Search

Background: A cluster of severe lung disease occurred at a manufacturing facility making industrial machines. We aimed to describe disease features and workplace exposures. Methods: Clinical, functional, radiologic, and histopathologic features were characterized. Airborne concentrations of thoracic aerosol, metalworking fluid, endotoxin, metals, and volatile organic compounds were measured. Facility airflow was assessed using tracer gas. Process fluids were examined using culture, polymerase chain reaction, and 16S ribosomal RNA sequencing. Results: Five previously healthy male never‐smokers, ages 27 to 50, developed chest symptoms from 1995 to 2012 while working in the facility's production areas. Patients had an insidious onset of cough, wheeze, and exertional dyspnea; airflow obstruction (mean FEV1 = 44% predicted) and reduced diffusing capacity (mean = 53% predicted); and radiologic centrilobular emphysema. Lung tissue demonstrated a unique pattern of bronchiolitis and alveolar ductitis with B‐cell follicles lacking germinal centers, and significant emphysema for never‐smokers. All had chronic dyspnea, three had a progressive functional decline, and one underwent lung transplantation. Patients reported no unusual nonoccupational exposures. No cases were identified among nonproduction workers or in the community. Endotoxin concentrations were elevated in two air samples; otherwise, exposures were below occupational limits. Air flowed from areas where machining occurred to other production areas. Metalworking fluid primarily grew Pseudomonas pseudoalcaligenes and lacked mycobacterial DNA, but 16S analysis revealed more complex bacterial communities. Conclusion: This cluster indicates a previously unrecognized occupational lung disease of yet uncertain etiology that should be considered in manufacturing workers (particularly never‐smokers) with airflow obstruction and centrilobular emphysema. Investigation of additional cases in other settings could clarify the cause and guide prevention. [ABSTRACT FROM AUTHOR]

Constrictive Bronchiolitis (CB) has been reported in US Operation Iraqi Freedom/Enduring Freedom (OIF/OEF) deployers but not in those from prior US conflicts. A 62‐year old presented with progressive dyspnea 13 years after deployment to the Persian Gulf in 1991‐1992, where he was exposed to burning oil well fire emissions, dust storms, and other potential airborne hazards. In 2014, after a chest computed tomography (CT) scan demonstrated diffuse mosaic attenuation, he underwent surgical lung biopsy, which revealed CB. Deployers from both GWI and OIF/OEF share many exposures. As respiratory symptoms are a feature associated with Gulf War medically unexplained illness, there may be a role for renewed interest in evaluating GWI Veterans with unexplained respiratory symptoms for conditions such as CB, which may result from exposures relevant to deployers from both conflicts. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background and objective: Pneumothorax is a co‐morbidity in patients with idiopathic pulmonary fibrosis (IPF). However, its incidence, risk factors and prognostic significance in IPF remain unclear. The aim of this study was to clarify the incidence and prognostic significance of pneumothorax in patients with IPF, and to further investigate the risk factors for its onset. Methods: Eighty‐four consecutive patients with IPF based on the consensus guideline were included in this study. We retrospectively reviewed the medical records, pulmonary function tests and chest high‐resolution computed tomography images, and determined the incidence of pneumothorax. The prognostic significance of pneumothorax was evaluated using the Cox proportional hazards model analysis with time‐dependent covariates. We also assessed the cumulative incidence and the risk factors for pneumothorax. Results: Of the 84 patients, 17 (20.2%) developed pneumothorax. The cumulative incidence of pneumothorax was 8.5%, 12.5% and 17.7% at 1, 2 and 3 years, respectively. Univariate analysis demonstrated that pneumothorax was significantly related to poor prognosis (hazards ratio, 2.99; P = 0.002). Multivariate analysis, adjusting for sex, age and forced vital capacity (% predicted), revealed that pneumothorax was an independent predictor of poor outcome in IPF (hazards ratio, 2.85; P = 0.006). Lower BMI and the presence of extensive reticular abnormalities were significantly associated with developing pneumothorax. Conclusion: These results confirm that patients with IPF often develop pneumothorax during their clinical course and that the onset of pneumothorax predicts a poor outcome. [ABSTRACT FROM AUTHOR]

Pyoderma gangrenosum is a chronic sterile skin disorder that is frequently seen in association with systemic disorders such as inflammatory bowel disease. Extracutaneous pyoderma gangrenosum is rare and most commonly occurs in the lungs. It is particularly unusual for extracutaneous pyoderma gangrenosum to manifest prior to skin findings and without an associated systemic disorder. A 19-year-old white man presented with shortness of breath and a productive cough. His skin exam was normal. Unenhanced chest computed tomography showed peripheral consolidations, areas of cavitation, nodules and bilateral pleural effusions. A bronchoalveolar lavage and an autoimmune panel were unremarkable. Right lung wedge biopsies via thoracostomy was performed and showed pulmonary pyoderma gangrenosum.He was treated with corticosteroids and has returned back to his baseline. This is the first case of pulmonary pyoderma gangrenosum without any associated underlying systemic disorder and without any cutaneous manifestations to date. Serial follow-ups are necessary to assess for the development of an associated systemic disorder or skin lesions. [ABSTRACT FROM AUTHOR]

Background and objective Despite significant recent progress in the understanding of idiopathic pulmonary fibrosis ( IPF), the early phase of the disease is still poorly understood. We studied patients with IPF without pulmonary function impairment in order to determine the clinical features, natural history and key findings for physiological progression. Methods Twenty-five patients without pulmonary function impairment were identified from among patients with previously diagnosed IPF who underwent surgical lung biopsies between January 1997 and December 2006 at our institutions. 'Without pulmonary function impairment' was defined as both forced vital capacity ( FVC) and diffusing capacity for carbon monoxide ( DLco) >80% predicted. Patients diagnosed with IPF through multidisciplinary discussion based on the new IPF guidelines were the subjects of this study. Results Sixteen patients had a confirmed diagnosis of IPF. Eleven patients presented with chest X-ray abnormality found during an annual health examination. Seven patients were asymptomatic. Eleven patients showed physiological disease progression (median time; 19.9 ± 12.3 months) defined by a decline of at least 10% in FVC or at least 15% in DLco. Univariate analysis revealed that both usual interstitial pneumonia pattern and extent of honeycombing on high-resolution computed tomography (HRCT) were factors associated with disease progression (odds ratio 5.634, 95% confidence interval 1.364-23.278; odds ratio 2.371/5%, 95% confidence interval 1.042-5.395). Conclusions IPF patients without pulmonary function impairment have a progressive but slow clinical course. The existence and extent of honeycombing on HRCT are predictive of disease progression. [ABSTRACT FROM AUTHOR]

The histologic characteristics of air space enlargement with fibrosis ( AEF) are compared with usual interstitial pneumonia ( UIP), nonspecific interstitial pneumonia ( NSIP) and centrilobular emphysema ( CLE) to determine similarities and differences. Lung specimens from 39 patients were studied; 9 with AEF, 13 with UIP and 5 with CLE identified in lobectomy specimens for cancer and 12 NSIP cases identified on surgical lung biopsies. We determined the characteristics of cystic structures (i.e. abnormal airspace), degree of inflammation and severity of pneumocyte injury semi-quantitatively. In AEF, the wall thickness of the cystic lesions (0.8 mm) was thinner than in UIP (2.1 mm) and thicker than in CLE (0.07 mm). The degree of inflammation and granulation tissue were milder in AEF than in UIP and NSIP and CLE showed milder inflammatory cells than AEF. As for pneumocyte injury, AEF had fewer erosions (0.1/case) and fewer ubiquitin-positive pneumocytes than UIP (4.8 cells/slide) and NSIP (9.8 cells/slide). Our data suggested that the histological characteristics of AEF differed significantly from UIP, NSIP and CLE. [ABSTRACT FROM AUTHOR]

