Anne L Wright

Interests

Research

Epidemiology of Childhood Asthma,Faculty Development,Women in Academic Medicine

Courses

No activities entered.

Scholarly Contributions

Books

• Wright, A. L. (2002). integrating population outcomes, biological mechanisms and research methods in the study of human milk and lactation.

Journals/Publications

• Chang, E. H., Stern, D. A., Willis, A. L., Guerra, S., Wright, A. L., & Martinez, F. D. (2018). Early life risk factors for chronic sinusitis: a longitudinal birth cohort study. The Journal of allergy and clinical immunology.
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  Chronic sinusitis is a commonly diagnosed condition in adults who frequently present with late-stage disease and irreversible changes to the sinus mucosa. Understanding the natural history of chronic sinusitis is critical in developing therapies designed to prevent or slow the progression of disease.
• DeVries, A., Wlasiuk, G., Miller, S., Bosco, A., Stern, D., Lohman, I. C., Rothers, J. L., Jones, A., Nicodemus-Johnson, J., Vasquez, M., Curtin, J., Simpson, A., Custovic, A., Jackson, D., Gern, J., Lemanske, R., Guerra, S., Wright, A. L., Ober, C., , Halonen, M., et al. (2017). Epigenome-wide analysis identifies SMAD3 methylation at birth to asthma in children of asthmatic mothers. J. Allergy Clin. Immunol., 140(2), 534-542.
• Ball, T. M., Holberg, C. J., Martinez, F. D., & Wright, A. L. (2016). Is there a common cold constitution?. Ambulatory pediatrics : the official journal of the Ambulatory Pediatric Association, 2(4), 261-7.
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  Constitutional factors might play a role in the susceptibility to clinical illness during the common cold. This study seeks to determine if the likelihood of developing frequent common colds persists during childhood.
• Berry, C. E., Billheimer, D., Jenkins, I. C., Lu, Z. J., Stern, D. A., Gerald, L. B., Carr, T. F., Guerra, S., Morgan, W. J., Wright, A. L., & Martinez, F. D. (2016). A Distinct Low Lung Function Trajectory from Childhood to the Fourth Decade of Life. American journal of respiratory and critical care medicine, 194(5), 607-12.
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  Low maximally attained lung function increases the risk of chronic obstructive pulmonary disease irrespective of the subsequent rate of lung function decline.
• Carr, T. F., Beamer, P. I., Rothers, J., Stern, D. A., Gerald, L. B., Rosales, C. B., Van Horne, Y. O., Pivniouk, O. N., Vercelli, D., Halonen, M., Gameros, M., Martinez, F. D., & Wright, A. L. (2016). Prevalence of Asthma in School Children on the Arizona-Sonora Border. The journal of allergy and clinical immunology. In practice, 5(1), 114-120.e2.
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  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.
• Xu, H., Radabaugh, T., Lu, Z., Galligan, M., Billheimer, D., Vercelli, D., Wright, A. L., Monks, T. J., Halonen, M., & Lau, S. S. (2016). Exploration of early-life candidate biomarkers for childhood asthma using antibody arrays. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, 27(7), 696-701.
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  Proteomic approaches identifying biomarkers have been applied to asthma to only a very limited extent.
• Beamer, P. I., Lothrop, N., Lu, Z., Ascher, R., Ernst, K., Stern, D. A., Billheimer, D., Wright, A. L., & Martinez, F. D. (2015). Spatial clusters of child lower respiratory illnesses associated with community-level risk factors. Pediatric pulmonology.
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  Identifying geographic areas with increased incidence of disease may elucidate community-level risk factors for intervention development. Lower respiratory illnesses (LRIs) are the leading cause of death in children and are associated with other morbidities. We assessed geographic clustering of LRIs and evaluated if these spatial patterns and associated risk factors differed by phenotype. Participants enrolled at birth in the Tucson Children's Respiratory Study were followed through age three for physician diagnosed LRIs. Spatial clustering analysis, based upon each participant's birth address, was performed for four LRI phenotypes. We conducted principal component analysis at the census tract level to generate indices for lower socioeconomic status (SES), poorer housing conditions, and increased air pollution. Enrollment addresses were mapped for 812 subjects, of whom 58.4%, 33.5%, 34.2%, and 23.4% had any LRI, a wheezing LRI, a viral LRI, and a respiratory syncytial virus (RSV) LRI, respectively. Patterns of spatial clustering and associated risk factors differed by LRI phenotype. Multivariable regression analyses showed that wheezing LRI clusters were associated with increased air pollution (OR = 1.18, P = 0.01). Being in a viral cluster was associated with poorer housing conditions (OR = 1.28, P = 0.01), while being in a RSV cluster was associated with increased air pollution (OR = 1.14, P = 0.006), poorer housing conditions (OR = 1.54, P = 0.003), and higher SES (OR = 0.77, P = 0.001). Our use of social and environmental indices allowed us to identify broad contextual factors that may contribute to increased incidence of LRIs in specific geographic regions. To reduce LRI incidence, multifaceted interventions should be developed at the community level. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.
• Beamer, P. I., Lothrop, N., Stern, D. A., Billheimer, D., Wright, A. L., & Martinez, F. D. (2015). Increased wheezing risk with diesel exposure among children of younger mothers. The European respiratory journal, 46(3), 853-5.
• Chan, J. Y., Stern, D. A., Guerra, S., Wright, A. L., Morgan, W. J., & Martinez, F. D. (2015). Pneumonia in childhood and impaired lung function in adults: a longitudinal study. Pediatrics, 135(4), 607-16.
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  Diminished lung function and increased prevalence of asthma have been reported in children with a history of early lower respiratory illnesses (LRIs), including pneumonia. Whether these associations persist up to adulthood has not been established.
• Guerra, S., Halonen, M., Vasquez, M. M., Spangenberg, A., Stern, D. A., Morgan, W. J., Wright, A. L., Lavi, I., Tarès, L., Carsin, A., Dobaño, C., Barreiro, E., Zock, J., Martínez-Moratalla, J., Urrutia, I., Sunyer, J., Keidel, D., Imboden, M., Probst-Hensch, N., , Hallberg, J., et al. (2015). Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study. The Lancet. Respiratory medicine, 3(8), 613-20.
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  Low concentrations of the anti-inflammatory protein CC16 (approved symbol SCGB1A1) in serum have been associated with accelerated decline in forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD). We investigated whether low circulating CC16 concentrations precede lung function deficits and incidence of COPD in the general population.
• Oren, E., Gerald, L., Stern, D. A., Martinez, F. D., & Wright, A. L. (2017). Self-Reported Stressful Life Events During Adolescence and Subsequent Asthma: A Longitudinal Study. The journal of allergy and clinical immunology. In practice, 30416-20.
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  Although exposure to stressful life events in adolescence has been associated with poor health as measured by number of physicians' visits and symptom scores, little is known regarding stress in adolescence and either concurrent or subsequent asthma.
• Oren, E., Rothers, J., Stern, D. A., Morgan, W. J., Halonen, M., & Wright, A. L. (2015). Cough Duration in infancy and subsequent childhood asthma. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 45(9), 1439-46.
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  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.
• Voraphani, N., Stern, D. A., Wright, A. L., Guerra, S., Morgan, W. J., & Martinez, F. D. (2014). Risk of current asthma among adult smokers with respiratory syncytial virus illnesses in early life. American journal of respiratory and critical care medicine, 190(4), 392-8.
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  Risk of subsequent asthma-like symptoms after early-life lower respiratory illness (LRI) caused by respiratory syncytial virus (RSV) is increased during the first decade of childhood and diminished thereafter by adolescence.
• Guerra, S., Stern, D. A., Zhou, M., Sherrill, D. L., Wright, A. L., Morgan, W. J., & Martinez, F. D. (2013). Combined effects of parental and active smoking on early lung function deficits: a prospective study from birth to age 26 years. Thorax, 68(11), 1021-8.
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  Cross-sectional reports have suggested that, among active smokers, previous exposure to parental smoking may increase susceptibility to development of chronic obstructive pulmonary disease. We assessed prospectively whether parental smoking enhances the effects of active smoking on early deficits of lung function in young adults.
• Halonen, M., Lohman, I. C., Stern, D. A., Ellis, W. L., Rothers, J., & Wright, A. L. (2013). Perinatal tumor necrosis factor-α production, influenced by maternal pregnancy weight gain, predicts childhood asthma. American journal of respiratory and critical care medicine, 188(1), 35-41.
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  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.
• Marri, P. R., Stern, D. A., Wright, A. L., Billheimer, D., & Martinez, F. D. (2013). Asthma-associated differences in microbial composition of induced sputum. The Journal of allergy and clinical immunology, 131(2), 346-52.e1-3.
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  It is increasingly evident that microbial colonization of the respiratory tract might have a role in the pathogenesis of asthma.
• Thompson, E. E., Myers, R. A., Du, G., Aydelotte, T. M., Tisler, C. J., Stern, D. A., Evans, M. D., Graves, P. E., Jackson, D. J., Martinez, F. D., Gern, J. E., Wright, A. L., Lemanske, R. F., & Ober, C. (2013). Maternal microchimerism protects against the development of asthma. The Journal of allergy and clinical immunology, 132(1), 39-44.
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  Maternal asthma and child's sex are among the most significant and reproducible risk factors for the development of asthma. Although the mechanisms for these effects are unknown, they likely involve nonclassical genetic mechanisms. One such mechanism could involve the transfer and persistence of maternal cells to her offspring, a common occurrence known as maternal microchimerism (MMc). MMc has been associated with many autoimmune diseases but has not been investigated for a role in asthma or allergic disease.
• Custovic, A., Rothers, J., Stern, D., Simpson, A., Woodcock, A., Wright, A. L., Nicolaou, N. C., Hankinson, J., Halonen, M., & Martinez, F. D. (2011). Effect of day care attendance on sensitization and atopic wheezing differs by Toll-like receptor 2 genotype in 2 population-based birth cohort studies. The Journal of allergy and clinical immunology, 127(2), 390-397.e1-9.
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  Variation in the Toll-like receptor 2 gene (TLR2/-16934) is associated with allergic diseases among farmers' children but not among children not living on farms.
• Rothers, J., Halonen, M., Stern, D. A., Lohman, I. C., Mobley, S., Spangenberg, A., Anderson, D., & Wright, A. L. (2011). Adaptive cytokine production in early life differentially predicts total IgE levels and asthma through age 5 years. Journal of Allergy and Clinical Immunology, 128, 397-402 e2.
• Rothers, J., Halonen, M., Stern, D. A., Lohman, I. C., Mobley, S., Spangenberg, A., Anderson, D., & Wright, A. L. (2011). Adaptive cytokine production in early life differentially predicts total IgE levels and asthma through age 5 years. The Journal of allergy and clinical immunology, 128(2), 397-402.e2.
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  Although it has been postulated that allergic disease is associated with a predominance of T(H)2 cells, whether IgE levels and asthma might differ in their relation to early-life cytokine production is not known.
• Rothers, J., Wright, A. L., Stern, D. A., Halonen, M., & Camargo, C. A. (2011). Cord blood 25-hydroxyvitamin D levels are associated with aeroallergen sensitization in children from Tucson, Arizona. The Journal of allergy and clinical immunology, 128(5), 1093-9.e1-5.
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  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.
• Sherrill, D. L., Guerra, S., Wright, A. L., Morgan, W. J., & Martinez, F. D. (2011). Relation of early childhood growth and wheezing phenotypes to adult lung function. Pediatric pulmonology, 46(10), 956-63.
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  Several studies have reported associations between indicators of birth size and postnatal growth rates with levels of pulmonary function achieved as adults. The objective of this study was to determine if levels and/or rates of weight gain, measured in early life (birth-6 years), are associated with FVC or FEV1 levels achieved in young adulthood and if these associations differ by early childhood wheezing phenotypes.
• Maier, R. M., Palmer, M. W., Andersen, G. L., Halonen, M. J., Josephson, K. C., Maier, R. S., Martinez, F. D., Neilson, J. W., Stern, D. A., Vercelli, D., & Wright, A. L. (2010). Environmental determinants of and impact on childhood asthma by the bacterial community in household dust. Applied and environmental microbiology, 76(8), 2663-7.
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  Asthma increased dramatically in the last decades of the 20th century and is representative of chronic diseases that have been linked to altered microbial exposure and immune responses. Here we evaluate the effects of environmental exposures typically associated with asthma protection or risk on the microbial community structure of household dust (dogs, cats, and day care). PCR-denaturing gradient gel analysis (PCR-DGGE) demonstrated that the bacterial community structure in house dust is significantly impacted by the presence of dogs or cats in the home (P = 0.0190 and 0.0029, respectively) and by whether or not children attend day care (P = 0.0037). In addition, significant differences in the dust bacterial community were associated with asthma outcomes in young children, including wheezing (P = 0.0103) and specific IgE (P = 0.0184). Our findings suggest that specific bacterial populations within the community are associated with either risk or protection from asthma.
• Su, Y., Rothers, J., Stern, D. A., Halonen, M., & Wright, A. L. (2010). Relation of early antibiotic use to childhood asthma: confounding by indication?. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 40(8), 1222-9.
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  Findings from studies of the relation between early antibiotic use and subsequent asthma have been inconsistent, which may be attributable to methodologic issues.
• Halonen, M., Lohman, I. C., Stern, D. A., Spangenberg, A., Anderson, D., Mobley, S., Ciano, K., Peck, M., & Wright, A. L. (2009). Th1/Th2 patterns and balance in cytokine production in the parents and infants of a large birth cohort. Journal of immunology (Baltimore, Md. : 1950), 182(5), 3285-93.
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  Regulation of human immune cell cytokine production in vivo is not well understood due in part to limitations on imposing experimental conditions. We proposed that life-imposed conditions (pregnancy, birth, age, gender), combined with large sample size, repeat sampling, and family-based recruitment would serve to reveal peripheral blood cell-derived cytokine patterns reflective of in vivo regulation regarding Th1/Th2 balance and familial correlation. Mononuclear cells were obtained from 483 trios in the Tucson Infant Immune Study: from mothers pre- and postpartum, infants at birth and at 3 mo, and fathers. Con A/PMA-stimulated supernatants were assayed by ELISA for IFN-gamma, IL-4, IL-13, IL-5, and IL-10 and allergen-stimulated supernatants for IFN-gamma, IL-4, and IL-13. Mitogen-stimulated prepartum samples were not globally Th2 biased, differing from postpartum only by a modestly reduced IFN-gamma:IL-5 ratio. Prepartum samples actually produced less IL-10 and IL-13 although more IL-5 than paternal samples. Newborns were also not globally Th2 biased, with mitogen stimulation producing approximately 10-fold less IL-4, IL-5, and IFN-gamma than adults but only 2- to 3-fold less IL-13 and IL-10. Despite these group differences, all cytokines showed marked positive intraindividual correlations (all p < 0.001). Allergen stimulation gave results consistent with a lack of global Th2 bias. Mitogen stimulation revealed parent-child and parent-parent correlations. Thus, rather than a global Th2 bias, cytokine production in pregnant mothers and newborns appears regulated so as to maintain a relative balance among the cytokines, with the nature of the balance differing in mothers and infants and with production influenced by familial factors that include shared environment.
