Aspirin-exacerbated respiratory disease

1095:

in following what is a fairly stringent diet. Despite these findings, experts on the disease do not believe that dietary salicylates contribute to AERD symptoms. Dietary salicylates do not significantly inhibit the COX-1 enzyme, which is the cause of AERD reactions. One confounding factor in the study that showed a benefit from avoidance of dietary salicylates is that a low salicylate diet involves eliminating wine and beer. The majority of AERD patients react to wine and beer for reasons that do not involve their salicylate content. There is also a strong placebo effect involved with any dietary intervention. In contrast to aspirin, dietary salicylates are not acetylated and therefore do not block

567: 1082:. One study found that 83% reported such reactions. Of those who had reactions, 75% had a sinus reaction (runny nose, nasal congestion) and 51% had a lower respiratory reaction (wheezing, shortness of breath). The current theory on the cause of these reactions is that they may be related to polyphenols found in alcoholic beverages. A 2017 study found that alcohol sensitive patients reacted to catechins in red wine, but not to resveratrol. It has been suggested that steel fermented white wines and clear liquors may cause less of a reaction than other alcoholic beverages. Desensitization to aspirin has been found to reduce reactions to alcohol. 64: 704: 936: 1023:

A complete endoscopic sinus surgery followed by aspirin desensitization has been shown to reduce the need for revision surgeries. Exact cause of nasal polyp formation is unknown, however, differential gene expression analysis of AERD nasal polyp epithelial cells versus AERD non polyp nasal mucosa revealed DMRT3 could be potentially involved in nasal polyp development in AERD patients. Furthermore, several genes are down-regulated, hinting at the de-differentiation phenomenon in AERD polyps.

923:

desensitization. The recommended maintenance dose for symptom control is 650 mg to 1300 mg aspirin daily. While on daily aspirin, patients experience improved quality of life and reduced nasal symptoms, however, there is no improvement in smell compared to placebo and there is no reduction in the need for oral corticosteroids or rescue surgery. Once desensitized to aspirin, most patients can safely take other NSAID medications again as long the daily maintenance dose is continued.

359:

onset during childhood. It is more prevalent among women by up to a 2:1 margin, usually begins in the patient's twenties to forties, with mean age of onset around 35. AERD patients may not have any allergies, though allergies are significantly more common in AERD patients than the general population. While AERD has been found to affect essentially all ethnicities, it is less common in parts of Asia where nasal polyps caused by

1010:, have proven to be useful in treatment of nasal polyposis. However, there may be limited additional benefit when used in conjunction with intra-nasal corticosteroids. In a large survey, AERD patients reported that zileuton was more effective at controlling their symptoms than montelukast. Despite this, zileuton remains less prescribed than montelukast, likely due to concerns around risk of liver enzyme elevation. 429:, also are regarded as safe. Nonetheless, recent studies do find that these types of drugs, e.g. acetaminophen and celecoxib, may trigger adverse reactions in these patients; caution is recommended in using any COX inhibitors. In addition to aspirin and NSAIDs, consumption of even small amounts of alcohol also produces uncomfortable respiratory reactions in many patients. 445:, chronic viral infection and autoimmune mechanisms have been theorized, among others, though there is not sufficient evidence to support any specific theory. No strong genetic predisposition to or basis of AERD has been found, and familial AERD is rare. In addition, there is no relationship between past use of NSAIDs and onset of AERD 914:. Overall effectiveness is low-to-moderate, but wide availability and low cost make this a widely used treatment option. Stent, spray and exhalation delivery systems are generally among the most beneficial depending on outcome measured, while no major differences in adverse effects have been measured between delivery methods. 665:(including eosinophils), are also implicated in disease pathogenesis as well as acute aspirin-induced exacerbations. Additionally, after aspirin or other NSAID exposure, AERD patients generally become desensitized and tolerate a second exposure for around one week, which lines up with the half life of circulating platelets. 963:. Among treatment options, biologics have the highest certainty and magnitude of improvement effect. However, due to the high cost and systemic nature of biologics, some patients whose symptoms are sufficiently controlled with other treatments may prefer to avoid them or not qualify under stricter prescription guidelines. 267:) is extremely common, occurring in more than 90% of people with the disease. AERD most commonly begins in early- to mid-adulthood and has no known cure. While NSAID intolerance is a defining feature of AERD, avoidance of NSAIDs does not affect the onset, development or perennial nature of the disease. 1022:

