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The radiology and terminology of cryptogenic organizing pneumonia.

The clinical features, radiographic and computed tomographic findings of nine patients with histological proof of cryptogenic organizing pneumonia were analysed. Patients present with cough, dyspnoea and malaise and commonly have bilateral multifocal consolidation on chest radiography, which may show resolution or relapse with or without steroid treatment. A good response to steroids is the rule, usually with complete radiological resolution or minimal residual scarring. The relative merits of the terms cryptogenic organizing pneumonia and bronchiolitis obliterans organizing pneumonia, both currently used to describe this entity, are discussed.

Aged↗

The diagnostic value of bronchoalveolar lavage and transbronchial lung biopsy in cryptogenic organizing pneumonia.

In order to determine the diagnostic value of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) in cryptogenic organizing pneumonia (COP) a prospective study was carried out. Thirty seven consecutive patients (20 males and 17 females) with clinicoradiological features of COP were enrolled in the study. The statistical analyses were completed in 35 cases. Twenty eight patients were diagnosed to have COP, all of them with a confirmatory biopsy. In seven cases, a different diagnosis was made. BAL cytological and phenotypical criteria considered for the diagnosis of COP were: a lymphocytosis of more than 25% (with a CD4/CD8 ratio less than 0.9); combined with at least two of the following data (foamy macrophages of > 20%, and/or neutrophils of > 5%, and/or eosinophils of > 2% and < 25%). TBLB specimens were classified as positive for COP if they showed: buds of granulation tissue within the centrilobular air spaces; infiltration of alveolar walls with chronic inflammatory cells; and preservation of alveolar architecture. BAL was performed in 34 patients; 17 cases were consistent with the final diagnosis of COP (sensitivity 63%), and four cases were correctly classified as negative (specificity 57%). BAL had a positive predictive value (PPV) of 85% and a negative predictive value (NPV) of 29%. TBLB was performed in 32 patients; it correctly identified COP in 16 cases (sensitivity 64%), and six cases were correctly classified as negative (specificity 86%). TBLB had a PPV of 94% and a NPV of 40%. The accuracy of the examinations, that is the probability of correctly diagnosing both diseased and nondiseased patients by BAL or TBLB, was 62 and 69%, respectively. Our findings suggest that the combination of cytological bronchoalveolar lavage and histological transbronchial lung biopsy data obtained during a fibreoptic procedure appears to be an effective method for the initial investigation in cryptogenic organizing patients pneumonia presenting with patchy radiographic shadows.

Biopsy↗

[Cryptogenic organizing pneumonia: CT features and the effect of glucocorticoids].

OBJECTIVE: To study the CT manifestations of cryptogenic organizing pneumonia (COP) after glucocorticoid treatment. METHODS: The diagnosis of COP was made based on clinical and radiological features and confirmed by lung biopsy and pathological examination in 21 cases from 2001 to 2005. CT follow-up was carried out 5 - 75 days following therapy. The follow-up lasted 3 - 43 months. All data were analyzed and relevant literatures were reviewed. RESULTS: There were 2 male an 19 female patients with ages of 39 - 74 years. CT scans revealed multiple patchy shadows or patchy air-space consolidations, often by a predominantly subpleural and/or basal distribution. Ground-glass opacities and bronchiectasis were common findings. Migratory lesions were found in some patients. Glucocorticoid treatment resulted in significant improvement in most cases. Cure was achieved in 4 cases, significant improvement in 16, and failure in 1 case. Recurrence was found in 2 cases. CONCLUSIONS: The diagnosis of COP requires combination of clinical, CT and pathological manifestations. The effect of glucocorticoid therapy can be evaluated by repeated CT scanning.

Adult↗

Cryptogenic organizing pneumonia. A report of 25 cases and a review of the literature.

Cryptogenic organizing pneumonia (COP), also known as bronchiolitis obliterans organizing pneumonia (BOOP), is an uncommon lung disease characterized by the presence of granulation tissue within the alveolar ducts and alveoli. Because of the limited published literature on this topic and limited information on outcome we reviewed our own experience over an 8-year period and also critically evaluated the literature. We reviewed all cases of COP diagnosed from 1985 through 1992 at Vancouver General Hospital: 25 patients (14 male, 11 female) aged 20-77 years (mean, 49 yr, SD +/- 17 yr). Nine patients had myeloproliferative disorder, including 6 who had allogenic bone marrow transplants; 2 patients had connective tissue disease; and 14 patients had no underlying disease (idiopathic). Data retrieved retrospectively from clinical records included demographics, risk factors, symptoms, chest radiographs, computerized tomograms, lung function tests, therapy prescribed, and response to therapy. Symptoms included dyspnea and cough (n = 15) (60%), cough only (n = 10) (40%), and fever (n = 15) (60%). Twenty-two patients were diagnosed by open lung biopsy and 3 by transbronchial biopsy. Lung imaging showed bilateral patchy airspace consolidation or nodular opacities as the main finding in 22 patients. Pulmonary function tests showed a combined restrictive and obstructive pattern. All patients received prednisone therapy except 1 patient whose idiopathic findings resolved completely with minimal treatment. Eight patients died, including 4 of the 9 patients with myeloproliferative disorder--2 from a combination of respiratory failure due to COP and graft-versus-host disease. One of 2 patients with connective tissue disease died, and 3 of 14 patients with idiopathic COP died. COP is an uncommon condition but should be considered in patients with bilateral airspace disease, especially those who fail to respond to antibiotics for presumed pneumonia. Although pulmonary function tests and CT scan findings in conjunction with the clinical features usually suggest the diagnosis, definite confirmation usually requires either open lung biopsy or transbronchial biopsy. Histologic confirmation of the diagnosis is particularly warranted as therapy with corticosteroids is usually needed for a number of months. The prognosis is excellent with idiopathic cases but more guarded especially when COP is associated with lymphoproliferative or connective tissue disease.