• Schloss, E. P., Flanagan, D. M., Culler, C. L., & Wright, A. L. (2009). Some hidden costs of faculty turnover in clinical departments in one academic medical center. Academic medicine : journal of the Association of American Medical Colleges, 84(1), 32-6.
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  To calculate the costs of clinical faculty turnover in clinical departments at The University of Arizona College of Medicine, including some aspects of lost clinical income.
• Stern, D. A., Morgan, W. J., Halonen, M., Wright, A. L., & Martinez, F. D. (2008). Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study. Lancet (London, England), 372(9643), 1058-64.
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  Incidence of asthma increases during early adulthood. We aimed to estimate the contributions of sex and early life factors to asthma diagnosed in young adults.
• Tebow, G., Sherrill, D. L., Lohman, I. C., Stern, D. A., Wright, A. L., Martinez, F. D., Halonen, M., & Guerra, S. (2008). Effects of parental smoking on interferon gamma production in children. Pediatrics, 121(6), e1563-9.
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  Environmental tobacco smoke is associated with several negative health outcomes in children, including an increased susceptibility to infections. One of the postulated mechanisms for these effects is the impairment of the immune system function and/or development. Yet, it remains unknown whether cumulative exposure to parental smoking is associated with altered immune responses in childhood and whether these effects are independent of in utero exposure to maternal smoking. In a population-based birth cohort, we sought to determine the relation of parental smoking, as assessed prospectively since pregnancy, to the child's interferon gamma and interleukin 4 production at 11 years of age.
• Crestani, E., Lohman, I. C., Guerra, S., Wright, A. L., & Halonen, M. (2007). Association of IL-5 cytokine production and in vivo IgE levels in infants and parents. The Journal of allergy and clinical immunology, 120(4), 820-6.
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  Total IgE in human subjects tracks strongly from birth onward through unknown mechanisms. Regulation of IgE might occur in relation to adaptive immune cytokine production. In vitro studies have assessed the role of individual cytokines in regulating IgE production in human subjects.
• Guilbert, T. W., Stern, D. A., Morgan, W. J., Martinez, F. D., & Wright, A. L. (2007). Effect of breastfeeding on lung function in childhood and modulation by maternal asthma and atopy. American journal of respiratory and critical care medicine, 176(9), 843-8.
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  The protective effect of breastfeeding on early respiratory infections is well established, but its relationship to the development of subsequent asthma remains controversial.
• Oryszczyn, M., Bouzigon, E., Maccario, J., Siroux, V., Nadif, R., Wright, A., & Kauffmann, F. (2007). Interrelationships of quantitative asthma-related phenotypes in the Epidemiological Study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy. The Journal of allergy and clinical immunology, 119(1), 57-63.
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  Delineating asthma subphenotypes is of interest to understand the cause of the disease. Few studies have addressed the interrelationships of quantitative asthma-related traits.
• Rothers, J., Stern, D. A., Spangenberg, A., Lohman, I. C., Halonen, M., & Wright, A. L. (2007). Influence of early day-care exposure on total IgE levels through age 3 years. Journal of Allergy and Clinical Immunology, 120, 1201-7.
• Rothers, J., Stern, D. A., Spangenberg, A., Lohman, I. C., Halonen, M., & Wright, A. L. (2007). Influence of early day-care exposure on total IgE levels through age 3 years. The Journal of allergy and clinical immunology, 120(5), 1201-7.
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  Early day care is inversely associated with asthma and atopy in later childhood, but its association with early immunologic markers of asthma risk is not known.
• Stern, D. A., Guerra, S., Halonen, M., Wright, A. L., & Martinez, F. D. (2007). Low IFN-gamma production in the first year of life as a predictor of wheeze during childhood. The Journal of allergy and clinical immunology, 120(4), 835-41.
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  Diminished cytokine production in infancy has been associated with an increased risk for allergen sensitization and early-life wheeze.
• Stern, D. A., Morgan, W. J., Wright, A. L., Guerra, S., & Martinez, F. D. (2007). Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study.
• Stern, D. A., Morgan, W. J., Wright, A. L., Guerra, S., & Martinez, F. D. (2007). Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet (London, England), 370(9589), 758-64.
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  Together with smoking, the lung function attained in early adulthood is one of the strongest predictors of chronic obstructive pulmonary disease. We aimed to investigate whether lung function in early adulthood is, in turn, affected by airway function measured shortly after birth.
• Wright, A. L., Ryan, K., St Germain, P., Schwindt, L., Sager, R., & Reed, K. L. (2007). Compensation in academic medicine: progress toward gender equity. Journal of general internal medicine, 22(10), 1398-402.
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  Studies have documented substantial salary disparities between women and men in academic medicine. While various strategies have been proposed to increase equity, to our knowledge, no interventions have been evaluated.
• Cameron, L., Webster, R. B., Strempel, J. M., Kiesler, P., Kabesch, M., Ramachandran, H., Yu, L., Stern, D. A., Graves, P. E., Lohman, I. C., Wright, A. L., Halonen, M., Klimecki, W. T., & Vercelli, D. (2006). Th2 cell-selective enhancement of human IL13 transcription by IL13-1112C>T, a polymorphism associated with allergic inflammation. Journal of immunology (Baltimore, Md. : 1950), 177(12), 8633-42.
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  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.
• LeVan, T. D., Guerra, S., Klimecki, W., Vasquez, M. M., Lohman, I. C., Martinez, F. D., Halonen, M., & Wright, A. L. (2006). The impact of CD14 polymorphisms on the development of soluble CD14 levels during infancy. Genes and immunity, 7(1), 77-80.
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  CD14 is a receptor involved in the recognition of lipopolysaccharide and other bacterial wall components that may be involved in the balance between infectious and allergic disease and the early polarization towards TH1. Our group has shown an association between polymorphisms in the 5' flanking region of the CD14 gene and plasma soluble CD14 (sCD14) levels at 11 years of age. However, whether this association is present at birth and in infancy remains to be determined. In this study, we measured sCD14 levels in plasma from the umbilical cord (n = 387) and at 3 months (n = 357) and 1 year (n = 312) of age in non-selected healthy infants to assess their relationship with CD14 genotypes at -4190, -2838, -1720 and -260 (relative to translation start site). There was no relation of CD14 genotypes with sCD14 at birth. However, there was a significant association between CD14 genotypes and sCD14 as early as 3 months. Longitudinal analysis suggests that CD14 polymorphisms modulate sCD14 levels up to 1 year of age. This association early in life may have an impact on TH1 polarization and subsequent protection against allergic disease.
• Wright, A. L., Stern, D. A., Kauffmann, F., & Martinez, F. D. (2006). Factors influencing gender differences in the diagnosis and treatment of asthma in childhood: the Tucson Children's Respiratory Study. Pediatric pulmonology, 41(4), 318-25.
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  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.
• Guerra, S., Graves, P. E., Morgan, W. J., Sherrill, D. L., Holberg, C. J., Wright, A. L., & Martinez, F. D. (2005). Relation of beta2-adrenoceptor polymorphisms at codons 16 and 27 to persistence of asthma symptoms after the onset of puberty. Chest, 128(2), 609-17.
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  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.
• Kurzius-Spencer, M., Halonen, M., Carla Lohman, I., Martinez, F. D., & Wright, A. L. (2005). Prenatal factors associated with the development of eczema in the first year of life. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, 16(1), 19-26.
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  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
• Kurzius-Spencer, M., Wind, S., Van Sickle, D., Martinez, P., & Wright, A. (2005). Presentation and treatment of asthma among native children in southwest Alaska delta. Pediatric pulmonology, 39(1), 28-34.
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  Our objective was to determine if a different presentation of asthma among Eskimo children in southwest Alaska influenced treatment for asthma. Data regarding symptoms, medication use, and hospitalization were obtained from the medical records of 58 Eskimo children diagnosed with asthma. Half of the children also had a diagnosis of chronic lung disease (CLD), and 57% had a history of allergies. CLD was associated with significantly more visits for wheeze (P=0.02), asthma (P
• Morgan, W. J., Stern, D. A., Sherrill, D. L., Guerra, S., Holberg, C. J., Guilbert, T. W., Taussig, L. M., Wright, A. L., & Martinez, F. D. (2005). Outcome of Asthma and Wheezing in the First Six Years of Life: Follow-up through Adolescence. American Journal of Respiratory and Critical Care Medicine.
• Morgan, W. J., Stern, D. A., Sherrill, D. L., Guerra, S., Holberg, C. J., Guilbert, T. W., Taussig, L. M., Wright, A. L., & Martinez, F. D. (2005). Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence. American journal of respiratory and critical care medicine, 172(10), 1253-8.
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  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).
• Mosley, E. E., Wright, A. L., McGuire, M. K., & McGuire, M. A. (2005). trans Fatty acids in milk produced by women in the United States. The American journal of clinical nutrition, 82(6), 1292-7.
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  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.
• Sherrill, D. L., Guerra, S., Minervini, M. C., Wright, A. L., & Martinez, F. D. (2005). The relation of rhinitis to recurrent cough and wheezing: a longitudinal study. Respiratory medicine, 99(11), 1377-85.
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  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.
• Crestani, E., Guerra, S., Wright, A. L., Halonen, M., & Martinez, F. D. (2004). Parental asthma as a risk factor for the development of early skin test sensitization in children. The Journal of allergy and clinical immunology, 113(2), 284-90.
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  Recent epidemiologic evidence has challenged the paradigm suggesting a direct causal relationship between allergic sensitization and asthma.
• Guerra, S., Carla Lohman, I., LeVan, T. D., Wright, A. L., Martinez, F. D., & Halonen, M. (2004). The differential effect of genetic variation on soluble CD14 levels in human plasma and milk. American journal of reproductive immunology (New York, N.Y. : 1989), 52(3), 204-11.
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  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.
• Guerra, S., Lohman, I. C., Halonen, M., Martinez, F. D., & Wright, A. L. (2004). Reduced interferon gamma production and soluble CD14 levels in early life predict recurrent wheezing by 1 year of age. American journal of respiratory and critical care medicine, 169(1), 70-6.
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  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.
• Guerra, S., Wright, A. L., Morgan, W. J., Sherrill, D. L., Holberg, C. J., & Martinez, F. D. (2004). Persistence of asthma symptoms during adolescence: role of obesity and age at the onset of puberty. American journal of respiratory and critical care medicine, 170(1), 78-85.
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  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.
• Stern, D. A., Lohman, I. C., Wright, A. L., Taussig, L. M., Martinez, F. D., & Halonen, M. (2004). Dynamic changes in sensitization to specific aeroallergens in children raised in a desert environment. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 34(10), 1563-669.
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  Allergen skin test reactivity and total serum IgE are objective measures used to characterize and help diagnose allergic diseases. Cross-sectional studies have shown that overall aeroallergen skin test reactivity increases throughout childhood. However, little attention has been paid to whether individual aeroallergen remittance occurs, which could distort or mask relationships to disease.
• Wind, S., Van Sickle, D., & Wright, A. L. (2004). Health, place and childhood asthma in southwest Alaska. Social science & medicine (1982), 58(1), 75-88.
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  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.
• Epple, C., Wright, A. L., Joish, V. N., & Bauer, M. (2003). The role of active family nutritional support in Navajos' type 2 diabetes metabolic control. Diabetes care, 26(10), 2829-34.
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  We examined if active family nutritional support is associated with improved metabolic outcomes for Diné (Navajo) individuals living with type 2 diabetes.
• Oddy, W. H., Halonen, M., Martinez, F. D., Lohman, I. C., Stern, D. A., Kurzius-Spencer, M., Guerra, S., & Wright, A. L. (2003). TGF-beta in human milk is associated with wheeze in infancy. The Journal of allergy and clinical immunology, 112(4), 723-8.
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  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.
• Taussig, L. M., Wright, A. L., Holberg, C. J., Halonen, M., Morgan, W. J., & Martinez, F. D. (2003). Tucson Children's Respiratory Study: 1980 to present. The Journal of allergy and clinical immunology, 111(4), 661-75; quiz 676.
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  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.
• Van Sickle, D., Morgan, F., & Wright, A. L. (2003). Qualitative study of the use of traditional healing by asthmatic Navajo families. American Indian and Alaska native mental health research (Online), 11(1), 1-18.
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  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.
• Wright, A. L., Schwindt, L. A., Bassford, T. L., Reyna, V. F., Shisslak, C. M., St Germain, P. A., & Reed, K. L. (2003). Gender differences in academic advancement: patterns, causes, and potential solutions in one US College of Medicine. Academic medicine : journal of the Association of American Medical Colleges, 78(5), 500-8.
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  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.
• Ball, T. M., Holberg, C. J., Aldous, M. B., Martinez, F. D., & Wright, A. L. (2002). Influence of attendance at day care on the common cold from birth through 13 years of age. Archives of pediatrics & adolescent medicine, 156(2), 121-6.
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  To describe trends in the occurrence of the common cold during the first 13 years of life among children who attended different childcare settings early in life.
• Karakoc, F., Remes, S. T., Martinez, F. D., & Wright, A. L. (2002). The association between persistent eosinophilia and asthma in childhood is independent of atopic status. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 32(1), 51-6.
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  Although peripheral blood eosinophilia is associated with risk of asthma, the relation with atopy has not been established.
• Castro-Rodríguez, J. A., Holberg, C. J., Morgan, W. J., Wright, A. L., & Martinez, F. D. (2001). Increased incidence of asthmalike symptoms in girls who become overweight or obese during the school years. American journal of respiratory and critical care medicine, 163(6), 1344-9.
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  The possibility of a causal relationship is suggested by recent concomitant increases in the prevalence of obesity and asthma. In a general population sample, prevalence and incidence of asthma symptoms, skin tests, and body mass index (BMI) were ascertained at mean ages of 6.3 (n = 688) and 10.9 (n = 600) yr. Lung function, bronchodilator responsiveness, and daily peak flow variability were measured at 11 yr of age. There was no association between BMI at age 6 and wheezing prevalence at any age. Females, but not males, who were overweight or obese at 11 yr of age were more likely to have current wheezing at ages 11 and 13 but not at ages 6 or 8. This effect was strongest among females beginning puberty before the age of 11. Females who became overweight or obese between 6 and 11 yr of age were 7 times more likely to develop new asthma symptoms at age 11 or 13 (p = 0.0002); at age 11 their peak flow variability and bronchodilator responsiveness were significantly more likely to be increased. In females, becoming overweight or obese between 6 and 11 yr of age increases the risk of developing new asthma symptoms and increased bronchial responsiveness during the early adolescent period.