is required to remove nasal polyps, although they typically recur, particularly if aspirin desensitization is not undertaken. Approximately, 90% of patients have been shown to have recurrence of nasal polyps within five years after surgery, with 47% requiring revision surgery in the same time period.

1094:

to see if they benefit AERD patients. For example, a prospective randomized trial with 30 patients following a low-salicylate diet for six weeks demonstrated a clinically significant decrease in both subjective and objective scoring of severity of disease, but made note of the challenge for patients

358:

AERD affects an estimated 0.3–0.9% of the general population in the US, including around 7% of all asthmatics, about 14% of adults with severe asthma, and ~5-10% of patients with adult onset asthma. AERD is uncommon among children, with around 6% of patients, predominantly female, reporting disease

299:

A history of respiratory reactions to aspirin or others NSAIDs is sufficient to diagnose AERD in a patient that has both asthma and nasal polyps. However, diagnosis can be challenging during disease onset, as symptoms do not usually begin all at once. As symptoms appear, AERD may be misdiagnosed as

966:

Among biologics and aspirin desensitization and therapy, dupilumab (Dupixent) was show to be the most effective across six different patient-important outcomes. Dupilumab and omalizumab have been shown to increase aspirin tolerance in AERD patients, however mepolizumab does not appear to have this

922:

Avoidance of NSAID medications will not stop the progression of the disease. However, one treatment option is desensitization to aspirin, undertaken at a clinic or hospital specializing in such treatment. Patients who are desensitized then take a maintenance dose of aspirin daily to maintain their

870:

Since nasal polyps have been identified as an important source of inflammatory compounds in AERD, much effort goes into the prevention of polyp growth and control of sinus symptoms in general. There is evidence supporting four different long-term pharmacological treatments to this end: intra-nasal

1161:

and Beers in reports published in 1968, which brought full clinical characterization. The recognition Samter brought to the disease through his studies led to it being called "Samter's triad", although today "aspirin-exacerbated respiratory disease" is preferred to better reflect the progressive

1152:

The first adverse reactions to aspirin were described in 1902 in Germany, only four years after aspirin's commercial introduction. The first published report of an aspirin-induced asthma attack was in 1911. Initial reports on the linkage between asthma, aspirin, and nasal polyposis were made by

926:

Risk of adverse advents such as bleeding or gastrointestinal side effects is relatively high with daily aspirin therapy. Even a 81 mg daily aspirin regimen for cardiovascular benefits has been shown to increase risk of long-term bleeding, so the significantly higher aspirin doses used for

2911:

Priyadharshini, V.S.; Jiménez-Chobillon, M.A.; de Graaf, J.; Porras Gutiérrez de Velasco, R.; Gratziou, C.; Ramírez-Jiménez, F.; Teran, L.M. Transcriptome Analysis Identifies Doublesex and Mab-3 Related Transcription Factor (DMRT3) in Nasal Polyp Epithelial Cells of Patients Suffering from

773:

Basophils, which are degranulated in AERD nasal polyps, also appear to be important sources of IL-4 and IL-13. In addition to activating immune cells, IL-4 and IL-13 have been shown to significantly increase 15-LO activity, further playing into the cycle of dysregulation and disease.

