Potential benefits of the UK Cystic Fibrosis Database.
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Adolescent↗
Biomedical subjects
E J Sims
Publications and source records attributed to E J Sims.
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↗
Effects of fexofenadine and desloratadine on subjective and objective measures of nasal congestion in seasonal allergic rhinitis.
BACKGROUND: In vitro studies have shown much higher H1-receptor antagonist potency with desloratadine (DL) compared to fexofenadine (FEX), although it is unclear whether this has any clinical relevance on disease control parameters in seasonal allergic rhinitis (SAR), especially for nasal congestion. OBJECTIVE: To compare the relative efficacy between presently recommended doses of DL and FEX on daily measurements of peak nasal inspiratory flow (PNIF) and nasal symptoms in SAR. METHODS: Forty-nine patients with SAR were randomized into a double-blind, placebo-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 180 mg FEX or (b) 5 mg DL, taken in the morning. There was a 7-10 day placebo run-in and washout prior to each randomized treatment. Measurements were made in the morning (AM) and in the evening (PM) for PNIF (the primary outcome variable), nasal and eye symptoms. The average of AM/PM values were used for analysis. RESULTS: There were significant (P < 0.05) improvements, compared to placebo, with FEX and DL, for PNIF, nasal blockage, nasal irritation, and total nasal symptoms, but not nasal discharge or eye symptoms. There were no significant differences between active treatments. Values for PNIF (L/min) for mean placebo baseline, mean difference from baseline (95% CI for difference) were 126, 10 (4-16) for FEX; and 122, 11 (4-17) for DL. The mean difference (95% CI) between FEX vs. DL was 1 L/min (-7-8). Values for total nasal symptoms (out of 12) were: 3.2, 0.7 (0.2-1.2) for FEX; and 3.4, 0.9 (0.3-1.5) for DL, and for nasal blockage (out of 3) were: 1.1, 0.2 (0.1-0.4) for FEX; and 1.2, 0.3 (0.1-0.5) for DL. The mean difference (95% CI) in total nasal symptoms and nasal blockage between FEX vs. DL was 0.1 (-0.6-0.8) and 0.1 (-0.2-0.3), respectively. CONCLUSIONS: Recommended once daily doses of fexofenadine and desloratadine were equally effective in improving nasal peak flow and nasal symptoms in SAR.
Adult↗
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↗
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. OBJECTIVE: To compare oral montelukast with inhaled plus intranasal budesonide in patients with seasonal allergic rhinitis and asthma. PATIENTS AND METHODS: A single-blind double-dummy placebo-controlled crossover study was performed comparing once daily 10 mg oral montelukast with 400 microg inhaled plus 200 microg intranasal budesonide in 12 patients with allergic rhinitis and asthma: mean (S.E.) age 34.0 years (2.7), forced expiratory volume in 1 s (FEV1) 91.2 (3.8)% predicted. Each treatment was for 2 weeks with a 1-week placebo run-in and washout. Measurements were made after each active treatment and placebo for: adenosine monophosphate bronchial challenge, exhaled and nasal nitric oxide. Patients also recorded their domiciliary peak expiratory flow, nasal peak inspiratory flow, asthma and seasonal allergic rhinitis symptoms. RESULTS: There were no significant differences between the placebos for any measurement. For adenosine monophosphate PC20, geometric mean fold differences (95% confidence interval (CI) for difference) were 6.4 (2.2-18.6) for placebo vs. budesonide, 2.9 (1.0-8.4) for placebo vs. montelukast, and 2.1 (1.1-4.5) for budesonide vs. montelukast. For exhaled nitric oxide (p.p.b.) there was significant (P < 0.05) suppression with both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For nasal nitric oxide and nasal peak flow there were only significant differences with budesonide compared with placebo. Both treatments reduced total seasonal allergic rhinitis symptoms but only budesonide had a significant effect on nasal symptoms. CONCLUSION: Once-daily inhaled plus intranasal budesonide and once daily montelukast showed comparable efficacy on lower airway, but only the budesonide had significant efficacy on upper airway inflammatory markers. Both treatments significantly reduced allergic rhinitis symptoms.
Acetates↗
Vaginal birth after cesarean: to induce or not to induce.
