SARS-CoV-2 vaccine testing and trials in the pediatric population: biologic, ethical, research, and implementation challenges.

As the nation implements SARS-CoV-2 vaccination in adults at an unprecedented scale, it is now essential to focus on the prospect of SARS-CoV-2 vaccinations in pediatric populations. To date, no children younger than 12 years have been enrolled in clinical trials. Key challenges and knowledge gaps that must be addressed include (1) rationale for vaccines in children, (2) possible effects of immune maturation during childhood, (3) ethical concerns, (4) unique needs of children with developmental disorders and chronic conditions, (5) health inequities, and (6) vaccine hesitancy. Because COVID-19 is minimally symptomatic in the vast majority of children, a higher acceptable risk threshold is required when evaluating pediatric clinical trials. Profound differences in innate and adaptive immunity during childhood and adolescence are known to affect vaccine responsiveness for a variety of childhood diseases. COVID-19 and the accompanying social disruption, such as the school shutdowns, has been disproportionately damaging to minority and low-income children. In this commentary, we briefly address each of these key issues, specify research gaps, and suggest a broader learning health system approach to accelerate testing and clinical trial development for an ethical and effective strategy to implement a pediatric SARS-CoV-2 vaccine as rapidly and safely as possible. IMPACT: As the US begins an unprecedented implementation of SARS-CoV-2 vaccination, substantial knowledge gaps have yet to be addressed regarding vaccinations in the pediatric population. Maturational changes in the immune system during childhood have influenced the effectiveness of pediatric vaccines for other diseases and conditions, and could affect SARS-CoV-2 vaccine responsiveness in children. Given that COVID-19 disease is far milder in the majority of children than in adults, the risk-benefit of a pediatric SARS-CoV-2 vaccine must be carefully weighed. The needs of children with developmental disabilities and with chronic disease must be addressed. Minority and low-income children have been disproportionately adversely affected by the COVID-19 pandemic; care must be taken to address issues of health equity regarding pediatric SARS-CoV-2 vaccine trials and allocation. Research and strategies to address general vaccine hesitancy in communities must be addressed in the context of pediatric SARS-CoV-2 vaccines.

Exploration of Barriers and Facilitators to Implementing Best Practice in Exercise Medicine in Primary Pediatric Care-Pediatrician Perspectives.

PURPOSE: Despite the known health benefits of physical activity (PA), few primary care pediatricians discuss, evaluate, or prescribe PA for children. The goal of this study was to examine pediatricians' thoughts and practices related to child PA and the perceived facilitators and barriers to implementing PA evaluation and prescription in pediatric primary care clinics. METHODS: The Consolidated Framework for Implementation Research was used to explore implementation barriers and facilitators. A mixed-method design combined questionnaires and focus groups with 27 pediatricians. RESULTS: Despite the pediatricians' beliefs that PA is important for patients, there was wide practice variability in their approaches to discussing PA. Several perceived barriers to implementing PA evaluation and prescription were identified, including lack of knowledge and training, managing time for PA with multiple demands, the need for a team approach and simple PA tools and resources, support for patient tailoring of PA messaging, and a need for PA best practice champions. CONCLUSION: The identified barriers to implementing evidence in PA suggest several directions for improvement, including a care-team approach; quick, inexpensive, and simple PA tools; community PA partnerships; PA training in medical education; evidence-based strategies; and PA directories for families. These efforts could facilitate the implementation of PA best practices in pediatrics.

Exercise and lifestyle changes in pediatric asthma.

PURPOSE OF REVIEW: The purpose of this review is to discuss the most recent studies on lifestyle interventions in pediatric asthma. We include studies on physical activity and exercise, sedentary time, nutrition, behavioral therapy and the role of schools. RECENT FINDINGS: Several small studies in children with asthma suggest that exercise interventions can improve aerobic fitness, asthma symptoms or control and quality of life. Existing evidence supports recommending higher intake of fruits and vegetables for asthma risk and control. In contrast, the 'Western diet' - high in refined grains, highly processed foods, red meats and fried foods with low intake of fruits and vegetables - has a proinflammatory effect and may alter microbiota composition leading to worse asthma outcomes. Finally, there are opportunities to utilize schools to promote physical activity, though standardization of asthma management in the schools is needed. SUMMARY: Assessing physical activity/fitness levels, sedentary time and nutritional status is important in the management of children with asthma, as they are modifiable factors. Larger rigorous studies evaluating lifestyle interventions are needed to better inform current asthma guidelines as well as to understand the underlying mechanism(s) related to physical activity and diet in asthma.

