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Joanne K Fagan

Publications and source records attributed to Joanne K Fagan.

10 recordsLinked to original sources
PubMed2006

Validating an asthma case detection instrument in a Head Start sample.

Although specific tests screen children in preschool programs for vision, hearing, and dental conditions, there are no published validated instruments to detect preschool-age children with asthma, one of the most common pediatric chronic conditions affecting children in economically disadvantaged communities of color. As part of an asthma education intervention, a 15-item Brief Respiratory Questionnaire (BRQ) was developed to detect children with probable asthma in Head Start and subsidized preschool settings in communities with high asthma prevalence and associated morbidity. Preschool personnel administered the BRQ to consenting parents of 419 enrolled children. Trained interviewers administered validation interviews (VALs) to parents of 149 case-positive children and 51 case-negative children. Three physicians independently assessed deidentified summaries of the VALs that captured responses about signs and symptoms of asthma, diagnosis and treatment, and use of medical services. The physicians' assessments of the summarized VALs were the validated standard to which the BRQ classifications were compared. A simple algorithm of 4 items was identified that can be administered and scored by nonmedical preschool personnel in less than 5 minutes. The chance-corrected agreement between these 4 items of the BRQ and the VAL was good: kappa, .73 (95% confidence interval, 0.62-0.84); specificity, 96%; sensitivity, 73%; and positive predictive value, 97%. The BRQ appears to be a valid instrument for detecting children with probable asthma in Head Start and other subsidized preschool settings in communities with high prevalence of asthma.

Allergens↗
PubMed2005

CD14 tobacco gene-environment interaction modifies asthma severity and immunoglobulin E levels in Latinos with asthma.

BACKGROUND: A recent family-based genomewide screen revealed linkage between the 5q31 region and the diagnosis of asthma, but only in those exposed to environmental tobacco smoke (ETS). Among the candidate genes in this region is CD14. METHODS: To determine whether polymorphisms in the CD14 gene are related to this gene-by-environment interaction in Latinos, we used both family-based and cross-sectional cohort analysis to test for interactions between CD14 genotypes/haplotypes, exposure to ETS, and asthma-related phenotypes in 659 Mexican and Puerto Rican families. RESULTS: We identified 21 single nucleotide polymorphisms (SNPs) in the CD14 gene by sequencing 72 Puerto Ricans, Mexicans, and African Americans with asthma. Three SNPs, -810, -159, and +1437, were further genotyped in families with asthma. Among all subjects with asthma exposed to ETS, without regard to ethnicity, CD14 +1437 genotypes were associated with asthma severity. SNP +1437 GG or GC genotypes were significantly associated with lower baseline FEV1 using both family-based (p = 0.0009) and cross-sectional cohort (p = 0.03) analyses. Subjects with asthma with the GG or GC genotypes who were exposed to ETS had mean baseline FEV1 (% predicted) values 8.6% lower than subjects not exposed to ETS (p = 0.03). As previously observed in whites, we found an interaction between plasma IgE levels, SNP -159 genotypes, and ETS exposure (p = 0.0002). The lowest IgE levels were in those subjects with the TT genotype and who were exposed to ETS regardless of ethnicity. CONCLUSIONS: Our data suggest a gene-by-environment interaction between CD14 genotypes and ETS, which affects pulmonary function and IgE levels among Latinos with asthma.

Adolescent↗
PubMed2005

Daily versus as-needed corticosteroids for mild persistent asthma.

BACKGROUND: Although guidelines recommend daily therapy for patients with mild persistent asthma, prescription patterns suggest that most such patients use these so-called controller therapies intermittently. In patients with mild persistent asthma, we evaluated the efficacy of intermittent short-course corticosteroid treatment guided by a symptom-based action plan alone or in addition to daily treatment with either inhaled budesonide or oral zafirlukast over a one-year period. METHODS: In a double-blind trial, 225 adults underwent randomization. The primary outcome was morning peak expiratory flow (PEF). Other outcomes included the forced expiratory volume in one second (FEV1) before and after bronchodilator treatment, the frequency of exacerbations, the degree of asthma control, the number of symptom-free days, and the quality of life. RESULTS: The three treatments produced similar increases in morning PEF (7.1 to 8.3 percent; approximately 32 liters per minute; P=0.90) and similar rates of asthma exacerbations (P=0.24), even though the intermittent-treatment group took budesonide, on average, for only 0.5 week of the year. As compared with intermittent therapy or daily zafirlukast therapy, daily budesonide therapy produced greater improvements in pre-bronchodilator FEV1 (P=0.005), bronchial reactivity (P<0.001), the percentage of eosinophils in sputum (P=0.007), exhaled nitric oxide levels (P=0.006), scores for asthma control (P<0.001), and the number of symptom-free days (P=0.03), but not in post-bronchodilator FEV1 (P=0.29) or in the quality of life (P=0.18). Daily zafirlukast therapy did not differ significantly from intermittent treatment in any outcome measured. CONCLUSIONS: It may be possible to treat mild persistent asthma with short, intermittent courses of inhaled or oral corticosteroids taken when symptoms worsen. Further studies are required to determine whether this novel approach to treatment should be recommended.

