Inhaled Corticosteroids as Rescue Medication in Acute Severe Asthma

Gustavo J Rodrigo

Expert Rev Clin Immunol. 2008;4(6):723-729.

Abstract and Introduction

Abstract

Systemic corticosteroids (CS) should be considered as first-line treatment for acute asthma exacerbations, especially severe exacerbations. They may sometimes require a few hours or more to achieve their maximum effect. This time delay observed between administration of CS and improvement in lung function or hospital admissions is consistent with the belief that these effects of CS, involving the modification of gene expression, occur with a time lag of hours or days (genomic effect). On the other hand, CS also have effects initiated by specific interactions with membrane-bound or cytoplasmic receptors for CS, or nonspecific interactions with the cell membrane, with a much more rapid response (seconds or minutes; nongenomic effect). This review analyzes the clinical evidence regarding the use of inhaled CS in acute asthma patients, according to the characteristics of the nongenomic effect, and presents a proposal for the use of inhaled CS as a rescue medication in the emergency-department setting.

Introduction

All patients with asthma may experience exacerbations or attacks, characterized by a progressive increase in shortness of breath, cough, wheezing or chest tightness, and a decrease in expiratory airflow.^[40] Acute asthma is a medical emergency that must be diagnosed and treated urgently, and its intensity ranges from mild episodes, which may even go unnoticed by the patient, to extremely serious episodes that place a patient's life at risk and may even result in death (fatal or near-fatal asthma).^[1] The severity of the asthma exacerbations determines the treatment administered and the goals of treatment can be summarized as maintenance of adequate arterial oxygen saturation with supplemental oxygen, relief of airflow obstruction with repetitive administration of rapid-acting inhaled bronchodilators (β-agonists and anticholinergics) and reduction of airway inflammation and prevention of future relapses with early administration of systemic corticosteroids (CS).^[2]

Systemic CS should be considered as a first-line treatment for acute asthma exacerbations, especially severe exacerbations.^[3,4,40] These agents are extremely effective at reducing the airway inflammation present in virtually all asthmatics. Despite controversy regarding their efficacy, route of delivery and dosage, data summarized in two systematic reviews suggest that:

Systemic CS require more than 4-6 h to improve pulmonary function and reduce hospitalizations;
Intravenous and oral CS appear to have equivalent effects in most patients with acute asthma;
While precise dose-response relationships are not well described, there is a tendency toward greater and more rapid improvement in pulmonary function with medium (parenteral hydrocortisone 100 mg every 6 h) and high (200 mg every 6 h) doses, although these effects are likely to plateau at very high dosing, without additional benefit.^[3,4]

The time delay observed between administration and improvement in lung function or hospital admissions is consistent with the belief that these effects of CS result from changes in gene transcription and altered protein synthesis (genomic effect).^[5]

1 2 3 4 5

Next Section

No writing assistance was utilized in the production of this manuscript.

Cite this: Inhaled Corticosteroids as Rescue Medication in Acute Severe Asthma - Medscape - Nov 01, 2008.

Table 1. Characteristics of Studies That Compared Inhaled Corticosteroids With Placebo in Acute Asthma
Study	n (age range) baseline FEV₁	Inhaled CS dose	Results	Ref.
Rodrigo and Rodrigo	94 (18–50 years of age) FEV₁ < 50%	Flunisolide 1 mg/10 min (MDI) for 3 h	PEF, FEV₁, CI 120, 150 and 180 min Hospitalizations 180 min: flunisolide > placebo	[9]
Singhi et al.	60 (6–13 years of age) PEF = 50–70%	Budesonide 400 µg/30 min × 3 (MDI)	PEF, FR, CI, SaO₂ 120 min, CS use hospitalizations 4 h: budesonide > placebo	[29]
Rodrigo and Rodrigo	116 (18–50 years of age) FEV₁ < 50%	Flunisolide 1 mg /10 min (MDI) for 3 h.	PEF, FEV₁, 120, 150and 180 min and hospitalizations 180 min: flunisolide > placebo	[30]
Estrada-Reyes et al.	100 (>5 years of age)	Fluticasone 500 µg /15 min × 3 (neb)	CI 120 min fluticasone > placebo PEF and SaO₂ 120 min fluticasone = placebo	[31]
Afilalo et al.	54 (>18 years of age) FEV₁ = 40–59%	Beclomethasone 1 mg/60 min × 5 (MDI)	PEF, FEV₁ 60, 120 and 240 min and hospitalizations 6 h: beclomethasone = placebo	[32]
Sekerel et al.	67 (6–15 years of age) FEV₁ = 70–90%	Budesonide 1 mg/60 min × 3 (neb)	FEV₁ 210 min: budesonide = placebo	[33]
Pansegrouw	40 (18–70 years of age) FEV₁ < 70%	Beclomethasone 200 µg × 1 (MDI)	FEV₁ 60 min: beclomethasone > placebo	[7]
Tsai et al.	24 (6–17 years of age) PEF = 100 l/min	Budesonide 0.05 mg/kg × 1 (neb)	PEF, CI 60 and 180 min: budesonide = placebo	[34]