A new approach to estimate aerobic fitness using the NHANES dataset.

INTRODUCTION: Physical activity and fitness are essential for healthy growth in children. The National Health and Nutrition Examination Survey (NHANES) evaluated fitness by estimating V̇O2 max from submaximal measurements of heart rate (HR) during graded treadmill exercise. Our aims were (a) to examine how well NHANES methodology used to estimate V̇O2 max correlated with actual VO2 max and (b) to evaluate a novel fitness metric using actual data collected during exercise and its relationship to physical activity and sedentary time, lipid profiles, and body composition. METHODS: Fifty-three adolescents completed NHANES submaximal exercise protocol and maximal graded cardiopulmonary exercise testing. We used a novel approach to quantifying fitness (Δvelocity × incline × body mass (VIM)/ΔHR slopes) and evaluated its relationship to physical activity and sedentary time using NHANES data (n = 4498). In a subset (n = 740), we compared ΔVIM/ΔHR slopes to NHANES estimated V̇O2 max and examined their relationship to cardiovascular risk factors (BMI percentiles and lipid levels). RESULTS: Measured V̇O2 peak was moderately correlated with NHANES estimated V̇O2 max (r = 0.53, P < 0.01). Significantly higher ΔVIM/ΔHR slopes were associated with increased physical activity and decreased sedentary time. ΔVIM/ΔHR slopes were negatively associated with LDL, triglycerides, and BMI percentiles (P < 0.01). In general, the two fitness models were similar; however, ΔVIM/ΔHR was more discriminating than NHANES in quantifying the relationship between fitness and LDL levels. CONCLUSION: We found that the NHANES estimated V̇O2 max accounted for approximately 28% of the variability in the measured V̇O2 peak. Our approach to estimating fitness (ΔVIM/ΔHR slopes) using actual data provided similar relationships to lipid levels. We suggest that fitness measurements based on actually measured data may produce more accurate assessments of fitness and, ultimately, better approaches linking exercise to health in children.

Inter- and intra-subject variability of nitric oxide levels in leukocyte subpopulations.

Assessment of nitric oxide (NO) dynamics in immune cells, commonly measured using NO surrogates such as inducible nitric oxide synthase (iNOS) rather than NO itself, has been effective in understanding pathophysiology across a wide range of diseases. Although the intracellular measurement of NO is now feasible, many technical issues remain unresolved. The principle aim of our study was to determine the effect of storage time of whole blood on nitric oxide (NO) level expression in leukocytes. This is important because immune cells remain chemically dynamic even after they are removed from the circulation, and the impact of storage time must be known to optimally quantify the effect of a disease or condition on NO dynamics in circulating leukocytes. We measured NO levels using the fluorescent probe, diaminofluorescein (DAF-2DA), and flow cytometry in monocytes, neutrophils, and natural killer cells from healthy subjects immediately after blood draw (Time 0) and 30, 60, and 120 min following the blood draw. There was no significant difference among the 4 study time points in NO (DAF-2) levels, though there was wide intra-subject variability at all time points. Using LPS stimulation, we compared iNOS (the more traditional surrogate marker of NO dynamics) with NO (by DAF-2) in natural killer cells and monocytes and, we found no difference in the response patterns. In summary, we did find that within a 2-hour interval from blood draw to sample processing, there was a remarkably wide intra-subject variability in expression of intracellular NO (DAF-2) in leukocytes of healthy individuals at baseline and over time. The mechanism(s) for these differences are not known but could clearly confound efforts to detect changes in NO metabolism in white blood cells. We speculate that rapid pulsatility of NO could explain the wide variability seen.

Glucocorticoid receptor expression on circulating leukocytes in healthy and asthmatic adolescents in response to exercise.

BackgroundPoor aerobic fitness is associated with worsening of asthma symptoms, and fitness training may improve asthma control. The mechanism linking fitness with asthma is not known. We hypothesized that repeated bouts of exercise would lead to a downregulation of glucocorticoid receptor (GR) expression on circulating leukocytes, reflecting a reduced responsiveness to stress.MethodsIn a prospective exercise training intervention of healthy and asthmatic adolescents, GR expression in leukocytes was measured using flow cytometry in response to an acute exercise challenge before and after the exercise training intervention. Peripheral blood mononuclear cell (PBMC) gene expression of GR, GRß, HSP70, TGFß1, and TGFß2 was determined using reverse-transcriptase PCR (RT-PCR).ResultsPeak VO2 increased by 14.6±2.3%, indicating an effective training (P<0.01). There was a significant difference in GR expression among leukocyte subtypes, with highest expression in eosinophils. Following the exercise training intervention, there was a significant decrease in baseline GR expression (P<0.05) in leukocyte and monocyte subtypes in both healthy and asthmatic adolescents.ConclusionsThis is the first study in adolescents to show that exercise training reduces GR expression in circulating leukocytes. We speculate that exercise training downregulates the stress response in general, manifested by decreased GR expression, and may explain why improving fitness improves asthma health.

