Circulating TSLP associates with decreased wheezing in non-atopic preschool children: data from the URECA birth cohort.

BACKGROUND: Mouse models of atopic march suggest that systemic, skin-derived thymic stromal lymphopoietin (TSLP) mediates progression from eczema to asthma. OBJECTIVE: We investigated whether circulating TSLP is associated with eczema, allergic sensitization, or recurrent wheezing in young children. METHODS: A prospective analysis of the relationship between plasma levels of TSLP to allergic sensitization and recurrent wheezing was conducted in the birth cohort from the Urban Environment and Childhood Asthma (URECA) study. Plasma TSLP levels were measured at 1, 2, and 3 years of age and analysed for correlation with clinical parameters in each of the three years. Only those children with consecutive samples for all three years were included in this analysis. RESULTS: We detected TSLP in 33% of 236 children for whom plasma samples were available for all three years. Overall, a consistently significant association was not found between TSLP and eczema or allergic sensitization. With regard to recurrent wheezing, children with detectable TSLP at one year of age were significantly less likely to experience recurrent wheezing by 3 years compared with those children without detectable TSLP, but this was only seen in children without aeroallergen sensitization at 3 years (P < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Contrary to our expectations, circulating TSLP was not significantly associated with eczema, allergen sensitization, or recurrent wheezing during the first three years of life. Early presence of circulating TSLP was significantly associated with reduced incidence of recurrent wheeze in those children not sensitized to aeroallergen. These findings suggest a possible underlying distinction between pathogenesis of developing atopic vs. non-atopic recurrent wheeze.

Age-dependent interaction between atopy and eosinophils in asthma cases: results from NHANES 2005-2006.

BACKGROUND: Atopy is an established risk factor for asthma, and an elevated eosinophil level is a hallmark of atopic and non-atopic asthma. Whether atopy and eosinophils act independently or interact to influence asthma has clinical and public health implications. OBJECTIVE: To investigate the relationship between atopy and eosinophils in asthma. METHODS: Data on current asthma, atopy (IgE positive to ≥ 1 allergen), and blood eosinophil percent (dichotomized at the median) were obtained for persons aged ≥ 6 years from the National Health and Nutrition Examination Survey 2005-2006. Interaction on an additive scale was evaluated by estimating the prevalences of asthma for combinations of atopy (yes or no) and eosinophil percent (high or low) and calculating the excess prevalence due to interaction. RESULTS: For all ages combined, the adjusted prevalences of asthma were 4.6%, 7.6%, 6.9% and 17.2% for persons with neither factor, atopy alone, a high eosinophil percent alone and both factors respectively. The excess prevalence of asthma due to interaction was 7.2%, indicating synergism. The excess prevalence was greatest in children aged 6-17 years (15.3%), and it decreased with each older age category until it was absent in adults aged ≥ 55 years (-0.2%). In children, 94% of asthma cases attributable to the 2 factors were attributable to the interaction, whereas in the oldest adults, no cases were attributable to the interaction. CONCLUSIONS AND CLINICAL RELEVANCE: Interaction between atopy and an elevated eosinophil level in asthma cases was very strong in children but absent in the oldest adults, which suggests different mechanistic pathways for these factors by age and supports the notion that asthma is a heterogeneous disease. In addition, the age-dependent interaction between the factors has potential implications for the selection of asthma patients for treatments that would target either IgE or a high eosinophil level.

Allergen-specific IgE as a biomarker of exposure plus sensitization in inner-city adolescents with asthma.

BACKGROUND: Relationships among allergen-specific IgE levels, allergen exposure and asthma severity are poorly understood since sensitization has previously been evaluated as a dichotomous, rather than continuous characteristic. METHODS: Five hundred and forty-six inner-city adolescents enrolled in the Asthma Control Evaluation study underwent exhaled nitric oxide (FE(NO)) measurement, lung function testing, and completion of a questionnaire. Allergen-specific IgE levels and blood eosinophils were quantified. Dust samples were collected from the participants' bedrooms for quantification of allergen concentrations. Participants were followed for 12 months and clinical outcomes were tracked. RESULTS: Among sensitized participants, allergen-specific IgE levels were correlated with the corresponding settled dust allergen levels for cockroach, dust mite, and mouse (r = 0.38, 0.34, 0.19, respectively; P < 0.0001 for cockroach and dust mite and P = 0.03 for mouse), but not cat (r = -0.02, P = 0.71). Higher cockroach-, mite-, mouse-, and cat-specific IgE levels were associated with higher FE(NO) concentrations, poorer lung function, and higher blood eosinophils. Higher cat, dust mite, and mouse allergen-specific IgE levels were also associated with an increasing risk of exacerbations or hospitalization. CONCLUSIONS: Allergen-specific IgE levels were correlated with allergen exposure among sensitized participants, except for cat. Allergen-specific IgE levels were also associated with more severe asthma across a range of clinical and biologic markers. Adjusting for exposure did not provide additional predictive value, suggesting that higher allergen-specific IgE levels may be indicative of both higher exposure and a greater degree of sensitization, which in turn may result in greater asthma severity.

Effect of environmental allergen sensitization on asthma morbidity in inner-city asthmatic children.

BACKGROUND: Asthma causes significant morbidity in children, and studies have demonstrated that environmental allergies contribute to increased asthma morbidity. OBJECTIVE: We investigated the differences between allergen skin tests and specific IgE (SIgE) and the role of IgG in regards to allergen exposure levels, and asthma morbidity in inner-city children. METHODS: Five hundred and six serum samples from the National Cooperative Inner City Asthma Study (NCICAS) were evaluated for SIgE to cockroach (Blattella germanica), dust mite (Dermatophagoides farinae), and Alternaria as well as specific IgG (SIgG) and IgG(4) to cockroach (B. germanica) and total IgE levels. Associations between sensitization to these allergens, exposures, and asthma morbidity were determined. RESULTS: Sensitization to environmental allergens and total IgE correlated with increased health care and medication use, but not with symptoms of wheeze. Sensitization with exposure to cockroach was associated with increased asthma morbidity, whereas dust mite sensitization was correlated with asthma morbidity independent of exposure. There was also a strong correlation between SIgE levels and skin test results, but the tests did not always agree. The relationship between SIgE and asthma morbidity is linear with no obvious cutoff value. Increased Bla g 1 in the home was a good predictor for sensitization; however, this relationship was not demonstrated for Der f 1. Cockroach SIgG correlated with increased health care use, however, there was no modifying effect of SIgG or SIgG(4) on the association between cockroach SIgE and asthma morbidity. CONCLUSIONS: SIgE levels and skin prick test results to environmental allergens can serve as markers of severe asthma for inner-city children. Asthma morbidity increased in a linear manner with SIgE levels. IgG was not an important predictor or modifier of asthma morbidity.

The association of allergen skin test reactivity and respiratory disease among whites in the US population. Data from the Second National Health and Nutrition Examination Survey, 1976 to 1980.

Data collected on 12- to 74-year-old whites (N = 10,854) during the second National Health and Nutrition Examination Survey, 1976 to 1980, a sample of the US population, were used to determine the association between various respiratory symptoms and the degree of allergen skin test reactivity. Prick-puncture testing using eight unstandardized allergens was performed. Allergen skin test reactivity was classified by means of the mean diameter of the erythema reaction at the 20-minute reading. Nonreactors were the comparison group. The prevalence of allergic rhinitis increased as allergen skin test reactivity increased, with the odds ratio exceeding 8 for the group with two or more positive test results. The prevalence of asthma increased with increasing allergen skin test reactivity only in nonsmokers. The odds ratio for allergic rhinitis with allergen skin test reactivity was higher with outdoor than indoor allergens. The association of allergic rhinitis with allergen skin test reactivity was higher when a physician had previously diagnosed allergic rhinitis. Chronic rhinitis was not associated with allergen skin test reactivity.

National survey of prevalence of asthma among children in the United States, 1976 to 1980.

The trend in the prevalence of reported asthma was determined from data collected by the National Center for Health Statistics. The reported prevalence of ever having asthma increased among 6- to 11-year-old children between the first (1971 to 1974) and second (1976 to 1980) National Health and Nutrition Examination Surveys (4.8% to 7.6%, P less than .01). The epidemiology of asthma among children and adolescents 3 to 17 years of age in the United States was examined using data collected in the second National Health and Nutrition Examination Survey. In this paper, asthma is defined as current disease diagnosed by a physician and/or frequent trouble with wheezing during the past 12 months, not counting colds or the flu. Asthma was reported for 6.7% of youths overall and was higher in black than white children (9.4% v 6.2%, P less than .01), boys than girls (7.8% v 5.5%, P less than .01), and urban than rural areas (7.1% v 5.7%, P less than .05). Asthmatic children had a higher prevalence of other allergies (42.6% v 13.2%, P less than .01) and of allergen skin test reactivity (44.5% v 20.7%, P less than .01) than nonasthmatic children. Most asthmatics had their first asthmatic episode before their third birthday. No effect of socioeconomic status on the prevalence of asthma was noted.

Race, income, urbanicity, and asthma hospitalization in California: a small area analysis.

STUDY OBJECTIVES: To explicate the interrelationship between asthma hospitalization and race/ethnicity and income. DESIGN: Small area ecologic analysis using census and administrative data. SETTING AND PARTICIPANTS: All asthma hospitalizations in California were identified using the 1993 California Hospital Discharge file. Small area analyses of Los Angeles (LA) were compared with published rates in New York City (NYC). RESULTS: In 1993, the age-adjusted asthma hospitalization rate in California for nonelderly blacks was 42.5/10,000-approximately four times higher than other populations. Black rates remained fourfold higher after stratification by age, income, and urbanicity. Multivariate analyses suggest that the association between black race and asthma hospitalization is independent of income. Regardless of race, children and persons living in poverty were at increased risk for asthma hospitalization. Urbanicity was not a predictor for asthma hospitalization. Overall, asthma hospitalization rates in NYC were 2.8 times higher compared with rates in LA; while rates were similar among blacks (60 vs 40/10,000, respectively), Puerto Rican Hispanics in NYC had dramatically higher rates compared with Mexican Hispanics in LA (63 vs 14/10,000, respectively). CONCLUSIONS: After controlling for socioeconomic status, notable differences in asthma hospitalization by race and ethnicity persist. The reasons for the significantly elevated risk of asthma morbidity among blacks remain unclear.

The effect of pulmonary impairment on all-cause mortality in a national cohort.

The association between pulmonary impairment and all-cause mortality was investigated among white subjects in a follow-up study of a large national cohort. Pulmonary function was measured during the National Health and Nutrition Examination Survey (NHANESI) (1971 to 1975); subsequent mortality information was obtained from the 1987 NHANES I Epidemiologic Follow-up Study (1982 to 1987). Of 4,764 white sample persons, ages 25 to 74 years examined during NHANES I, 658 (13.8 percent) were identified as having pulmonary impairment defined as a FEV1/FVC < or = 69 percent. A total of 743 (15.6 percent) sample persons died during the follow-up period. The association between pulmonary impairment and all-cause mortality was examined for male and female subjects separately using the Cox proportional hazards model controlling for age, smoking, educational level, body mass index, and respiratory diseases. The analysis suggests that reduced FEV1 percent predicted was a significant risk factor for mortality among both sexes, and the FEV1/FVC ratio was significantly associated with all-cause mortality among male subjects only.

National trends in the morbidity and mortality of asthma in the US. Prevalence, hospitalization and death from asthma over two decades: 1965-1984.

National population-based data systems of the National Center for Health Statistics (NCHS) were used to study the epidemiology of asthma in the United States over the last 20 years. Asthma is more prevalent among males, those living below the poverty level, persons living in the South and West, and blacks; however, this difference did not attain statistical significance. Death rates from asthma among the older age groups probably increased between 1968 and 1982, with a substantial increase since 1979. For children, the evidence is less clear, but the death rate has increased for children over five years of age during the period from 1979 to 1982. Between 1964 and 1980, asthma has become more prevalent in children under 17 years of age, but this does not reflect an increase in the severity of asthma over this same time period. Hospitalization rates for asthma between 1965 and 1983 increased by 50 percent in adults and by over 200 percent in children. Rates for black patients are 50 percent higher in adults and 150 percent greater in children. It is concluded that there has been a marked increase in hospitalization rates for asthma, a moderate increase in death rates from asthma and a smaller increase in overall prevalence of the disease in the United States.

Trends in asthma-related admissions among American Indian and Alaskan native children from 1979 to 1989. Universal health care in the face of poverty.

OBJECTIVE: To describe changes in asthma-related hospitalizations in Indian Health Service facilities and compare with national trends. DESIGN: Trend analysis. PATIENTS AND SETTING: Hospital discharge records of patients aged 17 years and younger treated by the Indian Health Service between 1979 and 1989. MAIN OUTCOME MEASURES: Patients discharged with asthma as the first listed diagnosis. RESULTS: The rates of asthma-related hospitalizations increased an average of 2.6% (95% confidence interval [CI], 0.1 to 5.2) per year between 1979 and 1989 among American Indian and Alaskan Native children aged 0 to 17 years. The increase was 3.7% among the 0- to 4-year age group (95% CI, 2.0 to 5.5) and 0.3% (95% CI, 0.26 to 0.3) among the 5- to 17-year age group. Boys tended to have a higher rate of increase (4.3% [95% CI, -0.1 to 8.7]) compared with girls (2.6% [95% CI, -0.2 to 5.4]). The rates for any hospitalization decreased during this period for 0- to 4-year-olds (-7.5% [95% CI, -10.5 to -4.5]). Little change was noted in hospitalization rates for lower respiratory tract diseases. Diagnostic transfer from bronchitis/bronchiolitis to asthma could not explain the increase. Both first admission and readmission for treatment of asthma contributed to the increase. Compared with previously published data, 0- to 4-year-old American Indian and Alaskan Native children more closely approximate white children than black children in both rates of hospitalization (1979-1987) and annual percentage increase in hospitalization (1979-1989 for American Indian and Alaskan Native children and 1979-1987 for white and black children) for the treatment of asthma. CONCLUSIONS: American Indian and Alaskan Native children who are cared for by the Indian Health Service have asthma-related hospitalization patterns that are similar to those seen in white children despite having socioeconomic characteristics more similar to those of black children.

Mexican-American mothers' reports of the weights and heights of children 6 months through 11 years old.

OBJECTIVE: To determine the accuracy of mothers' reports of their children's weights and heights. DESIGN AND SETTING: Cross-sectional survey of Mexican Americans in five southwestern states. SUBJECTS: Interviews were held with mothers of 2,578 children aged 6 months to 11 years old. MAIN OUTCOME MEASURES: Sensitivity and specificity of categories formed from reported values, and correlation of reported and measured values. RESULTS: Probability of mothers answering "don't know" was 24% for children's weights and 51% for heights. On the average, mothers overestimated weights at the 15th percentile or lower for age and sex and underestimated weights at the 85th percentile or higher. On the average, they underestimated heights. Categories of low and high weight, height, and body mass index were created by applying absolute-value cutoffs to reported values. All the categories had low sensitivity or specificity. Age-group-specific correlation coefficients between reported and measured values ranged from .79 to .89 for weight and from .32 (for 6- through 23-month-olds) to .70 (for 9- through 11-year-olds) for height. APPLICATIONS: The use of categories formed by applying absolute-value cutoffs to mother-reported values results in frequent misclassification of individuals. Therefore, such categories should not be used to estimate relative risks associated with weight, height, and body mass index. The good correlation of mother-reported and measured weights indicates that despite their inaccuracies, reported weights well reflect the relative ranking of measured weights. Thus, the use of reported weights as a continuous variable in multivariate analyses might cause only small errors in the coefficient for weight.

Self-described weight status of Mexican-American adolescents.

PURPOSE: To evaluate Mexican-American adolescents' descriptions of their weight status. METHODS: Data were from the Hispanic Health and Nutrition Examination Survey, conducted in 1982-1983 among Mexican-Americans in five southwestern states. The current study used data on 429 males and 485 non-pregnant females 12-19 years old. In an interview, participants were asked to describe their weight status (underweight, about the right weight, overweight); in an examination (performed two to four weeks after the interview), weights and heights were measured. Each participant's body-mass index (weight/height2) was calculated, and single year of age-and-sex-specific BMI cutoffs were used to determine each participant's BMI decile. RESULTS: The overweight description was chosen by 46% of females and 23% of males, and the underweight description by 7% of females and 17% of males. The percentage of adolescents self-described as overweight rose with increasing BMI percentile, the rise starting in the 30-39th percentiles for females and in 60-69th percentiles for males. CONCLUSIONS: These findings suggest that many Mexican-American adolescents misperceive their weight status.

Cost of hospitalizations associated with sickle cell disease in the United States.

OBJECTIVE: This study estimated the number and cost of hospitalizations associated with sickle cell disease in the United States. METHODS: To estimate the number of hospitalizations per year in the United States of people with sickle cell disease, the authors used data for the years 1989 through 1993 from national hospital discharge surveys conducted by the National Center for Health Statistics. The authors derived cost estimates using data from a 1992 national hospital discharge survey conducted by the Agency for Health Care Policy and Research and a 1992 survey of physicians conducted by the American Medical Association. RESULTS: During the years 1989 through 1993, there were on average an estimated 75,000 hospitalizations per year of children and adults with sickle cell disease. The average direct cost per hospitalization (in 1996 dollars) was estimated at $6300, for a total direct cost of $475 million per year. In 66% of hospital discharge records, government programs were listed as the expected principal source of payment. CONCLUSIONS: The cost of hospitalizations associated with sickle cell disease is substantial. Because government programs pay most of this cost, further government-funded research to develop interventions that prevent complications of the disease has great potential for cost savings as well as for reducing the suffering of those afflicted with this painful genetic disorder. These national cost estimates contribute to an understanding of the impact of sickle cell disease and should be useful in establishing research priorities.

Geographic differences in mortality of young children with sickle cell disease in the United States.

OBJECTIVES: Because geographic differences in health care have been found for many diseases, including those affecting children, there are probably geographic differences in the health care of young children with sickle cell disease. Consequently, survival of young children with sickle cell disease might differ among geographic areas. This study's objective was to identify areas in the United States where young children with sickle cell disease are at especially high and low risk of dying. METHODS: Using U.S. death certificate data from 1968 through 1992, the authors calculated the mortality rates of 1- through 4-year-old black children with sickle cell disease for states, counties, and cities. Deaths from trauma, congenital anomalies, and perinatal conditions were excluded. RESULTS: From 1968 through 1980 and from 1981 through 1992, 1- through 4-year-old black children with sickle cell disease in Florida had a markedly higher risk of dying, and those in Pennsylvania had a markedly lower risk of dying, than the average 1- through 4-year-old black child with the disease in the United States. From 1981 through 1992, 1- through 4-year-old black children with sickle cell disease in Maryland had the lowest mortality rate in the nation. During the same time period, 1- through 4-year-old black children with sickle cell disease in five counties in Florida were at especially high risk, while in Baltimore no young black children with the disease died. These geographic differences in mortality of black children with sickle cell disease greatly exceeded geographic differences in mortality of black children without the disease. CONCLUSIONS: Marked differences exist across the United States in mortality of young black children with sickle cell disease. To improve survival for children with the disease in high mortality areas, evaluations should be made of the accessibility and quality of medical care, and of parents' health care seeking behavior and compliance with antibiotic prophylaxis. In addition, efforts should be made to understand and duplicate the success of treatment programs in low mortality areas.

Differences in asthma prevalence between samples of American Indian and Alaska Native children.

