Aggravated Airway Inflammation: Research on Genomics and Optimal Medical Care (AirGOs-medical)
Aggravated Airway Inflammation: Research on Genomics and Optimal Medical Care (AirGOs-medical)
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.
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