Transbronchial Lung Biopsy Samples Research Articles

Cell pellet from fixative medium of transbronchial lung biopsy sample improves lung cancer ancillary test

ObjectivesLung cancer tissue obtained using small biopsies are relatively fragile, leaving behind some tiny tissue fragments or cell clusters in the fixative medium that are difficult to collect for processing as a paraffin-embedded tissue block. Usually, the cellular component of the residual fixative medium is discarded as medical waste as per routine laboratory protocol. No protocol exists for utilizing the cellular component of the residual fixative medium after processing the tissue blocks to improve lung cancer ancillary testing. This study aimed to undercover the potential value of these samples for lung cancer diagnosis and targeted therapy development. Materials and MethodsA protocol was developed for cell pellet sample collection from the residual fixative medium of a transbronchial forceps lung biopsy sample. Tumour cell number and fraction in a paired cell pellet and matching formalin-fixed paraffin-embedded tissue section were evaluated from 324 non-smallcell lung carcinoma (NSCLC) cases. We defined the adequacy of the cell pellet for molecular analysis as ≥ 200 tumour cells and ≥ 10 % tumour cells. Real-time polymerase chain reaction and next-generation sequencing were performed on adequate cell pellet samples. ResultsWe discovered that the fixative medium of most transbronchial forceps lung biopsy samples was enriched in tumour cells. Among 324 biopsy samples, 70 (21.6%) exhibited inadequate formalin-fixed paraffin-embedded tissue sections, whereas 53 (75.7%) yielded adequate cell pellet samples. Somatic mutations detected in the formalin-fixed paraffin-embedded tissue section samples were also detected in the matching cell pellets. ConclusionsCell pellets collected from the fixative medium of thoracic small biopsies are a beneficial supplemental material for ancillary testing. Combined use of cell pellets with traditional tissue-based samples can enhance the detection rate of informative mutations in patients with advanced NSCLC.

Evaluation of Predictors of the Effectiveness of Bronchoscopic Biopsies with Navigation by Endobronchial Ultrasound Mini Probes in Peripheral Lung Masses of Various Etiologies

The objective of the study: to evaluate and compare the predictors of effectiveness of navigation bronchobiopsy – radial endobronchial ultrasound with mini probes (rEBUS) in patients with peripheral pulmonary tumors of tuberculosis and oncological origin.Subjects and Methods. The effectiveness of rEBUS-guided bronchoscopic biopsies and predictors of this effectiveness were retrospectively analyzed in 152 patients (71 men and 81 women) with pulmonary tumors visualized by chest computed tomography (CT) as peripheral lung masses. All patients were divided into 2 groups according to the verified diagnoses: TB Group included 83 patients with pulmonary tuberculosis without bacterial excretion at the time of bronchological examination; NEO Group included 69 patients with pulmonary neoplasms.In all patients of both groups, a bronchological examination was performed for diagnostic purposes and included several types of biopsies (a set of biopsies): at least one of the liquid biopsies (bronchoalveolar lavage (BAL) or bronchial lavage) and one tissue biopsy (transbronchial lung biopsy (TBLB) or brush biopsy). Specimens of all types of bronchobiopsy were sent for microbiological and cytological tests, and the TBLB samples were additionally sent for histological examination.Results. The efficiency of diagnosing bronchobiopsy with rEBUS navigation in TB and NEO Groups was comparable – 81.9% (68/83) and 81.2% (56/69) (pχ2 > 0.05), respectively. The factors (predictors) that statistically significantly influenced on effectiveness of bronchobiopsy in both groups were the following: signs of draining bronchus on chest CT, visualization of the mass in general during rEBUS, central position of the ultrasound probe in the mass during navigation, localization of the mass in the upper lobe of the right lung versus the lower lobe (summarized in two groups).Additionally for TB Group, the predictor was the size of the mass exceeding 20 mm.The effectiveness of cytological and histological verification in NEO Group with brush biopsy and TBLB samples significantly surpassed the effectiveness in TB Group, but the microbiological diagnosis of M. tuberculosis in BAL/bronchial lavage specimens increased the effectiveness in TB Group and made it comparable to NEO Group.

