Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus that is defined by the histologic finding of esophageal eosinophilia (≥15 eosinophils/high-power field [eos/hpf]) in the presence of symptoms of esophageal dysfunction.1 The prevalence of EoE in the general population is estimated at 0.05% and has been increasing worldwide.2 In adults, typical symptoms of EoE include solid food dysphagia and esophageal food impactions. Patients may also experience nausea, vomiting, abdominal pain, and reflux.

When Portier and Richet demonstrated in 1902 that repeated injections of a foreign substance could lead to increasingly severe reactions up to and including rapid death, they used a jellyfish toxin to immunize dogs and the Greek term ἀνά-φύλαξισ or nonprotection. Thus there is no doubt that animal models can provide important information about these reactions and that they can be very severe. In their article in the current issue of the Journal of Allergy and Clinical Immunology, Gertie et al1Gertie J.A. Zhang B. Liu E.G. Hoyt L.R. Yin X. Xu L. et al.Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations.J Allergy Clin Immunol. 2022; 149: 262-274Abstract Full Text Full Text PDF Scopus (2) Google Scholar present a detailed investigation of the factors influencing the severity of allergic reactions in 2 strains of mice. The data presented provide compelling evidence that the differences in reactions following oral exposure are not due to genetic differences in Toll-like receptor 4 or dedicator of cytokinesis 8, which had been proposed, and do not reflect differences between C3H/HeJ and C57BL/6 mice either in IgE responses to peanut or in the microbiome. On the other hand, they demonstrate significantly increased levels of gut absorption in the C3H/HeJ mice that correlate with their reactions to oral challenge.1Gertie J.A. Zhang B. Liu E.G. Hoyt L.R. Yin X. Xu L. et al.Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations.J Allergy Clin Immunol. 2022; 149: 262-274Abstract Full Text Full Text PDF Scopus (2) Google Scholar Speaking as known agnostics about the use of mouse models to study allergic disease, Gertie et al1Gertie J.A. Zhang B. Liu E.G. Hoyt L.R. Yin X. Xu L. et al.Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations.J Allergy Clin Immunol. 2022; 149: 262-274Abstract Full Text Full Text PDF Scopus (2) Google Scholar create an opportunity to consider which aspects of anaphylaxis in mice can provide useful or even important information about the phenomenon in humans. Several criticisms of animal models of anaphylaxis are well known. In mice, the primary marker used to assess reactions is a decrease in body temperature, which has not been recognized as a useful marker of reactions in humans. In most mouse studies, all the animals are fully inbred and essentially identical genetically; thus, demonstrating differences between 2 or more strains is not comparable to reporting results on 260 outbred Homo sapiens patients.2Wilson J.M. Schuyler A.J. Workman L. Gupta M. James H.R. Posthumus J. et al.Investigation into the alpha-Gal syndrome: characteristics of 261 children and adults reporting red meat allergy.J Allergy Clin Immunol Pract. 2019; 7: 2348-2358.e4Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar On the other hand, there are many questions that are difficult to approach in patients or healthy subjects, and some interesting experiments that are truly impossible. We would like to focus on 2 elements that are a challenge in our own current work. First, it would be ill-advised to propose carrying out experimental studies that include immunizing naive human individuals if the sensitization could lead to a potentially dangerous outcome. Second, some reactions to food, even in subjects with high-titer IgE antibodies, take 3 or more hours to occur and nonetheless can be severe. Carrying out food challenges to investigate anaphylaxis, especially when symptom onset can be delayed by as much as 4 hours, is a challenge for the investigators3Commins S.P. James H.R. Stevens W. Pochan S.L. Land M.H. King C. et al.Delayed clinical and ex vivo response to mammalian meat in patients with IgE to galactose-alpha-1,3-galactose.J Allergy Clin Immunol. 