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The characteristics of patients with rheumatoid arthritis (RA) who develop obliterative bronchiolitis characterised by severe airflow obstruction have been hitherto poorly investigated. A retrospective study of 25 patients with RA and functional evidence of obliterative bronchiolitis (forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) <50% and/or residual volume (RV)/total lung capacity (TLC) >140% predicted) was conducted. Patients (mean+/-SD age 64+/-11 yrs) included 17 never-smokers and eight ex-smokers (10.5+/-5.4 pack-yrs). The diagnosis of RA preceded respiratory symptoms in 88% of cases. Dyspnoea on exertion was present in all patients and bronchorrhea in 44%. High-resolution computed tomography findings included: bronchial wall thickening (96%), bronchiectasis (40%), mosaic pattern (40%), centrilobular emphysema (56%), and reticular and/or ground-glass opacities (32%). Pulmonary function tests showed: FEV(1) 41+/-12% pred, FEV(1)/FVC 49+/-14%, FVC 70+/-20% pred, RV 148+/-68% pred and RV/TLC 142+/-34% pred. Lung biopsy, available in nine patients, demonstrated constrictive, follicular and mixed bronchiolitis. Patients were followed for 48.2+/-49 months. Treatment was poorly effective. Chronic respiratory failure occurred in 40% of patients, and four patients died. Obliterative bronchiolitis associated with rheumatoid arthritis is a severe and under-recognised condition leading to respiratory failure and death in a high proportion of patients.

The process leading to irreversible fibrotic constriction of the bronchioles was studied in two cases of bronchiolitis obliterans (BO) after bone marrow transplantation. Because lysyl oxidase (LOX) is the main collagen cross-linking enzyme that might account for irreversible fibrosis, its expression was studied together with expression of extracellular matrix (ECM) proteins. Characteristic types of lesions could be distinguished on the basis of histological and immunohistological criteria. An inflammatory stage was characterised by infiltration restricted to the bronchioles by lymphocytes and dendritic cells. A fibro-inflammatory stage was characterised by the coexistence of a persistent immune cellular lesion pattern with further focal modelling of a sub-epithelial neo-synthesised connective matrix. LOX expression was observed at the tips of intra-luminal fibrotic protrusions, together with tenascin and cellular fibronectin. A fibrotic stage was characterised by dense ECM deposits spreading throughout the peri-bronchiolar connective tissue, resulting in bronchiole obliteration and final disappearance. In contrast to reversible cases of fibrosis, persistence of long-term LOX expression reflecting continuing fibrosing activity might account for the irreversible status of BO. Our two cases illustrated that, at inflammatory and fibro-inflammatory stages, BO may be stabilised by immunosuppressive treatment, while the persistence of LOX expression in the fibrotic stage might correspond to a disease that becomes irreversible and fatal.

Respiratory bronchiolitis (RB) is defined by the accumulation of pigmented macrophages in the lumen and wall of respiratory and membranous bronchioles of smokers. The aim of this study was to determine whether spontaneous pneumothorax was associated with a high prevalence of RB. Seventy-nine consecutive patients who underwent a surgical procedure (thoracotomy or thoracoscopy) for recurrence or persistence of primary spontaneous pneumothorax despite thoracic drainage were studied retrospectively. RB was found in 70 of 79 (88.6%) smokers operated for spontaneous pneumothorax. Associated interstitial pathological abnormalities were present in 53 of 79 cases (67.1%). In nine patients, the pathological lesions were severe and resembled desquamative interstitial pneumonia. Emphysematous lesions were present in about one-third of the patients. Although the possible pathophysiological consequences of respiratory bronchiolitis remain speculative, this study demonstrates the high prevalence of this pathological abnormality in patients with pneumothorax requiring surgical treatment.

