Childhood Asthma Management Program Research Articles

Effects of ambient air pollution on symptom severity and medication use in children with asthma

Exposure to air pollutants has been investigated as a possible cause of asthma attacks in children. To investigate the short-term effects of air pollutants on a panel of 133 children with asthma who enrolled in the Childhood Asthma Management Program. During screening, the children completed daily diary cards for an average of 58 days to indicate their medication use and asthma severity. We used ordinal logistic regression to compare the odds of a more serious relative to a less serious asthma attack, and we used a Poisson model to analyze medication use. In both analyses we accommodate dependence in the data and different periods of observation for study subjects. Our results indicate that a 10-microg/m3 increase in particulate matter less than or equal to 2.5 microm (PM2.5) lagged 1 day was associated with a 1.20 times increased odds of having a more serious asthma attack [95% confidence interval (CI), 1.05 to 1.37] and a 1.08-fold increase in medication use (95% CI, 1.01 to 1.15). A 10-microg/m3 increase in particulate matter less than or equal to 10 microm (PM10) increased the odds of a more serious asthma attack (odds ratio = 1.12; 95% CI, 1.04 to 1.22) and also increased medication use (relative risk = 1.05; 95% CI, 1.00 to 1.09). Increases in PM2.5 and PM10 are significantly associated with an increased risk of more severe asthma attacks and medication use in Seattle area children with asthma. We also found associations with carbon monoxide, but we believe that carbon monoxide is a marker for exposure to combustion byproducts.

In My Opinion - Interview with the Experts

A NDREW H. Liu, M.D., is the Training Program Director and an Associate Professor in Pediatric Allergy & Immunology at the National Jewish Medical & Research Center and the University of Colorado Health Sciences Center inDenver. He serves as the Pediatric Asthma & Allergy Consultant to the Health & Hospitals System for the City & County of Denver. In addition, he runs teaching clinics at National Jewish, Denver Health, and The Children's Hospital of Denver. Dr. Liu researches the immune development underlying asthma and allergies in young children, seeking early intervention strategies for therapy and prevention. He is an investigator for the National Institutes of Health (NIH) in several research programs in this field. These include a recent NIH Career Development Award on Endotoxin and Asthma Prevention in Young Children, and several NIH-funded intervention studies for childhood asthma: Childhood Asthma Management Program (CAMP); Childhood Asthma Prevention Study (CAPS); and Prevention of Early Asthma in Kids study (PEAK). Dr. Liu has written articles for such peer-reviewed journals as The Lancet, Journal of Allergy and Clinical Immunology, Journal of Experimental Medicine, and Proceedings of the National Academy of Sciences. He is a Fellow of the American Academy of Pediatrics and the American College of Allergy, Asthma, and Immunology, and a member of the American Academy of Allergy, Asthma, and Immunology and the American Association of Immunologists. Dr. Liu received his medical degree from the University of Massachusetts Medical School and completed his Internship and Residency in Pediatrics at the University of Colorado School of Medicine. He completed his Fellowships in Allergy & Immunology and in Clinical & Laboratory Immunology at the National Jewish Medical and Research Center.

Hospitalization for asthma: atopic, pulmonary function, and psychological correlates among participants in the Childhood Asthma Management Program.

