Erika J. Sims

Leukotriene Antagonists as First-Line or Add-on Asthma-Controller Therapy

BACKGROUND Most randomized trials of treatment for asthma study highly selected patients under idealized conditions. METHODS We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score ≤6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score ≥1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial. RESULTS Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups. CONCLUSIONS Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group. (Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others; Controlled Clinical Trials number, ISRCTN99132811.).

Effects of monotherapy with intra‐nasal corticosteroid or combined oral histamine and leukotriene receptor antagonists in seasonal allergic rhinitis

The combination of a leukotriene receptor antagonist with an antihistamine may have beneficial effects in seasonal allergic rhinitis (SAR).

A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma

Background Allergic rhinitis and asthma commonly coexist and are both mediated by similar inflammatory mechanisms. Leukotriene antagonists may therefore be an alternative to corticosteroid therapy.

Effects of intranasal corticosteroids on adrenal, bone, and blood markers of systemic activity in allergic rhinitis

BACKGROUND Intranasal corticosteroids are regarded as the first-line treatment for allergic rhinitis, but few studies have directly compared their systemic effects. OBJECTIVE The purpose of this study was to compare the systemic bioactivity of aqueous formulations of intranasal budesonide, mometasone furoate (MF), and triamcinolone acetonide (TAA) in terms of adrenal, bone, and white blood cell markers. METHODS Twenty patients with allergic rhinitis, mean age (SE) 35.7 (3.5) years were studied in a single-blind, randomized, 4-way crossover design, with treatments separated by 7-day washout periods, comparing placebo with budesonide 200 micro(g) once daily, MF 200 micro(g) once daily, and TAA 220 micro(g) once daily. After 5 days of treatment at steady-state, serial blood and urine samples were taken for 24 hours. Collective and fractionated measurements (daytime, overnight, and 8 AM) were done on plasma cortisol and urine cortisol/creatinine excretion. Plasma osteocalcin and blood eosinophil counts were measured at 8 AM. RESULTS There was no significant difference between placebo and the active treatments with any of the markers of adrenal suppression. Mean values (SE) for 24-hour area under the curve plasma cortisol (nmol/L.hr) were placebo, 6312.9 (564.4); budesonide, 5908.8 (496.8); MF, 6374.1 (509.9); and TAA, 6239.2 (552.0). Twenty-four hour urinary cortisol/creatinine ratio (nanomoles per millimoles) showed placebo, 9.2 (0.5); budesonide, 8.5 (0.5); MF, 8.6 (0.4); and TAA, 8.6 (0.4). The diurnal circadian rhythm was unaffected, and there were only occasional patients with abnormally low cortisol values. There was also no suppression in terms of osteocalcin (placebo, 1.27 nmolL; budesonide, 1.22 nmol/L; MF, 1.33 nmol/L; and TAA, 1.24 nmol/L) and blood eosinophil count (placebo, 0.29 x 10(9)/L; budesonide, 0.27 x 10(9)/L; MF, 0.25 x 10(9)/L; and TAA, 0.24 x 10(9)/L). CONCLUSION Neither budesonide, MF, nor TAA produced significant systemic suppression of adrenal, bone, or white blood cell markers at the doses studied. This reflects the good safety profile of these aqueous intranasal formulations when taken at clinically recommended doses.

Cystic Fibrosis Diagnosed After 2 Months of Age Leads to Worse Outcomes and Requires More Therapy

OBJECTIVE. Newborn screening for cystic fibrosis remains controversial because improved pulmonary function has not been established. Studies to date have not accounted for differences in treatments delivered to clinically diagnosed children and newborn-screened controls. Here, we compare outcomes and treatment of patients clinically diagnosed within the newborn-screening reporting window (early-clinically diagnosed), those presenting after this period (late-clinically diagnosed), and patients diagnosed by newborn screening. PATIENTS AND METHODS. In a cross-sectional analysis of cohorts retrospectively ascertained, patients who were homozygous ΔF508 with cystic fibrosis, attending specialist cystic fibrosis centers, and 1 to 10 years of age between 2000 and 2002 were identified from the United Kingdom Cystic Fibrosis Database and stratified into newborn-screened, early-clinically diagnosed, or late-clinically diagnosed cohorts. Two analyses were performed: (1) after restricting to the most recent year of data collection, early-clinically diagnosed and late-clinically diagnosed cohorts were matched to newborn-screened patients by patient age and year of data collection (133 patients per cohort were identified); and (2) for all years of data collection, annual sets of data for early-clinically diagnosed and late-clinically diagnosed patients were matched to newborn-screened patients by patient age and year of data collection (291 data sets per cohort were identified). Median height and weight z scores, proportion of patients with height and weight <10th percentile, prevalence of chronic Pseudomonas aeruginosa infection, Shwachman-Kulczyki morbidity scores, percent predicted forced expiratory volume in 1 second, and numbers of long-term therapies were compared. RESULTS. In both analyses, newborn screening was associated with higher height z score, higher Shwachman-Kulczyki score, lower likelihood of height <10th percentile, and fewer long-term therapies compared with late-clinically diagnosed patients. No other differences were found. CONCLUSIONS. Newborn screening was associated with improved growth, reduced morbidity, and reduced therapy, yet generated equivalent pulmonary outcome compared with late clinical diagnosis, suggesting that newborn screening may slow cystic fibrosis lung disease progression.

Economic implications of newborn screening for cystic fibrosis: a cost of illness retrospective cohort study

BACKGROUND Newborn screening for cystic fibrosis might not be introduced if implementation and running costs are perceived as prohibitive. Compared with clinical diagnosis, newborn screening is associated with clinical benefit and reduced treatment needs. We estimate the potential savings in treatment costs attributable to newborn screening. METHODS Using the UK Cystic Fibrosis Database, we used a prevalence strategy to undertake a cost of illness retrospective snapshot cohort study. We estimated yearly costs of long-term therapies and intravenous antibiotics for 184 patients who were diagnosed as a result of screening as newborn babies, and 950 patients who were clinically diagnosed aged 1-9 years in 2002. Costs of adding cystic fibrosis screening to an established newborn screening service in Scotland were adjusted to 2002 prices and applied to the UK as a whole. Costs were recalculated in US

Evaluation of treatment response in patients with seasonal allergic rhinitis using domiciliary nasal peak inspiratory flow

. FINDINGS Cost of therapy for patients diagnosed by newborn screening was significantly lower than equivalent therapies for clinically diagnosed patients: mean (

Opportunities to diagnose chronic obstructive pulmonary disease in routine care in the UK: a retrospective study of a clinical cohort.

7228 vs

Effects of fexofenadine and desloratadine on subjective and objective measures of nasal congestion in seasonal allergic rhinitis

12 008, 95% CI of difference -6736 to -2028, p<0.0001) and median (

A comparison of once daily fexofenadine versus the combination of montelukast plus loratadine on domiciliary nasal peak flow and symptoms in seasonal allergic rhinitis

352 vs