1059:(DHA). EPA and DHA are precursors for anti-inflammatory compounds that modulate leukotrienes, prostaglandins and thromboxanes that have been implicated in AERD pathogenesis. Initial studies have shown that decreasing omega-6 intake and increasing omega-3 intake decrease urinary LTE 402:. Gastrointestinal reactions have also been reported in a subset of patients, and may be difficult to treat. Factors that affect reaction severity include NSAID dosage, underlying asthma control, leukotriene modifier usage and the state of the patient's nasal polyps. 381:

Reactions to NSAIDs range in severity and expression. Onset is usually relatively rapid, with a mean time of around one hour after ingestion, though reactions as late as three hours have been reported. Respiratory reactions are essentially universal, with

887:. Each treatment has benefits and drawbacks, so no one option can be recommended for all patients. Asthma symptoms, if not controlled via biologics or other means, are managed with standard asthma treatments such as inhaled corticosteroids and 3245:

Sommer DD, Rotenberg BW, Sowerby LJ, Lee JM, Janjua A, Witterick IJ, et al. (April 2016). "A novel treatment adjunct for aspirin exacerbated respiratory disease: the low-salicylate diet: a multicenter randomized control crossover trial".

3671: 3652: 2030:

Bochenek G, Stachura T, Szafraniec K, Plutecka H, Sanak M, Nizankowska-Mogilnicka E, Sladek K (March 2018). "Diagnostic Accuracy of Urinary LTE4 Measurement to Predict Aspirin-Exacerbated Respiratory Disease in Patients with Asthma".

1204:

Kowalski ML, Asero R, Bavbek S, Blanca M, Blanca-Lopez N, Bochenek G, et al. (October 2013). "Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs".

452:

metabolic cascade and dysregulation of various innate immune cells. These two components feed into each other in a highly complex negative cycle of increasing inflammation and dysregulation that is still under active research.

2868:

Adappa ND, Ranasinghe VJ, Trope M, Brooks SG, Glicksman JT, Parasher AK, et al. (January 2018). "Outcomes after complete endoscopic sinus surgery and aspirin desensitization in aspirin-exacerbated respiratory disease".

2396:

Pleskow WW, Stevenson DD, Mathison DA, Simon RA, Schatz M, Zeiger RS (January 1982). "Aspirin desensitization in aspirin-sensitive asthmatic patients: clinical manifestations and characterization of the refractory period".

2222:

Bognanni A, Chu DK, Rank MA, Bernstein J, Ellis AK, Golden D, et al. (December 2022). "Topical corticosteroids for chronic rhinosinusitis with nasal polyposis: GRADE systematic review and network meta-analysis".

927:

maintenance therapy are of some concern. This is borne out in studies on AERD patients—compared against standard of care and biologic medicines, aspirin therapy has a significantly higher rate of adverse outcomes.

370:(inflammation or irritation of the nasal mucosa), which may manifest as sneezing, runny nose, or congestion. The disorder typically progresses to asthma, then nasal polyposis, with aspirin sensitivity coming last. 278:, though the initial cause of this dysregulation is currently unknown. This dysregulation leads to an imbalance of immune related molecules, including an overproduction of inflammatory compounds such as 759:

2 and immunoglobulin E responses. These responses cause the epithelial cells to release more cytokines and inflammatory molecules, creating a feed-forward negative cycle of increasing inflammation.

5442: 2704:

San Nicoló M, Habermann N, Havel M (2020). "AERD Associated Nasal Polyposis: Efficacy of Postoperative Antileukotriene Therapy in Comparison with Aspirin Desensitization. A Retrospective Study".

4831: 4117: 326:

Reactions to aspirin and other NSAIDs range in severity but almost always have a respiratory component; severe reactions can be life threatening. The symptoms of NSAID-induced reactions are

578:

inhibitors lead to acute respiratory reactions is still under investigation. AERD patients exhibit a seemingly paradoxical response to COX-1 inhibition, as it leads to greatly increased PGD

5934: 1036:

Given that dysregulation of the arachidonic acid cascade has been implicated in AERD pathogenesis and that production of arachidonic acid and its downstream products is influenced by the

857:

concentration is generally around 3 to 5 times higher in patients with AERD that it is in those with aspirin-tolerant asthma, and increases 2 to 30 fold during an aspirin challenge test.

