Comparison of High-Dose Inhaled Flunisolide to Systemic Corticosteroids in Severe Adult Asthma

doi:10.1378/chest.122.4.1208

Chest

Volume 122, Issue 4, October 2002, Pages 1208-1213

https://doi.org/10.1378/chest.122.4.1208 Get rights and content

Objective

To investigate whether, after 48 h of IV treatment with corticosteroids, the use of high-dose inhaled flunisolide is as effective as systemic corticosteroids in adults hospitalized for a severe asthma exacerbation.

Design

Randomized, double-blind, placebo-controlled study.

Setting

Inpatient, an urban teaching hospital medical ward; outpatient, asthma clinic affiliated with the hospital.

Participants

Forty patients aged 18 to 55 years with asthma exacerbation requiring hospitalization.

Interventions

Inhaled flunisolide via metered-dose inhaler (250 μg per activation) eight puffs bid compared to systemic corticosteroids alone, following eight doses of IV corticosteroids.

Measurements and results

Peak expiratory flow rate (PEFR), FEV₁, and symptom scores were recorded on day 1 (at presentation to the emergency department) and day 7, at an outpatient follow-up visit. From day 1 to day 7, mean PEFR increased from 190 to 379 L/min in the flunisolide group, and from 207 to 347 L/min in the systemic corticosteroids group (p = 0.95; 95% confidence interval [CI], − 66.3, ∞). Mean FEV₁ increased from 1.6 to 2.3 L in the flunisolide group, and from 1.4 to 2.1 L in the systemic corticosteroids group (p = 0.33; 95% CI, − 21.7, ∞). Changes in symptom scores were − 0.7 in the flunisolide group and − 0.9 in the systemic corticosteroids group (p = 0.39; 95% CI, − 0.4, ∞). Hospital readmission rates on day 7 were zero for both groups.

Conclusions

High-dose inhaled corticosteroids are as effective as systemic corticosteroids during a 7-day period following admission to the hospital for severe asthma.

Section snippets

Materials and Methods

All adult patients aged 18 to 55 years admitted from the ED to the inpatient medical service of Beth Israel Medical Center (BIMC) for an acute asthma exacerbation (International Classification of Disease code 493.91) were eligible for the study. The decision to hospitalize a patient on the inpatient medical service for an acute asthma exacerbation was made by senior BIMC ED staff. Implicit to study design is that the investigators had no involvement with the treatment or admission decision for

Results

Forty patients met the inclusion criteria, and all 40 patients were enrolled in the study. Twenty-one patients were randomized to the ICS group, and 19 patients were randomized to the prednisone group. One patient in the prednisone group completed only four doses of methylprednisolone in the hospital. One patient in the ICS group did not attend the follow-up appointment. This patient was interviewed by telephone, reported no readmission, and was able to measure PEFR at the time of the

Discussion

National Asthma Education and Prevention Program guidelines for the diagnosis and management of asthma recommend that patients with asthma of sufficient severity to require hospitalization be administered SS.¹ They also recommend that the patient be discharged on oral corticosteroids at a recommended dose of 20 mg bid for 3 to 10 days.¹ In addition, they recommend ICS should be started before the course of systemic corticosteroids is completed.¹ The reason provided is that ICS have a gradual

ACKNOWLEDGMENT

The authors thank Paul Bailyn, PhD (Chairman, Mathematics Department, The Cooper Union, New York, NY) for statistical analysis.