• Castro-Rodríguez, J. A., Holberg, C. J., Morgan, W. J., Wright, A. L., Halonen, M., Taussig, L. M., & Martinez, F. D. (2001). Relation of two different subtypes of croup before age three to wheezing, atopy, and pulmonary function during childhood: a prospective study. Pediatrics, 107(3), 512-8.
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  Some retrospective evidence suggests that children with a history of croup may be at increased risk of subsequently developing asthma, atopy, and diminished pulmonary function. The objective of this study was to determine the long-term outcome of croup (as diagnosed by a physician) in early life.
• Castro-Rodríguez, J. A., Stern, D. A., Halonen, M., Wright, A. L., Holberg, C. J., Taussig, L. M., & Martinez, F. D. (2001). Relation between infantile colic and asthma/atopy: a prospective study in an unselected population. Pediatrics, 108(4), 878-82.
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  To assess whether children with history of infantile colic may be at increased risk of subsequently developing asthma and/or atopy.
• Remes, S. T., Castro-Rodriguez, J. A., Holberg, C. J., Martinez, F. D., & Wright, A. L. (2001). Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy. Journal of Allergy and Clinical Immunology, 108, 509-15.
• Van Sickle, D., & Wright, A. L. (2001). Navajo perceptions of asthma and asthma medications: clinical implications. Pediatrics, 108(1), E11.
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  Despite the large number of asthma patients, relatively little is known about the beliefs of asthmatic children and their parent(s), or the extent to which these beliefs influence management of the disease.
• Wright, A. L. (2001). The rise of breastfeeding in the United States. Pediatric clinics of North America, 48(1), 1-12.
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  What factors influenced the resurgence of breastfeeding in the last decades of the twentieth century? This article has considered several explanations. Demographic trends, particularly the increased birth rate among black and Hispanic women, coupled with the resurgence of breastfeeding in these groups, may have contributed to the increase in the breastfeeding rate during the 1990s but likely played a minimal role in the earlier, more dramatic increase. The decrease in breastfeeding in the earlier part of the twentieth century may be partly attributable to increased maternal employment, but the resurgence of breastfeeding occurred during the late twentieth century--a period of unprecedented influx of new mothers into the workforce. There is no evidence that health care practitioners are providing more support for breastfeeding, and most international and US policies postdated the resurgence of breastfeeding, although they may have influenced the increase in the 1990s. A more plausible explanation of the resurgence of breastfeeding in all major segments of society is the pervasive influence of the natural-childbirth movement of the 1960s and 1970s, with its effects on the standard management of childbirth. Also, the increase in breastfeeding among low-income women may be attributable partly to programmatic changes in the provision of supplemental food through the WIC program and the targeting of breastfeeding-promotion efforts to the specific concerns of these women. Although breastfeeding increased at the end of the twentieth century relative to earlier decades, the disparity between the recommended rates and those achieved by US women is great. Thus, efforts to increase breastfeeding initiation and duration should continue, particularly for the groups that are at greatest risk for illness, such as minority and low-income infants. This article suggests that the strategies likely to have a lasting effect on future breastfeeding rates will be social pressures that affect existing barriers to breastfeeding. Such pressures may come from health maintenance organizations, insurance companies, and the US government, which are likely to increasingly recognize the costs of not breastfeeding to their institutions. The provision of flexible work hours and paid maternity leave, either by the US government or family-friendly workplaces, could increase the ability of employed women to optimally feed their infants. As Retsinas noted in an article on the cultural context of breastfeeding, "While it is 'known' that breastfeeding is better, our society is not structured to facilitate that choice." Efforts to improve breastfeeding rates need to make visible the wider cultural context in which infant-feeding choices are made and alter components that make it difficult for US women to feed their infants optimally.
• Wright, A. L., Holberg, C. J., Taussig, L. M., & Martinez, F. D. (2001). Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood. Thorax, 56(3), 192-7.
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  The relationship between infant feeding and childhood asthma is controversial. This study tested the hypothesis that the relation between breast feeding and childhood asthma is altered by the presence of maternal asthma.
• Wright, A. L., Stern, D. A., & Halonen, M. (2001). The association of allergic sensitization in mother and child in breast-fed and formula-fed infants. Advances in experimental medicine and biology, 501, 249-55.
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  Human milk contains immunologically active substances potentially capable of altering infant immune response. As part of the prospective Children's Respiratory Study, we assessed whether the association between maternal allergic status and allergic status of the child was altered by breast-feeding. Skin-prick tests for 7 common allergens were administered to 702 6-year-old children and their mothers. The percentage of children sensitized to specific allergens, maternal skin test response to that allergen, and whether or not the child was ever breast-fed was determined. Findings indicated that specific sensitization in the mother was associated with specific sensitization in the child only if the child was breast-fed. This indirectly supports the hypothesis that contents of milk differ with maternal allergic status, and appear to affect allergic status in the child. These results suggest that milk from allergic mothers either promotes a Th2 type immune response or suppresses Th1 immune response in the child.
• Wright, A., & Schanler, R. (2001). The resurgence of breastfeeding at the end of the second millennium. The Journal of nutrition, 131(2), 421S-5S.
• Ball, T. M., Castro-Rodriguez, J. A., Griffith, K. A., Holberg, C. J., Martinez, F. D., & Wright, A. L. (2000). Siblings, day-care attendance, and the risk of asthma and wheezing during childhood.
• Castro-Rodriguez, J. A., Holberg, C. J., Wright, A. L., & Martinez, F. D. (2000). A clinical index to define risk of asthma in young children with recurrent wheezing.
• Castro-Rodríguez, J. A., Holberg, C. J., Wright, A. L., & Martinez, F. D. (2000). A clinical index to define risk of asthma in young children with recurrent wheezing. American journal of respiratory and critical care medicine, 162(4 Pt 1), 1403-6.
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  Because most cases of asthma begin during the first years of life, identification of young children at high risk of developing the disease is an important public health priority. We used data from the Tucson Children's Respiratory Study to develop two indices for the prediction of asthma. A stringent index included frequent wheezing during the first 3 yr of life and either one major risk factor (parental history of asthma or eczema) or two of three minor risk factors (eosinophilia, wheezing without colds, and allergic rhinitis). A loose index required any wheezing during the first 3 yr of life plus the same combination of risk factors described previously. Children with a positive loose index were 2.6 to 5.5 times more likely to have active asthma between ages 6 and 13 than children with a negative loose index. Risk of having subsequent asthma increased to 4.3 to 9.8 times when a stringent index was used. We found that 59% of children with a positive loose index and 76% of those with a positive stringent index had active asthma in at least one survey during the school years. Over 95% of children with a negative stringent index never had active asthma between ages 6 and 13. We conclude that the subsequent development of asthma can be predicted with reasonable accuracy using simple, clinically based parameters.
• Wright, A. L., Holberg, C. J., Taussig, L. M., & Martinez, F. (2000). Maternal asthma status alters relation of infant feeding to asthma in childhood. Advances in experimental medicine and biology, 478, 131-7.
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  The relation of infant feeding to childhood asthma is controversial. This study tested the hypothesis that maternal asthma alters the relation of breastfeeding to childhood asthma. Questionnaires were completed at age 6, 9 or 11 years by parents of 1043 children enrolled at birth. Active MD asthma was defined as a physician diagnosis of asthma plus asthma symptoms reported on one of the questionnaires. Duration of exclusive breastfeeding, categorized as never, < 4 months, or > or = 4 months, was based on prospective physician reports or questionnaires completed at 18 months. The relationship between breastfeeding and asthma differed by maternal asthma status. For children with maternal asthma, the percent developing active MD asthma increased significantly with longer duration of exclusive breastfeeding. Odds of developing asthma among these children were significantly elevated (OR: 5.7,CI: 2.8-11.5), after adjusting for confounders. This association of longer exclusive breastfeeding with increased risk of reported asthma among children with asthmatic mothers may be biologically based, or may reflect reporting biases.
• Ball, T. M., & Wright, A. L. (1999). Health care costs of formula-feeding in the first year of life. Pediatrics, 103(4 Pt 2), 870-6.
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  To determine the excess cost of health care services for three illnesses in formula-fed infants in the first year of life, after adjusting for potential confounders.
• Barton, L. L., Wright, A. L., & Lloyd, J. D. (1999). Evaluation of a pediatric residency curriculum on well-child care. Clinical pediatrics, 38(4), 245-7.
• Castro-Rodríguez, J. A., Holberg, C. J., Wright, A. L., Halonen, M., Taussig, L. M., Morgan, W. J., & Martinez, F. D. (1999). Association of radiologically ascertained pneumonia before age 3 yr with asthmalike symptoms and pulmonary function during childhood: a prospective study. American journal of respiratory and critical care medicine, 159(6), 1891-7.
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  Epidemiologic evidence suggests an association between reports of pneumonia in early life and the subsequent development of diminished lung function. However, no studies are available in which the diagnosis of pneumonia was based on radiologic evidence. Lower respiratory illnesses with or without a radiologically confirmed diagnosis of pneumonia were assessed in a study of 888 children enrolled at birth. Pulmonary function tests, markers of atopy, asthma diagnosis, and prevalence of respiratory symptoms were assessed at different ages between birth and 11 yr. Incidence of pneumonia during the first 3 yr of life was 7.4%. Respiratory syncytial virus was the most frequent agent identified both in children with pneumonia and in those with lower respiratory tract illness (LRI) without pneumonia (36.4% versus 35.6%, respectively). Children with a diagnosis of pneumonia were more likely to have physician-diagnosed asthma and current wheezing at ages 6 and 11 yr than were those who had no LRIs. When compared with children without LRIs, those with a diagnosis of pneumonia had lower levels of maximal flows at FRC at mean age of 2 mo (albeit not significantly) and at age 6 yr, and lower levels of FEV1 and FEF25-75 at age 11 yr. These deficits were independent of known confounders, including wheezing at the time of study, and were partly and significantly reversed after administration of a bronchodilator. We conclude that children with radiologically confirmed pneumonia have diminished airway function that is probably present shortly after birth. These deficits are at least in part due to alterations in the regulation of airway muscle tone.
• Halonen, M., Stern, D. A., Lohman, C., Wright, A. L., Brown, M. A., & Martinez, F. D. (1999). Two subphenotypes of childhood asthma that differ in maternal and paternal influences on asthma risk. American journal of respiratory and critical care medicine, 160(2), 564-70.
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  Asthma is a phenotypically heterogeneous disease. Two subgroups are defined here based initially on skin test reactivity to the allergen Alternaria at age 6 from among a large population of children born and raised in the Southwestern desert environment of Tucson, Arizona. When compared with asthma among Alternaria-positive subjects, asthma among Alternaria-negative subjects was associated with lower levels of total serum IgE, no relation to local aeroallergen skin tests, a younger age at diagnosis, greater remittance by age 11, and more frequent wheezing lower respiratory illnesses (LRIs) in the first year of life. Despite the difference in total serum IgE, however, IgE concentrations were significantly higher in each asthma group compared with its respective control group. Asthma in each parent contributed approximately equivalent risk for Alternaria-positive asthma in the child. However, neither parental skin test sensitization nor total serum IgE levels provided risk for asthma in the child. Inheritance patterns for Alternaria-negative asthma revealed a contribution from maternal but not paternal asthma. Thus, dividing asthma in children at age 6 into Alternaria-positive and Alternaria-negative groups identifies subphenotypes that are further distinguished by differences in phenotypic markers and parental influences.
• Holberg, C. J., Halonen, M., Wright, A. L., & Martinez, F. D. (1999). Familial aggregation and segregation analysis of eosinophil levels. American journal of respiratory and critical care medicine, 160(5 Pt 1), 1604-10.
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  The number of circulating eosinophils is associated with the risk of asthma in population samples. Therefore, eosinophil levels may be an intermediate phenotype for asthma amenable to genetic analysis. We examined familial aggregation of the number of eosinophils x 10(6) L(-1) and the percentage of eosinophils based on a 300 count differential in 644 Hispanic and non-Hispanic white families, with 2, 097 subjects, enrolled in the Tucson Children's Respiratory Study. Both measures were adjusted for age, season and year at the time blood was drawn, sex, and ethnicity. Segregation analysis was conducted in the 458 non-Hispanic white families, as there were no significant familial correlations in the Hispanic families, and there was significant heterogeneity by ethnic group. Familial correlations (rho) in the non-Hispanic white families were as follows: mother-father, 0.05; mother-child, 0.18 (p < 0.001); father-child, 0.07; sibling-sibling, 0.31 (p < 0.001). Without covariates analyses indicated a polygenic/multifactorial mode of inheritance. After adjusting for current and past asthma an oligogenic mode of inheritance was suggested, plus additional residual familial components that were mainly maternally mediated. This study supports the notion of multiple, relatively common genes interacting to determine genetic susceptibility to asthma. Holberg CJ, Halonen M, Wright AL, Martinez FD. Familial aggregation and segregation analysis of eosinophil levels.
• Sherrill, D. L., Stein, R., Halonen, M., Holberg, C. J., Wright, A., & Martinez, F. D. (1999). Total serum IgE and its association with asthma symptoms and allergic sensitization among children. The Journal of allergy and clinical immunology, 104(1), 28-36.
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  Asthma and wheezing during childhood are associated with elevated total serum IgE and with allergic sensitization to local aeroallergens. However, little is known about the longitudinal relationship between total serum IgE and the development of wheezing and allergic sensitization during childhood.
