A retrospective cohort study to evaluate the relationship of airway hyperresponsiveness to type 2 biomarkers in persistent asthma

Airway hyperresponsiveness (AHR) is a hallmark of persistent asthma measured using direct or indirect airway bronchial challenge testing. The purpose of this study is to investigate the putative relationships between type 2 inflammatory biomarkers, airway geometry (FEV1 and FEF25-75) and specific IgE (RAST or skin prick) to AHR. We performed a retrospective analysis of our database (n = 131) of patients with asthma. Of these subjects, 75 had a histamine challenge and 56 had a mannitol challenge. Fractional exhaled nitric oxide (FeNO) and specific immunoglobulin E (IgE) but not blood eosinophils were significantly higher in patients with AHR to either histamine or mannitol. FEV1 % and FEF25 - 75 % were significantly lower in patients with AHR. Elevated Type 2 biomarkers including FeNO and specific IgE but not blood eosinophils were associated with AHR. Highlights: FeNO and specific IgE but not blood eosinophils are raised in patients with airway hyperresponsiveness. Abbreviations: AHR: Airway Hyperresponsiveness; AMP: Adenosine Monophosphate; AUC: Area Under Curve; EOS: Eosinophils; FeNO: Fractional exhaled Nitric Oxide; FEV1: Forced Expiratory volume in 1 Second; FEF25-75: Forced mid Expiratory Flow Rate Between 25% and 75% of Forced Vital Capacity (FVC); ICS: Inhaled Corticosteroid; IgE: Immunoglobulin E; µg: microgram; Mg/Ml: Milligrams per millilitre; PD15: Provocative Dose of Mannitol Resulting in 15% Drop in FEV1; PC20: Provocative Concentration of Histamine Resulting in 20% Drop in FEV1 ; Ppb: Parts per billion; RAST: Radioallergosorbent Testing for Specific IgE; ROC: Receiver Operator Characteristics; SEM: Standard Error of Means; T2: Type 2 Inflammation