Association of ambient air‐pollution levels with acute asthma exacerbation among children in Singapore

BACKGROUND: Air-pollution levels have been shown to be associated with increased morbidity of respiratory diseases. METHODS: Data for ambient air-pollutant levels, meteorologic factors, and hospitalization or emergency room (ER) visits for acute asthma in Singapore children over a 5-year period (1990-4) were obtained and analyzed for associations by time-series methods. RESULTS: Throughout this period, the annual mean and 24-h mean levels for sulfur dioxide (SO2), nitrogen dioxide (NO2), and total suspended particles (TSP) and maximum 1-h daily average for ozone were generally within the air-quality guidelines established by the World Health Organization (WHO). However, positive correlation between levels of each of these pollutants and daily ER visits for asthma was observed in children aged 3-12 years, but not among adolescents and young adults (13-21 years old). The association with SO2 and TSP persisted after standardization for meteorologic and temporal variables. An adjusted increase in 2.9 ER visits for every 20 microg/m3 increase in atmospheric SO2 levels, lagged by 1 day, was observed on days when levels were above 68 microg/m3. With TSP, an adjusted increase of 5.80 ER visits for every 20 microg/m3 increase in its daily atmospheric levels, lagged by 1 day, was observed on days with levels above 73 microg/m3. Similar results were also obtained after controlling for autocorrelation by time-series analysis. CONCLUSIONS: These associations were observed even though the overall levels of all pollutants were generally within the air-quality guidelines established by the WHO. These findings suggest that asthmatic children are susceptible to increased levels of air pollutants, particularly SO2 and TSP, although the ambient levels are generally within "acceptable" ranges.     

Temporal relationship between air pollution and hospital admissions for asthmatic children in Hong Kong

BACKGROUND: Many epidemiological studies have shown positive association between respiratory health and current levels of outdoor air pollution in Europe and America. OBJECTIVE: The aim of this study was to investigate the association between air pollution and the number of childhood admissions for asthma in Hong Kong. METHODS: Daily counts of childhood admission for asthma to a large teaching Hospital were obtained from the computerized database for the period 1993-1994. A Poisson regression allowing for seasonal patterns and meteorological conditions was used to assess the associations between the number of Hospital admissions and the three pollutants: nitrogen dioxide, sulphur dioxide and inhalable particles (measured as PM10, particles < 10 microm in aerodynamic diameter). RESULTS: A total of 1217 children under 15 years of age were admitted for asthma during the study period. The calculated annual hospitalization rates were 283 and 178 per 100 000 for boys and girls, respectively. The mean PM10, NO2 and SO2 levels were 44.1 microg/m3, 43.3 microg/m3, and 12.2 microg/m3, respectively. Daily admission for asthma increased significantly with increasing ambient level of nitrogen dioxide (relative risk (RR) = 1.08 per 10 microg/m3 increase), sulphur dioxide (RR = 1.06) and inhalable particles (RR = 1.03). No association was found between hospital admission and humidity, temperature or atmospheric pressure. CONCLUSION: This is the first daily time series study of childhood admissions for asthma and air pollution in Hong Kong. The results support that current levels of air pollution contribute to the respiratory morbidity in asthmatic children in Hong Kong.     

Low level atmospheric sulfur dioxide pollution and childhood asthma

Quarterly analysis (1983-1987) of childhood asthma in Hong Kong from 13,620 hospitalization episodes in relation to levels of pollutants (SO2, NO2, NO, O3, TSP, and RSP) revealed a seasonal pattern of attack rates that correlates inversely with exposure to sulfur dioxide (r = -.52, P less than .05). The same cannot be found with other pollutants. Many factors may contribute to the seasonal variation of asthma attacks. We speculate that prolonged exposure (in terms of months) to low level SO2 is one factor that might induce airway inflammation and bronchial hyperreactivity and predispose to episodes of asthma.     

Effects of inhaled corticosteroids on exhaled leukotrienes and prostanoids in asthmatic children

BACKGROUND: Lipid mediators play an important pathophysiologic role in atopic asthmatic children, but their role in the airways of atopic nonasthmatic children is unknown. OBJECTIVE: We sought (1) to measure leukotriene (LT) E 4 , LTB 4 , 8-isoprostane, prostaglandin E 2 , and thromboxane B 2 concentrations in exhaled breath condensate in atopic asthmatic and atopic nonasthmatic children; (2) to measure exhaled nitric oxide (NO) as an independent marker of airway inflammation; and (3) to study the effect of inhaled corticosteroids on exhaled eicosanoids. METHODS: Twenty healthy children, 20 atopic nonasthmatic children, 30 steroid-naive atopic asthmatic children, and 25 atopic asthmatic children receiving inhaled corticosteroids were included in a cross-sectional study. An open-label study with inhaled fluticasone (100 microg twice a day for 4 weeks) was undertaken in 14 steroid-naive atopic asthmatic children. RESULTS: Compared with control subjects, exhaled LTE 4 ( P <.001), LTB 4 ( P <.001), and 8-isoprostane ( P <.001) levels were increased in both steroid-naive and steroid-treated atopic asthmatic children but not in atopic nonasthmatic children (LTE 4 , P=.14; LTB 4 , P=.23; and 8-isoprostane, P=.52). Exhaled NO levels were increased in steroid-naive atopic asthmatic children ( P <.001) and, to a lesser extent, in atopic nonasthmatic children ( P <.01). Inhaled fluticasone reduced exhaled NO (53%, P <.0001) and, to a lesser extent, LTE 4 (18%, P <.01) levels but not LTB 4 , prostaglandin E 2 , or 8-isoprostane levels in steroid-naive asthmatic children. Conclusions Exhaled LTE 4 , LTB 4 , and 8-isoprostane levels are increased in atopic asthmatic children but not in atopic nonasthmatic children. In contrast to exhaled NO, these markers seem to be relatively resistant to inhaled corticosteroids.     

Hospitalization rates in an urban cohort after the introduction of highly active antiretroviral therapy

OBJECTIVE: Previous studies have shown a decrease in hospitalization rates associated with the introduction of highly active antiretroviral therapy (HAART). To evaluate hospitalization rates and patterns in discharge diagnoses that changed between 1995 and 1998 and to examine risk factors for hospitalization in HIV-positive patients, we conducted a cohort study. PATIENTS AND METHODS: All inpatient hospitalizations of 2,151 HIV-positive patients enrolled in our university-based HIV clinic between January 1, 1994 and December 31, 1998 with a CD4 count within a 6-month calendar semester were examined to evaluate hospitalization rates, discharge diagnoses, and intensive care department use. Negative binomial regression was used to assess the effect of various risk factors on hospitalization. RESULTS: Hospitalization rates decreased between 1995 and 1996 but increased between 1997 and 1998. In multivariate regression, female gender (incidence rate ratio [IRR], 1.45; p <.001), injection drug use (IRR, 1.36; p <.001), and having received no antiretroviral therapy were strong predictors of total hospitalization. White race, low CD4 count, and no antiretroviral treatment were strong predictors of hospitalization for an opportunistic infection. Female gender (IRR, 1.45; p <.001), African-American ethnicity (IRR, 1.22, p =.05), no antiretroviral treatment, and low CD4 counts were predictive of higher hospitalization rates for nonopportunistic infection-related diagnoses. Intensive care department-use was associated with white ethnicity (IRR, 1.86; p =.028), heterosexual transmission of HIV (IRR, 1.90; p =.009), no antiretroviral treatment, and low CD4 count at enrollment. CONCLUSIONS: Our data indicate that hospitalization rates decreased between 1995 and 1997 after introduction of HAART, but that they then increased between 1997 and 1998, particularly for diagnosed nonopportunistic infections. If these trends continue, it indicates that patients may be developing previously unseen comorbidities and that HAART may have reached or exceeded a threshold in its effectiveness in reducing the clinical morbidity that results in hospital admission.     

Bronchial hyperresponsiveness in younger children with asthma

We have previously reported a new technique of evaluating bronchial responsiveness by monitoring the transcutaneous oxygen pressure (tcPO2). This method is so simple, painless, and effortless with high reproducibility that it is possible to use the technique on children as young as 2 years old. Consequently, we used this method to study bronchial hyperresponsiveness in 141 children with asthma and 46 disease controls without asthma or chronic respiratory disorder. The bronchial responsiveness in asthmatic children aged 2 to 5 years was higher than in the disease controls (P less than .001). Further, bronchial responsiveness was significantly higher in moderately as opposed to minimally affected asthmatics (P less than .01), and was gradually higher according to clinical severity. In other age groups as well, the bronchial responsiveness of asthmatic children was higher than of disease controls. There was a close relationship between the level of increased bronchial responsiveness and the clinical severity of asthmatic children.     

Erythrocyte glutathione peroxidase activity in asthmatic children

Erythrocyte glutathione peroxidase (GPX) levels were determined in 56 asthmatic children. Lowest levels were found during acute asthmatic attack (13.53 +/- 2.94 IU) which were significantly less than controls (20.4 +/- 5.44 IU) (P less than .001). Post-attack levels 1 week later rose significantly (16.77 +/- 2.63 IU), but were still less than normal values (P = .001). GPX levels (16.96 +/- 3.28 IU) were less than controls (P less than .03) even in patients with mild symptomatology. Asymptomatic patients receiving theophylline had normal levels. Low GPX activity in asthmatic patients may play a role in the pathogenesis of the disease.     

Medically inappropriate hospital use in a pediatric population

To assess the extent of inappropriate hospital use in pediatric inpatients, I modified the Appropriateness Evaluation Protocol (AEP)--developed to assess inappropriate hospital use in adults--to apply to children and used it to evaluate pediatric inpatients retrospectively for every 10th day, from July 1982 to July 1983, at the University of Wisconsin Hospital. Of 1098 patient-days evaluated, 21.4 percent were judged to represent inappropriate hospital use on the basis of the protocol's criteria. The rate of inappropriate use varied according to admitting specialty, ranging from 7 of 70 days (10 percent) for pulmonary medicine to 43 of 61 days (70 percent) for neurology (P less than 0.005). There was a tendency toward lower rates of inappropriate use in uninsured patients (6 of 44 days [14 percent] vs. 226 of 1038 days [22 percent] in patients with Medicaid or private insurance, P = 0.13), and rates were lower in younger children (74 of 432 days [17 percent] in children less than or equal to 5 years of age vs. 162 of 656 days [25 percent] in children greater than 5 years of age, P less than 0.005). There was no variation according to sex, day of the week, or month. Contrary to expectations, inappropriate use decreased with increased lengths of stay (for stays of 1 day, 8 of 13 days were inappropriate [61 percent]; for stays of 2 to 6 days, 118 of 410 days were inappropriate [29 percent]; for 7 to 13 days, 58 of 291 [20 percent]; and for greater than or equal to 14 days, 51 of 362 [14 percent], P less than 0.001). I conclude that there is a substantial rate of inappropriate hospital use in pediatrics and that such use is more likely during short admissions than during long ones. Cost-containment efforts directed at limiting the length of hospitalization may therefore not reduce inappropriate hospital use in this population.     

Air pollution and daily mortality in Inchon, Korea.

The association between total daily mortality and air pollution was investigated for a 1-year period (January 1995 to December 1995) in Inchon, Korea. The purpose of this study was to evaluate the relative importance of particulate and gaseous air pollution as predictors of daily mortality. Concentration of total suspended particulates (TSP), inhalable particles (PM10), and gaseous pollutants, such as sulfur dioxide, nitrogen dioxide, ozone, carbon monoxide, were measured daily during the study period. A generalized additive model was used to regress daily death counts on each air pollutant, controlling for time trend and meteorologic influences such as temperature or relative humidity. Total mortality was found to increase 1.2% (95% CI: 0.2 to 2.2%) for each 10 microg/m3 increase in 6-day moving average of TSP, and 1.2% (95% CI 0.2 to 2.1%) for each 10 microg/m3 increase in 5-day moving average of PM10. The association is similar in magnitude to associations between particulate air pollution and mortality found in several other communities in America and Europe. Associations with gaseous pollutants were all statistically insignificant in the generalized additive model. The relative risk of death increased at particulate levels that were well below the current Korean Ambient Air Quality Standard.     

Leptin: does it have any role in childhood asthma?

BACKGROUND: Although there is evidence of a positive association between asthma and obesity in adults and children, very little is known about the role of leptin in asthmatic children. OBJECTIVES: The aims of this study were to evaluate the relation between leptin and parameters of atopy and asthma in children. METHODS: Body mass index (BMI) and serum leptin levels were measured in 102 (37 female, 65 male; mean age, 5.9 +/- 3.4 years) asthmatic and 33 (14 female, 19 male; mean age, 6.1 +/- 3.4 years) healthy children. Skin prick tests, total serum IgE, and pulmonary function tests were performed and were completed. RESULTS: A significant difference was observed in serum leptin levels between asthmatic and healthy children. Median (interquartile range) levels were 3.53 (2.06-7.24) ng/mL and 2.26 (1.26-4.71) ng/mL, respectively (P=.008). Subgroup analysis revealed that this difference in leptin levels was confined entirely to boys: 3.09 (1.99-7.51) ng/mL in boys with asthma versus 1.52 (1.06-3.17) ng/mL in boys without asthma (P=.003). By logistic regression analysis, we found that leptin was a predictive factor for having asthma (odds ratio, 1.98; CI, 1.10-3.55; P=.021), whereas sex, age, or BMI were not. In a stepwise multiple regression analysis including sex (P=.001), age (P=.016), BMI (P <.001), and asthma (P=.022), all of these variables were found to affect log leptin levels (R2=0.404). There was no significant sex difference in serum leptin levels among asthmatic children, whereas healthy boys had significantly lower leptin levels than healthy girls (P=.019). Atopic asthmatic subjects had significantly higher leptin levels than nonatopic asthmatic subjects (P=.038) with similar BMI. A significant, but weak, correlation was observed between leptin levels and IgE in the overall group of asthmatic children (r=0.231; P=.019). Again, this correlation was confined entirely to boys (r=0.319; P=.010). There was no relation between leptin levels and skin prick tests, pulmonary function tests, passive smoking, birth weight, and duration of breast-feeding. CONCLUSION: Our findings suggest that leptin may play a role in atopic asthma. High serum leptin levels in asthmatic boys may partly explain the higher prevalence of childhood asthma in male sex.     

Asthma mortality rate in Swedish children and young adults 1973–88

To investigate the asthma mortality rate in Sweden for the period 1973–88, we reviewed all death certificates for suspected death from asthma coded as 493 of the International Classification of Diseases (ICD)-8 and ICD-9 for the age group 1–24 years. Age-related mortality rates were calculated and compared with the results from a previous Swedish study of 1952–72. To identify factors contributing to death, we assessed hospital records. The mortality rate was 3.46 for the period 1973–88 and 3.31 for the earlier period, a net increase of 5%. This small overall increase includes a minor decrease in deaths for the age group 1–14 years and a rather pronounced increase for 15–24-year-old asthmatic patients. More deaths among "mild" asthmatic patients were found in the higher age group for 1986–8 than 1973–81. In younger children, asthma was more severe, and no difference was found between the two periods of the study. Asthma mortality is increasing in Sweden in adolescents and young adults, and there is a tendency to increasing mortality from less severe asthma not treated with anti-inflammatory drugs.     

Pattern of C3, iC3b, and C3d in patients hospitalized for acute asthma.

Twenty-three patients hospitalized for acute asthma were studied for a peripheral blood complement profile consisting of C3, C4, C3d, iC3b, C4d, and Bb concentrations. Compared with normals (n = 22) and patients (n = 10) with acute bacterial infections (ABI), asthmatic patients had significantly higher serum C3 concentrations (P less than .001). Plasma C3d levels and iC3b in asthmatic patients were both comparable to those observed in normal controls, whereas patients with ABI had significantly higher iC3b levels than both other groups. The ratio of iC3b to C3 concentrations were similar in asthmatic patients and controls, and iC3b levels were correlated with total serum C3 levels in asthmatic patients (r = .55, p less than .001) as well as in normal (r = .69, p less than .001). Both of these groups had significantly lower iC3b to C3 ratios compared with the ABI group (P less than .0001). Also observed in asthmatic patients were a significant correlation between serum C4 and C3 levels (r = .83, P less than .001) and a lower mean ratio of plasma C4d to C4 compared with normals (P less than .005). This profile of complement alterations is distinct from that observed in acute bacterial infection. These changes in asthmatic patients may relate to an acute phase reaction phenomenon affecting complement and/or complement regulatory proteins.     

Leukotrienes and 8-isoprostane in exhaled breath condensate of children with stable and unstable asthma

BACKGROUND: Cysteinyl-leukotrienes (cys-LTs) and 8-isoprostane are biomarkers of airway inflammation and oxidative stress. OBJECTIVE: The aim of this study was to evaluate cys-LT and 8-isoprostane levels in exhaled breath condensate (EBC) of children with different degrees of asthma severity. METHODS: EBC was collected from 14 steroid-naive children with mild persistent asthma, 13 children with stable mild- to-moderate persistent asthma treated with inhaled corticosteroids (ICS), 9 ICS-treated children with unstable asthma, and 19 healthy children. RESULTS: In the three groups of asthmatic children, EBC concentrations of cys-LTs and 8-isoprostane were significantly higher than in control children (steroid-naive asthmatic children: cys-LTs median, 10.8 pg/mL, P <.001, 8-isoprostane, 16.2 pg/mL, P <.001; ICS-treated stable asthmatic children: cys-LTs, 12.7 pg/mL, P <.001, 8-isoprostane, 18.1 pg/mL, P <.001; children with unstable asthma: cys-LTs, 106.0 pg/mL, P <.01, 8-isoprostane, 29.7 pg/mL, P <.01; control children: cys-LTs, 4.3 pg/mL, 8-isoprostane, 3.5 pg/mL). Cys-LT levels were higher in children with unstable asthma than in the other two asthmatic groups (P <.05). FE(NO) levels were significantly higher in steroid-naive and in children with unstable asthma compared with ICS-treated children with stable asthma (P <.01). CONCLUSIONS: Our study shows that EBC cys-LTs and 8-isoprostane concentrations are higher in asthmatic children than in healthy control children, with scattered values in patients with unstable asthma. These findings suggest that EBC eicosanoid measurement may have useful clinical implications for investigating phenotype differences among asthmatic patients.     

Trends in hospitalizations for anaphylaxis, angioedema, and urticaria in Australia, 1993-1994 to 2004-2005

BACKGROUND: Recent investigations in developed countries have found marked increases in the prevalence of allergic conditions. OBJECTIVE: We sought to examine recent time trends in the prevalence of anaphylaxis, angioedema, and urticaria by describing trends and age and sex differentials in hospitalizations for these conditions in Australia. METHODS: Data on hospital admissions and deaths for anaphylaxis, angioedema, and urticaria were extracted for the periods 1993-1994 to 2004-2005 and 1997-2004, respectively. For hospital admissions, age-standardized rates were calculated. Time trends and sex differences were quantified by using negative binomial models. RESULTS: During the study period, there was a continuous increase in the rate of hospital admissions for angioedema (3.0% per year), urticaria (5.7% per year), and, most notably, anaphylaxis (8.8% per year). There was a particularly steep increase in the incidence of hospitalization for food-related anaphylaxis among children aged less than 5 years. Admissions for non-food-related anaphylaxis occurred predominantly in adults, particularly those more than 35 years of age. Among children, admission rates were higher in boys, but the sex difference was reversed among adults. Over an 8-year period, there were 106 deaths associated with anaphylaxis or angioedema. CONCLUSION: Hospitalization rates for allergic conditions are on the increase, but the nature and causative factors differ between adults and children. The relation of these changes to those in the prevalence of specific allergen sensitization in the community requires further investigation in population studies. CLINICAL IMPLICATIONS: Among older persons, angioedema is becoming an increasing problem. Among children, hospitalization because of food-induced anaphylaxis is a growing concern.     

Variations in rates of hospitalization of children in three urban communities

Hospitalization accounts for a large portion of the expenditures for child health care, and differences in the rate of hospitalization may produce important variations in the cost of that care. We studied the rates of hospitalization in Boston, Rochester (N.Y.), and New Haven (Conn.) in 1982. We assigned the risk of hospitalization in Rochester a score of 1.00. Boston children were hospitalized at more than twice the rate of Rochester children for most medical diagnostic categories (relative risk, 2.65; 95 percent confidence interval, 2.53 to 2.78), and the rate for the New Haven group was intermediate (relative risk, 1.80; 95 percent confidence interval, 1.68 to 1.93). Rates of inpatient surgery differed less (Boston relative risk, 1.12; New Haven relative risk, 0.93). The relative risks of hospitalization (as compared with Rochester children) for Boston and New Haven children, respectively, were 3.8 and 2.3 for asthma, 6.1 and 2.9 for toxic ingestions, and 2.6 and 2.7 for head injuries. Fractures of the femur, appendicitis, and bacterial meningitis (conditions uniformly treated in the hospital) had similar rates of hospitalization across the three cities, but the relative risk of hospitalization for aseptic meningitis was 3.7 in Boston. The rates of hospitalization of children in all three communities were below the national averages in 1982. Although this study does not define the reasons for the variation in rates of hospitalization, it is possible that they were related in part to differences in socioeconomic status or access to primary care. The implications of these data for the cost and quality of pediatric care therefore remain to be determined.     

Trends and ethnic differences in asthma hospitalization rates in Singapore, 1991 to 1998.

BACKGROUND: A few reports have indicated that asthma hospitalization rates in several countries have stopped rising or started falling in the 1990s. AIM: To describe recent trends and ethnic differences in asthma hospitalization rates in Singapore from 1991 to 1998. METHODS: Asthma hospitalization rates in all hospitals were analyzed by age groups, sex, ethnicity, and individual years, using aggregated data for asthma (ICD-9 493 and ICD-10 J45, J46) from 1991 to 1998, when nationwide data from the Central Claims Processing System were available. RESULTS: Between 1991 and 1998 there were a total of 37,615 hospital admissions for asthma, giving an annual average rate of 17.1 hospital admissions per 10,000 persons. Overall, the rates of asthma hospitalization fell by 28% from 21.7 per 10,000 in 1991 to 15.4 per 10,000 in 1998 (3.5% annually). The trends were broadly based across all age, sex, and ethnic groups. Hospitalizations were more common in boys than in girls aged 0 to 4 (male/female ratio 1.69), but less common in men than women aged 35 to 64 (male/female ratio 0.81). Rates of asthma hospital admissions were higher in Malays (32.8 per 10,000) and Indians (40.8 per 10,000) than Chinese (11.9 per 10,000). CONCLUSIONS: In line with findings from several countries, there have been recent declines in rates of hospital admissions for asthma in Singapore in the 1990s. The declines were broadly based across all population subgroups and parallel previously observed declines in mortality in adults. However, considerable ethnic differences in levels of asthma hospitalization still exist.     

Trends in hospital admissions for childhood asthma in Oslo, Norway, 1980-95

BACKGROUND: The prevalence of asthma and quality of asthma care both influence hospital admission rates for childhood asthma. Therefore, we aimed to assess possible changes in the hospital admission rate for acute asthma in Oslo, Norway, from 1980 to 1995, as well as evaluate the possible effect of changes in asthma treatment upon hospitalization for acute asthma in this period. METHODS: All pediatric patient records from the two municipal hospitals in Oslo from 1980 through 1995 with the discharge diagnoses (ICD-9) acute asthma, acute bronchitis/bronchiolitis, pneumonia, and/or atelectasis were thoroughly reviewed. RESULTS: Of the 3,538 children admitted for acute asthma, 66% were boys and 75% were younger than 4 years, and the admittance rate increased significantly among children aged 0-3 years. First admissions increased throughout the study, whereas readmissions, as well as the mean duration of hospital stay, decreased significantly. Prophylactic treatment with inhaled steroids prior to admission increased over 1980-89, but stabilized thereafter. The use of a short course of systemic steroids during admission increased markedly from 1991. CONCLUSIONS: The findings of increasing first admission rate as well as overall admission rate for acute asthma in children under 4 years of age, but decreasing readmissions as well as number of treatment days in hospital, probably reflect changes in the management of the disease, as well as an increasing prevalence of childhood asthma.     

Improved bronchodilator effect of deep inhalation after allergen avoidance in asthmatic children

BACKGROUND: In healthy adults and children, deep inhalation (DI) is able to reverse induced bronchoconstriction. This ability is impaired in asthma, but the reasons are still to be elucidated. OBJECTIVES: This study investigated whether the bronchodilator effect of DI during methacholine-induced bronchoconstriction can be improved by allergen avoidance in asthmatic children, and its relationship with airway inflammation. METHODS: The effect of DI on methacholine-induced bronchoconstriction was studied at the beginning and the end of a 3-month allergen avoidance period at high altitude in 14 allergic asthmatic children who had severe asthma attacks. Changes in airway caliber were inferred from the respiratory resistance (Rrs) measured by a forced oscillation technique. Results were related to the percentage of eosinophils in induced sputum and compared with those obtained in 9 age-matched nonasthmatic children. RESULTS: In asthmatic subjects, DI had no significant effect on methacholine-induced increase in Rrs before (P=.62) but significantly reversed it after (P <.01) allergen avoidance. However, the ability of DI to reverse a methacholine-induced increase in Rrs tended to remain less in asthmatic than nonasthmatic children even after allergen avoidance (P=.05). In the asthmatic children, the percentage of eosinophils in induced sputum was decreased at the end of the allergen avoidance period (P <.001), without any significant correlation between sputum eosinophils and airway responsiveness to methacholine or effect of DI. CONCLUSION: A short period of allergen avoidance may improve the ability of DI to reverse induced bronchoconstriction in some asthmatic children. This effect is associated, yet not correlated, with a reduction in airway inflammation.     

Associations of the IL12B promoter polymorphism in longitudinal data from asthmatic patients 7 to 42 years of age

BACKGROUND: The IL12B gene encodes the p40 chain of IL-12, a proinflammatory cytokine that antagonizes TH2 expression and hence may play a critical role in the pathogenesis of airway inflammation observed in asthma. A promoter polymorphism of the gene was recently shown to be associated with asthma severity in children but only in heterozygotes. OBJECTIVE: The aim of the present study was to test the hypothesis that the IL12B promoter polymorphism is associated with asthma susceptibility, severity, and related phenotypes in a cohort with longitudinal phenotypic data, from childhood to adulthood. METHODS: Four hundred one 7-year-old children (106 control children, 295 asthmatic children) and 83 10-year-old children with severe asthma were recruited from a 1957 birth cohort. Atopic status and respiratory functions were determined at ages 7, 10, 14, 21, 28, 35, and 42 years. At age 42 years, blood samples were taken from 244 individuals for genotyping and the determination of plasma IgE levels and PHA- and house dust mite-induced IFN-gamma responses. Genotyping was done by the PCR restriction fragment length polymorphism method, using Alu I, and confirmed in 10% of the samples by direct sequencing. RESULTS: The IL12B genotypes were not associated with asthma susceptibility, severity, or atopy at ages 7 and 42 years. Total serum IgE levels at age 42 of men with at least one CTCTAA allele were higher than those homozygous for the GC allele (P = .042), whereas no difference was observed for women. At all ages, female subjects with at least 1 copy of the CTCTAA allele had lower mean percent predicted levels of FEV1 and FVC compared with those without this allele; these differences were significant at ages 10 and 14 years (P < .05) and in the asthmatic subgroup at age 7 years (P = .001). CONCLUSIONS: In this long-term study of asthmatic subjects with comprehensive data on asthma severity, we found no evidence to support the presence of a heterozygote effect of the IL12B promoter polymorphism on the level of asthma in early childhood or adulthood. The polymorphism was also not associated with asthma susceptibility, but the CTCTAA allele may have been associated with elevated serum IgE levels in male subjects and reduced pulmonary function in female subjects in early childhood.