Administration, Inhalation↗
PubMed2004

Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma.

BACKGROUND: In the United States, Puerto Ricans and Mexicans have the highest and lowest asthma prevalence, morbidity, and mortality, respectively. Ethnic-specific differences in the response to drug treatment may contribute to differences in disease outcomes. Genetic variants at the beta(2)-adrenergic receptor (beta(2)AR) may modify asthma severity and albuterol responsiveness. We tested the association of beta(2)AR genotypes with asthma severity and bronchodilator response to albuterol in Puerto Ricans and Mexicans with asthma. METHODS: We used both family-based and cross-sectional tests of association with 8 beta(2)AR single nucleotide polymorphisms in 684 Puerto Rican and Mexican families. Regression analyses were used to determine the interaction between genotype, asthma severity, and bronchodilator drug responsiveness. RESULTS: Among Puerto Ricans with asthma, the arginine (Arg) 16 allele was associated with greater bronchodilator response using both family-based and cross-sectional tests (p = 0.00001-0.01). We found a strong interaction of baseline FEV(1) with the Arg16Glycine (Gly) polymorphism in predicting bronchodilator response. Among Puerto Ricans with asthma with baseline FEV(1) < 80% of predicted, but not in those with FEV(1) > 80%, there was a very strong association between the Arg16 genotype and greater bronchodilator responsiveness. No association was observed between Arg16Gly genotypes and drug responsiveness among Mexicans with asthma. CONCLUSIONS: Ethnic-specific pharmacogenetic differences exist between Arg16Gly genotypes, asthma severity, and bronchodilator response in Puerto Ricans and Mexicans with asthma. These findings underscore the need for additional research on racial/ethnic differences in asthma morbidity and drug responsiveness.

Adolescent↗
PubMed2003

Lower bronchodilator responsiveness in Puerto Rican than in Mexican subjects with asthma.

In the United States, Puerto Ricans and Mexicans have the highest and lowest asthma prevalence, morbidity, and mortality, respectively. To determine whether ethnicity-specific differences in therapeutic response, clinical response, and/or genetic factors contribute to differences in asthma outcomes, we compared asthma-related clinical characteristics among 684 Mexican and Puerto Rican individuals with asthma recruited from San Francisco, New York City, Puerto Rico, and Mexico City. Puerto Ricans with asthma had reduced lung function, greater morbidity, and longer asthma duration than did Mexicans with asthma. Bronchodilator responsiveness, measured as percentage change from baseline FEV1, was significantly lower among Puerto Ricans with asthma than among Mexicans with asthma. Puerto Ricans with asthma had on average 7.3% (95% confidence interval [CI], 4.6 to 9.9; p < 0.001) lower bronchodilator reversibility in FEV1, higher risk of an emergency department visit in the previous year (odds ratio, 2.63; 95% CI, 1.6 to 4.3; p < 0.001), and of previous hospitalization for asthma (odds ratio, 1.94; 95% CI, 1.2 to 3.2; p = 0.009) than Mexicans. Subgroup analysis corroborated that Puerto Ricans with asthma had more severe disease than did Mexicans on the basis of lung function measurements, responsiveness to beta2-adrenergic agonists, and health care use. We conclude that Puerto Ricans with asthma respond less to albuterol than do Mexicans with asthma. These findings underscore the need for additional research on racial/ethnic differences in asthma morbidity and response to therapy.

Asthma↗
PubMed2002

Systemic effect comparisons of six inhaled corticosteroid preparations.