Vacuolar processing enzymes ( VPEs) are important cysteine proteases that are implicated in the maturation of seed storage proteins, and programmed cell death during plant-microbe interactions and development. Here, we introduce a specific, cell-permeable, activity-based probe for VPEs. This probe is highly specific for all four Arabidopsis VPEs, and labeling is activity-dependent, as illustrated by sensitivity for inhibitors, pH and reducing agents. We show that the probe can be used for in vivo imaging and displays multiple active isoforms of VPEs in various tissues and in both monocot and dicot plant species. Thus, VPE activity profiling is a robust, simple and powerful tool for plant research for a wide range of applications. Using VPE activity profiling, we discovered that VPE activity is increased during infection with the oomycete pathogen Hyaloperonospora arabidopsidis ( Hpa). The enhanced VPE activity is host-derived and EDS1-independent. Sporulation of Hpa is reduced on vpe mutant plants, demonstrating a role for VPE during compatible interactions that is presumably independent of programmed cell death. Our data indicate that, as an obligate biotroph, Hpa takes advantage of increased VPE activity in the host, e.g. to mediate protein turnover and nutrient release. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective: In some patients, desquamative interstitial pneumonia may progress to lung fibrosis. The aim of this study was to assess the long-term radiological follow-up results in patients with desquamative interstitial pneumonia. Methods: Among 75 patients suspected of having desquamative interstitial pneumonia, 31 who fulfilled the criteria were included in this study. Clinical characteristics at presentation, responses to treatment and long-term follow-up were evaluated. Results: The 31 patients were predominantly males (94%), and the mean age was 55 years; 93% (28/30) had a history of smoking. The clinical findings included high serum levels of lactate dehydrogenase and immunoglobulin G. Bronchoalveolar lavage (26 patients, 84% of cases) frequently showed an increased percentage of eosinophils (mean 17%). Computed tomography (CT) or high resolution (HR) CT at presentation showed ground glass opacities and/or consolidation in all patients, with one third of patients also showing thin-walled cysts within the ground glass opacities. There was no honeycombing on CT or HRCT scans at presentation. Corticosteroid therapy was effective early in the course of the disease; long-term follow-up (mean 99 months) of 31 patients showed only one death due to progression of the disease, but long-term follow-up of 14 patients (mean 125 months) by HRCT showed the development of new thin-walled cysts and honeycombing in five and lung cancer in four patients, respectively. Conclusions: In a proportion of patients, desquamative interstitial pneumonia may progress to lung fibrosis with honeycombing on HRCT, despite therapy. [ABSTRACT FROM AUTHOR]

Conidiospores are the asexual propagation units of many plant-pathogenic fungi. In this article, we report an annotated proteome map of ungerminated conidiospores of the ascomycete barley powdery mildew pathogen, Blumeria graminis f.sp. hordei. Using a combination of two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, we have identified the proteins in 180 spots, which probably represent at least 123 distinct fungal gene products. Most of the identified proteins have a predicted function in carbohydrate, lipid or protein metabolism, indicating that the spore is equipped for the catabolism of storage compounds as well as for protein biosynthesis and folding on germination. [ABSTRACT FROM AUTHOR]

Background: Recent studies have documented good patient and graft outcomes and a low risk of acute rejection with steroid-avoidance immunosuppression in kidney-transplant recipients, but the risk of progressive graft fibrosis is not well studied. Methods: All adult primary kidney transplant or combined kidney and pancreas transplant recipients on steroid avoidance immunosuppression were eligible for study. All recipients received induction with antithymocyte globulin or basiliximab. Corticosteroids were stopped after day 4 post-transplantation. Patients were maintained with tacrolimus and mycophenolate mofetil. Protocol biopsies were done at reperfusion and at one, four, and 12 months after transplantation. Results: Eighty one-yr protocol biopsies with adequate specimens were obtained from 132 kidney or kidney–pancreas transplant recipients. Fifteen (19%) of the biopsies showed moderate to severe graft interstitial fibrosis (GIF) (Banff ci score ≥2). Recipients with GIF were older, had lower body mass index, greater human lymphocyte antigen (HLA) mismatch, older donors, serum creatinine ≥1.6 mg/dL at one month, a Banff ci score >0 on one-month biopsy, BK nephropathy, and interstitial cellular infiltrates on the one-yr biopsy. In the unadjusted logistic regression analysis, BK nephropathy, serum creatinine ≥1.6 mg/dL at one month, recipient age, Banff ci score >0 on one-month biopsy, and donor age were the only variables associated with a higher risk of GIF on the one-year biopsy. In the multivariate logistic regression model adjusted for these variables, BK nephropathy, serum creatinine ≥1.6 mg/dL at one month after transplantation, and recipient age were independently associated with the risk of GIF on the one-year biopsy. Conclusion: In this small study of primary kidney or combined kidney–pancreas transplant recipients on steroid-avoidance immunosuppression, we found that 19% had GIF on a one-year protocol biopsy. BK nephropathy, serum creatinine ≥1.6 mg/dL one month after transplantation, and recipient age correlated with an increased risk for GIF on the one-yr biopsy. [ABSTRACT FROM AUTHOR]

Reversible phosphorylation of proteins is an important mechanism by which organisms regulate their reactions to external stimuli. To investigate the involvement of phosphorylation during acquisition of desiccation tolerance, we have analysed dehydration-induced protein phosphorylation in the desiccation tolerant resurrection plant Craterostigma plantagineum. Several dehydration-induced proteins were shown to be transiently phosphorylated during a dehydration and rehydration (RH) cycle. Two abundantly expressed phosphoproteins are the dehydration- and abscisic acid (ABA)-responsive protein CDeT11-24 and the group 2 late embryogenesis abundant (LEA) protein CDeT6-19. Although both proteins accumulate in leaves and roots with similar kinetics in response to dehydration, their phosphorylation patterns differ. Several phosphorylation sites were identified on the CDeT11-24 protein using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The coincidence of phosphorylation sites with predicted coiled-coil regions leads to the hypothesis that CDeT11-24 phosphorylations influence the stability of coiled-coil interactions with itself and possibly other proteins. [ABSTRACT FROM AUTHOR]

Reports on developments in the study of pulmonary vascular diseases. Basis for the clinical definition of pulmonary artery hypertension; Characteristics of the pulmonary veno-occlusive disease; Distinction between pulmonary capillary haemangiomatosis and pulmonary veno-occlusive disease; Most common differential diagnosis for pulmonary capillaritis; Histologic features of pulmonary capillaritis; General approach to lung biopsy of Wegener's granulomatosis.

Studies the various sub-areas of pleural pathology. Comparison between mesothelial hyperplasia and mesothelioma; Elements of asbestos body and asbestos fiber analysis in mesothelioma patients; Primary solid tumors of the pleura other than diffuse malignant mesothelioma; Characteristics of lymphoreticular malignancies of the pleura; Unusual metastases to and from the pleura.

Objective: To study lymphocyte markers in rheumatoid arthritis (RA)-associated interstitial pneumonitis (IP) compared with idiopathic IP., Methods: Paraffin-embedded lung biopsy specimens from patients with RA (n = 15) and from those without RA (n = 16), all of whom had a diagnosis of either nonspecific IP or usual IP, were studied. Tissue sections from each patient were reviewed by a pathologist, who was blinded to the clinical data. Age and pulmonary function test results were similar in RA and non-RA patients. After high-temperature antigen unmasking, sections were incubated with mouse monoclonal antibodies directed against CD3, CD4, CD8, CD16, and CD20. All slides were coded, and digital images (100x magnification) of the entire tissue area were obtained. Staining was quantified using computer-assisted image analysis., Results: Staining for CD4 was more prominent in patients with RA than in the non-RA comparison group (median 9.3 cells/mm(2), interquartile range [IQR] 5.5-27.3 versus 0.6 cells/mm(2), IQR 0.2-1.9; P = 0.002). CD4+ cell counts were increased in RA patients with nonspecific IP as well as in RA patients with usual IP, with no major difference between these groups. Results were similar for quantification of CD3 (P = 0.012). There was a less striking trend toward more CD8+ cells in RA patients (P = 0.27 versus those with non-RA lung disease)., Conclusion: IP lesions in patients with RA are characterized by an increased number of CD4+ cells, as compared with that in patients with idiopathic IP. This finding suggests that CD4+ T cells are critical for the development of pulmonary manifestations in RA, and may have implications for the treatment of RA-associated lung disease.