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Comparisons between ICS and systemic corticosteroids have also been conflicting. OCS were superior to ICS in reducing hospital admission rates in some studies124-126 and others showed superiority of ICS.127 A systematic review of 12 trials concluded that there was no benefit to the addition of ICS to systemic corticosteroids in reducing the relapse rate of acute asthma.128
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The efficacy of single-high dose inhaled corticosteroid versus oral prednisone treatment on exhaled leukotriene and 8-isoprostane levels in mild to moderate asthmatic children with asthma exacerbation
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Even though the use of inhaled steroids during an asthma exacerbation has been proposed as an alternative, there is some concern about its efficacy.1–3 While some authors have suggested that inhaled steroids seem to act faster than oral steroids on symptoms and airway obstruction,2,4–6 and the recent Cochrane review of early use of ICS in the emergency department treatment of acute asthma found that there was a reduction from 32 to 17 hospital admissions per 100 patients treated with ICS agents compared with placebo, the same Cochrane review concluded that there was not sufficient evidence to support using ICS agents alone as a replacement for systemic corticosteroid therapy in acute asthma attacks.7 In addition, its exact mechanism of action in this setting is largely unknown.
The anti-inflammatory effect of high-dose inhaled corticosteroids (ICS) in children with asthma exacerbation is unknown. We aimed to investigate the efficacy of single-high dose ICS versus oral prednisone treatment followed by a course of six day high-dose ICS or oral prednisone (P) treatment on the concentrations of Cys-LTs and 8-isoprostane levels in the exhaled breath condensate (EBC) of children with asthma exacerbation.
Ninety-four children with moderate–severe asthma exacerbation were evaluated with asthma scores, peak expiratory flow rate (PEF), forced expiratory volume in first second (FEV1) and exhaled Cys-LT and 8-isoprostane levels before and after treatment. EBC was collected from 52 patients before and four hours after treatment with inhaled fluticasone propionate (FP) (4000 μg) or P and after six days of treatment with FP-1000 μg/day or P. Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit.
Both single high-dose FP (n = 59) and p (n = 35) treatment resulted in a significant improvement in asthma score (p < 0.0001), PEF (p < 0.0001), and FEV1 (p < 0.0001). Cys-LT concentration in the EBC decreased significantly both after the initial treatment (p = 0.001), and at the end of the six-day period in the FP group (p < 0.0001). 8-Isoprostane concentration was lower only after six days of treatment with FP-1000 μg/day in the FP group (p = 0.023). There was a significant decrease in exhaled Cys-LTs after four hours (p = 0.012) and six days of P treatment (p = 0.018) in children with asthma exacerbation.
High-dose ICS treatment may be useful in the treatment of children with asthma exacerbation. The effects start as early as after four hours. The suppression of Cys-LTs production contributes to the early effects. Suppression of both Cys-LTs and oxidants may favourably contribute to the effects observed later.
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Oral corticosteroids effectively treat asthma exacerbations but are associated with well-described side effects.
This study compared the efficacy and safety of a high dose of an inhaled corticosteroid with oral prednisolone in patients with worsening of their asthma after medication withdrawal.
Patients tapered off their inhaled corticosteroids until they reached predefined criteria of “worsening asthma”. Randomized patients (n = 130) were treated double blind with either ciclesonide 800 μg twice daily (starting with 800 μg hourly for 3 h after randomization) or prednisolone 40 mg once daily for 2 weeks. Spirometry, daily asthma symptoms, morning and evening peak expiratory flow and blood parameters were assessed in all, methacholine challenge and inflammatory measures were determined in induced sputum in a subset of patients.
Ciclesonide was as effective as prednisolone in improving forced expiratory flow in 1 s, morning peak expiratory flow and symptoms, the latter improving more rapidly with ciclesonide. No differences were found in methacholine responsiveness or inflammatory measures in sputum or blood. Ciclesonide caused significantly less reduction in morning plasma cortisol levels (p < 0.0001).
This study shows that inhaled ciclesonide (800 μg twice daily) has comparable efficacy to oral prednisolone (40 mg once daily) to regain asthma control in patients with asthma worsening. The more rapid onset and smaller effect on cortisol suppression suggest a better safety profile of ciclesonide.
Inhaled fluticasone propionate is effective as well as oral prednisone in reducing sputum eosinophilia during exacerbations of asthma which do not require hospitalization
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The aim of this study was to evaluate whether fluticasone propionate (FP) is effective as well as prednisone (P) in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbations not requiring hospitalization. We measured, in a parallel-group, double-blind double-dummy, randomized study, sputum and blood inflammatory cell counts and soluble mediators in 37 asthmatic subjects during a spontaneous exacerbation of asthma (Visit 1) and after a 2 week (Visit 2) treatment with inhaled FP (1000 μg bid) (Group A, $n = 18$ ) or a reducing course of oral P (Group B, $n = 19$ ). Asthma exacerbation was accompanied by sputum eosinophilia (eosinophils >2%) in almost all patients (95%). FP improved FEV₁ (from 53.9%±16.8 at Visit 1 to 76.4%±21.2 at Visit 2, $p = 0.0001$ ) and reduced the percentage of sputum eosinophils (from 38%[0–78] to 3%[1–31, $p = 0.0008$ ) as well as oral P (FEV₁: from 51.5%±14.4 to 83.6%±21.1, $p = 0.0001$ ; sputum eosinophils: from 52%[1–96] to 11%[0–64], $p = 0.0003$ ). At Visit 2, sputum eosinophils were significantly lower in Group A than in Group B. P but not FP induced significant decrease in blood and sputum ECP. Oxygen saturation, PEF variability, symptom score and use of rescue medication similarly improved in both groups. We conclude that FP is effective at least as well as P in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbation. However, the cost/effectiveness ratio of this option should be further evaluated.
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View all citing articles on Scopus

: All work was performed at Beth Israel Medical Center.

: Dr. Dayrit's current institutional affiliation is The Regional Medical Center, Orangeburg and Calhoun Counties, Orangeburg, SC.

: This research was supported by a grant from Forest Laboratories, Inc.

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Chest

Clinical InvestigationsComparison of High-Dose Inhaled Flunisolide to Systemic Corticosteroids in Severe Adult Asthma

Objective

Design

Setting

Participants

Interventions

Measurements and results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

ACKNOWLEDGMENT

Chest

Ann Emerg Med

Ann Emerg Med

J Allergy Clin Immunol

Chest

Chest

Ann Allergy Asthma Immunol

Guidelines for the emergency management of asthma in adults

Can Med Assoc J

The British guidelines on asthma management: 1995 review and position statement; British Thoracic Society

Thorax

Inhaled flunisolide for acute severe asthma

Am J Respir Crit Care Med

The effects of combined intravenous and inhaled steroids (beclomethasone dipropionate) for the emergency treatment of acute asthma

Acad Emerg Med

Acute resistant asthma caused by excessive β2-adrenoreceptor agonist inhalation and reversed by inhalation of beclomethasone

S Afr Med J

Clinical Investigations
Comparison of High-Dose Inhaled Flunisolide to Systemic Corticosteroids in Severe Adult Asthma

Acute resistant asthma caused by excessive β₂-adrenoreceptor agonist inhalation and reversed by inhalation of beclomethasone