Operationalizing Community Assessment Results to Enhance Preparedness for a Radiological Emergency.

OBJECTIVE: A radiological emergency such as the detonation of a radiological dispersal device would have catastrophic health, environmental, and economic consequences. Community assessments can provide useful information about radiological and other emergency preparedness at the household level. Tools such as logic models can be applied to link data collected in a community assessment to planned activities and targeted outcomes. This study sought to answer how public health departments can use the results of a community assessment to improve preparedness for radiological and other types of emergencies and to present a sample logic model demonstrating how questions asked in a community assessment can be used to drive intended outcomes. DESIGN: Surveys were fielded in 2019 to professionals with experience in radiological emergency preparedness, state and local health and emergency management, and journalism. Questions included the role of health departments in radiological emergency preparedness, the operationalization of results from a community assessment for preparedness, and information sharing in a radiological emergency. Descriptive statistics and a modified framework approach were used for open-ended questions. RESULTS: Nearly three-fourths of state/local officials reported that it would be at least somewhat difficult (73%; 11 of 15 state/local officials) for a local health department to operationalize the results of a community health assessment for radiological emergency preparedness. Potential barriers included competing priorities, lack of funds, and limited staff. Resources such as pretested communication materials, tailored messaging, and technical tools and training can assist health departments and emergency management agencies in using the information collected from a community assessment. CONCLUSIONS: To address implementation challenges in operationalizing the results of a community assessment, officials can use tools such as logic models to illustrate how the information gathered from a community health assessment will create an intended preparedness outcome and to advocate for funds for this type of assessment.

Developing an instrument to measure household radiological emergency preparedness using the Community Assessment for Public Health Emergency Response (CASPER) methodology: An evidence-informed approach.

INTRODUCTION: Community assessments to measure emergency preparedness can inform policies, planning, and communication to the public to improve readiness and response if an emergency was to occur. Public health and emergency management officials need an effective assessment tool to measure community preparedness for a radiological emergency. METHODS: The authors created a survey instrument to collect data on household radiological emergency preparedness that could be implemented using the Community Assessment for Public Health Emergency Response (CASPER) methodology, developed by the U.S. Centers for Disease Control and Prevention. To inform the development of the tool, the authors examined existing CASPER surveys, focusing on identifying best practices for creating a survey instrument, as well as analyzing the results of a survey of radiation preparedness experts and state/local health and emergency management officials. RESULTS: The developed survey tool includes 32 questions covering four domains: communication in an emergency, preparedness planning, physical/behavioral health, and demographics. The instrument captures information related to identified barriers in communicating in a radiological emergency as well as self-reported behaviors that could potentially be influenced through awareness and education. DISCUSSION: Using the proposed survey instrument and following the existing rapid assessment methodology provided by CASPER, public health and emergency management agencies can collect valuable information on the radiation preparedness needs of their communities, which can then be used to improve household readiness for an emergency.

Prioritizing Communication About Radiation Risk Reduction in the United States: Results from a Multi-criteria Decision Analysis.

OBJECTIVES: The lack of radiation knowledge among the general public continues to be a challenge for building communities prepared for radiological emergencies. This study applied a multi-criteria decision analysis (MCDA) to the results of an expert survey to identify priority risk reduction messages and challenges to increasing community radiological emergency preparedness. METHODS: Professionals with expertise in radiological emergency preparedness, state/local health and emergency management officials, and journalists/journalism academics were surveyed following a purposive sampling methodology. An MCDA was used to weight criteria of importance in a radiological emergency, and the weighted criteria were applied to topics such as sheltering-in-place, decontamination, and use of potassium iodide. Results were reviewed by respondent group and in aggregate. RESULTS: Sheltering-in-place and evacuation plans were identified as the most important risk reduction measures to communicate to the public. Possible communication challenges during a radiological emergency included access to accurate information; low levels of public trust; public knowledge about radiation; and communications infrastructure failures. CONCLUSIONS: Future assessments for community readiness for a radiological emergency should include questions about sheltering-in-place and evacuation plans to inform risk communication.

