Diagnosis Of Aspirin-exacerbated Respiratory Disease Research Articles

Is endoscopic sinus surgery sufficient to modify the evolution of adult AERD? Aspirin desensitization as a maintenance factor: systematic review.

Aspirin desensitization (AD) and aspirin therapy after desensitization (ATAD) are therapeutic interventions for patients with aspirin-exacerbated respiratory disease (AERD). Our aim is to investigate whether its addition to endoscopic sinus surgery (ESS) improves the overall prognosis of the disease. A systematic review of the current literature including adult patients with a positive diagnosis of AERD undergoing endoscopic sinus surgery (ESS) in the context or in absence of upper airway comorbidity, prior to AD + ATAD. This review concludes that the surgical approach is beneficial in AERD, but its effects are short-lived. Surgery should be considered initially with subsequent AD + ATAD in AERD patients, due to the sustained improvement achieved compared to those receiving ESS alone.

SNIFFING AROUND FOR CLINICAL SCREENING MARKERS TO PREDICT AERD IN CRSWNP PATIENTS

<h3>Introduction</h3> Aspirin-exacerbated respiratory disease(AERD) is a sub-group of chronic rhinosinusitis with nasal polyps(CRSwNP) associated with asthma and cyclooxygenase-1 inhibitor sensitivity. AERD pathogenesis involves dysregulation of arachidonic acid metabolism which favors pro-inflammatory mediator overproduction. A significant proportion of AERD patients are suspected to be undiagnosed, as aspirin sensitivity is frequently unreported. There are no standard AERD screening modalities but aspirin challenge(AC) is an effective diagnostic tool. <h3>Methods</h3> A retrospective, observational study was conducted from 1/1/2016-12/29/2021. 210 subjects met inclusion criteria of CRSwNP patients who underwent AC, desensitization or had clinically diagnosed AERD. Baseline level of serum eosinophils(EOS), basophils, immunoglobulins, complements, tryptase, spot urine leukotriene E4(LTE4), fractional exhaled nitric oxide(FeNO) and Lund-Mackay CT-sinus score(LMCT) were evaluated. 33 subjects on biologic therapy were excluded. <h3>Results</h3> AERD was diagnosed in 74/177(41.80%) subjects. 61 subjects denied NSAID sensitivity and then completed AC, from which 14/61(22.95%) were positive. Several markers showed significant correlation with positive AC including LMCT, EOS and LTE4. Total complement(CH50) showed a slight but significant negative trend with positive AC but values remained within normal range. Other markers showed no correlation. <h3>Conclusion</h3> Contemporary literature reports different AERD endotypes which may obscure clinical phenotypes and hamper diagnosis. Clinical markers could prove valuable screening tools for atypical phenotypes. Prior studies have correlated AERD with serum basophils, EOS, IgE, LTE4 and LMCT. Our data correlates AERD diagnosis with LMCT, EOS, LTE4 and CH50. Further studies are needed to confirm our CH50 results. These clinical, laboratory and radiologic markers could prove useful screening tools for identifying candidates for AC.

The Challenge Of When To Challenge: An Investigation Into Aspirin-Exacerbated Respiratory Disease (AERD) Screening Methodology

Aspirin-exacerbated respiratory disease(AERD), a phenotype of chronic rhinosinusitis with nasal polyposis(CRSwNP), has a distinct pathophysiology and therapeutic approach. NSAID allergy is a frequently unreported but essential AERD feature that leads to missed diagnoses. Aspirin challenge is the predominant practice for diagnosis of obscured AERD cases. Reports suggest a correlation between AERD and elevated markers including eosinophils, basophils, serum IgE and urine leukotriene E4(LTE4), but data is inconclusive. We sought to identify clinical screening markers for CRSwNP correlating with positive challenge and AERD diagnosis.

