An inventory of clinical sarcoidosis status in the United States.

Background: The landscape of sarcoidosis in the United States is unclear, which makes it difficult to optimize the allocation of health care resources, clinical care programs, and research activities for sites which specialize in sarcoidosis.

Research Question: Define the features of sarcoidosis in patients requiring specialty care in the United States to inform the design of clinical management and research programs.

Study Design And Methods: Adult patients were enrolled in this multi-center, longitudinal cohort study.

Single Cell Transcriptome Signatures of Sarcoidosis in Lung Immune Cell Populations.

Rationale: To identify cell specific molecular changes associated with sarcoidosis risk and progression, we aimed to characterize the cellular composition, gene expression patterns, and cell-cell interactions in BAL cells from patients with sarcoidosis (both progressive and non-progressive) and healthy controls.

Methods: Single cell RNA-seq data were collected on 12 sarcoidosis and 4 control participants. We combined scRNA-seq data from these participants with our previously collected data on 4 sarcoidosis and 10 control participants for a final sample size of 16 sarcoidosis cases (8 progressive and 8 non-progressive) and 14 controls.

The textures of sarcoidosis: quantifying lung disease through variograms.

. Sarcoidosis is a granulomatous disease affecting the lungs in over 90% of patients. Qualitative assessment of chest CT by radiologists is standard clinical practice and reliable quantification of disease from CT would support ongoing efforts to identify sarcoidosis phenotypes.

Sarcoidosis in Beryllium Exposed Workers: A Case-Case Study.

Background: Despite the utility of the beryllium lymphocyte proliferation test (BeLPT), distinguishing sarcoidosis, a disease of unknown etiology, from chronic beryllium disease (CBD), has long posed a diagnostic challenge. It is unclear if beryllium-exposed sarcoidosis cases (Be-exp-Sarc) are clinically distinct from CBD, or are misdiagnosed cases of CBD.

Methods: We performed a case-case study of 40 beryllium-exposed individuals diagnosed with Be-exp-Sarc compared to 40 frequency-matched CBD cases.

Limitations of Clustering with PCA and Correlated Noise.

It is now common to have a modest to large number of features on individuals with complex diseases. Unsupervised analyses, such as clustering with and without preprocessing by Principle Component Analysis (PCA), is widely used in practice to uncover subgroups in a sample. However, in many modern studies features are often highly correlated and noisy (e.

Multi-omic signatures of sarcoidosis and progression in bronchoalveolar lavage cells.

Background: Sarcoidosis is a heterogeneous granulomatous disease with no accurate biomarkers of disease progression. Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify molecular changes associated with sarcoidosis and disease progression that might illuminate underlying mechanisms of disease and potential biomarkers.

Methods: Bronchoalveolar lavage cells from 64 sarcoidosis subjects and 16 healthy controls were used.

Understanding the Added Value of High-Resolution CT Beyond Chest X-Ray in Determining Extent of Physiologic Impairment.

Background: Sarcoidosis staging primarily has relied on the Scadding chest radiographic system, although chest CT imaging is finding increased clinical use.

Research Question: Whether standardized chest CT scan assessment provides additional understanding of lung function beyond Scadding stage and demographics is unknown and the focus of this study.

Study Design And Methods: We used National Heart, Lung, and Blood Institute study Genomics Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) cases of sarcoidosis (n = 351) with Scadding stage and chest CT scans obtained in a standardized manner.

The textures of sarcoidosis: quantifying lung disease through variograms.

Objective: Sarcoidosis is a granulomatous disease affecting the lungs in over 90% of patients. Qualitative assessment of chest CT by radiologists is standard clinical practice and reliable quantification of disease from CT would support ongoing efforts to identify sarcoidosis phenotypes. Standard imaging feature engineering techniques such as radiomics suffer from extreme sensitivity to image acquisition and processing, potentially impeding generalizability of research to clinical populations.

Developmental drugs for sarcoidosis.

Sarcoidosis is a multi-organ granulomatous inflammatory disease of unknown etiology. Over 50% of patients will require treatment at some point in their disease and 10%-30% will develop a chronic progressive disease with pulmonary fibrosis leading to significant morbidity and mortality. Recently published guidelines recommend immunosuppressive therapy for sarcoidosis patients at risk of increased disease-related morbidity and mortality, and in whom disease has negatively impacted quality of life.

