Janet Rothers

Cord blood 25-hydroxyvitamin D levels are associated with aeroallergen sensitization in children from Tucson, Arizona

BACKGROUND The association between vitamin D status at birth and childhood allergic outcomes is uncertain. The desert climate of Tucson offers a unique setting for studying the health effects of higher exposure to vitamin D. OBJECTIVE To assess the relationship between cord blood 25-hydroxyvitamin D (25[OH]D) levels and allergic outcomes through age 5 years. METHODS Cord blood 25(OH)D levels were measured in 219 participants in the Tucson Infant Immune Study, a population-based birth cohort. Plasma total IgE and specific IgE levels to 6 aeroallergens were measured at 1, 2, 3, and 5 years. Skin prick test (SPT) positivity (wheal diameter ≥ 3 mm) and physician-diagnosed active allergic rhinitis and asthma were assessed at age 5 years. Longitudinal models were used to assess the relationship between 25(OH)D and IgE levels. Logistic regression models were used to assess the relationship of 25(OH)D level with SPT positivity, allergic rhinitis, and asthma. RESULTS The median cord blood 25(OH)D level was 64 nmol/L (interquartile range, 49-81 nmol/L). Relative to the reference group (50-74.9 nmol/L), both low (<50 nmol/L) and high (≥ 100 nmol/L) levels were associated with increased total IgE (coefficient = 0.27, P = .006 and coefficient = 0.27, P = .04, respectively) and detectable inhalant allergen-specific IgE (odds ratio = 2.4, P = .03 and odds ratio = 4.0, P = .01, respectively) through age 5 years. High 25(OH)D levels were also associated with increased SPT positivity (odds ratio = 4.0, P = .02). By contrast, the 25(OH)D level was not significantly associated with allergic rhinitis or asthma. CONCLUSION Both low and high levels of cord blood 25(OH)D were associated with increased aeroallergen sensitization. The association between vitamin D status and actual allergic diseases merits further study.

Community Health Workers and Community Advocacy: Addressing Health Disparities

The Community Health Worker model is recognized nationally as a means to address glaring inequities in the burden of adverse health conditions that exist among specific population groups in the United States. This study explored Arizona CHW involvement in advocacy beyond the individual patient level into the realm of advocating for community level change as a mechanism to reduce the structural underpinnings of health disparities. A survey of CHWs in Arizona found that CHWs advocate at local, state and federal political levels as well as within health and social service agencies and business. Characteristics significantly associated with advocacy include employment in a not for profit organization, previous leadership training, and a work environment that allows flexible work hours and the autonomy to start new projects at work. Intrinsic characteristics of CHWs associated with advocacy include their belief that they can influence community decisions, self perception that they are leaders in the community, and knowledge of who to talk to in their community to make change. Community-level advocacy has been identified as a core CHW function and has the potential to address structural issues such as poverty, employment, housing, and discrimination. Agencies utilizing the CHW model could encourage community advocacy by providing a flexible working environment, ongoing leadership training, and opportunities to collaborate with both veteran CHWs and local community leaders. Further research is needed to understand the nature and impact of CHW community advocacy activities on both systems change and health outcomes.

Perinatal Tumor Necrosis Factor-α Production, Influenced by Maternal Pregnancy Weight Gain, Predicts Childhood Asthma

