Evaluation of Nasal Inflammatory Biomarkers

Biomarkers will be sampled by nasal filter paper (NFP) adsorption and lavage (NLF) prior to and following NAC. Samples from initial subjects (Cohort A; n~6) will be used primarily for validation of biomarker assays in nasal filter paper eluates. Validated biomarker assays will be applied to analyze biomarker changes in a further cohort of subjects (Cohort B; n~12) with the aim of fully defining the optimum panel and sampling time points for future studies.

Inclusion criteria

• Able and willing to give written informed consent.
• Male or female, age 18-65 years.

Women will be considered for inclusion if they are:

• Not pregnant, as confirmed by pregnancy test, and not nursing.
• Of non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is pre-menarchal, or post-menopausal with documented proof of hysterectomy or tubal ligation, or meets clinical criteria for menopause and has been amenorrhoeic for more than 1 year prior to the screening visit).
• Of childbearing potential and using a highly effective method of contraception during the entire study, as defined by at least one of the following

• vasectomised partner
• sexual abstinence (the lifestyle of the female should be such that there is complete abstinence from intercourse from two weeks prior to Visit 2 procedures until at least 72 hours after NAC)
• implants, injectables, combined oral contraceptives, hormonal IUDs or double-barrier methods (i.e. any double combination of IUD, condom with spermicidal gel, diaphragm, sponge, and cervical cap)
• History of seasonal allergic rhinitis to grass pollen with symptoms during the 2016 and 2017 allergen season requiring treatment with anti-histamines, nasal corticosteroids or leukotriene antagonists.
• Absence of significant current symptoms of allergic rhinitis consistent with being out of season for their principal allergen (eg grass).
• Skin prick test positive for mixed grass pollen allergen at Visit 1 or within one year prior to screening.

Exclusion criteria

• Asthma requiring more than inhaled short-acting beta-2 agonists.
• Spirometry showing FEV1 <80% predicted
• Subjects who have smoked more than 5 cigarettes in the last 6 months or have a smoking history of ≥10 pack years.
• Upper or lower respiratory tract infection in the prior 4 weeks.
• Nasal or lung provocation procedure (eg, allergen challenge) conducted in the prior 4 weeks.
• Significant nasal deformity, recent nasal surgery or obstructing nasal polyps.
• History of anaphylaxis (any cause), or previous severe hypersensitivity reaction to any of the test agents for SPT or NAC.
• Recent participation in a study of an investigational medicinal product (IMP) which could interfere with markers evaluated in this research
• Use of any medications according to section 5.2 in the period indicated before Visit 1