CI = Clinical index; CS = Corticosteroid; FEV₁ = Forced expiratory volume in 1 s; MDI = Metered-dose inhaler; neb = Nebulizer route; PEF = Peak expiratory flow; RF = Respiratory frequency; SaO₂ = Arterial oxygen saturation.
Reprinted with permission from [1].

Table 2. Characteristics of Studies Comparing Inhaled Corticosteroids With Systemic Corticosteroids in Acute Asthma
Study	n (age range) baseline FEV₁	Inhaled CS dose	Results	Ref.
Scarfone et al.	105 (1–17 years of age) CI = moderate	Dexamethasone 1.5 mg/kg every 30 min (neb) vs prednisone 2 mg/kg (VO)	Discharge rate 120 min: dexametasone > prednisone Hospitalizations 6 h: dexamethasone = prednisone	[35]
Devidayal Singhi et al.	80 (2–12 years of age) PEF = 63%	Budesonide 800 µg/30 min Neb × 3 vs prednisone 2 mg/kg VO	SaO₂, RF, CI and discharge rate 120 min: budesonide > prednisone	[36]
Rodrigo	106 (18–50 years of age) FEV₁ < 50%	Fluticasone 500 µg every 10 min (MDI) × 3 h vs hydrocortisone 500 mg iv.	PEF, FEV₁, 120, 150 and 180 min and discharge rate 120 min: fluticasone > hydrocortisone Hospitalizations 180 min: fluticasone = hydrocortisone	[11]
Volovitz et al.	22 (6–16 years of age) PEF = 35–75%	Budesonide 1.6 mg × 1 (Turb) vs prednisone 2 mg/kg (VO)	PEF, CI 60, 120 and 180 min: budesonide = prednisone	[37]
Milani et al.	34 (2–7 years of age) CI = moderate-severe	Budesonide 2 mg × 1 (neb) vs prednisone 1 mg/kg (VO)	CI, SaO₂ 60, 120 and 240 min: budesonide = prednisone Hospitalizations 6 h: budesonide = prednisone	[38]
Schu et al.	101 (5–18 years of age) FEV₁ < 60%	Fluticasone 2 mg × 1 (MDI) vs prednisone 2 mg/kg (VO)	FEV₁, FVC and hospitalizations 4 h: fluticasone < prednisone	[13]

CI = Clinical index; CS = Corticosteroid; FEV₁ = Forced expiratory volume in 1 s; FVC = Forced vital capacity; iv. = Intravenous; MDI = Metered-dose inhaler; neb = Nebulizer route PEF = Peak expiratory flow; RF = Respiratory frequency; SaO₂ = Arterial oxygen saturation; Turb = Turbohaler^®; VO = Oral route.
Reprinted with permission from [1].

Box 1. Proposal on the Use of Inhaled Corticosteroids as Rescue Medication in Acute Asthma
Use in acute severe asthma patients with incomplete response to initial treatment Always add to short-acting β₂-agonists Use repeated doses every 10–30 min for 90–120 min Fluticasone or budesonide are preferable Minimum effective doses for fluticasone and budesonide are 500 µg every 15–20 min, via metered-dose inhaler

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.