• Stein, R. T., Holberg, C. J., Sherrill, D., Wright, A. L., Morgan, W. J., Taussig, L., & Martinez, F. D. (1999). Influence of parental smoking on respiratory symptoms during the first decade of life: the Tucson Children's Respiratory Study. American journal of epidemiology, 149(11), 1030-7.
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  Compelling evidence suggests a causal relation between exposure to parental cigarette smoking and respiratory symptoms during childhood. Still, the roles of prenatal versus postnatal parental smoking need clarification. In this study, the authors assessed the effects of passive smoking on respiratory symptoms in a cohort of over 1,000 children born during 1980-1984. The children were enrolled in the Tucson Children's Respiratory Study in Tucson, Arizona, and were followed from birth to age 11 years. The population was generally middle class and consisted of two main ethnic groups, non-Hispanic Whites (75%) and Hispanics (20%), reflecting Tucson's population. Information on parental smoking and on wheeze and cough in their children was elicited from parents by using questionnaires at five different surveys. Data were analyzed both cross-sectionally and by using the generalized estimation equation approach, a longitudinal mixed-effects model. The best-fitting model indicated that maternal prenatal but not postnatal smoking was associated with current wheeze (odds ratio = 2.3, 95% confidence interval 1.4-3.8) independently of a family history of asthma, socioeconomic factors, and birth weight. This effect was time dependent and significant only below age 3 years; although independent of gender, the association was stronger for girls (odds ratio = 3.6, 95% confidence interval 1.6-8.0). Cough was not associated with parental smoking during the first decade of life. This transitory effect of maternal prenatal smoking on wheezing could be due to changes that affect the early stages of lung development.
• Stein, R. T., Sherrill, D., Morgan, W. J., Holberg, C. J., Halonen, M., Taussig, L. M., Wright, A. L., & Martinez, F. D. (1999). Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet (London, England), 354(9178), 541-5.
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  The relation between lower respiratory tract illnesses in early life caused by the respiratory syncytial virus (RSV) and the subsequent development of wheezing and atopy in childhood is not well understood. We studied this relation in children who had lower respiratory tract illnesses that occurred before 3 years of age.
• Wright, A. L., Sherrill, D., Holberg, C. J., Halonen, M., & Martinez, F. D. (1999). Breast-feeding, maternal IgE, and total serum IgE in childhood. The Journal of allergy and clinical immunology, 104(3 Pt 1), 589-94.
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  There is controversy regarding the relationship of the effect of breast-feeding on markers of allergy such as total serum IgE in childhood.
• Holberg, C. J., Morgan, W. J., Wright, A. L., & Martinez, F. D. (1998). Differences in familial segregation of FEV1 between asthmatic and nonasthmatic families. Role of a maternal component. American journal of respiratory and critical care medicine, 158(1), 162-9.
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  Studies have demonstrated familial aggregation of lung function. This study employed segregation analysis to investigate the mode of inheritance of FEV1 using regressive models for continuous traits. The study population comprised 309 families (1,163 individuals) enrolled in the Tucson Children's Respiratory Study who had both parents and at least one child with FEV1 data. Results showed significant genetic heterogeneity among the 87 families (328 individuals) with at least one member with asthma and the 222 families (835 individuals) with no asthmatic members. In families with no asthmatic members, all statistical models were rejected, indicating the absence of a major gene controlling lung function. However, a significant familial component indicated a strong polygenic/multifactorial mode of inheritance. In families with asthmatic member(s), results suggested polygenic/multifactorial inheritance with weak evidence for a Mendelian component expressed in a recessive fashion. However, while both father-offspring and mother-offspring correlations were statistically significant in families with no asthmatic members, only the mother-offspring correlation was significant in families with asthmatic members. The data suggest that lung function is inherited as a polygenic/multifactorial trait, but in asthmatic families a major element of intergenerational correlation is associated with a maternal influence, which may be genetically or environmentally mediated.
• Martinez, F. D., Stern, D. A., Wright, A. L., Taussig, L. M., & Halonen, M. (1998). Differential immune responses to acute lower respiratory illness in early life and subsequent development of persistent wheezing and asthma. The Journal of allergy and clinical immunology, 102(6 Pt 1), 915-20.
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  Recent epidemiologic evidence suggests that 2 wheezing syndromes coexist in early life: transient wheezing, limited to early childhood, and persistent wheezing, which starts in early childhood and persists beyond that age.
• Wright, A. L., & Taussig, L. M. (1998). Lessons from long-term cohort studies. Childhood asthma. The European respiratory journal. Supplement, 27, 17s-22s.
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  Cohort studies, which are longitudinal studies that follow a group of people with reference to the development of disease, have been a cornerstone of research on childhood asthma. These studies are uniquely suited to address questions concerning the incidence of illness, the natural history of disease, and the sequence of events linking exposures with outcomes. Three findings from on-going cohort studies are particularly relevant for the design of future intervention studies. First, most childhood asthma begins in infancy, with 80% of children who develop asthma having their first episode of wheeze before the age of 3 yrs. Second, events in early life, possibly including allergen exposure, infant feeding practices and viral infections, may be critical to the development of asthma in childhood. Finally, wheezing presents as separate phenotypes at different ages, with each phenotype having distinct characteristics, risk factors and prognoses. Additional cohort studies are required to determine to what extent events occurring in infancy, both viral and allergic, trigger expression of asthma, what are the mechanisms whereby they foster development of the disease, and whether their effect can be prevented.
• Wright, A. L., Bauer, M., Naylor, A., Sutcliffe, E., & Clark, L. (1998). Increasing breastfeeding rates to reduce infant illness at the community level. Pediatrics, 101(5), 837-44.
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  Although breastfeeding is associated with lower rates of a variety of infant illnesses, skeptics have suggested that much of the association is attributable to confounding, even after appropriate statistical adjustment. This article utilizes a novel design to investigate changes in infant illness at the community level after a successful breastfeeding promotion program.
• Halonen, M., Stern, D. A., Wright, A. L., Taussig, L. M., & Martinez, F. D. (1997). Alternaria as a major allergen for asthma in children raised in a desert environment. American Journal of Respiratory and Critical Care Medicine, 155, 1356-61.
• Halonen, M., Stern, D. A., Wright, A. L., Taussig, L. M., & Martinez, F. D. (1997). Alternaria as a major allergen for asthma in children raised in a desert environment. American journal of respiratory and critical care medicine, 155(4), 1356-61.
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  The relationships of asthma and allergic rhinitis with individual immediate skin test responses were examined for preferential associations and for changes with age in children raised in a semiarid environment. Prevalence of physician-diagnosed asthma was 9.8% at age 6 (n = 948) and 15.5% at age 11 (n = 895). Immediate skin test responses to Bermuda grass were the most prevalent among children with allergic rhinitis and control subjects, whereas responses to the mold, Altenaria alternata, were the most prevalent among asthmatics. Skin test responses for crude house dust, Dermatophagoides farinae, and cat had low prevalences in all groups. By logistic regression, Alternaria was the only allergen independently associated with increased risk for asthma at both ages 6 and 11. Allergic rhinitis showed independent association with sensitization to Bermuda grass and mulberry tree pollen at age 11 but did not show an independent relation to any single allergen at age 6. Logistic regression further revealed that persistent asthma (diagnosed before age 6) was independently associated with Alternaria skin tests at both ages 6 and 11, whereas new asthma (diagnosed after age 6) was associated with Alternaria skin tests at age 6 but not at age 11. We conclude that Alternaria is the major allergen associated with the development of asthma in children raised in a semiarid environment and that skin test responses at age 6 are more closely linked to asthma than those at age 11.
• Lombardi, E., Morgan, W. J., Wright, A. L., Stein, R. T., Holberg, C. J., & Martinez, F. D. (1997). Cold air challenge at age 6 and subsequent incidence of asthma. A longitudinal study. American Journal of Respiratory and Critical Care Medicine, 156, 1863-9.
• Lombardi, E., Morgan, W. J., Wright, A. L., Stein, R. T., Holberg, C. J., & Martinez, F. D. (1997). Cold air challenge at age 6 and subsequent incidence of asthma. A longitudinal study. American journal of respiratory and critical care medicine, 156(6), 1863-9.
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  The aim of this study was to assess the relation between bronchial hyperresponsiveness to dry, cold air at age 6 and the subsequent incidence of asthma. The cumulative incidence of newly diagnosed asthma between ages 6 and 11 among 360 children included in this study was 12.0%. Survival analysis showed that hyperresponsiveness to cold air at age 6 was associated with an increased risk of developing subsequent asthma (hazard ratio = 2.6, 95% CI = 1.2-5.4; p = 0.01). However, after adjusting for potential confounders, only mild wheezing at age 6 (adjusted hazard ratio 7.5, 95% CI = 3.6-15.9; p < 0.001) and skin test reactivity to allergens at age 6 (adjusted hazard ratio 3.6, 95% CI = 1.5-8.5; p < 0.01), but not hyperresponsiveness to cold air (adjusted hazard ratio = 0.9, 95% CI = 0.4-2.2; p = 0.8), remained significant predictors of subsequent development of asthma. These findings were substantially confirmed after stratifying for wheezing illnesses before age 3. We conclude that hyperresponsiveness to cold air at age 6 was associated with subsequent development of a diagnosis of asthma but this effect was not independent of atopy and mild wheezing at age 6.
• Stein, R. T., Holberg, C. J., Morgan, W. J., Wright, A. L., Lombardi, E., Taussig, L., & Martinez, F. D. (1997). Peak flow variability, methacholine responsiveness and atopy as markers for detecting different wheezing phenotypes in childhood. Thorax, 52(11), 946-52.
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  There is increasing evidence that wheezing during childhood may be a heterogeneous condition, and that different forms of wheezing may be associated with different risk factors and prognosis. The aim of this study was to determine if measures of airway lability and of atopy could identify distinct wheezing phenotypes during childhood.
• Wright, A. L., Naylor, A., Wester, R., Bauer, M., & Sutcliffe, E. (1997). Using cultural knowledge in health promotion: breastfeeding among the Navajo. Health education & behavior : the official publication of the Society for Public Health Education, 24(5), 625-39.
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  Although many attempts have been made to promote breastfeeding in a variety of contexts, few programs have explicitly incorporated cultural beliefs in these efforts. This article describes a breastfeeding promotion program conducted on the Navajo reservation. This program was designed to be culturally appropriate. Background information regarding beliefs and factors affecting infant feeding practices in this setting is provided, followed by a description of the intervention. The intervention, which incorporated both social marketing and community participation techniques, consisted of three components: an intervention in the health care system, a community intervention, and an individual intervention. Based on medical records review of feeding practices of all the infants born the year before (n = 988) and the year after (n = 870) the intervention, the program was extremely successful. This combination of techniques, including qualitative and quantitative research into local definitions of the problem, collaboration with local institutions and individuals, reinforcement of traditional understandings about infant feeding, and institutional change in the health care system, is an effective way of facilitating behavioral change.
• Aldous, M. B., Holberg, C. J., Wright, A. L., Martinez, F. D., & Taussig, L. M. (1996). Evaporative cooling and other home factors and lower respiratory tract illness during the first year of life. Group Health Medical Associates. American journal of epidemiology, 143(5), 423-30.
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  Lower respiratory tract illness (LRI) is associated with exposure to various environmental factors. The relation between home environment and LRI in infants was studied with the use of data from the Children's Respiratory Study in Tucson, Arizona. Healthy infants from a health maintenance organization were recruited at birth (1980-1984). Analysis was restricted to one infant per family, and to those followed through the first year (n=936). Environmental data were collected at enrollment, and clinicians diagnosed LRI according to predetermined criteria. During the first year of life, 196 infants (21%) had wheezing LRI, and 60 (6%) had nonwheezing LRI. The risk of wheezing LRI was higher in infants with evaporative home cooling (24%) than in those without evaporative home cooling (15%) (odds ratio = 1.8, 95% confidence interval 1.1-3.0); this association was stronger among infants who lived with other children in the home. The risk of nonwheezing LRI was associated with parents' rating of neighborhood dustiness, ranging from 5% in the least dusty environments to 12% in the dustiest (p for trend = 0.002). Neither association could be explained by confounding factors. LRI was not related to the type of home heating, cooking fuel, or the numbers of indoor dogs or cats.
• Bauer, M., & Wright, A. L. (1996). Integrating qualitative and quantitative methods to model infant feeding behavior among Navajo mothers. Human Organization, 55(2), 183-192.
• Holberg, C. J., Elston, R. C., Halonen, M., Wright, A. L., Taussig, L. M., Morgan, W. J., & Martinez, F. D. (1996). Segregation analysis of physician-diagnosed asthma in Hispanic and non-Hispanic white families. A recessive component?. American journal of respiratory and critical care medicine, 154(1), 144-50.
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  The inheritance of asthma, evident from its high family concordance, is not well understood. To investigate whether asthma may be inherited through a major gene with two alleles, segregation analyses were conducted in 3,369 individuals from 906 nuclear families enrolled, without selection, in a longitudinal study of respiratory health in Tucson, Arizona. Physician-diagnosed asthma and its age of onset were ascertained for each family member when children were at a mean age of 7 yr. Age of asthma diagnosis was allowed for in analyses, and the impact of the covariate total serum IgE level on age of onset was examined. Segregation analyses were conducted with and without residual family effects, with and without the covariate IgE. The hypothesis of a single two-allele locus for asthma was rejected. However, depending on the method of assessment of the residual familial effects, either a polygenic/multifactorial mode of inheritance alone, or an oligogenic model with some evidence of a recessive component present in the population with the high frequency of 0.67, were compatible with the data. Results were unchanged with the addition of the covariate IgE.
• Lombardi, E., Stein, R. T., Wright, A. L., Morgan, W. J., & Martinez, F. D. (1996). The relation between physician-diagnosed sinusitis, asthma, and skin test reactivity to allergens in 8-year-old children. Pediatric pulmonology, 22(3), 141-6.
