Repository corticotropin for Chronic Pulmonary Sarcoidosis.

PURPOSE: The dose of repository corticotropin (RCI) and need for a loading dose in sarcoidosis patients receiving chronic corticosteroids are unclear. We performed a single-blind prospective study, comparing two doses of RCI in sarcoidosis. METHODS: Chronic pulmonary sarcoidosis patients receiving prednisone therapy with deterioration by 5% in FVC in the previous year were studied. RCI was administered subcutaneously at a loading dose of 80 units RCI for 10 days. Patients were randomized at day 14 to receive either 40- or 80-unit RCI twice a week. The dose of prednisone was modified by the clinician who was blinded to the patient's dosage of RCI. RESULTS: Sixteen patients completed the full 24 weeks of the study. At week 24, there was a decrease in the dose of prednisone, and improvements in DLCO, King's Sarcoidosis Questionnaire health status and fatigue score. There was no significant change in FVC % predicted. For the PET scan, there was a significant fall in the standard uptake value (SUV) of the lung lesions. Only 3/8 patients remained on 80 units RCI for full 24 weeks. There was no significant difference in the response to therapy for those treated with 40- versus 80-unit RCI. CONCLUSIONS: Repository corticotropin treatment was prednisone-sparing and associated with significant improvement in DLCO, PET scan, and patient-reported outcome measures. A dose of 40-unit RCI twice a week was as effective as 80-unit RCI and was better tolerated.

A 30-year mortality and respiratory morbidity study of refractory ceramic fiber workers.

AIM: Report mortality (n = 1119), cancer incidence (n = 1207) and radiographic (n = 1451) findings from a 30-year investigation of current and former refractory ceramic fiber (RCF) workers. METHODS: Cause of death, health and work histories, radiographs and spirometry were collected. Mortality and cancer incidence were analyzed. Logistic regression analysis investigated the associations of latency and cumulative fiber exposure (CFE) on radiographic changes. RESULTS: The mortality study showed no increase in standardized mortality rates (SMR) for lung cancer, but urinary cancers were significantly elevated in the higher exposed group (SMR = 3.62, 95% CI: 1.33-7.88) and leukemia in the total cohort (SMR = 2.51, 95% CI: 1.08-4.94). One death attributed to mesothelioma was identified (SMR = 2.86, 95% CI: 0.07-15.93) in a worker reporting some asbestos exposure. The overall rate of pleural changes was 6.1%, attaining 21.4% in the highest CFE category for all subjects (adjusted odds ratio (aOR) = 6.9, 95% CI: 3.6-13.4), and 13.0% for those with no reported asbestos exposure (OR= 9.1, 95% CI: 2.5-33.6). Prevalence for recent hires (≥1985) was similar to the background. Interstitial changes were not elevated. Localized pleural thickening was associated with small decreases in spirometry results. CONCLUSION: Increases in leukemia and urinary cancer but not lung cancer mortality were found. One death attributed to mesothelioma was observed in a worker with self-reported asbestos exposure and a work history where occupational asbestos exposure may have occurred, rendering uncertainties in assigning causation. Radiographic analyses indicated RCF exposure alone is associated with increased pleural but not interstitial changes. Reductions in RCF exposure should continue. The mortality study is ongoing.

Admission chest radiograph lacks sensitivity in the diagnosis of community-acquired pneumonia.

INTRODUCTION: : The clinical and epidemiological significance of community-acquired pneumonia (CAP) with a chest radiograph demonstrating no parenchymal infiltrate has not been studied. We determined the percentage of patients with a clinical diagnosis of CAP who did not have radiographic opacifications and compared this group with patients with CAP and radiographic infiltrates. METHODS: : Patients admitted with a diagnosis of CAP were identified. Clinical history, physical examination, laboratory studies, and microbiological cultures were reviewed in a random sample of 105 patients. Admission and subsequent chest radiographs were interpreted without knowledge of the clinical data. RESULTS: : Twenty-one percent (22/105) of patients with a clinical diagnosis of CAP had negative chest radiographs at presentation. Demographic, clinical, and laboratory data were the same in both groups. Fifty-five percent of patients with initially negative chest radiographs who had follow-up studies developed an infiltrate within 48 hours. CONCLUSIONS: : In patients admitted with a clinical diagnosis of CAP, the initial chest radiograph lacks sensitivity and may not demonstrate parenchymal opacifications in 21% of patients. Moreover, greater than half of patients admitted with a negative chest radiograph will develop radiographic infiltrates within 48 hours. Further studies are needed to develop evidence-based criteria for the diagnosis of CAP.

