Dosage and Time Effects of Inhaled Budesonide on Bronchial Hyperreactivity

Kraan, Jan; Koeter, Gh; Vandermark, Tw; Boorsma, Martin; Kukler, J.; Sluiter, Hj; Devries, K

doi:10.1164/ajrccm/137.1.44

Cited by 150 publications

(77 citation statements)

References 4 publications

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“…In contrast to other studies [9,[15][16][17] the improvement in PC20 methacholine in the present study is high (approximately 3.5 doubling doses after 6 and 12 weeks). This may be due to differences between the patients studied (atopic asthmatics [15] versus nonatopic asthmatics [9]), or to a difference in study medication prescribed [9,[15][16][17], or dosage used [9,[15][16][17].…”

Section: Discussioncontrasting

confidence: 99%

“…This may be due to differences between the patients studied (atopic asthmatics [15] versus nonatopic asthmatics [9]), or to a difference in study medication prescribed [9,[15][16][17], or dosage used [9,[15][16][17]. Also, the difference in provocative concentration used [18] makes comparison difficult, although we know that in asthma PC20 is similar for histamine and methacholine [18,19].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of fluticasone propionate on methacholine dose-response curves in nonsmoking atopic asthmatics

Overbeek¹,

Vons²,

Mulder³

et al. 1996

Eur Respir J

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E Ef ff fe ec ct ts s o of f f fl lu ut ti ic ca as so on ne e p pr ro op pi io on na at te e o on n m me et th ha ac ch ho ol li in ne e d do os se e--r re es sp po on ns se e c cu ur rv ve es s i in n n no on ns sm mo ok ki in ng g a at to op pi ic c a as st th hm ma at ti ic cs s ABSTRACT: Methacholine is frequently used to determine bronchial hyperresponsiveness (BHR) and to generate dose-response curves. These curves are characterized by a threshold (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) =sensitivity), slope (reactivity) and maximal response (plateau). We investigated the efficacy of 12 weeks of treatment with 1,000 µg fluticasone propionate in a double-blind, placebo-controlled study in 33 atopic asthmatics. The outcome measures used were the influence on BHR and the different indices of the methacholine dose-response (MDR) curve. After 2 weeks run-in, baseline lung function data were obtained and a MDR curve was measured with doubling concentrations of the methacholine from 0.03 to 256 mg·mL -1 . MDR curves were repeated after 6 and 12 weeks. A recently developed, sigmoid cumulative Gaussian distribution function was fitted to the data. Although sensitivity was obtained by linear interpolation of two successive log 2 concentrations, reactivity, plateau and the effective concentration at 50% of the plateau value (EC50) were obtained as best fit parameters.In the fluticasone group, significant changes occurred after 6 weeks with respect to means of PC20 (an increase of 3.4 doubling doses), plateau value fall in forced expiratory volume in one second (FEV1) (from 58% at randomization to 41% at 6 weeks) and baseline FEV1 (from 3.46 to 3.75 L) in contrast to the placebo group. Stabilization occurred after 12 weeks. Changes for reactivity were less marked, whereas changes in log 2 EC50 were not significantly different between the groups.We conclude that fluticasone is very effective in decreasing the maximal airway narrowing response and in increasing PC20. However, it is likely that part of this increase is related to the decrease of the plateau of maximal response.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of fluticasone propionate on methacholine dose-response curves in nonsmoking atopic asthmatics

Overbeek¹,

Vons²,

Mulder³

et al. 1996

Eur Respir J

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“…Whilst established anti-inflammatory agents, such as steroids, reduce BHR, most studies have examined this effect after two or more weeks of treatment. Moreover, the maximal effects of treatment may not be seen for several weeks or more [46]. It is possible, therefore, that the treatment period used in this study was insufficient to clearly establish whether or not CDP840 has an effect on BHR.…”

