What are the pulmonary side effects of Lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor)?

Pulmonary Side Effects of Lisinopril

The most common and significant pulmonary side effect of lisinopril is a persistent dry cough, occurring in approximately 5-10% of patients (up to 50% in Chinese patients), which is a class effect of all ACE inhibitors and is the most common reason for discontinuation of these medications. 1

Cough Characteristics

• Typically dry and nonproductive
• Associated with a persistent and annoying "tickle" in the back of the throat
• Usually appears within the first months of therapy (can occur within hours to months after starting)
• Disappears within 1-4 weeks after discontinuation (may take up to 3 months in some cases)
• Recurs within days of rechallenge with the same or different ACE inhibitor
• Not dose-dependent
• More common in:
  • Women
  • Nonsmokers
  • Chinese patients (nearly 50% incidence vs. 5-10% in white patients)

Mechanism of ACE Inhibitor-Induced Cough

The cough is likely related to:

• Accumulation of bradykinin in the upper respiratory tract
• Increased levels of substance P (a neurochemical mediator of the cough reflex)
• Stimulation of prostaglandin E2 production
• Stimulation of lung afferent C fibers

Management of Lisinopril-Induced Cough

1. Rule out other causes of cough first, particularly pulmonary congestion
2. Confirm diagnosis by demonstrating that cough disappears after drug withdrawal and recurs after rechallenge
3. Treatment options:
   • If cough is not severe, encourage continued use of lisinopril due to long-term benefits 1
   • If cough is persistent and troublesome, consider:
     • Discontinuing lisinopril (only uniformly effective treatment)
     • Switching to an angiotensin receptor blocker (ARB) as alternative therapy 1, 2
     • Pharmacologic agents that may attenuate cough (though evidence is limited):
       • Inhaled sodium cromoglycate
       • Theophylline
       • NSAIDs
       • Calcium channel blockers
       • Ferrous sulfate

Other Pulmonary Considerations

• Angioedema: Occurs in <1% of patients taking ACE inhibitors (more frequent in Black patients)

  • Can be life-threatening
  • If suspected, requires permanent discontinuation of all ACE inhibitors
  • ARBs may be considered as alternative therapy, though cross-reactivity has been reported 1

• Bronchospasm: Not specifically mentioned in the evidence for lisinopril, but caution is advised in patients with asthma or reactive airway disease

Monitoring Recommendations

• Monitor for cough development, particularly within the first few months of therapy
• If cough develops, evaluate for other potential causes before attributing to lisinopril
• If lisinopril is discontinued due to cough, expect resolution within 1-4 weeks (may take up to 3 months)
• When switching to an ARB, be aware that a small percentage of patients may still experience cough, though at a significantly lower rate than with ACE inhibitors 2

Remember that while cough is annoying and may significantly impact quality of life, it is not dangerous. The decision to discontinue lisinopril should balance the benefits of ACE inhibitor therapy against the impact of cough on the patient's quality of life.