Clinical evaluation and diagnosis of aspirin-exacerbated respiratory disease

Clinical evaluation and diagnosis of aspirin-exacerbated respiratory disease

COVID-19 in a series of patients with aspirin-exacerbated respiratory disease

COVID-19 in a series of patients with aspirin-exacerbated respiratory disease

Dupilumab increases aspirin tolerance in aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease (AERD) is a triad of asthma, nasal polyposis, and intolerance to nonsteroidal anti-inflammatory drugs. Although AERD affects 7% of patients with asthma and 10% of patients with nasal polyposis, it may affect up to 25% to 30% of patients with both asthma and nasal polyps. 1 White AA Stevenson DD. Aspirin-exacerbated respiratory disease. N Engl J Med. 2018; 379: 2281-2282 PubMed Google Scholar Furthermore, although many patients are diagnosed based on their clinical history, the gold standard of diagnosis remains an aspirin challenge. After the diagnosis of AERD, treatment is often stepwise, aimed at controlling both lower and upper airway inflammation with topical corticosteroids and leukotriene modifiers. For patients failing typical therapies, aspirin desensitization has been found to improve symptoms, decrease reliance on medications, including systemic steroids, and increase the interval between the surgical interventions for nasal polyposis. 2 Berges-Gimeno MP Simon RA Stevenson DD. Long-term treatment with aspirin desensitization in asthmatic patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2003; 111: 180-186 Abstract Full Text Full Text PDF PubMed Scopus (265) Google Scholar

The importance of timely diagnosis of aspirin-exacerbated respiratory disease for patient health and safety.

BackgroudAspirin-exacerbated respiratory disease (AERD) is a difficult-to-treat syndrome where timely diagnosis and initiation of disease-specific therapies are pertinent to improved patient outcomes.ObjectiveTo characterize the most common timeline for development of the clinical triad [asthma, nasal polyposis, and reactions to nonsteroidal anti-inflammatory drugs (NSAIDs)], identify barriers to prompt diagnosis of AERD, and describe indications for an aspirin challenge to facilitate accurate diagnosis.MethodsSix hundred ninety-seven patients with diagnosed AERD and history of at least one sinus surgery to remove nasal polyps were identified in the Brigham and Women's Hospital AERD registry. Patient reported age at disease onset of asthma, nasal polyposis, and age of first NSAID reaction were obtained from 2013 to 2019 at enrollment.ResultsOf the 697 patients identified, diagnosis of asthma preceded diagnosis of nasal polyposis and first NSAID reaction, although there was considerable variability between patients.ConclusionsPrompt diagnosis of AERD is important for patient and provider education and improved care of this difficult-to-treat population of patients. Consider diagnostic aspirin challenge in patients without historical reactions to NSAIDs who have an otherwise compatible clinical history, specifically in patients who take daily low-dose aspirin, leukotriene modifiers, avoid NSAIDs, or who are severely symptomatic at baseline where it would be difficult to identify an acute worsening of symptoms.

Dupilumab as Add-on Therapy for Chronic Rhinosinusitis With Nasal Polyposis in Aspirin Exacerbated Respiratory Disease.

Aspirin-exacerbated respiratory disease (AERD) affects 7% of asthmatics. Usual therapies are inadequate for asthma and/or nasal polyposis, leading to decreased quality of life. Our objective was to evaluate the efficacy of dupilumab in AERD patients with uncontrolled, chronic rhinosinusitis with nasal polyposis (CRSwNP). Patients 18 years and older with a physician diagnosis of AERD and sino-nasal outcome test 22 (SNOT 22) score ≥19 despite standard medical therapy were eligible for the study. Patients received one month of placebo dosing, followed by 6 months of dupilumab. Patients were blinded to the order of therapy. Wilcoxon-paired rank sum test was used to compare study outcomes at baseline and the completion of the study. Ten patients completed the study. The median baseline SNOT 22 score improved from 46 [IQR: 34 to 64.8] to 9.5 [IQR: 2.5 to 19] after 6 months of therapy (p = 0.0050). The median baseline Lund MacKay score improved from 21.5 [IQR: 17 to 23.3] to 4 [IQR: 1.2 to 6] after 6 months of therapy (p = 0.0050). There was also improvement in the following secondary outcomes: asthma control test (ACT), mini asthma quality of life questionnaire (AQLQ), and University of Pennsylvania Smell Identification test (UPSIT). Exhaled nitric oxide (FeNO), total serum IgE, 24-hour urinary leukotriene E4, and serum thymus and activation regulated cytokine (TARC) also decreased. There were no significant study-related adverse events. Dupilumab was highly effective as add-on therapy for CRSwNP in AERD, improving patient-reported outcomes, sinus opacification, and markers of T2 inflammation.

