Chronic Beryllium Disease and Sensitization at a Beryllium Processing Facility

We conducted a medical screening for beryllium disease of 577 former workers from a beryllium processing facility. The screening included a medical and work history questionnaire, a chest radiograph, and blood lymphocyte proliferation testing for beryllium. A task exposure and a job exposure matrix were constructed to examine the association between exposure to beryllium and the development of beryllium disease. More than 90% of the cohort completed the questionnaire, and 74% completed the blood and radiograph component of the screening. Forty-four (7.6%) individuals had definite or probable chronic beryllium disease (CBD), and another 40 (7.0%) were sensitized to beryllium. The prevalence of CBD and sensitization in our cohort was greater than the prevalence reported in studies of other beryllium-exposed cohorts. Various exposure measures evaluated included duration; first decade worked; last decade worked; cumulative, mean, and highest job; and highest task exposure to beryllium (to both soluble and nonsoluble forms). Soluble cumulative and mean exposure levels were lower in individuals with CBD. Sensitized individuals had shorter duration of exposure, began work later, last worked longer ago, and had lower cumulative and peak exposures and lower nonsoluble cumulative and mean exposures. A possible explanation for the exposure–response findings of our study may be an interaction between genetic predisposition and a decreased permanence of soluble beryllium in the body. Both CBD and sensitization occurred in former workers whose mean daily working lifetime average exposures were lower than the current allowable Occupational Safety and Health Administration workplace air level of 2 μg/m(3) and the Department of Energy guideline of 0.2 μg/m(3)

Role of imaging in progressive-fibrosing interstitial lung diseases

Imaging techniques are an essential component of the diagnostic process for interstitial lung diseases (ILDs). Chest radiography is frequently the initial indicator of an ILD, and comparison of radiographs taken at different time points can show the rate of disease progression. However, radiography provides only limited specificity and sensitivity and is primarily used to rule out other diseases, such as left heart failure. High-resolution computed tomography (HRCT) is a more sensitive method and is considered central in the diagnosis of ILDs. Abnormalities observed on HRCT can help identify specific ILDs. HRCT also can be used to evaluate the patient's prognosis, while disease progression can be assessed through serial imaging. Other imaging techniques such as positron emission tomography-computed tomography and magnetic resonance imaging have been investigated, but they are not commonly used to assess patients with ILDs. Disease severity may potentially be estimated using quantitative methods, as well as visual analysis of images. For example, comprehensive assessment of disease staging and progression in patients with ILDs requires visual analysis of pulmonary features that can be performed in parallel with quantitative analysis of the extent of fibrosis. New approaches to image analysis, including the application of machine learning, are being developed

Interstitial lung disease in the elderly

Background Despite the relationship between idiopathic pulmonary fibrosis (IPF) and advancing age, little is known about the epidemiology of interstitial lung disease (ILD) in the elderly. We describe the diagnoses, clinical characteristics, and outcomes of patients who were elderly at the time of ILD diagnosis. Methods Among subjects from a prospective cohort study of ILD, elderly was defined as age ≥ 70 years. Diagnoses were derived from a multidisciplinary review. Differences between elderly and nonelderly groups were determined using the χ2 test and analysis of variance. Results Of the 327 subjects enrolled, 80 (24%) were elderly. The majority of elderly subjects were white men. The most common diagnoses were unclassifiable ILD (45%), IPF (34%), connective tissue disease (CTD)-ILD (11%), and hypersensitivity pneumonitis (8%). Most elderly subjects (74%) with unclassifiable ILD had an imaging pattern inconsistent with usual interstitial pneumonia (UIP). There were no significant differences in pulmonary function or 3-year mortality between nonelderly and elderly subjects combined or in a subgroup analysis of those with IPF. Conclusions Although IPF was the single most common diagnosis, the majority of elderly subjects had non-IPF ILD. Our findings highlight the need for every patient with new-onset ILD, regardless of age, to be surveyed for exposures and findings of CTD. Unclassifiable ILD was common among the elderly, but for most, the radiographic pattern was inconsistent with UIP. Although the effect of ILD may be more pronounced in the elderly due to reduced global functionality, ILD was not more severe or aggressive in this group

Reliability and validity of cutaneous sarcoidosis outcome instruments among dermatologists, pulmonologists, and rheumatologists