Evaluating Perceived Emergency Preparedness and Household Preparedness Behaviors: Results from a CASPER Survey in Fairfax, Virginia.

OBJECTIVES: Using data collected from a Community Assessment for Public Health Emergency Response (CASPER) conducted in Fairfax Health District, Virginia, in 2016, we sought to assess the relationship between household-level perceived preparedness and self-reported preparedness behaviors. METHODS: Weighted population estimates and 95% confidence intervals were reported, and Pearson's chi-squared test was used to investigate differences by group. RESULTS: Examining responses to how prepared respondents felt their household was to handle a large-scale emergency or disaster, an estimated 7.4% of respondents (95% CI: 4.3-12.3) reported that their household was "completely prepared," 37.3% (95% CI: 31.4-43.7) were "moderately prepared," 38.2% (95% CI: 31.6-45.2) were "somewhat prepared," and 14.4% (95% CI: 10.2-20.0) were "unprepared." A greater proportion of respondents who said that their household was "completely" or "moderately" prepared for an emergency reported engaging in several behaviors related to preparedness. However, for several preparedness behaviors, there were gaps between perceived preparedness and self-reported readiness. CONCLUSIONS: Community assessments for public health preparedness can provide valuable data about groups who may be at risk during an emergency due to a lack of planning and practice, despite feeling prepared to handle a large-scale emergency or disaster.

The Acute Effects of Age and Particulate Matter Exposure on Heart Rate and Heart Rate Variability in Mice.

Exposure to ambient particulate matter (PM) is associated with increased cardiac morbidity and mortality with the elderly considered to be the most susceptible. The purpose of this study was to determine if exposure to PM would cause a greater impact on heart regulation in older DBA/2 (D2) male mice as determined by changes in heart rate (HR) and heart rate variability (HRV). D2 mice at the ages of 4, 12, and 19 months were instilled with 100 µg of PM or saline by aspiration. Before and after the aspiration, 3-min echocardiogram (ECG) samples for HR and HRV were recorded at 15-min intervals for 3 h along with corresponding measurements of homeostasis, such as temperature, metabolism, and ventilation. PM exposure resulted in an increase in HRV, declines in HR, and altered measures of homeostasis for a subset of the 12-mo mice. The PM aspiration did not affect cardiac or homeostasis parameters in the 4- or 19-mo mice. Our results suggest that a select group of middle-age mice are more susceptible to alterations in their heart rhythm after PM exposure and highlight that there are acute age-related differences in heart rhythm following PM exposure.

Perioperative participation of orthopedic patients and surgical staff in a nasal decolonization intervention to reduce Staphylococcus spp surgical site infections.

With the goal of reducing rates of surgical site infections in our spine patients, we initiated a trial to investigate the impact of adding perisurgical nasal decolonization involving patients and surgical and nursing staff. We combined immediate presurgical application of a nonantibiotic alcohol-based nasal antiseptic with existing chlorhexidine bath or wipes in a comprehensive pre- and postoperative decolonization protocol. Mean infection rates were significantly decreased by 81% from 1.76 to 0.33 per 100 surgeries during the 15-month trial, when compared with the prior 9-month baseline.

Reduction of nasal Staphylococcus aureus carriage in health care professionals by treatment with a nonantibiotic, alcohol-based nasal antiseptic.

BACKGROUND: Antibiotics used to reduce nasal colonization by Staphylococcus aureus in patients before admission are inappropriate for carriage reduction on a regular basis within a hospital community. Effective nonantibiotic alternatives for daily use in the nares will allow reduction of this bacterial source to be addressed. METHODS: Our study tested the effectiveness of a nonantibiotic, alcohol-based antiseptic in reducing nasal bacterial carriage in health care professionals (HCPs) at an urban hospital center. HCPs testing positive for vestibular S aureus colonization were treated 3 times during the day with topical antiseptic or control preparations. Nasal S aureus and total bacterial colonization levels were determined before and at the end of a 10-hour workday. RESULTS: Seventy-eight of 387 HCPs screened (20.2%) tested positive for S aureus infection. Of 39 subjects who tested positive for S aureus infection who completed the study, 20 received antiseptic and 19 received placebo treatment. Antiseptic treatment reduced S aureus colony forming units from baseline by 99% (median) and 82% (mean) (P < .001). Total bacterial colony forming units were reduced by 91% (median) and 71% (mean) (P < .001). CONCLUSIONS: Nasal application of a nonantibiotic, alcohol-based antiseptic was effective in reducing S aureus and total bacterial carriage, suggesting the usefulness of this approach as a safe, effective, and convenient alternative to antibiotic treatment.

