How do Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) cause bronchospasm?

From the Guidelines

NSAIDs can trigger bronchospasm primarily through their inhibition of the cyclooxygenase (COX) enzyme pathway, leading to an increase in leukotriene production, which are potent bronchoconstrictors, as noted in the study by 1. When NSAIDs like aspirin, ibuprofen, naproxen, or diclofenac block COX-1 enzymes, they prevent the production of protective prostaglandins while simultaneously shunting arachidonic acid metabolism toward the lipoxygenase pathway. This mechanism is particularly significant in patients with aspirin-exacerbated respiratory disease (AERD), also known as Samter's triad, which includes asthma, nasal polyps, and aspirin sensitivity, as described in the study by 1. In susceptible individuals, even a single dose of an NSAID can trigger severe bronchospasm within minutes to hours of ingestion. The reaction is not a true allergy but rather a pharmacological effect. Some key points to consider include:

• The prevalence of NSAID-exacerbated respiratory disease is higher in adults with asthma, approximately 10-20% compared to the general population, as mentioned in the study by 1.
• Patients with a history of NSAID-induced bronchospasm should avoid all traditional NSAIDs and consider alternative pain relievers like acetaminophen (paracetamol) or, under medical supervision, selective COX-2 inhibitors like celecoxib, which may be better tolerated, as suggested by 1.
• It is essential to identify NSAID hypersensitivity in patients to enable avoidance and consideration of aspirin desensitization in those who are sensitized, as noted in the study by 1.

From the FDA Drug Label

A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, celecoxib capsules are contraindicated in patients with this form of aspirin sensitivity When celecoxib capsules are used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.

NSAIDs can cause bronchospasm in patients with aspirin-sensitive asthma, which may include severe, potentially fatal bronchospasm.

• This is due to cross-reactivity between aspirin and other NSAIDs in aspirin-sensitive patients.
• Patients with preexisting asthma should be monitored for changes in the signs and symptoms of asthma when using NSAIDs 2, 2, 2.

From the Research

Mechanism of NSAID-Induced Bronchospasm

• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) induce bronchospasm in some asthma patients by inhibiting cyclooxygenase-1 (Cox-1) 3
• This inhibition activates the lipoxygenase pathway, leading to an increase in the release of cysteinyl leukotrienes (Cys-LTs) that induce bronchospasm and nasal obstruction 3
• NSAID-intolerant asthmatic patients have higher basal levels of Cys-LT than NSAID-tolerant asthmatics, and their Cys-LT levels increase remarkably following NSAID provocation testing 3

Clinical Evidence of NSAID-Induced Bronchospasm

• Between 8-20 percent of adult asthmatics experience bronchospasm following ingestion of aspirin and other NSAIDs, a condition known as aspirin-induced asthma 4
• Asthmatics with chronic rhinitis or a history of nasal polyps are at greater risk of developing bronchospasm after taking NSAIDs 4
• Symptoms of NSAID-induced bronchospasm can occur within 20 minutes to 3 hours of taking a NSAID and include bronchospasm, rhinorrhoea, dyspnoea, cough, or urticaria-angiodema 4

Safety of COX-2 Inhibitors in Aspirin-Induced Asthma

• COX-2 inhibitors, such as celecoxib, are safe in patients with aspirin-induced asthma and do not cause bronchospasm 5, 6
• Studies have shown that celecoxib does not affect lung function or urinary excretion of leukotriene E(4) (LTE(4)) in patients with aspirin-induced asthma 5
• Another COX-2 inhibitor, rofecoxib, has also been shown to be safe in patients with aspirin-induced asthma, with no changes in urinary LTE(4) or 9alpha11betaPGF2 levels 7