Sex Differences in the Relationship between Fitness and Obesity on Risk for Asthma in Adolescents.

OBJECTIVE: To evaluate the relationship of fitness and obesity on asthma risk in adolescent girls and boys. STUDY DESIGN: A cross-sectional assessment of participants 12-19 years of age was conducted by the use of data from the 1999-2004 National Health and Nutrition Examination Survey. Participants completed cardiorespiratory fitness testing, body composition measurements, and respiratory questionnaires. RESULTS: A total of 4828 participants were included. Overweight/obesity was associated with increased odds of history of asthma (aOR 1.63, 95% CI 1.16-2.30), current asthma (aOR 1.73, 95% CI 1.13, 2.64), and wheezing (aOR 1.40, 95% CI 1.03-1.91) in girls. Overweight/obesity also was associated with increased odds of asthma attacks (aOR 2.67, 95% CI 1.56-4.65) and wheezing related to exercise (aOR 1.60, 95% CI 1.07-2.38) in girls. High fitness was associated with lower odds of asthma-related visits to the emergency department (aOR 0.24, 95% CI 0.07-0.89), wheezing-related medical visits (aOR 0.31, 95% CI 0.13-0.75), wheezing-related missed days (aOR 0.14, 95% CI 0.06-0.33), and wheezing related to exercise (aOR 0.43, 95% CI 0.24-0.76) in boys. CONCLUSION: Overweight/obesity is associated with increased asthma prevalence and morbidity in girls but not in boys, independent of fitness. High fitness is associated with decreased rates of asthma morbidity in boys but not in girls, independent of weight status. Obesity and fitness may each influence asthma onset and severity in different ways for girls compared with boys.

Atopy, but not obesity is associated with asthma severity among children with persistent asthma.

BACKGROUND AND OBJECTIVE: Obesity is associated with an increased risk of asthma in children. Atopic sensitization is a major risk factor for asthma including severe asthma in children. It is unclear if obesity is associated with worse asthma control or severity in children and how its effects compare to atopy. We sought to examine relationships of weight status and atopy to asthma control and severity among a population of predominantly low income, minority children and adolescents with persistent asthma. METHODS: A cross-sectional analysis of 832 children and adolescents, age range 5-17 years, with persistent asthma was performed. Clinical assessments included asthma questionnaires of symptoms, asthma severity score, health care utilization and medication treatment step, lung function testing, and skin prick testing as well as measures of adiposity. Data were collected between December 2010 and August 2014 from Johns Hopkins Hospital in Baltimore, MD and Children's Hospital of Boston, MA. RESULTS: Obesity was not associated with worse asthma control or severity in this group of predominantly low income, minority children and adolescents with persistent asthma. However, a greater degree of atopy was associated with lower lung function, higher asthma severity score, and higher medication treatment step. CONCLUSION: Atopy may be a more important risk factor for asthma severity than obesity among low-income minority children and adolescents with persistent asthma living in Northeastern cities in the United States.

Obesity, Asthma, and Exercise in Child and Adolescent Health.

Obesity increases the risk of asthma throughout life but the underlying mechanisms linking these all too common threats to child health are poorly understood. Acute bouts of exercise, aerobic fitness, and levels of physical activity clearly play a role in the pathogenesis and/or management of both childhood obesity and asthma. Moreover, both obesity and physical inactivity are associated with asthma symptomatology and response to therapy (a particularly challenging feature of obesity-related asthma). In this article, we review current understandings of the link between physical activity, aerobic fitness and the asthma-obesity link in children and adolescents (e.g., the impact of chronic low-grade inflammation, lung mechanics, and direct effects of metabolic health on the lung). Gaps in our knowledge regarding the physiological mechanisms linking asthma, obesity and exercise are often compounded by imprecise estimations of adiposity and challenges of assessing aerobic fitness in children. Addressing these gaps could lead to practical interventions and clinical approaches that could mitigate the profound health care crisis of the increasing comorbidity of asthma, physical inactivity, and obesity in children.

Being overweight increases susceptibility to indoor pollutants among urban children with asthma.

BACKGROUND: Both being overweight and exposure to indoor pollutants, which have been associated with worse health of asthmatic patients, are common in urban minority populations. Whether being overweight is a risk factor for the effects of indoor pollutant exposure on asthma health is unknown. OBJECTIVES: We sought to examine the effect of weight on the relationship between indoor pollutant exposure and asthma health in urban minority children. METHODS: One hundred forty-eight children (age, 5-17 years) with persistent asthma were followed for 1 year. Asthma symptoms, health care use, lung function, pulmonary inflammation, and indoor pollutants were assessed every 3 months. Weight category was based on body mass index percentile. RESULTS: Participants were predominantly African American (91%) and had public health insurance (85%). Four percent were underweight, 52% were normal weight, 16% were overweight, and 28% were obese. Overweight or obese participants had more symptoms associated with exposure to fine particulate matter measuring less than 2.5 µm in diameter (PM2.5) than normal-weight participants across a range of asthma symptoms. Overweight or obese participants also had more asthma symptoms associated with nitrogen dioxide (NO2) exposure than normal-weight participants, although this was not observed across all types of asthma symptoms. Weight did not affect the relationship between exposure to coarse particulate matter measuring between 2.5 and 10 µm in diameter and asthma symptoms. Relationships between indoor pollutant exposure and health care use, lung function, or pulmonary inflammation did not differ by weight. CONCLUSION: Being overweight or obese can increase susceptibility to indoor PM2.5 and NO2 in urban children with asthma. Interventions aimed at weight loss might reduce asthma symptom responses to PM2.5 and NO2, and interventions aimed at reducing indoor pollutant levels might be particularly beneficial in overweight children.

Breathing Room: Industrial Zoning and Asthma Incidence Using School District Health Records in the City of Santa Ana, California.

Background: Traffic and industrial emissions are associated with increased pediatric asthma morbidity. However, few studies have examined the influence of city industrial zoning on pediatric asthma outcomes among minoritized communities with limited access to air monitoring. Methods: In this cross-sectional analysis of 39,974 school-aged students in Santa Ana, CA, we investigated the effect of proximity to areas zoned for industrial use on pediatric asthma prevalence, physical fitness, school attendance, and standardized test scores. Results: The study population was 80.6% Hispanic, with 88.2% qualifying for free/reduced lunch. Compared to students living more than 1 km away from industrial zones, those living within 0.5 km had greater odds of having asthma (adjusted OR 1.21, 95% CI 1.09 to 1.34, p < 0.001). Among children with asthma, those living between 0.5−1.0 km had greater odds of being overweight or obese (aOR 1.47, 95% CI 1.00, 2.15, p = 0.047). Industrial zone proximity was not significantly associated with worse fitness and academic outcomes for students with asthma. Conclusion: These findings suggest that industrial zone proximity is associated with increased pediatric asthma in a predominantly Latino community in Southern California.

US School-Based Physical Fitness Assessments and Data Dissemination.

BACKGROUND: Low physical fitness (PF) levels during childhood affect healthy growth and development, and increase the risk of cardiovascular diseases. Physical education standards exist for nearly all states in the United States, but evaluation of PF in youth has yet to be systematic, reproducible, and harmonized. The purpose of this project was to describe publicly available data of school-based PF testing (SB-PFT). METHODS: A list of state-mandated SB-PFT programs published by SHAPE 2016 was confirmed by contacting appropriate authorities. SB-PFT data were obtained through each state's department of education. RESULTS: Sixteen states mandate SB-PFT, with 10 states providing publicly available data; 92% to 100% of states perform the pacer/mile, curl-up, and push-up; 54.2% to 78.5% of elementary and 44% to 66.5% of high-school youth are in the "healthy fitness zone" for aerobic capacity. CONCLUSIONS: SB-PFT provided PF data in children across the United States. The variability and inconsistency in reporting and in the values, however, raises questions about the current status of SB-PFT data and its utility in assessing PF in children. The critical nature of PF assessments is highlighted in the current COVID-19 pandemic, during which physical education has been curtailed, and emerging data demonstrate worsening of the already low levels of PF in youth.

Low fitness and increased sedentary time are associated with worse asthma-The National Youth Fitness Survey.

BACKGROUND: Asthma is the most common chronic illness in children and is independently impacted by obesity and by fitness. The National Youth Fitness Survey collected data on aerobic fitness, body composition, and health outcomes in children 6 to 11 years old. The goal of this study is to test hypotheses regarding relationships between asthma, aerobic fitness, and sedentary time in this uniquely studied cohort of young children. METHODS: A total of 665 children (6-11 years old; 49% male) were included in analyses. We explored relationships between asthma outcomes and aerobic fitness (measured by endurance time), self-reported sedentary time, and body mass index categories. Fitness was categorized as unfit (lowest 25% of endurance times) or fit. Multivariate logistic regression models were created for asthma outcomes and adjusted for race, age, sex, poverty status, and overweight/obesity. RESULTS: Among the participants, 17.9% had a previous history of asthma and 11.4% had current asthma. Additionally, 37.3% of participants were overweight or obese. Low fitness was significantly associated with increased odds of past asthma, current asthma, asthma attacks, wheeze with exercise, and wheeze with activity limitations in multivariate models. Increased sedentary time was significantly associated with increased odds of previous asthma, current asthma, asthma attacks, and wheeze with activity limitations. CONCLUSION: Decreased aerobic fitness and increased sedentary time were associated with worse asthma outcomes in this group of children (6-11 years old). This data suggest that fitness and sedentary time, both modifiable factors, each have an independent effect on asthma and should be included in assessments and management of asthma health.

Weight Loss for Children and Adults with Obesity and Asthma. A Systematic Review of Randomized Controlled Trials.

Background: Asthma and obesity are major public health problems, affecting hundreds of millions of people worldwide. Obesity is associated with increased asthma risk and severity, and lower asthma-related quality of life. Objective: In this systematic review, we aimed to evaluate whether weight loss in subjects with obesity and asthma leads to improvement in asthma-related outcomes. Data Sources and Extraction: We searched PubMed and Google Scholar for all studies in English published January 2000-December 2018. Studies were included if they were randomized, controlled clinical trials (RCTs) for overweight/obese children or adults with asthma, with sufficient data to assess outcomes and study quality. Non-randomized and non-controlled studies were excluded, as well as those in subjects without overweight/obesity, or with non-asthmatic controls. Synthesis: We identified four RCTs involving children (total n = 246) and six involving adults (n = 502). All interventions were designed for weight loss and varied from dietary restrictions to multifactorial interventions with exercise training and cognitive behavioral therapy; the duration of intervention ranged from 8 weeks to 18 months. All RCTs reported successful improvements in weight or body mass index (-0.14 standard deviation scores to -15.9% BMI reduction in children, 1.8%-14.5% weight loss in adults). RCTs generally reported improvements in asthma-related quality of life and, to some degree, asthma control. RCTs involving adults also reported improvements in lung function (FEV1, FVC, TLC), while RCTs in children showed less consistent results. Conclusions: These findings suggest that weight loss in subjects with obesity and asthma may improve asthma outcomes. However, there was wide variability in populations studied, baseline and post-intervention assessments, follow-up length, outcome definition and reporting, and statistical approaches, which hindered the ability to compare studies, perform a pooled analysis, or assess generalizability. Primary Source of Funding: U.S. National Institutes of Health (NIH).

A Six Week Therapeutic Ballet Intervention Improved Gait and Inhibitory Control in Children With Cerebral Palsy-A Pilot Study.

Children with cerebral palsy (CP) have motor impairments that make it challenging for them to participate in standard physical activity (PA) interventions. There is a need to evaluate adapted PA interventions for this population. Dance can promote coordination, posture, muscle strength, motor learning, and executive functioning. This pilot study evaluated the feasibility and the effects of a new therapeutic ballet intervention specifically designed for children with CP. Methods: Eight children with CP (9-14 y/o; 75% female) participated in a 6-week therapeutic ballet intervention. Outcomes were measured in multiple domains, including body composition (DXA), muscle strength (hand-grip dynamometer), habitual physical activity, gait and selective motor control functions, and executive functioning. Follow-up assessments of habitual physical activity, gait, and executive functioning were completed 4 to 5 weeks post-intervention. Results: Five of the eight participants were overfat or obese based on DXA percentage of body fat. All participants were below the 50th percentile for their age and gender for bone density. Four participants showed a trend to improve hand-grip strength in one hand only, while one improved in both hands. There were significant improvements in gait across time points (pre, post, and follow-up), specifically in time of ambulation (X pre = 4.36, X post = 4.22, X follow-up = 3.72, d = 0.056, p = 0.02), and in step length (cm) on the right: X pre = 48.29, X post = 50.77, X follow-up = 52.11, d = 0.22, p = 0.027, and left stride: X pre = 96.29, X post = 102.20, X follow-up = 104.20, d = 0.30, p = 0.027, indicating gait changes in bilateral lower extremities. There was improvement in inhibitory control (d = 0.78; 95% Confidence Limit = ±0.71, p < 0.05) with large individual responses primarily among those above the mean at baseline. Conclusions: Therapeutic ballet may prove to be a useful intervention to promote physiological and cognitive functions in children with CP. Results demonstrated feasibility of the physical, physiological, and cognitive assessments and suggested improvements in participants' gait and inhibitory control with large individual responses. Modifications to personalize the intervention may be needed to optimize positive outcomes. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03681171.

Four Months of a School-Based Exercise Program Improved Aerobic Fitness and Clinical Outcomes in a Low-SES Population of Normal Weight and Overweight/Obese Children With Asthma.

Introduction: Fitness can improve asthma management. However, children from disadvantaged and minority communities generally engage less in physical activity, and have increased obesity and asthma disease burden. The goal of this pilot study is to evaluate (1) the feasibility of an exercise intervention program in a school-based setting (attendance and fitness improvement) and (2) the effect of the intervention on fitness, asthma, and clinical outcomes in normal weight and overweight/obese children with asthma from low-SES population. Materials and Methods: Nineteen children, ages 6-13 years, from two elementary schools in Santa Ana, CA, a population with high percentage of Hispanic and low socioeconomic status, participated. Training sessions occurred at the schools during afterschool hours (3 sessions weekly × 4 months) and included mainly aerobic age-appropriate activities/games and a small component of muscle strength. Before and after the intervention, evaluations included pulmonary function testing, cardiopulmonary exercise testing (peak V ˙ O2), assessments of habitual physical activity, body composition (DXA), asthma questionnaires, and blood (cardiometabolic risk factors). Results: Seventeen of 19 participants completed the study. Adherence to the program was 85%. Based on BMI %ile, 11 of the participants were overweight/obese and 8 were normal weight. Ten participants had persistent asthma and 9 children had intermittent asthma. Training was effective as peak V ˙ O2 improved significantly (8.1%, SD ± 10.1). There was no significant change in BMI %ile but a significant improvement in lean body mass (1%, SD ± 2.0) and decrease in body fat (1.9%, SD ± 4.6). Asthma quality of life outcomes improved following the intervention in symptoms, emotional function, and overall. There was no change in asthma control or pulmonary function. Five of 10 participants with persistent asthma decreased their maintenance medications. Lipid levels did not change except HDL levels increased (46.1 ± 8.4 mg/dL to 49.5 ± 10.4 mg/dL, p = 0.04). Discussion: A school-based exercise intervention program designed specifically for children with asthma for a predominantly economically disadvantaged and minority population was feasible with good adherence to the program and substantial engagement from the schools, families and participants. The exercise intervention was effective with improvement in aerobic fitness, body composition, asthma quality of life, and lipid outcomes, setting the stage for a larger multicenter trial designed to study exercise as an adjunct medicine in children with asthma.

Glucocorticoid receptor expression on circulating leukocytes differs between healthy male and female adults.

INTRODUCTION: The glucocorticoid receptor (GR) is a key receptor involved in inflammatory responses and is influenced by sex steroids. This study measured GR expression on circulating leukocyte subtypes in males and females. METHODS: A total of 23 healthy adults (12 female) participated in this study. GR expression was measured in leukocyte subtypes using flow cytometry. Peripheral blood mononuclear cell (PBMC) gene expression of GR (NR3C1), GR ß, TGF-ß1 and 2, and glucocorticoid-induced leucine zipper (GILZ) were determined by real-time polymerase chain reaction. RESULTS: Leukocyte GR was lower in females, particularly in granulocytes, natural killer cells, and peripheral blood mononuclear cells (p≤0.01). GR protein expression was different across leukocyte subtypes, with higher expression in eosinophils compared with granulocytes, T lymphocytes, and natural killer cells (p<0.05). There was higher gene expression of GR ß in males (p=0.03). CONCLUSIONS: This is the first study to identify sexual dimorphism in GR expression in healthy adults using flow cytometry. These results may begin to explain the sexual dimorphism seen in many diseases and sex differences in glucocorticoid responsiveness.