Biomedical subjects

Anne L Wright

Publications and source records attributed to Anne L Wright.

At least 19 recordsLinked to original sources

PubMed2006

Th2 cell-selective enhancement of human IL13 transcription by IL13-1112C>T, a polymorphism associated with allergic inflammation.

IL-13 is a central mediator of allergic inflammation. The single nucleotide polymorphism IL13-1112C>T (rs1800925) is associated with allergic phenotypes in ethnically distinct populations, but the underlying mechanism(s) remain unknown. Using in vivo, in vitro, and in silico analysis, we show that the IL13-1112T allele enhanced IL13 promoter activity in primary human and murine CD4(+) Th2 lymphocytes. Increased expression of IL13-1112T in Th2 cells was associated with the creation of a Yin-Yang 1 binding site that overlapped a STAT motif involved in negative regulation of IL13 expression and attenuated STAT6-mediated transcriptional repression. Because IL-13 secretion was increased in IL13-1112TT homozygotes, we propose that increased expression of IL13-1112T in vivo may underlie its association with susceptibility to allergic inflammation. Interestingly, IL13-1112T had opposite transcriptional effects in nonpolarized CD4(+) T cells, paralleled by distinct patterns of DNA-protein interactions at the IL13 promoter. Our findings suggest the nuclear milieu dictates the functional outcome of genetic variation.

Animals↗

PubMed2006

Factors influencing gender differences in the diagnosis and treatment of asthma in childhood: the Tucson Children's Respiratory Study.

Studies identified gender differences in diagnosed asthma, but the extent to which they can be attributed to differences in symptom experience and frequency rather than factors influencing diagnosis has not been established. We investigated prevalence of, and consultation for, asthma symptoms, as well as diagnosis and treatment in 533 boys and 556 girls enrolled in the Tucson Children's Respiratory Study, a population-based birth-cohort study. Questionnaires regarding respiratory symptoms and diagnoses were obtained at ages 2, 3, 6, 8, 11, 13, 16, and 18 years. Boys were significantly more likely than girls to experience both wheeze and frequent wheeze most years in the first decade of life. However, girls with symptoms were less likely than boys to see a physician (74.1% vs. 83.4%, P < 0.001) and to be labeled as having asthma (43.3% vs. 53.8%, P < 0.009), even after adjusting for symptom frequency. A difference in symptom presentation also appeared to influence diagnosis: nocturnal cough without frequent wheeze was more prevalent among girls, and was associated with reduced diagnosis of asthma. Among subjects who consulted a physician for wheeze, boys were significantly more likely than girls to have taken medication (81.5% vs. 73.5%, P < 0.01). The lag time between age at first wheeze and first use of medication among those consulting a physician for wheeze or asthma was greater for girls, especially among subjects with frequent wheeze (2.8 vs. 1.6 years, P < 0.005). These findings indicate that gender differences in the diagnosis and treatment of asthma cannot be explained completely by differences in symptom prevalence and frequency.

Adolescent↗

PubMed2005

Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence.

RATIONALE: The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birth cohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before age 3 yr and active wheeze at age 6 yr: never wheezers (n = 425), transient early wheezers (n = 164), persistent wheezers (n = 113), and late-onset wheezers (n = 124). OBJECTIVE: We sought to determine the prognosis for these phenotypes, with reference to lung function and symptoms, through adolescence. METHODS: Current wheeze was assessed by questionnaire, lung function was measured by conventional spirometry, and atopy was determined by skin prick tests. RESULTS: The prevalence of atopy and wheeze by age 16 yr was similar for never and transient wheezers and for persistent and late-onset wheezers. Both transient early, and persistent wheezers had significantly lower FEF(25-75) (-259 ml/s, p < 0.001, and -260 ml/s, p = 0.001, respectively), FEV1 (-75 ml, p = 0.02, and -87 ml, p = 0.03, respectively), and FEV1:FVC ratio (-1.9%, p = 0.002, and -2.5%, p = 0.001, respectively) through age 16 yr compared with never wheezers. Late-onset wheezers had levels of lung function similar to those of never wheezers through age 16 yr. There was no significant change in lung function among subjects with any of the four phenotypes, relative to their peers, from age 6 to 16 yr. CONCLUSION: Patterns of wheezing prevalence and levels of lung function are established by age 6 yr and do not appear to change significantly by age 16 yr in children who start having asthma-like symptoms during the preschool years.

