{"id":"e849353d-8905-562d-9813-ac5d263d958f","stable_key":"7de430a5-1a36-5231-b931-35cc01d8f3bf:apap-cross-desensitisation-shows-shared-mechanism","predicate":"causes","statement":"Three aspirin-sensitive asthmatic subjects with a history of reactions underwent double-blind placebo-controlled challenges and reacted to 1000 milligrams of acetaminophen with a greater than 20% fall in forced expiratory volume in one second, two were desensitized to aspirin and then rechallenged with 1000 milligrams of acetaminophen without reaction, and two were desensitized to acetaminophen achieving refractoriness to 1500 but not 2000 milligrams, so cross sensitivity was documented at large challenge doses and the cross desensitization suggests similar mechanisms are responsible for reactions to aspirin, non-steroidal anti-inflammatory drugs and acetaminophen.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"0f063cb5-a489-5657-afaa-a1c889084eec","mechanism_event_label":"Desensitise the patient to aspirin and they stop reacting to paracetamol, so it is the same mechanism at work.","subject":{"id":"a901be21-7915-543c-ac67-c39ef72b0d03","slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"},"object":{"id":"85e284fb-b6d4-5b80-a1a2-c5d5a7f86aab","slug":"fev1-fall","display_name":"A fall in forced expiratory volume in one second","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0f063cb5-a489-5657-afaa-a1c889084eec","stable_key":"7de430a5-1a36-5231-b931-35cc01d8f3bf:apap-cross-desensitisation-shows-shared-mechanism-event","event_type":"observed_intervention","label":"Desensitise the patient to aspirin and they stop reacting to paracetamol, so it is the same mechanism at work.","description":"Three aspirin-sensitive asthmatic subjects with a history of reactions underwent double-blind placebo-controlled challenges and reacted to 1000 milligrams of acetaminophen with a greater than 20% fall in forced expiratory volume in one second, two were desensitized to aspirin and then rechallenged with 1000 milligrams of acetaminophen without reaction, and two were desensitized to acetaminophen achieving refractoriness to 1500 but not 2000 milligrams, so cross sensitivity was documented at large challenge doses and the cross desensitization suggests similar mechanisms are responsible for reactions to aspirin, non-steroidal anti-inflammatory drugs and acetaminophen.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8ac405bf-3ea0-539a-8e5e-abf503dc7081","slug":"aspirin","display_name":"Aspirin / acetylsalicylic acid","entity_type_key":"drug"},"role":"cross_reacting_drug","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3f745fea-645b-5b10-8a9a-989940e5b826","slug":"aspirin-sensitive-subject","display_name":"Subject with aspirin-sensitive asthma or aspirin-induced urticaria","entity_type_key":"cellular_process"},"role":"studied_group","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a3e35374-db8f-592d-bf1f-e72ac741186f","slug":"cross-desensitisation","display_name":"Cross-desensitisation between analgesics after aspirin desensitisation","entity_type_key":"cellular_process"},"role":"demonstrated_property","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6284d26c-01e2-5e12-b192-ee391dd107e2","slug":"ptgs1","display_name":"Cyclooxygenase-1 (PTGS1)","entity_type_key":"protein"},"role":"shared_target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"a901be21-7915-543c-ac67-c39ef72b0d03","slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"85e284fb-b6d4-5b80-a1a2-c5d5a7f86aab","slug":"fev1-fall","display_name":"A fall in forced expiratory volume in one second","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; 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The cross-desensitisation result is what identifies the shared mechanism.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Desensitise the patient to aspirin and they stop reacting to paracetamol, so it is the same mechanism at work.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[apap-p2666482] Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma. (1989). https://pubmed.ncbi.nlm.nih.gov/2666482/ DOI: 10.1016/0091-6749(89)90174-7","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Airway","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"0cb5ce97-eaa3-5ad6-ab3f-249a729d9061","evidence_kind":"source_excerpt","locator":"Lines 454-465","start_line":454,"end_line":465,"excerpt":"### apap-cross-desensitisation-shows-shared-mechanism\nThree aspirin-sensitive asthmatic subjects with a history of reactions underwent double-blind placebo-controlled challenges and reacted to 1000 milligrams of acetaminophen with a greater than 20% fall in forced expiratory volume in one second, two were desensitized to aspirin and then rechallenged with 1000 milligrams of acetaminophen without reaction, and two were desensitized to acetaminophen achieving refractoriness to 1500 but not 2000 milligrams, so cross sensitivity was documented at large challenge doses and the cross desensitization suggests similar mechanisms are responsible for reactions to aspirin, non-steroidal anti-inflammatory drugs and acetaminophen.\nCondition category: biomarker_context\nnutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404.\nplain_language: Desensitise the patient to aspirin and they stop reacting to paracetamol, so it is the same mechanism at work.\norganism: Human\ntissue_or_cell_type: Airway\nexperimental_model: Double-blind placebo-controlled oral challenge and desensitisation in three aspirin-sensitive asthmatic subjects\nlimitations: Three subjects, selected for a history of reacting, so the frequency of cross-reactivity cannot be read from it. The cross-desensitisation result is what identifies the shared mechanism.\nexposure: 1000 to 2000 milligram acetaminophen challenges, with aspirin desensitisation and acetaminophen desensitisation\nevidence_span: {\"source_cache\": \"artifacts/paracetamol-research/2666482.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9c731e77d65955b683aa03e7df1252729e11b1fb8bed714b9138f22c725eac2b\", \"start_char\": 0, \"end_char\": 1081, \"text_sha256\": \"9c731e77d65955b683aa03e7df1252729e11b1fb8bed714b9138f22c725eac2b\"}\n[apap-p2666482] Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma. (1989). https://pubmed.ncbi.nlm.nih.gov/2666482/ DOI: 10.1016/0091-6749(89)90174-7","model_system":"Double-blind placebo-controlled oral challenge and desensitisation in three aspirin-sensitive asthmatic subjects","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [apap-p2666482] Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma. 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