2014; 134: 108-115Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar (Fig 1). Experiments in naive mice have established that immunization through mildly abraded or tape-stripped skin can induce serum IgE antibodies, leading to sensitization of an unexposed organ such as the lungs.4Spergel J.M. Mizoguchi E. Brewer J.P. Martin T.R. Bhan A.K. Geha R.S. Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice.J Clin Invest. 1998; 101: 1614-1622Crossref PubMed Scopus (507) Google Scholar This has provided extensive background for understanding the relevance of skin exposure to the onset of peanut allergy.5Brough H.A. Nadeau K.C. Sindher S.B. Alkotob S.S. Chan S. Bahnson H.T. et al.Epicutaneous sensitization in the development of food allergy: what is the evidence and how can this be prevented?.Allergy. 2020; 75: 2185-2205Crossref PubMed Scopus (48) Google Scholar In addition, the mouse experiments have provided a solid background for the investigation of tick bites as a cause of sensitization to cetuximab and red meat.6Chandrasekhar J.L. Cox K.M. Loo W.M. Qiao H. Tung K.S. Erickson L.D. Cutaneous exposure to clinically relevant lone star ticks promotes IgE production and hypersensitivity through CD4+ T Cell–and MyD88-dependent pathways in mice.J Immunol. 2019; 203: 813-824Crossref PubMed Scopus (18) Google Scholar,7Choudhary S.K. Karim S. Iweala O.I. Choudhary S. Crispell G. Sharma S.R. et al.Tick salivary gland extract induces alpha-gal syndrome in alpha-gal deficient mice.Immun Inflamm Dis. 2021; 9: 984-990Crossref PubMed Scopus (4) Google Scholar A recent series of experiments used tick saliva extracts to immunize alpha-gal knockout (AGKO) mice.7Choudhary S.K. Karim S. Iweala O.I. Choudhary S. Crispell G. Sharma S.R. et al.Tick salivary gland extract induces alpha-gal syndrome in alpha-gal deficient mice.Immun Inflamm Dis. 2021; 9: 984-990Crossref PubMed Scopus (4) Google Scholar Those studies produced high titers of IgE antibodies as well as marked increases in total IgE level. Furthermore, the mice reacted rapidly to oral challenge with pork kidney allergens. Another problem is to understand why most clinical reactions to mammalian meat in individuals with IgE to galactose alpha-1,3-galactose are delayed.2Wilson J.M. Schuyler A.J. Workman L. Gupta M. James H.R. Posthumus J. et al.Investigation into the alpha-Gal syndrome: characteristics of 261 children and adults reporting red meat allergy.J Allergy Clin Immunol Pract. 2019; 7: 2348-2358.e4Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar Gertie et al1Gertie J.A. Zhang B. Liu E.G. Hoyt L.R. Yin X. Xu L. et al.Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations.J Allergy Clin Immunol. 2022; 149: 262-274Abstract Full Text Full Text PDF Scopus (2) Google Scholar report measurements of ovalbumin protein entering the circulation within 30 minutes after gavage. In keeping with the stronger allergic reactions, they also document greater quantities of ovalbumin in the circulation of C3H/HeJ mice than in other mouse strains, including C57BL/6. Interestingly, the recent studies of challenges of alpha-gal–sensitized mice using homogenized pork kidney reported a rapid decrease in temperature in the AGKO mice, which are on a C57BL/6 background (Fig 1).7Choudhary S.K. Karim S. Iweala O.I. Choudhary S. Crispell G. Sharma S.R. et al.Tick salivary gland extract induces alpha-gal syndrome in alpha-gal deficient mice.Immun Inflamm Dis. 2021; 9: 984-990Crossref PubMed Scopus (4) Google Scholar In a sense, the results of that study challenge the possibility that the C57BL/6 mice have a general difference that decreases gut absorption of foreign antigens. On the other hand, these observations in 2 different models of gut absorption using mice bring to light the difficulty of studying delayed absorption in humans or in mouse studies. This is particularly relevant to food-related exercise-induced anaphylaxis and delayed reactions to red meat. In patients with food-dependent exercise-induced anaphylaxis, the response depends on exposure to a specific allergen followed by exercise up to 3 hours later (Fig 1).8Christensen M.J. Eller E. Mortz C.G. Brockow K. Bindslev-Jensen C. Wheat-dependent cofactor-augmented anaphylaxis: a prospective study of exercise, aspirin, and alcohol efficacy as cofactors.J Allergy Clin Immunol Pract. 