Biomedical subjects

James Kiley

Publications and source records attributed to James Kiley.

4 recordsLinked to original sources

PubMed2007

Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma.

RATIONALE: One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control. OBJECTIVES: To determine if the response to an inhaled corticosteroid or a leukotriene receptor antagonist is attenuated in individuals with asthma who smoke. METHODS: In a multicenter, placebo-controlled, double-blind, double-dummy, crossover trial, 44 nonsmokers and 39 light smokers with mild asthma were assigned randomly to treatment twice daily with inhaled beclomethasone and once daily with oral montelukast. MEASUREMENTS AND MAIN RESULTS: Primary outcome was change in prebronchodilator FEV(1) in smokers versus nonsmokers. Secondary outcomes included peak flow, PC(20) methacholine, symptoms, quality of life, and markers of airway inflammation. Despite similar FEV(1), bronchodilator response, and sensitivity to methacholine at baseline, subjects with asthma who smoked had significantly more symptoms, worse quality of life, and lower daily peak flow than nonsmokers. Adherence to therapy did not differ significantly between smokers and nonsmokers, or between treatment arms. Beclomethasone significantly reduced sputum eosinophils and eosinophil cationic protein (ECP) in both smokers and nonsmokers, but increased FEV(1) (170 ml, p = 0.0003) only in nonsmokers. Montelukast significantly increased a.m. peak flow in smokers (12.6 L/min, p = 0.002), but not in nonsmokers. CONCLUSIONS: In subjects with mild asthma who smoke, the response to inhaled corticosteroids is attenuated, suggesting that adjustments to standard therapy may be required to attain asthma control. The greater improvement seen in some outcomes in smokers treated with montelukast suggests that leukotrienes may be important in this setting. Larger prospective studies are required to determine whether leukotriene modifiers can be recommended for managing asthma in patients who smoke.

Acetates↗

PubMed2007

Asthma phenotypes.

PURPOSE OF REVIEW: Asthma is a heterogeneous disorder presenting with many phenotypes. Precise phenotypic definition has eluded the medical research community for years, despite recognition of different disease subtypes. Improved phenotypic characterization and knowledge of underlying pathobiology is necessary for linkage of specific genotypes with clinical disease manifestations. RECENT FINDINGS: Phenotyping has been difficult because asthma is likely to be comprised of overlapping syndromes with varying origins and heterogeneous pathobiology. Currently, the field is too reliant on classification by trigger or symptoms. Since genotypic and phenotypic heterogeneity are inherent in asthma, patients presenting with different asthma phenotypes may need tailored therapies. Studies have begun to link genetics with disease mechanism and therapeutic response. As disease etiology, onset, progression and severity vary greatly among patients, however, the relative contribution of genetic factors may be difficult to ascertain. Definition of the full array of complex biological consequences of molecular target modulation is a prerequisite for therapies based on this concept. SUMMARY: The advent of targeted therapies for asthma and clinical trials based on phenotype and genotype have raised interest in more accurate description of asthma phenotypes. Therapies based on phenotypic and genotypic characteristics may be useful in asthma management. A variety of factors, however, must be addressed before such approaches become standard.

Aspirin↗

PubMed2006

Association of obesity with pulmonary and nonpulmonary complications of pregnancy in asthmatic women.

OBJECTIVE: To evaluate whether maternal obesity is associated with pulmonary and nonpulmonary pregnancy complications in asthmatic women. METHODS: This is a secondary analysis of the prospective cohort Asthma During Pregnancy Study. Asthma patients were classified as having either mild or moderate to severe disease at the beginning of the study. Rates of pulmonary complications of asthma in asthmatic women and rates of nonpulmonary complications of pregnancy among asthma patients and controls, were compared between obese (body mass index > or = 30 kg/m2) and nonobese women. RESULTS: Maternal body mass index and pregnancy outcome data were available for 1,699 of 1,812 asthmatic women and for 867 of 881 controls. Of the asthma subjects, 30.7% (521) were obese compared with 25.5% of the controls, P = .006. Obese women, regardless of whether they had asthma, were more likely to undergo cesarean delivery (OR 1.6, 95% confidence interval [CI]1.3-2.0) to develop preeclampsia or gestational hypertension (OR 1.7 95% CI 1.3-2.3) and gestational diabetes (OR 4.2, 95% CI 2.8-6.3). There were no differences in the rates of overall asthma improvement (20.6% compared with 23.6%, P = .36) or deterioration (33.3% compared with 28.8%, P = .20) between obese and nonobese asthma patients. After adjustment for confounding variables, obesity, not asthma, was associated with nonpulmonary complications of pregnancy, and obesity was associated with an increase in asthma exacerbations as well (OR 1.3, 95% CI 1.1-1.7). CONCLUSION: Obesity is associated with an increased risk of asthma exacerbations during pregnancy. The increased rate of nonpulmonary complications of pregnancy in asthma patients is associated with obesity in this population and not with asthma status. LEVEL OF EVIDENCE: II-1.

Adult↗

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↗