What is the best treatment approach for a patient with a history of asthma or chronic obstructive pulmonary disease (COPD) who is allergic to salbutamol (albuterol) and experiencing a chronic cough?

Management of Chronic Cough in Patients with Asthma/COPD Who Are Allergic to Salbutamol

In patients with asthma or COPD experiencing chronic cough who cannot use salbutamol due to allergy, initiate treatment with inhaled corticosteroids combined with alternative bronchodilators such as ipratropium bromide (anticholinergic) or tiotropium, while simultaneously addressing the most common causes of chronic cough through sequential empiric therapy starting with first-generation antihistamine/decongestant combinations for upper airway cough syndrome. 1, 2

Initial Critical Actions

Discontinue ACE inhibitors immediately if the patient is taking one, as this alone can resolve cough within days to 2 weeks (median 26 days) in affected patients 2, 3. This is a common overlooked cause that must be addressed before proceeding with other treatments.

Counsel aggressive smoking cessation, as 90% of patients with chronic bronchitis will have cough resolution after quitting 2, 3. This is non-negotiable for smokers.

Obtain chest radiograph and spirometry to rule out serious pathology and assess for obstructive or restrictive patterns before initiating empiric therapy 1, 2.

Sequential Treatment Algorithm for Chronic Cough

Step 1: Treat Upper Airway Cough Syndrome (UACS) First (Weeks 1-2)

Start with a first-generation antihistamine/decongestant combination (such as brompheniramine with sustained-release pseudoephedrine) as first-line empiric therapy 1, 2. This addresses UACS, the most common cause of chronic cough.

• Newer non-sedating antihistamines are ineffective for UACS and should not be used 2, 3
• Expect initial response within 1-2 weeks, though complete resolution may take several weeks to months 1, 2
• Add intranasal corticosteroids if nasal symptoms persist after initial treatment 1, 2
• Consider sinus imaging if symptoms persist despite topical therapy to evaluate for sinusitis 1

Step 2: Treat Asthma/COPD Component (Weeks 2-6)

For patients with asthma causing chronic cough who cannot use salbutamol, initiate inhaled corticosteroids (ICS) as the primary controller medication 1, 2. ICS addresses the underlying airway inflammation that drives cough in asthma.

Add ipratropium bromide as the bronchodilator of choice for patients allergic to salbutamol 1. For acute severe asthma attacks, use ipratropium 500 µg combined with oxygen, repeated 4-6 hourly if improving 1.

For COPD patients, consider tiotropium (long-acting anticholinergic) as an alternative maintenance bronchodilator 4. Tiotropium is indicated for long-term maintenance treatment of COPD including chronic bronchitis and emphysema, and has demonstrated efficacy in reducing COPD exacerbations 4.

Add leukotriene receptor antagonists (LTRAs) to the regimen, as these appear particularly effective in treating cough due to asthma and can be used before escalating to oral corticosteroids 1, 2.

If cough persists despite ICS and alternative bronchodilators, give a limited trial of oral corticosteroids (prednisone 40 mg/day for 5-10 days) to definitively establish or exclude asthma as the cause 1. Complete resolution of asthmatic cough may require up to 8 weeks of treatment 1.

Step 3: Treat Gastroesophageal Reflux Disease (GERD) (Months 1-3)

If cough persists after treating UACS and asthma, initiate proton pump inhibitor (PPI) therapy with dietary modifications 1, 2, 3. GERD is the third most common cause of chronic cough.

• Assess response over 1-3 months, as GERD-related cough takes longer to resolve 2, 3
• Do not assume GERD is ruled out if empiric treatment fails—the therapy may not have been intensive enough 2

Step 4: Consider Non-Asthmatic Eosinophilic Bronchitis (NAEB)

If diagnoses of UACS and asthma have been eliminated or treated without cough resolution, consider NAEB with induced sputum testing for eosinophils 1. If testing cannot be performed, an empiric trial of inhaled corticosteroids should be the next step 1, 2.

Alternative Bronchodilator Options for Salbutamol-Allergic Patients

Ipratropium bromide (short-acting anticholinergic) is the primary alternative for acute symptom relief in patients who cannot use salbutamol 1. Dosing for acute severe asthma is 500 µg added to treatment regimen, repeated as needed 1.

Tiotropium (long-acting anticholinergic) is appropriate for maintenance therapy in COPD patients, dosed as two inhalations once daily 4. However, tiotropium is not indicated for asthma treatment 4.

Levalbuterol (R-albuterol) may be considered if the allergy is specifically to the S-isomer of racemic salbutamol, though this would require careful allergy evaluation 5, 6, 7, 8. Levalbuterol provides bronchodilation at lower doses than racemic albuterol with potential for reduced adverse effects 8.

Critical Pitfalls to Avoid

Never assume a single cause—use sequential AND additive therapy as multiple conditions frequently coexist (UACS, asthma, and GERD often occur together) 1, 2, 3. Do not stop partially effective treatments when adding new therapies 2.

Do not use newer non-sedating antihistamines for UACS treatment—they are completely ineffective and first-generation agents are required 2, 3.

Do not use tiotropium or other long-acting anticholinergics for acute asthma exacerbations—these are maintenance medications only 4. Use ipratropium bromide for acute situations 1.

Exercise caution with ipratropium in elderly patients with glaucoma risk—consider using a mouthpiece rather than mask to minimize ocular exposure 1.

Monitor patients with moderate to severe renal impairment closely for anticholinergic effects when using tiotropium 4.

When to Refer or Escalate

Refer to a cough specialist if cough remains undiagnosed after systematically treating UACS, asthma/COPD, and GERD 1, 2. This typically means 4-6 weeks of sequential empiric therapy for all three common causes has failed 2.

Red flags requiring immediate investigation include: fever, night sweats, weight loss, hemoptysis, history of tuberculosis or cancer, or abnormal chest radiograph 2.

Consider bronchoprovocation testing with methacholine if available and if the diagnosis of asthma remains uncertain despite normal spirometry 1. A negative test essentially excludes asthma from the differential diagnosis 1.

Expected Timeline for Resolution

• UACS: 1-2 weeks for initial improvement, several weeks to months for complete resolution 1, 2, 3
• Asthma: 2-8 weeks, with some patients requiring oral corticosteroids for definitive response 1, 2
• GERD: 1-3 months 2, 3
• Overall resolution may require maintaining all partially effective treatments for several months 2, 3