Immunohistochemical characterization of granulomatosis with polyangiitis exhibiting spontaneous regression.

Granulomatosis with polyangiitis (GPA) is characterized by granulomatous inflammation, vasculitis, and elevated levels of serum proteinase 3 (PR3)-anti-neutrophil cytoplasmic antibody (PR3-ANCA). We tried to characterize immune cells accumulated into the lung lesions of a GPA patient exhibiting spontaneous regression. Transbronchial lung biopsy (TBLB) samples were subjected to immunohistochemical analyses. Multiple lung nodules were detected by CT. TBLB showed granulomatous inflammation and small vessel vasculitis. This case was diagnosed as GPA based on pathological findings and elevation of PR-3 ANCA levels. Spontaneous disappearance of multiple lung nodules was observed in CT. CD3+ T cells and CD20+ B cells accumulated in the inflammatory lesions surrounding the vessels whereas granulomatous inflammation was mainly comprised of CD3+ T cells and CD68+ macrophages, but not B cells or myeloperoxidase+ neutrophils. We characterized immune cell compositions of the lung lesions of a patient with GPA exhibiting spontaneous regression.

Updates in using a molecular classifier to identify usual interstitial pneumonia in conventional transbronchial lung biopsy samples.

A molecular classifier using a machine-learning algorithm based on genomic data could provide an objective method to aid clinicians and multidisciplinary teams to establish the diagnosis of IPF in less-invasive transbronchial lung biopsy samples https://bit.ly/2QLdWim

Use of a molecular classifier to identify usual interstitial pneumonia in conventional transbronchial lung biopsy samples: a prospective validation study

In the appropriate clinical setting, the diagnosis of idiopathic pulmonary fibrosis (IPF) requires a pattern of usual interstitial pneumonia to be present on high-resolution chest CT (HRCT) or surgical lung biopsy. A molecular usual interstitial pneumonia signature can be identified by a machine learning algorithm in less-invasive transbronchial lung biopsy samples. We report prospective findings for the clinical validity and utility of this molecular test. We prospectively recruited 237 patients for this study from those enrolled in the Bronchial Sample Collection for a Novel Genomic Test (BRAVE) study in 29 US and European sites. Patients were undergoing evaluation for interstitial lung disease and had had samples obtained by clinically indicated surgical or transbronchial biopsy or cryobiopsy for pathology. Histopathological diagnoses were made by experienced pathologists. Available HRCT scans were reviewed centrally. Three to five transbronchial lung biopsy samples were collected from all patients specifically for this study, pooled by patient, and extracted for transcriptomic sequencing. After exclusions, diagnostic histopathology and RNA sequence data from 90 patients were used to train a machine learning algorithm (Envisia Genomic Classifier, Veracyte, San Francisco, CA, USA) to identify a usual interstitial pneumonia pattern. The primary study endpoint was validation of the classifier in 49 patients by comparison with diagnostic histopathology. To assess clinical utility, we compared the agreement and confidence level of diagnosis made by central multidisciplinary teams based on anonymised clinical information and radiology results plus either molecular classifier or histopathology results. The classifier identified usual interstitial pneumonia in transbronchial lung biopsy samples from 49 patients with 88% specificity (95% CI 70-98) and 70% sensitivity (47-87). Among 42 of these patients who had possible or inconsistent usual interstitial pneumonia on HRCT, the classifier showed 81% positive predictive value (95% CI 54-96) for underlying biopsy-proven usual interstitial pneumonia. In the clinical utility analysis, we found 86% agreement (95% CI 78-92) between clinical diagnoses using classifier results and those using histopathology data. Diagnostic confidence was improved by the molecular classifier results compared with histopathology results in 18 with IPF diagnoses (proportion of diagnoses that were confident or provisional with high confidence 89% vs 56%, p=0·0339) and in all 48 patients with non-diagnostic pathology or non-classifiable fibrosis histopathology (63% vs 42%, p=0·0412). The molecular test provided an objective method to aid clinicians and multidisciplinary teams in ascertaining a diagnosis of IPF, particularly for patients without a clear radiological diagnosis, in samples that can be obtained by a less invasive method. Further prospective clinical validation and utility studies are planned. Veracyte.