Section: Discussionmentioning

confidence: 94%

The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects

Harbinson

MacLeod²,

Hawksworth³

et al. 1997

Eur Respir J

115

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Recent studies have suggested that theophylline, a nonspecific phospho-diesterase inhibitor, has useful anti-inflammatory actions in asthma. Phosphodiesterase 4 (PDE4) represents the predominant PDE isoenzyme present in inflammatory cells. PDE4 inhibitors might, therefore, have beneficial effects in asthma. Sideeffects, specifically nausea, have limited the use of existing agents. CDP840 is an orally active, potent and selective PDE4 inhibitor. We have examined the effect of CDP840 on the allergen-induced asthmatic response, its possible modes of action, and its tolerability at therapeutic doses.A total of 54 patients were recruited to three double-blind, placebo-controlled studies. The first study examined the effect of CDP840 (15 mg b.i.d. for 9.5 days) on the allergen-induced asthmatic response in patients with known dual response to allergen. A second study examined the effect of CDP840 (15 mg b.i.d. for 9.5 days) on airway responsiveness to histamine. A third study examined whether single dose CDP840 (15 and 30 mg) had significant bronchodilatory effects.In all studies, CDP840 was well-tolerated, with no patients reporting nausea. CDP840 did not lead to changes in baseline forced expiratory volume in one second (FEV1) as compared to placebo. The late asthmatic response (LAR) to allergen, expressed as area under the curve at 3-8 h (AUC3-8h), was inhibited by 30% (p=0.016), an effect which persisted to the end of the observation period. The early asthmatic response (EAR) was unaffected, and there was no bronchodilatory effect at the doses used. Treatment with CDP840 did not affect bronchial hyperresponsiveness to histamine.In conclusion, CDP840 significantly attenuated the late asthmatic response to allergen challenge in the absence of any bronchodilatory or histamine antagonist effect. This suggests that CDP840 may exert its effects via an anti-inflammatory mechanism.

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“…AHR is a fundamental component of the definition of asthma, and has been associated with asthma exacerbations [23], airway inflammation [24] and decline in lung function [25]. Previous studies have shown a dose-dependent improvement in AHR with inhaled corticosteroid treatment [26,27], and asthma outcomes and basement membrane thickness improved when AHR was added to a treatment algorithm [7]. A recent study by MEIJER et al [11] showed that high-dose fluticasone was more effective in improving AHR than oral prednisolone.…”

Section: Discussionmentioning

confidence: 99%

Optimal asthma control, starting with high doses of inhaled budesonide

et al. 2000

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The aim of this study was to determine whether outcomes in poorly controlled asthma can be further improved with a starting dose of inhaled budesonide higher than that recommended in international guidelines.The study had a parallel-group design and included 61 subjects with poorly controlled asthma, randomized to receive 3,200 mg or 1,600 mg budesonide daily by Turbuhaler1 for 8 weeks (double-blind), then 1,600 mg . day -1 for 8 weeks (single-blind), followed by 14 months of open-label budesonide dose down-titration using a novel algorithm, with a written asthma crisis plan based on electronic peak expiratory flow monitoring. The primary outcome variable for weeks 1±16 was change in airway hyperresponsiveness (AHR), and, for the open-label phase, mean daily budesonide dose.By week 16, there were large changes from baseline in all outcomes, with no significant differences between the 3,200-and 1,600-mg . day -1 starting dose groups (AHR increased by 3.2 versus 3.0 doubling doses, p=0.7; morning peak flow increased by 134 versus 127 L . min -1 , p=0.8). Subjects starting with 3,200 mg . day -1 were 3.8 times more likely to achieve AHR within the normal range, as defined by a provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (PD20) of $3.92 mmol by week 16 (p=0.03). During dose titration, there was no significant difference in mean budesonide dose (1,327 versus 1,325 mg . day -1 , p>0.3). Optimal asthma control was achieved in the majority of subjects (at completion/withdrawal: median symptoms 0.0 days . week -1 , b 2 -agonist use 0.2 occasions . day -1 , and PD20 2.4 mmol).In subjects with poorly controlled asthma, a starting dose of 1,600 mg . day -1 budesonide was sufficient to lead to optimal control in most subjects. The high degree of control achieved, compared with previous studies, warrants further investigation. Eur Respir J 2000; 15: 226±235.

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Dosage and Time Effects of Inhaled Budesonide on Bronchial Hyperreactivity

Cited by 150 publications

References 4 publications

Effects of fluticasone propionate on methacholine dose-response curves in nonsmoking atopic asthmatics

Effects of fluticasone propionate on methacholine dose-response curves in nonsmoking atopic asthmatics

The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects

Optimal asthma control, starting with high doses of inhaled budesonide

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