Examination of eQTL Polymorphisms Associated with Increased Risk of Progressive Complicated Sarcoidosis in European and African Descent Subjects.

Background: A limited pool of SNPs are linked to the development and severity of sarcoidosis, a systemic granulomatous inflammatory disease. By integrating genome-wide association studies (GWAS) data and expression quantitative trait loci (eQTL) single nuclear polymorphisms (SNPs), we aimed to identify novel sarcoidosis SNPs potentially influencing the development of complicated sarcoidosis.

Methods: A GWAS (Affymetrix 6.

Compartment-specific protein interactions in beryllium lung disease.

https://bit.ly/3PLNTXC.

Standardization of flow cytometry and cell sorting to enable a transcriptomic analysis in a multi-site sarcoidosis study.

The contribution and regulation of various CD4+ T cell lineages that occur with remitting vs progressive courses in sarcoidosis are poorly understood. We developed a multiparameter flow cytometry panel to sort these CD4+ T cell lineages followed by measurement of their functional potential using RNA-sequencing analysis at six-month intervals across multiple study sites. To obtain good quality RNA for sequencing, we relied on chemokine receptor expression to identify and sort lineages.

Efzofitimod for the Treatment of Pulmonary Sarcoidosis.

Background: Pulmonary sarcoidosis is characterized by the accumulation of immune cells that form granulomas affecting the lungs. Efzofitimod (ATYR1923), a novel immunomodulator, selectively binds neuropilin 2, which is upregulated on immune cells in response to lung inflammation.

Research Question: What is the tolerability, safety, and effect on outcomes of efzofitimod in pulmonary sarcoidosis?

Study Design And Methods: In this randomized, double-blind, placebo-controlled study evaluating multiple ascending doses of efzofitimod administered intravenously every 4 weeks for 24 weeks, randomized patients (2:1) underwent a steroid taper to 5 mg/d by week 8 or < 5 mg/d after week 16.

Multiomic Signatures of Chronic Beryllium Disease Bronchoalveolar Lavage Cells Relate to T-Cell Function and Innate Immunity.

Chronic beryllium disease (CBD) is a Th1 granulomatous lung disease preceded by sensitization to beryllium (BeS). We profiled the methylome, transcriptome, and selected proteins in the lung to identify molecular signatures and networks associated with BeS and CBD. BAL cell DNA and RNA were profiled using microarrays from CBD ( = 30), BeS ( = 30), and control subjects ( = 12).

Occupational and environmental exposures in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study.

Introduction: Sarcoidosis is a granulomatous disorder thought to be caused by exposures in genetically susceptible individuals. This study investigated whether specific exposures were associated with different sarcoidosis phenotypes.

Methods: Extensive demographic, occupational and environmental exposure data was analyzed from subjects enrolled in the NHLBI Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study.

Rationale and design of the SARCoidosis Outcomes in all respiratory Viral Infectious Diseases (SARCOVID) Study.

Introduction: Respiratory infections are ubiquitous. The COVID-19 pandemic has refocused our attention on how morbid and potentially fatal they can be, and how host factors have an impact on the clinical course and outcomes. Due to a range of vulnerabilities, patients with sarcoidosis may be at higher risk of poor outcomes from respiratory infections.

Realistic biomarkers from plasma extracellular vesicles for detection of beryllium exposure.

Purpose: Exposures related to beryllium (Be) are an enduring concern among workers in the nuclear weapons and other high-tech industries, calling for regular and rigorous biological monitoring. Conventional biomonitoring of Be in urine is not informative of cumulative exposure nor health outcomes. Biomarkers of exposure to Be based on non-invasive biomonitoring could help refine disease risk assessment.

Sex-Specific Differences in MicroRNA Expression During Human Fetal Lung Development.

Sex-specific differences in fetal lung maturation have been well described; however, little is known about the sex-specific differences in microRNA (miRNA) expression during human fetal lung development. Interestingly, many adult chronic lung diseases also demonstrate sex-specific differences in prevalence. The developmental origins of health and disease hypothesis suggests that these sex-specific differences in fetal lung development may influence disease susceptibility later in life.