How should I manage an adult with a cough due to uncontrolled asthma according to current step‑wise asthma guidelines, including both maintenance therapy and acute exacerbation treatment?

Management of Cough Due to Uncontrolled Asthma

For adults with cough due to uncontrolled asthma, immediately initiate or optimize inhaled corticosteroids (ICS) combined with a long-acting β₂-agonist (LABA), then escalate therapy in a stepwise fashion by adding a leukotriene receptor antagonist before considering oral corticosteroids. 1

Initial Assessment and Diagnosis

Before escalating therapy, confirm the diagnosis and exclude common mimics:

• Perform bronchial provocation testing (methacholine challenge) in patients with chronic cough and normal spirometry to demonstrate airway hyperresponsiveness, which distinguishes cough variant asthma from other causes 2, 1
• A negative bronchial provocation test excludes asthma but does not rule out steroid-responsive cough, emphasizing the need for empirical corticosteroid trials in persistent cases 2, 1
• Assess for sputum eosinophilia when available, as this predicts corticosteroid responsiveness and has important treatment implications 2, 1
• Exclude gastroesophageal reflux disease (GERD), as failure to consider GERD is a common reason for treatment failure, and reflux-associated cough may occur without gastrointestinal symptoms 2
• Rule out upper airway disease (rhinosinusitis), ACE inhibitor use, and poor inhaler technique/adherence before escalating therapy 1

Stepwise Maintenance Therapy Algorithm

Step 1: Optimize ICS-LABA Combination Therapy

• Start with low-to-medium dose ICS-LABA (equivalent to beclomethasone 200-800 μg daily) as first-line therapy, as this combination provides synergistic anti-inflammatory and bronchodilatory effects 1, 3
• ICS-LABA demonstrates efficacy equivalent to or better than doubling the ICS dose alone and improves adherence while reducing high-dose ICS-related adverse effects 3
• Never use LABA as monotherapy, as this increases the risk of serious asthma-related events and mortality 1, 4
• Ensure proper inhaler technique using metered-dose inhalers with large volume spacers, or consider dry powder inhalers for ease of use 2, 1
• Allow 4-8 weeks for full therapeutic response, though partial improvement may occur within 1 week 1

Step 2: Increase ICS Dose if Inadequate Response

• Escalate ICS dose up to beclomethasone-equivalent 2000 μg daily while continuing the LABA if cough persists after initial therapy 1, 3
• Reassess compliance and inhaler technique before dose escalation, as apparent treatment failure is often due to poor adherence 2, 1
• Be aware that prolonged high-dose ICS therapy may lead to systemic adverse effects including osteoporosis, hypothalamic-pituitary-adrenal axis suppression, and increased pneumonia risk 3

Step 3: Add Leukotriene Receptor Antagonist (LTRA)

• Add montelukast or another LTRA to the existing ICS-LABA regimen when cough remains refractory after maximal ICS dosing 1, 3
• Leukotriene inhibitors have demonstrated an 88% response rate and can suppress cough even in patients refractory to high-dose ICS alone 1
• This combination has specific evidence supporting efficacy in cough variant asthma through enhanced modulation of inflammatory mediators acting on sensory cough receptors 1

Step 4: Consider Triple Therapy or Oral Corticosteroids

• Triple combination inhalers (ICS-LABA-LAMA) can be prescribed to improve symptoms, lung function, and reduce exacerbations when asthma remains uncontrolled on medium- or high-dose ICS-LABA 3
• For severe or refractory cough, prescribe oral prednisolone 30-40 mg daily for 1-2 weeks, then transition back to inhaled corticosteroids 1, 4, 3
• Approximately 80% of patients require ongoing long-term ICS therapy to maintain cough suppression after completing the oral steroid course 1
• Low-dose oral corticosteroids (≤7.5 mg/day prednisone equivalent) may be added as a last choice for adults with severe asthma 3

Acute Exacerbation Management

Early Intervention for Mild-to-Moderate Exacerbations

• When using budesonide-formoterol as maintenance and reliever therapy, patients may take 1-2 additional inhalations (160/4.5 μg strength) in early exacerbations, not exceeding 8 inhalations daily 3
• Short-acting β₂-agonists remain the preferred reliever medication for acute symptom relief 5

Severe Exacerbations Requiring Systemic Corticosteroids

• Administer prednisolone 30-40 mg daily (or equivalent) until lung function returns to previous best, typically 7 days but may require up to 21 days 2
• Oral steroids are equally effective as intravenous administration and offer no disadvantages 2
• When used in short courses up to two weeks, oral steroids do not need to be tapered; they can be stopped from full dosage 2
• Deliver short-acting β₂-agonists via nebulizer or large volume spacer depending on exacerbation severity 2

Special Considerations for Cough Variant Asthma

• Treatment principles for cough variant asthma are identical to typical asthma, with most patients responding to ICS or ICS-LABA 3, 6
• ICS-LABA is recommended as first choice and should be used for more than 8 weeks to prevent progression to classic asthma 3, 6
• For CVA patients with poor therapeutic response and severe airway inflammation, consider adding LTRA or short-term oral corticosteroids (10-20 mg/day for 3-5 days) 3
• 30-40% of adult patients with cough variant asthma may progress to classic asthma unless adequately treated with inhaled corticosteroids 6

Assessment of Treatment Response and Refractory Cases

• Measure sputum eosinophil counts or fractional exhaled nitric oxide (FENO) in patients with persistent cough despite treatment, as ongoing eosinophilia identifies those who may benefit from more aggressive anti-inflammatory therapy 1
• Patients without sputum eosinophilia do not respond to corticosteroids, suggesting alternative diagnoses should be considered 1
• If asthma remains uncontrolled despite Step 4 treatment with correct inhaler technique and adherence, refer to asthma specialists or specialized clinics for further evaluation 3
• Consider biologic agents (anti-IgE, anti-IL-5, anti-IL-5Rα, anti-IL-4Rα monoclonal antibodies) for patients with severe allergic and eosinophilic asthma 3, 5

Common Pitfalls to Avoid

• Do not jump directly to systemic steroids without trying inhaled therapy first, as this exposes patients to unnecessary systemic side effects when inhaled medications are highly effective 4
• Avoid cough suppressants when cough clearance is important, as suppression may be relatively contraindicated 2
• Do not prescribe newer non-sedating antihistamines for asthma cough management, as they are completely ineffective 4
• In the presence of prominent upper airway symptoms, trial topical corticosteroid rather than relying on antihistamines with disparity in reported efficacy 2
• For patients with cough and typical reflux symptoms, offer empirical treatment with intensive acid suppression (proton pump inhibitors and alginates for minimum 3 months) before oesophageal testing 2

Follow-Up and Monitoring

• Schedule follow-up visits every 2-4 weeks after initial therapy, then every 1-3 months if there is a response 3
• Regularly train patients in correct inhaler technique, as this is essential for optimal asthma control 3
• Use validated tools such as the Asthma Control Test or asthma APGAR to assess control at subsequent visits 5
• A systematic approach to diagnosis and treatment remains the most effective way to manage chronic cough, combining selected diagnostic testing with empirical trials of treatment 2