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  The purpose of this study was to assess the prevalence of sinusitis in a nonselected sample of children, and the relation of sinusitis to allergic rhinitis (AR), atopy, asthma, and cough in the same population sample. Of 1246 children enrolled at birth in the Tucson Children's Respiratory Study, 835 were studied at a mean age +/-SD of 8.6 +/- 0.7 years. Questionnaires asking about MD-Sinusitis, MD-AR, MD-Asthma, and cough were completed by parents. Skin tests for seven common aeroallergens in the Tucson area had been performed in 630 of the participating children at the mean age +/-SD of 6.3 +/- 0.9 years. Prevalence of MD-Sinusitis was 13.1%; 78% of subjects with MD-Sinusitis also had MD-AR. Detailed analysis of the relation between MD-Sinusitis and individual environmental allergens tested for showed that only a response to Bermuda grass pollen was significantly associated with MD-Sinusitis after controlling for MD-AR [adjusted odds ratio 2.3 (95% CI 1.2-4.3)]. Having MD-Sinusitis was also significantly associated with MD-Asthma and cough [odds ratios 3.0 (95% CI 1.8-5.2)] and 2.5 (95% CI 1.6-3.8), respectively]. However, logistic regression demonstrated that, after controlling for MD-AR and skin test reactivity, MD-Sinusitis was no longer significantly associated with MD-Asthma or cough. We conclude that MD-Sinusitis is a common condition in childhood. The main independent risk factors in our community for MD-Sinusitis were grass pollen and current MD-AR. MD-Sinusitis was not associated with MD-Asthma or with cough after controlling for skin test reactivity and for MD-AR.
• Miller, A. L., Stern, D. A., Martinez, F. D., Wright, A. L., Taussig, L. M., & Halonen, M. (1996). Serum levels of the soluble low affinity receptor for IgE and soluble interleukin-2 receptor in childhood, and their relation to age, gender, atopy and allergic disease. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, 7(2), 68-74.
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  Identifying immune factors associated with the development of atopy can enhance our understanding of the in vivo mechanisms involved and may have utility in paradigms designed to prevent disease. Two candidates suggested for such roles are the soluble low affinity receptor for IgE (sCD23) and the soluble interleukin-2 receptor (sCD25). To assess serum levels of these factors blood samples were collected at birth and at age 6 in a large nonselected population from Tucson, AZ. Log mean sCD23 and sCD25 levels decreased from birth to age 6, (for sCD23 0.60 ffi 0.26pg/l, n = 340 and 0.53 + 0.28pg/l, n = 333 and for sCD25 1.95 i 0.14pM, n = 304 and 1.86 ffi 0.20pM, n = 327, for the two ages respectively. Anglo children had lower sCD23 levels at birth compared to Hispanic children (p < 0.01); no effect of gender was observed. Skin test reactivity at age 6 was directly related to sCD25 levels at age 6 (p = 0.007) and even levels at birth showed a similar trend (p = 0.06). These relations were distinct from any relation to total serum IgE. No relation was observed with sCD23 levels for either skin test reactivity or serum IgE. The prevalences of asthma, rhinitis and eczema by age 6 were unrelated to sCD25 or sCD23 levels. The results indicate that soluble CD23 and CD25 have higher levels at birth than later in childhood and that the development of skin test reactivity may be associated with regulatory mechanisms involving sCD25, whereas sCD23 was not similarly implicated.
• Wright, A. L., Holberg, C. J., Morgan, W. J., Taussig, L. M., Halonen, M., & Martinez, F. D. (1996). Recurrent cough in childhood and its relation to asthma. American journal of respiratory and critical care medicine, 153(4 Pt 1), 1259-65.
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  Risk factors for recurrent cough (RC) in childhood, and its relation to asthma were investigated as part of the prospective, longitudinal Tucson Children's Respiratory Study. RC, defined as > or = 2 episodes of cough without a cold in the past year, was assessed by questionnaire in 987 children at age 6. Children having RC without wheeze (n = 154) did not differ from children with neither symptom (n = 610) in serum IgE levels, skin test response, size-corrected forced expiratory flow, or percentage of decline following cold air challenge. In contrast, children with both RC and wheeze (n = 116) had significantly more respiratory illness, more atopy, lower flow at end-tidal expiration (V'maxFRC), and greater declines in lung function following cold air challenge than children with neither symptom. Current parental smoking was a risk for RC without wheeze, whereas male gender, maternal allergy, wheezing lower respiratory tract illness (LRI) in early life, and high IgE were significant risks for RC with wheeze, compared with children having neither symptom. RC early in life resolved in the majority of children, between ages 2-3 yr and age 6, and between age 6 and age 11. High IgE and positive skin prick test were associated with persistence of RC to age 6 among children who wheezed, and markers of allergy were associated with persistence of RC between 6 and 11 yr. These findings suggest that recurrent cough in the absence of wheeze differs in important respects from classic asthma, and using the same label to refer to these distinct syndromes may obscure their diverse pathophysiologies.
• Wright, A., Rice, S., & Wells, S. (1996). Changing hospital practices to increase the duration of breastfeeding. Pediatrics, 97(5), 669-75.
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  To change the breastfeeding policy in a university teaching hospital in accord with the Ten Steps to Successful Breastfeeding of the United Nations Children's Fund and World Health Organization and to assess the impact of hospital practices on the duration of breastfeeding.
• Ey, J. L., Holberg, C. J., Aldous, M. B., Wright, A. L., Martinez, F. D., & Taussig, L. M. (1995). Passive smoke exposure and otitis media in the first year of life. Group Health Medical Associates. Pediatrics, 95(5), 670-7.
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  This study examined, in a health maintenance organization population of children, the associations between parents' smoking and otitis media (OM) in their children while controlling for other known risk factors.
• Martinez, F. D., Stern, D. A., Wright, A. L., Holberg, C. J., Taussig, L. M., & Halonen, M. (1995). Association of interleukin-2 and interferon-gamma production by blood mononuclear cells in infancy with parental allergy skin tests and with subsequent development of atopy. The Journal of allergy and clinical immunology, 96(5 Pt 1), 652-60.
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  The mechanisms regulating the onset of atopic sensitization in human beings are not yet fully clarified. We assessed the capacity of mitogen-stimulated umbilical and peripheral blood mononuclear cells to produce interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) at birth and at 9 months of age in 159 infants. Mononuclear cell production of both IFN-gamma and IL-2 at 9 months, but not at birth, was found to be inversely related to parental immediate skin test reactivity to seven local aeroallergens. Skin test reactivity at the age of 6 years was also inversely related to IFN-gamma and IL-2 production at 9 months of age. However, no relationship was evident between total serum IgE levels at 6 years and production of these cytokines at 9 months. The proportions of circulating lymphocytes and CD4+ or CD8+ cells were also unrelated to skin test reactivity at the age of 6 years. These data suggest that mechanisms regulating skin test reactivity to inhaled allergens may involve deficient IFN-gamma production, deficient IL-2 production, or both during or preceding the time of initial sensitization and that additional mechanisms are involved in regulating total serum IgE level.
• Martinez, F. D., Stern, D. A., Wright, A. L., Taussig, L. M., & Halonen, M. (1995). Association of non-wheezing lower respiratory tract illnesses in early life with persistently diminished serum IgE levels. Group Health Medical Associates. Thorax, 50(10), 1067-72.
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  The role of lower respiratory tract illnesses (LRIs) in the development of allergies is not well understood. The relation of wheezing and non-wheezing LRIs to serum IgE levels and atopy was studied in 888 children.
• Martinez, F. D., Wright, A. L., Taussig, L. M., Holberg, C. J., Halonen, M., & Morgan, W. J. (1995). Asthma and wheezing in the first six years of life. The Group Health Medical Associates. New England Journal of Medicine, 332, 133-8.
• Martinez, F. D., Wright, A. L., Taussig, L. M., Holberg, C. J., Halonen, M., & Morgan, W. J. (1995). Asthma and wheezing in the first six years of life. The Group Health Medical Associates. The New England journal of medicine, 332(3), 133-8.
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  Many young children wheeze during viral respiratory infections, but the pathogenesis of these episodes and their relation to the development of asthma later in life are not well understood.
• Wright, A. L., Holberg, C. J., Taussig, L. M., & Martinez, F. D. (1995). Relationship of infant feeding to recurrent wheezing at age 6 years. Archives of pediatrics & adolescent medicine, 149(7), 758-63.
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  To investigate the relationship of infant feeding to recurrent wheezing at age 6 years and to assess whether this relationship is altered by a history of wheezing lower respiratory tract illnesses.
• Martinez, F. D., Holberg, C. J., Halonen, M., Morgan, W. J., Wright, A. L., & Taussig, L. M. (1994). Evidence for Mendelian inheritance of serum IgE levels in Hispanic and non-Hispanic white families. American journal of human genetics, 55(3), 555-65.
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  Considerable evidence is available suggesting a significant genetic component in the pathogenesis of asthma, but the mechanism of inheritance is not well understood. The main objective of this study was to assess if total serum IgE level, a known intermediate phenotype for asthma, is under the control of a major autosomal gene. We studied nuclear families participating in the Tucson Children's Respiratory Study in Tucson and originally selected because they belonged to a health maintenance organization. One hundred twenty-five Hispanic and 673 non-Hispanic White nuclear families were eligible; 50 Hispanic families (with 191 subjects) and 241 non-Hispanic White families (with 886 subjects) were included. Prevalence of asthma, hay fever, and parental smoking was similar among eligible families who were included and those who were not. Segregation analyses using regressive models for continuous traits showed that the best fit to the data was given by a model of Mendelian codominant inheritance of a major autosomal gene associated with higher serum IgE level. Log-likelihood for this model was not significantly different from that of the best-fitting ("unrestricted") model (P = .3) and was significantly better than log-likelihood for a dominant model (P < .0001) and a recessive model (P < .0001). An environmental model showed significant departure (P < .0001) from the unrestricted model. Tests for genetic heterogeneity showed no significant difference between the two ethnic groups. The data strongly suggest that total serum IgE levels are controlled by a major autosomal codominant gene.
• Martinez, F. D., Wright, A. L., & Taussig, L. M. (1994). The effect of paternal smoking on the birthweight of newborns whose mothers did not smoke. Group Health Medical Associates. American journal of public health, 84(9), 1489-91.
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  We examined the relationship of paternal smoking habits to birthweight in a cohort of infants enrolled at birth (n = 1219). To assess validity of parental smoking reports, cord serum levels of cotinine were measured in 175 newborns. A mean birthweight deficit of 88 g was found in newborns of nonsmoking mothers whose fathers smoked more than 20 cigarettes/day. Only 2 of 138 newborns whose mothers said they were nonsmokers had cotinine levels indicating that their mothers were active smokers. Among infants of nonsmoking mothers, detectability of cotinine in cord blood was significantly correlated with the number of cigarettes smoked daily by fathers. These data suggest that fetal growth may be adversely affected when the mother is passively exposed to tobacco smoke during pregnancy.
• Wright, A. L., Holberg, C. J., Martinez, F. D., Halonen, M., Morgan, W., & Taussig, L. M. (1994). Epidemiology of physician-diagnosed allergic rhinitis in childhood. Pediatrics, 94(6 Pt 1), 895-901.
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  To investigate the natural history of and risk factors for allergic rhinitis in the first 6 years of life.
• Camilli, A. E., Holberg, C. J., Wright, A. L., & Taussig, L. M. (1993). Parental childhood respiratory illness and respiratory illness in their infants. Group Health Medical Associates. Pediatric pulmonology, 16(5), 275-80.
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  Parental histories of childhood respiratory trouble (CRT) were examined as risk factors for lower respiratory tract illnesses in healthy infants enrolled in the Children's Respiratory Study, Tucson, Arizona. A parental history of childhood respiratory trouble before age 16 was a risk factor for infantile lower respiratory tract illnesses (LRIs). Early age of onset of the parental CRT and those illnesses described as asthma or bronchiolitis showed the greatest risk: odds ratio = 2.8, P < 0.05. After controlling for known and suspected confounders, a parental history of CRT described as asthma or bronchiolitis with onset before age 3 was associated with wheezing LRIs in their children, with an odds ratio of 2.6, P < 0.05. A parental history of CRT described as bronchitis/croup was associated with nonwheezing LRIs in their children: odds ratio = 2.2, P < 0.05. These findings suggest a familial component to childhood respiratory trouble which may have a hereditary basis.
• Duncan, B., Ey, J., Holberg, C. J., Wright, A. L., Martinez, F. D., & Taussig, L. M. (1993). Exclusive breast-feeding for at least 4 months protects against otitis media. Pediatrics, 91(5), 867-72.
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  This study was designed to assess the relation of exclusive breast-feeding, independent of recognized risk factors, to acute and recurrent otitis media in the first 12 months of life.
• Holberg, C. J., Wright, A. L., Martinez, F. D., Morgan, W. J., & Taussig, L. M. (1993). Child day care, smoking by caregivers, and lower respiratory tract illness in the first 3 years of life. Group Health Medical Associates. Pediatrics, 91(5), 885-92.
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  Day-care attendance has been associated with an increased risk of hospitalization for lower respiratory tract illnesses (LRIs). This study examines, in a health maintenance organization population of children, the associations between child day care and the occurrence of LRIs in the first 3 years of life. Smoking by caregivers and a possible protective effect of longer day-care enrollment in relation to LRIs are also addressed.
• Ray, C. G., Holberg, C. J., Minnich, L. L., Shehab, Z. M., Wright, A. L., & Taussig, L. M. (1993). Acute lower respiratory illnesses during the first three years of life: potential roles for various etiologic agents. The Group Health Medical Associates. The Pediatric infectious disease journal, 12(1), 10-4.
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  Lower respiratory tract illnesses (LRIs) occurring during the first 3 years of life among children enrolled in the Tucson Children's Respiratory Study have been studied for evidence of viral, mycoplasmal and Chlamydia trachomatis infections. This report examines those from whom adequate acute and convalescent sera were available at the time of the LRI. Two groups were compared: those in whom culture and/or antigen detection yielded an etiologic agent (N = 110); and those who did not (culture negative, N = 124). Seroconversions (> or = 4-fold titer rise) to respiratory syncytial virus; influenza virus types A and B; parainfluenza virus types 1, 2 and 3; or adenovirus were found in only 0 to 5% of the culture negative group. No significant differences between groups with regard to frequencies of seroconversion to influenza type C, parainfluenza virus type 4, human coronaviruses 229E and OC43 or cytomegalovirus were detected, which suggests that these agents may not be frequent primary causes of LRIs among otherwise healthy children. Significant differences in seroconversions to Epstein-Barr virus were detected, suggesting that Epstein-Barr virus may contribute to LRI morbidity; however, its exact role remains to be defined.
• Ray, C. G., Minnich, L. L., Holberg, C. J., Shehab, Z. M., Wright, A. L., Barton, L. L., & Taussig, L. M. (1993). Respiratory syncytial virus-associated lower respiratory illnesses: possible influence of other agents. The Group Health Medical Associates. The Pediatric infectious disease journal, 12(1), 15-9.
