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L C Orr

Publications and source records attributed to L C Orr.

7 recordsLinked to original sources

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

BACKGROUND: The combination of montelukast (ML) and loratadine (LT) has previously been shown to be superior to either drug alone in managing seasonal allergic rhinitis (SAR), whilst fexofenadine (FEX) has been shown to be better than LT as monotherapy. OBJECTIVES: We wished to compare ML + LT vs. FEX alone for effects on daily measurements (am/pm) of peak inspiratory flow (PIF) and symptoms. METHODS: Thirty-seven patients with SAR (skin prick positive to grass pollen) were randomised into a single-blind, double-dummy placebo (PL)-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 120mg FEX or (b) 10mg ML + 10mg LT. There was a 7-10 day placebo run-in and washout prior to each randomised treatment. The average of am/pm PIF (the primary outcome variable) was analysed. Patients recorded their symptom scores (from 0 to 3) twice daily, for nasal blockage, discharge, itching and sneezing with; total eye symptoms, ocular cromoglycate use, and daily activity. The total nasal symptom score was calculated as a composite (out of 24). RESULTS: There were no significant differences between baselines after the run-in and washout placebos for any variables. There were significant (P < 0.05, Bonferroni) improvements in all symptoms and PIF compared to pooled placebo with both treatments for all end-points, but no differences between the two treatment regimes (as means and within-treatment 95% confidence intervals): PIF: PL 102 (98-107), FEX 111 (107-116), ML+LT 113 (109-118); total nasal symptoms: PL 7.4 (6.7-2.0), FEX 5.0 (4.3-5.7), ML + LT 4.0 (3.3-4.7). CONCLUSIONS: Once daily FEX as monotherapy was equally effective as the combination of once daily ML + LT in improving nasal peak flow and controlling symptoms in SAR. Further studies are indicated to assess whether ML confers additional benefits to FEX in SAR.

Acetates↗

Airway and systemic effects of hydrofluoroalkane fluticasone and beclomethasone in patients with asthma.

BACKGROUND: With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers, it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids. We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate (FLU-HFA) and beclomethasone dipropionate (BEC-HFA) at recommended labelled doses. METHODS: Twenty mild to moderate asthmatics were randomised in crossover fashion to receive 6 weeks of 500 micro g/day followed by 1000 micro g/day FLU-HFA and BEC-HFA. Measurements were made at baseline after placebo run in and washout, and after each randomised treatment. The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second (FEV(1)) of 20% or more (methacholine PD(20)) and for systemic adverse effects was overnight urinary cortisol/creatinine (OUCC). RESULTS: For mean responses, both doses of BEC-HFA and FLU-HFA produced significant improvements in PD(20) compared with baseline. The improvement was not significantly greater with 1000 micro g/day FLU-HFA versus BEC-HFA, a 1.69 fold difference (95% CI 0.94 to 3.04). Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline, with significantly (p<0.05) lower values at 1000 micro g/day for BEC-HFA versus FLU-HFA (1.97 fold difference (95% CI 1.28 to 3.02)). CONCLUSION: There was no difference in the airway and systemic effects in patients with mild to moderate asthma between FLU-HFA and BEC-HFA at a dose of 500 micro g/day. At 1000 micro g/day there was increased systemic bioactivity with BEC-HFA compared with FLU-HFA, without any gain in airway efficacy.

Adult↗

Effects of topical corticosteroid and combined mediator blockade on domiciliary and laboratory measurements of nasal function in seasonal allergic rhinitis.

BACKGROUND: Both domiciliary and laboratory measures of nasal function have been used to evaluate treatment response in allergic airways disease; however, these measures have not been compared. OBJECTIVE: To determine the relationship of domiciliary measures (daily symptoms, peak inspiratory nasal flow, and nasal oral index) and laboratory measures (rhinomanometry, acoustic rhinometry) in assessing treatment response with topical steroids and specific inflammatory mediator blockage. METHODS: Twenty-one patients with seasonal allergic rhinitis and asthma were enrolled into a single-blind, placebo-controlled, crossover study comparing 2 weeks of 1) 400 microg inhaled plus 200 microg intranasal budesonide once daily and 2) 10 mg montelukast plus 10 mg cetirizine once daily. Before each treatment, patients received 7 to 10 days of placebo period. Laboratory measurements were made of nasal resistance by posterior rhinomanometry, and nasal volume between 0 and 5 cm by acoustic rhinometry after both placebo and active treatment periods. Daily domiciliary recordings were made of allergic rhinitis nasal symptoms scores and peak nasal and oral inspiratory flow rate (enabling the calculation of a nasal/oral index) throughout the study. RESULTS: There were significant (P < 0.05) improvements for all allergic rhinitis symptoms with both therapies, after factoring for pollen count. Spearman's rank correlation for comparison among nasal symptoms and the objective responses were: nasal inspiratory flow rate (R = -0.50, P = 0.02); nasal/oral index (R = -0.55 P = 0.01); rhinomanometry (R = 0.24, P = 0.30); and acoustic rhinometry (R = -0.21, P = 0.36). CONCLUSIONS: Both treatments were effective in managing allergic rhinitis symptoms, and patients' symptoms were more closely associated with domiciliary measurements of nasal flow than laboratory measurements of nasal function.

Acetates↗

Dose-response for adrenal suppression with hydrofluoroalkane formulations of fluticasone propionate and beclomethasone dipropionate.