Pneumocystis Jirovecii Pneumonia in Immunocompetent Japanese Male

SESSION TITLE: Unusual Pulmonary Infections SESSION TYPE: Global Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Pneumocystis jiroveci pneumonia (PCP) is a common opportunistic infection in acquired immune deficiency syndrome (AIDS) patients. The risk factors are low CD4+ lymphocyte count (in HIV patients), underlying malignancies, organ transplantation or immunosuppressive medications. PCP without those risk factors is extremely rare. We herein report a case of PCP in an immunocompetent patient. CASE PRESENTATION: A 37-year-old Japanese male presented with a non-productive cough for two weeks. He had a history of intracerebral hemorrhage at the age of two. He had never smoked and drunk alcoholic beverages. Initial vital signs were almost unremarkable other than low oxygen saturation (93% in room air). Physical examinations were unremarkable. Chest radiograph revealed a diffuse airspace consolidation on the both lungs. Chest computed tomography (CT) scan revealed bilateral airspace consolidation, ground-glass opacity, and traction bronchiectasis on the upper lobes. Laboratory tests were remarkable for the elevated white blood cell (8,850/mm3), lactate dehydrogenase (425 U/l), C-reactive protein (9.18 mg/dl), KL-6 (2,940 U/ml), and decreased total protein (5.3 g/dl) and albumin (2.1 g/dl). Serum rheumatoid factor and anti-nuclear antibody were negative. Serum levels of immunoglobulin A, G and M were within normal range. Sputum and blood culture did not yield any organisms, and the patient underwent bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB). The cytological analysis of BAL fluid (BALF) was unremarkable, and routine cultures of BALF were negative. TBLB sample from the right upper lobe revealed alveolar septal thickening by chronic inflammatory cells infiltration with collagen-type fibrosis. From these results, the patient was diagnosed with acute exacerbation of chronic fibrosing interstitial pneumonia, and received intravenous levofloxacin with corticosteroid pulse therapy followed by a prednisolone maintenance therapy. On the 5th day of the treatment, his respiratory condition worsened and cyclophosphamide (500 mg/body) was added intravenously. On the same day, the additional laboratory examination revealed an elevated serum β-D glucan level (104.3 pg/ml), and voriconazole and sulfamethoxazole trimethoprim were started. The additional HIV antibody test was negative. Despite the anti-fungal therapy, he died on the 12th day due to respiratory failure. Autopsy revealed alveolar spaces filled with foamy amorphous material composed of abundant numbers of cystic forms of Pnemocystis jirovecii and cell debris, and also inflammatory reaction with hyaline membranes. Retrospectively, Gomori-Grocott’s methenamine silver-nitrate staining of the BALF and TBLB samples obtained on the admission day revealed a little amount of cystic forms of Pneumocystis jirovecii, therefore, it was thought that he had been PCP from the admission day. DISCUSSION: PCP in patients without underlying immunosuppressive diseases is exclusively rare, and to our best knowledge, only 19 cases have been reported to date. In Cano’s case series, two patients had previous or simultaneous infection by another microorganisms, and they speculated that a transitory alteration in the immunocompetency condition due to a previous or concomitant infection of PCP might develop. However, our patient did not show the evidence of infection other than Pneumocystis jirovecii. In our patient, we finally suspected PCP from the resistance immunosuppressive therapy and the elevated β-D glucan level, and it is thought that we should perform the Gomori-Grocott’s methenamine silver-nitrate staining of BALF, retrospectively. CONCLUSIONS: We experienced a case of PCP without any underlying risk factors. Although this condition is exclusively rare, but it may be necessary to perform serum β-D glucan assay and Gomori-Grocott’s methenamine silver-nitrate staining of BALF in patients with diffuse ground-glass opacity, regardless of immune status. Reference #1: Palella Jr FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. New England Journal of Medicine. 1998;338(13):853-60. Reference #2: Jacobs JL, Libby DM, Winters RA, et al. A cluster of Pneumocystis carinii pneumonia in adults without predisposing illnesses. New England Journal of Medicine. 1991;324(4):246-50. Reference #3: Koshy G, Koshy JM, John M, Deodhar D. Pneumocystis jirovecii pneumonia in an immunocompetent host. Annals of Tropical Medicine and Public Health. 2015;8(4):122. DISCLOSURE: The following authors have nothing to disclose: Masanobu Okahisa, Kazunori Tobino No Product/Research Disclosure Information

