What is the management of refractory asthma (Acute Severe Asthma) exacerbation?

From the Guidelines

Management of refractory asthma exacerbation requires immediate and aggressive treatment with high-dose systemic corticosteroids, continuous albuterol nebulization, and addition of ipratropium bromide to enhance bronchodilation. The most recent and highest quality study 1 recommends that all patients presenting with an asthma exacerbation should be evaluated and triaged immediately, with treatment instituted promptly on determination of a moderate, severe, or life-threatening exacerbation. Primary treatment consists of administration of oxygen, inhaled b2-agonists, and systemic corticosteroids, with the dose and frequency of administration, along with the frequency of patient monitoring, dependent on the severity of the exacerbation. Some key points to consider in the management of refractory asthma exacerbation include:

• Administering high-dose systemic corticosteroids (methylprednisolone 60-125 mg IV or prednisone 40-60 mg orally) and continuous albuterol nebulization (10-15 mg/hour or 2.5-5 mg every 20 minutes) as initial treatment.
• Adding ipratropium bromide (0.5 mg every 20 minutes for 3 doses, then every 2-4 hours) to enhance bronchodilation through a different mechanism, as recommended by the National Asthma Education and Prevention Program Expert Panel Report 3 guidelines for the management of asthma exacerbations 1.
• Considering magnesium sulfate (2 grams IV over 20 minutes) for additional bronchodilation, particularly in severe cases with FEV1 <25-30% predicted.
• Initiating non-invasive positive pressure ventilation (BIPAP) with settings of 10-15 cmH2O inspiratory pressure and 5 cmH2O expiratory pressure to reduce work of breathing and avoid intubation, if necessary.
• Maintaining oxygen saturation >92% and monitoring for pneumothorax throughout treatment.
• Addressing potential triggers like infection with appropriate antibiotics if indicated.
• Developing a comprehensive discharge plan including inhaled corticosteroids, long-acting bronchodilators, and a tapering course of oral steroids (typically prednisone 40-60 mg daily for 5-7 days, then tapered over 1-2 weeks) after stabilization. It is essential to prioritize the patient's morbidity, mortality, and quality of life when making treatment decisions, and to consider the most recent and highest quality evidence available, such as the study by the National Asthma Education and Prevention Program Expert Panel Report 3 guidelines for the management of asthma exacerbations 1.

From the FDA Drug Label

If the patient needs more doses of albuterol sulfate inhalation aerosol than usual, this may be a marker of destabilization of asthma and requires re-evaluation of the patient and treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids. The use of beta-adrenergic-agonist bronchodilators alone may not be adequate to control asthma in many patients. Early consideration should be given to adding anti-inflammatory agents, e.g., corticosteroids, to the therapeutic regimen.

The management of refractory asthma exacerbation may require re-evaluation of the patient and treatment regimen. Consideration should be given to adding anti-inflammatory agents, such as corticosteroids, to the therapeutic regimen, as beta-adrenergic-agonist bronchodilators alone may not be adequate to control asthma in many patients 2.

From the Research

Management of Refractory Asthma Exacerbation

• Refractory asthma exacerbation poses a significant clinical challenge, and its management requires a systematic approach to evaluate adherence, ensure a correct diagnosis, and identify coexisting disorders and trigger factors 3.
• Patients with severe refractory asthma often require regular oral corticosteroid use, which increases the risk of steroid-related adverse events 3.
• Immunomodulatory and biologic therapies may be considered for patients with severe refractory asthma, but their efficacy varies across studies, limiting their generalizability 3.
• The use of ipratropium bromide in combination with beta2-agonists has been shown to improve lung function and reduce hospitalization rates in acute asthma exacerbations 4, 5.
• For adults with severe asthma, low-dose oral corticosteroids (≤7.5 mg/day prednisone equivalent) may be added as the last choice 6.
• Biologic therapy may be considered for patients with severe type 2 asthma, and those who respond well to type 2-targeted biologic therapies can prioritize decreasing or stopping maintenance oral corticosteroid therapy 6.
• The treatment of severe refractory asthma involves the use of various biological options, including monoclonal antibodies, which target specific molecular mechanisms and can help achieve asthma control without oral corticosteroids 7.

Treatment Options

• Inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) are commonly used in the treatment of asthma, and their combination has been shown to demonstrate synergistic anti-inflammatory and anti-asthmatic effects 6.
• Triple combination inhalers can be prescribed to improve symptoms, lung function, and reduce exacerbations when asthma remains uncontrolled on medium- or high-dose ICS-LABA 6.
• Subcutaneous immunotherapy may be considered for adults with asthma who are sensitized to house dust mites, and it can reduce symptoms and the required dosage of ICS 6.
• Bronchial thermoplasty is indicated for adult patients whose asthma remains uncontrolled despite optimized asthma treatment and referral to a specialist severe asthma center 6.

Diagnosis and Assessment

• A bronchial provocation test should be considered when forced expiratory volume in one second (FEV1) is ≥70% predicted, excluding respiratory infections within the past 4 weeks 6.
• Diagnostic anti-inflammatory therapy may be initiated to confirm the diagnosis of asthma if certain criteria are met, including a positive response to a bronchodilation test or FEV1 variability ≥12% and absolute change ≥200 ml between two prior tests 6.
• Induced sputum eosinophil is a gold standard biomarker for airway inflammation assessment, asthma phenotype classification, corticosteroid response prediction, and exacerbation risk assessment 6.
• Peripheral blood eosinophil ≥ 150/μl can be used to identify the eosinophil phenotype or type 2 inflammatory endotype and predict biologic responses 6.