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  Acute lower respiratory illnesses were prospectively investigated in a cohort of 1246 healthy infants who were enrolled at birth in the Tucson Children's Respiratory Study and followed through the first 3 years of life. Respiratory syncytial virus (RSV) infection was documented by culture, antigen detection or both in 276 episodes. In 21 (7.6%) of these 276, other viruses were simultaneously detected. Further serologic studies of 50 episodes in which RSV had been found increased the apparent viral codetection rate to 24%. When culture results for Chlamydia trachomatis and Mycoplasma pneumoniae were also considered, the rate of codetection was found to be 10.9% (30 of 276); this increased to 28% for the subgroup of episodes (14 of 50) that was further studied serologically. Illnesses associated with more than one agent were not significantly different from those involving RSV alone, with respect to month of onset, age at illness, illness type or duration of illness. We conclude that when RSV has been detected in previously healthy infants, routine searches for the concomitant presence of other viruses are usually not warranted.
• Williams, R., Boyce, W. T., & Wright, A. L. (1993). The relationship of family structure and perceived family support to length of hospital stay. Family practice research journal, 13(2), 185-93.
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  Membership in an extended family has been viewed as beneficial, particularly in time of crisis, because of the support and resources that can be provided a member. In an attempt to confirm this view of the family, a study was conducted among Navajo Indians at the time of hospitalization. Instruments assessed family characteristics regarding extended or nuclear structure and the amount of family support the patient perceived. Scores obtained were correlated with the patient's subsequent length of hospital stay. Perceived support was related to length of stay (r = .28, p < .001), while family structure was not (r = .10, p = .10). As hypothesized, greater perceived support was associated with longer length of stay. The results are consistent with other findings suggesting social systems gain importance from function, not structure. If these results are confirmed in other groups, use of a simple tool for assessing support may assist in predicting length of hospital stay.
• Wright, A. L., Bauer, M., Clark, C., Morgan, F., & Begishe, K. (1993). Cultural interpretations and individual beliefs about breastfeeding among the Navajo. American Ethnologist, 20(4), 781-796.
• Wright, A. L., Clark, C., & Bauer, M. (1993). Maternal employment and infant feeding practices among the Navajo. Medical Anthropology Quarterly, 7(3), 260-281.
• Halonen, M., Stern, D., Taussig, L. M., Wright, A., Ray, C. G., & Martinez, F. D. (1992). The predictive relationship between serum IgE levels at birth and subsequent incidences of lower respiratory illnesses and eczema in infants. The American review of respiratory disease, 146(4), 866-70.
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  Cord serum IgE levels are predictive of subsequent atopic diseases early in life. Lower respiratory illnesses (LRI) have often been included with atopic diseases in infancy but have not been examined as a separate entity for a relation to cord IgE levels. Among 767 healthy newborns in Tucson, Arizona studied longitudinally, cord serum IgE levels were directly related to the subsequent incidence of eczema. In contrast, the incidence of LRI not only failed to show a direct relationship to IgE levels but actually decreased with increasing cord IgE levels from 34.8% in the lowest cord IgE group to 22.2% in the highest IgE group (greater than 1.0 IU/ml IgE; p for trend chi-square less than 0.03). Limiting LRI to those with wheeze did not alter the inverse relationship with IgE levels. The inverse LRI-IgE relationship was strong for non-RSV LRI, whereas RSV LRI had neither a direct nor an inverse relationship. These inverse LRI-IgE relationships were significant for LRI occurring in infants before but not after 6 months of age. Maternal (but not paternal) allergic history was associated with higher cord IgE levels and with an increased incidence of LRI, the latter effect being independent of IgE. This study suggests that most LRI in the first year of life are not early manifestations of an allergic predisposition.
• Martinez, F. D., Wright, A. L., Holberg, C. J., Morgan, W. J., & Taussig, L. M. (1992). Maternal age as a risk factor for wheezing lower respiratory illnesses in the first year of life. American journal of epidemiology, 136(10), 1258-68.
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  Postneonatal mortality due to respiratory illnesses is known to be inversely related to maternal age, but the possible role of young motherhood as a risk factor for respiratory morbidity in infants has not been thoroughly explored. The authors studied the incidence of lower respiratory tract illnesses during the first year of life, as ascertained by health plan pediatricians, in over 1,200 infants enrolled at birth between 1980 and 1984 in Tucson, Arizona. The incidence of wheezing lower respiratory tract illnesses increased significantly (p = 0.005) with decreasing maternal age, whereas the incidence of nonwheezing lower respiratory tract illness was independent of maternal age. A logistic regression was used to control for the effects of several known confounding factors. When compared with infants of mothers aged more than 30 years, adjusted odds ratios were 2.4 (95% confidence interval 1.8-3.1) for infants whose mothers were less than age 21 years (p < 0.0001), 1.8 (95% confidence interval 1.4-2.3) for infants whose mothers were aged 21-25 (p < 0.0001); and 1.4 (95% confidence interval 1.1-1.6) for infants whose mothers were aged 26-30 (p < 0.001). These results suggest that young motherhood is an important risk factor for wheezing lower respiratory tract illnesses during the first year of life. Both biological and social factors related to maternal age may explain these findings.
• Stern, D. A., Hicks, M. J., Martinez, F. D., Holberg, C. J., Wright, A. L., Pinnas, J., Halonen, M., & Taussig, L. M. (1992). Lymphocyte subpopulation number and function in infancy. Developmental immunology, 2(3), 175-9.
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  Normal values for percentages of lymphocyte subpopulations and functional responses to mitogen stimulation in infancy are not well established. In the present study, lymphocyte subpopulations were examined in umbilical cord blood samples and in peripheral blood samples drawn before 7 and 24 months of age (mean age 10.4 months) from a healthy population of infants born in Tucson, Arizona. Results indicate significant increases occurred from birth to later infancy in the percentages of total T cells (CD3), T-cell subsets (CD4, CD8) and B cells (CD20). The CD4/CD8 ratio and the functional responses to ConA and PWM mitogens significantly decreased from birth to later infancy. PHA responsiveness did not show a significant change. Results from cross-sectional analyses (n = 271) were supported in a smaller longitudinal subset (n = 37). There were no detectable ethnic- or gender-related differences in cord blood or samples obtained in later infancy. The normal values established in this study will be useful in studies of immune-system maturation and in the clinical evaluation of newborns, infants, and toddlers suspected of either acquired or congenital immune-deficiency states.
• Williams, R., Zyzanski, S. J., & Wright, A. L. (1992). Life events and daily hassles and uplifts as predictors of hospitalization and outpatient visitation. Social science & medicine (1982), 34(7), 763-8.
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  Increased occurrence of major life events and daily "hassles" and "uplifts" have been shown to be associated with several measures of health status and health care utilization. In order to test for such an association with hospital admission, a prospective study was designed. Navajo Indians presenting for either inpatient or outpatient health care at a U.S. Indian Health Service facility were questioned regarding the occurrence of major life events in the preceding six months and of hassles and uplifts in the preceding week. Two years later the subsequent numbers of outpatient visits and of hospital admissions were determined for each subject. An increased number of either major life events (relative risk 1.66) or daily hassles and uplifts (relative risk 1.87) was found to be associated with an increased risk of hospital admission. The effects of major and daily life events were additive on the risk of admission. In addition, hassles were predictive of subsequent outpatient utilization. While further demonstrating the influence of major and daily life occurrences on health care utilization, this study also shows their importance in an additional cultural setting.
• Halonen, M., Stern, D., Lyle, S., Wright, A., Taussig, L., & Martinez, F. D. (1991). Relationship of total serum IgE levels in cord and 9-month sera of infants. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 21(2), 235-41.
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  To characterize IgE levels at birth and changes in those levels during the first year of life and to identify factors that might influence IgE levels in infancy, we measured IgE levels in 1074 umbilical cord sera and in 697 sera obtained at 9 months of age in a healthy population of infants enrolled at birth into the Children's Respiratory Study in Tucson, Arizona, U.S.A. Serum IgE levels at birth and 9 months were log normally distributed with geometric means of 0.09 and 3.87 IU/ml, respectively. Cord serum IgE levels were unaffected by maternal smoking. Levels varied according to month of birth with a nadir in September. Cord and 9-month serum IgE levels were higher in boys than in girls, Hispanics compared with Anglos, and infants who developed eczema compared with those who did not, but the mean increases in log IgE from birth to 9 months were not significantly affected by these factors. A significant correlation between IgE levels at cord and 9 months was observed (r = 0.44; P less than 0.0001). Also, mean log IgE levels at 9 months in infants grouped according to cord serum IgE levels maintained the same rank order of mean values as the cord groups. These data indicate that 9-month IgE levels are influenced by cord serum IgE levels and that the main influence of gender, ethnicity and susceptibility to eczema on IgE levels occurs before birth.
• Holberg, C. J., Wright, A. L., Martinez, F. D., Ray, C. G., Taussig, L. M., & Lebowitz, M. D. (1991). Risk factors for respiratory syncytial virus-associated lower respiratory illnesses in the first year of life. American journal of epidemiology, 133(11), 1135-51.
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  The relation of breast feeding and other factors to the incidence of respiratory syncytial virus-associated lower respiratory tract illness (RSV-LRI) in the first year of life is examined. The study population is 1,179 healthy infants enrolled at birth between May 1980 and January 1984 into the Tucson Children's Respiratory Study, Tucson, Arizona. Each subject's data were assessed at each month of age during the first year of life, during those months when respiratory syncytial virus was isolated. A number of significant relations were observed, particularly between 1 and 3 months of age. At this age, the risk of having a RSV-LRI increased in association with less than 1-month or no breast feeding, with being male, and with increasing numbers of others sharing the child's bedroom. In multivariate analysis, only sex and the number of others sharing the room remained as significant direct effects. However, a significant interaction demonstrated that breast feeding has a protective role in relation to RSV-LRIs for those infants of mothers with a lower education level. The risk of having a RSV-LRI increases with combinations of risk factors. Being in day care was a significant risk factor in the 7- to 9-month age range. The RSV-LRI rate also varies by birth month. A separate case-control study assessed relations of RSV-LRIs with cord serum RSV antibody. Those with lower cord serum RSV antibody, who also have minimal breast feeding, were found to be especially at risk for RSV-LRIs in the first 5 months of life.
• Martinez, F. D., Morgan, W. J., Wright, A. L., Holberg, C., & Taussig, L. M. (1991). Initial airway function is a risk factor for recurrent wheezing respiratory illnesses during the first three years of life. Group Health Medical Associates. The American review of respiratory disease, 143(2), 312-6.
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  We recently reported a significant relationship between lung function measured prior to any lower respiratory tract illness and subsequent wheezing illnesses during the first year of life (N Engl J Med 1988; 319:1112-7). Follow-up has continued for this group of infants during the second and third years of life. When compared with never wheezers, infants who wheezed during the first year of life and had at least one additional lower respiratory illness had 22% lower initial levels of an indirect index of airway conductance derived from the shape of tidal breathing curves (p less than or equal to 0.01), 22% lower respiratory conductance (p less than or equal to 0.05), 25% lower maximal flows at the end-expiratory point (p less than or equal to 0.01), and 10% lower functional residual capacity (p less than or equal to 0.05). Infants who wheezed only once during the first 3 yr of life or who started wheezing during the second year of life had normal tidal breathing curves but significantly lower maximal expiratory flows (p less than or equal to 0.05). Their functional residual capacity was also lower than that of never wheezers (p less than or equal to 0.05). We conclude that diminished initial airway function may be a predisposing factor for recurrent wheezing respiratory illnesses starting in the first year of life. Infants who will have only one wheezing respiratory illness or who will start wheezing after the first year of life seem to have lower levels for some but not for all lung function tests performed in this study.
• Wright, A. L., Holberg, C., Martinez, F. D., & Taussig, L. M. (1991). Relationship of parental smoking to wheezing and nonwheezing lower respiratory tract illnesses in infancy. Group Health Medical Associates. The Journal of pediatrics, 118(2), 207-14.
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  The relationship between parental smoking and lower respiratory tract illness (LRI) was studied in a large cohort of infants followed prospectively from birth. Illnesses were diagnosed by physicians using agreed-on criteria, and parental smoking histories were obtained by questionnaire. The LRIs were differentiated into wheezing and nonwheezing episodes, and the age at first illness of either type was evaluated in relation to smoking by parents. The odds of having an LRI were significantly higher in children whose mothers smoked (odds ratio 1.52; confidence interval 1.07 to 2.15). The odds were higher if the mother smoked a pack of cigarettes or more per day and if the child stayed home rather than attending day care (odds ratio 2.8; confidence interval 1.43 to 5.5). Logistic regression indicated that the LRI rate was significantly elevated both in children exposed to heavy maternal smoke in the absence of day care, and in those who use day care but were not exposed to maternal smoking of a pack or more per day. These findings could not be attributed to other confounding variables. Neither paternal smoking nor smoking by other household members was consistently related to the LRI rate. The relationship of maternal smoking to LRI rate was evident for both wheezing and nonwheezing illnesses. Maternal smoking of a pack or more per day was also related to an early age at first LRI, for both wheezing (p less than 0.05) and nonwheezing (p less than 0.002) illnesses. In sum, maternal smoking is associated with a higher rate of LRIs in the first year, particularly when mothers smoked a pack or more per day and when the child did not use day care.
• Wright, A. L., & Morgan, W. J. (1990). On the creation of 'problem' patients. Social science & medicine (1982), 30(9), 951-9.
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  Recent debates regarding clinical transactions oppose a macro-level approach which emphasizes political, economic and institutional forces, and those analysts who consider patient perceptions regarding illness to be major influences on the outcome of clinical encounters. This paper utilizes both approaches to illuminate the interactions between medical personnel and 'problem patients'. The macro-level approach draws attention to the way power is negotiated and expressed in clinical interactions, and to medicalization that gives priority to medical values and condemns patients who do not act in accord with these values. The patient belief approach explores one of the major weapons in the struggle for control, the disease model of illness. Use of both approaches permits a better understanding of clinical medicine in these problematic interactions.