Asthma in childhood has a significant impact on children and families, in part because of the frequent need for hospital-based care for acute exacerbations. Sensitization and exposure to inhalant allergens have been identified as risk factors for asthma hospitalization. The Childhood Asthma Management Program (CAMP), comprised of 1041 children aged 5 to 12 with mild-to-moderate asthma, provides the opportunity to identify specific risk factors for prior hospitalization for asthma. Data gathered during the screening period from CAMP were evaluated to elucidate differences between patients who had ever been hospitalized for asthma before enrollment in CAMP and those who had never been hospitalized. Univariate analyses indicated that prior hospitalization for asthma was associated with a younger age of asthma onset, longer duration of asthma, greater number of positive allergy skin tests, higher serum immunoglobulin E level, greater peripheral blood eosinophilia, greater recent inhaled corticosteroid use, greater airflow obstruction, greater airway hyperresponsiveness, and lower patient intelligence quotient (IQ). Gender, race, and family income did not differ between hospitalized and never-hospitalized patients. The combination of both sensitization and exposure to high levels of dog allergen (Can f1) was associated with greater likelihood of prior hospitalization. Forward multivariate logistic regression analysis identified younger age of asthma onset, longer duration of asthma, recent use of asthma controller therapy, greater airflow obstruction, and lower patient IQ as significant risk factors for prior hospitalization when all risk factors identified by univariate analysis were included in the model. Children with mild-to-moderate asthma who had a past hospitalization for acute asthma had greater asthma severity, younger age of onset, and lower patient IQ at the time of entry into CAMP. They also had more markers of atopy than children without prior hospitalization, although atopy was not associated with prior hospitalization on multivariate analysis. Although we have identified these risk factors in a retrospective manner, one can speculate that the persistence of these features should alert the clinician to closely follow abnormalities on pulmonary function tests and general features of atopy to potentially identify patients at risk for future hospitalization.

Minimizing attrition in a long-term clinical trial of pediatric asthma

Despite increased attention focused on the need to prevent patient attrition in long-term clinical trials, high dropout rates have threatened the success of numerous studies. To evaluate the disease, demographic, and psychological factors associated with missed visits and study dropout to help improve patient management in long-term clinical trials. Predictors of attrition were examined within the Childhood Asthma Management Program (CAMP), a large, multicenter clinical trial that followed up 1,041 children with asthma for 4 to 6 years. Eighty-two percent of patients attended all study visits. The tendency to miss visits was increased among older children with milder asthma, lower intellectual and social competence, and more symptoms of behavioral problems and emotional distress. Forty-two patients who missed 3 or more visits in a row and did not attend the final visit were considered study dropouts; these patients at baseline had milder asthma; lower cognitive, academic, and social competence skills; and more family conflict and distress than found among participants who remained in the study. The 49 children who had erratic attendance but did not drop out also had lower intellectual and academic skills and less family social support. The 4% dropout rate in CAMP was lower than reported in any previous long-term asthma trial. The findings of milder disease, decreased psychological resources, and increased distress in problem-attendance patients can assist in identifying patients who are at risk for missed visits or dropout during the trial either to block their entry into the trial or to focus efforts at maintaining their attendance once enrolled in the trial.

Chromosome 12q harbors multiple genetic loci related to asthma and asthma-related phenotypes.

Chromosome 12q13-24 is among the regions most frequently identified in genome-wide surveys for asthma susceptibility loci, with reports of two distinct clusters of positive linkage signals: one near the interferon gamma locus, the other near the nitric oxide synthase 1 locus. These results suggest that 12q harbors several asthma susceptibility loci. We evaluated this possibility in a subset of families ascertained through the Childhood Asthma Management Program (CAMP) Genetics Ancillary Study. Fifty-five nuclear families with at least two asthmatic siblings (212 individuals) were genotyped using 32 microsatellite markers. Non-parametric linkage analysis was performed for the asthma phenotype (qualitative). Multipoint variance component-based linkage analysis was performed for five quantitative asthma-related traits: (i) percent predicted forced expiratory volume in one second (FEV(1)); (ii) dose of methacholine resulting in 20% fall in FEV(1) from baseline (PC(20)); (iii) post-bronchodilator percent change in FEV(1) (BDPR); (iv) serum eosinophil levels (EOS); and (v) total serum IgE levels (IgE). Three separate and distinct loci demonstrated evidence suggestive of linkage: asthma at 68 cM (exact P-value=0.05), airways responsiveness (PC(20)) at 147 cM (P=0.01), and indices of pulmonary function (FEV1, BDPR) at 134 cM (P=0.05 and P<0.01, respectively). No linkage was observed for the atopy-related phenotypes. We provide further evidence supporting the presence of an asthma susceptibility locus at the proximal end of chromosome 12q, as well as new evidence for additional loci more distally that account for unique features of the asthma phenotype. Fine mapping efforts for these loci are warranted.

Assessing the economic burden of asthma

Assessing the economic burden of asthma

Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma

Objective Exhaled nitric oxide (FENO) was evaluated in children with asthma after 4 to 6 years of treatment with budesonide, nedocromil, or albuterol as needed. Study design FENO, spirometry, total eosinophil count, and serum eosinophil cationic protein levels were obtained from 118 children at the Denver site of the Childhood Asthma Management Program upon completion of treatment and after a 2- to 4-month washout. Results Budesonide-treated patients had significantly lower median (1st, 3rd quartile) FENO (21.5 [13.2, 84.4] vs 62.5 [26.2, 115.0] ppb, P <.01) and eosinophil cationic protein levels (17.4 [10.1, 24.3] vs 24.0 [15.4, 33.9] mg/dL, P =.05) compared with placebo, whereas no differences were noted between nedocromil and placebo groups. After washout, FENO levels were similar between the three treatments. FENO levels significantly correlated with degree of bronchial hyperresponsiveness, bronchodilator reversibility, allergen skin prick tests, serum IgE, and total eosinophil count. FENO levels were also higher in patients with nocturnal symptoms and in patients requiring β-agonist use at least once weekly. Conclusions Budesonide therapy was more effective than nedocromil in reducing FENO. Unfortunately, the effects of long-term budesonide were not sustained after its discontinuation. FENO may be a complementary tool to current practice guidelines in assessing asthma control and medication response. (J Pediatr 2003;142:469-75 )

Growth and bone density in children with mild-moderate asthma: A cross-sectional study in children entering the Childhood Asthma Management Program (CAMP)

Objectives We sought to determine whether mild-moderate persistent asthma sufficient to produce a decrease in baseline lung function is associated with an adverse effect on growth and bone mineral density (BMD) in children. Methods This was a cross-sectional study of 1041 children, 5 to 12 years old (32% ethnic/racial minorities and 40% female), enrolled into the Childhood Asthma Management Program (CAMP). Measures of asthma severity included: Spirometry; bronchial hyperresponsiveness; duration of asthma symptoms; and symptom-based assessment of severity. Multiple regression analyses were used to relate the asthma severity on the primary outcome variables: Height by stadiometry and BMD by dual energy radiographic absorptiometry. Results The mean ± SD height percentile was 56.0 ± 28.5 percentile for the population. The only significant relationship between asthma severity and height percentile was with methacholine bronchoprovocation in girls (β 2.98, P = .019, covariate multiple regression). The mean ± SD BMD was 0.65 ± 0.10 g/cm2 for the population. The past use of corticosteroids did not adversely affect either growth or BMD. Conclusions We found that mild-moderate asthma of as long as 4 to 7 years duration in children does not produce an adverse effect on linear growth or BMD. (J Pediatr 2003;142:286-91)

Factors Influencing Parent Reports on Quality of Life for Children with Asthma

Children and parents often differ in their perceptions of a complex disease such as asthma. This ancillary study of children with mild to moderate asthma that was conducted at four of the eight clinics in the Childhood Asthma Management Program had two aims: (1) to relate quality of life to asthma symptoms, sociodemographic characteristics, child psychosocial adjustment and family social support and (2) to relate agreement between child- and parent-reported quality of life to child age. For this study participants completed the Caregiver's Pediatric Asthma Quality of Life Questionnaire (C-PAQLQ), Pediatric Asthma Quality of Life Questionnaire, and a battery of psychosocial health outcomes questionnaires at the 12-month follow-up. The average asthma symptom score from diary cards for the 2 weeks before the visit was also collected. Parent-reported family burden was the strongest correlate of C-PAQLQ scores. Although the average asthma symptom score was not associated with parent-reported quality of life, the study had low power to detect a relationship because of the few episodes of asthma reported during the assessment period. The correlation between child and parent reported quality of life improved with increasing age of the child, suggesting increased child-parent agreement about quality of life outcomes was associated with increasing age of the child. Family characteristics, such as degree of cohesion among family members, are not associated with quality of life ratings.

Univariate and multivariate family-based association analysis of the IL-13 ARG130GLN polymorphism in the Childhood Asthma Management Program.

Interleukin 13 (IL-13) has been demonstrated to have a crucial role in animal models of allergy and asthma. In human case-control genetic-association studies, the Arg130Gln polymorphism has been associated with elevated total serum IgE and an asthma diagnosis in atopic and nonatopic individuals (Graves et al. [2000] J. Allergy Clin. Immunol. 105:506-513; Heinzmann et al. [2000] Hum. Mol. Genet. 9:549-559). To apply family-based association methods, we obtained DNA samples from 685 asthmatic children from 640 sibships and their parents in the Childhood Asthma Management Program (CAMP). Six hundred and sixty-six asthmatic children had complete phenotypic information and were used for this analysis. We performed quantitative association analysis using the transmission disequilibrium test (TDT) on 22 individual phenotypes and 5 grouped phenotypes relating to allergy, airway responsiveness, pulmonary function, bronchodilator responsiveness, and asthma severity, using genotypes at the Arg130Gln polymorphism of the IL-13 gene. A positive association was obtained between Arg130Gln and a grouped phenotype of allergy (consisting of the individual phenotypes of eosinophils, IgE, and positive skin tests), using FBAT-GEE, a multivariate extension of the family-based association test (Lange et al. [2002] Biostatistics 1:1-15). The three phenotypes were then evaluated individually and revealed a significant association between total eosinophil count and the Arg130Gln locus; there was a trend for association between total IgE and the Arg130Gln polymorphism. The Arg130Gln polymorphism is associated with an elevated eosinophil count as well as with a grouped allergy phenotype, in children with mild to moderate asthma. No evidence for association was found between Arg130Gln and airway responsiveness, asthma diagnosis, or asthma severity.

Irreversible airway obstruction in childhood asthma? A clinician's viewpoint.

Even though childhood asthma is assumed to comprise reversible airway obstruction, some children develop irreversible airway obstruction (not reversed by a bronchodilator or corticosteroids); this may be due to inflammation that has caused remodeling. Lately, it has been claimed that in the absence of treatment with inhaled corticosteroids, most patients will develop progressive irreversible obstruction. Several studies culminating with the Childhood Asthma Management Program (CAMP) study, which was the first randomized placebo-controlled prospective long-term study designed to test for irreversible obstruction, did not show the development of such progressive irreversible obstruction. Nevertheless, deterioration in pulmonary function does occur in some patients, probably due to inadequate anti-inflammatory treatment, and possibly also due to maintenance adrenergic treatment. Most previous studies concentrated on forced expiratory volume in 1 sec (FEV(1)), a test assessing mostly large airway obstruction. More studies are needed to investigate the presence of small airway obstruction.

Childhood asthma: New insights into management

Recently, a concerted effort has been made to reverse the trend of increasing asthma mortality and morbidity. One additional strategy might be to recognize patients at risk for persistent asthma and to intervene early. This review summarizes new information on asthma pathogenesis that has helped shape a new direction in managing childhood asthma. At the core is the recognition that asthma is a chronic inflammatory disease. Subsequently, inhaled steroids, the most potent anti-inflammatory asthma medications, have emerged as the cornerstone of the management of persistent asthma. The recent report of the National Heart, Lung, and Blood Institute’s Childhood Asthma Management Program provides a comprehensive “profile of performance” for 3 treatment choices for the management of persistent asthma. This study answers questions regarding the benefits and shortcomings of the medications evaluated and prompts a closer evaluation of the long-term effects of other treatment strategies, including medications currently being developed. Although intervention with inhaled steroids offers new opportunities to control the development of asthma, one must be cognizant of potential risks in early and long-term therapeutic intervention. This review provides a perspective on our present knowledge, the rationale for early intervention, and opportunities for more aggressive therapy, as well as speculation on how ongoing clinical research will continue to play a role in advancing asthma care and moving toward a “cure” for this life-threatening disease. (J Allergy Clin Immunol 2002;109:3-13.)

Nocturnal awakening due to asthma in children with mild to moderate asthma in the childhood asthma management program

Nocturnal awakening due to asthma in children with mild to moderate asthma in the childhood asthma management program

Predicting children's quality of life in an asthma clinical trial: What do children's reports tell us?

Objective: To define predictors of disease-specific quality of life (QOL) and the relationship between asthma symptoms and disease-specific QOL. Study design: Three hundred thirty-nine children participated at 4 of 8 Childhood Asthma Management Program clinical centers. Included in the analyses were 2 weeks of asthma symptom data, child-reported health status, and QOL scores from the Pediatric Asthma Quality of Life Questionnaire. Data were obtained 12 months after randomization into the Childhood Asthma Management Program. Results: Children were rated at baseline as having “moderate” asthma (63%) and “mild” asthma (37%). QOL scores were correlated with the child-reported anxiety measures. Factor analysis of the QOL measure resulted in 2 factors. Stepwise multiple regression indicated that the strongest independent predictors of QOL were the child's anxiety level, age, sex, and a measure of the child's tendency to minimize or exaggerate symptoms. Conclusions: Children had few asthma symptoms in the 2 weeks before their 12-month follow-up clinic visit and a generally positive QOL, suggesting that mild-to-moderate asthma does not significantly impair QOL. A child's QOL was predicted primarily by their level of anxiety. (J Pediatr 2001;139:854–61)

Asthma outcome measures

Asthma outcome measures

Challenges in assessing outcomes for pediatric asthma

Although progress has been made in understanding asthma, much remains unknown; as a result, diagnosis and treatment are not optimal. Information is still needed about the natural history of asthma to better understand which patients are at risk of inflammation and at what point during their disease that inflammation occurs. In the case of children, a greater understanding of the disease’s natural history is needed to establish criteria for early diagnosis and to evaluate progressive aspects of the disease so that appropriate measures of progression can be defined. The safety of various medications used as long-term controllers must also be evaluated. The growing information about medication effects on asthma provides unique opportunities to design studies that will guide improvement in asthma care. A number of disease outcomes can be used as surrogate markers of clinically significant endpoints, and a number of adverse effects may serve as surrogate markers. The consequences of poor control of pediatric asthma can be observed in a variety of clinical markers, including clinical features of the disease that worsen as it progresses, pulmonary function deterioration, lung hyperexpansion, and inflammation increases. The Childhood Asthma Management Program is an ongoing clinical trial designed to improve the diagnosis and treatment of asthma in children. Its hypothesis is that anti-inflammatory treatment of childhood asthma will not only relieve morbidity but will also improve lung growth. (J Allergy Clin Immunol 2001;107:S456-64.)

Budesonide and nedocromil did not improve lung function in children with asthma

(2000) N Engl J Med 343, 1054. The Childhood Asthma Management Program Research Group. . Long-term effects of budesonide or nedocromil in children with asthma. . Oct 12; . :...

Budesonide and nedocromil did not improve lung function, but budesonide improved symptom control in asthmatic children

TherapeuticsMay 1, 2001Budesonide and nedocromil did not improve lung function, but budesonide improved symptom control in asthmatic childrenFrancine M. Ducharme, MD, MScFrancine M. Ducharme, MD, MScMcGill University, Montreal, Quebec, Canada (F.M.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2001-134-3-099 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinkedInRedditEmail Source CitationThe Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med. 2000 Oct 12;343:1054-63. https://pubmed.ncbi.nlm.nih.gov/11027739Reference1 Sharek PJ, Bergman DA. Beclomethasone for asthma in children: effects on linear growth. Cochrane Database Syst Rev. 2001;(1):CD001282. Google Scholar Author, Article, and Disclosure InformationAffiliations: McGill University, Montreal, Quebec, Canada (F.M.D.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails May 1, 2001Volume 134, Issue 3Page: 99KeywordsAsthmaBoneBronchodilatorsChildrenDepressionDrug delivery system preparationDrugsHospitalizationsLungsMethacholine challengeRespiratory system proceduresSafetySodiumSystematic reviews ePublished: 9 March 2020 Issue Published: May 1, 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

The prevalence of environmental exposure to perceived asthma triggers in children with mild-to-moderate asthma: Data from the Childhood Asthma Management Program (CAMP)

Background: The Childhood Asthma Management Program, a 5-year randomized clinical trial of treatments for childhood asthma, has enrolled and characterized a cohort of 1041 children with mild-to-moderate asthma. Objective: We sought to describe self-reported sensitivities and environmental exposures and investigate the relationships between self-report of these exposures as asthma triggers and their prevalence in the home. Methods: Self-reports of sensitivities and home exposures were obtained by interview with the child or parent. Sensitivities were further assessed by using allergy skin testing (prick or puncture) against a core battery of allergens. Home exposures were further assessed by using analysis of a home dust sample. Results: Environmental exposures were surprisingly common despite self-reported sensitivities to environmental factors. Of patients reporting that cigarette smoking frequently causes asthma symptoms, 26% reported having at least one parent who smokes cigarettes. Thirty-nine percent of patients reporting that exposure to animals frequently causes asthma symptoms live with a furry pet in their home. We found a smaller proportion of homes with a high level of cat allergen (P < .001) among the children who reported that animals frequently or always trigger asthma symptoms compared with those who reported that animals never or occasionally trigger asthma symptoms, suggesting modification of the home environment. No such results were seen for dog exposure. However, clinical symptoms did not reduce exposure to parental cigarette smoking (P = .15), house dust (P = .31), or damp and musty areas (P = .51). Conclusion: These data suggest that children with mild-to-moderate asthma are frequently symptomatic and exposed to a wide variety of environmental exposures that are perceived to trigger symptoms by means of self-report. Although environmental modification of asthmatic homes may occur, many children remain exposed to agents that are known to trigger their asthma. (J Allergy Clin Immunol 2001;107:634-40.)

House dust mite and cockroach exposure are strong risk factors for positive allergy skin test responses in the Childhood Asthma Management Program

Background: Children with asthma have a high prevalence of environmental allergies, especially to indoor allergens. The relationships of exposure to indoor allergens (dust mites, cat, dog, cockroach, and molds) and other host factors to allergy sensitization have not been evaluated simultaneously in a large cohort. Objectives: We studied 1041 children aged 5 to 12 years with mild-to-moderate asthma to determine risk factors associated with having positive allergy skin test responses to indoor allergens. Also, we described, compared, and contrasted 6 allergens in the home environments of these children from 8 North American cities. Methods: Data were used from baseline visits of the Childhood Asthma Management Program. Patients’ sensitivities to house dust mites (Dermatophagoides farinae and Dermatophagoides pteronyssinus), cats, dogs, cockroaches, and molds were examined for relationships to demographic variables, home dust allergen exposures, number of other positive allergy skin test responses, total serum IgE levels, and smoking in the home. Results: San Diego (78.5%) and Toronto (59.3%) had the topmost percentages of homes with moderate-to-high house dust mite levels. Boston (21.5%), St Louis (16.3%), and Baltimore (13.4%) had the highest percentages of homes with detectable levels of cockroach allergen. For house dust mites, the higher the level of allergen exposure, the more likely patients were to have positive allergy skin test responses, with relative odds of 9.0 (95% confidence interval, 5.4-15.1) for those exposed to high mite levels (>10.0 μg/g dust) relative to those unexposed. Even exposure to low levels of mite allergen (0.020-2.0 μg/g) was found to be a significant risk factor for sensitization. For cockroach allergen, those with detectable home exposure were more likely to have positive skin test responses (relative odds, 2.2; 95% confidence interval, 1.3-3.8) than those with undetectable exposure. In contrast, levels of exposure to cat, dog, and mold allergens were not related to sensitization rates. For cat allergen, this may reflect lower rates of cat ownership among highly sensitized subjects. Furthermore, the number of allergy skin test responses that were positive, excluding the test for the outcome of interest for each model, and total serum IgE levels were strong independent predictors of sensitization. Conclusions: Levels of exposure determined by house dust analysis are important determinants of sensitization for dust mite and cockroach allergen. This relationship was not demonstrable for cat, dog, or mold allergens, possibly because of confounding factors. For all allergens studied, the degree of atopy, determined by the total number of positive skin test responses or by total serum IgE levels, is an important contributing risk factor for sensitization. (J Allergy Clin Immunol 2001;107:48-54.)