Sex effects in the association between airway microbiome and asthma.

BACKGROUND: Sex differences exist in asthma susceptibility and severity. Accumulating evidence has linked airway microbiome dysbiosis to asthma, and airway microbial communities have been found to differ by sex. However, whether sex modifies the link between airway microbiome and asthma has not been investigated. OBJECTIVE: To evaluate sex effects in the association between airway microbiome and asthma. METHODS: We analyzed induced sputum samples from 47 subjects (n = 23 patients with asthma and n = 24 normal controls) using 16S ribosomal RNA gene sequencing methods. The bacterial composition was analyzed for sex differences. Bacterial associations with asthma were assessed for each sex at the core taxa and genus levels. RESULTS: The microbiome in induced sputum differed in women vs men at the community level. A total of 5 core bacterial taxa were found in all samples. No sex-specific core taxa were detected. The most abundant core taxon, Streptococcus salivarius, was significantly enriched in women than in men (P = .02). Within each sex, individuals with relatively lower abundance of S salivarius were more likely to have asthma (P = .006). For both sexes, increased Lactobacillus species were found in sputum samples of patients with patients compared with normal controls (adjusted P = .01). Haemophilus species were associated with asthma in men and not in women. CONCLUSION: The airway microbiome differed by sex, and sex effects exist in the association of airway microbial markers and asthma. Future airway microbiome studies may yield better resolution if the context of specific sex is considered. The airway microbiome is a potential mechanism driving sex differences in asthma.

Modeling Ketogenesis for Use in Pediatric Diabetes Simulation.

BACKGROUND: Simulation is being increasingly integrated into medical education. Diabetes simulation is well-received by trainees and has demonstrated improved clinical results, including reduced adult inpatient hyperglycemia. However, no pediatric-specific diabetes simulation programs exist for use in medical education. None of the existing diabetes models incorporate ketones as an input or an output, which is essential for use in teaching pediatric diabetes management. METHODS: We created a pediatric diabetes simulation incorporating both blood sugar and urine ketones as output. Ketone output is implemented as a state variable but is obfuscated to simulate hospital experience. Blood sugar output is similar to other models and incorporates the current blood sugar, insulin on board (IOB) and carbohydrates on board (COB), and insulin and carbohydrate sensitivities. The program calculates all IOB and COB every 15 minutes based on user input and provides written summary feedback at the end of the simulation about inaccurate dosing and timing. RESULTS: The simulation realistically incorporated both blood glucose and urine ketones in clinically valid and actionable formats. After completing this simulation, 16/17 pediatric residents indicated that they wanted more simulated diabetes cases integrated into their curriculum. CONCLUSION: Implementing simulation into pediatric diabetes education was feasible and well-received. More work is needed to further study the role of simulation in pediatric diabetes education when used adjunctively or in lieu of lectures when time or resources are limited.

A Pragmatic Trial of Symptom-Based Inhaled Corticosteroid Use in African-American Children with Mild Asthma.

BACKGROUND: Symptom-based adjustment (SBA) of inhaled corticosteroids may be an alternative patient-centered approach in which day-to-day inhaled corticosteroid use is adjusted by symptoms and short-acting ß-agonist need. OBJECTIVE: To evaluate the effectiveness of SBA in the primary care setting. METHODS: We conducted a randomized, open-label, pragmatic equivalence trial in African-American children (6-17 years old) with mild asthma managed by 12 primary care providers (PCPs). A total of 206 participants were randomized to SBA (as-needed beclomethasone 80 µg with rescue short-acting ß-agonist) or provider-based guideline-directed adjustment (PBA): maintenance beclomethasone 80 µg/d (6-11 years old), 160 µg/d (12-17 years old), with subsequent guideline-based dose adjustment by PCPs. PCPs implemented both treatment assignments, with outcomes measured by blinded staff. All participants received symptom recognition and albuterol use education from peer educators. Primary outcome was change in asthma control (measured by Asthma Control Test [ACT]/childhood ACT [cACT]) over 12 months. RESULTS: Participants had adequately controlled asthma (mean ACT or cACT score = 21.6 ± 2.8) at baseline. After 1 year, there was no significant between-group difference in change in ACT scores (SBA - PBA): ACT: -0.88 (95% CI, -2.19 to 0.42), cACT: -0.73 (-2.09 to 0.62), or combined ACT and cACT (P = .10), and was within the predefined statistical clinical equivalence. The proportion with an exacerbation and measures of lung function were similar between groups. Compared with PBA, SBA led to less beclomethasone use (SBA: 526 µg/mo [95% CI, 412-639 µg] vs PBA: 1961 µg/mo [95% CI, 1681-2241]; P < .0001). More parents in the SBA arm felt they were managing their child's asthma. CONCLUSIONS: SBA in African-American children with mild asthma was similar to PBA in asthma control and events when implemented by PCPs with lower inhaled corticosteroid exposure.

Gender and race influence metabolic benefits of fitness in children: a cross-sectional study.

BACKGROUND: Increasing obesity and poor cardiovascular fitness (CVF) contribute to higher rates of type 2 diabetes mellitus (T2DM) in children. While the relative contributions of fitness and body fat on development of insulin resistance (IR) in children and adolescents remains unresolved, gender- and race-specific differences likely exist in the degree to which CVF influences IR and risk for T2DM. Better understanding of how gender and race affect interactions between body fat, CVF, and metabolic health would be helpful in designing effective and targeted strategies to reduce obesity-associated disease risk. We evaluated whether metabolic benefits of fitness on reducing inflammation and insulin resistance (IR) are affected by gender and race. METHODS: This cross-sectional study included 203 healthy children (mean age 12.2 y, 50% male, 46% non-Hispanic white (NHW), 54% racially diverse (RD)). Fasting insulin, glucose, hsCRP, and adiponectin were measured; race was self-reported; cardiovascular fitness (CVF) was evaluated by the Progressive Aerobic Cardiovascular Endurance Run. Associations between inflammation and gender, race, and CVF were evaluated using analysis of covariance. Multivariate regression analysis identified independent predictors of IR. RESULTS: Fitness and inflammation were inversely related in both males and females (p < 0.01); this effect was marginally stronger in RD children (p = 0.06) and non-overweight males (p = 0.07). High BMI (p < 0.001), low fitness (p = 0.006), and (female) gender (p = 0.003) were independently associated with higher HOMA-IR. In males, BMI and fitness, but not race independently predicted HOMA-IR. In females, BMI and race, but not fitness independently predicted HOMA-IR. CONCLUSIONS: In middle school children, the beneficial effects of fitness vary based on gender and race. High CVF has an enhanced anti-inflammatory effect in male and RD children. While BMI is the strongest predictor of IR in the study group as a whole, fitness is a significant predictor of IR only in males, and race is a significant predictor of IR only in females.

Boosting The Late Blooming Male: Use of growth promoting agents in the athlete with constitutional delay of growth and puberty.

CONTEXT: The indications for use of growth hormone (GH) have broadened with the availability of unlimited recombinant human growth hormone (rhGH). The FDA's approval for use of growth hormone in GH-sufficient patients with idiopathic short stature includes some children with constitutional delay of growth and puberty (CGD), a normal growth pattern variation which includes delayed puberty and prolonged linear growth, usually leading to normal adult height. Use of rhGH to increase growth in short-statured children with CGD has been challenged for its modest efficacy in increasing ultimate height, high cost, limited evidence for psychosocial benefit, and some unresolved concerns about long-term post-treatment safety. An additional controversy for the young athlete with CGD is the concern for fairness in competition. EVIDENCE ACQUISITION: Data sources were limited to peer-reviewed publications. RESULTS: RhGH is a safe and effective therapy for increasing growth rate in very short children with CGD, but does not markedly increase ultimate stature nor confer a clear benefit in athletic performance. (SORT A) CONCLUSIONS: Prescribing physicians should use rhGH treatment responsibly to bring children disabled by short stature just into the "normal" range. (SORT C).

An after-school exercise program improves fitness, and body composition in elementary school children.

Reduced cardiovascular fitness (CVF) is a risk factor for obesity and cardiovascular disease. It has previously shown that a school-based fitness curriculum can improve CVF, and other health indicators in middle school aged children. Whether an afterschool program improves CVF and other health markers in elementary-school children is unresolved. The objective of this study was therefore to determine whether an on-site afterschool-based fitness program improves body composition, cardiovascular fitness level, in elementary school children. 80 elementary school children were evaluated in a "fitness-oriented" afterschool program managed by the local YMCA. Children underwent evaluation of cardiovascular fitness by maximal VO2 treadmill testing and body composition by dual x-ray absorptiometry (DXA), at baseline (prior to the school-year) and again at end of the school year. Findings revealed that, at baseline, children had a mean age of 8.8 years, BMI of 18.7± 3, with a maximal VO2 of 40.03 ± 7.6 ml/kg/min, and percent body fat of 28.7 ± 7%. After a 9-month intervention, children maximal VO2 increased to 44.8 ± 7.5 ml/kg/min (p=0.04) and percent body fat decreased to 25.8 ± 6.2% (p=0.033). The study concluded that on-site afterschool programming focusing on fitness improved body composition and cardiovascular fitness, in elementary school children. Combined with prior studies, these data demonstrate that afterschool-based fitness curricula can benefit both obese and non-obese children. It was therefore recommended that, partnerships with schools to promote fitness even outside of school time should be a part of a school approach to improving children's health.

Community Asthma Program improves appropriate prescribing in moderate to severe asthma.

Asthma guidelines, established by the National Asthma Education and Prevention Panel (NAEPP), seek to guide physicians in the appropriate assessment and treatment of asthma. Poor physician adherence to these guidelines has been documented because of a variety of reported barriers. We sought to test the efficacy of the Community Asthma Program (CAP), which was designed to help primary care physicians (PCP) assess asthma severity and to prescribe medications according to NAEPP guidelines. A prospective, observational study was conducted in 723 patients with asthma (aged < 1-85 years) in two primary care clinics. PCPs had access to patient responses to asthma symptom questions at each visit. The correlations between patient self-reported and PCP-classified asthma severity, treatment prescribed, and missed days from work or school were determined. The effect of the intervention on guideline adherence was assessed by asthma severity level and time. An overall moderate measure of agreement was found between patient self-reported and PCP-classified asthma severity (kappa = 0.48; p < 0.001) although this agreement decreased with increasing severity of asthma. Patient self-reported (r = 0.14; p < 0.001) and PCP-classified (r = 0.17; p < 0.001) asthma severity was weakly correlated with missed days from work or school. Those with severe persistent asthma were 89% less likely to be appropriately treated than the mild intermittent group (OR = 0.11; 95% CI-0.1-0.2). This relationship was not influenced by the different clinics or providers nor by the age of the patient. Over time, the CAP-trained PCPs were more likely to appropriately prescribe asthma medications for those with moderate to severe asthma (Mantel-Haenszel chi2 = 5.11; p = 0.02). Despite appropriate assessment of asthma severity, physicians are undertreating patients with severe asthma, the group with the highest health care use. Use of the CAP over time aided PCPs in appropriately medicating patients with moderate to severe asthma in accordance with guidelines.