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NSAID-exacerbated respiratory disease (NERD)

Authoring team

NSAIDs are cautioned or contra-indicated in people with asthma, depending on their previous history of NSAID use, as they may worsen asthma symptoms (1).

Patients allergic to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) who develop respiratory reactions such as bronchospasm or asthma exacerbation have aspirin-induced asthma or NSAIDs-exacerbated respiratory disease (NERD) (2).

NSAID-exacerbated respiratory disease (NERD)

  • is a chronic, inflammatory, respiratory disorder occurring in people with asthma and/or chronic rhinosinusitis with nasal polyps, symptoms of which are exacerbated by NSAIDs, including aspirin
  • is a risk of immediate hypersensitivity reactions, bronchospasms and acute asthma exacerbations occurring within 30 minutes to 3 hours of taking an NSAID
    • may be life-threatening in some cases
  • main mechanism by which NSAIDs cause hypersensitivity in people with asthma includes inhibition of cyclooxygenase (COX) enzymes, particularly COX-1
  • been shown in patients with NERD that free immunoglobulin E (IgE) in the circulation tends to increase independently of atopy; on the other hand, the increased local IgE in nasal polyps plays a role in mast cell activation
  • may also be related to the overproduction of leukotrienes; reactions to NSAIDs are likely to be dose-dependent
    • in some cases, people are highly sensitive and develop worsening of their asthma even with low oral doses of NSAIDs such as an aspirin dose of 75mg
  • based on prevalence data, approximately 80-90% of adult asthmatics will be able to tolerate NSAID
  • is a chronic eosinophilic inflammatory airway disease that occurs in patients with asthma and/or chronic rhinosinusitis with nasal polyps (3)

Risk factors for NSAID sensitivity

People who are likely to be at risk of NERD should either avoid using NSAIDs or use them with caution. These include people who are or have:

  • severe or poorly controlled asthma
  • chronic rhinosinusitis and/or profuse rhinorrhoea
  • nasal polyps
  • female gender
  • history of NERD or atopic disease
  • aged 20-50 years
  • long-term smoking
  • family history of asthma or NERD or allergic rhinitis

if NSAID naive

  • use oral or topical NSAIDs with caution and monitor for symptoms such as exacerbation of asthma
  • previous tolerance to NSAIDs
  • use oral or topical NSAIDs with caution and monitor for symptoms such as exacerbation of asthma
  • counsel people on the risk of developing NERD, particularly in later life

History of NERD

  • do not use oral or topical NSAIDs
  • if an NSAID is clinically necessary and there are no suitable alternatives, consider referring the person to an allergy or respiratory specialist for managing and preventing NERD. Treatment options include:
    • NSAID desensitisation therapy (aims to slowly increase a person’s tolerance to NSAIDs)
    • leukotriene receptor agonists (such as montelukast)
    • biological medicines (such as mepolizumab, benralizumab, reslizumab, dupilumab and omalizumab)
  • these treatment options are off-label and may not be suitable for everyone. There are limited and variable efficacy data for using leukotriene receptor agonists and biologics

Currently, aspirin is not recommended for children <12 years of age because it causes severe side effects such as the Reye syndrome (2)

  • therefore, because of safety concerns for children, physicians prescribe NSAIDs instead of aspirin
  • study showed that short-term aspirin, ibuprofen, and diclofenac use probably correlated with asthma exacerbation in children with asthma (2)

Reference:

  1. NHS Specialist Pharmacy Service (July 17th 2024). Using NSAIDs in asthma
  2. Lo PC, Tsai YT, Lin SK, Lai JN. Risk of asthma exacerbation associated with nonsteroidal anti-inflammatory drugs in childhood asthma: A nationwide population-based cohort study in Taiwan. Medicine (Baltimore). 2016 Oct;95(41):e5109.
  3. Tepetam FM, Özden Ş, Kılıç FK, Örçen C, Yakut T. Does NSAID exacerbated respiratory disease (N-ERD) accompanying severe asthma affect biological treatment response? Efficacy of omalizumab and mepolizumab in N-ERD. World Allergy Organ J. 2023 Sep 23;16(9):100817.

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