Localization of Propionibacterium acnes in granulomas supports a possible etiologic link between sarcoidosis and the bacterium

Sarcoidosis likely results from the exposure of a genetically susceptible subject to an environmental agent, possibly an infectious one. Mycobacterial and propionibacterial organisms are the most commonly implicated potential etiologic agents. Propionibacterium acnes is the only microorganism, however, found in sarcoid lesions by bacterial culture. To evaluate the pathogenic role of this indigenous bacterium, we screened for the bacterium in sarcoid and non-sarcoid tissues using immunohistochemical methods with novel P. acnes-specific monoclonal antibodies that react with cell-membrane-bound lipoteichoic acid (PAB antibody) and ribosome-bound trigger-factor protein (TIG antibody). We examined formalin-fixed and paraffin-embedded samples of lungs and lymph nodes from 196 patients with sarcoidosis, and corresponding control samples from 275 patients with non-sarcoidosis diseases. The samples were mostly from Japanese patients, with 64 lymph node samples from German patients. Immunohistochemistry with PAB antibody revealed small round bodies within sarcoid granulomas in 20/27 (74%) video-assisted thoracic surgery lung samples, 24/50 (48%) transbronchial lung biopsy samples, 71/81 (88%) Japanese lymph node samples, and 34/38 (89%) German lymph node samples. PAB antibody did not react with non-sarcoid granulomas in any of the 45 tuberculosis samples or the 34 samples with sarcoid reaction. In nongranulomatous areas, small round bodies detected by PAB antibody were found in alveolar macrophages of lungs and paracortical macrophages of lymph nodes from many sarcoid and some non-sarcoid patients. Large-spheroidal acid-fast bodies, Hamazaki–Wesenberg bodies, which were found in 50% of sarcoid and 15% of non-sarcoid lymph node samples, reacted with both PAB and TIG antibodies. Electron microscopy revealed that these Hamazaki–Wesenberg bodies had a single bacterial structure and lacked a cell wall with occasional protrusions from the body. The high frequency and specificity of P. acnes, detected by PAB antibody within sarcoid granulomas, indicates that this indigenous bacterium might be the cause of granuloma formation in many sarcoid patients.

The sarcoid granuloma: ‘epithelioid’ or ‘lymphocytic-epithelioid’ granuloma?

Background: This study aims to analyze the structure and quantities of cellular elements in sarcoid granulomas. Methods: We investigated 34 transbronchial lung biopsy samples obtained from 34 sarcoid patients. The quantity and composition of the cellular elements inside a granuloma were determined by the quantitative stereometry method, employing the numerical density as a stereological method. Results: A total of 102 sarcoid granulomas were analyzed. The central part of all granulomas was occupied by epithelioid cells. Besides these, giant cells, lymphocytes, macrophages and plasma cells were also seen. The mean numerical density of all the cells in the central part of a sarcoid granuloma was 111,751 mm-3. Lymphocytes prevailed in number, exceeding the total count of all other cells. With a mean numerical density of 74,321 mm-3, lymphocytes were twice as numerous as both epithelioid cells and macrophages with a mean numerical density of 37,193 mm-3. Conclusions: Lymphocytes are the predominant cell type in the central part of a sarcoid granuloma, significantly exceeding both epithelioid cells and macrophages in number, raising the question if the term “epithelioid granuloma”, routinely used to designate sarcoid granulomas, is correct, or if it would be more logical to call them “lymphocytic-epithelioid granulomas” instead. Trial registration: This study was supported by the Serbian Ministry of Science and Environmental Protection Grant Number 175006/2011.