RATIONALE Innate immune responses marked by increases in tumor necrosis factor (TNF)-α have been associated with asthma but whether such alterations are evident before symptoms is not yet clear. OBJECTIVES To determine if prevalence of childhood asthma or asthma-related traits is predicted by perinatal innate immune status and if maternal factors related to pregnancy influence asthma prevalence and innate immune status. METHODS In the Tucson Infant Immune Study (a nonselected birth cohort), presence of eczema and wheezing in the childs first year and physician-diagnosed asthma through age 9 and asthma in the parents was obtained from parent-completed questionnaires. TNF-α, IL-6, IL-10, and IL-12 were measured in supernatants of LPS-stimulated peripheral blood mononuclear cells at birth and 3 months as was TNF-α in plasma. TNF-α single nucleotide polymorphisms were genotyped by Sequenom. Percent predicted FEV1/FVC was measured at age 9. Maternal weight gain during pregnancy and prepregnancy weight were ascertained from medical records. MEASUREMENTS AND MAIN RESULTS Infants with persistently elevated LPS-induced TNF-α at birth and 3 months were at increased risk for childhood asthma (odds ratio [OR], 4.1; confidence interval [CI], 1.9-8.8; n = 233; P = 0.0003) and had decreased FEV1/FVC ratios at age 9. Children with mothers in the top tertile for pregnancy weight gain had increased risk for asthma (OR, 3.4; CI, 1.7-6.9; n = 225; P = 0.001) and persistently elevated TNF-α in early life (OR, 2.9; CI, 1.4-8.2; n = 195; P = 0.013). These relations were independent of maternal asthma and rhinitis. CONCLUSIONS Persistently elevated LPS-induced TNF-α production early in life acts as a predictive biomarker for childhood asthma, and excess pregnancy weight gain in the mother seems to contribute to both.

Relation of early antibiotic use to childhood asthma: confounding by indication?

Background Findings from studies of the relation between early antibiotic use and subsequent asthma have been inconsistent, which may be attributable to methodologic issues.

Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers.

Background The timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception. Objective We sought to assess whether the trajectory to asthma begins already at birth and whether epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception. Methods We used the Methylated CpG Island Recovery Assay chip to survey DNA methylation in cord blood mononuclear cells from 36 children (18 nonasthmatic and 18 asthmatic subjects by age 9 years) from the Infant Immune Study (IIS), an unselected birth cohort closely monitored for asthma for a decade. SMAD3 methylation in IIS (n = 60) and in 2 replication cohorts (the Manchester Asthma and Allergy Study [n = 30] and the Childhood Origins of Asthma Study [n = 28]) was analyzed by using bisulfite sequencing or Illumina 450K arrays. Cord blood mononuclear cell–derived IL‐1&bgr; levels were measured by means of ELISA. Results Neonatal immune cells harbored 589 differentially methylated regions that distinguished IIS children who did and did not have asthma by age 9 years. In all 3 cohorts methylation in SMAD3, the most connected node within the network of asthma‐associated, differentially methylated regions, was selectively increased in asthmatic children of asthmatic mothers and was associated with childhood asthma risk. Moreover, SMAD3 methylation in IIS neonates with maternal asthma was strongly and positively associated with neonatal production of IL‐1&bgr;, an innate inflammatory mediator. Conclusions The trajectory to childhood asthma begins at birth and involves epigenetic modifications in immunoregulatory and proinflammatory pathways. Maternal asthma influences epigenetic mechanisms that contribute to the inception of this trajectory. Graphical abstract Figure. No Caption available.

Prevalence of Asthma in School Children on the Arizona-Sonora Border

BACKGROUND Mexican-born children living in the United States have a lower prevalence of asthma than other US children. Although children of Mexican descent near the Arizona (AZ)-Sonora border are genetically similar, differences in environmental exposures might result in differences in asthma prevalence across this region. OBJECTIVE The objective of this study was to determine if the prevalence of asthma and wheeze in these children varies across the AZ-Sonora border. METHODS The International Study of Asthma and Allergy in Children written and video questionnaires were administered to 1753 adolescents from 5 middle schools: Tucson (school A), Nogales, AZ (schools B, C), and Nogales, Sonora, Mexico (schools D, E). The prevalence of asthma and symptoms was compared, with analyses in the AZ schools limited to self-identified Mexican American students. RESULTS Compared with the Sonoran reference school E, the adjusted odds ratio (OR) for asthma was significantly higher in US schools A (OR 4.89, 95% confidence interval [CI] 2.72-8.80), B (OR 3.47, 95% CI 1.88-6.42), and C (OR 4.12, 95% CI 1.78-9.60). The adjusted OR for wheeze in the past year was significantly higher in schools A (OR 2.19, 95% CI 1.20-4.01) and B (OR 2.67, 95% CI 1.42-5.01) on the written questionnaire and significantly higher in A (OR 2.13, 95% CI 1.22-3.75), B (OR 1.95, 95% CI 1.07-3.53), and Sonoran school D (OR 2.34, 95% CI 1.28-4.30) on the video questionnaire compared with school E. CONCLUSIONS Asthma and wheeze prevalence differed significantly between schools and was higher in the United States. Environmental factors that may account for these differences could provide insight into mechanisms of protection from asthma.