2019; 7: 114-121Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar The interesting point here is that the most common allergen source is wheat and the relevant protein component has been shown to be omega-5-gliadin or Triticum aestivum 19. Furthermore, there is a well-known form of this condition in which sensitization to the relevant protein occurs as a result of use of a wheat-containing face cream that is applied to the skin.9Yokooji T. Kurihara S. Murakami T. Chinuki Y. Takahashi H. Morita E. et al.Characterization of causative allergens for wheat-dependent exercise-induced anaphylaxis sensitized with hydrolyzed wheat proteins in facial soap.Allergol Int. 2013; 62: 435-445Abstract Full Text PDF PubMed Scopus (54) Google Scholar There is an interesting model of exercise in a mouse strain in which there is an associated increase in absorption of a relevant allergen.10Yano H. Kato Y. Matsuda T. Acute exercise induces gastrointestinal leakage of allergen in lysozyme-sensitized mice.Eur J Appl Physiol. 2002; 87: 358-364Crossref PubMed Scopus (48) Google Scholar However, how it would be possible to explain the relevance of a specific wheat allergen is difficult to work out. A significant problem with animal models of allergic disease arises because the quantities of allergen are higher than those in cases of natural exposure of patients experiencing symptoms. Clearly, there is a very wide range of sensitivity among individuals with allergy, such that some individuals with peanut allergy react to quantities of the allergen that are difficult to measure. With delayed reactions to red meat, the patients may eat or be challenged orally with large quantities of the antigen in the form of beef or pork kidney. However, the quantity of the allergen that is present in the circulation at the time of reactions may be only a tiny fraction of the quantity eaten. In 1 series of experiments in Gertie et al,1Gertie J.A. Zhang B. Liu E.G. Hoyt L.R. Yin X. Xu L. et al.Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations.J Allergy Clin Immunol. 2022; 149: 262-274Abstract Full Text Full Text PDF Scopus (2) Google Scholar almost 50% of the mice either died or had a symptom score of 4 and were humanely killed.1Gertie J.A. Zhang B. Liu E.G. Hoyt L.R. Yin X. Xu L. et al.Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations.J Allergy Clin Immunol. 2022; 149: 262-274Abstract Full Text Full Text PDF Scopus (2) Google Scholar Clearly, that number implies a high dose because the mortality rate in naturally occurring episodes of anaphylaxis in patients with allergy is generally considered to be less than 1%. So, the question has to be whether it would be possible to study delays in time effects by using lower doses of allergens in the challenges. We recognize that Gertie et al1Gertie J.A. Zhang B. Liu E.G. Hoyt L.R. Yin X. Xu L. et al.Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations.J Allergy Clin Immunol. 2022; 149: 262-274Abstract Full Text Full Text PDF Scopus (2) Google Scholar provide important information about the basis for the severity of anaphylaxis to peanut in 2 strains of mice. In humans, however, there is a high degree of interpersonal and intrapersonal variation in the “threshold doses” of allergen needed to elicit a reaction and in the severity of symptoms observed. That is, in human subjects allergic reactions to a known allergen exposure are highly variable. There are several well-recognized factors that can influence anaphylactic responses, including alcohol, aspirin, nonsteroidal anti-inflammatory drugs, and exercise. However, in addition, there must be other factors that make human responses difficult to predict. Thus, there are major differences in both the timing and the severity of humans' allergic reactions to food, and it is always important to keep in mind the problems that exist when investigating the mechanisms of anaphylaxis either in patients or in sensitized mice. Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutationsJournal of Allergy and Clinical ImmunologyVol. 149Issue 1PreviewThe etiology of food allergy is poorly understood; mouse models are powerful systems to discover immunologic pathways driving allergic disease. C3H/HeJ mice are a widely used model for the study of peanut allergy because, unlike C57BL/6 or BALB/c mice, they are highly susceptible to oral anaphylaxis. However, the immunologic mechanism of this strain’s susceptibility is not known. Full-Text PDF