Adolescent↗

PubMed2005

The relation of rhinitis to recurrent cough and wheezing: a longitudinal study.

BACKGROUND: Recurrent cough can be a clinical manifestation of rhinitis. However, it remains unclear if the association between rhinitis and recurrent cough among children is independent of asthma. OBJECTIVE: The aim of the present study was to determine, in a large longitudinal cohort, whether rhinitis is significantly associated with recurrent cough alone, wheezing alone, or the combination of both symptoms during childhood. METHODS: We investigated determinants of recurrent cough, with or without wheezing, using longitudinal data from the Tucson Children's Respiratory Study. Among the 1246 subjects originally enrolled, 1024 children completed at least one questionnaire between the ages of 6 and 18 years and were included in the present study. In any survey, wheezing was defined as at least one wheezing episode during the past year and recurrent cough as two or more coughing episodes lasting at least 1 week without a cold during the past year. Generalized estimating equations were used to determine significant risk factors. RESULTS: After adjusting for sex, skin test reactivity and parental asthma, both rhinitis (OR = 2.47 CI = 1.84, 3.30) and sinusitis (OR = 1.54 CI = 1.11, 2.14) were associated with an increased risk of recurrent cough plus wheezing. The OR associated with rhinitis were significantly reduced for subjects reporting only recurrent cough or only wheezing (OR = 1.43, CI = 1.03, 1.99; and OR = 1.30, CI = 1.07, 1.58, respectively). Recurrent cough and wheezing, when examined independently, showed different patterns of risk factors. CONCLUSION: We found rhinitis to be an independent risk factor for both recurrent cough and wheezing during childhood. Different pathways may be involved in the association of rhinitis with recurrent cough and wheezing.

Adolescent↗

PubMed2005

trans Fatty acids in milk produced by women in the United States.

BACKGROUND: trans Fatty acids (FAs) have been identified as negatively affecting human health. The trans FA composition of human milk fat must be examined to establish its influence on the nutritional quality of milk consumed by infants. OBJECTIVE: We sought to ascertain the individual and total trans FA isomers (sum of FAs containing at least one trans double bond) in human milk and to identify relations between individual FAs and milk fat concentration (% by wt). DESIGN: The FA composition of milk samples (n = 81) from women living in the southwestern United States was ascertained. The individual 18:1t isomers were separated. Correlations between each FA, total trans FAs, groups of similar FAs, and milk fat concentrations were examined. RESULTS: The mean total trans FA concentration was 7.0 +/- 2.3% (range: 2.5-13.8%). The concentration of total 18:1t was 5.1 +/- 2.0% (range: 1.5-11.6%), and Delta10t (range: Delta9-12t) was the most abundant isomer. CONCLUSIONS: Milk fat from women living in the United States contains concentrations of trans FAs similar to those in milk from Canadian women but greater than those reported in milk from women in other countries. In decreasing order of concentration, the Delta10t, Delta11t, Delta9t, and Delta12t isomers represented 78.9% of the total 18:1t. These FAs generally originate from partially hydrogenated vegetable oils and ruminant fat in the diet. No relation was found between the concentration of total trans FAs and milk fat concentration.

Adult↗

PubMed2005

Prenatal factors associated with the development of eczema in the first year of life.