Adrenal Cortex Hormones↗

Cryptogenic organizing pneumonia: increased expression of interleukin-8 and fibronectin genes by alveolar macrophages.

Cryptogenic organizing pneumonia (COP) is a fibrotic process that primarily involves the alveolar spaces, alveolar ducts, and small conducting airways. The pathogenesis is not understood. Recent histopathologic studies have shown that during the cellular phase of COP, fibronectin deposits are present in the lung. Moreover, a neutrophil alveolitis is frequently seen in COP. Little is known about the involvement of alveolar macrophages in the pathogenesis of COP. However, alveolar macrophages are the principal resident cells in the airways, and they are thought to play a central role in the fibrotic process by virtue of their ability to express and release cytokines such as interleukin-8 (IL-8; a neutrophil chemotactic factor) and fibronectin (FN; a fibrogenic matrix-associated protein). We have quantified the spontaneous gene expression of IL-8 and FN by alveolar macrophages from five nonsmoking individuals with COP and compared them with 10 normal, healthy volunteers (five smokers, five nonsmokers). Expression of IL-8 and FN was measured by a quantitative assay employing reverse transcription of mRNA and the polymerase chain reaction. beta-actin mRNA expression was quantified as an internal standard, and the expression of FN and IL-8 transcripts was calculated as a ratio with beta-actin. The mean +/- SEM of the IL-8/beta-actin ratio in alveolar macrophages from patients with COP was 0.45 +/- 0.07, which was significantly higher than the level from either normal smokers (0.19 +/- 0.02, P = 0.008) or normal nonsmokers (0.16 +/- 0.01, P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The role of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in cryptogenic organizing pneumonia.

BACKGROUND: The processes observed in interstitial lung disease are associated with the production, deposition, and proteolysis of the extracellular matrix (ECM), which may lead to irreversible pulmonary structural remodeling or to appropriate repair without fibrosis. Matrix metalloproteinases (MMPs) and a tissue inhibitor of metalloproteinases (TIMPs) are known to regulate remodeling of the ECM and thus to be important in the process of lung fibrosis. Pulmonary structures are extensively remodeled in usual interstitial pneumonia (UIP), whereas severe architectural remodeling is minimally present in cryptogenic organizing pneumonia (COP). However, not much is known about the roles of MMP-9 and/or TIMP-1 in COP. METHODS: Levels of MMP-9, TIMP-1 and the molar ratio of MMP-9/TIMP-1 in BAL fluids were investigated in 11 patients with UIP, in 8 patients with COP, and in 10 control subjects. We checked the levels of MMP-9 and TIMP-1 by means of enzyme immunoassay, and the hydrolytic activity of MMP-9 in BAL fluids was measured by gelatin zymography. Further, we evaluated the expression of MMP-9 and TIMP-1 in lung tissue by immunohistochemistry. RESULTS: The concentrations of MMP-9 and TIMP-1 were significantly increased in patients with UIP and were even higher in patients with COP compared with control subjects. The levels of MMP-9 and TIMP-1 were significantly higher in patients with COP than in patients with UIP. The molar ratio of MMP-9/TIMP-1 was significantly higher in patients with COP than in control subjects. In patients with COP, the concentration of MMP-9 significantly correlated with the number of neutrophils and lymphocytes. Zymographic analysis revealed that the activity of the 92-kd pro-MMP-9 was increased in patients with UIP and was even higher in patients with COP, compared with control subjects. CONCLUSIONS: These data suggest that overproduction of MMP-9 and TIMP-1, and an imbalance between MMP-9 and TIMP-1, may have a role as diagnostic references in COP.

Bronchoalveolar Lavage Fluid↗

Cryptogenic organizing pneumonia. Characteristics of relapses in a series of 48 patients. The Groupe d'Etudes et de Recherche sur les Maladles "Orphelines" Pulmonaires (GERM"O"P).