Lipopolysaccharide-induced phosphorylation of c-Met tyrosine residue 1003 regulates c-Met intracellular trafficking and lung epithelial barrier function.

c-Met, the receptor tyrosine kinase whose natural ligand is hepatocyte growth factor, is known to have a key role in cell motility. We have previously shown that lysophosphatidic acid (LPA) induced a decrease in c-Met activation via serine phosphorylation of c-Met at cell-cell contacts. Here, we demonstrate that lipopolysaccharide (LPS) treatment of human bronchial epithelial cells induced internalization of c-Met via phosphorylation at its tyrosine residue 1003. In addition, it induced epithelial barrier dysfunction as evidenced by a decrease in transepithelial resistance (TER) in a time-dependent manner. Pretreatment with a c-Met inhibitor (PHA-665752) or inhibition of protein kinase C (PKC)-α attenuated the LPS-mediated phosphorylation of c-Met and its internalization. LPS-induced c-Met tyrosine 1003 phosphorylation, activation of PKCα, and c-Met internalization were, however, reversed by pretreatment of cells with LPA, which increased c-Met accumulation at cell-cell contacts. Inhibition of LPS-mediated c-Met tyrosine (Y1003) phosphorylation and internalization by prior treatment with PHA-665752, inhibition of PKCα, or overexpression of c-MetY1003A mutant attenuated LPS-induced reduction of TER. Furthermore, we found that c-Met accumulation at cell-cell contacts contributed to LPA-enhanced epithelial barrier integrity, since downregulation of c-Met by specific small-interfering RNA attenuated LPA-increased TER. The data reveal a novel biological function of c-Met in the regulation of lung epithelial barrier integrity.

Characterization of a portable method for the collection of exhaled breath condensate and subsequent analysis of metal content.

Using exhaled breath condensate (EBC) as a biological media for analysis of biomarkers of exposure may facilitate the understanding of inhalation exposures. In this study, we present method validation for the collection of EBC and analysis of metals in EBC. The collection method was designed for use in a small scale longitudinal study with the goal of improving reproducibility while maintaining economic feasibility. We incorporated the use of an Rtube with additional components as an assembly, and trained subjects to breathe into the apparatus. EBC was collected from 8 healthy adult subjects with no known elevated exposures to Mn, Cr, Ni, and Cd repeatedly (10 times) within 7 days and analyzed for these metals via ICP-MS. Method detection limits were obtained by mimicking the process of EBC collection with ultrapure water, and resulted in 46-62% of samples falling in a range less than the method detection limit. EBC metal concentrations were found to be statistically significantly associated (p < 0.05) with room temperature and relative humidity during collection, as well as with the gender of the subject. The geometric mean EBC metal concentrations in our unexposed subjects were 0.57 µg Mn per L, 0.25 µg Cr per L, 0.87 µg Ni per L, and 0.14 µg Cd per L. The overall standard deviation was greater than the mean estimate, and the major source in EBC metals concentrations was due to fluctuations in subjects' measurements over time rather than to the differences between separate subjects. These results suggest that measurement and control of EBC collection and analytical parameters are critical to the interpretation of EBC metals measurements. In particular, rigorous estimation of method detection limits of metals in EBC provides a more thorough evaluation of accuracy.

Antioxidant components of naturally-occurring oils exhibit marked anti-inflammatory activity in epithelial cells of the human upper respiratory system.