Prenatal factors have been implicated in childhood eczema, but the relationship between maternal cytokine production during pregnancy and infant eczema is unknown. Non-selected women in their third trimester were enrolled in the Tucson Infant Immune Study. Data from three sources were used to define MD-eczema: parent-completed illness questionnaires at age 2, 3, 4, 6 and 9 months regarding physician-seen eczema, parent-completed questionnaires at 12 months regarding physician-diagnosed eczema, and medical record reviews. Blood samples were taken from mothers during their third trimester and from the umbilical cord at birth. Maternal peripheral blood mononuclear cells and cord blood mononuclear cells were stimulated with ConA/PMA, and supernatants were assayed for IFN-gamma and IL-4, -5, -10, and -13. Of 364 children, 28% were seen by a physician for eczema by 1 yr of age. After adjustment for potential confounders using logistic regression, the odds for development of eczema in infancy were significantly higher when mothers had active eczema in pregnancy (OR, 2.46, CI 1.0-5.8, p <0.042) and when mothers were in the highest tertile of serum IgE production (OR 2.28, CI 1.2-4.4, p <0.013). Colds in the third trimester were associated with lower odds of eczema (OR 0.32, CI 0.16-0.63, p <0.001). Our findings from this cohort study suggest that in utero factors, including maternal IgE, colds, and eczema, may influence the risk of infant eczema.

Arizona↗

PubMed2005

Relation of beta2-adrenoceptor polymorphisms at codons 16 and 27 to persistence of asthma symptoms after the onset of puberty.

BACKGROUND: It has long been recognized that many children with asthma outgrow the disease after the onset of puberty, but little is known about genetic factors influencing this outcome. OBJECTIVES: The aim of the present study was to determine whether the polymorphisms at codons 16 and 27 of the beta2-adrenoceptor are significant predictors of the persistence of asthma during adolescence. DESIGN AND PARTICIPANTS: We used data from the prospective Tucson Children's Respiratory Study. Children were genotyped for the polymorphisms at codons 16 and 27. The presence of wheezing/asthma was assessed by questionnaire from age 6 years up to the reported onset of puberty (prepubertal period) and after the onset of puberty up to age 16 years (adolescence). RESULTS: Among children who wheezed in the prepubertal period (n = 168), subjects homozygous for Gly at codon 16 were at significantly increased risk for persistent wheezing after puberty, as compared with carriers of the other genotypes (relative risk [RR], 1.43; 95% confidence interval [CI], 1.06 to 1.92; p = 0.019). This relation was present among boys (RR, 2.17; 95% CI, 1.41 to 3.36) but not girls (RR, 0.85; 95% CI, 0.55 to 1.30), and increased linearly according to the frequency of wheezing episodes after the onset of puberty. These findings persisted after adjusting for ethnicity and other potential confounders and after selecting only white children. The polymorphism at codon 27 showed no relation with risk for persistent wheezing. CONCLUSIONS: This study provides evidence for a strong gender-specific effect of the Gly16 polymorphism on the persistence of asthma after the onset of puberty.

Adolescent↗

PubMed2004

Persistence of asthma symptoms during adolescence: role of obesity and age at the onset of puberty.

Little is known about rates and predictors of remission of childhood asthma after the onset of puberty. We used data collected at ages 6, 8, 11, 13, and 16 years from the Tucson Children's Respiratory Study, a population-based birth cohort. The onset of puberty was defined as the age of appearance of the first pubertal signs as reported by parents. Information on wheezing both before and after onset of puberty (mean +/- SD follow-up from onset of puberty, 4.2 +/- 1 year) was available for 781 children. Of these, 166 had asthma (either frequent wheezing or a physician-confirmed diagnosis plus any wheezing) in at least one survey before puberty. In this group, 58% of the children (97 of 166) reported the presence of wheezing after the onset of puberty (unremitting asthma). In contrast, only 30% (39 of 131) of the children with infrequent wheezing before puberty experienced wheezing episodes after the onset of puberty (unremitting wheezing). In addition to frequent wheezing before puberty, obesity, early onset of puberty, active sinusitis, and skin test sensitization were significant and independent predictors of unremitting asthma after the onset of puberty. Our findings from a population-based longitudinal cohort challenge the commonly held view that asthma usually remits during adolescence.

Adolescent↗

PubMed2004

The epidemiology of the atopic child: who is at risk for what?