Low-level fiber-induced radiographic changes caused by Libby vermiculite: a 25-year follow-up study.

RATIONALE: From 1921 to 1990, vermiculite ore from Libby, Montana, was shipped worldwide for commercial and residential use. A 1980 study of a manufacturing facility using Libby vermiculite was the first to demonstrate a small but significant prevalence of pleural chest radiographic changes associated with amphibole fibers contained in the ore. OBJECTIVES: This follow-up study of the original cohort evaluated the extent of radiographic changes and cumulative fiber exposure (CFE) 25 years after cessation of exposure. METHODS: From the original cohort of 513 workers, 431 (84%) were living and available for participation and exposure reconstruction. Of these, 280 (65%) completed both chest radiographs and interviews. Primary outcomes were pleural and/or interstitial changes. MEASUREMENTS AND MAIN RESULTS: Pleural and interstitial changes were demonstrated in 80 (28.7%) and 8 (2.9%) participants, respectively. Of those participants with low lifetime CFE of less than 2.21 fiber/cc-years, 42 (20%) had pleural changes. A significant (P < 0.001) exposure-response relationship of pleural changes with CFE was demonstrated, ranging from 7.1 to 54.3% from the lowest to highest exposure quartile. Removal of individuals with commercial asbestos exposure did not alter this trend. CONCLUSIONS: This study indicates that exposure within an industrial process to Libby vermiculite ore is associated with pleural thickening at low lifetime CFE levels. The propensity of the Libby amphibole fibers to dramatically increase the prevalence of pleural changes 25 years after cessation of exposure at low CFE levels is a concern in view of the wide national distribution of this ore for commercial and residential use.

Cardiopulmonary imaging in sarcoidosis.

Sarcoidosis is a disease with protean clinical manifestations ranging from no symptoms to sudden death. Radiologic tests are often the key to diagnosis. In this article, the authors review current imaging techniques and discuss emerging technologies used in the noninvasive cardiopulmonary evaluation of the patient who has sarcoidosis.

Radiological manifestations of sarcoidosis.

Sarcoidosis is an immune system disorder characterised by non-necrotising granulomas. Pulmonary involvement is the most common presentation of sarcoidosis, but it can manifest in any organ. Other commonly involved organ systems include the lymph nodes (especially the intrathoracic nodes); the skin; the eyes; the liver; the heart; and the nervous, musculoskeletal, renal, and endocrine systems. The typical and atypical imaging features of multisystemic involvement of sarcoidosis have been discussed with review of the gamut of radiological manifestations of thoracic, cardiac, CNS, abdominal and musculoskeletal sarcoidosis.

The complimentary role of transbronchial lung cryobiopsy and endobronchial ultrasound fine needle aspiration in the diagnosis of sarcoidosis.

PURPOSE: Transbronchial lung cryobiopsy (TBLC) is a novel technique that has proved to be useful in diagnosing various interstitial lung diseases (ILD). The use of TBLC to diagnose sarcoidosis in an unselected patient population is unknown, and could be complimentary to endobronchial ultrasound fine needle aspiration (EBUS-FNA). METHODS: A retrospective analysis of 36 patients in a single, tertiary-care, academic medical center was conducted to describe the yield of both EBUS-FNA and TBLC in the diagnosis of suspected sarcoidosis over a three year period. A grading system to evaluate the presence and extent of specific radiographic features on computed tomography chest imaging studies was compared to the results of EBUS-FNA and TBLC. Complications associated with the procedures were also noted. RESULTS: The overall diagnostic yield in our cohort (all pathologic diagnosis considered) was 80.6% (29 out of 36 patients had a definite pathologic diagnosis). Eighteen patients referred for possible sarcoidosis had a positive bronchoscopic specimen confirming the diagnosis of sarcoidosis. For those patients with a pathologic diagnosis of sarcoidosis, the diagnostic yield for EBUS-FNA and TBLC was 66.7% each (12 out of 18 patients), while the combined diagnostic yield for EBUS-FNA and TBLC increased to 100%. For all cases, the pneumothorax rate was 11.1%. CONCLUSIONS: TBLC appears to be a safe and complimentary technique to diagnose sarcoidosis and could be considered part of the diagnostic armamentarium in bronchoscopic centers.

