Anne L. Wright

Asthma and wheezing in the first six years of life. The Group Health Medical Associates.

BACKGROUND 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. METHODS In a prospective study, we investigated the factors affecting wheezing before the age of three years and their relation to wheezing at six years of age. Of 1246 newborns in the Tucson, Arizona, area enrolled between May 1980 and October 1984, follow-up data at both three and six years of age was available for 826. For these children, assessments in infancy included measurement of cord-serum IgE levels (measured in 750 children), pulmonary-function testing before any lower respiratory illness had occurred (125), measurement of serum IgE levels at nine months of age (672), and questionnaires completed by the childrens parents when the children were one year old (800). Assessments at six years of age included measurement of serum IgE levels (in 460), pulmonary-function testing (526), and skin allergy testing (629). RESULTS At the age of six years, 425 children (51.5 percent) had never wheezed, 164 (19.9 percent) had had at least one lower respiratory illness with wheezing during the first three years of life but had no wheezing at six years of age, 124 (15.0 percent) had no wheezing before the age of three years but had wheezing at the age of six years, and 113 (13.7 percent) had wheezing both before three years of age and at six years of age. The children who had wheezing before three years of age but not at the age of six had diminished airway function (length-adjusted maximal expiratory flow at functional residual capacity [Vmax FRC]) both before the age of one year and at the age of six years, were more likely than the other children to have mothers who smoked but not mothers with asthma, and did not have elevated serum IgE levels or skin-test reactivity. Children who started wheezing in early life and continued to wheeze at the age of six were more likely than the children who never wheezed to have mothers with a history of asthma (P < 0.001), to have elevated serum IgE levels (P < 0.01), to have normal lung function in the first year of life, and to have elevated serum IgE levels (P < 0.001) and diminished values for VmaxFRC (P < 0.01) at six years of age. CONCLUSIONS The majority of infants with wheezing have transient conditions associated with diminished airway function at birth and do not have increased risks of asthma or allergies later in life. In a substantial minority of infants, however, wheezing episodes are probably related to a predisposition to asthma.

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.

SIBLINGS, DAY-CARE ATTENDANCE, AND THE RISK OF ASTHMA AND WHEEZING DURING CHILDHOOD

BACKGROUND Young children with older siblings and those who attend day care are at increased risk for infections, which in turn may protect against the development of allergic diseases, including asthma. However, the results of studies examining the relation between exposure to other children and the subsequent development of asthma have been conflicting. METHODS In a study involving 1035 children followed since birth as part of the Tucson Childrens Respiratory Study, we determined the incidence of asthma (defined as at least one episode of asthma diagnosed by a physician when the child was 6 to 13 years old) and the prevalence of frequent wheezing (more than three wheezing episodes during the preceding year) in relation to the number of siblings at home and in relation to attendance at day care during infancy. RESULTS The presence of one or more older siblings at home protected against the development of asthma (adjusted relative risk for each additional older sibling, 0.8; 95 percent confidence interval, 0.7 to 1.0; P=0.04), as did attendance at day care during the first six months of life (adjusted relative risk, 0.4; 95 percent confidence interval, 0.2 to 1.0; P=0.04). Children with more exposure to other children at home or at day care were more likely to have frequent wheezing at the age of 2 years than children with little or no exposure (adjusted relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.8; P=0.01) but were less likely to have frequent wheezing from the age of 6 (adjusted relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0; P=0.03) through the age of 13 (adjusted relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). CONCLUSIONS Exposure of young children to older children at home or to other children at day care protects against the development of asthma and frequent wheezing later in childhood.

Diminished Lung Function as a Predisposing Factor for Wheezing Respiratory Illness in Infants

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.

Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood

BACKGROUND 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. METHODS Healthy non-selected newborn infants (n=1246) were enrolled at birth. Asthma was defined as a physician diagnosis of asthma plus asthma symptoms reported on ⩾2 questionnaires at 6, 9, 11 or 13 years. Recurrent wheeze (⩾4 episodes in the past year) was reported by questionnaire at seven ages in the first 13 years of life. Duration of exclusive breast feeding was based on prospective physician reports or parental questionnaires completed at 18 months. Atopy was assessed by skin test responses at the age of 6 years. RESULTS The relationship between breast feeding, asthma, and wheeze differed with the presence or absence of maternal asthma and atopy in the child. After adjusting for confounders, children with asthmatic mothers were significantly more likely to have asthma if they had been exclusively breast fed (OR 8.7, 95% CI 3.4 to 22.2). This relationship was only evident for atopic children and persisted after adjusting for confounders. In contrast, the relation between recurrent wheeze and breast feeding was age dependent. In the first 2 years of life exclusive breast feeding was associated with significantly lower rates of recurrent wheeze (OR 0.45, 95% CI 0.2 to 0.9), regardless of the presence or absence of maternal asthma or atopy in the child. Beginning at the age of 6 years, exclusive breast feeding was unrelated to prevalence of recurrent wheeze, except for children with asthmatic mothers in whom it was associated with a higher odds ratio for wheeze (OR 5.7, 95% CI 2.3 to 14.1), especially if the child was atopic. CONCLUSION The relationship between breast feeding and asthma or recurrent wheeze varies with the age of the child and the presence or absence of maternal asthma and atopy in the child. While associated with protection against recurrent wheeze early in life, breast feeding is associated with an increased risk of asthma and recurrent wheeze beginning at the age of 6 years, but only for atopic children with asthmatic mothers.

Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study

BACKGROUND 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. METHODS Non-selected infants were enrolled at birth in the Tucson Childrens Respiratory Study between 1980 and 1984. We measured maximal expiratory flows at functional residual capacity (Vmax(FRC)) in 169 of these infants by the chest compression technique at a mean of 2.3 months (SD 1.9). We also obtained measurements of lung function for 123 of these participants at least once at ages 11, 16, and 22 years. Indices were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC (FEF25-75), both before and after treatment with a bronchodilator (180 microg of albuterol). FINDINGS Participants who had infant Vmax(FRC) in the lowest quartile also had lower values for the FEV1/FVC ratio (-5.2%, p<0.0001), FEF25-75 (-663 mL/s, p<0.0001), and FEV1 (-233 mL, p=0.001) up to age 22, after adjustment for height, weight, age, and sex, than those in the upper three quartiles combined. The magnitude and significance of this effect did not change after additional adjustment for wheeze, smoking, atopy, or parental asthma. INTERPRETATION Poor airway function shortly after birth should be recognised as a risk factor for airflow obstruction in young adults. Prevention of chronic obstructive pulmonary disease might need to start in fetal life.

Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study

BACKGROUND 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. METHODS 1246 healthy newborn babies were enrolled in the Tucson Childrens Respiratory Study. Parental characteristics, early-life wheezing phenotypes, airway function, and bronchial hyper-responsiveness to cold dry air and sensitisation to Alternaria alternata were determined before age 6 years. Physician-diagnosed asthma, both chronic and newly diagnosed, and airway function were recorded at age 22 years. FINDINGS Of 1246 babies enrolled, 849 had follow-up data at 22 years. Average incidence of asthma at age 16-22 years was 12.6 per thousand person-years. 49 (27%) of all 181 cases of active asthma at 22 years were newly diagnosed, of which 35 (71%) were women. Asthma remittance by 22 years was higher in men than in women (multinomial odds ratio [M-OR] 2.0, 95% CI 1.2-3.2, p=0.008). Age at diagnosis was linearly associated with the ratio of forced expiratory volume at 1 s to forced vital capacity at age 22 years. Factors independently associated with chronic asthma at 22 years included onset at 6 years (7.4, 3.9-14.0) and persistent wheezing (14.0, 6.8-28.0) in early life, sensitisation to A alternata (3.6, 2.1-6.4), low airway function at age 6 years (2.1, 1.1-3.9), and bronchial hyper-responsiveness at 6 years (4.5, 1.9-10.0). Bronchial hyper-responsiveness (6.9, 2.3-21.0), low airway function at 6 years (2.8, 1.1-6.9), and late-onset (4.6, 1.7-12.0) and persistent wheezing (4.0, 1.2-14.0) predicted newly diagnosed asthma at age 22 years. INTERPRETATION Asthma with onset in early adulthood has its origins in early childhood.

Breast feeding and lower respiratory tract illness in the first year of life. Group Health Medical Associates.

OBJECTIVE--To assess the relation between breast feeding and subsequent experience of lower respiratory tract illness. DESIGN--Prospective (from well child visits) and retrospective (from maternal recall) study of breast feeding and prospective assessment by paediatricians of lower respiratory tract illness in infants during first year of life. SETTING--Health maintenance organisation. PARTICIPANTS--Over 1000 infants who were healthy at birth and whose parents used the paediatricians of a local health maintenance organisation. MAIN OUTCOME MEASURES--Duration of breast feeding and type of lower respiratory tract illness (wheezing and non-wheezing) at different age intervals during the first year of life. RESULTS--Breast feeding was associated with a decreased incidence of wheezing illnesses only in the first four months of life. Interactions existed between breast feeding and sharing a room, being Mexican American, and being a boy. Multivariate techniques showed that after controlling for a variety of factors children who received minimal breast milk had a greater risk of early wheezing illnesses; the risk was further increased by simultaneous exposure to sharing a room. CONCLUSION--Breast feeding seems to protect against wheezing respiratory tract illnesses in the first four months of life, particularly when other risk factors are present.

Association of interleukin-2 and interferon-γ production by blood mononuclear cells in infancy with parental allergy skin tests and with subsequent development of atopy

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.

Gender differences in academic advancement: Patterns, causes, and potential solutions in one U.S. College of Medicine

Purpose The influx of women into academic medicine has not been accompanied by equality for male and female faculty. Women earn less than men in comparable positions, progress more slowly through academic ranks, and have not attained important leadership roles. This study tested hypotheses about why gender disparities exist in salary, rank, track, leadership, and perceptions of campus climate at one academic center, the University of Arizona College of Medicine, Tucson. Method Salary, rank, and track data were obtained from institutional databases for the 1999–2000 fiscal year. A structured, online questionnaire was made available to 418 faculty members to collect information about their goals, attitudes, and experiences. Results A total of 198 faculty members completed the questionnaire. The data showed significant gender differences in faculty salaries, ranks, tracks, leadership positions, resources, and perceptions of academic climate. On average, women earned