A Comparison of Sphenoid Sinus Osteoneogenesis in Aspirin-Exacerbated Respiratory Disease.

BackgroundAspirin-exacerbated respiratory disease (AERD) is characterized by excessive leukotriene production, diffuse polyp burden and osteitic bone changes. These bony changes have not been previously characterized.ObjectiveThe aim of this radiographic study is to characterize the bony changes noted on computed tomography (CT) scans of the sphenoid sinus in patients with AERD compared to other diseased sinonasal inflammatory states and non-diseased controls.MethodsA retrospective review of 43 patients with clinically confirmed AERD were included and compared to 22 non-diseased, 9 allergic fungal sinusitis, and 43 chronic rhinosinusitis controls (23 without polyps and 18 with polyps). Comparative measurements were performed using fine-cut CT scans. Sites of comparison were the intersinus septum, the left and right lateral sphenoid wall, the roof, and left and right floor of the sphenoid sinus. Standardized measurements were averaged by two separate rhinologists.ResultsPatients with AERD had an average statistically significant increase in bone thickness compared to healthy and diseased controls in nearly every site with the most pronounced changes in the intersinus septum (p < 0.05).ConclusionPatients with AERD have significantly increased thickness of the sphenoid bone compared to control groups with the most pronounced difference in the intersinus septum. These findings may help clinicians increase suspicion for a diagnosis of AERD who clinically have diffuse nasal polyposis.

Aspirin-exacerbated respiratory disease: longitudinal assessment of a large cohort and implications of diagnostic delay.

Aspirin-exacerbated respiratory disease (AERD) refers to the combination of asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and acute respiratory tract reactions to ingestion of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). There have been no in the literature investigating diagnostic delay in AERD. We aimed to investigate whether delay of diagnosis of AERD is associated with poorer clinical outcomes as well as to characterize the role of specialty evaluation in diagnosis. We conducted a retrospective observational study of 254 subjects with incident AERD diagnoses between 2009 and 2016 among Kaiser Permanente Northern California (KPNC) members. Descriptive and bivariate statistics were employed to analyze clinical characteristics and outcomes of AERD subjects with and without delay in diagnosis (defined as 1 year or greater from symptom onset to diagnosis). Of the 254 patients in the AERD cohort, 24.4% had a delayed diagnosis. Patients with allergies were significantly less likely to have a delay in diagnosis (p < 0.01). Patients with a delay in diagnosis were more likely to have 2 or more courses of systemic steroids (p = 0.04). Allergists, otolaryngologists, and primary care physicians diagnosed 56%, 36%, and 8% of patients, respectively. There was no association between provider specialty at time of diagnosis and delay in diagnosis (p = 0.22). A substantial proportion of AERD patients have a diagnostic delay. Patients with allergies have a lower risk for this delay. This study is the first to describe diagnostic delay in AERD patients.

Effect of Zileuton Treatment on Sinonasal Quality of Life in Patients with Aspirin-Exacerbated Respiratory Disease.