910:

are often used as a first line treatment for AERD. They can be delivered topically to the nasal and sinus mucosa via a variety of methods, such as nasal spray, rinse, drops, stents and

786:. AERD is generally diagnosed based on a patient's medical history, however an oral aspirin challenge at a specialized facility is considered the most definitive method of diagnosis. 2349:"Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: A systematic review and network meta-analysis" 1051:

A diet low in omega-6 fatty acids and high in omega-3 fatty acids—the opposite of an average modern western diet—has been shown to reduce arachidonic acid precursors and increase

6151: 1585:

Rajan JP, Wineinger NE, Stevenson DD, White AA (March 2015). "Prevalence of aspirin-exacerbated respiratory disease among asthmatic patients: A meta-analysis of the literature".

998:

are a family of inflammatory mediators derived from arachidonic acid that include CysLTs implicated in AERD pathophysiology. Drugs that prevent leukotriene production, such as

6070: 2612:

Picado C, Mullol J, Roca-Ferrer J (September 2022). "Mechanisms by which dupilumab normalizes eicosanoid metabolism and restores aspirin-tolerance in AERD: A hypothesis".

378:—reduction or loss of the ability to smell—are reported in more than 90% of patients, as inflammation within the nose and sinuses likely reaches the olfactory receptors. 323:-based drugs are all commonly used, among other treatment options. Paradoxically, daily aspirin therapy after an initial desensitization can also help manage symptoms. 5790: 5435: 5310: 1688:

Chen BS, Virant FS, Parikh SR, Manning SC (February 2013). "Aspirin sensitivity syndrome (Samter's Triad): an unrecognized disorder in children with nasal polyposis".

5494: 4824: 3736: 4581: 766:, which in turn further active ILC2. Likewise, mast cells are also activated by epithelial-cell released IL-25, IL-33 and TSLP, leading to further CysLT and PGD 1887:

Narayanankutty A, Reséndiz-Hernández JM, Falfán-Valencia R, Teran LM (May 2013). "Biochemical pathogenesis of aspirin exacerbated respiratory disease (AERD)".

700:(ILC2) cells have all been found at increased levels in the nasal polyps of AERD patients and appear to be part of the negative cycle of inflammation in AERD. 259:(NSAIDs). Compared to aspirin tolerant patients, AERD patients' asthma and nasal polyps are generally more severe. Reduction or loss of the ability to smell ( 5535: 309: 5951: 5428: 5947: 5519: 4817: 3385:

Amar YG, Frenkiel S, Sobol SE (February 2000). "Outcome analysis of endoscopic sinus surgery for chronic sinusitis in patients having Samter's triad".

967:

effect. The mechanism through which dupilumab treats AERD and restores aspirin tolerance is not fully understood, but it is theorized that by blocking

6200: 5976: 5851: 4336: 3412:

Bochenek G, Bánska K, Szabó Z, Nizankowska E, Szczeklik A (March 2002). "Diagnosis, prevention and treatment of aspirin-induced asthma and rhinitis".

5817: 5602: 5393: 5388: 4989: 6036: 5530: 5344: 4360: 3192: 850: 894:

Despite optimal medical management, many patients continue to require oral steroid medications to alleviate asthma and chronic nasal congestion.

5166: 5988: 5855: 5831: 4107: 3369: 1181: 888: 6176: 6091: 6053: 5648: 5625: 5744: 5716: 5700: 4793: 4576: 4331: 3729: 3686: 1482:

O'Brien EK, Jerschow E, Divekar RD (October 2023). "Management of Aspirin-Exacerbated Respiratory Disease: What Does the Future Hold?".

1439:

Haque R, White AA, Jackson DJ, Hopkins C (August 2021). "Clinical evaluation and diagnosis of aspirin-exacerbated respiratory disease".

1019: 720: 256: 188: 54: 2825:

Mendelsohn D, Jeremic G, Wright ED, Rotenberg BW (March 2011). "Revision rates after endoscopic sinus surgery: a recurrence analysis".

