Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine.

BACKGROUND: Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine. METHODS: In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases. RESULTS: A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%). CONCLUSIONS: The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.).

Effect of Benralizumab on Mucus Plugs in Severe Eosinophilic Asthma.

INTRODUCTION: Mucus plugs are associated with airway obstruction in severe asthma and are involved in the formation of activated eosinophils. Benralizumab, an anti-interleukin-5 receptor antibody, markedly reduces not only peripheral blood eosinophils but also airway eosinophils; however, its effects on mucus plugs have not been clarified. In this study, we examined the efficacy of benralizumab on mucus plugs using computed tomography (CT) imaging. METHODS: Twelve patients who were administered benralizumab and underwent CT before and approximately 4 months after the introduction of benralizumab were included in this study, and the number of mucus plugs before and after benralizumab administration was compared. The correlation between the clinical background and treatment effect was also examined. RESULTS: The number of mucus plugs significantly decreased after the introduction of benralizumab. The number of mucus plugs was correlated with sputum eosinophil percentage and eosinophil cationic protein in the sputum supernatants and inversely correlated with forced expiratory volume in 1 s (FEV1). Benralizumab induction resulted in a marked decrease in blood and sputum eosinophil levels and a significant improvement in asthma symptoms, quality of life scores, FEV1, and exacerbation frequency. Furthermore, there was a significant correlation between the reduction in mucus plugs and changes in the symptom score or FEV1. DISCUSSION/CONCLUSION: These data suggest that benralizumab may have the potential to improve symptoms and respiratory function in patients with severe eosinophilic asthma by reducing mucus plugs.

Effects of Benralizumab on Three-Dimensional Computed Tomography Analysis in Severe Eosinophilic Asthma.

INTRODUCTION: Benralizumab, an anti-interleukin-5 receptor chain monoclonal antibody, is used to treat severe asthma and control asthma symptoms or exacerbations. The aim of this study was to examine the changes in airway morphology using computed tomography (CT) images in accordance with clinical efficacy following the administration of benralizumab. METHODS: The clinical efficacy of benralizumab was evaluated in 11 patients with severe asthma by analyzing the changes in parameters, such as the asthma control test, asthma quality of life questionnaire, pulmonary function, and exacerbation count. We also investigated the airway wall thickness of the right bronchus (B1) and the total airway count (TAC) using CT images. RESULTS: Most patients treated with benralizumab showed improvements in asthma symptoms and exacerbations. CT imaging analyses showed a decrease in the right B1 airway wall thickness and an increase in the TAC. Correlations between blood eosinophil count and changes in CT imaging were observed. DISCUSSION/CONCLUSION: The data suggested that benralizumab has the potential to improve airway wall thickening and ventilation by alleviating the obstruction and clearing an obstructed airway.

Assessing Detection Efficiencies for Continuous Methane Emission Monitoring Systems at Oil and Gas Production Sites.

Continuous monitoring systems, consisting of multiple fixed sensors, are increasingly being deployed at oil and gas production sites to detect methane emissions. While these monitoring systems operate continuously, their efficiency in detecting emissions will depend on meteorological conditions, sensor detection limits, the number of sensors deployed, and sensor placement strategies. This work demonstrates an approach to assess the effectiveness of continuous sensor networks in detecting infinite-duration and fixed-duration emission events. The case studies examine a single idealized source and a group of nine different sources at varying heights and locations on a single pad. Using site-specific meteorological data and dispersion modeling, the emission detection performance is characterized. For these case studies, infinite-duration emission events are detected within 1 h to multiple days, depending on the number of sensors deployed. The percentage of fixed-duration emission events that are detected ranged from less than 10% to more than 90%, depending on the number of sources, emission release height, emission event duration, and the number of sensors deployed. While these results are specific to these case studies, the analysis framework described in this work can be broadly applied in the evaluation of continuous emission monitoring network designs.

Effect of Dupilumab on Depression in Asthma with Eosinophilic Chronic Rhinosinusitis in the Japanese Population.

INTRODUCTION: Psychological disorders, such as depression, are markedly prevalent in patients with airway diseases. In this study, we assessed the effect of treatment with dupilumab, an IL-4 receptor α chain antibody, on depressive symptoms in a cohort of patients with asthma with eosinophilic chronic rhinosinusitis (ECRS). METHODS: The study participants, diagnosed with asthma and ECRS, were assessed for symptoms and quality of life (QOL) scores for asthma and ECRS and medications. The Patient Health Questionnaire-9 (PHQ-9) scores were used to evaluate the depressive state. The depressive symptoms were compared with asthma and ECRS symptoms both at the time of initiation and after 4 months of dupilumab treatment. RESULTS: Ultimately, 31 patients were included in the study. Most patients demonstrated a depressive state that was correlated with the nasal symptom score. In the evaluation 4 months after dupilumab treatment, the PHQ-9 score was significantly reduced, and the decrease was remarkable in patients whose nasal symptom score was reduced by 50% or more. Additionally, the PHQ-9 scores in patients with improved nasal and asthma symptoms were significantly reduced. DISCUSSION/CONCLUSION: Dupilumab may improve QOL in patients with bronchial asthma with ECRS by reducing depressive symptoms through the improvement of clinical symptoms.

What is the optimal nutritional assessment tool for predicting decline in the activity of daily living among older patients with heart failure?

The clinical importance of nutritional management in activities of daily living (ADL) among older inpatients with heart failure (HF) is greatly increasing. We determined the optimal nutritional assessment tool that can predict ADL decline among older inpatients with HF. We prospectively investigated 91 inpatients aged ≥ 65 years with HF in an acute hospital. We measured their nutritional status at admission using nutrition indices: the controlling nutritional status (CONUT), the geriatric nutritional risk index, the prognostic nutritional index, and the mini nutritional assessment. Logistic regression analysis was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the relationships between the malnutrition status assessed by each nutritional index category and the ADL decline measured by the Barthel index (BI) in the univariate and multivariate analyses. Among the participants, 28.6% (n = 26; median age 81.5 years; 69.2% men) of the participants were included in the Reduced BI group and 71.4% (n = 65; median age 79.0 years; 67.7% men) in the Maintained BI group. The Reduced BI group showed a significantly higher CONUT value than the Maintained BI group, but there were no significant differences in other nutritional indices. In the multivariate logistic regression analysis, a higher CONUT score was associated with a significantly elevated risk of Reduced BI (adjusted OR 0.24; 95%CI 0.08-0.75; p = 0.014). We found that CONUT is an appropriate nutritional assessment tool for predicting ADL decline among older inpatients with HF in the early phase of hospitalization.

Physical Exercise Improves Cognitive Function in Older Adults with Stage 3-4 Chronic Kidney Disease: A Randomized Controlled Trial.

INTRODUCTION: Patients with chronic kidney disease (CKD) exhibit a higher probability of having cognitive impairment or dementia than those without CKD. The beneficial effects of physical exercise on cognitive function are known in the general older population, but more research is required in older adults with CKD. METHODS: Eighty-one outpatients (aged ≥65 years) with CKD stage G3-G4 were assessed for eligibility. Among them, 60 were randomized (single-center, unblinded, and stratified) and 53 received the allocated intervention (exercise n = 27, control n = 26). Patients in the exercise group undertook group-exercise training at our facility once weekly and independent exercises at home twice weekly or more, for 24 weeks. Patients in the control group received general care. General and specific cognitive functions (memory, attention, executive, and verbal) were measured, and differences in their scores at baseline and at the 24-week follow-up visit were assessed between the 2 groups. RESULTS: Forty-four patients completed the follow-up at 24 weeks (exercise n = 23, control n = 21). Patients in the exercise group showed significantly greater changes in Wechsler Memory Scale-Revised Logical Memory delayed recall (exercise effect: 2.82, 95% CI: 0.46-5.19, p = 0.03), and immediate and delayed recall (exercise effect: 5.97, 95% CI: 1.13-10.81, p = 0.02) scores than those in the control group. CONCLUSIONS: The 24-week exercise intervention significantly improved the memory function in older adults with pre-dialysis CKD. This randomized controlled trial suggests that physical exercise is a useful nonpharmacological strategy for preventing cognitive decline in these patients.

A Searchable Database for Prediction of Emission Compositions from Upstream Oil and Gas Sources.

Atmospheric emissions from oil and gas production operations are composed of multiple hydrocarbons and can have large variations in composition. Accurate estimates of emission compositions are needed to estimate the fate and impacts of emissions and to attribute emissions to sources. This work presents a database, constructed with empirical data and thermodynamic models, that can be queried to estimate hydrocarbon compositions from emission sources present at oil and gas production sites. The database can be searched for matches using between two and seven well parameters as query inputs (gas-to-oil ratio, API gravity, separator pressure, separator temperature, methane molar fraction in produced gas, ethane molar fraction of produced gas, and propane molar fraction in produced gas). Database query performance was characterized by comparing returns from database queries to a test data set. Application of the database to well parameters for tens of thousands of wells in the Barnett, Eagle Ford, and Fayetteville production regions demonstrates variations in emission compositions. Ethane to methane ratio varies by more than an order of magnitude from well to well and source to source. VOC to methane ratios are comparable in variability to ethane to methane ratios for most emission sources, but have a higher variability for emissions from flashing of liquid hydrocarbon tanks.

Cysteinyl Leukotriene Synthesis via Phospholipase A2 Group IV Mediates Exercise-induced Bronchoconstriction and Airway Remodeling.

It is well known that the prevalence of asthma is higher in athletes, including Olympic athletes, than in the general population. In this study, we analyzed the mechanism of exercise-induced bronchoconstriction by using animal models of athlete asthma. Mice were made to exercise on a treadmill for a total duration of 1 week, 3 weeks, or 5 weeks. We analyzed airway responsiveness, BAL fluid, lung homogenates, and tissue histology for each period. In mice that were treated (i.e., the treatment model), treatments were administered from the fourth to the fifth week. We also collected induced sputum from human athletes with asthma and analyzed the supernatants. Airway responsiveness to methacholine was enhanced with repeated exercise stimulation, although the cell composition in BAL fluid did not change. Exercise induced hypertrophy of airway smooth muscle and subepithelial collagen deposition. Cysteinyl-leukotriene (Cys-LT) levels were significantly increased with exercise duration. Montelukast treatment significantly reduced airway hyperresponsiveness (AHR) and airway remodeling. Expression of PLA2G4 (phospholipase A2 group IV) and leukotriene C4 synthase in the airway epithelium was upregulated in the exercise model, and inhibition of PLA2 ameliorated AHR and airway remodeling, with associated lower levels of Cys-LTs. The levels of Cys-LTs in sputum from athletes did not differ between those with and without sputum eosinophilia. These data suggest that AHR and airway remodeling were caused by repeated and strenuous exercise. Cys-LTs from the airway epithelium, but not inflammatory cells, may play an important role in this mouse model.

Relationship between Sarcopenia and Swallowing Capacity in Community-Dwelling Older Women.

BACKGROUND: Swallowing disorders are a serious health concern among older adults. Previous studies reported that sarcopenia may affect swallowing disorders; however, whether sarcopenia is related to the capacity to swallow (measured according to swallowing speed) in community-dwelling older adults is unclear. OBJECTIVES: The aim of this study was to investigate the relationship between sarcopenia and swallowing capacity in community-dwelling older women. METHODS: This cross-sectional observational study was conducted among community-dwelling older women in Japan. The inclusion criteria were as follows: women aged ≥65 years, with the ability to walk independently, and without dysphagia. The exclusion criterion was a history of stroke or Parkinson's disease that directly caused dysphagia. The participants were divided into a sarcopenia and a healthy group based on the criteria of the Asian Working Group for Sarcopenia 2019. We measured swallowing speed (mL/s) as the swallowing capacity by conducting a 100-mL water-swallowing test. To assess the relationship between sarcopenia and swallowing capacity, we performed a multiple regression analysis. RESULTS: Two-hundred and sixty participants were enrolled in the study. Their mean age was 82.3 ± 6.9 years, and 61 (23.5%) of them displayed sarcopenia. The mean swallowing speed was 11.5 ± 4.9 mL/s, and 17 women (6.5%) exhibited choking or a wet-hoarse voice. Multiple regression analysis revealed that sarcopenia was related to the swallowing capacity after adjusting for age, the Mini-Mental State Examination, and the number of comorbidities (ß = -0.20, 95% CI -3.78 to -0.86, p = 0.002). CONCLUSIONS: We found that sarcopenia was related to the swallowing capacity in older women in this study. Future research should clarify whether a similar relationship exists in older men as well as the effect of sarcopenia on the swallowing capacity in older adults over a period of time.

Relationship between tongue muscle quality and swallowing speed in community-dwelling older women.

OBJECTIVE: The aim of this study was to investigate the relationship between tongue muscle quality index, which was represented as tongue muscle pressure divided by tongue muscle mass, and swallowing speed in community-dwelling older women. METHODS: The inclusion criteria for this cross-sectional study were that participants be community-dwelling older women aged 65 years and above without dysphagia. The exclusion criteria were stroke and Parkinson's disease that directly cause dysphagia. We measured tongue muscle thickness and maximum tongue pressure and the tongue muscle quality index, which was defined as the maximum tongue pressure divided by tongue muscle thickness. We investigated swallowing speed via a 100 ml water swallowing test. To assess the relationship between tongue muscle characteristics and swallowing speed, we performed stepwise multiple regression analysis. RESULTS: Ninety-three participants were enrolled in this study (mean age: 84.2 ± 4.7 years). A stepwise multiple regression analysis showed that age (ß = - 0.292, p < 0.01) and tongue muscle quality index (ß = 0.267, p < 0.01) were related to swallowing speed. CONCLUSION: We found that tongue muscle quality index was related to swallowing speed in community-dwelling older women. According to our findings, it is possible that the tongue muscle quality index is a useful parameter for assessing swallowing speed in older women without dysphagia.

Characterization of low adherence population in asthma patients from Japan using Adherence Starts with Knowledge-12.

BACKGROUND: Adherence Starts with Knowledge-12 (ASK-12) is a useful indicator of drug adherence. In this study, we analyzed patient background including social and psychological factors in a low-adherence group of patients with asthma defined using ASK-12. METHODS: From a questionnaire survey for patients with asthma from the Niigata Prefecture, Japan, conducted in the fall of 2016, we enrolled patients who answered all ASK-12 items and underwent a measured respiratory function test within 1 year. The low-adherence group (ASK-12 ≥ 28) was compared with the control group (ASK-12 < 28), and we conducted a cluster analysis of the low-adherence group. RESULTS: There were 170 patients in the low-adherence group and 402 patients in the control group. There was a significant difference between age, gender, working status, smoking history, the percentage of forced expiratory volume in one second (%FEV1), asthma control test (ACT), and Patient Health Questionnaire-9 (PHQ-9) score between the two groups. Logistic analysis revealed that working status (working), % FEV1 (<90%), and PHQ-9 score (>5) were independent factors for the low-adherence group. The cluster analysis identified three clusters in the low-adherence group. Among these, one cluster was characterized by elderly males with chronic obstructive pulmonary disease and another by middle-aged nonsmoking females with a depression tendency, had problems with asthma control. CONCLUSIONS: Several factors were considered to be attributed to low drug-adherence. There were several phenotypes in the low-adherence population correlated with incomplete asthma control. Intervention with drug adherence should be a future goal for asthma treatment.

Use of Light Alkane Fingerprints in Attributing Emissions from Oil and Gas Production.

Spatially resolved emission inventories were used with an atmospheric dispersion model to predict ambient concentrations of methane, ethane, and propane in the Eagle Ford oil and gas production region in south central Texas; predicted concentrations were compared to ground level observations. Using a base case inventory, predicted median propane/ethane concentration ratios were 106% higher (95% CI: 83% higher-226% higher) than observations, while median ethane/methane concentration ratios were 112% higher (95% CI: 17% higher-228% higher) than observations. Predicted median propane and ethane concentrations were factors of 6.9 (95% CI: 3-15.2) and 3.4 (95% CI: 1.4-9) larger than observations, respectively. Predicted median methane concentrations were 7% higher (95% CI: 39% lower-37% higher) than observations. These comparisons indicate that sources of emissions with high propane/ethane ratios (condensate tank flashing) were likely overestimated in the inventories. Because sources of propane and ethane emissions are also sources of methane emissions, the results also suggest that sources of emissions with low ethane/methane ratios (midstream sources) were underestimated. This analysis demonstrates the value of using multiple light alkanes in attributing sources of methane emissions and evaluating the performance of methane emission inventories for oil and natural gas production regions.

Variability in Spatially and Temporally Resolved Emissions and Hydrocarbon Source Fingerprints for Oil and Gas Sources in Shale Gas Production Regions.

A gridded inventory for emissions of methane, ethane, propane, and butanes from oil and gas sources in the Barnett Shale production region has been developed. This inventory extends previous spatially resolved inventories of emissions by characterizing the overall variability in emission magnitudes and the composition of emissions at an hourly time resolution. The inventory is divided into continuous and intermittent emission sources. Sources are defined as continuous if hourly averaged emissions are greater than zero in every hour; otherwise, they are classified as intermittent. In the Barnett Shale, intermittent sources accounted for 14-30% of the mean emissions for methane and 10-34% for ethane, leading to spatial and temporal variability in the location of hourly emissions. The combined variability due to intermittent sources and variability in emission factors can lead to wide confidence intervals in the magnitude and composition of time and location-specific emission inventories; therefore, including temporal and spatial variability in emission inventories is important when reconciling inventories and observations. Comparisons of individual aircraft measurement flights conducted in the Barnett Shale region versus the estimated emission rates for each flight from the emission inventory indicate agreement within the expected variability of the emission inventory for all flights for methane and for all but one flight for ethane.

Combination of Low Body Mass Index and Low Serum Albumin Level Leads to Poor Functional Recovery in Stroke Patients.

BACKGROUND: Nutritional status is associated with the functional recovery of stroke patients. This study aimed to examine the influence of the combination of body mass index (BMI) and serum albumin level on functional recovery in subacute stroke patients. METHODS: This retrospective cohort study included 259 subacute stroke patients (mean age 68.9 ± 12.3 years). Patients were categorized into 4 groups according to their BMI and serum albumin level: group 1, low BMI (<18.5 kg/m2) and low serum albumin level (<3.5 g/dL); group 2, low BMI and high serum albumin level (≥3.5 g/dL); group 3, normal weight (≥18.5 kg/m2) and low serum albumin level; and group 4, normal weight and high serum albumin level. The outcome variable was the motor subscale of the Functional Independence Measure (M-FIM) effectiveness. We defined the first quartile of M-FIM effectiveness as poor functional recovery. Multivariate logistic regression analysis was performed to examine the influence of the combination of BMI and serum albumin level on poor functional recovery. RESULTS: Multivariate logistic regression analysis adjusted for baseline characteristics (reference, group 4) showed that group 1 was mostly associated with a significant risk of poor functional recovery (odds ratio, 4.13; 95% confidence interval, 1.53-11.15). CONCLUSIONS: Our results suggested that the combination of low BMI and low serum albumin level was more significantly associated with poor functional recovery in subacute stroke patients than either factor alone. The combination of BMI and serum albumin level should be taken into account when predicting functional recovery in subacute stroke patients.

Dynamic Management of NOx and SO2 Emissions in the Texas and Mid-Atlantic Electric Power Systems and Implications for Air Quality.

Cap and trade programs have historically been designed to achieve annual or seasonal reductions in emissions of nitrogen oxides and sulfur dioxide from power plants. Emissions reductions may not be temporally coincident with meteorological conditions conducive to the formation of peak ozone and fine particulate matter concentrations. Integrated power system and air quality modeling methods were developed to evaluate time-differentiated emissions price signals on high ozone days in the Mid-Atlantic portion of the Pennsylvania-New Jersey-Maryland (PJM) Interconnection and Electric Reliability Council of Texas (ERCOT) grids. Sufficient flexibility exists in the two grids with marked differences in demand and fuel generation mix to accommodate time-differentiated emissions pricing alone or in combination with a season-wide program. System-wide emissions reductions and production costs from time-differentiated pricing are shown to be competitive with those of a season-wide program on high ozone days and would be more cost-effective if the primary policy goal was to target emissions reductions on these days. Time-differentiated pricing layered as a complement to the Cross-State Air Pollution Rule had particularly pronounced benefits for the Mid-Atlantic PJM system that relies heavily on coal-fired generation. Time-differentiated pricing aimed at reducing ozone concentrations had particulate matter reduction co-benefits, but if particulate matter reductions are the primary objective, other approaches to time-differentiated pricing may lead to greater benefits.

The Effects of All-Trans Retinoic Acid on the Induction of Oral Tolerance in a Murine Model of Bronchial Asthma.

BACKGROUND: Active suppression induced by regulatory T (Treg) cells is reported to be one of the mechanisms involved in oral tolerance. All-trans retinoic acid (ATRA) has been reported to affect Treg cell differentiation. The present study examined the effects of ATRA on the induction of oral tolerance in a murine model of bronchial asthma. METHODS: BALB/c mice were sensitized to and challenged with ovalbumin (OVA) through feeding followed by OVA challenges. In some study groups ATRA was orally administered concomitantly with OVA feeding either in the presence or absence of the retinoic acid receptor antagonist LE135. Lung CD4+ T cells were isolated from mice exposed to ATRA and/or OVA, and transferred to control mice. Airway hyperresponsiveness (AHR), cell counts and cytokine levels in bronchoalveolar lavage (BAL) fluid, and lung histology were assessed. RESULTS: Concomitant administration of ATRA with OVA ameliorated AHR, airway eosinophilia, elevation of cytokines in BAL fluid and goblet cell metaplasia. The proportion of Treg cells in the lungs was increased in mice treated with OVA and ATRA, as compared to those treated with OVA only. Transfer of lung CD4+ T cells from mice treated with OVA and ATRA induced suppression of AHR and airway inflammation. LE135 completely reversed the effects of ATRA on AHR, airway allergic inflammation and the number of Treg cells in the lungs. CONCLUSION: These data suggested that oral administration of ATRA with OVA had the potential to enhance oral tolerance in this murine model of bronchial asthma. These effects were mediated, at least in part, by Treg cell expansion.

Regional ozone impacts of increased natural gas use in the Texas power sector and development in the Eagle Ford shale.

The combined emissions and air quality impacts of electricity generation in the Texas grid and natural gas production in the Eagle Ford shale were estimated at various natural gas price points for the power sector. The increased use of natural gas in the power sector, in place of coal-fired power generation, drove reductions in average daily maximum 8 h ozone concentration of 0.6-1.3 ppb in northeastern Texas for a high ozone episode used in air quality planning. The associated increase in Eagle Ford upstream oil and gas production nitrogen oxide (NOx) emissions caused an estimated local increase, in south Texas, of 0.3-0.7 ppb in the same ozone metric. In addition, the potential ozone impacts of Eagle Ford emissions on nearby urban areas were estimated. On the basis of evidence from this work and a previous study on the Barnett shale, the combined ozone impact of increased natural gas development and use in the power sector is likely to vary regionally and must be analyzed on a case by case basis.

Characteristics of eosinophilic and non-eosinophilic asthma during treatment with inhaled corticosteroids.

OBJECTIVE: Eosinophilic inflammation in the respiratory tract is a hallmark of bronchial asthma. In naïve cases, the inflammatory profile is associated with disease severity and reactivity to inhaled corticosteroids (ICS). Sustained airway eosinophilia has been reported during ICS treatment. However, the immunological characteristics of these cases are not known and it is unclear if this situation contributes to asthma control. This study was performed to determine the answer of these questions. METHODS: To compare phenotypes of eosinophilic and non-eosinophilic asthma (EA and NEA, respectively) under ICS treatment, clinical data were obtained from asthmatic subjects (n = 22) and healthy controls (n = 10), and the leukocyte compositions of induced sputum and peripheral blood were determined. T lymphocyte profiles in systemic blood were assessed by flow cytometry. RESULTS: A higher frequency of emergency room visits was observed in the NEA group, which had a higher neutrophil count relative to the total inflammatory cell population in induced sputum than the EA group (59.5 versus 36.6%; p < 0.01). The fraction of helper T (Th)17 lymphocytes as well as the ratio of Th17 to regulatory T cells (Treg) in the peripheral blood was higher in the NEA than in the EA group (0.24 versus 0.13; p < 0.05). CONCLUSIONS: Th17 were more prevalent than Treg cells in the peripheral blood of NEA patients under ICS treatment, corresponding to neutrophil-dominant airway inflammation and a severe asthmatic phenotype. Thus, an imbalance in Th17/Treg may be associated with the pathogenesis of NEA in patients undergoing ICS treatment.