Cryptogenic organizing pneumonia (COP) is a clinicopathologic syndrome characterized by rapid resolution with corticosteroids, but frequent relapses when treatment is tapered or stopped. We retrospectively studied relapses in 48 cases of biopsy-proven COP. One or more relapses (mean 2.4 +/- 2.2) occurred in 58%. At first relapse, 68% of patients were still under treatment for the initial episode. Compared with the no-relapse group, nine patients with multiple (>/= 3) relapses had longer delays between first symptoms and treatment onset (22 +/- 17 versus 11 +/- 8 wk, p = 0.02), and elevated gamma-glutamyltransferase (124 +/- 98 versus 29 +/- 13 IU/L, p = 0.001) and alkaline phosphatase (190 +/- 124 versus 110 +/- 68 IU/L, p = 0.04) levels. Relapses did not adversely affect outcome. Corticosteroid treatment side effects occurred in 25% of patients. Standardized treatment in 14 patients allowed a reduction of prednisone cumulated doses (p < 0.05) without affecting outcome or relapse rate. We conclude that: (1) delayed treatment increases the risk of relapses; (2) mild cholestasis identifies a subgroup of patients with multiple relapses; (3) relapses do not affect outcome, and prolonged therapy to suppress relapses appears unnecessary; (4) a standardized treatment allows a reduction in steroid doses.

Adult↗

Laminin-5 gamma2 chain in cryptogenic organizing pneumonia and idiopathic pulmonary fibrosis.

Insufficient reepithelialization of injured alveolar walls may be important in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Laminin-5 is expressed in epithelial cells of healing wounds, promoting cell attachment and migration. In this study we have studied the extent of reepithelialization of newly formed intraluminal connective tissue, the immunohistochemical expression and ultrastructural localization of the laminin-5 gamma2 chain protein, and the synthesis of the laminin-5 gamma2 chain mRNA in regenerating epithelial cells in cryptogenic organizing pneumonia (COP) and IPF. The results show that the mean extent of reepithelialization of intraluminal connective tissue lesions was 76% (SD, +/- 27%) in COP, and 54% (SD, +/- 23%) in IPF (p < 0.025). The laminin-5 gamma2 chain was synthesized and widely expressed in regenerating epithelial cells in both diseases. Immunohistochemistry for surfactant-associated protein A suggests a pneumocyte origin for the regenerating epithelial cells in IPF. It is concluded that both in COP and IPF, regenerating epithelial cells are capable of synthesizing the laminin-5 gamma2 chain needed for adhesive connections to the underlying basement membrane. However, in IPF, the reepithelialization seems to be disturbed or delayed.

Basement Membrane↗

[A case of cryptogenic organizing pneumonia accompanied by large bullae].

A 66-year-old man complaining of fever was given intravenous antibiotic therapy, but he did not improve. After subsequent admission, chest X-ray film and computed tomography scans showed large bullae and consolidation in the right lung field. A transbronchial lung biopsy specimen revealed infiltration of mononuclear cells in alveolar septa and organizing lesions in alveolar ducts. We considered this case to be cryptogenic organizing pneumonia (COP) from its clinical course and pathological findings. Treatment with corticosteroid resulted in disappearance of the large bullae and consolidations. COP accompanied by large bullae is very rare. The large bullae may have been caused by check-valve mechanism.

Aged↗

Pathologic manifestations of bronchiolitis, constrictive bronchiolitis, cryptogenic organizing pneumonia, and diffuse panbronchiolitis.

This article reviews the histopathological findings in a variety of inflammatory bronchiolar diseases. The emphasis is on differentiating syndromes of idiopathic airflow limitation (constrictive bronchiolitis and diffuse panbronchiolitis) from cryptogenic organizing pneumonia (idiopathic bronchiolitis obliterans organizing pneumonia). The histopathological findings in each of these conditions are relatively nonspecific; therefore, it is imperative that pathological findings are correlated with clinical and roentgenographic information before a specific diagnosis is made.

Acute Disease↗

Cryptogenic organizing pneumonia after radiotherapy for breast cancer.

We report a case of lasting fever and cough with pulmonary infiltrates progressing 4 months after adjuvant radiotherapy following surgery for breast cancer. Chest radiography and computed tomography demonstrated alveolar opacities outside the irradiated pulmonary area. Laboratory data revealed neutrophilia and increased levels of C-reactive protein. Bronchoalveolar lavage fluid displayed increased lymphocyte counts, and transbronchial lung biopsy revealed histological patterns compatible with cryptogenic organizing pneumonia (COP). Corticosteroid therapy resulted in marked clinical improvement. From the histological and clinical findings, this case was judged to be a case of COP induced after radiotherapy for breast cancer, similar to those reported recently.

Adrenal Cortex Hormones↗