BACKGROUND: The upper respiratory tract functions to protect lower respiratory structures from chemical and biological agents in inspired air. Cellular oxidative stress leading to acute and chronic inflammation contributes to the resultant pathology in many of these exposures and is typical of allergic disease, chronic sinusitis, pollutant exposure, and bacterial and viral infections. Little is known about the effective means by which topical treatment of the nose can strengthen its antioxidant and anti-inflammatory defenses. The present study was undertaken to determine if naturally-occurring plant oils with reported antioxidant activity can provide mechanisms through which upper respiratory protection might occur. METHODS: Controlled exposure of the upper respiratory system to ozone and nasal biopsy were carried out in healthy human subjects to assess mitigation of the ozone-induced inflammatory response and to assess gene expression in the nasal mucosa induced by a mixture of five naturally-occurring antioxidant oils--aloe, coconut, orange, peppermint and vitamin E. Cells of the BEAS-2B and NCI-H23 epithelial cell lines were used to investigate the source and potential intracellular mechanisms of action responsible for oil-induced anti-inflammatory activity. RESULTS: Aerosolized pretreatment with the mixed oil preparation significantly attenuated ozone-induced nasal inflammation. Although most oil components may reduce oxidant stress by undergoing reduction, orange oil was demonstrated to have the ability to induce long-lasting gene expression of several antioxidant enzymes linked to Nrf2, including HO-1, NQO1, GCLm and GCLc, and to mitigate the pro-inflammatory signaling of endotoxin in cell culture systems. Nrf2 activation was demonstrated. Treatment with the aerosolized oil preparation increased baseline levels of nasal mucosal HO-1 expression in 9 of 12 subjects. CONCLUSIONS: These data indicate that selected oil-based antioxidant preparations can effectively reduce inflammation associated with oxidant stress-related challenge to the nasal mucosa. The potential for some oils to activate intracellular antioxidant pathways may provide a powerful mechanism through which effective and persistent cytoprotection against airborne environmental exposures can be provided in the upper respiratory mucosa.

Th2 cytokines associated with chronic rhinosinusitis with polyps down-regulate the antimicrobial immune function of human sinonasal epithelial cells.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a disorder characterized by persistent eosinophilic Th2 inflammation and frequent sinonasal microbial colonization. It has been postulated that an abnormal mucosal immune response underlies disease pathogenesis. The relationship between Th2 inflammatory cytokines and the innate immune function of sinonasal epithelial cells (SNECs) has not been explored. METHODS: Human SNECs (HSNECs) isolated from control subjects and patients with CRS were assessed for expression of antimicrobial innate immune genes and proinflammatory cytokine genes by real-time polymerase chain reaction, ELISA, and flow cytometry. A model of the Th2 inflammatory environment was created by exposure of primary HSNEC to the Th2 cytokine interleukin (IL)-4 or IL-13 for 36 hours, with subsequent assessment of innate immune gene expression. RESULTS: HSNEC obtained from CRSwNP patients displayed decreased expression of multiple antimicrobial innate immune markers, including toll-like receptor 9, human beta-defensin 2, and surfactant protein A. Baseline expression of these genes by normal and CRS HSNEC in culture is significantly down-regulated after incubation with IL-4 or IL-13. CONCLUSION: Expression of multiple innate immune genes by HSNEC is reduced in CRSwNP. One mechanism appears to be a direct effect of the leukocyte-derived Th2 cytokines present in the sinonasal mucosa in CRSwNP. Impaired mucosal innate immunity may contribute to microbial colonization and abnormal immune responses associated with CRSwNP.

Chronic rhinosinusitis with nasal polyps is associated with decreased expression of mucosal interleukin 22 receptor.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disorder of the sinonasal mucosa that is frequently associated with microbial colonization. Innate defense mechanisms at the mucosal surface are critical in protecting the host from airborne environmental pathogens. Recent studies of skin and gastrointestinal tract inflammatory diseases have shown that stimulation of the interleukin-22 receptor (IL-22R1) nonspecifically increases innate immune responses. The potential role of IL-22R1 in the pathogenesis of CRSwNP has never been explored. STUDY DESIGN: Prospective. METHODS: Nine controls and 19 subjects with CRS were prospectively enrolled prior to undergoing endoscopic sinus surgery. Nasal epithelial cells were cultured from surgically obtained ethmoid mucosa and IL-22R1 protein expression was examined via flow cytometry. RNA was extracted from whole mucosal samples and real-time polymerase chain reaction (PCR) was employed to determine expression of IL22 and IL-22R1. Subjects were followed for at least 6 months postoperative to assess for recurrence or persistence of polyps. RESULTS: Flow cytometry demonstrated the expression of IL-22R1 protein on the surface of cultured nasal epithelial cells. IL-22R1 mRNA was expressed in 100% of the controls and CRSsNP. However, IL-22R1 was only expressed in 55% of patients with recalcitrant CRSwNP. Additionally, levels of IL22R1 were significantly lower in recalcitrant CRSwNP compared to controls and CRSsNP. IL22 levels did not reach statistical significance. CONCLUSIONS: In this study, we demonstrate IL-22R1 mRNA and protein expression on nasal epithelial cells. Failure of medical and surgical therapy in CRSwNP is associated with significantly decreased expression of IL-22R1. Further research is needed to determine the potential of IL-22R1 as a therapeutic target in CRSwNP.

Sinonasal epithelial cell expression of toll-like receptor 9 is decreased in chronic rhinosinusitis with polyps.

BACKGROUND: Innate immune recognition of pathogens by sinonasal epithelial cells may play an important role in the pathogenesis of chronic rhinosinusitis (CRS). Previous studies have indicated that toll-like receptor (TLR) mRNA is present in sinonasal mucosa, and levels of TLR9 expression are decreased in recalcitrant CRS with nasal polyps (CRSwNP). However, the cellular source and function of TLR9 in the sinonasal epithelium is not known. In this study, primary epithelial cell cultures were analyzed from control subjects and CRSwNP patients to determine the presence and function of TLR9 protein. METHODS: Primary epithelial cell cultures were established from 5 controls and 10 CRSwNP patients undergoing sinus surgery. Flow cytometry was used to confirm purity of epithelial cells and to assess expression of TLR9 protein. Epithelial cells were stimulated with TLR9 agonist, and mRNA was analyzed by real-time PCR for expression of human beta-defensin (HBD) 2 and interleukin (IL)-8. RESULTS: Flow cytometry showed TLR9 protein in 100% of epithelial cells from controls and CRSwNP patients. The level of expression was 50% lower in CRS patients than in controls. Stimulation of epithelial cells with TLR9 agonist produced a 1.5- to 9-fold increase in HBD-2 and IL-8 mRNA expression. CONCLUSION: Functional TLR9 protein is expressed by normal and diseased sinonasal epithelial cells. The level of TLR9 expression is decreased in CRSwNP patients, consistent with the previous finding of decreased TLR9 mRNA in whole sinonasal tissue. These findings suggest that impaired innate immune responses to pathogens via TLR9 on sinonasal epithelial cells may represent a critical mechanism in chronic inflammatory sinus disease.

The cigarette smoke component acrolein inhibits expression of the innate immune components IL-8 and human beta-defensin 2 by sinonasal epithelial cells.

BACKGROUND: Tobacco use is associated with poorer outcomes of medical and surgical therapy for chronic rhinosinusitis (CRS), although the underlying mechanism is unknown. Acrolein (AC) is a major component of cigarette smoke that has been shown to suppress innate immune gene expression by human bronchial epithelial cells and murine macrophages. In this study, we explore whether exposure of human sinonasal epithelial cells (HSNECs) to AC similarly reduces their innate immune gene expression. METHODS: Primary HSNECs from CRS patients were grown in culture, either differentiated or submerged. HSNECs were treated for 30 minutes with 0-50 microM of AC and were subsequently analyzed by real-time polymerase chain reaction and ELISA to determine IL-8 and human beta-defensin (HBD) 2 expression. Total glutathione was measured to see the oxidative stress within the treatment range. RESULTS: In primary HSNEC, IL-8 mRNA levels decreased dose dependently in the range of 10-50 microM of AC with an eightfold decrease at 50 microM. In addition, a 125-fold decrease at 50 microM for IL-8 protein was observed. HBD-2 mRNA decreased twofold and HBD-2 protein decreased fourfold at 50 microM of AC in primary HSNEC. However, differentiated HSNEC showed a marginal decrease in a dose-dependent manner for both IL-8 and HBD-2 within the range of 10-50 microM of AC. There was no oxidative stress observed over this range of AC concentration. CONCLUSION: The tobacco smoke component AC has the capacity to suppress the inflammatory and innate immune function of sinonasal epithelial cells. Whether this effect contributes to the negative clinical impact of smoking on CRS outcomes merits additional investigation.