5826: 4586: 4382: 6163: 5939: 5499: 5383: 5161: 4783: 4563: 4063: 3758: 3753: 1037: 762:

Eosinophils are also activated by ILC2-released IL-5 and epithelial-cell released IL-33, causing them to release more CysLTs and PGD

782:

Diagnosis of AERD can be difficult, as symptoms develop over time and can often be attributed to allergies, common asthma, and/or

6024: 6012: 5020: 347: 114: 5156: 1090:

Given that aspirin is a salicylate, specifically acetyl salicylic acid, research has gone into low-salicylate diets such as the

6211: 6141: 5894: 5507: 5202: 5064: 4527: 1725:"Cross-reactivity to Acetaminophen and Celecoxib According to the Type of Nonsteroidal Anti-inflammatory Drug Hypersensitivity" 673: 5778: 5059: 845:

concentration alone cannot be used to diagnose AERD, however it may be possible to rule out AERD in patients without high uLTE

5962: 5806: 5567: 4798: 3722: 2303:"Selection of aspirin dosages for aspirin desensitization treatment in patients with aspirin-exacerbated respiratory disease" 680:

are reduced. It's possible that increased 15-LO activity and preferential conversion of arachidonic acid into 15-Oxo-ETE and

4264: 6146: 6109: 5282: 4372: 1622:"Pediatric-onset aspirin-exacerbated respiratory disease: Clinical characteristics, prevalence, and response to dupilumab" 1070:

levels and significantly improved overall symptoms. AERD specialists routinely recommend this diet as a treatment option.

841:) concentration is also a sign of AERD, especially when noted in conjunction with the criteria listed above due. High uLTE 6075: 3028:"Dietary Fatty Acid Modification for the Treatment of Aspirin-Exacerbated Respiratory Disease: A Prospective Pilot Trial" 2657:"Rapid and sustained effect of dupilumab on clinical and mechanistic outcomes in aspirin-exacerbated respiratory disease" 2566:

Mustafa SS, Vadamalai K (June 2021). "Dupilumab increases aspirin tolerance in aspirin-exacerbated respiratory disease".

1670: 987:

prevents inflammatory mediator release from mast cells and inhibits 5-LO function, which decreases production of CysLTs.

676:

and 15-Oxo-ETE are significantly elevated in nasal polyps from AERD patients while other products like anti-inflammatory

5339: 4571: 4522: 4355: 4293: 736: 461:

AERD is associated with an aberrant arachidonic acid metabolism that leads to changes in levels of two major classes of

63: 2266:

Waldram JD, Simon RA (November 2016). "Performing Aspirin Desensitization in Aspirin-Exacerbated Respiratory Disease".

6188: 5241: 5044: 4532: 485: 6063: 5737: 5725: 2747:

Ta V, White AA (September 2015). "Survey-Defined Patient Experiences With Aspirin-Exacerbated Respiratory Disease".

6126: 5909: 5460: 5272: 4950: 4718: 911: 876: 603: 180: 803:

Further, if a patient meets two or more of the following criteria, then an AERD diagnosis is strongly considered:

448:

AERD is generally thought to have two major components contributing to disease pathogenesis: abnormalities in the

6000: 5574: 5555: 5487: 5302: 5125: 4591: 4216: 4190: 3915: 3816: 3546:

Samter M, Beers RF (May 1968). "Intolerance to aspirin. Clinical studies and consideration of its pathogenesis".

5869: 4367: 3075:

Healy E, Newell L, Howarth P, Friedmann PS (December 2008). "Control of salicylate intolerance with fish oils".

5917: 5679: 5620: 5216: 4985: 4971: 4195: 4180: 4173: 4078: 4039: 3986: 3964: 3922: 3850: 3697: 3210:

Ta V, White AA (July 2018). "Survey-Defined Patient Experiences With Aspirin-Exacerbated Respiratory Disease".

