Can ipratropium bromide (anticholinergic) be used to improve cough in patients with chronic obstructive pulmonary disease (COPD)?

Ipratropium Bromide for Cough in COPD

Ipratropium bromide should be offered to patients with chronic bronchitis/COPD to improve cough symptoms, as it reduces cough frequency and severity while also decreasing sputum volume. 1

Mechanism and Efficacy

• Ipratropium bromide is an anticholinergic (parasympatholytic) agent that inhibits vagally mediated reflexes by antagonizing acetylcholine action, preventing increases in intracellular cyclic GMP that cause bronchial smooth muscle contraction 2
• Long-term studies have demonstrated that ipratropium bromide therapy in stable patients with chronic bronchitis results in patients coughing fewer times with less severe cough 1
• The bronchodilatory effect is primarily local and site-specific rather than systemic, with minimal systemic absorption (only about 7% of an administered dose) 2
• Clinical studies show significant improvements in pulmonary function (FEV₁ increases of 15% or more) within 15-30 minutes of administration, reaching peak effect in 1-2 hours and persisting for 4-5 hours in most patients 2, 3

Dosing and Administration

• The standard recommended dosage is two inhalations (36 micrograms) four times daily via metered-dose inhaler 4
• When administered as a nebulized solution, the optimal dose appears to be 0.4 mg, which provides superior bronchodilation compared to the metered-dose inhaler 3
• The bronchodilatory effect begins within 15 minutes, with a mean dose-dependent duration of effect of three to five hours 4

Comparison with Other Bronchodilators

• In stable COPD patients, ipratropium bromide's bronchodilator action is at least equal to, and in most cases superior to, sympathomimetic agents or methylxanthines in terms of both peak effect and duration of action 5
• While tiotropium (a newer long-acting anticholinergic) shows improved lung function, fewer hospital admissions, and better quality of life compared to ipratropium bromide, studies specifically examining tiotropium's effect on cough have not shown significant improvement 6, 1
• The American College of Chest Physicians (ACCP) evidence-based guidelines give ipratropium bromide a grade A recommendation for improving cough in stable patients with chronic bronchitis 1

Clinical Considerations and Caveats

• Unlike short-acting β-agonists which show inconsistent results for cough improvement, ipratropium bromide has demonstrated more reliable effects on cough reduction 1
• In addition to reducing cough frequency and severity, ipratropium bromide significantly decreases the volume of sputum expectorated 1
• For acute exacerbations of chronic bronchitis, ipratropium bromide is recommended alongside short-acting β-agonists, with the addition of the other agent at maximal dose if the patient doesn't show prompt response 1
• Adverse effects are generally mild and include cough, dry mouth, nervousness, and gastrointestinal distress 4
• The incidence of anticholinergic adverse events possibly related to treatment is very low (approximately 1%) 7

Treatment Algorithm

1. For stable COPD patients with chronic cough:

   • Start with ipratropium bromide 36 μg (2 inhalations) four times daily 4
   • Monitor for improvement in cough frequency and severity 1

2. If response is inadequate:

   • Consider adding a short-acting β-agonist for additional bronchodilation and potential cough relief 1
   • For patients with severe airflow obstruction (FEV₁ < 50%) or frequent exacerbations, consider adding an inhaled corticosteroid with a long-acting β-agonist 1

3. For acute exacerbations:

   • Use ipratropium bromide or short-acting β-agonists as first-line therapy 1
   • Add the other agent at maximal dose if response is inadequate 1
   • Avoid theophylline during acute exacerbations 1