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Homer A Boushey

Publications and source records attributed to Homer A Boushey.

18 recordsLinked to original sources
PubMed2005

beta-Adrenergic receptor polymorphisms and response to salmeterol.

RATIONALE: Several studies suggest that patients with asthma who are homozygous for arginine at the 16th position of the beta2-adrenergic receptor may not benefit from short-acting beta-agonists. OBJECTIVES: We investigated whether such genotype-specific effects occur when patients are treated with long-acting beta-agonists and whether such effects are modified by concurrent inhaled corticosteroid (ICS) use. METHODS: We compared salmeterol response in patients with asthma homozygous for arginine at B16 (B16Arg/Arg) with those homozygous for glycine at B16 (B16Gly/Gly) in two separate cohorts. In the first, subjects were randomized to regular therapy with salmeterol while simultaneously discontinuing ICS therapy. In the second, subjects were randomized to regular therapy with salmeterol while continuing concomitant ICS. RESULTS: In both trials, B16Arg/Arg subjects did not benefit compared with B16Gly/Gly subjects after salmeterol was initiated. In the first cohort, compared with placebo, the addition of salmeterol was associated with a 51.4 L/min lower A.M. peak expiratory flow (PEF; p = 0.005) in B16Arg/Arg subjects(salmeterol, n = 12; placebo, n = 5) as compared with B16Gly/Gly subjects (salmeterol, n = 13; placebo, n = 13). In the second cohort, B16Arg/Arg subjects treated with salmeterol and ICS concurrently (n = 8) had a lower A.M. PEF (36.8 L/min difference, p = 0.048) than B16Gly/Gly subjects (n = 22) treated with the same regimen. In addition, B16 Arg/Arg subjects in the second cohort had lower FEV1 (0.42 L, p = 0.003), increased symptom scores (0.2 units, p = 0.034), and increased albuterol rescue use (0.95 puffs/d, p = 0.004) compared with B16Gly/Gly subjects. CONCLUSIONS: Relative to B16Gly/Gly patients with asthma, B16Arg/Arg patients with asthma may have an impaired therapeutic response to salmeterol in either the absence or presence of concurrent ICS use. Investigation of alternate treatment strategies may benefit this group.

Administration, Inhalation↗
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↗
PubMed2005

Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids.

BACKGROUND: Although inhaled corticosteroids (ICSs) are effective in preventing deterioration in asthma control, at least half of subjects with mild-to-moderate asthma will remain stable when these agents are discontinued. OBJECTIVE: We sought to determine whether noninvasive markers of inflammation predict which individuals maintain asthma control after discontinuation of ICSs. METHODS: We analyzed data obtained from 164 subjects with mild-to-moderate asthma who participated in a 16-week trial comparing the effects of continued ICS use with the effects of a switch to salmeterol or placebo. RESULTS: In comparison with continued ICS use, a switch to salmeterol or placebo was associated with increased rates of asthma deterioration over 16 weeks (9.3% vs 24.1% and 37.5%, respectively; P = .04 and P < .001, respectively). We found that neither exhaled nitric oxide nor methacholine PC 20 , when measured at randomization or 2 weeks after randomization, were significant predictors of subsequent asthma control in subjects who discontinued ICSs. However, both induced sputum eosinophil counts measured 2 weeks after a switch from ICS to placebo and changes in sputum eosinophil counts from before cessation of ICSs to after a switch to placebo predicted subsequent asthma deterioration (area under the receiver-operating characteristic curve, 0.771 [ P < .001] and 0.825 [ P < .001], respectively). CONCLUSION: On the basis of a model treatment strategy, we estimate that allocating subjects to ICS therapy on the basis of changes in sputum eosinophil counts after a trial discontinuation could allow 48% of subjects with mild-to-moderate asthma to discontinue ICS therapy without an increased risk of asthma deterioration over a period of at least 14 weeks.

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↗
PubMed2004

Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study.