The sarcoid granuloma: ‘epithelioid’ or ‘lymphocytic-epithelioid’ granuloma?

BackgroundThis study aims to analyze the structure and quantities of cellular elements in sarcoid granulomas.MethodsWe investigated 34 transbronchial lung biopsy samples obtained from 34 sarcoid patients. The quantity and composition of the cellular elements inside a granuloma were determined by the quantitative stereometry method, employing the numerical density as a stereological method.ResultsA total of 102 sarcoid granulomas were analyzed. The central part of all granulomas was occupied by epithelioid cells. Besides these, giant cells, lymphocytes, macrophages and plasma cells were also seen. The mean numerical density of all the cells in the central part of a sarcoid granuloma was 111,751 mm-3. Lymphocytes prevailed in number, exceeding the total count of all other cells. With a mean numerical density of 74,321 mm-3, lymphocytes were twice as numerous as both epithelioid cells and macrophages with a mean numerical density of 37,193 mm-3.ConclusionsLymphocytes are the predominant cell type in the central part of a sarcoid granuloma, significantly exceeding both epithelioid cells and macrophages in number, raising the question if the term “epithelioid granuloma”, routinely used to designate sarcoid granulomas, is correct, or if it would be more logical to call them “lymphocytic-epithelioid granulomas” instead.Trial registrationThis study was supported by the Serbian Ministry of Science and Environmental Protection Grant Number 175006/2011.

Pathologic analysis of transbronchial lung biopsy in workers exposed to dusts

To explore the role of transbronchial lung biopsy (TBLB) in pathologic diagnosis of pneumoconiosis. In our hospital during May 2011 and Sep 2011, the TBLB samples from 35 cases occupationally exposed to dusts were compared with the video-assisted thoracoscopic surgery or lobectomy samples from 27 cases not exposed to dusts for pathological indexes, including fibrotic proliferation, nodule or nodule-like, dust deposition and needle-shaped birefringent particles. In group exposed to dusts, there were 6 cases (17.1%) with the moderate dust deposition and 28 cases (80.0%) with fibrotic proliferation. But in group not exposed to dusts, there were 0 case with the moderate dust deposition and 11 cases (40.0%) with fibrotic proliferation. There were significant differences between two groups (P < 0.05). In group exposed to dusts, there were 6 cases (17.1%) with Nodules-like and needle-shaped birefringent particles, but in group not exposed to dusts, there was 0 case with Nodules-like and needle-shaped birefringent particles. TBLB could provide the evidence of pathological changes in lung tissue induced by dusts, and TBLB play an important role in pneumoconiosis diagnosis.

Gene Set Analysis of Lung Samples Provides Insight into Pathogenesis of Progressive, Fibrotic Pulmonary Sarcoidosis

Approximately 60 to 70% of patients with pulmonary sarcoidosis have disease that resolves spontaneously; the rest follow a chronic course with varying levels of fibrosis. It is unclear why some patients progress and if treatment affects outcome. To determine differential gene expression profile in lungs of patients with self-limiting sarcoidosis compared to those with progressive-fibrotic disease, and to analyze the biological relevance of these differentially expressed genes. We examined microarray expression of 26,626 genes in transbronchial biopsies of granulomatous areas in lungs of patients with active but self-limiting (n = 8) versus those with active, progressive (+/- fibrotic) pulmonary disease (n = 7). Three hundred thirty-four genes were differentially expressed between the two groups (P < 0.01, Bayesian moderated t test). Gene Set Enrichment Analysis showed over-representation of gene-sets (defined by Gene Ontology) related to host immune activation, proliferation, and defense, among genes up-regulated in the progressive-fibrotic group (FDR q < 0.0001 for the top 43 gene sets), and a marked enrichment of, and similarity in gene expression profiles between, progressive-fibrotic sarcoidosis and hypersensitivity pneumonitis (HP), (q < 0.001), but not idiopathic pulmonary fibrosis (IPF). The findings suggest that patients with progressive/fibrotic pulmonary sarcoidosis have intense immune activity related to host defense in their lungs, with processes more similar to HP than IPF. The study also demonstrates that transbronchial lung biopsy samples can provide good-quality RNA for gene expression profiling, supporting its potential use as a prognostic classifier for pulmonary sarcoidosis.