• Boyce, W. T., Schaefer, C., Harrison, H. R., Haffner, W. H., Lewis, M., & Wright, A. L. (1989). Sociocultural factors in puerperal infectious morbidity among Navajo women. American journal of epidemiology, 129(3), 604-15.
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  From 1980 to 1982, a sample of 968 pregnant Navajo women in New Mexico was enrolled in a prospective study of biologic and sociocultural factors in puerperal infectious morbidity. Past studies have independently implicated both genital infection and psychosocial stressors in perinatal complications, but, to the authors' knowledge, no previous work has concurrently investigated the interactive effects of genital pathogens and psychosocial processes. Endocervical cultures for Mycoplasma hominis and Chlamydia trachomatis were obtained during prenatal visits, and structured interviews were conducted assessing social support and the degree of cultural traditionality, in this context a proxy measure of acculturative stress. The incidences of postpartum fever, endometritis, and premature rupture of membranes were significantly associated with the concurrence of two factors: the presence of genital tract M. hominis and a highly traditional cultural orientation. When demographic and conventional obstetric risk factors were controlled for, women with both M. hominis and high traditionality experienced infectious complications at a rate twice that of women with either factor alone. Among the plausible explanations for this result is the possibility that acculturative stress undermines physiologic resistance to infectious genital tract disease.
• Taussig, L. M., Wright, A. L., Morgan, W. J., Harrison, H. R., & Ray, C. G. (1989). The Tucson Children's Respiratory Study. I. Design and implementation of a prospective study of acute and chronic respiratory illness in children. American journal of epidemiology, 129(6), 1219-31.
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  The Tucson Children's Respiratory Study, Tucson, Arizona, has been established as a long-term, longitudinal, prospective study of the risk factors for acute lower respiratory tract illnesses in early childhood and for chronic obstructive airways disease in later life. A total of 1,246 newborns were enrolled into the study between May 1980 and January 1984, representing 78% of eligible infants. Cord blood for immunologic studies, neonatal blood specimens for blood counts and differentials, and blood specimens at nine to 15 months of age for immunologic studies, blood counts, and differentials have been obtained on the majority of enrolled children. Pre-illness physiologic and more detailed immunologic studies have also been done on large subgroups of subjects. The majority of lower respiratory tract illnesses suffered by these children in the first three years of life have been assessed in detail for etiologic agents by means of culture and serologic techniques; 1,052 illnesses have been evaluated thus far. The type of illness and nature of etiologic agents are very similar to those reported in other epidemiologic studies. Thus, this group of enrolled infants and their family members constitute an appropriate population for the long-term study of risk factors for acute and chronic respiratory disorders.
• Wright, A. L., Holberg, C. J., Martinez, F. D., Morgan, W. J., & Taussig, L. M. (1989). Breast feeding and lower respiratory tract illness in the first year of life. Group Health Medical Associates. BMJ (Clinical research ed.), 299(6705), 946-9.
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  To assess the relation between breast feeding and subsequent experience of lower respiratory tract illness.
• Wright, A. L., Taussig, L. M., Ray, C. G., Harrison, H. R., & Holberg, C. J. (1989). The Tucson Children's Respiratory Study. II. Lower respiratory tract illness in the first year of life. American journal of epidemiology, 129(6), 1232-46.
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  Lower respiratory tract illnesses occurring during the first year of life in 1,179 healthy infants enrolled in the Children's Respiratory Study, Tucson, Arizona, are described. The children, who use the pediatricians of a health maintenance organization, were enrolled into the study between May 1980 and January 1984. Data were collected on signs, symptoms, and diagnosis for each illness; nasopharyngeal and throat swabs were collected at the acute visit for viral, chlamydial, and mycoplasmal cultures. The cumulative incidence of illness in the first year of life was 32.88 per 100 children. Of the 348 initial lower respiratory tract illnesses occurring in these infants, 60% were diagnosed as bronchiolitis. At least one infecting agent was identified in 66% of the specimens collected at the time of the first illness. Respiratory syncytial virus was the most common isolate; 12 other agents were also identified. There was a strong (p less than 0.0001) relation between agent identified, symptoms reported, and diagnosis; bronchiolitis was predominantly associated with respiratory syncytial virus and croup with parainfluenza viruses. Sex and ethnicity were unrelated to illness experience or to characteristics of the first illness. Lower respiratory tract illness occurrence in the Children's Respiratory Study appears to be similar to patterns observed elsewhere, suggesting that diagnoses (and infecting agents) have changed little over the past decades.
• Geller, D. E., Morgan, W. J., Cota, K. A., Wright, A. L., & Taussig, L. M. (1988). Airway responsiveness to cold, dry air in normal infants. Pediatric pulmonology, 4(2), 90-7.
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  Reactive airway disease may be related to genetic, infectious, and environmental factors. The latter two have been well documented, but there are no data on nonspecific airway responsiveness in normal infants prior to any insult to the respiratory tract. We measured forced expiratory flow by the thoracic compression technique and lung volume in 30 normal infants before and after challenge with cold, dry air (CDA) and compared the results with those in 12 infants who did not receive CDA challenge. As a group, infants challenged with CDA had a mean decrease in VmaxFRC of 17.9 +/- 24.1% SD. This was significantly different (P less than 0.01) from the lack of change (+ 1.3 +/- 18.1% SD) seen in the control group. We conclude that nonspecific airway reactivity may exist from early infancy and may predate any known lung injury. The relationship of this airway responsiveness to subsequent reactive airway disease and other respiratory illnesses is unknown and requires longitudinal study.
• Martinez, F. D., Morgan, W. J., Wright, A. L., Holberg, C. J., & Taussig, L. M. (1988). Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. The New England journal of medicine, 319(17), 1112-7.
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  In a prospective study of 124 infants enrolled as newborns, we assessed the relation between initial lung function and the subsequent incidence of lower respiratory tract illness during the first year of life. The risk of having a wheezing illness was 3.7 times higher (95 percent confidence interval, 0.9 to 15.5; P = 0.06) among infants whose values for total respiratory conductance (the reciprocal of the resistance to air flow of the entire respiratory system) were in the lowest third, as compared with infants with values in the upper two thirds of the range of values for the group. Boys with initial values in the lowest third for an indirect index of airway conductance had a 10-fold increase (95 percent confidence interval, 2.2 to 44.2; P = 0.001) in the risk of having a wheezing illness. A 16-fold increase (95 percent confidence interval, 1.7 to 147.1; P = 0.002) in the risk of having a wheezing illness was found among girls whose initial values for lung volume at the end of tidal expiration were in the lowest third. We conclude that diminished lung function is a predisposing factor for the development of a first wheezing illness in infants.
• Wright, A. L. (1988). Models of mystery: physician and patient perceptions of sudden infant death syndrome. Social science & medicine (1982), 26(6), 587-95.
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  Sudden infant death syndrome or SIDS is the term applied to unexplained infant deaths. This syndrome is distinguished by a lack of knowledge about its cause, pathophysiology, and possibilities for prevention. Given these uncertainties, SIDS provides an opportunity to investigate what types of explanatory models are constructed by physicians and patients when relatively little is known about a condition, and how these models may be translated into clinical practice. Interviews about SIDS were conducted with members of a Pediatric Pulmonary Section and their high risk patients, and the clinical interactions between the staff and families were observed. The pulmonary model focused on physiological causes which might affect respiration, and reflected uncertainty in both content and variability. Parents largely accepted the respiratory hypothesis, although they also considered nonphysiological causes. They tended to manage the uncertainty by focusing on ways to prevent SIDS and by believing they could predict which babies might die. However, observations of clinical interactions revealed that very little of the uncertainty as perceived by either the staff or the parents was discussed. The staff is able to emphasize hope for a particular patient, despite the uncertainty that surrounds SIDS, by following an explicit protocol which states how to handle a child despite the theoretical unknowns, and focusing on the knowns about the particular baby's condition.
• Wright, A. L., Holberg, C., & Taussig, L. M. (1988). Infant-feeding practices among middle-class Anglos and Hispanics. Pediatrics, 82(3 Pt 2), 496-503.
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  Feeding practices have been analyzed prospectively in a sample of 1,112 healthy infants selected from families using an HMO. Data were collected at well-child visits during the first year of life regarding breast-feeding, formula feeding, and use of solid foods and cow's milk. Seventy percent of all infants were breast-fed, with the mean duration of breast-feeding being almost 7 months. Factors positively associated with breast-feeding included education and marriage, whereas maternal employment outside the home and ethnicity (being Hispanic rather than Anglo-American) were related to bottle feeding. Solid foods were introduced earlier by Hispanics and, also, among less well educated and single women; maternal employment was unrelated to the introduction of solid foods. Multiple regression analysis indicated different patterns for the two ethnic groups: education and employment were related to almost all feeding practices for Anglo-Americans, whereas education and employment predicted few feeding practices for the Hispanics. These findings suggest that the effects of ethnicity are independent of those of education.
• Boyce, W. T., Schaefer, C., Harrison, H. R., Haffner, W. H., Lewis, M., & Wright, A. L. (1986). Social and cultural factors in pregnancy complications among Navajo women. American journal of epidemiology, 124(2), 242-53.
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  A population of 968 pregnant Navajo women was followed in a prospective study conducted from 1980 to 1983 at the Indian Health Service Hospitals in Gallup and Crownpoint, New Mexico. The purpose of the study was to examine social and cultural influences on obstetric and neonatal complications. The extent of traditional cultural practices and the availability of social support were ascertained in structured interviews completed during each woman's first prenatal visit. In a subsample of women, the occurrence of stressful life events was also measured during a final prenatal visit in the third trimester of pregnancy. Controlling for a variety of conventional risk factors and other potential confounders, traditional women sustained complications at a rate greater than twice that of the least traditional, most acculturated women (approximate relative risk = 2.1; p = 0.001). Social support and life events were modestly associated with maternal complications (approximate relative risk = 0.7, 0.8, respectively; p = 0.07), with poorer outcomes found among those with low social support and low numbers of life events. It is proposed that the relationship of maternal complications to all three sociocultural variables--traditionality, social support, and life events--may reflect the influences of social isolation on the course and outcomes of pregnancy.
• Kibler, R., Hicks, M. J., Wright, A. L., & Taussig, L. M. (1986). A comparative analysis of cord blood and adult lymphocytes: interleukin-2 and interferon production, natural killer cell activity, and lymphocyte populations. Diagnostic immunology, 4(4), 201-8.
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  A comprehensive comparative analysis of lymphocyte populations, natural killer cell activity, and interleukin-2 (IL-2) and interferon production was performed on cord blood and adult peripheral blood mononuclear cell populations. Analysis of the cell types present demonstrated significantly lower percentages of T3+, T8+, and Leu 11+ cells for the cord blood samples compared to the adult samples. Also, both natural killer cell activity and gamma interferon production were significantly lower in the cord blood group. These findings may correlate with the increased susceptibility of young infants to infection. Differences between the two groups were not evident for the percentages of T4+ cells, B cells, and large granular lymphocytes. IL-2 production by cells stimulated with concanavalin A and a phorbol ester was higher in cord blood. Individually, half of the cord blood samples contained more IL-2 than any of the adult samples. This result could be caused either by greater production of IL-2 by the cord blood samples or by greater utilization of IL-2 by the adult samples.
• Tepper, R. S., Morgan, W. J., Cota, K., Wright, A., & Taussig, L. M. (1986). Physiologic growth and development of the lung during the first year of life. The American review of respiratory disease, 134(3), 513-9.
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  Pulmonary function tests were performed on a total of 125 healthy infants younger than 25 postconception (pc) months of age. Maximal expiratory flow at functional residual capacity (VmaxFRC) was measured from partial expiratory flow-volume curves, and functional residual capacity (FRC) was measured by the helium dilution technique. There was a highly significant (p less than 0.01) linear regression for both VmaxFRC and FRC with increasing body length. The highest size-corrected flows (VmaxFRC/FRC) were obtained in the healthy premature (2.7 FRC/s, n = 6) and full-term (2.5 FRC/s, n = 5) infants, and there was a relatively constant value between 13 and 25 pc months of age (1.2 FRC/s), which was similar to those reported in older children and adults. In an age-matched group of infants 10 to 16 pc months of age, females had both higher absolute flows (126 versus 102 ml/s, p less than 0.03) and size-corrected flows (1.4 versus 1.0 FRC/s, p less than 0.001) than did males. These physiologic data support the concepts that neonates have proportionately larger airways relative to their lung volume at FRC, infants have size-corrected flows similar to those in older children and adults, and female infants have proportionately larger airways relative to their lung size than do male infants.
• Wright, A. L. (1983). A cross cultural comparison of menopausal symptoms. Medical Anthropology, 7(3), 20-35.
• Wright, A. (1982). An ethnography of the Navajo reproductive cycle. American Indian quarterly, 6(1-2), 52-70.
• Wright, A. L. (1981). On the calculation of climacteric symptoms. Maturitas, 3(1), 55-63.
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  Survey techniques, which are widely used to estimate the prevalence of climacteric symptoms, are generally unable to distinguish symptoms which relate to physiological changes from those which may be attributable to other factors. New data collection techniques developed in a study of menopause among a group of American Indians are reported here, which permit the evaluation of the cause of the reported symptoms. Two classes of complaints were than calculated: "gross" symptoms and "climacteric" symptoms. It was found that differences between prevalence, as estimated by the two classes of complaints, were smallest for vasomotor symptoms and greatest for psychological complaints, reflecting presumed physiological relationships. Further, climacteric-related symptoms demonstrated a clearer relationship to factors hypothesized by other researchers as affecting the experience of climacteric symptoms. While not feasible for all studies, these techniques demonstrate that more accurate estimates of symptom experience are possible.

