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Avraham Beigelman,
Tonya S King,
David Mauger, Robert S Zeiger,
Robert C Strunk,
H William Kelly,
Fernando D Martinez,
Robert F Lemanske,
Katherine Rivera-Spoljaric,
Daniel J Jackson,
Theresa Guilbert,
Ronina Covar,
Leonard B Bacharier
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ABSTRACT: BACKGROUND: Oral corticosteroids (OCSs) are recommended for severe wheezing episodes in children. However, limited evidence supports this intervention in preschool children with outpatient wheezing illnesses. OBJECTIVE: We sought to investigate whether OCSs reduce symptom scores during acute lower respiratory tract illnesses (LRTIs) in preschool children with recurrent wheeze. METHODS: We performed post hoc and replication analyses in 2 outpatient cohorts of children aged 1 to 5 years with episodic wheezing participating in clinical trials. We compared symptom scores during LRTIs that were or were not treated with OCSs, adjusting for differences in disease and episode severity covariates. We stratified episodes by severity by using a propensity model. The primary outcome was the area under the curve (AUC) of total symptom scores among the more severe episodes. RESULTS: Two hundred fifteen participants from the Acute Intervention Management Strategies trial experienced 798 acute LRTIs, 112 of which were defined as severe based on propensity scores. The AUCs of total symptom scores did not differ between the episodes that were (n = 70) and were not (n = 42) treated with OCSs (P = .46) nor was there an OCS treatment effect on individual symptom scores. Similar analyses of the Maintenance Versus Intermittent Inhaled Corticosteroids in Wheezing Toddlers trial, involving 278 participants with 133 severe LRTIs, confirmed the above findings (P = .46 for AUC of total symptoms score comparison). CONCLUSION: In 2 separate cohorts of preschool children with episodic wheezing, OCS treatment during clinically significant LRTIs did not reduce symptom severity during acute LRTIs, despite asthma controller medication use during most episodes. These findings need to be confirmed in a prospective randomized controlled trial.
The Journal of allergy and clinical immunology 03/2013; · 9.17 Impact Factor
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Blanca E Himes,
Keith Sheppard,
Annerose Berndt,
Adriana S Leme,
Rachel A Myers,
Christopher R Gignoux,
Albert M Levin,
W James Gauderman,
James J Yang,
Rasika A Mathias, [......],
L Keoki Williams,
Esteban G Burchard,
Dan L Nicolae,
Carole Ober,
Dawn L Demeo,
Edwin K Silverman,
Beverly Paigen,
Gary Churchill,
Steve D Shapiro,
Scott T Weiss
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ABSTRACT: Asthma is a common chronic respiratory disease characterized by airway hyperresponsiveness (AHR). The genetics of asthma have been widely studied in mouse and human, and homologous genomic regions have been associated with mouse AHR and human asthma-related phenotypes. Our goal was to identify asthma-related genes by integrating AHR associations in mouse with human genome-wide association study (GWAS) data. We used Efficient Mixed Model Association (EMMA) analysis to conduct a GWAS of baseline AHR measures from males and females of 31 mouse strains. Genes near or containing SNPs with EMMA p-values <0.001 were selected for further study in human GWAS. The results of the previously reported EVE consortium asthma GWAS meta-analysis consisting of 12,958 diverse North American subjects from 9 study centers were used to select a subset of homologous genes with evidence of association with asthma in humans. Following validation attempts in three human asthma GWAS (i.e., Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG) and two human AHR GWAS (i.e., SHARP, DAG), the Kv channel interacting protein 4 () gene was identified as nominally associated with both asthma and AHR at a gene- and SNP-level. In EVE, the smallest association was at rs6833065 (P-value 2.9e-04), while the strongest associations for Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG were 1.5e-03, 1.0e-03, 3.1e-03 at rs7664617, rs4697177, rs4696975, respectively. At a SNP level, the strongest association across all asthma GWAS was at rs4697177 (P-value 1.1e-04). The smallest P-values for association with AHR were 2.3e-03 at rs11947661 in SHARP and 2.1e-03 at rs402802 in DAG. Functional studies are required to validate the potential involvement of in modulating asthma susceptibility and/or AHR. Our results suggest that a useful approach to identify genes associated with human asthma is to leverage mouse AHR association data.
