Spontaneous pneumothorax is an important, recurrent manifestation of pulmonary involvement in patients with BHD, and pleurodesis should be considered following the initial pneumothorax to reduce the risk of recurrent episodes. In general, in patients with BHD, pneumothorax occurs in about 1-2 per 1,000 flights, and the risk is lower among patients with a history of prior pleurodesis.
Neutrophil extracellular traps (NETs) provide host defense but can contribute to the pathobiology of diverse human diseases. We sought to determine the extent and mechanism by which NETs contribute to human airway cell inflammation. Primary normal human bronchial epithelial cells (HBEs) grown at air-liquid interface and wild-type (wt)CFBE41o- cells (expressing wtCFTR) were exposed to cell-free NETs from unrelated healthy volunteers for 18 h in vitro. Cytokines were measured in the apical supernatant by Luminex, and the effect on the HBE transcriptome was assessed by RNA sequencing. NETs consistently stimulated IL-8, TNF-α, and IL-1α secretion by HBEs from multiple donors, with variable effects on other cytokines (IL-6, G-CSF, and GM-CSF). Expression of HBE RNAs encoding IL-1 family cytokines, particularly IL-36 subfamily members, was increased in response to NETs. NET exposure in the presence of anakinra [recombinant human IL-1 receptor antagonist (rhIL-1RA)] dampened NET-induced changes in IL-8 and TNF-α proteins as well as IL-36α RNA. rhIL-36RA limited the increase in expression of proinflammatory cytokine RNAs in HBEs exposed to NETs. NETs selectively upregulate an IL-1 family cytokine response in HBEs, which enhances IL-8 production and is limited by rhIL-1RA. The present findings describe a unique mechanism by which NETs may contribute to inflammation in human lung disease in vivo. NET-driven IL-1 signaling may represent a novel target for modulating inflammation in diseases characterized by a substantial NET burden.
Background: Marietta, Ohio, is an Appalachian-American community whose residents have long struggled with understanding their exposure to airborne manganese (Mn). Although community engagement in research is strongly endorsed by the National Institutes of Health and the National Institute of Environmental Health Sciences in particular, little has been documented demonstrating how an academic–community partnership that implements the community-based participatory research (CBPR) principles can be created and mobilized for research.Objectives: We created a bidirectional, academic–community partnership with an Appalachian-American community to a) identify the community’s thoughts and perceptions about local air quality, its effect on health, and the perception of risk communication sources and b) jointly develop and conduct environmental health research.Methods: We formed a community advisory board (CAB), jointly conducted pilot research studies, and used the results to develop a community-driven research agenda.Results: Persons in the community were “very concerned” to “concerned” about local air quality (91%) and perceived the air quality to have a direct impact on their health and on their children’s health (93% and 94%, respectively). The CAB identified the primary research question: “Does Mn affect the cognition and behavior of children?” Although the community members perceived research scientists as the most trusted and knowledgeable regarding risks from industrial emissions, they received very little risk information from research scientists.Conclusions: Engaging a community in environmental health research from its onset enhanced the quality and relevance of the research investigation. The CBPR principles were a useful framework in building a strong academic–community partnership. Because of the current disconnect between communities and research scientists, academic researchers should consider working collaboratively with community-based risk communication sources.
Introduction
Statistics is an essential training component for a career in clinical and translational science (CTS). Given the increasing complexity of statistics, learners may have difficulty selecting appropriate courses. Our question was: what depth of statistical knowledge do different CTS learners require?
Methods
For three types of CTS learners (principal investigator, co-investigator, informed reader of the literature), each with different backgrounds in research (no previous research experience, reader of the research literature, previous research experience), 18 experts in biostatistics, epidemiology, and research design proposed levels for 21 statistical competencies.
Results
Statistical competencies were categorized as fundamental, intermediate, or specialized. CTS learners who intend to become independent principal investigators require more specialized training, while those intending to become informed consumers of the medical literature require more fundamental education. For most competencies, less training was proposed for those with more research background.
Discussion
When selecting statistical coursework, the learner’s research background and career goal should guide the decision. Some statistical competencies are considered to be more important than others. Baseline knowledge assessments may help learners identify appropriate coursework.
Conclusion
Rather than one size fits all, tailoring education to baseline knowledge, learner background and future goals increases learning potential while minimizing classroom time.
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