While EoE is associated with atopic disease, the prevalence of EoE symptoms in patients with atopic conditions is unknown. The objective of this pilot study was to assess the prevalence of dysphagia and food impaction in atopic patients compared to healthy controls. We conducted a case-control study of adult patients with confirmed allergic disease seen at the UVA Allergy/Immunology Clinic (cases) and healthy controls recruited as part of a separate vaccine study. Participants completed the validated Brief Esophageal Dysphagia Questionnaire. The prevalence of dysphagia was calculated for each group and compared using t tests. Multivariable logistic regression was used to assess the association between specific allergic conditions and dysphagia, adjusting for age, gender, and race/ethnicity. Overall, 182 subjects (80 cases; 102 controls) were recruited. Twenty-four(31%) cases reported dysphagia to solid foods compared to 2(2%) healthy controls (p < 0.001). Among atopics, co-diagnosis of IgE-mediated food allergy, but not eczema, asthma, or atopic dermatitis, was associated with an increased odds of dysphagia (OR 2.5, 95%Cl 1.00-6.50, p = 0.049). In multivariable models, an increased number of concomitant atopic conditions was associated with an increased odds of dysphagia (OR 0.046, 95%Cl 1.00-2.94, p = 0.046). Seven atopic patients, and 0 control patients, reported a food impaction lasting > 30 minutes in the past year. Given the high prevalence of dysphagia symptoms in this cohort of atopic patients, allergists should screen patients for dysphagia as part of routine care. The prevalence of undiagnosed EoE in this population is unknown and warrants further study.

Cannabidiol is used in the care of treatment-resistant epilepsy. It has been associated with varying side effects, ranging from somnolence to diarrhea and weight loss. We present a patient on chronic cannabidiol therapy who had persistent diarrhea, abdominal pain, weight loss, and esophageal eosinophilia that improved with cannabidiol dose adjustment.

Introduction: Eosinophilic esophagitis (EoE) is a chronic condition characterized by symptoms of esophageal dysfunction and tissue eosinophilia. One barrier to clinical care in EoE is the need for repeat upper endoscopy (EGD) with biopsies to assess for tissue esophageal eosinophilia. A non-endoscopic esophageal cytology collection device (CytospongeTM) may be a viable alternative to assess for esophageal eosinophilia, but few studies have examined its use in EoE. Methods: We first performed a pilot study in which individuals with confirmed EoE underwent CytospongeTM procedure prior to a clinically-indicated EGD. The cytology results were compared to histology obtained via EGD (gold standard). Cytology and histology from mucosal biopsies were classified as active disease (≥1 eos/hpf cytology; ≥15 eos/hpf, respectively) or remission (0 eos/hpf; < 15 eos/hpf, respectively). The eosinophil-associated protein, eosinophil-derived neurotoxin (EDN) was assayed in the supernatant using ELISAs. We subsequently used the CytospongeTM to assess for mucosal eosinophils, in place of standard EGD with biopsy, in a subset of patients for clinical care. Results: For the pilot study, 7 patients (ages 20-53; 57% males) underwent the CytospongeTM procedure 1 hour prior to EGD. When using a cut-off of 1 eos/hpf on cytology, there was 100% concordance between the CytospongeTM cytology and esophageal biopsies for identifying active EoE and remission (3 active, 4 remission). There was also a trend towards higher concentrations of EDN in the CytospongeTM supernatant of active EoE (median 34.11 ng/mL) versus remission (median 9.5 ng/mL, p=0.057). Between September 2020 and May 2022, 15 