HRCT/CT and associated spirometric effects of low Libby amphibole asbestos exposure.

OBJECTIVE: Evaluate the relationship between cumulative fiber exposure and high-resolution or conventional chest computed tomography (HRCT/CT) changes and spirometry of workers with Libby amphibole asbestos exposure. METHODS: Of the original 1980 cohort (n = 513), 431 were living and asked to participate. Images were evaluated for localized pleural thickening (LPT), diffuse pleural thickening (DPT), and parenchymal changes. RESULTS: A total of 306 participants provided either HRCT/CT scans (n = 191) or chest radiographs (n = 115). Of the 191 with HRCT/CT, 52.9% had pleural changes and 13.1% had parenchymal changes. Those with LPT only, LPT and/or DPT, or DPT and/or parenchymal changes had mean 6.1, 8.0, and 18.0 loss in percent predicted forced vital capacity, respectively. CONCLUSIONS: Exposure to vermiculite containing amphibole fibers is associated with pleural and parenchymal HRCT/CT changes at low cumulative fiber exposure; these changes are associated with spirometric decrements.

Benign metastasizing leiomyoma: a rare type of lung metastases-two case reports and review of the literature.

Benign metastasizing leiomyoma (BML) is a rare disease that usually occurs in women of reproductive age. They typically have history of uterine leiomyoma treated with hysterectomy. BML can metastasize to distant organs, with the lung being the most common organ. We report two patients who presented with benign metastasizing leiomyoma to the lung. Our first case was a fifty-two-year-old female who presented with multiple lung masses, with a past medical history of uterine leiomyoma who underwent hysterectomy 17 years ago. A CT-guided biopsy showed benign appearing spindle cells and pathology confirmed her diagnosis with additional positive estrogen/progesterone receptor stains. Our second case was a fifty-six-year-old female who presented with multiple cavitary pulmonary nodules. She subsequently underwent a video-assisted thoracoscopic surgery (VATS) with wedge resection of one of the nodules. Pathology confirmed the diagnosis based on morphology and immunohistochemical staining strongly positive for estrogen/progesterone receptors. Benign metastasizing leiomyoma is a rare condition which may affect women of reproductive age. This should be considered in the differential in patients who present with multiple pulmonary nodules, especially with a history of uterine leiomyoma. Additional stains, such as estrogen/progesterone receptors, may need to be done to confirm the diagnosis.

Thyroid metastasis from nonsmall cell lung cancer.

Background. Thyroid metastases are rare. Clinically, they represent less than 4% of thyroid malignancy in clinical studies. Aim. To assess various presentations and therapy for patients with lung cancer metastatic in the thyroid. Materials and Methods. We report a case of metastatic adenocarcinoma of the lung to the thyroid. We reviewed similar reports through PubmMed search from 1997 until 2013. Case Presentation. A 48-year-old lady was seen in the clinic for an adenocarcinoma of left upper lobe (LUL) of the lung; she received neoadjuvant chemotherapy then LUL lobectomy. After 9 months she presented with diffuse goiter initially believed to be a solitary metastatic lesion as it was positive for adenocarcinoma of lung origin on histopathological exam with TTF-1 positivity. Unfortunately, PET scan showed additional mediastinal lymphadenopathy. Conclusion. The treatment strategy for metastatic thyroid disease is based on a multidisciplinary approach, where thyroidectomy would have been considered in case of a solitary metastatic involvement, but further metastatic workup is mandated to direct further systemic therapy versus palliative radiation therapy.

Vitamin D deficiency and reduced lung function in connective tissue-associated interstitial lung diseases.