Incidence of fungal isolation in clinical specimens from the respiratory tract

The incidence of fungal isolation in 711 clinical specimens from the respiratory tract was investigated in 159 patients with pulmonary diseases. Fungi were isolated from 14/19 pharynx swab samples, 246/342 sputum samples, 34/147 bronchial aspirate samples, 18/97 bronchial lavage samples, 4/17 transbronchial lung biopsy samples, and 5/60 plugged catheter brush samples. Contamination by fungi in normal flora was prevented by using an aseptic procedure for sampling specimens from the respiratory tract. The isolation rate of Candida spp. from sputum was 70.0% (C. albicans: 151 strains, C. glabrata: 43 strains, C. tropicalis: 25 strains, C. lusitaniae: 4 strains, C. krusei: 3 strains, C. guilliermondii: 3 strains and C. paraspilosis: 1 strain). The isolation rates of C. neoformans and A. fumigatus from sputum were 6.4% and 8.8%, respectively. Isolated fungi from bronchial aspirate included 12 strains of C. albicans, 6 strains of C. tropicalis, 5 strains of A. fumigatus and 2 strains of C. neoformans. Isolated fungi from bronchial aspirate revealed 6 strains of C. albicans, 2 strains of C. glabrata, 1 strain of C. neoformans and 6 strains of A. fumigatus. The isolation rates of fungi from sputum obtained from patients with pulmonary aspergilloma and cryptococcosis were 66.5% and 50.0%, respectively. The isolation rate of fungi from sputum of patients with underlying diseases was higher than that of patients with no underlying disease.

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.

Methotrexate pneumonia lacking dyspnea and radiographic interstitial patterns during treatment for early rheumatoid arthritis: bronchoalveolar lavage and transbronchial lung biopsy in a differential diagnosis

Methotrexate (MTX) pneumonia is an unpredictable and sometimes life-threatening adverse effect occurring in the treatment of rheumatoid arthritis (RA). We present a case of MTX pneumonia lacking severe respiratory symptoms and typical radiographic findings. A 66-year-old man with early RA presented with intermittent fever and nonproductive cough during the MTX therapy, but neither hypoxemia nor dyspnea was a complaint. His chest X-ray films revealed multiple bilateral consolidations, but interstitial infiltrates were not observed. High-resolution computed tomography showed no ground-glass opacities. In contrast, the histological findings of transbronchial lung biopsy (TBLB) samples were characterized by the interstitial infiltration of mononuclear cells and hyperplasia of type II alveolar cells, which are the main features of drug-induced interstitial inflammation. Special stains for microorganisms were negative for the TBLB samples. Although cultures of bronchoalveolar lavage (BAL) fluids were slightly positive for Haemophilus influenzae, intensive antibiotic therapy was ineffective. A discontinuation of MTX followed by steroid therapy induced the patient's dramatic recovery. A new treatment with tacrolimus was started for RA. We would like to emphasize that the histological examinations and microbiological studies using BAL and TBLB are useful for the exclusion of other causes and the diagnosis of MTX pneumonia, especially in a case without typical respiratory symptoms and radiographic patterns.