692:

Various innate immune cells also appear to play important roles in AERD pathogenesis. Eosinophils, mast cells,

4346: 3120:"Re: Alcohol-induced respiratory symptoms are common in patients with aspirin exacerbated respiratory disease" 1381:"Aspirin-exacerbated respiratory disease: Prevalence, diagnosis, treatment, and considerations for the future" 3524: 1538:"Innate immune cell dysregulation drives inflammation and disease in aspirin-exacerbated respiratory disease" 6242: 5922: 5757: 5089: 4852: 4495: 4137: 4053: 3928: 2519:"Appraisal of the Real-World Effectiveness of Biologic Therapies in Aspirin-Exacerbated Respiratory Disease" 2180:"Natural history of aspirin-induced asthma. AIANE Investigators. European Network on Aspirin-Induced Asthma" 630: 275: 2434:"Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement" 5669: 5663: 5503: 5220: 4621: 4474: 4435: 4350: 4303: 4002: 3845: 2912:

Non-Steroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease (AERD). Biomolecules 2021, 11, 1092.

1779:"Alcohol-induced respiratory symptoms are common in patients with aspirin exacerbated respiratory disease" 1171: 968: 570:

Simplified overview of the arachidonic acid metabolic cascade and some of its relevant downstream products

155: 6130: 5523: 5451: 3883: 3855: 2782:

McMains KC, Kountakis SE (2006). "Medical and surgical considerations in patients with Samter's triad".

2481:

Tuttle KL, Buchheit KM, Schneider T, Hsu Blatman KS, Barrett NA, Laidlaw TM, Cahill KN (February 2018).

1154: 1131: 1052: 566: 442: 33: 1078:

The majority of those with aspirin exacerbated respiratory disease experience respiratory reactions to

707:

An overview of some of the immune cells and molecules involved in the negative cycle of disease in AERD

1048:

essential fatty acids, dietary interventions targeting the two essential fatty acids are under study.

6237: 5551: 5482: 5378: 5373: 5357: 5267: 5197: 5054: 4966: 4500: 4452: 4440: 4254: 4212: 3811: 1056: 783: 343: 305: 164: 5865: 5861: 5542: 5400: 4768: 4735: 4481: 4430: 4058: 3878: 3745: 3675: 3161:"Activation of Basophils and Eosinophils by EtOH in Alcohol Sensitive Patients with CRS and Asthma" 1099:

and hence, there is no rationale why a low salicylate diet would be beneficial for AERD patients.

944: 383: 360: 320: 81: 3476:"Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension" 789:

Patients are considered candidates for an AERD diagnosis if they meet the following three points:

5839: 5405: 5287: 5277: 5171: 5069: 5049: 4886: 4844: 4626: 4491: 4447: 4279: 4200: 4127: 3997: 3271: 3100: 2894: 2850: 2807: 2729: 2637: 2591: 2463: 2378: 2248: 2108: 1958: 1651: 1507: 1464: 1304: 1230: 1045: 1041: 339: 331: 96: 5097: 5880: 5753: 5729: 5709: 5705: 5107: 5102: 4902: 4891: 4748: 3992: 3821: 3782: 3615: 3563: 3505: 3456: 3429: 3394: 3365: 3357: 3320: 3263: 3227: 3141: 3092: 3057: 3008: 2956: 2886: 2842: 2799: 2764: 2721: 2686: 2629: 2583: 2548: 2483:"A pragmatic analysis of mepolizumab in patients with aspirin-exacerbated respiratory disease" 2455: 2414: 2370: 2324: 2283: 2240: 2201: 2160: 2100: 2048: 2012: 1950: 1904: 1866: 1808: 1754: 1705: 1643: 1602: 1567: 1499: 1456: 1410: 1358: 1296: 1222: 880: 301: 293: 184: 160: 145: 76: 3291:"Can Diet Modification Be an Effective Treatment in Aspirin-Exacerbated Respiratory Disease?" 2927:"Can Diet Modification Be an Effective Treatment in Aspirin-Exacerbated Respiratory Disease?" 2432:

Davidson KW, Barry MJ, Mangione CM, Cabana M, Chelmow D, Coker TR, et al. (April 2022).

1837:"New concepts for the pathogenesis and management of aspirin-exacerbated respiratory disease" 315:

As there is no cure, treatment of AERD revolves around managing the symptoms of the disease.