Cough during infancy and subsequent childhood asthma

Wheezing in infancy has been associated with subsequent asthma, but whether cough similarly influences asthma risk has been little studied. We sought to determine whether prolonged cough and cough without cold in the first year of life are associated with childhood asthma.

Maternal cytokine profiles during pregnancy predict asthma in children of nonasthmatic mothers

&NA; Little is known about whether maternal immune status during pregnancy influences asthma development in the child. We measured cytokine production in supernatants from mitogen‐stimulated peripheral blood immune cells collected during and after pregnancy from the mothers of children enrolled in the Tucson Infant Immune Study, a nonselected birth cohort. Physician‐diagnosed active asthma in children through age 9 and a history of asthma in their mothers were assessed through questionnaires. Maternal production of each of the cytokines IL‐13, IL‐4, IL‐5, IFN‐&ggr;, IL‐10, and IL‐17 during pregnancy was unrelated to childhood asthma. However, IFN‐&ggr;/IL‐13 and IFN‐&ggr;/IL‐4 ratios during pregnancy were associated with a decreased risk of childhood asthma (n = 381; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.17‐0.66; P = 0.002; and n = 368; OR, 0.36; 95% CI, 0.18‐0.71; P = 0.003, respectively). The inverse relations of these two ratios with childhood asthma were only evident in mothers without asthma (n = 309; OR, 0.18; 95% CI, 0.08‐0.42; P = 0.00007; and n = 299; OR, 0.17; 95% CI, 0.07‐0.39; P = 0.00003, respectively) and not in mothers with asthma (n = 72 and 69, respectively; P for interaction by maternal asthma = 0.036 and 0.002, respectively). Paternal cytokine ratios were unrelated to childhood asthma. Maternal cytokine ratios in mothers without asthma were unrelated to the childrens skin‐test reactivity, total IgE, physician‐confirmed allergic rhinitis at age 5, or eczema in infancy. To our knowledge, this study provides the first evidence that cytokine profiles in pregnant mothers without asthma relate to the risk for childhood asthma, but not allergy, and suggests a process of asthma development that begins in utero and is independent of allergy.

Predictors of neonatal production of IFN-γ and relation to later wheeze

Supernatant IFN-γ levels from mitogen-stimulated cord blood mononuclear cells were inversely associated with wheeze through age 2, but only among boys. This relation was not due to other factors associated with cord IFN-γ production.

Nucleic-acid amplification testing of urine vs. patient complaint-driven evaluation.

The present pilot study compared the ability of a conventional patient complaint-driven approach to that of nucleic-acid amplification testing (NAAT) of urine to identify those individuals among an adult, urban, Emergency Department (ED) population infected with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Urine for NAAT was collected for testing after individuals had completed a questionnaire and before being seen by a physician. A total of 614 subjects were enrolled, and complete physical examinations were performed on 348 (56.6%) individuals, with women being significantly more likely to receive such an evaluation (odds ratio [OR] 3.09; 95% confidence interval [CI] 1.96-4.86); p < 0.001). A total of 153 (24.9%) of the study cohort tested positive for a least one sexually transmitted disease (STD), and only a reported history of STD (OR 1.74; 95% CI (1.18-2.57); p = 0.005) and a history of a new sexual partner in the last 3 months (OR 1.79; 95% CI 1.13-2.82); p = 0.012) were predictive of a positive STD test. NAAT of urine samples on patients who did not receive a complete physical examination resulted in a 33% (51/153) increase in diagnostic yield in this cohort of ED attendees.