Endogenous lipoid pneumonia associated with primary sclerosing cholangitis

In July, 2005, a 63-year-old non-smoking white woman was admitted to hospital with a 3-month history of nonproductive cough, slightly febrile body temperature, and right upper quadrant abdominal pain. The patient had no history of previous medical problems. On admission, physical examination was normal. Blood test results showed a cholestatic pattern with increased γ-glutamyl transferase (γGT) of 321 U/L and alkaline phosphatase of 204 IU/L. Total serum cholesterol concentration was 7·6 mmol/L. Despite 3 weeks’ antibiotic therapy before admission, C-reactive protein was high at 180 mg/L. Screening for autoantibodies (antinuclear, anti mitochondrial, and anti cytoplasmic antibodies) was negative. Chest radiography on admission showed no abnormalities; high-resolution CT of the lungs showed consolidation of the lingula and the middle lobe region (fi gure A). Fibreoptic bronchoscopy was done; cytological examination of the lavage-fl uid showed predominantly foam cell macrophages (fi gure B) containing large fatty vesicles, and lipid droplets were detected on Sudan III staining, characteristic for lipoid pneumonia. Histological examination of the subsequent transbronchial lung biopsy sample showed mild interstitial infl ammation, without signs of malignancy or other interstitial lung disease. The patient denied mineral oil ingestion or nasal drop misuse. She was therefore diagnosed with endogenous lipoid pneumonia due to hypercholesterolaemia. To clarify the cause of the cholestasis, magnetic resonance cholangio-pancreaticography was done, which showed a narrowed hepatic bile duct system together with vanishing of the small bile ducts—characteristic for primary sclerosing cholangitis. Liver biopsy confi rmed the diagnosis by showing concentric sclerosis around bile ducts with little infl ammatory infi ltration, periductal fi brosis, multifocal strictures, and dilatations. We started our patient on 15 mg/kg ursodeoxycholic acid and 40 mg atorvastatin daily. Her condition improved substantially, and she became completely asymptomatic after 6 weeks. Total serum cholesterol dropped to 4·6 mmol/L and γGT to 100 U/L; alkaline phosphatase and C-reactive protein concentration returned to normal values. CT scan showed marked improvement with complete resolution of lung infi ltration after 6 weeks of treatment. Lipoid pneumonia may be classifi ed as exogenous or endogenous. Endogenous lipoid pneumonia usually develops when lipids that normally are found in the lung tissue escape from destroyed alveolar cell wall distal to an obstructing, usually malignant, airway lesion or from lung tissue damaged by a suppurative process. Less commonly, endogenous lipids appear in the lung with fat embolism or thromboembolism, Wegener’s granulomatosis, pulmonary alveolar proteinosis, or lipid storage diseases. Hypercholesterolaemia is common in patients with primary sclerosing cholangitis and can lead to an accumulation of cholesterol in diff erent tissues and can be the underlying cause of an ongoing infl ammatory process. The lungs are actively involved in lipid metabolism, and macrophages help to clear lipids from the lungs. The mechanisms involved in lipoid pneumonia are unclear but may involve an infl ammatory response that is linked to increased lipid uptake by alveolar macrophages. The activity of the disease is not necessarily mirrored by the serum total cholesterol concentration, which might explain the discrepancy of the severity of disease in our patient and the relatively moderate elevation of the serum cholesterol concentration. Treatment of endogenous lipiod pneumonia is not standardised. Successful treatment with total lung lavage or with systemic steroids has been reported, proposing an underlying autoimmune phenomenon of the disease (supported by our case). Our patient was successfully treated by lowering her serum cholesterol concentration and thereby terminating the underlying cause of infl ammation, strongly supporting the link between endogenous lipoid pneumonia and pathogenic role of serum lipids.

Iron Accumulation in Lung Allografts Is Associated With Acute Rejection But Not With Adverse Outcome

Iron content in lung allografts is increased after transplantation. It was hypothesized that this may lead to fibrosis and posttransplant bronchiolitis obliterans syndrome (BOS). In a prospective study, we evaluated 399 BAL fluid (BALF) and transbronchial lung biopsy samples obtained concurrently from 72 consecutive lung transplant recipients. The hemosiderin scores (HSs) of the BALF samples increased steadily during the postoperative period (p < 0.001). Patients with at least one acute rejection episode (AR) grade > or = A2 event had higher mean HSs, the difference being significant after the second (p < 0.008) and the sixth postoperative months (p < 0.05). The HS correlated with the number of ARs (p < 0.004), and it significantly increased after the first AR (p < 0.04). Except for oral anticoagulation, no other risk factors for elevated iron content were found. There was no correlation between HS or number of ARs and the development of BOS or survival, respectively. Progressive iron accumulation in lung allografts seems to be caused mainly by an AR, possibly due to perivascular leakage of erythrocytes. Neither increased HS nor the frequency of ARs were risk factors for subsequent development of BOS. Early detection and treatment of ARs might uncouple their association with BOS.