Background Aspirin-exacerbated respiratory disease (AERD) is a subtype of chronic sinusitis comprised of asthma, chronic rhinosinusitis with nasal polyps, and a non-IgE hypersensitivity to cyclooxygenase-1 inhibitors. AERD is typically refractory to medical and often surgical management and causes significant quality-of-life concerns for patients. Objective This study aimed to retrospectively assess the rhinologic disease-specific outcomes as well as quality-of-life metrics in a cohort of AERD patients who medically manage their condition with zileuton, a 5-lipoxygenase inhibitor. Methods Retrospective review of 45 patients at a tertiary care center with diagnosis of AERD who underwent functional endoscopic sinus surgery (FESS) with at least 6 months of pre- and postoperative clinical data were included in the study. Zileuton cohort chosen based on intention-to-treat after initial FESS. Background data collected included patient demographics, surgery information, and zileuton initiation dates. Zileuton and control cohorts were followed for 2.8 and 2.4 years, respectively. Outcomes measured were rhinosinusitis disability index (RSDI) scores, antibiotics use, corticosteroid use, otolaryngology visits, and time to revision surgery. Results RSDI scores, antibiotics use, corticosteroid use, otolaryngology visits, and time to revision surgery had no statistically significant difference between cohorts. However, those taking zileuton tended to undergo fewer revision surgeries during the study. Conclusion Zileuton therapy for AERD patients shows no statistical benefit for rhinologic quality-of-life symptoms but may be useful in diminishing frequency of surgical intervention. In addition, pulmonary symptoms may be improved by treatment but were not assessed. Future study is warranted.

A One-day, 90-minute Aspirin Challenge and Desensitization Protocol in Aspirin-Exacerbated Respiratory Disease

Aspirin challenge and desensitization remains the gold standard in diagnosis and treatment of patients with aspirin-exacerbated respiratory disease (AERD), but the protocols can be time and resource intensive. The objective of this study is to provide evidence that oral aspirin challenge and desensitization can be safely performed in an outpatient setting in one day. Forty-four patients with confirmed diagnosis of AERD, stable asthma and baseline FEV1 ≥70% of predicted completed an oral aspirin challenge and desensitization protocol. The starting dose was 40.5mg with escalating doses of aspirin (81, 162.5, 325mg) at 90-minute intervals until symptoms were provoked. Desensitization was defined as tolerating a repeated administration of the provocative dose and at least one subsequent aspirin dose, bringing total aspirin ingested during the in-clinic desensitization to ≥325mg. Ninety-three percent of patients completed the challenge and desensitization in one day, with an average protocol completion time of 9 hours and 29 minutes. Two patients (4.6%) chose to complete the protocol over two days. One patient (2.3%) was discontinued from the protocol due to on-going abdominal discomfort and diarrhea. No patient required epinephrine, emergency department visit or hospitalization. Patients with AERD on a stable asthma regimen and with a baseline FEV1≥70% can be safely desensitized to aspirin using a 90-minute dose escalation protocol, starting at a dose of 40.5mg, and defining desensitization as tolerance of the repeated provocation dose and at least one subsequent aspirin dose, bringing total cumulative daily dose to ≥325mg. This protocol can routinely be completed in one day.

Sinus Surgery Is Associated with a Decrease in Aspirin-Induced Reaction Severity in Patients with Aspirin Exacerbated Respiratory Disease

Nasal polyps influence the burden of aspirin-exacerbated respiratory disease (AERD) by contributing to eicosanoid production. AERD is diagnosed through graded aspirin challenges. It is not known how sinus surgery affects aspirin challenge outcomes. To investigate the effects of endoscopic sinus surgery (ESS) on aspirin-induced reaction severity and on the levels of eicosanoids associated with these reactions. Twenty-eight patients with AERD were challenged with aspirin before and 3 to 4 weeks after ESS. Respiratory parameters and plasma and urine levels of eicosanoids were compared before and after challenges. Before ESS, AERD diagnosis was confirmed in all study patients by aspirin challenges that resulted in hypersensitivity reactions. After ESS, reactions to aspirin were less severe in all patients and 12 of 28 patients (43%, P < .001) had no detectable reaction. A lack of clinical reaction to aspirin was associated with lower peripheral blood eosinophilia (0.1 K/μL [interquartile range (IQR) 0.1-0.3] vs 0.4 K/μL [IQR 0.2-0.8]; P= .006), lower urinary leukotriene E4 levels after aspirin challenge (98 pg/mg creatinine [IQR 61-239] vs 459 pg/mg creatinine [IQR 141-1344]; P= .02), and lower plasma prostaglandin D2 to prostaglandin E2 ratio (0[±0] vs 0.43 [±0.2]; P= .03), compared with those who reacted. Sinus surgery results in decreased aspirin sensitivity and a decrease in several plasma and urine eicosanoid levels in patients with AERD. Diagnostic aspirin challenges should be offered to patients with suspected AERD before ESS to increase diagnostic accuracy. Patients with established AERD could undergo aspirin desensitizations after ESS as the severity of their aspirin-induced hypersensitivity reactions lessens.