CytospongeTM procedures were performed for clinical care (9 patients; ages 30-61; 56% male). Eight patients were undergoing food elimination diets and one was undergoing surveillance after sustained deep remission. No eosinophilia was seen in 10/15 cytology specimens and 5/15 had eosinophilia (range 1-15 eos)(Table). One patient underwent EGD shortly after CytospongeTM (1 eos on cytology), which demonstrated 10-30 eos/hpf on mucosal biopsy. The CytospongeTM procedure was well-tolerated with no significant adverse events. (Figure) Conclusion: The CytospongeTM is a novel mucosal assessment tool that is easily performed and correlates well with gold standard esophageal biopsies in EoE. It should be considered for use in eosinophilic esophagitis to avoid numerous EGD procedures.Figure 1.: a) Esophageal cytology collection device (CytospongeTM), b) Histology from standard esophageal biopsy, c) Cytology from CytospongeTM (same patient as b). Arrows point to eosinophils. Note: images previously published in McGowan EC, Aceves SS, CME Review: Noninvasive tests for eosinophilic esophagitis: Ready for use?. Ann Allergy Asthma Immunol 129 (2022); 27-34. Table 1. - Esophageal Cytology Collection Device (CytospongeTM) Results in Clinical Use Patient Age/Sex Current Treatment CytospongeTM Results Interpretation 1 61M Food Elimination Diet - reintroduced soy 0 eos/hpf Soy is not a trigger 2 50F Food Elimination Diet - reintroduced dairy 2 eos/hpf Dairy is a trigger 3a 30F Food elimination diet - reintroduced soy 0 eos/hpf Soy is not a trigger 3b Food elimination diet - reintroduced egg 0 eos/hpf Egg is not a trigger 3c Food elimination diet - reintroduced wheat 0 eos/hpf Wheat is not a trigger 4 44F Food elimination diet - four food elimination (4FED) 3 eos/hpf Not in remission on 4FED 5a 40F Food elimination diet - reintroduced wheat 0 eos/hpf Wheat is not a trigger 5b Food elimination diet - reintroduced dairy 1 eos/hpf Dairy is a trigger 6a 32M Food elimination diet - two food elimination (2FED) 0 eos/hpf Remission on 2FED Food elimination diet - reintroduced wheat 0 eos/hpf Wheat is not a trigger 7a 43M Food elimination diet - reintroduced fish 0 eos/hpf Fish is not a trigger Food elimination diet - reintroduced soy 0 eos/hpf Soy is not a trigger 8a 39M Food elimination diet - two food elimination (2FED) 6 eos/hpf Not in remission on 2FED Food elimination diet - four food elimination (4FED) 15 eos/hpf Not in remission on 4FED 9 36M Swallowed steroids twice daily and PPI 0 eos/hpf Maintenance of remission

Patients with IBD are at increased risk for developing EoE, but little is known about the clinical characteristics or risk factors for developing EoE in this population. The objective of this study was to assess the prevalence of EoE in patients with IBD and compare characteristics between patients with both IBD/EoE and EoE alone. ICD-10 codes identified pediatric patients with IBD seen at the University of Virginia between October 2015 and June 2020. Charts were reviewed to identify those with esophageal eosinophilia (EE, ≥15 eos/hpf). IBD/EoE was defined as patients who developed EE after their diagnosis of IBD and had esophageal symptoms. These IBD/EoE patients were matched 6:1 to patients with EoE alone. We compared demographic and clinical characteristics of these populations. All analysis was conducted using Stata15.1(College Station,TX). A total of 464 children were identified with IBD, and 326(70.2%) had an esophagogastroduodenoscopy. Thirteen children(2.8%) developed EE after IBD, and 7(1.5%) also had esophageal symptoms (IBD/EoE). On average, patients developed EoE 17.5±6.9 months after IBD. Patients with IBD/EoE were less likely to present with dysphagia(p=.03) and more likely to present with weight loss(p=0.02) than children with EoE alone. All 7 children with IBD/EoE received anti-TNF medications at the time of EoE diagnosis. In this retrospective study, we found a high prevalence of EoE among children with IBD. The use of anti-TNF medications preceded the development of EoE in the patients with underlying IBD. Whether this represents a shared immunologic pathway or a consequence of anti-TNF therapy warrants further study.

