Intra-alveolar Buds Research Articles

Clinical features of relapsed connective tissue disease-associated organizing pneumonia

BackgroundOrganizing pneumonia (OP) is recognized as a nonspecific lung injury response characterized histopathologically by the presence of intra-alveolar buds of granulation tissue. Most OP patients show excellent responses to corticosteroids, but relapse is frequently seen when corticosteroids are tapered or discontinued. Although several factors associated with relapse have been reported in cryptogenic OP (COP), the clinical features and risk factors associated with relapse in connective tissue disease–associated OP (CTD-OP) have yet to be fully understood. MethodsWe retrospectively reviewed data on 47 CTD-OP patients. We investigated the frequency of relapse and compared the clinical data between CTD-OP with and without relapse to clarify the risk factors for relapse. ResultsEleven (23.4%) CTD-OP patients had relapses of OP during the study. In the multivariate analysis, no CTD treatment at OP diagnosis [O.R. 11.920, p = 0.012] and partial remission after steroid treatment [O.R. 35.944, p = 0.045] were independent risk factors for relapse. Among rheumatoid arthritis-associated OP (RA-OP) patients, partial remission after steroid treatment [O.R. 16.151, p = 0.047] and age at OP diagnosis [O.R. 0.899, p = 0.045] were independent risk factors for relapse. Most of the relapsed OP patients who were on no medication at OP diagnosis later developed CTD. ConclusionCTD-OP patients with residual disease on HRCT after treatment and who had OP diagnosis preceding CTD diagnosis were more likely to have an OP relapse. During the clinical course of relapsed OP patients, it is necessary to pay attention to the onset of CTD.

Secondary organizing pneumonia (bronchiolitis obliterans with organizing pneumonia) associated with adalimumab for treatment of chronic plaque psoriasis

Organizing pneumonia is defined histopathologically by intra-alveolar buds of granulation tissue, consisting of intermixed myofibroblasts and connective tissue. The pathological pattern of organizing pneumonia may be idiopathic or related to a determined cause, termed secondary organizing pneumonia. We report a 68-year-old woman with a longstanding history of chronic plaque psoriasis, treated with the tumor necrosis factor (TNF) inhibitor, adalimumab. After 8 years of treatment, she developed a gradual-onset, non-productive cough with associated generalized fatigue and mild dyspnea. Radiological investigations demonstrated ground-glass opacities in the left lower lobe and bronchoscopy revealed a fibroinflammatory process consistent with organizing pneumonia. Her biologic treatment was ceased and corticosteroid treatment commenced, with resolution of both her symptoms and the radiological findings. Given the increasing incidence of biologic treatment in the management of dermatological conditions, clinicians should be aware of secondary organizing pneumonia as a possible side effect of TNF inhibitor therapy.

Organizing Pneumonia in a Patient with Quiescent Crohn’s Disease

A 64-year-old man with Crohn's disease (CD) was admitted to our hospital due to moderate risk of pneumonia while receiving scheduled adalimumab maintenance therapy. Symptoms remained virtually unchanged following administration of antibiotics. A final diagnosis of organizing pneumonia (OP) was made based on findings of intra-alveolar buds of granulation tissue and fibrous thickening of the alveolar walls on pathological examination and patchy consolidations and ground glass opacities on computed tomography. Immediate administration of prednisolone provided rapid, sustained improvement. Although a rare complication, OP is a pulmonary manifestation that requires attention in CD patients.

CASO 5-2015: Cryptogenic organizing pneumonia

Cryptogenic organizing pneumonia (COP) is a distinct histopathologic entity characterized byMasson bodies which are intraalveolar buds of granulation tissue; consisting of connective tissue and myofibroblasts. This pathologic pattern when present with the characteristic imaging and clinical features of COP defines the diagnosis of the disease. A specific etiology is not found. Treatment with corticosteroids results in a rapid clinical and imaging improvement but unfortunately relapses are common upon decreasing the dose or stopping the treatment. This case report describes a typical case of COP with the characteristic improvement with corticosteroid therapy and relapse upon treatment taper

Acute fibrinous and organising pneumonia: a case report and review of the literature

