aggravated airway inflammation: research on genomics and optimal medical care (airgos-medical)

Conditions: Chronic Rhinosinusitis (Diagnosis)

Summary: the study is performed as a randomized double-blinded prospective controlled trial. a total of 72 adult acetyl salicylic acid (asa) -exacerbated respiratory disease (aerd) -patients with uncontrolled chronic rhinosinusitis with nasal polyps (crswnp) will be recruited. those negative to asa-challenge test will not enter the clinical trial . all patients entering the clinical trial, have undergone earlier ethmoidal surgery (partial/total) and have not gained disease control. f-helicobacter antigen is tested and treatment is given if indicated. the patients are recruited at the helsinki university hospital (huh). the study will be monitored by a professional monitor. electronic crf and paper/electronic patient questionnaires provided by hus will be used (ecrf and patient questionnairea, granitics).

randomization and the treatment arms i-ii: the patients are randomized to two treatment arms i) asa- desensitization po tablet daily for 11 months (n=36) ii) placebo po tablet daily for 11 months (n=18). asa challenge and desensitization (primaspan) /placebo: is conducted according to modified international protocol. fev1 should be at least 1.5 l and \> 60% of predicted before challenge or desensitization. on the first day every patient will receive 25 mg + 25 mg asa at a hospital setting. on the second day every patient will receive 50 mg + 25 mg asa at a hospital setting. on the third day every patient will receive 75 mg + 25 mg asa at a hospital setting. on the fourth day every patient will receive 100 mg + 25 mg asa at a hospital setting. during the asa challenge, patient who is asa-challenge positive is then randomized and starts the trial so that he/she uses blinded ½ tablet of 250 mg asa or ½ tablet of placebo daily at home for the next 1 month. after this period of 1 month, the dosing is increased at hospital setting, so that the patient receives blindly 250 mg asa 1/2 tablet + 1/2 tablet or placebo 1/2 tablet + 1/2 tablet. thereafter he/she will continue using blindly 250 mg asa 1 tablet or placebo 1 tablet daily at home for the next 10 months. if the patient does not tolerate the up-dosing of asa/placebo, he/she will continue using blindly ½ tablet of 250 mg asa/placebo daily at home for the next 10 months. the total duration of the asa/placebo treatment is 11 months. we additionally take nasal, blood and urine samples during the trial. follow-ups. the symptom questionnaire and interview of side-effects are performed during each visit. lung function (eno, nno, pef, spirometry) is monitored and the patient will visit doctor and/or nurse at 1, 5, 11, and 12 months post-starting with the treatment. samples are taken during recruitment visit, before and after asa-challenge and at 5, 11 and 12 months post-starting with the treatment. we also monitor side-effects, exacerbations, need of medication (po. cortisocteroids; antibiotics) and satisfaction to treatment. primary end point is change in nasal endoscopic nasal polyp score at -4 days vs. +11 months post-randomization. secondary end point is change in sinonasal outcome test -22 (snot-22) score at -4 days vs. +11 months post-randomization, and change in relative forced expiratory volume in 1 second (fev1 %) without bronchodilator at -1 month vs. +11 months post-randomization. safety (complications, adverse effects), costs and loss of productivity between study arms will be compared. trial medication will be discontinued, if surgery is needed before the end of follow-up.

Eligibility criteria:
inclusion criteria: all these need to be positive: * endoscopic nasal polyp score ≥4 * snot-22 ≥30 * sinus computed tomography lund-mackay score ≥14. the new sinus ct scans are needed if the previous sinus ct scans have been performed over 36 months before recruitment visit or if there is a suspicion of complication of crs (f.ex. mucocele, invasive fungal rhinosinusitis) * ≥1 previous partial/total ethmoidectomy surgery. in addition, patient should have a history of at least one of the following: \>1 oral corticosteroids during the past two years \>3 antibiotic courses during the past two years. in patients with contraindication/adverse effects in using oral steroids additional criteria are not required. exclusion criteria: * complication of crs (f.e. mucocele, invasive fungal rhinosinusitis) * bleeding diathesis * pregnancy/ breastfeeding * cystic fibrosis * primary ciliary dyskinesia (pcd) * sarcoidosis * granulomatosis with polyangitis (gpa) * eosinophilic granulomatosis with polyangitis (egpa) * immunosuppression (diagnosed spesific antibody deficiency (sad), cvi, hiv * use of biologicals/immunosuppressive medication * immunotherapy * daily use of systemic corticosteroids (prednisolon 10mg or equivalent) -communication problems (f.e. neurological/psychiatric disease, language skills) -unlikely to comply * other severe disease * uncontrolled asthma * asa-challenge negative * gastric ulcer * anticoagulant treatment * ssri-depression medication * beta-blocker * severe chronic urticaria * asa anaphylaxis

Keywords: chronic rhinosinusitis with nasal polyps acetyl salicylic acid exacerbated respiratory disease