Health Disparities: Interventions for Pulmonary Disease - A Narrative Review.

There is expansive literature documenting the presence of health disparities, but there are disproportionately few studies describing interventions to reduce disparity. In this narrative review, we categorize interventions to reduce health disparity in pulmonary disease within the US health care system to support future initiatives to reduce disparity. We identified 211 articles describing interventions to reduce disparity in pulmonary disease related to race, income, or sex. We grouped the studies into the following four categories: biologic, educational, behavioral, and structural. We identified the following five main themes: (1) there were few interventional trials compared with the breadth of studies describing health disparities, and trials involving patients with asthma who were Black, low income, and living in an urban setting were overrepresented; (2) race or socioeconomic status was not an effective marker of individual pharmacologic treatment response; (3) telehealth enabled scaling of care, but more work is needed to understand how to leverage telehealth to improve outcomes in marginalized communities; (4) future interventions must explicitly target societal drivers of disparity, rather than focusing on individual behavior alone; and (5) individual interventions will only be maximally effective when specifically tailored to local needs. Much work has been done to catalog health disparities in pulmonary disease. Notable gaps in the identified literature include few interventional trials, the need for research in diseases outside of asthma, the need for high quality effectiveness trials, and an understanding of how to implement proven interventions balancing fidelity to the original protocol and the need to adapt to local barriers to care.

Serum endostatin levels are associated with diffusion capacity and with tuberous sclerosis- associated lymphangioleiomyomatosis.

Endostatin is a naturally occurring collagen fragment with anti-angiogenic properties. We investigated the association between serum endostatin levels and DLCO in a cohort of patients with lymphangioleiomyomatosis (LAM). Associations of endostatin levels to clinical features of LAM were explored using logistic regression models. Endostatin levels were associated with DLCO and were higher in subjects with TSC-associated LAM compared to sporadic LAM. These data suggest that endostatin could be a predictive biomarker of decline in DLCO and that germline mutational inactivation of the TSC1 or TSC2 gene is associated with higher endostatin levels. These findings could offer novel insights into the pathogenesis of LAM.

Characterization of lymphangioleiomyomatosis patients with discordance between spirometric and diffusion measurements of pulmonary function.

Background: A subset of lymphangioleiomyomatosis (LAM) patients present with normal FEV1 and FVC but with reduced DLCO. Patients with an isolated reduction in DLCO in other diseases appear to be at higher risk for pulmonary hypertension and worse survival but this has not been previously described in LAM patients. Objective: To characterize the prevalence and clinical progression of LAM patients who present with discordantly low DLCO. Methods: This was a retrospective cohort study of LAM patients in two centers in the United States and Brazil. Discordant DLCO was defined as FEV1 >80% predicted, FVC >80% predicted, and DLCO<80% predicted. We compared the rate of decline in pulmonary function, pulmonary artery to aorta (PA-A) ratio, and VEGF-D levels in patients with concordant and discordant DLCO. Results: The overall prevalence of discordant DLCO was 26.0%. Patients with discordant DLCO did not have a higher rate of yearly decline in FEV1 (-1.0±0.6 vs -1.0±0.6, p=0.50), FVC (-1.0±0.7 vs -0.3±0.8, p=0.54), or DLCO (-2.2±0.9 vs -1.6±0.6, p=0.79). They did not have higher rates of PA-A ratio>1 (23.3% vs 20.1%, p=1.00). Patients with discordant DLCO did not have higher levels of VEGF-D (1214±1256 pg/mL vs 1706±1214 pg/mL, p=0.07). Conclusions: LAM patients who present with a discordantly low DLCO do not appear to have different rates of decline in pulmonary function. Additional biological and radiographic markers are needed to more fully characterize this population. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 206-212).

Lymphatic Changes in Respiratory Diseases: More than Just Remodeling of the Lung?

Advances in our ability to identify lymphatic endothelial cells and differentiate them from blood endothelial cells have led to important progress in the study of lymphatic biology. Over the past decade, preclinical and clinical studies have shown that there are changes to the lymphatic vasculature in nearly all lung diseases. Efforts to understand the contribution of lymphatics and their growth factors to disease initiation, progression, and resolution have led to seminal findings establishing critical roles for lymphatics in lung biology spanning from the first breath after birth to asthma, tuberculosis, and lung transplantation. However, in other diseases, it remains unclear if lymphatics are part of the overall lung remodeling process or real contributors to disease pathogenesis. The goal of this Translational Review is to highlight some of the advances in our understanding of the role(s) of lymphatics in lung disease and shed light on the critical needs and unanswered questions that might lead to novel translational applications.

Aberrant SYK Kinase Signaling Is Essential for Tumorigenesis Induced by TSC2 Inactivation.

Somatic or germline mutations in the tuberous sclerosis complex (TSC) tumor suppressor genes are associated closely with the pathogenesis of lymphangioleiomyomatosis, a rare and progressive neoplastic disease that predominantly affects women in their childbearing years. Serum levels of the lymphangiogenic growth factor VEGF-D are elevated significantly in lymphangioleiomyomatosis. However, there are gaps in knowledge regarding VEGF-D dysregulation and its cellular origin in lymphangioleiomyomatosis. Here, we show that increased expression and activation of the tyrosine kinase Syk in TSC2-deficient cells and pulmonary nodules from lymphangioleiomyomatosis patients contributes to tumor growth. Syk kinase inhibitors blocked Syk signaling and exhibited potent antiproliferative activities in TSC2-deficient cells and an immunodeficient mouse xenograft model of lymphangioleiomyomatosis. In TSC2-deficient cells, Syk signaling increased the expression of monocyte chemoattractant protein MCP-1, which in peripheral blood mononuclear cells (PBMC) stimulated the production of VEGF-D. In clinical isolates of PBMCs from lymphangioleiomyomatosis patients, VEGF-D expression was elevated. Furthermore, levels of VEGF-D and MCP-1 in patient sera correlated positively with each other. Our results illuminate the basis for lymphangioleiomyomatosis growth and demonstrate the therapeutic potential of targeting Syk in this and other settings driven by TSC genetic mutation. Cancer Res; 77(6); 1492-502. ©2017 AACR.

Evaluation of the Xpert Flu rapid PCR assay in high-risk emergency department patients.

We prospectively evaluated the performance of Cepheid's GeneXpert Xpert Flu assay in a target population of 281 adults presenting to the emergency department with an acute respiratory illness who met Centers for Disease Control and Prevention (CDC) criteria for recommended antiviral treatment. Compared with the Prodesse ProFlu+ assay, Xpert Flu had an overall sensitivity of 95.3% and specificity of 99.2%.