A case of polymyositis complicated with organizing pneumonia: case report and literature review

A 54-year-old man was admitted to hospital with fever, dyspnea, and polyarthralgia. A chest radiograph showed consolidations in the bilateral lungs, and histological examination of transbronchial lung biopsy samples revealed organizing pneumonia. He was also diagnosed with polymyositis because of muscle weakness, elevated muscle enzymes, myogenic findings on the electromyogram, and a positive test for the anti-Jo-1 antibody. Herein, we review 25 cases of organizing pneumonia with polymyositis/dermatomyositis with respect to their clinical features and treatment.

Hypersensitivity Pneumonitis Following Anthrax Vaccination

A case of hypersensitivity pneumonitis (HP) following anthrax vaccination is described. The patient is a 39-year-old, previously healthy man on active duty in the US Marine Corps, in whom a urticaral skin rash and progressive dyspnea on exertion developed following subcutaneous anthrax vaccination. A diagnosis of bronchiolitis obliterans with organizing pneumonia was made from transbronchial lung biopsy samples after evaluation excluded multiple infectious and collagen vascular etiologies. This appears to be the first recorded case of HP following an anthrax vaccination; however, a case report of pulmonary and cutaneous vasculitis following hepatitis B vaccination has been reported in the literature and is reviewed.

Pulmonary Manifestations in Cerebrotendinous Xanthomatosis.

We investigated five cases with cerebrotendinous xanthomatosis (CTX) with particular reference to biochemical and pathological pulmonary disorders. To date, few reports discuss the pathophysiology of pulmonary disorders of CTX patients. This study is the first investigation of such pulmonary disorders. All 5 patients had no pulmonary symptoms and no disturbances on radiological studies and pulmonary function tests. However, in bronchoalveolar lavage (BAL) fluids, many cells with cruciform reflexes, which is characteristic of intracellular sterol accumulation, were found under phase contrast microscopy. Biochemically, cholestanol was found to be increased in the BAL fluid as well as in serum. Pathological findings of transbronchial lung biopsy (TBLB) samples disclosed foamy macrophages and small granulomas in alveolar septa. In conclusion, the lung was apparently involved in CTX, and the lesions were characterized with the accumulation of foamy and giant cells with a high concentration of cholestanol, which likely results in the formation of foreign body granulomas.

Relation Between Polymerase Chain Reaction Findings and Morphological Changes During Cytomegalovirus Infection in Transplanted Lung

Cytomegalovirus (CMV) can be present as a latent or productive infection resulting in disease. The polymerase chain reaction (PCR) is a sensitive technique to document the presence of CMV (DNA). Negative reactions are indicative of its absence. The presence of CMV (DNA) was assessed longitudinally in 261 transbronchial lung biopsy (TBB) specimens from 37 patients over a 6-month period. The TBB specimens from six serologically CMV-negative recipients who received lungs from serologically CMV-negative donors never showed a positive CMV-PCR(DNA) reaction during the study. Based on a study of their TBB specimens, 10 serologically CMV-positive recipients who received lungs from serologically CMV-negative donors all developed a CMV-PCR(DNA)-positive reaction and five (50%) morphologically manifested CMV disease. The remaining 21 serologically CMV-positive recipients who received lungs from serologically CMV-positive donors all developed a CMV-PCR(DNA)-positive reaction and 15 (71%) developed CMV pneumonitis. The data show that development of a positive CMV-PCR(DNA) reaction in a TBB sample within the first month after transplantation indicates a greatly increased risk of developing CMV disease. In addition, a positive CMV-PCR(DNA) reaction preceded morphologically manifest disease on average by 2 weeks. Comparisons between TBB and bronchoalveolar lavage show the former to provide a more dependable template.