Aspirin intolerance in asthma: Detection by oral challenge

doi:10.1016/0091-6749(72)90014-0

Journal of Allergy and Clinical Immunology

Volume 50, Issue 4, October 1972, Pages 198-207

https://doi.org/10.1016/0091-6749(72)90014-0 Get rights and content

Abstract

Oral aspirin challenge was used to detect aspirin intolerance in selected asthmatic patients who did NOT give a history of asthma following aspirin ingestion. Forty-two asthmatic patients with either nasal polyps, sinusitis, or severe asthma requiring corticosteroid therapy were challenged with aspirin. Under carefully controlled circumstances and at a time when their asthma was stable, patients ingested 640 mg. of aspirin (Ascriptin) after taking all their usual maintenance medications. Several parameters of lung function and clinical symptomatology were followed serially over a 4 hour period. Eight of 42 challenges were positive. When these patients were combined with 14 patients who were intolerant to aspirin by history, the prevalence of aspirin intolerance in our asthmatic population was 8 per cent. Patients who were intolerant to aspirin showed a statistically significant increase in the prevalence of the hallmark criteria of nasal polyps, sinusitis, and steroid dependency when compared to all new asthmatic patients during a 2 year period. Aspirin challenge in selected patients can detect aspirin intolerance not recognized by history alone. These patients can be warned to avoid aspirin ingestion in the future. In addition, their management can be improved by recognizing this variant of the asthma syndrome.

