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Biomedical subjects

A L Wright

Publications and source records attributed to A L Wright.

At least 37 records · Page 2Linked to original sources

A clinical index to define risk of asthma in young children with recurrent wheezing.

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.

Adolescent↗

Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years.

BACKGROUND: 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. METHODS: Children were enrolled at birth and cases of lower respiratory tract illness were ascertained by a physician. Viral tests were done for specimens collected at the time of the illness. Children were classified into five groups according to type and cause of lower respiratory tract illness. Children were then followed prospectively up to age 13, and we measured frequency of wheezing, pulmonary function, and atopic status (allergy skin-prick tests, serum IgE concentrations). FINDINGS: RSV lower respiratory tract illnesses were associated with an increased risk of infrequent wheeze (odds ratio 3.2 [95% CI 2.0-5.0], p < 0.001), and an increased risk of frequent wheeze (4.3 [2.2-8.7], p < or = 0.001) by age 6. Risk decreased markedly with age and was not significant by age 13. There was no association between RSV lower respiratory tract illnesses and subsequent atopic status. RSV lower respiratory tract illnesses were associated with significantly lower measurements of forced expiratory volume (2.11 [2.05-2.15], p < or = 0.001) when compared with those of children with no lower respiratory tract illnesses, but there was no difference in forced expiratory volume after inhalation of salbutamol. INTERPRETATION: RSV lower respiratory tract illnesses in early childhood are an independent risk factor for the subsequent development of wheezing up to age 11 years but not at age 13. This association is not caused by an increased risk of allergic sensitisation.

Adolescent↗

Influence of parental smoking on respiratory symptoms during the first decade of life: the Tucson Children's Respiratory Study.

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.

Adult↗

Breast-feeding, maternal IgE, and total serum IgE in childhood.

BACKGROUND: There is controversy regarding the relationship of the effect of breast-feeding on markers of allergy such as total serum IgE in childhood. OBJECTIVE: This study, using longitudinal data, tested the hypothesis that the relation of breast-feeding to IgE in childhood differs depending on maternal total IgE level. METHODS: Total serum IgE was assessed with the paper radioimmunosorbent test at 4 ages in nonselected children enrolled at birth into the prospective Tucson Children's Respiratory Study. Children were classified as never breast-fed, breast-fed less than 4 months, or breast-fed 4 months or longer, on the basis of physician report or questionnaires completed by parents by the time the child was 18 months old. A longitudinal random effects model was used to test for group differences and temporal trends in IgE for children classified with reference to maternal IgE (high tertile vs all others) and breast-feeding history. A total of 664 children with 1457 observations were included. RESULTS: Among children whose mothers were in the 2 lower tertiles of IgE, breast-feeding was associated with lower total serum IgE at age 6 years (24.2 vs 44.3 IU/mL for never breast-fed children; P <.02); similar trends existed at age 11 years. In contrast, for children whose mothers were in the highest tertile of IgE, breast-feeding of 4 months or longer was associated with higher IgE levels in the child compared with those never breast-fed or breast-fed less than 4 months (97.0 vs 38.9 IU/mL; P <. 005). These cross-sectional analyses were confirmed with the longitudinal random effects model, which also showed no effect of confounders. Paternal IgE showed no similar relation with child IgE. CONCLUSION: Breast-feeding appears to have paradoxic relations with IgE in childhood, depending on maternal IgE level. These findings may help explain the contradictory results found in other investigations of the relation of breast-feeding to allergic symptoms and markers.

Breast Feeding↗

Association of radiologically ascertained pneumonia before age 3 yr with asthmalike symptoms and pulmonary function during childhood: a prospective study.

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.

Aging↗

Two subphenotypes of childhood asthma that differ in maternal and paternal influences on asthma risk.

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.

Alternaria↗

Familial aggregation and segregation analysis of eosinophil levels.

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.

Adult↗

Health care costs of formula-feeding in the first year of life.

OBJECTIVE: 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. METHODS: Frequency of health service utilization for three illnesses (lower respiratory tract illnesses, otitis media, and gastrointestinal illness) in the first year of life was assessed in relation to duration of exclusive breastfeeding in the Tucson Children's Respiratory Study (n = 944) and the Dundee Community Study (Scottish study, n = 644). Infants in both studies were healthy at birth and represented nonselected, population-based samples. Children were classified as never breastfed, partially breastfed, or exclusively breastfed, based on their feeding status during the first 3 months of life. Frequency of office visits and hospitalizations for the three illnesses was adjusted for maternal education and maternal smoking, using analysis of variance. Cost estimates, from the perspective of the health care provider/payer, were based on the direct medical costs during 1995 within a large managed care health care system. RESULTS: In the first year of life, after adjusting for confounders, there were 2033 excess office visits, 212 excess days of hospitalization, and 609 excess prescriptions for these three illnesses per 1000 never-breastfed infants compared with 1000 infants exclusively breastfed for at least 3 months. These additional health care services cost the managed care health system between $331 and $475 per never-breastfed infant during the first year of life. CONCLUSIONS: In addition to having more illnesses, formula-fed infants cost the health care system money. Health care plans will likely realize substantial savings, as well as providing improved care, by supporting and promoting exclusive breastfeeding.