PLoS ONE 01/2013; 8(2):e56179. · 4.09 Impact Factor
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Bradley E Chipps, Robert S Zeiger,
Alejandro Dorenbaum,
Larry Borish,
Sally E Wenzel,
Dave P Miller,
Mary Lou Hayden,
Eugene R Bleecker,
F Estelle R Simons,
Stanley J Szefler,
Scott T Weiss,
Tmirah Haselkorn
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ABSTRACT: Patients with severe or difficult-to-treat asthma account for substantial asthma morbidity, mortality, and healthcare burden despite comprising only a small proportion of the total asthma population. TENOR, a multicenter, observational, prospective cohort study was initiated in 2001. It enrolled 4,756 adults, adolescents and children with severe or difficult-to-treat asthma who were followed semi-annually and annually for three years, enabling insight to be gained into this understudied population. A broad range of demographic, clinical, and patient self-reported assessments were completed during the follow-up period. Here, we present key findings from the TENOR registry in relation to asthma control and exacerbations, including the identification of specific subgroups found to be at particularly high-risk. Identification of the factors and subgroups associated with poor asthma control and increased risk of exacerbations can help physicians design individual asthma management, and improve asthma-related health outcomes for these patients.
Current respiratory care reports. 12/2012; 1(4):259-269.
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ABSTRACT: The use of inhaled glucocorticoids for persistent asthma causes a temporary reduction in growth velocity in prepubertal children. The resulting decrease in attained height 1 to 4 years after the initiation of inhaled glucocorticoids is thought not to decrease attained adult height.
We measured adult height in 943 of 1041 participants (90.6%) in the Childhood Asthma Management Program; adult height was determined at a mean (±SD) age of 24.9±2.7 years. Starting at the age of 5 to 13 years, the participants had been randomly assigned to receive 400 μg of budesonide, 16 mg of nedocromil, or placebo daily for 4 to 6 years. We calculated differences in adult height for each active treatment group, as compared with placebo, using multiple linear regression with adjustment for demographic characteristics, asthma features, and height at trial entry.
Mean adult height was 1.2 cm lower (95% confidence interval [CI], -1.9 to -0.5) in the budesonide group than in the placebo group (P=0.001) and was 0.2 cm lower (95% CI, -0.9 to 0.5) in the nedocromil group than in the placebo group (P=0.61). A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height (-0.1 cm for each microgram per kilogram of body weight) (P=0.007). The reduction in adult height in the budesonide group as compared with the placebo group was similar to that seen after 2 years of treatment (-1.3 cm; 95% CI, -1.7 to -0.9). During the first 2 years, decreased growth velocity in the budesonide group occurred primarily in prepubertal participants.
The initial decrease in attained height associated with the use of inhaled glucocorticoids in prepubertal children persisted as a reduction in adult height, although the decrease was not progressive or cumulative. (Funded by the National Heart, Lung, and Blood Institute and the National Center for Research Resources; CAMP ClinicalTrials.gov number, NCT00000575.).
New England Journal of Medicine 09/2012; 367(10):904-12. · 53.30 Impact Factor
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ABSTRACT: Environmental control education is recommended for allergic patients with persistent asthma, but patients may not be willing to comply with recommendations. In a prior study from our group, only 24% of patients reported making any recommended environmental changes.
To determine what environmental changes allergic asthmatic patients say they would be willing to make and what changes they actually make.
Asthmatic patients with known perennial aeroallergen sensitization were asked by telephone to rate on a 1- to 5-point Likert scale their willingness to make specific environmental changes. Items with mean scores of 3 or higher were used to formulate a practical set of recommendations to be given to patients in stage 2 of the study. Stage 2 patients were given the advice formulated in stage 1 and then telephoned 2 months later to see what changes they actually made.
