men and women and is p robably more common in smokers than non-smokers. Typical COP Clinical and radiological features Most cases of COP present with symptoms, cli nical signs and chest radiography that are largely indistinguishable from community acquire d pneumonia, a far commoner condition. A diagnosis of COP is often \201 rst considered wh en there is failure to respond to empirical antibiotic therapy. \200 Typical symptoms of COP are dry cough, breathlessness, fatigue and anorexia. Sputum production is uncommon and haemoptysis is rare. AUTHOR \200\231S TIP The presentation of COP is often indistinguishable from community acqu ired pneumonia; failure to respond to antibiotic therapy and migratory CXR changes should a lways raise the possibility of COP. Fever with unilateral/bilateral crackles or clear chest are common examination \201 nding s. Bronchial breathing, even in the presence of radiographic evidence of consolida- tion, i s rarely reported. Table 7.7.1 Is it cryptogenic? Some causes of secondary organizing pneumonia Lung function tests play little or no role in diagnosing or monitoring COP. Airflow obstruc tion is uncom- mon despite the apparent \200\230bronchocentric \200\231 pattern of disease . Infective pneumonia Streptococcus pneumoniae, Mycoplasma pneumoniae, Legionella sp, oppourtunistic organisms, v iruses Blood tests usually reveal mild neutrophilia and raised Radiation Post breast-cancer radiotherapy in \202 ammatory markers (CRP, ESR) Connective tissue disease Rheumatoid arthritis, dermatomyositis/polymyositis, systemic sclerosis, systemic lupus eryt hematosus Chest radiography typically features unilateral or bilat- eral patchy non-segmental consoli dation, without a par- ticular zonal predilection. Presentation with a single area of lobar consolidation is far less common. Migratory or \200\230 \202 itting \200\231 radiograph changes over a period of weeks or months is suggestive of COP (Fig. 7.7.1). Pleural effusio n is rarely visible on CXR. Occasionally COP presents as a solitary lung nodule. Drugs Bleomycin, amiodarone, methotrexate and others In \202 ammatory bowel disease Crohn \200\231s, ulcerative colitis Neoplasms In vicinity of bronchial carcinoma, in association with hematological malignancies. The HRCT scan aids in the distinction of COP from \201 brotic ILDs, in particular IPF, bu t the distinction from other IIPs or from hypersensitivity pneumonitis is less reliable. Th ere are no pathognomic features on HRCT to distinguish COP from infection. Air-space con- s olidation, which is often peripheral and/or peribron- chial, is present on CT in 90% of pat ients with COP (Fig. 7.7.2). Epidemiology The incidence of COP is not known and has not been extensively studied. Whilst often considered a rare condi- tion, most chest physicians will have experience of seeing patients with COP and indeed the condition may be more (a) (b) Fig. 7.7.1 40-year-old female with \201 tting consolidation due to COP. (a) Right lower a nd left upper zone consolidation. (b) Three months later there is consolidation lateral to left heart border, medially at the right base and laterally in the right mid zone. CHAPTER 7.7 Cryptogenic organizing pneumonia 145 Relapses, both on and off treatment are quite common, and may be more common with short-cou rse (3 \200\2236 months) compared to extended-course (12 months) steroid therapy. However r elapses in typical COP are; (i) not associated with increased mortality; (ii) not associate d with progressive lung \201 brosis; and (iii) as responsive to corticosteroids as the in itial presentation. \200 On this basis, a suggested regimen, that may be modi \201 ed to suit the individual case, is oral prednisolone as follows: \200 \200 \200 \200 \200 0.75mg/kg for 4 weeks; 0.5mg/kg for 4 weeks; 20mg daily for 4 weeks; 10mg daily for 6 weeks ; 5mg daily for 6 weeks then stop. Relapses can be treated by re-instigating the regimen either with the initial dose, or with the lowest dose at which the disease was previously controlled. Fig. 7.7.2 HRCT scan of COP. Patchy peripheral consolidation with limited ground glass atte nuation. On occasion, COP can relapse and remit radiologically with few or no associated symptoms an d without a change in therapy. Thus relapses of COP do not always require treatment. Typically the consolidation seen on HRCT is accompanied by diffuse ground-glass opaci \201 cation and there may also be multiple small nodules not necessarily obvious on the plain c hest radiograph. Another common \201 nding is bronchial wall thickening and bronchial dil atation in involved areas. 