Analysis of Variance↗

Differential immune responses to acute lower respiratory illness in early life and subsequent development of persistent wheezing and asthma.

BACKGROUND: 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. OBJECTIVE: Whether the nature of the immune response occurring during acute lower respiratory illnesses (LRIs) in infancy differs between these 2 groups of wheezers has yet to be determined. METHODS: We compared total serum IgE levels and peripheral blood eosinophil counts obtained during the acute phase of the first LRI with those obtained during the convalescent phase or with well-baby samples in persistent (n = 49) and transient early wheezers (n = 88), as well as in children who had only nonwheezing LRIs (n = 43) during the first 3 years of life. RESULTS: Total serum IgE levels were significantly higher (P =.008) during the acute phase compared with the convalescent phase of the LRI in persistent wheezers, a response not observed in transient early wheezers (P =.7). Peripheral blood eosinophil counts were significantly reduced during the acute phase of the LRI (P =.009) in transient early wheezers, a response not observed among persistent wheezers (P =.7). Acute responses in children who had nonwheezing LRIs only were similar to those seen in transient early wheezers. CONCLUSION: Alterations in acute immune response to viral infection may be detected at the time of the first wheezing episode in subjects who will go on to have persistent wheezing symptoms.

Acute Disease↗

Differences in familial segregation of FEV1 between asthmatic and nonasthmatic families. Role of a maternal component.

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.

Adult↗

Increasing breastfeeding rates to reduce infant illness at the community level.

OBJECTIVE: 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. METHODS: In this population-based cohort study, the medical records of all infants born in one Navajo community the year before a breastfeeding promotion program (n = 977) and the year during the intervention (n = 858) were reviewed. Outcomes assessed include changes after the intervention in: proportion breastfeeding and/or breastfeeding exclusively; incidence of common infant illnesses in the first year of life; and feeding-group specific incidence of illness. RESULTS: The proportion of women breastfeeding exclusively for any period of time increased from 16.4% to 54.6% after the intervention. The percent of children having pneumonia and gastroenteritis declined 32. 2% and 14.6%, respectively, after the intervention. Feeding-group specific rates of these illnesses were unchanged, indicating that the decline observed was attributable to the increased proportion of infants breastfeeding. In contrast, rates of croup and bronchiolitis increased after the intervention among those fed formula from birth, suggesting a viral epidemic which was limited to those never exclusively breastfed. Finally, sepsis declined in both formula-fed and breastfed infants after the intervention, suggesting that other factors affected this illness outcome after the intervention. CONCLUSIONS: Increasing the proportion of exclusively breastfed infants seems to be an effective means of reducing infant illness at the community level. The experimental design suggests that the increased incidence of illness among minimally breastfed infants is causally related to lack of breast milk, rather than being attributable to confounding.

Breast Feeding↗

Lessons from long-term cohort studies. Childhood asthma.

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.

Asthma↗

Peak flow variability, methacholine responsiveness and atopy as markers for detecting different wheezing phenotypes in childhood.

BACKGROUND: 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. METHOD: In a cohort of children followed from birth peak flow variability (n = 600) was evaluated and methacholine challenge responsiveness (n = 397) was measured at age 11 in relation to wheezing before the age of three, and at age six and 11 years total serum IgE and skin test reactivity to allergens were determined. RESULTS: Neither positive peak flow variability nor methacholine hyperresponsiveness measured at age 11 were associated with wheezing occurring only during the first three years of life. Both methacholine hyperresponsiveness and positive peak flow variability were associated with wheezing at both ages six and 11 (OR 5.1 (95% CI 2.4 to 10.6) and 2.3 (1.2 to 4.5), respectively). In addition, positive peak flow variability was associated with wheezing up to the age of six but not at age 11 in non-atopic children (OR 2.9 (95% CI 1.0 to 8.8)). Methacholine hyperresponsiveness measured at age 11 was more frequently observed in boys (OR 2.1 (95% CI 1.2 to 3.5)) and was strongly associated with serum IgE levels measured at ages six and 11 (p < 0.001) and with positive skin test reactivity (OR 4.5 (95% CI 2.0 to 10.1)). Peak flow variability was unrelated to sex or markers of atopy (IgE and skin test reactivity). CONCLUSIONS: Methacholine responsiveness and peak flow variability assessed at age 11, together with markers of atopy (IgE and skin test reactivity to allergens) identify three different wheezing phenotypes in childhood: "transient early wheezing" limited to the first three years of life and unrelated to increased airway lability; "non-atopic wheezing" of the toddler and early school years associated with positive peak flow variability but not with methacholine hyperresponsiveness; and "IgE-associated wheeze/asthma" associated with persistent wheezing at any age and with methacholine hyperresponsiveness, peak flow variability, and markers of atopy.

Adolescent↗

Alternaria as a major allergen for asthma in children raised in a desert environment.

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.

Allergens↗

Cold air challenge at age 6 and subsequent incidence of asthma. A longitudinal study.

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.

Age Factors↗

Using cultural knowledge in health promotion: breastfeeding among the Navajo.

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.

Breast Feeding↗