IntroductionOrganising pneumonia is a distinct histopathological entity characterized by intra-alveolar buds of granulation tissue, called Masson bodies, which mainly comprise of activated fibroblasts and loose connective tissue. This histopathologic pattern has been described in idiopathic cases, characterizing cryptogenic organising pneumonia as well as in the context of pulmonary infection, drug-induced pneumonitis and following lung transplantation. Although distinct as a clinical and pathological entity, community organising pneumonia may present with atypical clinical and pathological features, such as intra-alveolar fillings of fibrin balls and organising tissue that resembles acute respiratory distress syndrome or diffuse alveolar damage. The latter characteristics constitute a recently described anatomoclinical entity called acute fibrinous and organising pneumonia.Case presentationHere, we describe a rare case of acute fibrinous and organising pneumonia, in an otherwise healthy 65-year-old Greek woman who complained of dry cough, fever, weight loss and progressive dyspnoea. She had never been a smoker. Her clinical symptoms showed a rapid deterioration in the two weeks before admission, despite a course of oral antibiotics. After excluding infection and malignancy with routine laboratory tests and flexible bronchoscopy, high resolution computed tomography and video assisted thoracoscopic lung biopsy were performed. Diagnosis was based on radiological features typical of community organising pneumonia coupled with pathologic features characteristic of acute fibrinous and organising pneumonia. The patient was treated with corticosteroids and showed excellent clinical and radiological response three months after treatment initiation.ConclusionAcute fibrinous and organising pneumonia is an extremely rare pathologic entity, often misdiagnosed as typical community organising pneumonia. To our knowledge, this is the seventh case of acute fibrinous and organising pneumonia in the literature, with no identifiable cause or association in a female patient, with no underlying lung disease or known exposures and with an unremarkable previous medical history. We highlight the need for careful review of lung biopsies from patients with clinical and radiologic characteristics typical of community organising pneumonia. Although it remains uncertain whether fibrin alters the favourable prognosis and treatment response of community organising pneumonia, it becomes obvious that a thorough pathologic review, apart from establishing the diagnosis of acute fibrinous and organising pneumonia, may predict a more unfavorable outcome therefore alerting the clinician to administer more aggressive and prolonged therapeutic regimens.

A simultaneous onset of organizing pneumonia and rheumatoid arthritis, along with a review of the literature

Organizing pneumonia (OP) is a specific type of interstitial pneumonia that has been noted as one of the pulmonary manifestations during the course of rheumatoid arthritis (RA). In this study, we report a case with a simultaneous development of OP and RA. The patient presented with concurrent flu-like symptoms and arthralgia of multiple joints, and antibiotic therapy was not effective. The rheumatoid factor (RF) and anti-cyclic citrullinated antibodies were both high. Multiple air-space opacities on chest radiographs and bilateral peripheral consolidations on high-resolution computed tomography films were evident. The histology of transbronchial lung biopsy samples was characterized by intra-alveolar buds of granulation tissue consisting of intermixed myofibroblasts and connective tissues. Treatment with prednisolone induced a complete recovery from OP without relapses. Our review of previous reports about RA-associated OP (RA-OP) suggested that the high titer of RF and increased disease activity of RA indicate a great risk of developing OP. This condition may represent a lung's reaction in the RA-associated inflammatory and/or immune process. We should be aware of RA-OP cases in which pulmonary manifestations precede articular symptoms. In these cases, respiratory manifestations are the main evidence of RA activity. In most cases of steroid-resistant RA-OP, the use of immunosuppressants was effective. Since OP may progress to fibrotic lung disease during the course of RA, we may consider performing a second lung biopsy for steroid-resistant patients, even if they have once been diagnosed as OP.

Cryptogenic organising pneumonia

Organising pneumonia is defined histopathologically by intra-alveolar buds of granulation tissue, consisting of intermixed myofibroblasts and connective tissue. Although nonspecific, this histopathological pattern, together with characteristic clinical and imaging features, defines cryptogenic organising pneumonia when no cause or peculiar underlying context is found. Rapid clinical and imaging improvement is obtained with corticosteroid treatment, but relapses are common after stopping treatment.

Update on cryptogenic organising pneumonia (idiopathic bronchiolitis obliterans organising pneumonia).

Organising pneumonia, defined by intraalveolar buds of connective tissue, may be a disorder secondary to a determined cause (infectious agents, drugs) or occurring in a specific context (as the connective tissue disorders). It may also be a cryptogenic interstitial pneumonia with characteristic clinical and imaging features and especially an excellent response to corticosteroids.

Update on cryptogenic organising pneumonia (idiopathic bronchiolitis obliterans organising pneumonia).

Organising pneumonia, defined by intraalveolar buds of connective tissue, may be a disorder secondary to a determined cause (infectious agents, drugs) or occurring in a specific context (as the connective tissue disorders). It may also be a cryptogenic interstitial pneumonia with characteristic clinical and imaging features and especially an excellent response to corticosteroids.

Evolution of three patterns of intra-alveolar fibrosis produced by bleomycin in rats.

