Aspirin-Exacerbated Respiratory Disease (AERD)

Epidemiology

History

  • 1902: aspirin sensitivity was a first described with aspirin exposure in an asthmatic patient
  • 1968: Samter and Beers described the triad of asthma, aspirin sensitivity, and nasal polyps, now known as “Samter’s triad” (Ann Intern Med, 1968) [MEDLINE]

Definition

  • Aspirin-Exacerbated Respiratory Disease
    • Asthma (see Asthma)
    • Chronic Rhinosinusitis with Nasal Polyposis
    • Reaction to Aspirin and Other COX-1 Inhibiting NSAID’s: with clinical symptoms of nasal congestion and bronchoconstriction beginning 20-180 min after exposure

Prevalence

  • Overall Prevalence from Meta-Analysis of 27 Studies
    • Aspirin-Exacerbated Respiratory Disease is Present in Approximately 7.15% of Typical Adult Asthma Patients and Approximately 14.89% of Patients with Severe Asthma (J Allergy Clin Immunol, 2015) [MEDLINE]
      • Prevalence in Patients with Chronic Rhinosinusitis: 8.7%
      • Prevalence in Patients with Nasal Polyposis: 9.69%
  • Iranian Study of Prevalence
    • Aspirin-Exacerbated Respiratory Disease is Common in Patients with Chronic Rhinosinusitis and Nasal Polyposis in Tehran, Iran (Am J Rhinol Allergy, 2014) [MEDLINE]

Etiology

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Physiology

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Diagnosis

Complete Blood Count (CBC) (see Complete Blood Count)

  • Peripheral Eosinophilia (see Peripheral Eosinophilia, [[Peripheral Eosinophilia]])
    • Peripheral Eosinophilia Occurs in Approximately 50% of Cases (Ann Allergy Asthma Immunol, 2013) [MEDLINE]
    • Degree of Peripheral Eosinophilia Correlates with the Severity of Chronic Rhinosinusitis (Arch Otolaryngol Head Neck Surg, 2007) [MEDLINE]

Serum Immunoglobulin E (IgE) (see Serum Immunoglobulin E, [[Serum Immunoglobulin E]])

  • Serum IgE is Variably Elevated and Does Not Does Not Appear to be Correlated with the Degree of Mucosal Sinus Disease (by CT) (Arch Otolaryngol Head Neck Surg, 2007) [MEDLINE]

Clinical Manifestations

General Comments

  • Natural History
    • Aspirin-Exacerbated Respiratory Disease is Usually Diagnosed in Adulthood
    • Symptoms Relevant to the Three Components of the Triad Usually Develop Sequentially Over a Period of Years (Eur Respir J, 2000) [MEDLINE] and Clin Rev Allergy Immunol, 2003) [MEDLINE]
      • However, Some Cases Present with Rapid Progression of Sinus/Nasal Symptoms to Asthma
  • Precipitation of Symptoms by Alcohol Consumption (see Ethanol, [[Ethanol]])
    • Ethanol Ingestion Precipitating Symptoms Has Been Reported in 77% of Patients with Aspirin-Exacerbated Respiratory Disease (by Survey) (J Allergy Clin Immunol Pract, 2015) [MEDLINE]
    • Symptoms Typically Occur within 1 hr of Ethanol Ingestion (J Allergy Clin Immunol Pract, 2014) [MEDLINE]
  • Precipitation of Symptoms by Dietary Elements
    • Dietary Triggers Have Been Reported in 63% of Patients with Aspirin-Exacerbated Respiratory Disease (by Survey) (J Allergy Clin Immunol Pract, 2015) [MEDLINE]

Allergic/Immunologic Manifestations

  • Atopy
    • Epidemiology: approximately 30-70% of patients are atopic
    • Diagnosis: some patients have elevated specific IgE against inhalant antigens (most commonly dust mite antigens)
  • Nonsteroidal Anti-Inflammatory Drug (NSAID) Sensitivity (see Nonsteroidal Anti-Inflammatory Drug, [[Nonsteroidal Anti-Inflammatory Drug]])
    • Epidemiology
      • Typically Develops After the Development of Sinus/Nasal Symptoms (with the Progression to Asthma): although may rarely develop first
        • NSAID Intolerance is an Independent Risk Factor for the Development of Asthma (Int J Epidemiol, 1999) [MEDLINE]
    • NSAID Exposure and Time Course
      • Symptoms Usually Develop 30-180 min After NSAID Exposure (and May Resolve Slowly)
      • Symptoms are Dose-Related: ranging from mild nasal symptoms to status asthmaticus (some cases may result in death)
    • Classical Clinical Features
      • Nasal and Ocular Symptoms
      • Asthmatic Symptoms
        • Chest Tightness (see Chest Pain, [[Chest Pain]])
        • Cough (see Cough, [[Cough]])
        • Wheezing (see Wheezing, [[Wheezing]]): with decrease in FEV1 and clinical response to bronchodilators
    • Other Clinical Features
      • Abdominal Cramps/Epigastric Pain (see Abdominal Pain, [[Abdominal Pain]])
      • Angioedema/Urticaria (see Angioedema, [[Angioedema]] and Urticaria, [[Urticaria]]): occur in approximately 15% of cases
      • Facial Flushing/Erythema (see Erythroderma, [[Erythroderma]])
      • Hypotension (see Hypotension, [[Hypotension]]): may mimic anaphylaxis
      • Laryngospasm (see Laryngospasm, [[Laryngospasm]])

Otolaryngologic Manifestations

  • Chronic Nasal Symptoms
    • Epidemiology
      • Nasal Symptoms/Impaired Sense of Smell are Common (J Allergy Clin Immunol Pract, 2015) [MEDLINE]
    • Diagnosis
      • Sinus CT (see Sinus Computed Tomography, [[Sinus Computed Tomography]])
        • Mucosal Thickening of Paranasal Sinuses
        • Nasal Polyps: rounded mucosal protrusions into the nasal or sinus cavities
    • Clinical: symptoms generally become more severe over time (even with aspirin avoidance)
      • Typically Becomes More Severe Over Time, Even with Aspirin Avoidance
      • Chronic Hypertrophic Eosinophilic Rhinosinusitis (see Chronic Rhinosinusitis, [[Chronic Rhinosinusitis]])
      • Nasal Congestion (see Nasal Congestion, [[Nasal Congestion]])
      • Nasal Polyps (see Nasal Polyps, [[Nasal Polyps]])
      • Refractory Rhinitis (see Rhinitis, [[Rhinitis]]): usually present in the early 30’s
  • Impaired Sense of Smell/Anosmia (se Anosmia, [[Anosmia]])
    • Epidemiology
      • Nasal Symptoms/Impaired Sense of Smell are Common (J Allergy Clin Immunol Pract, 2015) [MEDLINE]

Pulmonary Manifestations

  • Asthma (see Asthma, [[Asthma]])
    • Epidemiology
      • Typically Occurs After the Onset of Rhinosinusitis: however, not all cases develop asthma
    • Clinical: symptoms generally become more severe over time (even with aspirin avoidance)

Other Manifestations

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Treatment

Specific Management of Asthma (see Asthma, [[Asthma]])

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Avoidance of Nonsteroidal Anti-Inflammatory Drugs (NSAID) with COX-1 Inhibitory Properties (see Nonsteroidal Anti-Inflammatory Drug, [[Nonsteroidal Anti-Inflammatory Drug]])

  • NSAID Agents with COX-1 Inhibitory Properties

Leukotriene Modifier Agents

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References

General

  • Intolerance to aspirin. Clinical studies and consideration of its pathogenesis. Ann Intern Med. 1968;68(5):975 [MEDLINE]
  • Prevalence of asthma, aspirin intolerance, nasal polyposis and chronic obstructive pulmonary disease in a population-based study. Int J Epidemiol. 1999;28(4):717 [MEDLINE]
  • Aspirin-induced asthma: advances in pathogenesis, diagnosis, and management. J Allergy Clin Immunol. 2003;111(5):913 [MEDLINE]
  • Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. BMJ. 2004;328(7437):434 [MEDLINE]
  • Aspirin hypersensitivity in patients with chronic rhinosinusitis and nasal polyposis: frequency and contributing factors. Am J Rhinol Allergy. 2014;28(3):239 [MEDLINE]
  • Prevalence of aspirin-exacerbated respiratory disease among asthmatic patients: A meta-analysis of the literature. J Allergy Clin Immunol. 2015;135(3):676 [MEDLINE]

Clinical

  • Chronic sinusitis. Relationship of computed tomographic findings to allergy, asthma, and eosinophilia. JAMA. 1994;271(5):363 [MEDLINE]
  • Natural history of aspirin-induced asthma. AIANE Investigators. European Network on Aspirin-Induced Asthma. Eur Respir J. 2000;16(3):432 [MEDLINE]
  • Local and systemic eosinophilia in patients undergoing endoscopic sinus surgery for chronic rhinosinusitis with and without polyposis. Clin Otolaryngol Allied Sci. 2003 Feb;28(1):55-8 [MEDLINE]
  • Natural history and clinical features of aspirin-exacerbated respiratory disease. Clin Rev Allergy Immunol. 2003;24(2):113 [MEDLINE]
  • Total IgE levels and peripheral eosinophilia: correlation with mucosal disease based on computed tomographic imaging of the paranasal sinus. Arch Otolaryngol Head Neck Surg. 2007 Jul;133(7):701-4 [MEDLINE]
  • Characterization and treatment of patients with chronic rhinosinusitis and nasal polyps. Ann Allergy Asthma Immunol. 2013 Nov;111(5):337-41. Epub 2013 Aug 20 [MEDLINE]
  • Alcohol-induced respiratory symptoms are common in patients with aspirin exacerbated respiratory disease. J Allergy Clin Immunol Pract. 2014;2(2):208 [MEDLINE]
  • Survey-Defined Patient Experiences With Aspirin-Exacerbated Respiratory Disease. J Allergy Clin Immunol Pract. 2015;3(5):711. Epub 2015 Apr 7 [MEDLINE]

Treatment

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