Starting inhaled corticosteroids in asthma: when, how high, and how long

Molen, van der Thys; Kerstjens, Huib A. M.

doi:10.1183/09031936.00.15100300

Cited by 4 publications

(3 citation statements)

References 11 publications

(11 reference statements)

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“…11,24 We mostly used a starting dose of 400 mg twice daily and then applied a step down and step up strategy depending on necessity. A high or low starting dose has been widely discussed, 25 especially as the dose response curve for inhaled corticosteroids is fairly flat. 26 A Dutch study showed no difference in efficacy between a 200 and 800 mg per day of budesonide.…”

Section: Discussionmentioning

confidence: 99%

Asthma control and steroid doses 5 years after early or delayed introduction of inhaled corticosteroids in asthma: a real-life study

Selroos¹,

Löfroos²,

Pietinalho³

et al. 2004

Respiratory Medicine

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Section: Discussionmentioning

confidence: 99%

Asthma control and steroid doses 5 years after early or delayed introduction of inhaled corticosteroids in asthma: a real-life study

Selroos¹,

Löfroos²,

Pietinalho³

et al. 2004

Respiratory Medicine

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“…1 A systematic review found moderate doses of ICS as a starting dose to improve mPEF significantly better than a low dose. 8 In the study by Haahtela et al 2 asthma, initial treatment was given with a high-dose budesonide, 1200 mg daily via a pMDI plus spacer and followed after 2 years with 400 mg daily via Turbuhaler s for a third study year. Starting high has, thereafter, been the recommendation in the Finnish asthma guidelines, 6,22 and this recommendation was reinforced with the results of the Finnish 10-year asthma programme.…”

Section: Discussionmentioning

confidence: 99%

“…Whether treatment with ICS should be started at a high or low dose has been debated, 8 although it from a psychological point of view appears logical to start high in order to achieve asthma control as soon as possible. A systematic review of 13 trials (9 using budesonide, 3 using fluticasone propionate, and 1 using beclomethasone dipropionate [BDP]) found moderate doses of ICS (400-800 mg of BDP or equivalent) to significantly improve morning peak expiratory flow (mPEF) and nocturnal symptoms more than low doses (o400 mg of BDP or equivalent), but to have no further efficacy compared with high doses (4800 mg of BDP or equivalent).…”

Section: Introductionmentioning

confidence: 99%

Effect of disease duration on dose–response of inhaled budesonide in asthma

Selroos¹

2008

Respiratory Medicine

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Background: Inhaled corticosteroids (ICS) represent first-line treatment in persistent asthma with clinical studies showing benefits of initiating therapy early. Whether treatment should be started with a high or low dose remains controversial. We investigated the importance of disease duration on the response to the starting dose of the ICS, budesonide, in asthma patients not previously treated with ICS. Methods: Forty patients with newly detected asthma (symptoms for o12 months) and 41 patients with established asthma (mean duration 5.2 years, range 2-11) were randomized (double-blind, parallel-group) to treatment with budesonide Turbuhaler s 100 or 400 mg twice daily or placebo for 12 weeks. Results: For morning peak expiratory flow (mPEF), all four budesonide treatments resulted in statistically significant improvements from baseline and, after 12 weeks, the changes in all four groups were statistically significantly greater than placebo. In patients receiving early treatment, no significant differences were seen between budesonide doses. In patients with established symptoms, 800 mg/day improved mPEF significantly more than 200 mg/day. The 800 mg/day dose in the early treatment group improved mPEF significantly more than in the delayed treatment group. Changes in forced expiratory volume in 1 s (FEV 1 ), the concentration of inhaled histamine causing a 20% drop in FEV 1 , and use of as-needed medication behaved in very similar ways to mPEF. Asthma symptoms were reduced in all budesonide groups without a difference between doses. Conclusion:In patients with newly detected asthma treated early the initial ICS dose is not important. In contrast, in patients with symptoms for a longer duration a high starting dose improves airway function and hyperresponsiveness significantly better than a low dose.

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Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma

Ward

Pais

Bish³

et al. 2002

Thorax

371

310

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Background: There are few data in asthma relating airway physiology, inflammation and remodelling and the relative effects of inhaled corticosteroid (ICS) treatment on these parameters. A study of the relationships between spirometric indices, airway inflammation, airway remodelling, and bronchial hyperreactivity (BHR) before and after treatment with high dose inhaled fluticasone propionate (FP 750 µg bd) was performed in a group of patients with relatively mild but symptomatic asthma. Methods: A double blind, randomised, placebo controlled, parallel group study of inhaled FP was performed in 35 asthmatic patients. Bronchoalveolar lavage (BAL) and airway biopsy studies were carried out at baseline and after 3 and 12 months of treatment. Twenty two normal healthy non-asthmatic subjects acted as controls. Results: BAL fluid eosinophils, mast cells, and epithelial cells were significantly higher in asthmatic patients than in controls at baseline (p<0.01). Subepithelial reticular basement membrane (rbm) thickness was variable, but overall was increased in asthmatic patients compared with controls (p<0.01). Multiple regression analysis explained 40% of the variability in BHR, 21% related to rbm thickness, 11% to BAL epithelial cells, and 8% to BAL eosinophils. The longitudinal data corroborated the cross sectional model. Forced expiratory volume in 1 second improved after 3 months of treatment with FP with no further improvement at 12 months. PD 20 improved throughout the study. BAL inflammatory cells decreased following 3 months of treatment with no further improvement at 12 months (p<0.05 v placebo). Rbm thickness decreased in the FP group, but only after 12 months of treatment (mean change -1.9, 95% CI -3 to -0.7 µm; p<0.01 v baseline, p<0.05 v placebo). A third of the improvement in BHR with FP was associated with early changes in inflammation, but the more progressive and larger improvement was associated with the later improvement in airway remodelling. Conclusion: Physiology, airway inflammation and remodelling in asthma are interrelated and improve with ICS. Changes are not temporally concordant, with prolonged treatment necessary for maximal benefit in remodelling and PD 20 . Determining the appropriate dose of inhaled steroids only by reference to symptoms and lung function, as specified in current international guidelines, and even against indices of inflammation may be over simplistic. The results of this study support the need for early and long term intervention with ICS, even in patients with relatively mild asthma.

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Starting inhaled corticosteroids in asthma: when, how high, and how long

Cited by 4 publications

References 11 publications

Asthma control and steroid doses 5 years after early or delayed introduction of inhaled corticosteroids in asthma: a real-life study

Asthma control and steroid doses 5 years after early or delayed introduction of inhaled corticosteroids in asthma: a real-life study

Effect of disease duration on dose–response of inhaled budesonide in asthma

Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma

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