In pulmonary fibrosis, it is known that fibrotic changes develop in the intra-alveolar spaces and that intra-alveolar fibrosis can be classified into three patterns, namely intra-alveolar buds, mural incorporation and obliterative changes. In order to clarify the evolution of intra-alveolar fibrosis, immunohistochemical studies of extracellular matrix proteins and electron microscopic observations were made of the lungs of rats given a single intratracheal instillation of bleomycin. All three patterns of fibrosis developed in this model. Intra-alveolar buds changed into globular lesions with dense collagen deposition, the surface of which was covered by alveolar epithelium. Electron microscopy revealed that the buds often contained spiraling collagen fibrils and numerous microfibrils, but not mature elastic fibres, beneath the regenerating epithelial lining cells; the epithelial basement membranes were discontinuous. In contrast, mural incorporation and obliterative changes were associated with alveolar structural remodeling. Electron microscopically, these lesions had bundles of normal collagen fibrils, small elastic fibers, and continuous epithelial basement membranes. These results indicate that: (i) intra-alveolar buds, that become intra-alveolar collagen globules, with an unusual extracellular matrix, do not contribute to alveolar structural remodelling; and (ii) areas of mural incorporation and obliterative changes have the usual type of extracellular matrix and are essential for alveolar structural remodelling.

Immunohistochemical localization of transforming growth factor‐β1 in the lungs of patients with systemic sclerosis, cryptogenic fibrosing alveolitis and other lung disorders

To study the role of transforming growth factor-beta 1 (TGF-beta 1) in the pathogenesis of pulmonary fibrosis we have examined lung biopsies from nine patients with systemic sclerosis and interstitial lung disease, eight with 'lone' cryptogenic fibrosing alveolitis, two with cystic fibrosis, two with extrinsic allergic alveolitis, two with Langerhans' cell histiocytosis, one with lymphangioleiomyomatosis, one with giant cell interstitial pneumonia, and one adenocarcinoma of the lung. In cryptogenic fibrosing alveolitis, both 'lone' and associated with systemic sclerosis alveolar macrophages, bronchial epithelium and hyperplastic type II pneumonocytes expressed intracellular TGF-beta 1. Extracellular TGF-beta 1 was found in the fibrous tissue immediately beneath the bronchial and hyperplastic alveolar epithelium. In normal lung, however, the alveolar epithelium and alveolar interstitium were negative for both forms of TGF-beta 1. There was strong expression of TGF-beta 1 in hyperplastic mesothelium and its underlying connective tissue and in Langerhans' cells in the two cases of histiocytosis. In the organizing pneumonia in cystic fibrosis, the intraalveolar buds of granulation tissue reacted strongly for the extracellular form of TGF-beta 1 and the overlying hyperplastic epithelium expressed the intracellular form. In lymphangioleiomyomatosis, the aberrant smooth muscle cells strongly expressed intracellular TGF-beta 1 and the extracellular form was expressed in the adjacent connective tissue. In giant cell interstitial pneumonia, the numerous alveolar macrophage including the multinucleate forms, expressed intracellular TGF-beta 1, as did the hyperplastic alveolar epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Seasonal cryptogenic organising pneumonia with biochemical cholestasis: a new clinical entity

The term crytogenic organising pneumonia has been used for the combination of dyspnoea, cough, pleuritic pain, widespread shadows on chest radiographs, and histological evidence of intra-alveolar organisation with buds of granulation tissue within the alveoli. We report 12 patients with seasonal recurrence of this disorder for between 3 and 11 years. In all 12 patients, symptoms recurred between late February and early May every year, tending to increase in severity each year, and resolved between June and January. Chest radiography and computed tomography showed bilateral consolidation. Lung biopsy samples.showed intra-alveolar buds of granulation tissue. There were many neutrophils within the lumina of medium-sized airways and terminal bronchioles showed evidence of obstruction by granulation tissue. Functionally, the predominant defect was restrictive and only 2 patients (life-long non-smokers) had airflow limitation. All 12 patients had very high activities of liver enzymes, suggesting intrahepatic cholestasis, but no other evidence of liver disease. Cultures of blood, sputum, lung tissue, and bronchoalveolar lavage fluid, viral screening, and complement fixation tests were consistently negative. In all patients all abnormalities responded rapidly to oral steroid therapy. These findings suggest a seasonal syndrome of organising pneumonia and biochemical abnormalities indicative of intrahepatic cholestasis. No aetiological factor has been identified, but the nature and periodicity of the illness point to an inhaled agent present in the environment for a limited period every year.