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Inhaled drug delivery for the targeted treatment of asthma
2023, Advanced Drug Delivery Reviews
Asthma is a chronic lung disease affecting millions worldwide. While classically acknowledged to result from allergen-driven type 2 inflammatory responses leading to IgE and cytokine production and the influx of immune cells such as mast cells and eosinophils, the wide range in asthmatic pathobiological subtypes lead to highly variable responses to anti-inflammatory therapies. Thus, there is a need to develop patient-specific therapies capable of addressing the full spectrum of asthmatic lung disease. Moreover, delivery of targeted treatments for asthma directly to the lung may help to maximize therapeutic benefit, but challenges remain in design of effective formulations for the inhaled route. In this review, we discuss the current understanding of asthmatic disease progression as well as genetic and epigenetic disease modifiers associated with asthma severity and exacerbation of disease. We also overview the limitations of clinically available treatments for asthma and discuss pre-clinical models of asthma used to evaluate new therapies. Based on the shortcomings of existing treatments, we highlight recent advances and new approaches to treat asthma via inhalation for monoclonal antibody delivery, mucolytic therapy to target airway mucus hypersecretion and gene therapies to address underlying drivers of disease. Finally, we conclude with discussion on the prospects for an inhaled vaccine to prevent asthma.
Effect of LTRA in L-ASA Challenge for Aspirin-Exacerbated Respiratory Disease Diagnosis
2021, Journal of Allergy and Clinical Immunology: In Practice
Aspirin-exacerbated respiratory disease (AERD) consists of asthma, chronic rhinosinusitis with polyps, and hypersensitivity to aspirin and/or nonsteroidal anti-inflammatory drugs (NSAIDs). Nasal Lysine Aspirin Challenge is an effective tool for the diagnosis of hypersensitivity to aspirin and/or NSAIDs in patients with AERD. However, there is no unified international consensus version to perform nasal provocation tests (NPTs).
To investigate the effect of a leukotriene receptor antagonist (LTRA), montelukast, on the lysine-acetylsalicylate (L-ASA) nasal challenge.
We included 86 patients divided into 3 samples: group A (AERD without LTRA), group B (AERD with LTRA), and the control group (NSAID-tolerant asthmatics). NPT with L-ASA was performed with 25 mg of L-ASA every 30 minutes 4 times followed by rhinomanometry and spirometric measurements and evaluation of symptoms using a novel clinical scale.
In group A, 94.5% of patients (35 of 37) developed a positive response to NPT (drop >40% in total nasal flow), whereas only 46% of group B subjects (13 of 28) showed a positive response to the nasal challenge (P < .001). Control subjects did not show any response to the L-ASA challenge. A novel clinical score demonstrated accuracy in classifying the hypersensitivity to aspirin and/or NSAIDs when patients avoid LTRA (33 of 37).
Patients with AERD without LTRA showed a greater positive response to the L-ASA challenge than those taking this drug; therefore, LTRA treatment should be discontinued before the challenge for optimal diagnostic accuracy.
Genetic and Epigenetic Components of Aspirin-Exacerbated Respiratory Disease
2016, Immunology and Allergy Clinics of North America
Citation Excerpt :
The gold standard for diagnosis of AERD is oral aspirin challenge to provoke symptomatic response.91 During this response, CysLT production is dramatically increased, precipitating symptoms.88,89,91,92 After diagnosis, significant improvement in asthma symptoms and slowing of NP recurrence are achieved with aspirin desensitization and daily high-dose aspirin treatment.90
Prevalence of aspirin-exacerbated respiratory disease among asthmatic patients: A meta-analysis of the literature
2015, Journal of Allergy and Clinical Immunology
Citation Excerpt :
After database search and removal of duplicates, a total of 159 articles were identified for full-text review (Fig 1). These were assessed on the basis of inclusion/exclusion criteria, and a manual search was performed on all references of chosen studies, resulting in a total of 27 studies; the characteristics of these studies are listed in Table II.1-3,9-32 Of those in which oral challenges were performed (n = 6), 3 were single blind, 1 was open, and in 2 the blinding was not specified.
Aspirin-exacerbated respiratory disease (AERD) is manifested by adult-onset asthma, nasal polyposis, chronic rhinosinusitis, and aspirin sensitivity. Previously reported prevalence rates have been widely variable based on the population studied, method of diagnosis, and definition of aspirin sensitivity.
We sought to determine the prevalence of AERD among asthmatic adults.
A systematic review of databases was performed to identify all clinical trials published on or before June 16, 2013, that evaluated the prevalence of AERD. The studies were clustered into 7 different groups based on underlying disease (asthma, nasal polyps or chronic rhinosinusitis, or both), as well as on the methodology of prevalence determination.
A total of 1770 articles were identified, with 27 considered appropriate for inclusion. Prevalence rates of AERD ranged from 5.5% to 12.4% based on study type. Among all studies in asthmatic patients, regardless of method, the prevalence of AERD was 7.15% (95% CI, 5.26% to 9.03%). The prevalence of AERD was highest among patients with severe asthma (14.89% [95% CI, 6.48% to 23.29%]). Among patients with nasal polyps and chronic rhinosinusitis, the prevalence was 9.69% (95% CI, 2.16% to 17.22%) and 8.7% (95% CI, −1.02% to 18.34%), respectively.
AERD is a distinct and important subtype of asthma and polypoid sinus disease. The prevalence of AERD is 7% in typical adult asthmatic patients and twice that number in patients with severe asthma, which underscores the importance of recognizing this disorder. Early identification of this syndrome is critical in view of the increased morbidity and costs associated with asthma exacerbations and the option to treat patients with AERD with long-term aspirin treatment after desensitization.
Use of nasal inspiratory flow rates in the measurement of aspirin-induced respiratory reactions
2013, Annals of Allergy, Asthma and Immunology
Citation Excerpt :
Aspirin-exacerbated respiratory disease (AERD) is an aggressive inflammatory disease that consists of chronic hyperplastic eosinophilic sinusitis and nasal polyposis, asthma, and aspirin hypersensitivity.1 Although the prevalence of AERD ranges in all asthmatics from 7% to 10.6%, it may be up to 19.5% in patients with pansinusitis and nasal polyposis, making it a relatively common and important diagnosis that pulmonologists and allergists must consider.2,3 Although it has been previously shown that aspirin desensitization can improve different clinical outcomes, it is underused because it is time consuming and occasionally causes severe bronchospasm and adverse extrapulmonary effects.4-6
Nasal ketorolac challenge with modified oral aspirin challenge is a safe and effective alternative for desensitizing patients with aspirin-exacerbated respiratory disease. In addition to clinical judgment, objective tests assessing nasal flow may help in diagnosing nasal reactions.
To evaluate the feasibility of peak nasal inspiratory flow (PNIF) as an objective measurement in the assessment of a reaction to nasal ketorolac and to determine changes in PNIF that have adequate sensitivity and specificity.
One hundred fifty-one patients referred to the Scripps Clinic for aspirin challenge and desensitization and 14 healthy controls participated in the study. Percentages of decrease in PNIF during reactions were compared with the nonreactors' measurements. A receiver operating characteristic curve was constructed to assess the diagnostic performance of PNIF measurement during a clinically positive nasal challenge.
A total of 165 subjects participated in the study. One hundred fourteen patients (69.1%) clinically reacted to the nasal ketorolac challenge. There was no statistical difference between nasal reactors and nonreactors regarding sex, baseline forced expiratory volume in 1 second, and use of systemic steroid before challenge. The mean percentage of decrease in PNIF was significantly higher in the reactor group (−0.30 ± 0.29 vs −0.07 ± 0.16, P < .001). A cutoff value of 25% decrease in PNIF had the maximum sensitivity and specificity (56.1% and 94.1%).
The high specificity of a 25% decrease in PNIF found in receiver operating characteristic curve analysis indicated that PNIF measurements can be useful for assessing nasal reactions during nasal ketorolac challenges in the diagnosis of aspirin-exacerbated respiratory disease.
The prevalence of aspirin-induced asthma in Saudian asthmatic patients
2010, Allergologia et Immunopathologia
Aspirin-induced asthma (AIA), is a distinct clinical syndrome affecting some asthmatic patients. Although the name of the condition relates to aspirin, it is well established that affected patients are cross-sensitive to all non-steroidal anti-inflammatory drugs (NSAIDs).
Assessing the prevalence of AIA among Saudian asthmatic patients.
This is a retrospective study of the medical records of asthmatic patients.
The prevalence of AIA in the patients studied was found to be 12.6%. Statistical analyses indicated that AIA was associated with more severe asthma [odds ratio (OR) (95% Confidence interval (CI)) in Group I cases 2.86 (1.24 to 6.59) respectively (p<0.05)]. The results showed that some allergic conditions were significantly more common in Group I for allergic rhinitis (OR=2.19, 95% CI 0.89–5.37, p<0.05), pollinosis (OR=1.59, 95% CI 0.85–2.98, p<0.05) for antibiotic allergy (OR=1.25, 95% CI 0.65–2.41, p<0.05) and for atopic dermatitis (OR=1.34, 95% CI 0.70–2.55, p<0.05). Family history of allergy had a more significant role in Group I cases (OR=1.27, 95% CI 0.68–2.37, p<0.05). No gender difference on asthma severity was detected in either group (Chi²=2.19, p>0.05).
The prevalence of respiratory symptoms triggered by aspirin/NSAID use was 12.6% in the asthmatics studied. AIA appears to be a significant problem and further investigations of the mechanisms of these responses and the possible link between this syndrome and other allergic co-morbidities are required.

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^☆: Supported in part by Grant, No. AI-00214 and AI-10386 from the National Institutes of Health.

^☆☆: Presented in part at the Annual Meeting of the American Academy of Allergy, San Francisco, Calif., February 7, 1972.

^∗: United States Army-sponsored Allergy Fellowship Trainee.

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Aspirin intolerance in asthma: Detection by oral challenge☆,☆☆

Abstract

Lancet

J. Allergy

J. Allergy

J. Allergy

J. Allergy

J. Allergy

J. Allergy

Allergy in drug idiosyncrasy

J. A. M. A

Mittheilung über ein Fall von Nebenwirkung des Aspirin

Dtsch. Med. Wochenschr

Hypersensitivity to acetylsalicylic acid (aspirin)

J. A. M. A

Effect of salicylates in urticaria

Br. Med. J