Patients at a single pulmonary centre who developed obstructive lung disease after bone marrow transplantation (BMT) and lung transplantation (LT) were studied, in order to compare the clinical expression of post-transplant obstructive lung disease (PTOLD) (bronchiolitis obliterans) in these two conditions, which have so far been studied separately. Nine out of 179 patients surviving more than 100 days after BMT (5%) and 9 out of 44 patients surviving more than 100 days after LT (20%) developed post-transplant obstructive lung disease. This was defined by an irreversible airflow obstruction, as characterized by a forced expiratory volume in one second divided by forced vital capacity (FEV1/FVC) of less than 70%, and a FEV1 of less than 70% of predicted value. The mean interval between transplantation and the diagnosis of post-transplant obstructive lung disease was 262 days and 217 days for BMT and LT patients, respectively. In all cases, pulmonary symptoms consisted of dyspnoea and progressively productive cough. Bronchial dilatation on high-resolution computed tomography scans was the main imaging feature present in both groups of patients at the onset of post-transplant obstructive lung disease. The mean FEV1/FVC ratio was 51 and 54% for BMT and LT patients, respectively. All BMT and LT patients had normal transfer coefficient. Clinical chronic graft-versus-host disease was present in all BMT patients before or concurrent with the onset of post-transplant obstructive lung disease, and all LT patients had presented at least one episode of acute lung rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

The conviction that has rapidly forced itself upon clinicians is that COP is a clinicopathological syndrome relevant in pulmonary medicine. Obscured for a long time by both ambiguities in the clinical interpretation of the pathologic term "bronchiolitis obliterans" and the enduring concept that organizing pneumonia was almost always merely of usual infectious origin, it finally was characterized when clinical and pathologic data were carefully correlated using the clinicopathologic method advocated by Laënnec at the beginning of the last century. COP is now easily recognized in its typical form, in which patients present with a subacute inflammatory pulmonary disease with patchy alveolar opacities on chest imaging. A negative etiologic investigation and characteristic pathologic features confirm the diagnosis. Corticosteroids are a highly effective treatment, despite the relapses occurring when therapy is stopped too rapidly, further indicating that COP is an inflammatory process that may persist for prolonged periods. Less typical forms of COP, solitary focal and diffuse infiltrative COP, need further characterization to define their respective limits with typical COP and UIP. Whatever its origin(s), COP clearly merits recognition as a distinct entity on clinical, imaging, pathologic, and evolutive grounds. COP probably is not a new disease, but its delayed recognition proves that clinicopathologic studies are still of interest.

The aim of this study was to define the presence, histological types and extent of bronchiolitis obliterans (BO) after lung transplantation and to discuss the place of bronchiolitis obliterans in the progressive obstructive ventilatory disorder observed in some patients and considered to correspond to "chronic lung rejection". The histological lesions were studied in 16 subjects surviving for more than one month after lung transplantation or heart-lung transplantation: 12 autopsies, 3 surgical biopsies and one lung explanted for retransplantation. Thirteen subjects presented lesions of bronchiolitis obliterans: 5 cases of granulomatous BO, 6 cases of proliferative BO, one acute necrotising BO and one tuberculous granulomatous BO. Three of these patients presented an obstructive ventilatory disorder: one death on the 213rd day (acute necrotising BO), one retransplantation on the 672nd day (granulomatous BO), one death 53 days after surgical biopsy on the 247th day (proliferative BO). Two patients undergoing surgical biopsies with lesions of proliferative BO are still alive (cases 15 and 16) and do not present any signs of obstructive ventilatory disorder. This study suggests the existence of various histological types of BO in transplanted lungs, which is not exclusively of immunopathological origin, that infections and various inhalations also play a role and that alterations of pulmonary structures other than bronchioles are also involved in the pathogenesis of the obstructive ventilatory disorder (functional destruction of the transplant), corresponding to "chronic lung rejection".

In 40 to 60% of bone marrow grafts there are pulmonary complications of which the most frequent is the occurrence of an interstitial pneumonia. We report 7 cases here of a more rare complication, that of bronchiolitis obliterans (BO). Between December 1979 and November 1989, 7 patients (3.4% of our cases of GMO) have developed over several months a chronic obstructive respiratory failure (a mean VEMS of 43% of the theoretical value) in the year following the transplantation (mean delay 190 days). 6 patients presented with cutaneous, digestive or hepatic signs of chronic graft v host illness (GVH) whereas the prevalence of this complication in the population studied was 17%. Treatment combining bronchodilators and immunosuppressants was only successful in 2 cases and the outcome was fatal in the 5 other cases as a result of respiratory failure (mean delay 208 days between the appearance of respiratory symptoms and death). The pathogenesis of BO after GMO remains poorly understood. It may rest on an immune process during the course of which the BO would be the result of a chronic pulmonary GVH. Another hypothesis is that the state of the immunosuppression in these patients would favour the appearance of a bronchiolitis of an infectious origin, particularly viral. The prognosis of BO after GMO is very poor and in the absence of specific effective treatment the therapeutic strategy remains essentially that of prevention by the early detection of respiratory anomalies.

Bronchiolitis obliterans organizing pneumonia (BOOP) is defined by endoluminal obstruction of distal airspaces by a fibrous granulation tissue consisting of inflammatory cells, fibroblasts, and connective tissue. The morphogenesis of the process is the following: diffuse alveolar injury leading to basement membrane denudation and intra-alveolar exudate of fibrinogen, immunoglobulins, coagulation factors, fibronectin; intra-alveolar migration of interstitial fibroblasts through gaps of the epithelial basement membrane; intra-alveolar secretion of loose connective tissue (codistribution of collagens I, III, V, and fibronectin) by the fibroblasts-myofibroblasts. The main characteristic of this peculiar fibrosis is its possible reversibility. BOOP is not specific for any aetiology, and it is found in various conditions as infectious diseases, drug induced pulmonary diseases, connective tissue diseases. It is also present in other conditions where it is not the most contributive information to diagnosis (hypersensitivity pneumonitis, chronic eosinophilic pneumonia). But in some cases BOOP remains idiopathic and has to be individualized. Three clinical and imaging profiles are distinguished: the most characteristic consists of an inflammatory context with imaging patchy alveolar opacities, migrating and relapsing, and most steroid sensitive; the other two presentations are less remarkable: pseudo-neoplastic localized chronic pneumonia, and diffuse infiltrative lung disease. BOOP is a clinico-pathologic entity that the clinician must know because of the efficacy of corticosteroid treatment in most cases, and it further represents an unique model to understand the pathogenesis of fibrosing pulmonary diseases.

Idiopathic bronchiolitis obliterans-organizing pneumonia (BOOP) is characterized by air space fibrosis of unknown origin. Clinical resolution under steroid treatment suggests the removal of the fibrotic lesion. Open lung biopsies of four patients with idiopathic BOOP were studied by immunochemistry and electron microscopy. Three distinct cell-matrix patterns of intra-alveolar bud were found to represent the sequential evolution of the fibrotic process: fibrinoid inflammatory cell clusters in which immunoglobulins and procoagulant factors (fibrinogen, factors VII and X) were identified; fibroinflammatory buds in which desmin-containing fibroblasts were observed migrating, proliferating, and secreting matrix proteins; fibrotic buds in which myofibroblasts organized a loose connective matrix predominantly composed of fibronectin and type III collagen. Extending forms of fibrotic buds may join contiguous alveoli. Fibrotic bud remodeling ability is correlated to the nature and organization of the matrix components but the factors permitting intra-alveolar matrix degradation must be characterized.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a pathologic finding common to various injuries to the lung of either definite or idiopathic etiology. Since the presentation of patients with idiopathic BOOP varies, we studied 16 patients with BOOP on pulmonary histology to define more distinct and homogeneous clinical and imaging profiles of idiopathic BOOP. We distinguished three groups of patients: group 1 (n = 4), with multiple patchy migratory pulmonary involvement of the pneumonia type. Their clinical course was subacute, with cough, fever, weight loss, mild dyspnea, and increased ESR. Chest x-ray film and CT scan showed multiple alveolar opacities. All patients completely recovered with corticosteroid therapy but relapsed when therapy was stopped too rapidly. Group 2 (n = 5) had solitary pulmonary involvement of the pneumonia type occurring in a similar clinical context. Since carcinoma was suspected, they underwent surgical excision of the pneumonic area and recovered without relapse. Group 3 patients (n = 7) presented with diffuse pulmonary involvement of the interstitial lung disease type. They had more progressive onset of more severe dyspnea, crackles heard over all lung surfaces, and interstitial opacities with or without alveolar opacities on chest imaging. Improvement with corticosteroid therapy was obtained in only three patients. In all three groups, lung function test results showed a restrictive pattern. The obstructive pattern characteristic of pure bronchiolitis obliterans was found in none. BAL showed a mixed pattern (increase of both lymphocytes and polymorphonuclear cells) in the patients of the first two groups. Thus, we distinguished three characteristic clinical and imaging profiles in patients with idiopathic BOOP: multiple patchy pneumonia, solitary pneumonia, and diffuse interstitial lung disease. These profiles are so different that they should be distinguished in clinical studies of idiopathic BOOP.