A 1-Day, 90-Minute Aspirin Challenge and Desensitization Protocol in Aspirin-Exacerbated Respiratory Disease

Aspirin challenge and desensitization remains the criterion standard in diagnosis and treatment for patients with aspirin-exacerbated respiratory disease (AERD), but the protocols can be time and resource intensive. To provide evidence that oral aspirin challenge and desensitization can be safely performed in an outpatient setting in 1 day. Forty-four patients with a confirmed diagnosis of AERD, stable asthma, and baseline FEV1 value greater than or equal to 70% of predicted completed an oral aspirin challenge and desensitization protocol. The starting dose was 40.5 mg with escalating doses of aspirin (81, 162.5, 325 mg) at 90-minute intervals until symptoms were provoked. Desensitization was defined as tolerating a repeated administration of the provocative aspirin dose and at least 1 subsequent dose, bringing the total aspirin ingested during the in-clinic desensitization to 325 mg or more. Ninety-three percent of patients completed the challenge and desensitization in 1 day, with an average protocol completion time of 9 hours and 29 minutes. Two patients (4.6%) chose to complete the protocol over 2 days. One patient (2.3%) was discontinued from the protocol because of ongoing abdominal discomfort and diarrhea. No patient required epinephrine, emergency department visit, or hospitalization. Patients with AERD on a stable asthma regimen and with a baseline FEV1 value greater than or equal to 70% can be safely desensitized to aspirin using a 90-minute dose escalation protocol, starting at a dose of 40.5 mg, and defining desensitization as tolerance of the repeated provocation dose and at least 1 subsequent aspirin dose, bringing total cumulative daily dose to 325 mg or more. This protocol can routinely be completed in 1 day.

Diagnostic Accuracy of Urinary LTE4 Measurement to Predict Aspirin-Exacerbated Respiratory Disease in Patients with Asthma

Patients with aspirin-exacerbated respiratory disease (AERD) are distinguished from patients with aspirin-tolerant asthma (ATA) by significantly higher baseline concentrations of urinary leukotriene E4 (uLTE4). However, an overlap between the individual values of the groups exists. The objective of this study was to estimate the discriminative value of uLTE4 concentration in differentiating between patients with AERD and patients with ATA and evaluate the diagnostic accuracy of uLTE4 measurement alone and added to clinical parameters to predict AERD diagnosis in patients with asthma. Clinical data were collected from questionnaires. Spirometry, skin prick tests, total IgE, and blood eosinophilia were evaluated. ULTE4 concentrations were measured in morning urine samples by enzyme-linked immune assay (ELISA). Patients with AERD (n= 247) had significantly higher uLTE4 concentrations than those with ATA (n= 239). The uLTE4 concentration of 800.0 pg/mg creatinine as measured by ELISA on a spot sample best discriminated the 2 groups (area under the curve 0.7; 95% confidence interval 0.66-0.74, sensitivity 49%, specificity 81%). The positive predictive value and negative predictive value (NPV), after considering the prevalence of AERD in the population of asthmatics, were 16% and 96%, respectively. Nasal polyps, upper airway symptoms, nasal corticosteroid treatment, asthma exacerbations, forced expiratory volume in the 1 second predicted, and age of asthma onset were independent predictors of AERD diagnosis. The addition of elevated uLTE4 concentration to the set of clinical parameters enhanced slightly the prediction of AERD diagnosis beyond the level predicted by clinical parameters (P= .036). A set of typical clinical parameters has a superior accuracy in prediction of AERD diagnosis than the measurement of uLTE4 concentration alone. The addition of uLTE4 concentration to clinical parameters slightly enhances the prediction of AERD diagnosis, especially due to a high NPV.