AIMS: With the recent introduction of hydrofluoroalkane (HFA) inhalers it is important to know the relative systemic safety profiles of inhaled corticosteroids. We therefore decided to compare systemic bioavailability of HFA-beclomethasone dipropionate (BDP) vs HFA-fluticasone propionate (FP). METHODS: Sixteen healthy volunteers were randomised in placebo-controlled single blind cross-over fashion to receive 3 weeks with HFA-FP or HFA-BDP, given as 1 week cumulative doubling doses (nominal ex-valve) of 500, 1000 and 2000 microg day(-1), with a 1 week placebo run-in and wash-out. Overnight (22.00 h to 08.00 h) and early morning (08.00 h) urinary cortisol/creatinine excretion and 08.00 h serum cortisol were measured after each placebo and dosing period. All data were log-transformed to normalize their distribution. RESULTS: Urine and serum cortisol were suppressed by 2000 microg FP and BDP vs placebo and by 1000 microg BDP vs placebo for urinary cortisol/creatinine (P < 0.05). Overnight urinary cortisol/creatinine ratio (the primary endpoint) was suppressed more by 1000 microg BDP vs 1000 microg FP (P < 0.05), amounting to a geometric mean fold difference (95% CI) of 1.64 (1.04-2.56). There were also more individual low values less than 3 nmol mmol(-1) with BDP than FP at 1000 microg: n = 8/16 vs n = 2/16 (P < 0.05). CONCLUSIONS: There was dose-related suppression of corrected urinary cortisol/creatinine with the HFA formulations of BDP and FP. Suppression of overnight urinary cortisol/creatinine ratio was significantly greater with HFA-BDP than HFA-FP at 1000 microg. This suggests that the greater glucocorticoid potency of HFA-FP may be offset by the greater lung bioavailability of HFA-BDP.

Administration, Inhalation↗

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

BACKGROUND: The combination of a leukotriene receptor antagonist with an antihistamine may have beneficial effects in seasonal allergic rhinitis (SAR). OBJECTIVE: To determine how combined oral mediator blockade compares to monotherapy with intranasal corticosteroid in the treatment of SAR. METHODS: Twenty-two patients with seasonal allergic rhinitis were enrolled in a placebo controlled crossover study comparing 2 weeks therapy of either (a) 200 microg intranasal mometasone furoate (MF) once daily or (b) 10 mg oral montelukast plus 10 mg oral cetirizine once daily (MON/CZ), with a 7-10 day placebo period prior to each treatment period. Domiciliary measures of symptoms and nasal flow were recorded daily. Measurements of posterior rhinomanometry, acoustic rhinometry and nasal nitric oxide were made after all treatment and placebo periods. RESULTS: There were significant (P < 0.05) improvements in domiciliary peak nasal flow (l/min) with both MF (133 (3.8)) and MON/CZ (124 (3.8)) compared to pooled placebo (110 (4.0). Both treatments also showed significant improvement in terms of nasal blockage (units) (PL: 1.1(0.1), MF: 0.5 (0.1), MON/CZ 0.7 (0.1); and total nasal symptoms (units) (PL: 3.5 (0.3), MF 1.6 (0.3), MON/CZ 1.7 (0.3)), although there was no significant difference between the two active treatments. There were no significant differences between placebo and treatment for rhinomanometry, acoustic rhinometry or nitric oxide. CONCLUSIONS: Both intranasal mometasone furoate as monotherapy and oral cetirizine plus montelukast as cotherapy were equally effective for objective and subjective measures of treatment response in SAR. Domiciliary measurements of symptoms and peak flow were more sensitive than laboratory measurements of rhinomanometry, acoustic rhinometry and nasal nitric oxide.

Acetates↗

Antiasthmatic effects of mediator blockade versus topical corticosteroids in allergic rhinitis and asthma.

To compare the antiasthmatic efficacy of inflammatory mediator blockade versus topical corticosteroid therapy in patients with seasonal allergic rhinitis (SAR) and asthma, 14 patients were enrolled into a single-blind, double-dummy, placebo-controlled crossover study comparing 2 wk therapy of (1) 400 microgram orally inhaled budesonide plus 200 microgram intranasal budesonide (BUD) or (2) 10 mg oral montelukast plus 10 mg oral cetirizine (ML + CZ). Before each treatment period, patients received 7 to 10 d placebo washout. All treatments were given once daily in the morning. Throughout the study, patients recorded the following domiciliary measures: peak expiratory flow (PEF), rescue inhaler requirement, asthma symptoms, and daily activity score. Laboratory measurements were made at trough of adenosine monophosphate (AMP) bronchial challenge and exhaled nitric oxide (NO). Compared with pooled placebo (PL), there were significant (p < 0.05) improvements in all domiciliary measures with both treatments (mean PEF [L/min] PL: 463; BUD: 478; ML + CZ: 483). For geometric mean AMP PC(20) (mg/ml), there was an improvement (p < 0.05), compared with PL (47), for ML + CZ (133) but not for BUD (51); whereas for NO (ppb) there was significant suppression with BUD (7.6) but not ML + CZ (11.5) compared with PL (13.6). In conclusion, both combined mediator blockade and combined topical corticosteroids are equally effective antiasthma therapy in patients with asthma and SAR.

Acetates↗