OBJECTIVES: To better understand the prevalence of asthma among American Indian and Alaska Native (AI/AN) children and to explore the contribution of locale to asthma symptoms and diagnostic assignment, the authors surveyed AI/AN middle school students, comparing responses from metropolitan Tacoma, Washington (metro WA) and a non-metropolitan area of Alaska (non-metro AK). METHODS: Students in grades 6-9 completed an asthma screening survey. The authors compared self-reported rates of asthma symptoms, asthma diagnoses, and health care utilization for 147 children ages 11-16 self-reporting as AI/AN in metro WA and 365 in non-metro AK. RESULTS: The prevalences of self-reported asthma symptoms were similar for the metro WA and non-metro AK populations, but a significantly higher percentage of metro WA than of non-metro AK respondents reported having received a physician diagnosis of asthma (OR 2.33; 95% CI 1.23, 4.39). The percentages of respondents who reported having visited a medical provider for asthma-like symptoms in the previous year did not differ. CONCLUSIONS: The difference in rates of asthma diagnosis despite similar rates of asthma symptoms and respiratory-related medical visits may reflect differences in respiratory disease patterns, diagnostic labeling practices, or environmental factors. Future attempts to describe asthma prevalence should consider the potential contribution of non-biologic factors such as diagnostic practices.

Biological potency of German cockroach allergen extracts determined in an inner city population.

BACKGROUND: Cockroach allergy is an important cause of inner city asthma. To perform valid studies on the diagnosis and treatment of cockroach allergy, biological potencies of test extracts need to be established, and a surrogate in vitro test for biological potency should be chosen. METHODS: Sixty-two cockroach-allergic adult subjects were recruited for quantitative skin testing with three commercial German cockroach extracts. The intradermal D50 values were determined using linear interpolation, and the biologic potencies were determined from D50 data. The extracts were also analysed for relative potency, using a competition ELISA, and for specific allergen content, using a two-site ELISA. RESULTS: Estimates of each extract's D50 were analysable in 48-55 subjects, with D50s between 10.3 and 11.8. All three extracts were bioequivalent using pre-set criteria. The biological potencies of the extracts were 1738-8570 bioequivalent allergy units (BAU)/mL (geometric mean=3300), and these relative potencies were similar to those estimated by competition ELISA and specific allergen content. IgE against cockroach allergens were detected in sera from 34 subjects with analysable D50s, and 17 subjects had IgE directed against specific cockroach allergens. Although the presence of anti-Bla g 5 correlated with the subjects' skin test responses for 2/3 extracts, no single allergen was immunodominant. Antibody responses among the subjects were heterogeneous. CONCLUSIONS: Although commercial cockroach extracts are relatively low in potency, immunotherapeutic doses should be achievable. Biological potency may be estimated using D50 testing, a combination of specific allergen determinations, or by an overall potency assay such as the competition ELISA. CAPSULE SUMMARY: The biological potency of three German cockroach allergen extracts, determined in an inner city population, was 1738-8570 BAU/mL. No one allergen was immunodominant, and surrogate in vitro testing methods were examined.

Asthma and body weight change: a 20-year prospective community study of young adults.

OBJECTIVE: There is increasing evidence for an association between asthma and body weight change. The objectives of these analyses were to examine the temporal relationships of this association and to explore the role of childhood depression as an explanatory factor. METHODS: Data were derived from six subsequent semistructured interviews on health habits and health conditions from a single-age community study of 591 young adults followed up between ages 20 and 40 years. RESULTS: Cross-sectionally (over the whole study period), asthma was significantly associated with obesity (odds ratio=3.9 [95% confidence interval 1.2, 12.2]). Multivariate longitudinal analyses revealed that asthma was associated with increased later weight gain and later obesity among women after controlling for potentially confounding variables, whereas weight gain and obesity were not associated with later asthma. A secondary analysis showed that depressive symptoms during childhood were associated with adult obesity and asthma, partially explaining the asthma-obesity comorbidity. CONCLUSION: This study encourages further research on mechanisms underlying the asthma-obesity comorbidity, particularly on shared psychosocial factors operating during critical periods in childhood and adolescence that may influence the development and persistence of both obesity and asthma during adulthood.

Understanding the economic burden of asthma.

The economic impact of asthma is large and growing, and the use of economic outcomes is increasing. Such outcomes serve as the basis for studies of the efficiency of care and are being reported increasingly as outcomes of clinical trials. This article presents the basic components of a cost-of-illness study, the in-fluences that have an impact on these components, the relation of economic indicators to clinical outcomes, and the relative importance of the economic factors for differing groups in society.