Stage 1 patients (n = 60) were willing to institute 14 of the 18 proposed allergen-specific recommendations. Of 36 stage 2 patients who were allergic to mite, mold, and/or dander, 29 (80.6%) reported that they complied with at least 1 of the recommendations made in this study. Patients who owned their own home were significantly (P < .05) more likely (91.3%) to make at least 1 change than patients who rented their home (63.6%).
Pending additional information, we suggest that environmental control recommendations for mite, mold, and dander emphasize those used in this study because they appear to be practical for a substantial proportion of patients, especially if they own their home.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 08/2012; 109(2):99-102. · 2.83 Impact Factor
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Blanca E Himes,
Xiaofeng Jiang,
Ruoxi Hu,
Ann C Wu,
Jessica A Lasky-Su,
Barbara J Klanderman,
John Ziniti,
Jody Senter-Sylvia,
John J Lima,
Charles G Irvin, [......],
Maartje A E Nieuwenhuis,
Judith M Vonk,
Reynold A Panettieri,
Amy Markezich,
Elliot Israel,
Vincent J Carey,
Kelan G Tantisira,
Augusto A Litonjua,
Quan Lu,
Scott T Weiss
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ABSTRACT: Bronchodilator response (BDR) is an important asthma phenotype that measures reversibility of airway obstruction by comparing lung function (i.e. FEV(1)) before and after the administration of a short-acting β(2)-agonist, the most common rescue medications used for the treatment of asthma. BDR also serves as a test of β(2)-agonist efficacy. BDR is a complex trait that is partly under genetic control. A genome-wide association study (GWAS) of BDR, quantified as percent change in baseline FEV(1) after administration of a β(2)-agonist, was performed with 1,644 non-Hispanic white asthmatic subjects from six drug clinical trials: CAMP, LOCCS, LODO, a medication trial conducted by Sepracor, CARE, and ACRN. Data for 469,884 single-nucleotide polymorphisms (SNPs) were used to measure the association of SNPs with BDR using a linear regression model, while adjusting for age, sex, and height. Replication of primary P-values was attempted in 501 white subjects from SARP and 550 white subjects from DAG. Experimental evidence supporting the top gene was obtained via siRNA knockdown and Western blotting analyses. The lowest overall combined P-value was 9.7E-07 for SNP rs295137, near the SPATS2L gene. Among subjects in the primary analysis, those with rs295137 TT genotype had a median BDR of 16.0 (IQR = [6.2, 32.4]), while those with CC or TC genotypes had a median BDR of 10.9 (IQR = [5.0, 22.2]). SPATS2L mRNA knockdown resulted in increased β(2)-adrenergic receptor levels. Our results suggest that SPATS2L may be an important regulator of β(2)-adrenergic receptor down-regulation and that there is promise in gaining a better understanding of the biological mechanisms of differential response to β(2)-agonists through GWAS.
PLoS Genetics 07/2012; 8(7):e1002824. · 8.69 Impact Factor
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Bradley E Chipps, Robert S Zeiger,
Larry Borish,
Sally E Wenzel,
Ashley Yegin,
Mary Lou Hayden,
Dave P Miller,
Eugene R Bleecker,
F Estelle R Simons,
Stanley J Szefler,
Scott T Weiss,
Tmirah Haselkorn
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ABSTRACT: Patients with severe or difficult-to-treat asthma are an understudied population but account for considerable asthma morbidity, mortality, and costs. The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study was a large, 3-year, multicenter, observational cohort study of 4756 patients (n=3489 adults ≥ 18 years of age, n=497 adolescents 13-17 years of age, and n=770 children 6-12 years of age) with severe or difficult-to-treat asthma. TENOR's primary objective was to characterize the natural history of disease in this cohort. Data assessed semiannually and annually included demographics, medical history, comorbidities, asthma control, asthma-related health care use, medication use, lung function, IgE levels, self-reported asthma triggers, and asthma-related quality of life. We highlight the key findings and clinical implications from more than 25 peer-reviewed TENOR publications. Regardless of age, patients with severe or difficult-to-treat asthma demonstrated high rates of health care use and substantial asthma burden despite receiving multiple long-term controller medications. Recent exacerbation history was the strongest predictor of future asthma exacerbations. Uncontrolled asthma, as defined by the 2007 National Heart, Lung, and Blood Institute guidelines' impairment domain, was highly prevalent and predictive of future asthma exacerbations; this assessment can be used to identify high-risk patients. IgE and allergen sensitization played a role in the majority of severe or difficult-to-treat asthmatic patients.