Differential regulation of hyaluronan-induced IL-8 and IP-10 in airway epithelial cells.

Airway epithelium is emerging as a regulator of local inflammation and immune responses. However, the cellular and molecular mechanisms responsible for the immune modulation by these cells have yet to be fully elucidated. At the cellular level, the hallmarks of airway inflammation are mucus gland hypertrophy with excess mucus production, accumulation of inflammatory mediators, inflammation in the airway walls and lumen, and breakdown and turnover of the extracellular matrix. We demonstrate that fragments of the extracellular matrix component hyaluronan induce inflammatory chemokine production in primary airway epithelial cells grown at an air-liquid interface. Furthermore, hyaluronan fragments use two distinct molecular pathways to induce IL-8 and IFN-gamma-inducible protein 10 (IP-10) chemokine expression in airway epithelial cells. Hyaluronan-induced IL-8 requires the MAP kinase pathway, whereas hyaluronan-induced IP-10 utilizes the NF-kappaB pathway. The induction is specific to low-molecular-weight hyaluronan fragments as other glycosaminoglycans do not induce IL-8 and IP-10 in airway epithelial cells. We hypothesize that not only is the extracellular matrix a target of destruction in airway inflammation but it plays a critical role in perpetuating inflammation through the induction of cytokines, chemokines, and modulatory enzymes in epithelial cells. Furthermore, hyaluronan, by inducing IL-8 and IP-10 by distinct pathways, provides a unique target for differential regulation of key inflammatory chemokines.

Lipid phosphate phosphatase-1 regulates lysophosphatidic acid-induced calcium release, NF-kappaB activation and interleukin-8 secretion in human bronchial epithelial cells.

LPA (lysophosphatidic acid), a potent bioactive phospholipid, elicits diverse cellular responses through activation of the G-protein-coupled receptors LPA1-LPA4. LPA-mediated signalling is partially regulated by LPPs (lipid phosphate phosphatases; LPP-1, -2 and -3) that belong to the phosphatase superfamily. This study addresses the role of LPPs in regulating LPA-mediated cell signalling and IL-8 (interleukin-8) secretion in HBEpCs (human bronchial epithelial cells). Reverse transcription-PCR and Western blotting revealed the presence and expression of LPP-1-3 in HBEpCs. Exogenous [3H]oleoyl LPA was hydrolysed to [3H]-mono-oleoylglycerol. Infection of HBEpCs with an adenoviral construct of human LPP-1 for 48 h enhanced the dephosphorylation of exogenous LPA by 2-3-fold compared with vector controls. Furthermore, overexpression of LPP-1 partially attenuated LPA-induced increases in the intracellular Ca2+ concentration, phosphorylation of IkappaB (inhibitory kappaB) and translocation of NF-kappaB (nuclear factor-kappaB) to the nucleus, and almost completely prevented IL-8 secretion. Infection of cells with an adenoviral construct of the mouse LPP-1 (R217K) mutant partially attenuated LPA-induced IL-8 secretion without altering LPA-induced changes in intracellular Ca2+ concentration, phosphorylation of IkappaB, NF-kappaB activation or IL-8 gene expression. Our results identify LPP-1 as a key regulator of LPA signalling and IL-8 secretion in HBEpCs. Thus LPPs could represent potential targets in regulating leucocyte infiltration and airway inflammation.