20 \200\22330% patients are found to have small unilateral or bi lat- eral pleural effusions on CT. Sub-pleural reticulation is seen occasionally. Other manifestations of organizing pneumonia Acute fulminant COP \200 Occasionally COP pr esents with widespread CXR in \201 l- trates and acute respiratory failure, in a syndrome that overlaps with AIP and ARDS. The usual scenario is that such cases are initially misdia gnosed as severe commu- nity acquired pneumonia on the high dependency or intensive care un it, but fail to respond to conventional antibiotic therapy. Making a diagnosis of COP AUTHOR \200\231S TIP The diagnosis of COP is dependent upon integrating clinical, radiologi cal and wherever possible histological evidence. COP should never be diagnosed on the basis of histology alone. BAL plays an important role in excluding infection (noso- comial, antibiotic resistant bact eria or opportunistic organisms) in this setting, but a con \201 dent diagnosis of COP aga in requires transbronchial or preferably surgical lung biopsy. A con \201 dent diagnosis of COP requires integration of clinical, radiographic and histol ogical evidence. Typical COP may be diagnosed with reasonable con \201 dence on clinical a nd radiological grounds alone if infection can be excluded and a subsequent brisk response to corti- costeroids is observed. In general however, lung tissue biopsy should be sought w henever possible before treating COP. The diagnosis of acute fulminant COP is important since there is the prospect of recovery w ith high dose corti- costeroid therapy (e.g. methylprednisolone, 500 \200\2231000mg per day for 3 consecutive days followed by prednisolone 1 \200\2231.5mg/kg/day or equivalent). Post-radiotherapy organizing pneumonia \200 A well-recognized form of OP occurs in associ ation with radiotherapy, particularly tangential \201 eld radiotherapy for breast cancer. Transbronchial lung biopsy may be suf \201 cient to make a histological diagnosis of organ izing pneumonia, but a surgical lung biopsy should be sought if the diagnosis remains uncer tain. Post-radiotherapy OP is different to classic (sporadic) post-radiotherapy pneumonitis in th at it generally occurs later (9 \200\22312 months, as opposed to 1 \200\2232 months followi ng radiotherapy), involves non-radiated areas of lung, and does not progress to lung \201 brosis. The diagnosis of COP should never be made on histo- logical basis alone because the histolo gical pattern of organizing pneumonia can occur in other settings. For example, it is quite common to \201 nd OP in the vicinity of lung cancer. Post-radiotherapy OP is therefore very like the crypto- genic form of the disease and shoul d be treated in the same way. Treating typical COP and signi \201 cance of relapses \200 Corticosteroids are the mains tay of therapy in COP, although there are no randomized controlled studies upon which to ba se recommendations. Organizing pneumonia and \201 brotic interstitial lung disease \200 It is likely that a very small subgroup of COP is associated with treatment unresponsive disease and progressi on to lung \201 brosis. Prednisolone at initial doses of 0.75 \200\2231mg/kg/day, with continued therapy for up to 1 year are often cited in the literature, but in practice, the precise dose and length of t reatment should be judged on each individual case, tak- ing into consideration the severity of the disease, patient co-morbidity and likelihood of steroid side-effects. Some cases of \200\230 \201 brosing organizing pneumonia \200\231, whether cryptogenic or secondary to connective tissue diseases, are likely to represent \200\230overlap \200\231 syndromes. For example, radiological and histological features of organizing J MURCHISON & N HARANI 146 pneumonia are sometimes seen in cases in which the otherwise dominant lesion is a UIP or \201 brotic NSIP. \200 The outcome with corticosteroid therapy in organizing pneumonia ov erlapping with \201 brotic ILD is far less certain than for typical COP, but in general t he prognosis is determined by the dominant co-existing interstitial lung disease. Katzenstein AL, Zisman DA, Litzky LA, et al. Usual interstitial pneu- monia: histologic stu dy of biopsy and explant specimens. Am J Surg Pathol 2002; 26: 1567 \200\2231577. Lazor R, Vandevenne A, Pelletier A, et al. Cryptogenic organizing pneumonia. Characteristic s of relapses in a series of 48 patients. The Groupe d \200\231Etudes et de Recherche sur l es Maladles \200\230Orphelines \200\231 Pulmonaires (GERM \200\231O \200\231P).Am J Respir Crit Care Med 2000; 162: 571 \200\223577. Lee KS, Kullnig P, Hartman TE, Muller NL. Cryptogenic organizing pneumonia: CT \201 nding s in 43 patients. Am J Roentgenol 1994; 162: 543 \200\223546. AUTHOR \200\231S TIP The initial dose and duration of corticosteroid therapy should be tail ored to the individual case; the risks and consequences of relapse in typical COP may be le ss seri- ous than the risk of prolonged corticosteroid therapy. Nambu A, Araki T, Ozawa K, et al. Bronchiolitis obliterans organiz- ing pneumonia after tan gential beam irradiation to the breast: discrimination from radiation pneumonitis. Radiat M ed 2002; 20: 151 \200\223154. Romero S, Barroso E, Rodriguez-Paniagua M, et al. Organizing pneumonia adjacent to lung can cer: frequency and clinico-patho- logic features. Lung Cancer 2002; 35: 195 \200\223201. Further reading Cohen AJ, King TE Jr, Downey GP. Rapidly progressive bronchiolitis oblitera ns with organizing pneumonia. Am J Respir Crit Care Med 1994; 149: 1670 \200\2231675. Yousem SA, Lohr RH, Colby TV. Idiopathic bronchiolitis obliterans organizing pneumonia/cryp togenic organizing pneumonia with unfavorable outcome: pathologic predictors. Mod Pathol 19 97; 10: 864 \200\223871. Cordier JF. Cryptogenic organizing pneumonia. Eur Respir J 2006; 28: 422 \200\223446. Davison AG, Heard BE, McAllister WA, et al. Cryptogenic organiz- ing pneumonia. Q J Med 1983; 52: 382 \200\223394.