Nasal Ketorolac Challenge Using Acoustic Rhinometry in Patients With Aspirin-Exacerbated Respiratory Disease.

Safer and less time-consuming alternatives to single-blind placebo-controlled oral challenge (SBPCOC) have been sought for the diagnosis of aspirin-exacerbated respiratory disease (AERD). Nasal challenges with various nonsteroidal anti-inflammatory drugs and assessment methods have been developed. Objective: Our objective was to evaluate the utility and safety of nasal ketorolac challenge (NKC) using acoustic rhinometry in patients with suspected AERD. The study population comprised 36 patients with suspected AERD. NKC was performed with placebo (saline) and 13 mg of ketorolac sprayed as aerosol into both nostrils. A positive challenge result was defined as an increase of ≥30% in nasal symptoms (recorded using a visual analog scale) and a 30% drop in the sum of the volumes of both nasal cavities at 2-8 cm. Patients with a negative NKC result underwent SBPCOC with aspirin (cumulative dose of 750 mg). A naso-ocular reaction during NKC was detected in 21 patients. Four patients also developed mild asthma exacerbations (although only 1 experienced a decrease in FEV1 >15%). No other significant adverse events occurred. The remaining 15 patients with a negative NKC result had a negative response during aspirin SBPCOC. NKC assessed using acoustic rhinometry is a reliable method for the study of patients with AERD. We suggest that NKC assessed with acoustic rhinometry was useful and safe for selection of candidates for safe oral aspirin challenge.

Aspirin-exacerbated respiratory disease: an update.

The pathophysiology of aspirin-exacerbated respiratory disease (AERD) is not fully understood and diagnostic methods and so far, treatments for AERD have not been standardized. We summarize recent research into the pathological mechanisms of AERD, diagnostic methods, and treatments for AERD patients. In AERD pathophysiology, not only the reduced expression of E prostanoid 2 but also the dysfunction of its pathway could be involved. Moreover, eosinophils of AERD patients could be directly activated by aspirin to produce prostaglandin D2. Platelet activations are well known to be involved in AERD; however, plasma markers do not change during aspirin challenge tests. Additionally, novel genetic polymorphisms, such as P2RY12 and dipeptidyl peptidase 10 gene, and epigenetic predispositions of AERD were found. In AERD diagnosis, bronchial and nasal aspirin challenges have been applied in addition to oral challenge. Serum periostin has been suggested as a potential biomarker for AERD. Apart from standard pharmacological treatment and aspirin desensitization, biologics, including omalizumab and mepolizumab, as well as CRTH2 antagonists have been suggested as promising therapies for AERD treatment. AERD is usually associated with severe asthma phenotypes. AERD pathophysiology mainly involves the dysregulation of eicosanoid metabolisms, activations of effector cells, which could be influenced by genetic/epigenetic factors. Understanding the pathophysiology of AERD is key to improve the diagnostic methods and proper management of AERD patients.

Contemporary management of chronic rhinosinusitis with nasal polyposis in aspirin-exacerbated respiratory disease: an evidence-based review with recommendations.

Chronic rhinosinusitis (CRS) in aspirin-exacerbated respiratory disease (AERD) represents a recalcitrant form of sinonasal inflammation for which a multidisciplinary consensus on patient management has not been reached. Several medical interventions have been investigated, but a formal comprehensive evaluation of the evidence has never been performed. The purpose of this article is to provide an evidence-based approach for the multidisciplinary management of CRS in AERD. A systematic review of the literature was performed and the guidelines for development of an evidence-based review with recommendations were followed. Study inclusion criteria included: adult population >18 years old; CRS based on published diagnostic criteria, and a presumptive diagnosis of AERD. We focused on reporting higher-quality studies (level 2 or higher) when available, but reported lower-quality studies if the topic contained insufficient evidence. Treatment recommendations were based on American Academy of Otolaryngology (AAO) guidelines, with defined grades of evidence and evaluation of research quality and risk/benefits associated with each treatment. This review identified and evaluated the literature on 3 treatment strategies for CRS in AERD: dietary salicylate avoidance, leukotriene modification, and desensitization with daily aspirin therapy. Based on the available evidence, dietary salicylate avoidance and leukotriene-modifying drugs are options following appropriate treatment with nasal corticosteroids and saline irrigation. Desensitization with daily aspirin therapy is recommended following revision endoscopic sinus surgery (ESS).