6247: 5773: 5768: 5733: 5693: 5465: 5151: 5085: 5002: 4997: 4938: 4865: 4840: 4691: 4684: 4548: 4469: 4308: 4244: 4093: 3605: 3597: 3555: 3495: 3487: 3421: 3310: 3302: 3255: 3219: 3172: 3131: 3084: 3047: 3039: 2998: 2990: 2946: 2938: 2878: 2834: 2791: 2756: 2713: 2676: 2668: 2621: 2575: 2538: 2530: 2494: 2445: 2406: 2360: 2347:

Oykhman P, Paramo FA, Bousquet J, Kennedy DW, Brignardello-Petersen R, Chu DK (April 2022).

2314: 2275: 2232: 2191: 2150: 2142: 2090: 2040: 2002: 1992: 1940: 1896: 1856: 1848: 1798: 1790: 1744: 1736: 1697: 1633: 1594: 1557: 1549: 1491: 1448: 1400: 1392: 1348: 1338: 1286: 1214: 1176: 1064: 947:

medications that have come to market in recent years have been used to treat AERD including

935: 662: 541: 492: 474: 449: 327: 286: 271: 248: 4809: 751:. These cytokines lead to increased eosinophil recruitment, excessive mucus production via 6232: 5761: 5292: 5262: 5146: 5074: 4928: 4881: 4713: 4665: 4553: 4504: 4425: 4341: 4149: 2655:

Buchheit KM, Sohail A, Hacker J, Maurer R, Gakpo D, Bensko JC, et al. (August 2022).

884: 703: 418: 196: 176: 3362:

Enteroimmunology: A Guide to the Prevention and Treatment of Chronic Inflammatory Disease

2196: 2179: 1327:"Aspirin Exacerbated Respiratory Disease: Epidemiology, Pathophysiology, and Management" 6087: 5995: 5927: 5749: 5721: 5176: 5130: 4923: 4651: 4313: 4224: 4144: 3954: 3949: 3610: 3585: 3500: 3475: 3474:

Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, et al. (1911-04-29).

3315: 3290: 3052: 3027: 3003: 2978: 2951: 2926: 2681: 2656: 2543: 2518: 2155: 2130: 2007: 1980: 1861: 1836: 1803: 1778: 1777:

Cardet JC, White AA, Barrett NA, Feldweg AM, Wickner PG, Savage J, et al. (2014).

1749: 1724: 1562: 1537: 1405: 1380: 1353: 1326: 1096: 1079: 872: 831: 748: 732: 728: 526: 515: 504: 489: 316: 279: 3680: 1900: 1273:

Taniguchi M, Mitsui C, Hayashi H, Ono E, Kajiwara K, Mita H, et al. (July 2019).

17: 6226: 6095: 5785: 5547: 5420: 5351: 4943: 4743: 4457: 4168: 3714: 3338: 3275: 3088: 2733: 2641: 2595: 2467: 2410: 2382: 2252: 2112: 1962: 1655: 1511: 1468: 1308: 1091: 744: 740: 615: 556: 470: 3104: 2854: 2811: 1234: 6104: 6031: 5514: 5246: 5036: 4918: 4907: 4680: 4633: 4018: 3970: 3839: 2898: 2131:"Leukotriene antagonists in nasal polyposis: a meta-analysis and systematic review" 2129:

Wentzel JL, Soler ZM, DeYoung K, Nguyen SA, Lohia S, Schlosser RJ (November 2013).

960: 824: 438: 3702: 1852: 1701: 4933: 4913: 4897: 4778: 4725: 4708: 4703: 4656: 4611: 4462: 4410: 4377: 4249: 3978: 3910: 3873: 3828: 3763: 1007: 1003: 995: 952: 903: 752: 466: 414: 399: 244: 110: 85: 3559: 3306: 3223: 3177: 3160: 3136: 3119: 3043: 2942: 2838: 2760: 2672: 2625: 2579: 2534: 2499: 2482: 2365: 2348: 2319: 2302: 2236: 2095: 2078: 2044: 1945: 1928: 1794: 1638: 1621: 1598: 1553: 1452: 1291: 1275:"Aspirin-exacerbated respiratory disease (AERD): Current understanding of AERD" 1274: 5802: 4698: 4298: 4284: 4259: 4234: 4229: 4163: 4112: 4034: 4010: 3959: 3833: 3798: 3773: 3665: 3661: 2279: 2146: 1997: 1740: 1674: 1495: 1396: 1158: 1118: 956: 907: 724: 552: 462: 395: 387: 3491: 3425: 3026:

