Poly-unsaturated Fats for Improving Nasal Polyps and Asthma

Asthma is a syndrome compromising many phenotypes including N-ERD (caused by increased 4-series leukotriene (LT) production). n-3 PUFA supplementation modulates 4-series LT and has anti-inflammatory effects. However, other than in a pilot study with dietary manipulation, the effects of NERD are unknown. The primary objective is to determine whether n-3 PUFA supplementation in people with N-ERD can improve asthma control using the asthma control questionnaire (ACQ-7). Secondary objectives are to determine whether n-3 PUFA improves asthma and rhinitis symptoms and quality of life and airway calibre. Mechanistic objectives are to assess effects on red blood cell fatty acid composition, cyclooxygenase pathways and airway inflammation. This is a placebo controlled randomised controlled parallel multicentre study with of 6g per day of PUFA for 6 months in people with N-ERD and poor asthma control. Ninety-eight people will be included in the study if they have a reliable history of N-ERD or a positive nasal aspirin challenge, an ACQ-7 \> 1.5 and are on stable treatment. People with other significant disease, recent respiratory tract infection, receiving aspirin desensitisation, biological asthma therapies will be excluded, as will those with a significant smoking history or alcohol consumption. The intervention will be 6g of n-3 PUFA (EPA and DHA as six (5.04g EPA+DHA) taken once daily, or in divided doses, with food for 6 months. The control will be matched placebo. Measurements will be at be made at baseline, 3 months and 6 months for ACQ-7 (equivalent to ACQ-6 plus spirometry), exhaled nitric oxide (FeNO) and blood for red blood cell fatty acid concentration, blood eosinophil count and safety markers. The following questionnaires will also be undertaken at these time-points: Mini Asthma Quality of Life Questionnaire (mini-AQLQ), and Euroqol 5 dimension 5 level (EQ5D-5L). The ACQ-6 will be measured every 6 weeks throughout the study and the food frequency questionnaire will be measured at baseline and 6 months. Urine will be analysed for uLTE4 and prostaglandin D2 at baseline and 6 months. Induced sputum will be obtained at baseline and 6 months in a subgroup for differential cell count and specialised pro-resolving mediators.