For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively studied. A 1-year, randomized, stratified, double-blind, parallel-group study of 3,421 patients with uncontrolled asthma compared fluticasone propionate and salmeterol/fluticasone in achieving two rigorous, composite, guideline-based measures of control: totally and well-controlled asthma. Treatment was stepped-up until total control was achieved (or maximum 500 microg corticosteroid twice a day). Significantly more patients in each stratum (previously corticosteroid-free, low- and moderate-dose corticosteroid users) achieved control with salmeterol/fluticasone than fluticasone. Total control was achieved across all strata: 520 (31%) versus 326 (19%) patients after dose escalation (p < 0.001) and 690 (41%) versus 468 (28%) at 1 year for salmeterol/fluticasone and fluticasone, respectively. Asthma became well controlled in 1,071 (63%) versus 846 (50%) after dose escalation (p < 0.001) and 1,204 (71%) versus 988 (59%) at 1 year. Control was achieved more rapidly and at a lower corticosteroid dose with salmeterol/fluticasone versus fluticasone. Across all strata, 68% and 76% of the patients receiving salmeterol/fluticasone and fluticasone, respectively, were on the highest dose at the end of treatment. Exacerbation rates (0.07-0.27 per patient per year) and improvement in health status were significantly better with salmeterol/fluticasone. This study confirms that the goal of guideline-derived asthma control was achieved in a majority of the patients.

Adrenal Cortex Hormones↗
PubMed2003

Effects of individual self-management education on clinical, biological, and adherence outcomes in asthma.

BACKGROUND: Asthma guidelines urge teaching patients the knowledge and skills required for self-management, based on the assumption that education will lead to improved skills and better asthma control. METHODS: In a prospective, randomized controlled trial of 65 adults with mild-to-moderate asthma, we examined whether an educational self-management intervention would improve adherence to inhaled corticosteroid therapy, decrease markers of airway inflammation, and improve clinical control. Peak flow, symptoms, and adherence were monitored for 7 weeks. After a 1-week run-in, subjects were assigned randomly to either the educational intervention or control group. The 30-minute intervention was delivered and reinforced at biweekly intervals. RESULTS: Compared with the control group, the intervention group had improvements in adherence to inhaled corticosteroid therapy (by 30% vs. -5%, P = 0.01), self-reported control of asthma (by 14% vs. 5%, P = 0.04), and perhaps quality of life (by 37% vs. 21%, P = 0.06). The direction of change for all other clinical outcomes was more favorable in the intervention group, but not significantly so. Markers of inflammation in sputum decreased more in the intervention group, with sputum eosinophils declining significantly (P = 0.02). CONCLUSION: In asthmatic patients treated with inhaled corticosteroids, education and training in self-management improves adherence with inhaled therapy, perceived control of asthma, and sputum eosinophilia.

Administration, Inhalation↗
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↗
PubMed2003

ADAM33 is not associated with asthma in Puerto Rican or Mexican populations.

A recent study identified the ADAM33 gene as a promising candidate contributing to asthma. In Puerto Rican and Mexican populations, we have genotyped six single nucleotide polymorphisms (SNPs) that were used in the Genetics of Asthma in Latino Americans Study. We chose to study these two populations because in the United States, Puerto Ricans have the highest asthma prevalence, morbidity, and mortality and Mexicans the lowest. We used the transmission disequilibrium test to analyze associations between the ADAM33 gene variants and asthma, asthma severity, bronchodilator responsiveness, and total IgE levels using single SNPs, two to six SNP combinations, and specific haplotypes in 583 trios (proband with asthma and both biological parents). We also genotyped matched control samples to allow case-control analyses. None of the transmission disequilibrium test or case-control results showed significant association in either population. We found no evidence for association of single SNPs with asthma severity, bronchodilator response, or IgE levels in Mexicans or in the combined population. Two SNPs showed a modest association in Puerto Ricans, insignificant when the number of comparisons was taken into account. We conclude that the ADAM33 gene is not an important risk factor for asthma or for asthma-associated phenotypes in Mexicans or in Puerto Ricans.

ADAM Proteins↗
PubMed2003

Airway tissue mast cells in persistent asthma: predictor of treatment failure when patients discontinue inhaled corticosteroids.