The Journal of allergy and clinical immunology 06/2012; 130(2):332-42.e10. · 9.17 Impact Factor
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ABSTRACT: BackgroundThe Asthma Impact Survey (AIS-6) is a new six question asthma outcome tool for which information on validity has not been
published.
ObjectiveTo provide validation for the AIS-6 as a brief asthma-specific quality of life tool.
MethodsSurveys were sent to a random sample of members of a large managed care organization who were at least 35years of age and
in the two-year period preceding the survey had either (1) at least one documented asthma-related medical encounter, or (2)
at least a 6months supply of asthma medication dispensed. In addition to the AIS-6, the survey included a validated quality
of life tool [the mini-Asthma Quality of Life Questionnaire (AQLQ)]; a validated asthma control questionnaire [the Asthma
Therapy Assessment QuestionnaireTM (ATAQ)]; a validated symptom severity scale (AOMS); and information regarding demographics, co-morbidities, asthma severity,
and asthma management. The results of the AIS-6 were compared to the results of the other tools by means of correlation and
factor analysis. Independent predictors of AIS-6 and AQLQ scores were determined by multiple stepwise linear regression analyses.
ResultsAIS-6 scores were significantly related to female sex, educational level, income, smoking, body mass index (BMI), COPD, steroid
use, and hospitalization history in bivariate analyses. The AIS-6 score significantly correlated (r= − 0.84, p < 0.0001) with the AQLQ total score and loaded on the three factors (activity, symptoms, and concern/bother) reflected by
the survey information and on which the AQLQ also loaded. Significant but somewhat smaller correlations were found between
the AIS-6 and the ATAQ (r=0.70, p < 0.0001) and the AOMS (r=0.55, p < 0.0001). Independent predictors were the same for the AIS-6 and AQLQ and included oral steroid use, COPD history, BMI,
female sex, educational level, and hospitalization in the past year.
ConclusionThese data support the validity of the short six-question AIS-6 as an asthma-specific quality of life tool.
Quality of Life Research 04/2012; 16(2):345-355. · 2.30 Impact Factor
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ABSTRACT: Inherent asthma severity is difficult to assess clinically. The purpose of this study was to develop an Asthma Intensity Manifestations Score (AIMS) as a surrogate for asthma severity.
Three hundred and four patients treated with inhaled corticosteroids completed the Asthma Control Test (ACT), underwent spirometry, and fractional exhaled nitric oxide (FENO) testing, and reported their current medications. These parameters (defined as ACT < 16, forced expiratory volume in 1 second [FEV(1)] < 80% predicted, FENO > 50 ppb, and Expert Panel Report [EPR3] step care level >3) were related to prior year outcomes to develop the AIMS and to follow-up year outcomes to validate it.
FENO was independently related to prior year short-acting beta agonist (SABA) ≥ 7 (odds ratio [OR] 2.9); ACT (OR 4.9), FEV(1) (OR 3.3), and step care (OR 3.9) were independently related to prior year systemic corticosteroid (SCS) ≥ 2. Thus, all the four items were chosen for the AIMS (0-4 points). AIMSs were linearly related to follow-up year SABA ≥ 7, any SCS, SCS ≥ 2, and emergency hospital care (all p < .01). Compared to patients with AIMSs <2, patients with AIMSs ≥2 were at more than a fourfold greater risk of requiring ≥2 SCS in the following year and were at a 2-2.8-fold greater risk of experiencing other adverse outcomes during that time period.
The AIMS is linearly related to future year adverse asthma outcomes. Further studies will be necessary to confirm its utility as a surrogate for asthma severity in clinical practice and clinical research.
Journal of Asthma 03/2012; 49(2):172-7. · 1.52 Impact Factor
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ABSTRACT: The relationships between validated quality of life tools and control tools have not been explored for rhinitis. This study was designed to determine relationships of the Mini-Rhinitis Quality of Life Questionnaire (MiniRQLQ) and the Rhinitis Control Assessment Test (RCAT) to each other regarding content and predictive abilities.
Participants were adult members of a large integrated care organization with an encounter diagnosis of rhinitis in the prior 2 years. Patients completed mailed questionnaires at baseline that contained the MiniRQLQ and the RCAT and three follow-up questionnaires that contained those tools as well as questions regarding missed work or school because of rhinitis and frequency and effectiveness of medications used for rhinitis. Medications dispensed during the follow-up year were obtained from computerized pharmacy records. Results of allergy tests were retrieved for patients seen in the Allergy Department.
The final cohort included 1051 patients. Baseline RCAT scores were strongly correlated with baseline MiniRQLQ scores in both allergic (r = -0.80) and nonallergic (r = -0.84) patients. Baseline MiniRQLQ and RCAT scores were significantly related to patient reports of missed school/work, medication use, and effectiveness over the next 3 months and to dispensing during the following year of total and some individual rhinitis medications. Test-retest reliability, responsiveness, and a preliminary minimal important difference (>2.5) were shown for the RCAT, using the MiniRQLQ as an anchor.
The MiniRQLQ and RCAT are strongly related to each other and both predict subsequent rhinitis outcomes. Determining the comparative usefulness of these tools will require further study.
American Journal of Rhinology and Allergy 03/2012; 26(2):127-33.
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ABSTRACT: Accurate assessment of asthma control may help predict future asthma exacerbations.
To evaluate asthma guidelines impairment domain components as predictors of exacerbations in severe/difficult-to-treat asthma.
Children (aged 6-11 years; n = 289) and adolescents/adults (aged ≥ 12 years; n = 2,094) with complete baseline and 12-month data from The Epidemiology and Natural History of Asthma Outcomes and Treatment Regimens study were included. Asthma was categorized as very poorly controlled, not well-controlled, and well-controlled using impairment domain components. Effects of omitting each component on very poorly controlled and not well controlled groups were examined. Multivariable logistic regression determined the relationship of components in predicting asthma exacerbations.
Omission of individual impairment domain components led to misclassification of asthma control in 11% to 39% of patients. A baseline exacerbation was the strongest independent predictor of exacerbation at month 12 in children (odds ratio = 2.94; P < .001) and adolescents/adults (odds ratio = 2.93; P < .001). In children, very poorly controlled asthma-based short-acting β2-agonist use was associated with a 2-fold higher exacerbation risk (odds ratio = 2.03; P = .011). In adolescents/adults, not well controlled or very poorly controlled asthma based on short-acting β2-agonist use (odds ratio = 1.49), lung function (odds ratio = 1.66), and the Asthma Therapy Assessment Questionnaire (odds ratio = 1.94) were also independent predictors of exacerbations (P < .001).
Although the combined use of individual components of the impairment domain increases the sensitivity of identifying patients at high risk for future asthma exacerbations, specific components may be more important than others in severe/difficult-to-treat asthma. Prior exacerbations, short-acting β2-agonist use, lung function, and (in adolescents/adults) the Asthma Therapy Assessment Questionnaire were independent predictors of exacerbations.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 02/2012; 108(2):81-7. · 2.83 Impact Factor
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Robert S Zeiger,
David Mauger,
Leonard B Bacharier,
Theresa W Guilbert,
Fernando D Martinez,
Robert F Lemanske,
Robert C Strunk,
Ronina Covar,
Stanley J Szefler,
Susan Boehmer, [......],
Noah J Friedman,
Michael H Mellon,
Michael Schatz,
Wayne J Morgan,
Vernon M Chinchilli,
Hengameh H Raissy,
Elizabeth Bade,
Jonathan Malka-Rais,
Avraham Beigelman,
Lynn M Taussig
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ABSTRACT: Daily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations, as indicated by a positive value on the modified asthma predictive index (API) and an exacerbation in the preceding year, but concern remains about daily adherence and effects on growth. We compared daily therapy with intermittent therapy.
We studied 278 children between the ages of 12 and 53 months who had positive values on the modified API, recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment. Children were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during a predefined respiratory tract illness) or a daily low-dose regimen (0.5 mg nightly) with corresponding placebos. The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy.
The daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations, with a rate per patient-year for the daily regimen of 0.97 (95% confidence interval [CI], 0.76 to 1.22) versus a rate of 0.95 (95% CI, 0.75 to 1.20) for the intermittent regimen (relative rate in the intermittent-regimen group, 0.99; 95% CI, 0.71 to 1.35; P=0.60). There were also no significant between-group differences in several other measures of asthma severity, including the time to the first exacerbation, or adverse events. The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen.
A daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations. Daily administration led to greater exposure to the drug at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; MIST ClinicalTrials.gov number, NCT00675584.).
New England Journal of Medicine 11/2011; 365(21):1990-2001. · 53.30 Impact Factor
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ABSTRACT: Information comparing subjective and objective measurements of adherence to study medications and the effects of adherence on treatment-related differences in asthma clinical trials are limited.
We sought to compare subjective and objective measurements of children's adherence to inhaled corticosteroids or placebo and to determine whether adherence to study medications modified treatment-related differences in outcomes.
In an ancillary study conducted in 3 of 8 Childhood Asthma Management Program Clinical Centers, adherence was assessed by using self-reported and objective data in 5- to 12-year-old children with mild or moderate asthma who were randomly assigned to 200 μg of inhaled budesonide twice per day (n = 84) or placebo (n = 56) for 4 years. The κ statistic was used to evaluate agreement between self-reported adherence (daily diary cards) and objectively measured adherence (number of doses left in study inhalers). Multivariable analyses were used to determine whether adherence to study treatment modified treatment-related differences in outcomes.
Adherence of less than 80% was seen in 75% of 140 children when adherence was measured objectively but only in 6% of children when measured by means of self-report. There was poor agreement between objective and subjective measurements of adherence of at least 80% (κ = 0.00; 95% CI, -0.05 to 0.04); self-reported adherence over the 4-year period generally overestimated objectively measured adherence (93.6% vs 60.8%, P < .0001). There was little evidence to indicate that adherence modified treatment-related differences in outcomes.
Researchers should use objective rather than self-reported adherence data to identify clinical trial participants with low levels of adherence to study treatment.
The Journal of allergy and clinical immunology 11/2011; 129(1):112-8. · 9.17 Impact Factor
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ABSTRACT: The Test for Respiratory and Asthma Control in Kids (TRACK) is the first validated questionnaire to assess respiratory and asthma control exclusively in young children.
We sought to determine the minimally important difference (MID) for interpreting meaningful changes in individual patients' TRACK scores.
In this prospective, nonrandomized, longitudinal study conducted at 20 US pediatric sites, TRACK was administered at 2 separate clinic visits (4-6 weeks apart) to caregivers of children aged less than 5 years with symptoms consistent with asthma. Anchor-based methods were used to determine the MID from mean score differences between patients based on multiple criteria measures: physician guidelines-based respiratory control rating, physician-recommended changes to therapy, episodes of symptoms lasting more than 24 hours in the past 3 months, oral corticosteroid use for respiratory tract illnesses in the past year, physician-assessed change in control status at follow-up, and caregiver-reported change in respiratory status. The MID also was determined from distribution-based methods.
TRACK scores were assessed at baseline (426 caregivers) and follow-up (396 caregivers). Mean differences in TRACK scores between patients differing on criteria measures ranged from 3.4 to 16.4 points (mean, 11.1 points). Distribution-based techniques confirmed these findings. Based on logistic regression analyses, scoring 10 or more points less than 80 on TRACK was associated with an approximately 2-fold increased odds of having uncontrolled asthma or respiratory symptoms.
Changes in TRACK scores of 10 or more points represent clinically meaningful changes in respiratory control status in individual young children with respiratory symptoms consistent with asthma and should alert health care providers to re-evaluate asthma management.
The Journal of allergy and clinical immunology 09/2011; 128(5):983-8. · 9.17 Impact Factor
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ABSTRACT: Impairment and risk are considered separate domains of asthma control, but relationships between them are not completely understood. We compared three validated questionnaires reflecting asthma impairment in their ability to predict future exacerbations.
Two thousand six hundred eighty patients with persistent asthma completed a survey that included the Asthma Control Test (ACT), mini-Asthma Quality of Life Questionnaire (mAQLQ), and Asthma Impact Survey (AIS-6), as well as a history of exacerbations in the prior 12 months. An exploratory factor analysis was performed using the questions of the three tools, and individual patient factor scores were calculated. Independent relationships between predictors (tools and factors) and exacerbations the following year captured from administrative data were evaluated.
Each tool was significantly related (P < .0001) to future exacerbations above and beyond the risk conferred by prior exacerbations (relative risk [RR] = 1.3). When prior exacerbations were included in the model, the three impairment tools provided similar and overlapping information, such that only the mAQLQ entered the model (RR = 1.3; 95% CI, 1.1-1.5). Factor analysis revealed three factors (symptoms, activity, and bother) that were each significantly associated (P < .0001) with future asthma exacerbations. However, only the activity factor was independently related to future exacerbations.
Asthma impairment is significantly related to the risk of future exacerbations, but the ACT, mAQLQ, and AIS-6 do not provide independent information from each other in this regard. Interference with activities is the primary subjective component of asthma impairment that is related to the risk of future exacerbations.
Chest 08/2011; 141(1):66-72. · 5.25 Impact Factor
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ABSTRACT: Although nocturnal awakenings help categorize asthma severity and control, their clinical significance has not been thoroughly studied.
We sought to determine the clinical consequences of nocturnal asthma symptoms requiring albuterol (NASRAs) in children with mild-to-moderate persistent asthma outside of periods when oral corticosteroids were used for worsening asthma symptoms.
Two hundred eighty-five children aged 6 to 14 years with mild-to-moderate persistent asthma were randomized to receive one of 3 controller regimens and completed daily symptom diaries for 48 weeks. Diary responses were analyzed for the frequency and consequences of NASRAs.
NASRAs occurred in 72.2% of participants at least once, and in 24.3% of participants, they occurred 13 or more times. The majority (81.3%) of nocturnal symptoms occurred outside of exacerbation periods and were associated the next day with the following events: albuterol use (56.9% of days preceded by nocturnal symptoms vs 18.1% of days not preceded by nocturnal symptoms; relative risk [RR], 2.3; 95% CI, 2.2-2.4), school absence (5.0% vs 0.3%; RR, 10.6; 95% CI, 7.8-14.4), and doctor contact (3.7% vs 0.2%; RR, 8.8; 95% CI, 6.1-12.5). Similar findings were noted during exacerbation periods (RRs of 1.7 for albuterol use, 5.5 for school absence, and 4.9 for doctor contacts). Nocturnal symptoms did not predict the onset of exacerbations.
Nocturnal symptoms requiring albuterol in children with mild-to-moderate persistent asthma receiving controller therapy occurred predominantly outside of exacerbation periods. Despite being poor predictors of exacerbations, they were associated with increases in albuterol use, school absences, and doctor contacts the day after nocturnal symptom occurrences.
The Journal of allergy and clinical immunology 08/2011; 128(5):977-82.e1-2. · 9.17 Impact Factor
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Theresa W Guilbert,
David T Mauger,
David B Allen, Robert S Zeiger,
Robert F Lemanske,
Stanley J Szefler,
Robert C Strunk,
Leonard B Bacharier,
Ronina Covar,
Christine A Sorkness,
Lynn M Taussig,
Fernando D Martinez
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ABSTRACT: The effect on linear growth of daily long-term inhaled corticosteroid therapy in preschool-aged children with recurrent wheezing is controversial.
We sought to determine the effect of daily inhaled corticosteroid given for 2 years on linear growth in preschool children with recurrent wheezing.
Children aged 2 and 3 years with recurrent wheezing and positive modified Asthma Predictive Index scores were randomized to a 2-year treatment period of chlorofluorocarbon-delivered fluticasone propionate (176 μg/d) or masked placebo delivered through a valved chamber with a mask and then followed for 2 years off study medication. Height growth determined by means of stadiometry was compared between treatment groups.
In the study cohort as a whole, the fluticasone group did not have significantly less linear growth than the placebo group (change in height from baseline difference, -0.2 cm; 95% CI, -1.1 to 0.6) 2 years after discontinuation of study treatment. In post hoc analyses children 2 years old who weighed less than 15 kg at enrollment and were treated with fluticasone had less linear growth compared with those treated with placebo (change in height from baseline difference, -1.6 cm; 95% CI, -2.8 to -0.4; P = .009).
Linear growth was not significantly different in high-risk preschool-aged children with recurrent wheezing treated with 176 μg/d chlorofluorocarbon-delivered fluticasone compared with placebo 2 years after fluticasone is discontinued. However, post hoc subgroup analyses revealed that children who are younger in age and of lesser weight relative to the entire study cohort had significantly less linear growth, possibly because of a higher relative fluticasone exposure.
The Journal of allergy and clinical immunology 08/2011; 128(5):956-63.e1-7. · 9.17 Impact Factor
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The Journal of allergy and clinical immunology 08/2011; 128(2):412-4. · 9.17 Impact Factor
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ABSTRACT: The cost associated with asthma impairment in children with severe asthma has not been determined.
To assess the asthma cost burden in children with severe or difficult-to-treat asthma based on asthma impairment.
Children aged 6 to 12 years in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study with available data at baseline (n = 628), month 12 (n = 385), and month 24 (n = 280) corresponding to the National Heart, Lung, and Blood Institute asthma guidelines' impairment domain were included. Children were categorized as either very poorly controlled (VPC), not well controlled (NWC), or well controlled (WC) and assessed cross-sectionally and longitudinally. Mean total asthma costs based on direct (medication usage, unscheduled office visits, emergency department visits, hospitalizations) and indirect (school/work days lost) asthma costs were assessed.
Mean annual total asthma costs were more than twice as high in the VPC group compared with NWC and WC groups (baseline: $7,846, $3,526, $3,766.44, respectively; month 12: $7,326, $2,959, $2,043, respectively; month 24: $8,879, $3,308, $1,861, respectively (all P < .001). Indirect costs accounted for approximately half the total asthma costs for VPC asthma patients at each time point. Significantly lower costs were observed for patients whose impairment status improved or temporarily improved from VPC after baseline.
The economic burden of severe or difficult-to-treat asthma in children is associated with VPC asthma and improvement in asthma control and is associated with reducing cost. Further attention to patients with poorly controlled asthma, through better management strategies or more effective medications, may significantly reduce this burden of illness.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 08/2011; 107(2):110-119.e1. · 2.83 Impact Factor
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ABSTRACT: This article summarizes our experience using administrative, survey, and telephone information to define asthma severity, impairment, risk, and quality of care in our large Kaiser Permanente population. Our data suggest that the 2-year Healthcare Effectiveness Data and Information Set definition of persistent asthma is a good surrogate for survey-defined persistent asthma, and thus it would be reasonable to direct asthma population management and quality-of-care assessments at patients with Healthcare Effectiveness Data and Information Set-defined persistent asthma for 2 years in a row. For population management, the numbers of short-acting β-agonist (SABA) canisters dispensed and validated tools on mail or telephone surveys have been used to assess asthma impairment. Algorithms based on pharmacy data (SABA canister and oral corticosteroid dispensings and prior emergency hospital care) have been used to assess the risk domain of asthma control. The asthma medication ratio (controllers divided by controllers plus SABAs) has been shown to be related to improved outcomes and is recommended as an asthma quality-of-care marker. It is hoped that outreach to patients and providers based on these indicators will improve asthma outcomes in patients cared for in individual practices, as well as in large health plans.
The Journal of allergy and clinical immunology 04/2011; 128(2):273-7. · 9.17 Impact Factor