Presentations

• Oren, E., Gerald, L. B., Stern, D., Wright, A. L., & Martinez, F. (2015, May). Self-reported Stressful Life Events During Adolescence and Asthma. American Thoracic Society. Denver, CO.

Poster Presentations

• DeVries, A., Wlasiuk, G., Miller, S., Bosco, A., Stern, D., Lohman, I. C., Rothers, J. L., Jones, A., Nicodemus-Johnson, J., Curtin, J., Simpson, A., Custovic, A., Jackson, D., Gern, J., Lemanske, R., Guerra, S., Wright, A. L., Ober, C., Halonen, M., & Vercelli, D. (2016, Spring). Neonatal SMAD3 promoter hypermethylation predicts asthma in children of asthmatic mothers from three birth cohorts. International Conference, American Thoracic Society, San Francisco, CA.
• Beamer, P., Guerra, S., Lothrop, N. Z., Stern, D., Lu, Z., Billheimer, D. D., Halonen, M., Wright, A. L., & Martinez, F. (2015, May). Levels are Associated with Diesel Exposure at Birth. American Thoracic Society. Denver, CO.
• Beamer, P., Guerra, S., Lothrop, N., Stern, D., Lu, Z., Billheimer, D. D., Halonen, M., Wright, A. L., & Martinez, F. (2015, May). Childhood CC16 Levels are Associated with Diesel Exposure at Birth. American Thoracic Society International Conference.
• Berry, C. E., Berry, C. E., Lu, Z. J., Lu, Z. J., Jenkins, I. C., Jenkins, I. C., Billheimer, D., Billheimer, D., Stern, D. A., Stern, D. A., Gerald, L. B., Gerald, L. B., Carr, T. F., Carr, T. F., Guerra, S., Guerra, S., Wright, A. L., Wright, A. L., Morgan, W. J., , Morgan, W. J., et al. (2015, May). Lung Function Trajectories in the Tucson Children's Respiratory Study. American Thoracic Society. Denver, CO: American Thoracic Society.
• Berry, C. E., Jenkins, I., Billheimer, D. D., Stern, D., Guerra, S., Wright, A. L., Morgan, W. J., & Martinez, F. (2015, May). Lung Function Trajectories in the Tucson Children’s Respiratory Study. American Thoracic Society. Denver, CO.
• Carr, T. F., Stern, D., Halonen, M., Wright, A. L., & Martinez, F. (2015, May). Active Rhinitis at Age 6 Predicts Subsequent Development of Asthma Independent of Atopy. American Thoracic Society. Denver, CO.
• Chan, J. Y., Stern, D., Wright, A. L., Halonen, M., & Martinez, F. (2015, May). Association Between Early Life Interleukin-5 and Childhood Eosinophilic Asthma. American Thoracic Society. Denver, CO.
• DeVries, A., Wlasiuk, G., Miller, S. J., Bosco, A., Stern, D., Nicodemus-Johnson, J., Jones, A. C., Rothers, J. L., Lohman, I. C., Wright, A. L., Ober, C., Halonen, M., & Vercelli, D. (2015, May). Neonatal Epigenetic Predictors of Childhood Asthma Map to Immunoregulatory and Pro-Inflammatory Pathways. American Thoracic Society. Denver, CO.
• DeVries, A., Wlasiuk, G., Miller, S., Bosco, A., Stern, D., Nicodemus-Johnson, J., Jones, A., Rothers, J. L., Lohman, I. C., Wright, A. L., Ober, C., Halonen, M., & Vercelli, D. (2015, Spring). Neonatal epigenetic predictors of childhood asthma map to immunoregulatory and pro-inflammatory pathways. International Conference, American Thoracic Society.
• Kranch, R., Stern, D., Wright, A. L., Lohman, I. C., Spangenberg, A., Vercelli, D., Winzerling, J. J., Wilhelm, M. S., & Halonen, M. (2015, Spring). Temporal patterns of early life food-specific IgE and their relation to asthma, eczema, and allergic rhinitis at age 5. Frontiers in Immunobiology & Immunopathogenesis Symposium. University of Arizona.
• Oren, E., Gerald, L. B., Stern, D., Wright, A. L., & Martinez, F. (2015, May). Self-reported Stressful Life Events During Adolescence and Asthma. American Thoracic Society. Denver, CO: American Thoracic Society.
• Voraphani, N., Guerra, S., Stern, D., Halonen, M., Wright, A. L., Morgan, W. J., & Martinez, F. (2015, May). Circulating CC16 in Childhood Differentiates Between Persistent and Remitting Severe Asthma in Adult Life. American Thoracic Society. Denver, CO.

Others

• Bousquet, J., Gern, J. E., Martinez, F. D., Anto, J. M., Johnson, C. C., Holt, P. G., Lemanske, R. F., Le Souëf, P. N., Tepper, R. S., von Mutius, E. R., Arshad, S. H., Bacharier, L. B., Becker, A., Belanger, K., Bergström, A., Bernstein, D. I., Cabana, M. D., Carroll, K. N., Castro, M., , Cooper, P. J., et al. (2014, Jun). Birth cohorts in asthma and allergic diseases: report of a NIAID/NHLBI/MeDALL joint workshop. The Journal of allergy and clinical immunology.
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  Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts.
• Guilbert, T. W., & Wright, A. L. (2012, Apr). Does breastfeeding impact lung function and asthma risk?. American journal of respiratory and critical care medicine.
• Sevgican, U., Rothers, J., Stern, D. A., Lohman, I. C., & Wright, A. L. (2012, Feb). Predictors of neonatal production of IFN-γ and relation to later wheeze. The Journal of allergy and clinical immunology.