Schneider TR, Johns CB, Palumbo ML, Murphy KC, Cahill KN, Laidlaw TM (2018).

2994: 2795: 1927:

Mullol J, Boyce J, Dahlén SE, Dahlén B, Picado C, Bobolea I (November 2021).

6019: 6007: 5983: 4773: 4405: 4274: 4269: 4239: 3790: 3601: 948: 607: 598:, a leading explanation is that patients have an increased dependence on PGE 437:

The reason for onset of AERD is currently unknown. Allergic reaction to the

426: 422: 406: 292:. This imbalance, among other factors, leads to chronic inflammation of the 240: 106: 3619: 3509: 3433: 3398: 3324: 3267: 3231: 3145: 3096: 3061: 3012: 2960: 2890: 2846: 2803: 2768: 2725: 2690: 2633: 2587: 2552: 2459: 2450: 2433: 2374: 2328: 2287: 2244: 2205: 2164: 2104: 2052: 2016: 1954: 1908: 1870: 1812: 1758: 1709: 1647: 1606: 1571: 1503: 1460: 1414: 1362: 1300: 1226: 3567: 3460: 2418: 1343: 6137: 5971: 5843: 4788: 4673: 4073: 3806: 1723:

Kim YJ, Lim KH, Kim MY, Jo EJ, Lee SY, Lee SE, et al. (March 2014).

999: 716: 693: 650: 371: 367: 335: 260: 3644: 1620:

Bensko JC, McGill A, Palumbo M, Cahill KN, Laidlaw TM (September 2022).

4856: 4026: 3902: 2913: 677: 375: 264: 252: 89: 3259: 3199:. American Academy of Allergy Asthma & Immunology. August 3, 2018. 2882: 2717: 1218: 6183: 5889: 5847: 5225: 4123: 3936: 3865: 3656: 3159:

Payne SC, Peters RD, Negri JA, Steinke JW, Borish L (February 2017).

669: 417:(acetaminophen) in low doses is generally considered safe. Selective 366:

While disease progression varies, most commonly the first symptom is

236: 102: 2517:

Wangberg H, Spierling Bagsic SR, Osuna L, White AA (February 2022).

405:

In addition to aspirin, patients also react to other NSAIDs such as

6195: 6171: 5797: 5597: 5562: 5192: 4860: 3944: 934: 817: 681: 575: 410: 391: 1162:

nature of the condition even when patients abstain from NSAIDs.

983:

production and activity appear to play a key role in AERD, as PGE

235:, is a long-term disease defined by three simultaneous symptoms: 6158: 6082: 6058: 5688: 5643: 3893: 3691: 697: 551:), which exerts pro-inflammatory effects via its recruitment of 312:

of symptoms are present that the diagnosis of AERD can be made.

5424: 4813: 3718: 563:

2) cells in addition to its direct bronchoconstrictive action.

386:

occurring in close to 90% of patients and nasal congestion and

338:-induced asthma, rhinitis, or hives. AERD is not considered an 1536:

Eid R, Yan CH, Stevens W, Doherty TA, Borish L (August 2021).

488:(5-LO), causing increased conversion of arachidonic acid into 285:

and an underproduction of anti-inflammatory mediators such as

2979:"Clinical updates in aspirin-exacerbated respiratory disease" 971:, dupilumab increases expression of EP2, the receptor for PGE 409:, and to any medication that inhibits the cyclooxygenase-1 ( 346:. EAACI/WHO classifies the syndrome as one of five types of 27:

Chronic inflammatory disease affecting the sinuses and lungs

3295: