Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis Commentary: Dosage needs systematic and critical

Holt, Shaun; Suder, Agnieszka; Weatherall, Mark; Cheng, Shih-Lung; Shirtcliffe, Philippa; Beasley, Richard; Herxheimer, Andrew

doi:10.1136/bmj.323.7307.253

Cited by 201 publications

(134 citation statements)

References 30 publications

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“…A recent meta-analysis indicated that maximal symptom and lung function improvements were found at low-to-medium doses (table 1) of inhaled fluticasone propionate. 10 Similar observations were made in a 24-week study comparing increasing doses of inhaled fluticasone propionate and beclomethasone dipropionate. 11 A study employing bronchial biopsies also failed to confirm enhanced in vivo anti-inflammatory benefits with very high doses of fluticasone propionate.…”

Section: Introductionsupporting

confidence: 61%

Categorizing Asthma Severity: An Overview of National Guidelines

Colice¹

2004

Clinical Medicine & Research

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Section: Introductionsupporting

confidence: 61%

Categorizing Asthma Severity: An Overview of National Guidelines

Colice¹

2004

Clinical Medicine & Research

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“…However, these conventional parameters of asthma control may be more downstream from the underlying inflammatory process. The doseresponse curve with ICS for these conventional outcomes is rather shallow, as shown in a meta-analysis with fluticasone propionate (FP) [3], where a plateau effect on lung function was achieved above 100 m g twice daily, suggesting that other surrogate markers of inflammation may be more sensitive. Airway hyperresponsiveness is a noninvasive surrogate marker of airway inflammation and is a sensitive method of assessing the short-and long-term response to ICS [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Effects of hydrofluoroalkane formulations of ciclesonide 400 µg once daily vs fluticasone 250 µg twice daily on methacholine hyper‐responsiveness in mild‐to‐moderate persistent asthma

Lee

Haggart

Currie

et al. 2004

Brit J Clinical Pharma

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AimsThere are no data comparing the relative efficacy of hydrofluoroalkane (HFA) formulations of ciclesonide (CIC) and fluticasone propionate (FP) on airway hyperresponsiveness, in mild-to-moderate persistent asthma. We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life. MethodsNineteen mild-to-moderate asthmatic patients completed the study per protocol in randomized, double-blind, double-dummy, crossover fashion. Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study. Patients were commenced instead on salmeterol (SM) 50 m g one puff twice daily + montelukast (ML) 10 mg once daily for 2-week washout periods prior to each randomized treatment, in order to prevent dropouts. Patients received 4 weeks of either CIC 200 m g two puffs once daily (08.00 h) + CIC-placebo (PL) two puffs once daily (20.00 h) + FP-PL two puffs twice daily (08.00 h and 20.00 h), or FP 125 m g two puffs twice daily (08.00 h and 20.00 h) + CIC-PL two puffs twice daily (08.00 h and 20.00 h). SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits. ResultsThere was no significant difference between CIC vs. FP for the primary outcome of methacholine P C 20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4 dd (95% CI -0.4, 1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs FP second; mean difference: 0.2 dd (95% CI -1.3, 1.7) or FP first vs CIC second; mean difference: 0.9 dd (95% CI -0.1, 1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline. ConclusionsThere were no differences between 4 weeks of CIC 400 m g once daily and FP 250 m g twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma. Longer-term studies are indicated to evaluate their relative efficacy on asthma exacerbations. Ciclesonide vs fluticasone in asthmaBr J Clin Pharmacol 58 :1 27

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“…In recent years, it has become increasingly clear that they are clinically very effective from the lowest available doses upwards. Regarding their effects on the airways, the dose-response curve for these commercially-available doses is flat [1]. The effect on structural airway changes, the so-called airway remodelling, is less clear.…”

mentioning

confidence: 99%

Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats

Vanacker¹,

Palmans²,

Pauwels³

et al. 2002

European Respiratory Journal

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To examine whether fluticasone propionate (FP) dose-dependently inhibits inflammatory as well as structural changes, Brown Norway rats were sensitised to ovalbumin (OA) on day 0 and 7. From day 14-28, rats were exposed to aerosolised OA (1%) or phosphate buffered saline every 2 days. Thirty minutes before each allergen exposure, animals were pre-treated with aerosolised placebo or FP (0.1, 1 or 10 mg) or prednisolone 3 mg?kg -1 i.p.At day 29, 0.1 mg FP had no measurable effect, either on inflammatory or structural changes, such as goblet cell hyperplasia and airway wall thickening. The allergeninduced increase in eosinophilic inflammation in bronchoalveolar lavage fluid and in the airway mucosa, as well as increased fibronectin deposition, were inhibited by treatment with FP from a dose of 1 mg onwards. Inhibition of goblet cell hyperplasia and thickening of the airway wall required 10 mg inhaled FP. At this dose, systemic effects were observed. However, for a comparable degree of systemic activity, prednisolone was far less effective at preventing airway changes.The dose of inhaled fluticasone propionate required to inhibit allergen-induced structural alterations was higher than to prevent eosinophil influx, and caused systemic side-effects. However, for a similar systemic activity, prednisolone was ineffective in preventing airway remodelling.

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Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis Commentary: Dosage needs systematic and critical

Abstract: Objective To examine the dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma.

Cited by 201 publications

References 30 publications

Categorizing Asthma Severity: An Overview of National Guidelines

Categorizing Asthma Severity: An Overview of National Guidelines

Effects of hydrofluoroalkane formulations of ciclesonide 400 µg once daily vs fluticasone 250 µg twice daily on methacholine hyper‐responsiveness in mild‐to‐moderate persistent asthma

Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats

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