Lack of insurance coverage and urgent care use for asthma: A retrospective cohort study

BACKGROUND: Asthma is a common chronic disease with profound impacts upon individuals and the US health care system. Inadequate health care coverage has been associated with more frequent and severe exacerbations of the disease. We examined the relationship between adequacy of health care coverage and use of emergent care of adults with asthma. METHODS: The 2001 Behavioral Risk Factor Surveillance System was the source of data on adults with current asthma. Bivariate and multiple logistic regression analysis modeled identifiable factors in predicting urgent or emergent care. RESULTS: Key variables included demographics and information on self-reported gaps in health care coverage. The primary outcome was emergency room or urgent care visits for worsening of asthma symptoms. Of 16,234 subjects nationally with current asthma, 2,195 from eight states had valid responses to a supplemental module asking about emergency room use or urgent care visits because of asthma. Thirty four percent of these individuals required such care in the previous year. Having an interruption in health care coverage in the past year was associated with an increased risk of needed urgent or emergent care (crude Odds Ratio [OR] 1.48, 95% confidence intervals [CI]1.03, 2.1). The association was not statistically significant in the adjusted multivariate model including race/ethnicity, employment status, gender, age, education and the ability to identify a primary physician (adjusted OR 1.2, 95% CI 0.8, 1.8). CONCLUSION: This study provides population-level, generalizable evidence of increased risk of exacerbations of asthma in adults and (1) their demographic characteristics, and (2) continuous adequate health care coverage

Exuberant fibroblast activity compromises lung function via ADAMTS4

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Severe respiratory infections can result in acute respiratory distress syndrome (ARDS)1. There are no effective pharmacological therapies that have been shown to improve outcomes for patients with ARDS. Although the host inflammatory response limits spread of and eventually clears the pathogen, immunopathology is a major contributor to tissue damage and ARDS1,2. Here we demonstrate that respiratory viral infection induces distinct fibroblast activation states, which we term extracellular matrix (ECM)-synthesizing, damage-responsive and interferon-responsive states. We provide evidence that excess activity of damage-responsive lung fibroblasts drives lethal immunopathology during severe influenza virus infection. By producing ECM-remodelling enzymes—in particular the ECM protease ADAMTS4—and inflammatory cytokines, damage-responsive fibroblasts modify the lung microenvironment to promote robust immune cell infiltration at the expense of lung function. In three cohorts of human participants, the levels of ADAMTS4 in the lower respiratory tract were associated with the severity of infection with seasonal or avian influenza virus. A therapeutic agent that targets the ECM protease activity of damage-responsive lung fibroblasts could provide a promising approach to preserving lung function and improving clinical outcomes following severe respiratory infections

Publisher Correction: Exuberant fibroblast activity compromises lung function via ADAMTS4 (Nature, (2020), 587, 7834, (466-471), 10.1038/s41586-020-2877-5)

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. An amendment to this paper has been published and can be accessed via a link at the top of the paper

Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza

BackgroundInfluenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection.MethodsWe measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05).ResultsComparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation (RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared to those who recovered more rapidly from MODS (n=27). These neutrophil transcripts present in early samples predicted Prolonged MODS or death when compared to patients who recovered, however in paired longitudinal samples, they were not differentially expressed over time. Instead, five genes involved in protein metabolism and/or adaptive immunity signaling pathways (RPL3, MRPL3, HLA-DMB, EEF1G, CD8A) were associated with MODS recovery within a week.ConclusionThus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome