Study protocol for a randomized double-blinded placebo-controlled trial on ASA therapy for patients with chronic rhinosinusitis with nasal polyps, NSAID exacerbated respiratory disease and asthma

Sanna Katriina Toppila-Salmi^1*Annina Lyly²Viljami Salmi³Mikko Nuutinen³Michael Kilpiö⁴Tanzeela Hanif⁴Mikko Niemi⁵Anu Laulajainen-Hongisto⁶Lena Hafren⁶Mika J. Mäkelä²Paula Kauppi⁷Paula Virkula⁶Alma Helevä²

• ¹1Department of Otorhinolaryngology, University of Eastern Finland, Joensuu and Kuopio, Finland 2Department of Otorhinolaryngology, Wellbeing services county of Pohjois-Savo, Kuopio, Finland 3Department of Allergology, Inflammation Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland, University of Helsinki, Helsinki, Finland
• ²Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Uusimaa, Finland
• ³University of Helsinki, Helsinki, Finland
• ⁴Department of Otorhinolaryngology, Wellbeing services county of Pohjois-Savo, Kuopio, Finland, Kuopio, Northern Savonia, Finland
• ⁵Univeristy of Helsinki, Helsinki, Finland
• ⁶Department of Otorhinolaryngology, Helsinki University Hospital, Helsinki, Finland
• ⁷Department of Pulmonology and Allergy, Helsinki University Hospital, Helsinki, Finland

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the nose and paranasal sinuses characterized by intense inflammation, accompanied by decreased health-related quality of life (HRQoL). NSAID-exacerbated respiratory disease (N-ERD), affects 17.7% of CRSwNP patients and often requires frequent sinus surgeries and rescue treatment. Compared to non-N-ERD patients, those with N-ERD have greater risks of asthma exacerbations, severe allergic reactions, and anosmia. Acetyl salicylic acid (ASA) treatment after desensitization (ATAD) has been proposed for N-ERD with severe CRSwNP, showing potential benefits for symptom relief, polyp reduction, and improved QoL but carries risks such as gastritis and bleeding. This randomized double-blind placebo-controlled clinical trial (RDBCT) evaluates ATAD's efficacy and safety compared to placebo in patients with severe CRSwNP, N-ERD, and asthma.Outcomes include polyp size reduction, QoL improvement, side effects, and analyses of molecular and microbiome markers from nasal, blood, and urine samples. Methods: AirGOs Medical is an investigator driven RDBCT of Helsinki University Hospital. ATAD and placebo treatment arms are compared. The primary outcome is the change in the SNOT-22 score at the 11-month follow-up. Secondary outcomes include the change in the nasal polyp score, clinical control of CRS, general health-related quality of life (HRQoL), loss of productivity, peak nasal inspiratory flow (PNIF) ± acoustic rhinometry (ARM), olfaction test (Sniffin' Sticks, identification), spirometry and peak expiratory force (PEF) and findings in pathological analysis at 12 -months of follow-up.Discussion: AirGOs Medical trial will lead to a better understanding of the efficacy and safety of ATAD in patients with severe CRSwNP, N-ERD and asthma.