It has been hypothesized that solar and geomagnetic activity can affect the function of the autonomic nervous system (ANS) and melatonin secretion, both of which may influence immune response. We investigated the association between solar geomagnetic activity and white blood cell counts in the Normative Aging Study (NAS) Cohort between 2000 and 2013. Linear mixed effects models with moving day averages ranging from 0 to 28 days were used to evaluate the effects of solar activity measures, interplanetary magnetic field (IMF), and sunspot number (SSN), and a measure of geomagnetic activity, K Index (K), on total white blood cell (WBC), neutrophil, monocytes, lymphocyte, eosinophil, and basophil concentrations. After adjusting for demographic and health-related factors, there were consistently significant associations between IMF, SSN, and Kp index, with reductions in total WBC, neutrophils, and basophil counts. These associations were stronger with longer moving averages. The associations were similar after adjusting for ambient air particulate pollution and particle radioactivity. Our findings suggest that periods of increased solar and geomagnetic activity result in lower WBC, neutrophil, and basophil counts that may contribute to mil mild immune suppression.

The prevalence of chronic rhinosinusitis (CRS) is steadily increasing and becoming an increasing component of our medical practices. Most presentations of CRS with nasal polyposis (NP) (CRSwNPs) and close to half of CRS without NPs are associated with eosinophilia and type 2 (T2) inflammation (interleukin [IL]-4, IL-5, and IL-13). 1 Wang X. Zhang N. Bo M. et al. Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: a multicenter study in Europe, Asia, and Oceania. J Allergy Clin Immunol. 2016; 138: 1344-1353 Abstract Full Text Full Text PDF PubMed Scopus (280) Google Scholar ,2 Stevens W.W. Peters A.T. Tan B.K. et al. Associations between inflammatory endotypes and clinical presentations in chronic rhinosinusitis. J Allergy Clin Immunol Pract. 2019; 7 (e3): 2812-2820 Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar In the current issue of the Annals of Allergy, Asthma & Immunology, several state-of-the-art articles update our understanding of the pathogenesis of CRSwNPs and point to future interventions that will ameliorate the adverse impact CRS has on our patients’ quality of life.

Aspirin-exacerbated respiratory disease (AERD) is a complex inflammatory disorder that is not generally viewed as a disease involving the adaptive immune system but instead one largely driven by the innate immune system. This article focuses on the cellular dysregulation involving 4 central cell types: eosinophils, basophils, mast cells, and innate lymphoid type 2 cells. AERD can be envisioned as involving a self-perpetuating vicious circle in which mediators produced by a differentiated activated epithelial layer, such as IL-25, IL-33, and thymic stromal lymphopoietin, engage and activate each of these innate immune cells. The activation of these innate immune cells with their production of additional cytokine/chemokine and lipid mediators leads to further recruitment and activation of these innate immune cells. More importantly, numerous mediators produced by these innate immune cells provoke the epithelium to induce further inflammation. This self-perpetuating cycle of inflammation partially explains both current interventions suggested to ameliorate AERD (eg, aspirin desensitization, leukotriene modifiers, anti-IL-5/IL-5 receptor, anti-IL-4 receptor, and anti-IgE) and invites exploration of novel targets as specific therapies for this condition (prostaglandin D2 antagonists or cytokine antagonists [IL-25, IL-33, thymic stromal lymphopoietin]). Several of these interventions currently show promise in small retrospective analyses but now require definite clinical trials.

Eosinophils are potent proinflammatory leukocytes defined by their expression of preformed cationic granules. Eosinophils have historically primarily been understood to have evolved to mediate toxic immune responses to parasites, while, more problematically, being toxic to airway epithelial cells and other healthy tissues.1 Recently, however, a role of eosinophils in eliminating viral pathogens has emerged, including studies reporting the contribution of eosinophils in the elimination of respiratory syncytial virus (RSV), influenza, parainfluenza and, rhinovirus.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a condition of the upper and lower respiratory tract characterized by reactions to nonsteroidal anti-inflammatory drugs. The Severe Asthma Research Program reported a strong association between perimenstrual asthma (PMA) and aspirin-sensitive asthma. OBJECTIVE: To evaluate the prevalence and characteristics of PMA among a cohort of patients with AERD. METHODS: Women 18 years and older enrolled in the Brigham and Women's AERD registry were surveyed about their reproductive, asthma, and sinus history. Subjects reporting the development of asthma before menopause were included. Continuous and categorical variables were compared between those reporting menstruation as a trigger for asthma symptoms and those who did not. Covariates expected a priori to have a positive effect on the odds of PMA were included in a multivariate logistic regression model to test associations between PMA and clinical factors. RESULTS: Among females of childbearing potential, 369 of 695 responded to the survey and 322 met inclusion criteria. Twenty-four percent of subjects (n = 74) reported PMA. Earlier age of AERD onset, concurrent worsening of sinus symptoms the week before or during menstruation, increased emergency department visits for asthma, and a change in the severity of respiratory symptoms at menopause were more common in PMA. Earlier age at first nonsteroidal anti-inflammatory drug-induced respiratory reaction and emergency department visits increased the odds of reporting PMA. CONCLUSIONS: PMA and increased sinus symptoms with menstruation are common in females with AERD. Females with AERD should be counseled about upper and lower respiratory symptom deterioration with menstruation. (C) 2019 American Academy of Allergy, Asthma & Immunology

Aspirin-exacerbated respiratory disease (AERD) is a condition of the respiratory tract characterized by rhinosinusitis, asthma, eosinophilia, and respiratory reactions to nonsteroidal anti-inflammatory drugs. The pathophysiology of AERD involves a baseline dysregulation of arachidonic acid metabolism leading to the overproduction of leukotrienes. 1 Laidlaw T.M. Boyce J.A. Aspirin-exacerbated respiratory disease: new prime suspects. N Engl J Med. 2016; 374: 484-488 Crossref PubMed Scopus (111) Google Scholar Leukotrienes are inducers of bronchoconstriction and also attract eosinophils into the airways. 2 Dahlen S.E. Hansson G. Hedqvist P. Bjorck T. Granstrom E. Dahlen B. Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4, and E4. Proc Natl Acad Sci U S A. 1983; 80: 1712-1716 Crossref PubMed Scopus (353) Google Scholar The overproduction of leukotrienes in AERD is further exacerbated by cyclooxygenase-1 inhibitors. 1 Laidlaw T.M. Boyce J.A. Aspirin-exacerbated respiratory disease: new prime suspects. N Engl J Med. 2016; 374: 484-488 Crossref PubMed Scopus (111) Google Scholar Paradoxically, aspirin desensitization improves respiratory symptoms in 67% to 78% of patients. 3 Berges-Gimeno M.P. Simon R.A. Stevenson D.D. 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 (287) Google Scholar However, additional treatments are needed because some patients who fail to improve cannot tolerate aspirin. 3 Berges-Gimeno M.P. Simon R.A. Stevenson D.D. 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 (287) Google Scholar ,4 Cahill K.N. Bensko J.C. Boyce J.A. Laidlaw T.M. Prostaglandin D(2): a dominant mediator of aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2015; 135: 245-252 Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar

Aspirin-exacerbated respiratory disease (AERD) is a condition of the upper and lower respiratory tract characterized by chronic rhinosinusitis with nasal polyps (NPs), asthma, tissue eosinophilia, and respiratory reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase-1.1 Daily high-dose aspirin therapy has been shown to reduce the rate of NP regrowth and improve asthma symptoms in 67% to 78% of patients with AERD and is a recommended therapeutic.2,3 In addition to the acute respiratory symptoms following NSAID exposure, a subset of patients with AERD experience gastrointestinal symptoms including abdominal pain, cramping, and dyspepsia upon acute and long-term exposure to NSAIDs.