OBJECTIVE: Our purpose was to determine the impact of labor induction on both the success and safety of a trial of labor in women who are candidates for vaginal birth after cesarean. STUDY DESIGN: We performed a prospective observational analysis of 505 women consecutively presenting for delivery with a prior cesarean (September 1997-December 1999), of whom 236 (46.7%) underwent trial of labor. The following three cohorts were established: (1) repeat cesarean without trial of labor (n = 269), (2) spontaneous trial of labor (n = 179), and (3) induced trial of labor (n = 57). RESULTS: The vaginal delivery rate was significantly higher (77.1% vs 57.9%) in the spontaneous labor group compared with the induced labor group (odds ratio, 2.45; 95% confidence interval, 1.24-4.82; P =.008). Uterine scar separation occurred more frequently in the induced labor group (7%) than in the elective repeat cesarean group (1.5%) (odds ratio, 0.20; 95% confidence interval, 0.04-0.99; P =.034). CONCLUSION: Induction of labor in women attempting vaginal birth after cesarean is associated with a significantly reduced rate of successful vaginal delivery and an increased risk of serious maternal morbidity.
Cohort Studies↗
Evaluation of salmeterol or montelukast as second-line therapy for asthma not controlled with inhaled corticosteroids.
OBJECTIVE: To assess the addition of a leukotriene receptor antagonist and a long-acting beta(2)-agonist as second-line therapy in asthma. DESIGN: Placebo-controlled, double-dummy, crossover study. SETTING: Outpatient clinic. PATIENTS: Twenty patients with persistent asthma not controlled with inhaled corticosteroid therapy. INTERVENTIONS: Montelukast 10 mg once daily, or salmeterol, 50 microg bid, each for 2 weeks with 1-week run-in and washout placebo periods. MEASUREMENTS AND RESULTS: Adenosine monophosphate (AMP) bronchial challenge, blood eosinophil count (EOS), exhaled nitric oxide, and lung function after both placebo periods and after the first and last doses of each active treatment. Patients recorded their domiciliary peak expiratory flow (PEF), asthma symptoms, and rescue bronchodilator requirement (RES) twice daily throughout the study. For the primary end point of the provocative concentration of AMP causing a 20% fall in FEV(1), compared to placebo (47.5 +/- 13.0 mg/mL), there were significant differences with the first (114.1 +/- 36.9 mg/mL) and last (94.2 +/- 30.4 mg/mL) doses of montelukast as well as the first (160.1 +/- 64.5 mg/mL) but not the last (70.1 +/- 23.7 mg/mL) dose of salmeterol. Only montelukast produced significant suppression of the EOS. Neither drug affected exhaled nitric oxide levels. There were significant improvements with the first doses of salmeterol for all parameters of lung function. After 2 weeks of treatment, there were significant improvements with both drugs for RES and morning PEF. There were no significant differences between drugs for any end points except EOS. CONCLUSIONS: Montelukast and salmeterol exhibited significant improvements in asthma control when given as second-line therapy. Montelukast also produced significant effects on AMP challenge and EOS suggesting anti-inflammatory activity.
Acetates↗
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↗
Subjective and objective markers of treatment response in patients with seasonal allergic rhinitis.
BACKGROUND: Although there is a recognized association between upper and lower allergic airways disease, it is unknown how seasonal allergic rhinitis (SAR) therapy will effect sensitive markers of airway function in patients with no history of asthma. OBJECTIVE: To prospectively evaluate subjective and objective markers of treatment response in 26 patients with SAR who have been screened to exclude a diagnosis of asthma. METHODS: The patients' usual treatment, with antihistamine alone (n = 13) or in combination with intranasal corticosteroid (n = 13), was withheld for 1 week to achieve a baseline and then resumed. Measurements were made after baseline and after 2 and 4 weeks of treatment for nasal peak inspiratory flow rate (nPIFR); airways resistance (Raw) and specific conductance (sGaw); and nasal nitric oxide (NO). Patients reported their symptom (nasal, throat and eye) scores, daily activity scores, and ocular sodium cromoglycate usage over the preceding 24 hours. RESULTS: Compared with baseline, there were significant (P < .05) improvements with nPIFR, symptom scores and cromoglycate usage at 2 and 4 weeks of treatment. There was no significant suppression for NO at 2 or 4 weeks. There was a significant correlation between nPIFR and nasal symptoms (r = -0.52, P < .001). After 4 weeks of treatment there were significant (P < .05) improvements in sGaw (143.3% predicted) and Raw (91.6% predicted) compared with baseline (sGaw: 111.8%, Raw: 104.2% predicted). CONCLUSION: Treatment of SAR improves upper and lower airway parameters but not NO. Nasal PIFR correlates significantly with nasal symptoms.
Adult↗
Evaluation of treatment response in patients with seasonal allergic rhinitis using domiciliary nasal peak inspiratory flow.
BACKGROUND: Measurement of domiciliary nasal peak inspiratory flow rate (PIFR) may have a role in the objective assessment of treatment response in seasonal allergic rhinitis (SAR). OBJECTIVE: We wished to evaluate the relationship between domiciliary measurement of nasal PIFR and a variety of symptoms associated with rhinitis. METHODS: Thirty-eight nonasthmatic patients, mean age (SEM) 30 years (1.4), with symptomatic SAR were evaluated in a placebo-controlled, single-blind, double-dummy, three way parallel group study. Patients received oral cetirizine 10 mg once daily and were randomized to receive, in addition, either: (i) intranasal mometasone furoate 200 microgram (n = 14); (ii) oral montelukast 10 mg (n = 11); or (iii) placebo (n = 13). All treatments were given once daily for 4 weeks and were preceded by a 1 week placebo period. Domiciliary diary cards were used to record morning (am) and evening (pm) domiciliary nasal PIFR and symptom (nasal, eye, throat) scores and impact on daily activity. A total daily symptom score was then calculated from the sum of these separate symptom scores. RESULTS: Baseline values for symptom scores and PIFR after placebo run-in were not significantly different when comparing the three groups. After 4 weeks of active treatment, there were significant (P < 0.05) improvements in nasal symptoms, total daily symptoms and PIFR with all treatments, with there being no significant confounding effect of pollen count, when analysed as a covariate. There were significant (P < 0.01) correlations for nasal symptom scores vs PIFRam (r = - 0.51) and PIFRpm (r = - 0.56), and similarly for daily activity vs PIFRam (r = - 0.42) and PIFRpm (r = - 0.48). CONCLUSIONS: These results suggest that domiciliary measurements of nasal peak flow correlate significantly with symptoms of seasonal allergic rhinitis and may therefore be a potentially useful objective short-term marker of treatment response.
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↗
Screening for bronchial hyperresponsiveness using methacholine and adenosine monophosphate. Relationship to asthma severity and beta(2)-receptor genotype.
Bronchial hyperresponsiveness (BHR) is a key feature of asthma and may be measured by direct methacholine challenge or indirect adenosine monophosphate (AMP) challenge. We performed a retrospective analysis of our database (n = 487) of patients with asthma with the aim first, to compare methacholine and AMP challenge as screening tools, and second, to identify any relationships between BHR and disease severity markers or beta(2)-adrenoceptor genotype. Of these subjects, 258 had a methacholine challenge, 259 an AMP challenge and 185 both. Of subjects having both, 140 (76%) were methacholine responsive with PD(20) < 500 microgram (PC(20) < 5 mg/ml) and 92 (50%) were AMP responsive with PC(20) < 200 mg/ ml. For those who were AMP unresponsive 57% were methacholine responsive, whereas for the methacholine nonresponders 11% were AMP responsive. Methacholine (but not AMP)-responsive patients had a significantly (p < 0.05) lower % predicted FEV(1) and FEF(25-75) and higher inhaled corticosteroid dose than unresponsive patients. Finally, subjects with a glycine allele at codon 16 had significantly (p < 0.05) increased BHR to methacholine but not AMP. Our results suggest that methacholine is a more appropriate screening tool for BHR than AMP as it was more sensitive in our population and was also related to asthma severity. In addition, we have demonstrated an association between the glycine allele (codon 16) and increased BHR to methacholine.
Adenosine Monophosphate↗
Additive bronchoprotective and bronchodilator effects with single doses of salmeterol and montelukast in asthmatic patients receiving inhaled corticosteroids.