STUDY OBJECTIVES: To determine if persistent airway tissue mast cells are associated with treatment failure when patients discontinue inhaled corticosteroids (ICS). DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Multicenter, tertiary referral centers. PATIENTS OR PARTICIPANTS: Forty-five subjects with asthma recruited from six medical centers in the United States. INTERVENTIONS: The Asthma Clinical Research Network undertook a 28-week, randomized, multicenter, double-blind, placebo-controlled trial of 164 subjects with clinically stable, persistent asthma. A subset of subjects (n = 45) underwent bronchoscopy with endobronchial biopsy and BAL at the end of a 6-week run-in period, during which all subjects received triamcinolone acetonide (TAA), 400 microg bid. Airway tissue mast cells, eosinophils, neutrophils, macrophages, and T cells were quantified morphometrically along with determination of BAL tryptase. At the end of the run-in period, subjects were then randomized to receive salmeterol (42 micro g bid), placebo, or continue TAA for 16 weeks followed by a second bronchoscopy. MEASUREMENTS AND RESULTS: Outcome variables included airway tissue mast cells, eosinophils, neutrophils, macrophages, and T cells that were quantified morphometrically and BAL tryptase. Thirty-five subjects completed the treatment phase; an additional 10 subjects, who were randomized to either salmeterol or placebo after the run-in, had treatment failure. When the bronchoscopy results performed at the end of the run-in, prior to randomization, were analyzed, the treatment failure group demonstrated significantly more tissue mast cells as compared to the nontreatment failure group despite 6 weeks of therapy with TAA (p = 0.04). BAL tryptase was also significantly higher in the treatment failure group (p < 0.0001). Of those subjects who completed the study, tissue mast cells and BAL tryptase did not change significantly within any of the treatment groups during the treatment phase (p > 0.05). CONCLUSIONS: Persistent elevations in airway tissue mast cells and BAL tryptase after treatment with TAA predict treatment failure in patients for whom discontinuation of ICS is being considered.

Administration, Inhalation↗
PubMed2002

Microarray-based detection and genotyping of viral pathogens.

The detection of viral pathogens is of critical importance in biology, medicine, and agriculture. Unfortunately, existing techniques to screen for a broad spectrum of viruses suffer from severe limitations. To facilitate the comprehensive and unbiased analysis of viral prevalence in a given biological setting, we have developed a genomic strategy for highly parallel viral screening. The cornerstone of this approach is a long oligonucleotide (70-mer) DNA microarray capable of simultaneously detecting hundreds of viruses. Using virally infected cell cultures, we were able to efficiently detect and identify many diverse viruses. Related viral serotypes could be distinguished by the unique pattern of hybridization generated by each virus. Furthermore, by selecting microarray elements derived from highly conserved regions within viral families, individual viruses that were not explicitly represented on the microarray were still detected, raising the possibility that this approach could be used for virus discovery. Finally, by using a random PCR amplification strategy in conjunction with the microarray, we were able to detect multiple viruses in human respiratory specimens without the use of sequence-specific or degenerate primers. This method is versatile and greatly expands the spectrum of detectable viruses in a single assay while simultaneously providing the capability to discriminate among viral subtypes.

DNA Viruses↗
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↗
PubMed2002

Foreword.

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Anti-Asthmatic Agents↗
PubMed2002

Understanding how asthmatics perceive symptom distress during a methacholine challenge.

The way, or ways, in which asthmatics recognize specific symptom(s) with varying degrees of their airway obstruction, or asthma severity, is poorly understood. Our purpose was to gain a better understanding of how asthma patients during acute episodes, based on their symptom perception, decide when to seek symptom relief. A cross-sectional design was used to study 32, 16 per group, African Americans and Caucasians with a mean age of 34.5 years. All had mild, stable asthma (FEV1 > or = 70%), were non-smokers, atopic, and had not used inhaled or oral steroids for 3 months. Their mean baseline FEV1 was 97.5% predicted; all were controlled with intermittent use of a beta agonist inhaler. All had a bronchoconstrictor challenge using a provocative concentration of methacholine to achieve a 30% fall (PC30) in their FEV1. After achieving a PC30 and before their first dose of a bronchodilator was given, all subjects were asked: "If you felt this way at home would you take your inhaler?" Subjects were blinded to the fact that the yes/no question was asked when their FEV1 was reduced by 30%. In both groups, 44% responded "no" that they would not use their inhaler at that point in time. This finding suggests that those subjects, the 44% who failed to associate a change in their symptoms with increased airflow obstruction, may be at risk for life-threatening episodes.

Adult↗
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↗