In the past few decades, a number of epidemiologic studies have identified risk factors for the development of allergic disease. Although both maternal and paternal history of allergy are associated with an increased risk of atopy, maternal history of asthma confers the greater risk for childhood asthma, which suggests that environmental factors such as the in utero immunologic environment may confer additional susceptibility. Cytokine profiles at birth may also indicate a predisposition to allergic disease in later childhood. Specifically, low interferon-gamma appears to be associated with an increased risk for later development of allergic symptoms and atopic disease. Allergen exposure may also increase the risk of atopic consequences, but the outcome is highly dependent on dose of the allergen, timing of exposure, and, most interestingly, the nature of the allergen in question. Endotoxin exposure during infancy has been associated with increased wheezing during the first years of life, but several studies indicate that early exposure may confer some protection against allergy later in life. Clearly, all these factors should be evaluated in identifying the appropriate prevention measures and treatment for the child who is at risk for allergic disease.

Animals↗

PubMed2004

Parental asthma as a risk factor for the development of early skin test sensitization in children.

BACKGROUND: Recent epidemiologic evidence has challenged the paradigm suggesting a direct causal relationship between allergic sensitization and asthma. OBJECTIVE: We sought to investigate the role of a familial predisposition for asthma in the development of atopy in children. METHODS: Subjects were participants in the Tucson Children's Respiratory Study. Skin tests to aeroallergens were performed in parents and in children at ages 6, 11, and 16 years. Parents were considered asthmatic if they reported physician-confirmed asthma. Parents were divided into 4 phenotypes on the basis of skin sensitization (Skt+ or Skt-) and asthma status (As+ or As-): Skt-/As-, Skt-/As+, Skt+/As-, and Skt+/As+. RESULTS: Children's allergic sensitization differed among parental phenotypes at all ages (P <.0001). Children in the Skt+/As- and Skt+/As+ groups were significantly more likely to be allergic than children in the Skt-/As- group at all ages. Among children with allergic parents, those with at least one parent with asthma were significantly more likely to have positive skin test responses than those with nonasthmatic parents at age 6 years (52.4% vs 37.4%, P <.005) and 11 years (70.1% vs 55.6%, P <.005) but not at age 16 years (82.3% vs 75.1%, P =.180). Results were independent of wheezing in the child and of the characteristics of atopy in parents. The Skt-/As+ group had too few subjects for meaningful comparisons. CONCLUSION: Among children of atopic parents, parental asthma is a risk factor for allergic sensitization in early childhood. The strong association between allergic sensitization and asthma is at least in part explained by an increased susceptibility to allergen sensitization in subjects predisposed to asthma.

Adolescent↗

PubMed2004

Health, place and childhood asthma in southwest Alaska.

Social science theories of health and place posit that individuals perceive a relationship between characteristics of the geographic location in which they reside and their health, well-being, and self-identity. A number of ethnographies of health and place have studied how urban and suburban populations impacted by industrial pollution or waste have come to perceive a link between rates of cancer and their unhealthy environment. There has been little study of the applicability of the health and place framework to community perceptions of long-term chronic illness. This paper examines the asthma perceptions of Yup'ik parents of asthmatic children using data from semi-structured ethnographic interviews conducted in five villages and one town of the Yukon-Kuskokwim delta of southwest Alaska. Informants cited local climatic features, large-scale changes of the last 30 years to the village built landscape, and ongoing conditions of substandard housing and sanitation as etiological factors associated with childhood asthma. Our study suggests the need for further research concerning lay perceptions of one aspect of the epidemilogic transition-the association between chronic illness and place, especially in rural communities undergoing dramatic developmental change.

Adolescent↗

PubMed2004

The differential effect of genetic variation on soluble CD14 levels in human plasma and milk.

PROBLEM: The protein CD14 is a pattern recognition receptor for bacterial lipopolysaccharide (LPS). Whether genetic variation has the same influence on soluble CD14 (sCD14) levels in human plasma and milk remains to be determined. METHOD OF STUDY: We measured sCD14 levels in plasma during pregnancy (n = 196) and in milk in the postpartum (n = 152) for women genotyped for the single nucleotide polymorphisms (SNPs) at positions -1619, -550, and -159 from the transcription start site of the CD14 gene. RESULTS: Plasma- and milk-sCD14 levels differed significantly both by CD14/-1619 and CD14/-550 genotypes and by haplotypes. Most interestingly, sCD14 levels were regulated differentially by the same genetic variants in plasma and milk, with the CD14/-550T allele and the corresponding are ATC haplotype associated with high sCD14 in milk but low sCD14 in plasma. A correlation between sCD14 levels in plasma and milk was absent (r = 0.091, P = NS). CONCLUSIONS: Our findings suggest the existence of cell-specific regulation mechanisms of CD14 gene expression.

