Allergen Immunotherapy Enhances Airway Epithelial Antiviral Immunity in Patients With Allergic Asthma (VITAL Study): A Double-Blind Randomized Controlled Trial

To assess the effects of house dust mite (HDM) sublingual immunotherapy (SLIT) on the antiviral and inflammatory response of the bronchial epithelium in patients with allergic asthma.

This randomized, double-blind, placebo-controlled, study included nonsmoking adults 18 to 65 years old with a reported or objectively confirmed history of asthma on maintenance inhaled corticosteroid therapy with test positive HDM allergy. Exclusion criteria included recent treatment with oral steroids, any antibiotics, immunosuppressive medications, immunoglobulin or blood products, or prior allergy immunotherapy (AIT).

Subjects were treated with SLIT (n = 18) or placebo (n = 18) in addition to their maintenance therapy for 24 weeks. Bronchial epithelial samples, taken at baseline and at 24 weeks, were stimulated with poly (I:C) and cytokine production, including IFN-β, IFN-λ, IL-33, IL-25, IL-6, TNF-α, IL-4, IL-13, and IL-10, was measured by reverse transcription polymerase chain reaction and enzyme-linked immunoassay. Pulmonary function testing, quality of life asthma questionnaires, and in vitro testing for HDM allergy were evaluated at baseline and at 24 weeks.

There were no differences in the pulmonary function testing parameters, the asthma questionnaire scores, or the HDM IgE and IgG4 levels between AIT and placebo treated subjects at the end of the 24 week trial. The poly (I:C) stimulated IFN-β mRNA (P = .009) and protein (P = .020) and IFN-λ mRNA (P = .030) were relatively increased, but poly (I:C) stimulated IL-33 mRNA (P = .09) and protein (P = .009) was relatively decreased in the bronchial epithelial cells of HDM-SLIT treated subjects as compared with placebo at 24 weeks. Poly (I:C) stimulated IL-6 (P = .009), TNF-α (P = .08), IL-8 (P = .05) were also relatively increased in the HDM-SLIT treated group as compared with placebo. There were no statistically significant differences in the relative production of IL-4, IL-13, and IL-10 levels and other cytokines between HDM-SLIT and placebo treated subjects at the end of the trial. Three reported SAEs included one case each of angioedema and pleuritis in the treatment group and pyelonephritis in the placebo group.

HDM-AIT increased antiviral immunity and modified the inflammatory response of airway epithelial cells in patients with allergic asthma.

By modifying antiviral and inflammatory responses in the airway epithelium, this study suggests that AIT may help reduce the frequency of viral-triggered asthma exacerbations, which could impact asthma control and progression. Small sample size, adult subjects, and short duration of therapy are some of the limitations for the clinical implications. This study also does not address how poly- or mono-allergic sensitization could affect immune response as well the effects on the immune response in nonairway epithelial cells. However, these findings contribute to further elucidating the complicated immunomodulatory effects of AIT and could support the potential role of AIT as an integral part of the management in allergic asthma.