OBJECTIVE: We wished to evaluate whether the combination of a leukotriene receptor antagonist and long-acting beta(2)-agonist might confer additive beneficial effects in terms of bronchoprotection and bronchodilatation, in mild to moderate asthmatic patients who were suboptimally controlled on inhaled corticosteroids alone. METHODS: Twelve asthmatic patients were enrolled into a single-blind, placebo-controlled, crossover study, receiving additive therapy as either of the following: (1) montelukast alone, 10 mg (ML(10)); (2) inhaled salmeterol alone, 50 microg (SM(50)); (3) ML(10) and SM(50); (4) ML(10) and inhaled salmeterol, 100 microg (SM(100)); or (5) placebo inhaler and tablet. Trough measurements were made of adenosine monophosphate (AMP) bronchial challenge (the provocative concentration of a drug [AMP] causing a fall of >/= 20% in FEV(1) [PC(20)]) as the primary end point, and spirometry, following single doses of either placebo or active treatments (12 h after salmeterol, and 24 h after monteleukast, respectively). RESULTS: Compared to placebo, all active treatments led to significant improvements (p < 0.05) in geometric mean AMP-PC(20): placebo, 42 mg/mL; ML(10), 106 mg/mL; SM(50), 115 mg/mL; ML(10) and SM(50), 183 mg/mL; and ML(10) and SM(100), 247 mg/mL. The effects of montelukast and salmeterol were numerically additive, with ML(10) and SM(100) being significantly different (p < 0.05) from ML(10) alone. For mean FEV(1) and forced expiratory flow rate between 25% and 75% of vital capacity, there were significant differences (p < 0.05) between both combination therapies vs ML(10) alone. CONCLUSIONS: Our results suggest additive benefits of a single dose of a long-acting beta(2)-agonist and leukotriene antagonist, in terms of bronchoprotection and bronchodilation. Further studies in more severe asthmatics are required to evaluate long-term clinical effects.
Acetates↗
Differences in lung bioavailability between different propellants for fluticasone propionate.
The lung bioavailability (as adrenal suppression) of fluticasone propionate was about twofold greater with chlorofluorocarbons than hydrofluoroalkane as propellant. Direct switching between formulations on a microg equivalent may therefore be inadvisable.
Adult↗
Importance of drug-device interaction in determining systemic effects of inhaled corticosteroids.
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Androstadienes↗
Dose response with fluticasone propionate on adrenocortical activity and recovery of basal and stimulated responses after stopping treatment.
OBJECTIVE: To evaluate the dose-response relationship for adrenocortical activity with fluticasone propionate (FP) and to assess basal and dynamic markers after stopping treatment for 3 days. PATIENTS AND DESIGN: Fourteen asthmatic patients were recruited: mean age 33.3 years, forced expiratory volume in 1 s (FEV1): 91.3% predicted, forced mid expiratory flow rate (FEF25-75): 58.1% predicted. A single blind study design was used comparing a placebo run-in with sequentially low, medium and high doses of FP and a placebo washout. All active treatments, placebo and washout were each for 3 days. FP was given at steady-state with twice daily divided dosing at 0800 h and 2200 h at doses of 375 micrograms, 875 micrograms, and 1750 micrograms per day. MEASUREMENTS: A 100 micrograms i.v. bolus hCRF test was performed at 0800 h after the run-in and washout periods. Blood samples were taken for 0800 h serum cortisol and osteocalcin as well as an overnight 10 h urine collection for cortisol/creatinine excretion after the run-in period, each dose of active treatment and washout. RESULTS: For serum cortisol (pre and post hCRF stimulation) there was no significant difference between placebo and washout values. Mean (SE) cortisol (nmol/1) values pre hCRF were run-in: 644.5 (59.7), washout: 550.3 (42.8) and post hCRF were run-in: 690.9 (42.9), washout: 719.1 (43.8). There was a significant (P < 0.05) difference between run-in vs medium and high doses for 0800 h serum cortisol, overnight urinary cortisol and overnight urinary cortisol/creatinine excretion; and vs high dose for serum osteocalcin. The fold difference (95% CI for difference) between run-in and high dose was: 2.2 (1.5-3.2) for overnight urinary cortisol, 2.5 (1.5-4.1) for overnight urinary cortisol/creatinine, 2.0 (1.1-3.6) for serum cortisol, and 1.2 (1.1-1.3) for serum osteocalcin. CONCLUSION: Fluticasone propionate exhibited dose related adrenal suppression with treatment. The suppressive effects of fluticasone propionate on adrenocortical activity were greater than those observed on osteocalcin.
Adrenal Cortex↗