What is the management approach for a patient with poorly controlled asthma without elevated inflammatory markers?

From the Guidelines

For poorly controlled asthma without elevated inflammatory markers, I recommend a step-up in therapy while investigating potential alternative diagnoses, prioritizing the addition of a long-acting beta-agonist (LABA) to an inhaled corticosteroid (ICS) as the initial step, as suggested by the most recent and highest quality study 1. This approach is based on the understanding that well-controlled asthma can only be achieved in approximately 70% of patients across the strata of severity, and that a progressive increase in inhaled corticosteroid/long-acting beta2 agonist therapy may be necessary to achieve symptom control and reduce the risk of exacerbations 1. Key considerations in managing poorly controlled asthma include:

• Ensuring proper inhaler technique and adherence to current medications
• Adding a LABA like salmeterol or formoterol to an ICS such as fluticasone or budesonide in a combination inhaler, with typical combinations including Advair (fluticasone/salmeterol) or Symbicort (budesonide/formoterol) taken twice daily
• If symptoms persist, considering the addition of a long-acting muscarinic antagonist like tiotropium (Spiriva Respimat, 2.5 mcg, 2 inhalations once daily)
• Evaluating for alternative diagnoses such as vocal cord dysfunction, GERD, chronic sinusitis, or other conditions that mimic asthma, as the absence of elevated inflammatory markers suggests possible non-Type 2 inflammation or alternative diagnoses
• Addressing comorbidities and triggers is essential, as non-inflammatory asthma may respond better to bronchodilators than to increasing steroid doses A pulmonology referral is warranted if symptoms remain uncontrolled despite these interventions, as emphasized by the need for ongoing assessment of disease control and timely referrals 1.

From the Research

Poorly Controlled Asthma with No Elevated Markers

• Asthma is a major public health problem worldwide, associated with excess morbidity, mortality, and economic costs 2.
• The National Asthma Education and Prevention Program has released updated evidence-based recommendations for the treatment of patients with asthma, including the use of intermittent inhaled corticosteroids, add-on long-acting muscarinic antagonists, and fractional exhaled nitric oxide testing 2.
• For patients with poorly controlled asthma, the use of inhaled corticosteroids/long-acting β2-agonists (such as fluticasone furoate/vilanterol or budesonide/formoterol) may improve symptom control and reduce the risk of severe asthma exacerbations 3.
• A retrospective matched cohort study found that treatment with fluticasone furoate/vilanterol was associated with lower use of short-acting β2-agonists and fewer asthma-related exacerbations compared to budesonide/formoterol 3.
• The study suggests that the use of once-daily fluticasone furoate/vilanterol may be an effective treatment option for patients with asthma, particularly those with poorly controlled symptoms 3.

Treatment Options

• The 2020 Asthma Guideline Update recommends the use of daily low-dose inhaled corticosteroids plus as-needed short-acting β2-agonists for rescue therapy in patients with mild persistent asthma 2.
• For patients with moderate persistent asthma, the guideline recommends the use of formoterol in combination with an inhaled corticosteroid in a single inhaler (single maintenance and reliever therapy) 2.
• Add-on long-acting muscarinic antagonists are recommended for patients whose asthma is not controlled by inhaled corticosteroid-formoterol therapy 2.