High plasma IL-6 levels may enhance the adverse effects of mouse allergen exposure in urban schools on asthma morbidity in children.

BACKGROUND: Few data on the relationships between environmental exposures, asthma morbidity, and systemic IL-6 inflammation exist. OBJECTIVE: We sought to determine whether baseline plasma IL-6 level is associated with increased asthma morbidity in children exposed to mouse allergen in inner-city classrooms. METHODS: Data from the longitudinal School Inner-City Asthma Studies of 215 children with asthma, aged 4 to 14 years and recruited from urban elementary schools, were analyzed. Given the unknown threshold of IL-6 risk levels and skewness of the distribution, the children were stratified into tertiles as follows: low baseline IL-6 level (<0.013 pg/mL), moderate baseline IL-6 level (0.013-0.302 pg/mL), and high baseline IL-6 level (>0.302 pg/mL). Relationships between plasma IL-6 level and body mass index (BMI) percentile, inflammatory markers, lung function, mouse allergen exposure, and asthma outcomes were assessed. RESULTS: Cross-sectional analysis demonstrated that increasing IL-6 level was associated with higher BMI percentile (P < .0001), C-reactive protein level (P = .0006), and blood neutrophil count (P = .0024). IL-6 was not associated with type 2 inflammatory markers, including blood eosinophil count, allergic sensitization, or fractional exhaled nitric oxide level. Longitudinal analysis showed that children with high IL-6 levels had a higher number of days with asthma symptoms than did those children with moderate (incidence rate ratio = 1.74 [95% CI = 1.10-2.77]; P = .0187) or low (incidence rate ratio =1.83 [95% CI = 1.21-2.77]; P = .0043) IL-6 levels. Children with high IL-6 levels who were exposed to increasing levels of mouse allergen exhibited lower ratios of FEV1 value to forced vital capacity than did children with moderate IL-6 levels (ß = -0.0044 [95% CI = -0.0073 to -0.0015]; pairwise interaction P = .0028) or low IL-6 levels (ß = -0.0042 [95% CI = - 0.0070 to -0.0013]; pairwise interaction P = .0039). CONCLUSIONS: Inner-city children with asthma and high plasma IL-6 levels are more likely to have an increased BMI, elevated C-reactive protein level, elevated blood neutrophil count, and greater asthma symptoms. High IL-6 level appears to increase susceptibility to the effects of classroom exposure to mouse allergen on lung function in urban children.

Impact of Air Pollution on Atopic Dermatitis: A Comprehensive Review.

Air pollution is associated with multiple health problems worldwide, contributing to increased morbidity and mortality. Atopic dermatitis (AD) is a common allergic disease, and increasing evidence has revealed a role of air pollution in the development of atopic dermatitis. Air pollutants are derived from several sources, including harmful gases such as nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), as well as particulate matter (PM) of various sizes, and bioaerosols. Possible mechanisms linking air pollution to atopic dermatitis include damage to the skin barrier through oxidative stress, increased water loss, physicochemical injury, and an effect on skin microflora. Furthermore, oxidative stress triggers immune dysregulation, leading to enhanced sensitization to allergens. There have been multiple studies focusing on the association between various types of air pollutants and atopic dermatitis. Since there are many confounders in the current research, such as climate, synergistic effects of mixed pollutants, and diversity of study population, it is not surprising that inconsistencies exist between different studies regarding AD and air pollution. Still, it is generally accepted that air pollution is a risk factor for AD. Future studies should focus on how air pollution leads to AD as well as effective intervention measures.

Defects of the Innate Immune System and Related Immune Deficiencies.

The innate immune system is the host's first line of defense against pathogens. Toll-like receptors (TLRs) are pattern recognition receptors that mediate recognition of pathogen-associated molecular patterns. TLRs also activate signaling transduction pathways involved in host defense, inflammation, development, and the production of inflammatory cytokines. Innate immunodeficiencies associated with defective TLR signaling include mutations in NEMO, IKBA, MyD88, and IRAK4. Other innate immune defects have been associated with susceptibility to herpes simplex encephalitis, viral infections, and mycobacterial disease, as well as chronic mucocutaneous candidiasis and epidermodysplasia verruciformis. Phagocytes and natural killer cells are essential members of the innate immune system and defects in number and/or function of these cells can lead to recurrent infections. Complement is another important part of the innate immune system. Complement deficiencies can lead to increased susceptibility to infections, autoimmunity, or impaired immune complex clearance. The innate immune system must work to quickly recognize and eliminate pathogens as well as coordinate an immune response and engage the adaptive immune system. Defects of the innate immune system can lead to failure to quickly identify pathogens and activate the immune response, resulting in susceptibility to severe or recurrent infections.

The Indoor Environment and Childhood Asthma.

PURPOSE OF REVIEW: Sensitization and exposure to triggers in the indoor environment, including aeroallergens, indoor air pollution, and environmental tobacco smoke, have a significant role in asthma development and morbidity. This review discusses indoor environmental exposures and their effect on children with asthma as well as environmental interventions and their role in improving asthma morbidity. RECENT FINDINGS: Recent research has emphasized the role of aeroallergen sensitization and exposure in asthma morbidity and the importance of the school indoor environment. There is an established association between indoor exposures and asthma development and morbidity. Recent evidence has highlighted the importance of the indoor environment in childhood asthma, particularly the role of the school indoor environment. While home environmental interventions have had mixed results, interventions in the school environment have the potential to significantly impact the health of children, and ongoing research is needed to determine their effectiveness.

Allergic Endotypes and Phenotypes of Asthma.

Allergic asthma is defined as asthma associated with sensitization to aeroallergens, which leads to asthma symptoms and airway inflammation. Allergic asthma is the most common asthma phenotype. The onset of allergic asthma is most often in childhood and is usually accompanied by other comorbidities including atopic dermatitis and allergic rhinitis. It is often persistent although there is a wide variation in disease severity. It is a TH2-driven process. Biomarkers have been identified to distinguish patients with allergic asthma, particularly serum IgE levels, tests to indicate sensitization to aeroallergens such as specific IgE or skin prick test positivity, blood and sputum eosinophil levels, fraction of exhaled nitric oxide, and periostin. Treatments for allergic asthma include environmental control measures, allergen immunotherapy, and glucocorticoids. Biologics, targeting the TH2 pathway, have been shown to be effective in the treatment of allergic asthma.

Problem Representation, Background Evidence, Analysis, Recommendation: An Oral Case Presentation Tool to Promote Diagnostic Reasoning.

Oral case presentations provide an opportunity for trainees to communicate diagnostic reasoning at the bedside. However, few tools exist to enable faculty to provide effective feedback. We developed a tool to assess diagnostic reasoning and communication during oral case presentations.

Is the "July Effect" Real? Pediatric Trainee Reported Medical Errors and Adverse Events.

INTRODUCTION: The "July Effect" suggests an increase in patient adverse events in July compared with other months due to the introduction of new providers throughout the training continuum. The aim of this initiative was to analyze reported pediatric trainee medical errors from May through September 2015 at a tertiary care free-standing academic children's hospital to determine if there were more reported medical errors and more adverse events from those errors in July. METHODS: An error surveillance system is used to report and track near misses, adverse events, and medical errors. Three of the authors reviewed each report, which was electronically collected in the institution during the time period of interest. The reported medical error incidence per 1,000 trainee-days was compared against those in July for a significant difference. RESULTS: There are a total of 282 trainees (86 pediatric residents, 81 nonpediatric residents, and 115 fellows) who are clinically active in the hospital at any given month. Pediatric residents had more reported medical errors in July (31) compared with May (16; P = 0.015), June (16; P = 0.019), and August (19; P = 0.046). There was no significant difference in the number of adverse events from reported medical errors by trainees in July (7) compared with May (5), June (8), August (4), or September (8; P > 0.2). CONCLUSION: In this single-center evaluation, there is an increase in reported medical errors involving pediatric residents in July compared with the months surrounding July. However, there is no difference in numbers of adverse events from those errors between these months.