BACKGROUND: Vitamin D is a steroid hormone with pleiotropic effects including immune system modulation, lung tissue remodeling, and bone health. Vitamin D deficiency has been implicated in the development of autoimmune diseases. We sought to evaluate the prevalence of vitamin D deficiency in a cohort of patients with interstitial lung disease (ILD) and hypothesized that vitamin D deficiency would be associated with an underlying connective tissue disease (CTD) and reduced lung function. METHODS: Patients in the University of Cincinnati ILD Center database were evaluated for serum 25-hydroxyvitamin D levels as part of a standardized protocol. Regression analysis evaluated associations between 25-hydroxyvitamin D levels and other variables. RESULTS: One hundred eighteen subjects were included (67 with CTD-ILD, 51 with other forms of ILD). The overall prevalence of vitamin D deficiency and insufficiency in the study population was 38% and 59%, respectively. Those with CTD-ILD were more likely to have vitamin D deficiency (52% vs 20%, P < .0001) and insufficiency (79% vs 31%, P < .0001) than other forms of ILD. Diminished FVC was associated with lower 25-hydroxyvitamin D(3) levels (P = .01). The association between vitamin D insufficiency and CTD-ILD persisted (OR, 11.8; P < .0001) after adjustment for potential confounders. Among subjects with CTD-ILD, reduced 25-hydroxyvitamin D(3) levels were strongly associated with reduced lung function (FVC, P = .015; diffusing capacity for carbon monoxide, P = .004). CONCLUSIONS: There is a high prevalence of vitamin D deficiency in patients with ILD, particularly those with CTD-ILD, and it is associated with reduced lung function. Vitamin D may have a role in the pathogenesis of CTD-ILD.

Can lung cancer screening by computed tomography be effective in areas with endemic histoplasmosis?

OBJECTIVE: Low-dose chest computed tomography (CT) is being evaluated in several national trials as a screening modality for the early detection of lung cancer. The goal of the present study was to determine whether lung cancer screening could be done while minimizing the number of benign biopsy specimens taken in an area endemic for histoplasmosis. METHODS: The subjects were recruited by letters mailed to area physicians and local advertisement. The inclusion criteria were age older than 50 years and at least a 20 pack-year smoking history. The exclusion criteria were symptoms suggestive of lung cancer or a history of malignancy in the previous 5 years. The participants completed a questionnaire and underwent a chest CT scan at baseline and annually for 5 years. The management of positive screening results was determined using a defined algorithm: annual follow-up CT scan for nodules less than 5 mm; 6-month follow-up CT scan for nodules 5 to 7 mm; review by our multidisciplinary tumor board for nodules 8 to 12 mm; and biopsy for nodules greater than 12 mm. RESULTS: A total of 132 patients were recruited. Of the 132 patients, 61% had positive baseline CT findings and 22% had positive findings on the annual CT scans. Six cancers were detected. Of these 6 patients, 5 had stage I disease and underwent lobectomy, and 1 had stage IIIA disease and underwent induction chemotherapy and radiotherapy followed by lobectomy. All patients were alive and disease free at a mean follow-up of 41.7 ± 18.6 months. No biopsies were performed for benign lesions. Also, no cancers were missed when the protocol was followed. CONCLUSIONS: Screening with CT can be done effectively in an area endemic for histoplasmosis while minimizing benign biopsies.

Changes in chest roentgenogram of sarcoidosis patients during a clinical trial of infliximab therapy: comparison of different methods of evaluation.

BACKGROUND: The best method to interpret the chest roentgenogram and its sensitivity to detect effect of treatment for sarcoidosis remains unclear. In a double-blind, randomized trial of infliximab for chronic pulmonary sarcoidosis, changes in serial chest roentgenograms were examined by radiologists, blinded to order or treatment. METHODS: Chest roentgenograms were obtained at 0, 6, and 24 weeks of therapy with either placebo, 3 mg/kg infliximab, or 5 mg/kg infliximab. Films were reviewed in random order by two independent radiologists, unaware of treatment. The films were compared using two methods: the prespecified objective assessment, a scoring system previously proposed by Muers; and the post hoc assessment, a 5-point Likert scale global assessment between two films. RESULTS: Of 138 patients enrolled in the study, chest roentgenograms for all studies were available on 130 patients. There was only fair agreement between the two radiologists in the original stage of the chest roentgenogram (weighted kappa = 0.43; 95% confidence interval [CI], 0.32 to 0.54). For the Likert scale of global assessment of change, there was good agreement between the two readers (weighted kappa = 0.61; 95% CI, 0.51 to 0.71). There was good correlation between the two readers for the various components of the Muers score, especially the reticulonodular (R) score (R = 0.578; p < 0.05). The initial R score was positively correlated with improvement in FVC with infliximab therapy (R = 0.239; p < 0.05). CONCLUSION: Global assessment and the Muers scoring system were associated with good agreement between two expert readers. Improvement in both scores correlated with improvement in FVC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00073437.