Adult↗

PubMed2003

Reduced interferon gamma production and soluble CD14 levels in early life predict recurrent wheezing by 1 year of age.

It is unknown whether reduced production of IFNgamma in early life, before any lower respiratory tract illness, is a risk factor for recurrent wheezing in infancy. We followed 238 infants prospectively from birth to 1 year of age. At birth and at 3 months of age, IFNgamma production from polyclonally stimulated peripheral blood mononuclear cells and soluble CD14 (sCD14) levels in plasma were measured. The odds of developing recurrent wheezing (assessed by questionnaire) in the first year of life were up to 4.5 times higher for children in the lowest quartile of IFNgamma production at 3 months (p = 0.0005) and 3.2 times higher for children in the lowest quartile of sCD14 levels at birth (p = 0.004) as compared with children in the other 3 combined quartiles of IFNgamma and sCD14, respectively. Findings were confirmed in the multivariate analysis. IFNgamma production at 3 months and sCD14 levels at birth were correlated (r = 0.188, p = 0.031). Our findings from a longitudinal cohort suggest that impaired IFNgamma production at 3 months and reduced plasma-sCD14 levels at birth significantly increase the risk of developing recurrent wheezing in the first year of life.

Age Factors↗

PubMed2003

TGF-beta in human milk is associated with wheeze in infancy.

BACKGROUND: Cytokines secreted in human milk might play important roles in newborn health and in the development of infant immune responses. We investigated the relationship of the concentration and dose of cytokines in human milk to infant wheeze at 1 year of age. OBJECTIVE: Our objective was to test whether the cytokines in milk could account for some of the apparent protective effect of breast-feeding against wheeze in the first year of life. METHODS: Data on breast-feeding and infant wheeze were collected prospectively from birth to 1 year from 243 mothers participating in the Infant Immune Study in Tucson, Arizona. Breast milk samples obtained at a mean age of 11 days postpartum were assayed by means of ELISA for concentrations of TGF-beta1, IL-10, TNF-alpha, and the soluble form of CD14. The dose of each cytokine was assessed for a relationship with wheeze in bivariate and logistic regression analyses. RESULTS: Increasing duration of breast-feeding was significantly associated with a decreased prevalence of wheeze (P =.039). There was wide variability in levels of each cytokine in milk, as well as variability between women in the amount of each cytokine produced. There was a significant inverse association between the dose of TGF-beta1 received through milk with the percentage of wheeze (P =.017), and the relationship was linear (P =.006). None of the other cytokines showed a linear relationship with wheeze. In multivariate analyses the risk of wheeze was significantly decreased (odds ratio, 0.22; 95% CI 0.05-0.89; P =.034) with increasing TGF-beta1 dose (long breast-feeding and medium-high TGF-beta1 level compared with short breast-feeding and low TGF-beta. CONCLUSION: This analysis shows that the dose of TGF-beta1 received from milk has a significant relationship with infant wheeze, which might account for at least some of the protective effect of breast-feeding against wheeze.

Breast Feeding↗

PubMed2003

Tucson Children's Respiratory Study: 1980 to present.

The Tucson Children's Respiratory Study (TCRS), begun in 1980, has followed 1246 subjects from birth together with their family members to delineate the complex interrelationships between a large number of potential risk factors, acute lower respiratory tract illnesses, and chronic lung disorders later in childhood and early adult life, especially asthma. Nine hundred seventy-four (78%) of the original subjects are still being followed. Among its numerous findings, the TCRS has (1) described various wheezing disorders (transient, nonatopic, atopic) and their characteristics; (2) developed an Asthma Predictive Index; (3) delineated the respiratory and atopic outcomes for children who had respiratory syncytial virus-related wheezing illnesses in infancy; and (4) evaluated a large number of risk factors for acute respiratory tract illnesses during the first 3 years of life. Future TCRS studies will focus on (1) factors in infancy and early childhood that relate to persistent asthma and atopy; (2) role of genetic factors in persistent asthma; and (3) determinants of lung function decline in early adult life.

Acute Disease↗

PubMed2003

Gender differences in academic advancement: patterns, causes, and potential solutions in one US College of Medicine.

PURPOSE: The influx of women into academic medicine has not been accompanied by equality for male and female faculty. Women earn less than men in comparable positions, progress more slowly through academic ranks, and have not attained important leadership roles. This study tested hypotheses about why gender disparities exist in salary, rank, track, leadership, and perceptions of campus climate at one academic center, the University of Arizona College of Medicine, Tucson. METHOD: Salary, rank, and track data were obtained from institutional databases for the 1999-2000 fiscal year. A structured, online questionnaire was made available to 418 faculty members to collect information about their goals, attitudes, and experiences. RESULTS: A total of 198 faculty members completed the questionnaire. The data showed significant gender differences in faculty salaries, ranks, tracks, leadership positions, resources, and perceptions of academic climate. On average, women earned US dollars 12777 or 11% less than men, after adjusting for rank, track, degree, specialty, years in rank, and administrative positions (p <.0003). Of female faculty, 62% were assistant professors (49% of women were non-tenure-eligible assistant professors), while 55% of male faculty were promoted and tenured. Almost a third of women reported being discriminated against, compared with only 5% of men (p <.00001). CONCLUSION: Substantial gender differences in the rewards and opportunities of academic medicine remain, that can not be attributed to differences in productivity or commitment between women and men.

Analysis of Variance↗

PubMed2003

The role of active family nutritional support in Navajos' type 2 diabetes metabolic control.

OBJECTIVE: We examined if active family nutritional support is associated with improved metabolic outcomes for Diné (Navajo) individuals living with type 2 diabetes. RESEARCH DESIGN AND METHODS: The presence of family support, using variables identified in earlier ethnographic research, was assessed via surveys in a convenience sample of 163 diabetic individuals. Diabetes outcome measures (HbA(1c), serum glucose, triglycerides, total cholesterol, creatinine, and systolic and diastolic blood pressure measures) were extracted from participants' medical records. Bivariate analyses and multiple logistic regressions were conducted. RESULTS: All measures of family support showed a relation with one or more indicators of metabolic control in bivariate analyses. In multivariate analyses, respondents were more likely to be in the best tertile for triglyceride (P < 0.05), cholesterol (P < 0.05), and HbA(1c) (P < 0.05) if another person cooked most of the meals. Respondents in families who bought/cooked "light" foods were more likely to be in the best tertile for triglyceride (P < 0.005) and cholesterol levels (P < 0.005), and those in families whose members ate "light" foods with them were more likely to be in the best tertile for triglycerides (P < 0.005). When all three support variables were entered into a multivariate model, only the variable "other family members cook the majority of the meals" was significantly associated with being in the lowest triglyceride (P = 0.05), HbA(1c) (P < 0.05), or cholesterol tertiles (P < 0.05). These relationships were most evident for women with diabetes. CONCLUSIONS: Active family nutritional support, as measured by culturally relevant categories, is significantly associated with control of triglyceride, cholesterol, and HbA(1c) levels. The findings suggest that the family is a more useful unit of intervention for Diné individuals than for the individual alone when designing diabetes care strategies.

Cholesterol↗

PubMed2003

Qualitative study of the use of traditional healing by asthmatic Navajo families.

Despite increasing prevalence of asthma among American Indians and/or Alaska Natives, little is known about their use of traditional healing in its management. A convenience sample of 24 Navajo families with asthmatic members (n=35) was interviewed between June 1997 and September 1998. While 46% of families had previously used traditional healing, only 29% sought traditional healing for asthma. Use of traditional healing was unrelated to use of biomedical therapies, hospitalizations, or emergency services. Practical factors and questions about the nature and origins of asthma were the primary considerations determining use of traditional medicine. Little conflict between traditional healing and biomedical treatment was reported. The use of traditional healing for asthma is influenced by beliefs about the disease and factors specific to the individual, including their local social, economic, and cultural context.

Adolescent↗