Automated identification of an aspirin-exacerbated respiratory disease cohort

Aspirin-exacerbated respiratory disease (AERD) is characterized by 3 clinical features: asthma, nasal polyposis, and respiratory reactions to cyclooxygenase-1 inhibitors (nonsteroidal anti-inflammatory drugs). Electronic health records (EHRs) contain information on each feature of this triad. We sought to determine whether an informatics algorithm applied to the EHR could electronically identify patients with AERD. We developed an informatics algorithm to search the EHRs of patients aged 18years and older from the Partners Healthcare system over a 10-year period (2004-2014). Charts with search terms for asthma, nasal polyps, and record of respiratory (cohort A) or unspecified (cohort B) reactions to nonsteroidal anti-inflammatory drugs were identified as "possible AERD." Two clinical experts reviewed all charts to confirm a diagnosis of "clinical AERD" and classify cases as "diagnosed AERD" or "undiagnosed AERD" on the basis of physician-documented AERD-specific terms in patient notes. Our algorithm identified 731 "possible AERD" cases, of which 638 were not in our AERD patient registry. Chart review of cohorts A(n=511) and B (n=127) demonstrated a positive predictive value of 78.4% for "clinical AERD," which rose to 88.7% when unspecified reactions were excluded. Of those with clinical AERD, 12.4% had no mention of AERD by any treating caregiver and were classified as "undiagnosed AERD." "Undiagnosed AERD" cases were less likely than "diagnosed AERD" cases to have been seen by an allergist/immunologist (38.7% vs 93.2%; P<.0001). An informatics algorithm can successfully identify both known and previously undiagnosed cases of AERD with a high positive predictive value. Involvement of an allergist/immunologist significantly increases the likelihood of an AERD diagnosis.

Utility of low-dose oral aspirin challenges for diagnosis of aspirin-exacerbated respiratory disease

BackgroundAspirin-exacerbated respiratory disease (AERD) is diagnosed through graded aspirin challenges that induce hypersensitivity reactions and eicosanoid level changes. It is not known whether diagnostically useful changes also occur after low-dose aspirin challenges that do not induce hypersensitivity reactions. ObjectiveTo investigate the utility of low-dose oral aspirin challenges for diagnosing AERD by measuring different clinical parameters and eicosanoid changes. MethodsSixteen patients with AERD and 13 patients with aspirin-tolerant asthma underwent oral challenges with low-dose (20 or 40 mg) aspirin and diagnostic oral graded aspirin challenges (up to 325 mg of aspirin). Forced expiratory volume in 1 second, nasal peak flow, the fraction of exhaled nitric oxide (FeNO), and eicosanoid levels in plasma and urine were analyzed. ResultsIn patients with AERD but not in those with aspirin-tolerant asthma, 40-mg aspirin challenges induced a significant mean (SEM) decrease from baseline in FeNO (19% [5.1%]; P = .001) without causing any hypersensitivity reaction. The FeNO decrease also occurred after higher-dose aspirin challenges (27.8% [4.9%]; P < .001). The sensitivity and specificity of 40-mg aspirin-induced FeNO changes for identifying AERD were 90% and 100% with an area under the curve of 0.98 (95% CI, 0.92–1.00). The low-dose challenge also induced a significant leukotriene E4 urine increase in patients with AERD (from 6.32 [0.08] to 6.91 [0.15] log-pg/mg creatinine; P < .001), but the sensitivity and specificity of these changes were less than for the FeNO changes. ConclusionThe low-dose aspirin-induced decrease in FeNO in patients with AERD may be useful for the diagnosis of aspirin allergy without inducing a hypersensitivity reaction. Trial Registrationclinicaltrials.gov Identifier: NCT01320072.