The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects (microgram dose producing equal systemic cortisol suppression) of inhaled corticosteroids (ICS). Steroid naive asthma subjects (n = 156) were enrolled at six centers. A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses. Systemic effect was evaluated by hourly plasma cortisol concentrations (8 P.M. to 8 A.M.), 12- and 24-hour urine cortisol concentrations, and a morning blood osteocalcin. The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect. For the six ICS and matching placebos (beclomethasone-chlorofluorocarbon [CFC], budesonide dry powder inhaler [DPI], fluticasone DPI, fluticasone-CFC metered dose inhaler [MDI], flunisolide-CFC, and triamcinolone-CFC), only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect. Thus microgram comparison of all ICS could only be performed at a 10% cortisol suppression: flunisolide-CFC - 936; triamcinolone-CFC - 787; beclomethasone-CFC - 548; fluticasone DPI - 445; budesonide DPI - 268; fluticasone-CFC MDI - 111. This study represents the first step in evaluation of ICS efficacy based on equisystemic (cortisol suppression) effects of a given ICS, rather than doses judged arbitrarily to be comparable on a microgram basis.

Administration, Inhalation↗
PubMed2002

Significant variability in response to inhaled corticosteroids for persistent asthma.

BACKGROUND: A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy. OBJECTIVE: The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs. METHODS: A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day. RESULTS: Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years). CONCLUSIONS: Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.

Administration, Inhalation↗
PubMedDate not supplied

Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial.

BACKGROUND: The issue of whether regular use of an inhaled beta2-adrenergic agonist worsens airflow and clinical outcomes in asthma is controversial. Retrospective studies have suggested that adverse effects occur in patients with a genetic polymorphism that results in homozygosity for arginine (Arg/Arg), rather than glycine (Gly/Gly), at aminoacid residue 16 of the beta2-adrenergic receptor. However, the existence of any genotype-dependent difference has not been tested in a prospective clinical trial. METHODS: Patients with mild asthma, not using a controller medication, were enrolled in pairs matched for forced expiratory volume in 1 s (FEV1) according to whether they had the Arg/Arg (n=37; four of 41 matches withdrew before randomisation) or Gly/Gly (n=41) genotype. Regularly scheduled treatment with albuterol or placebo was given in a masked, cross-over design, for 16-week periods. During the study, as-needed albuterol use was discontinued and ipratropium bromide was used as needed. Morning peak expiratory flow rate (PEFR) was the primary outcome variable. The primary comparisons were between treatment period for each genotype; the secondary outcome was a treatment by genotype effect. Analyses were by intention to treat. FINDINGS: During the run-in period, when albuterol use was kept to a minimum, patients with the Arg/Arg genotype had an increase in morning PEFR of 23 L/min (p=0.0162); the change in patients with the Gly/Gly genotype was not significant (2 L/min; p=0.8399). During randomised treatment, patients with the Gly/Gly genotype had an increase in morning PEFR during treatment with regularly scheduled albuterol compared with placebo (14 L/min [95% CI 3 to 25]; p=0.0175). By contrast, patients with the Arg/Arg genotype had lower morning PEFR during treatment with albuterol than during the placebo period, when albuterol use was limited (-10 L/min [-19 to -2]; p=0.0209). The genotype-attributable treatment difference was therefore -24 L/min (-37 to -12; p=0.0003). There were similar genotype-specific effects in FEV1, symptoms, and use of supplementary reliever medication. INTERPRETATION: Genotype at the 16th aminoacid residue of the beta2-adrenergic receptor affects the long-term response to albuterol use. Bronchodilator treatments avoiding albuterol may be appropriate for patients with the Arg/Arg genotype.

Administration, Inhalation↗
PubMedDate not supplied

Oral beta2-agonist use by preschool children with asthma in East and Central Harlem, New York.

Although studies have documented underuse of controller medications and overuse of short-acting inhaled ss(2)-agonist among children with persistent asthma in disadvantaged communities, the persistence of oral ss(2)-agonist use in pediatric practice has not been studied since inhaled short-acting ss(2)-agonists became widespread. We describe medications used to treat asthma among children 3 to 5 years of age at 10 Head Start and other subsidized preschool centers in East and Central Harlem, New York City. We interviewed 149 parents/guardians of children who were identified as having probable asthma based on physician's diagnosis, persistent symptoms, hospitalization, and medication use. We classified 86 of the 149 children (58%) as having current persistent asthma. Only 15 of them (17%) were reported to have used controller medications at least 5 days/week in the last 4 weeks-only 2 of whom used inhaled corticosteroids. By contrast, 53 children (62%) used oral ss(2)-agonist in the last 4 weeks, often (72%) in conjunction with nebulized or inhaled short-acting ss(2)-agonist. Use of oral ss(2)-agonist was associated with more severe symptoms. This study documents the continued widespread use of oral ss(2)-agonist for treatment of children in a low-income community with high prevalence of asthma.

Administration, Oral↗