IMPORTANCE: Dermatologists, pulmonologists, and rheumatologists study and treat patients with sarcoidosis with cutaneous manifestations. The validity of cutaneous sarcoidosis outcome instruments for use across medical specialties remains unknown. OBJECTIVE: To assess the reliability and validity of cutaneous sarcoidosis outcome instruments for use by dermatologists and nondermatologists treating sarcoidosis. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study evaluating the use of the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) and Sarcoidosis Activity and Severity Index (SASI) to assess cutaneous sarcoidosis disease severity and the Physician's Global Assessment (PGA) as a reference instrument. Four dermatologists, 3 pulmonologists, and 4 rheumatologists evaluated facial cutaneous sarcoidosis in 13 patients treated at a cutaneous sarcoidosis clinic in a 1-day study on October 24, 2014; data analysis was performed from November through December 2014. MAIN OUTCOMES AND MEASURES: Interrater and intrarater reliability and convergent validity, with correlation with quality-of-life measures as the secondary outcome. RESULTS: All instruments demonstrated excellent intrarater reliability. Interrater reliability (reported as intraclass correlation coefficient [95% CI]) was good for the CSAMI Activity scale (0.69 [0.51-0.87]) and PGA (0.66 [0.47-0.85]), weak for the CSAMI Damage scale (0.26 [0.11-0.52]), and excellent for the modified Facial SASI (0.78 [0.63-0.91]). The CSAMI Activity scale and modified Facial SASI showed moderate correlations (95% CI) with the PGA (0.67 [0.57-0.75] and 0.57 [0.45-0.66], respectively). The CSAMI Activity scale but not the modified Facial SASI showed significant correlations (95% CI) with quality-of-life instruments, such as the Dermatology Life Quality Index (Spearman rank correlation, 0.70 [0.25-0.90]) and the Skin Stigma raw score of the Sarcoidosis Assessment Tool (Pearson product moment correlation, 0.56 [0.01-0.85]). CONCLUSIONS AND RELEVANCE: The CSAMI and SASI were reliable and valid in assessing cutaneous sarcoidosis among our diverse group of specialists. The CSAMI Activity score also correlated with quality-of-life measures and suggested construct validity. These results lend credibility to expand the use of the CSAMI and SASI by dermatologists and nondermatologists in assessing cutaneous sarcoidosis disease activity

Microbial lineages in sarcoidosis. A metagenomic analysis tailored for low–microbial content samples

RATIONALE: The etiology of sarcoidosis is unknown, but microbial agents are suspected as triggers. OBJECTIVES: We sought to identify bacterial, fungal, or viral lineages in specimens from patients with sarcoidosis enriched relative to control subjects using metagenomic DNA sequencing. Because DNA from environmental contamination contributes disproportionately to samples with low authentic microbial content, we developed improved methods for filtering environmental contamination. METHODS: We analyzed specimens from subjects with sarcoidosis (n = 93), control subjects without sarcoidosis (n = 72), and various environmental controls (n = 150). Sarcoidosis specimens consisted of two independent sets of formalin-fixed, paraffin-embedded lymph node biopsies, BAL, Kveim reagent, and fresh granulomatous spleen from a patient with sarcoidosis. All specimens were analyzed by bacterial 16S and fungal internal transcribed spacer ribosomal RNA gene sequencing. In addition, BAL was analyzed by shotgun sequencing of fractions enriched for viral particles, and Kveim and spleen were subjected to whole-genome shotgun sequencing. MEASUREMENTS AND MAIN RESULTS: In one tissue set, fungi in the Cladosporiaceae family were enriched in sarcoidosis compared with nonsarcoidosis tissues; in the other tissue set, we detected enrichment of several bacterial lineages in sarcoidosis but not Cladosporiaceae. BAL showed limited enrichment of Aspergillus fungi. Several microbial lineages were detected in Kveim and spleen, including Cladosporium. No microbial lineage was enriched in more than one sample type after correction for multiple comparisons. CONCLUSIONS: Metagenomic sequencing revealed enrichment of microbes in single types of sarcoidosis samples but limited concordance across sample types. Statistical analysis accounting for environmental contamination was essential to avoiding false positives

Chronic Beryllium Disease-disease severity and treatment

Objectives: 1. Understand when to suspect Chronic Beryllium Disease 2. Understand how to diagnose Chronic Beryllium Disease 3. Understand the pathogenesis of Chronic Beryllium Disease Presentation runs: 46 minute

NACA Advanced Confidential Reports

Report presenting an investigation that is part of a research program to obtain structures suitable for low-drag wings. The purpose of this particular investigation was to study the drag characteristics of an NACA 66(215)-(1.25)16 airfoil specimen of two-spar construction with hat-section chordwise stiffeners after a compressive load comparable with the maximum applied flight load of a modern military airplane has been applied and removed. Results regarding the variation of section drag coefficient with Reynolds number for the wing specimen of the airfoil, variation of section drag coefficient with section lift coefficient, and drag coefficients at specified Reynolds numbers are provided