House dust mite-sublingual allergen immunotherapy (HDM-SLIT) improves bronchial epithelial antiviral resistance to viral infection in patients with allergic asthma, according to a study in the American Journal of Respiratory and Critical Care Medicine.
Although allergen immunotherapy reduces asthma exacerbations and prevents respiratory infections that may require antibiotics, it is unknown whether allergen immunotherapy changes antiviral immunity. To explore the effects of this type of treatment, researchers investigated the effects HDM-SLIT on the bronchial epithelial antiviral and inflammatory responses in patients with allergic asthma.
The randomized, double-blinded, placebo-controlled VITAL study compared the effect of HDM-SLIT and placebo on the in vitro response to polyinosinic-polycytidylic acid (poly[I:C]), a viral infection mimic, in human bronchial epithelial cells (HBECs). Conducted at a hospital in Copenhagen, Denmark, from January 2020 through February 2022, the trial included nonsmoking adults aged 18 to 65 years with persistent-mild/moderate-severe HDM-induced rhinitis and asthma who were on a stable inhaled corticosteroid (ICS) regimen.
A total of 39 patients (mean [SD] age, 28 [8.0] years; 64% female) were randomly assigned to 24 weeks of HDM-SLIT (n=20) or placebo (n=19) as an add-on therapy for maintenance asthma treatment. They underwent a complete clinical and respiratory evaluation at baseline and at week 24 (prior to bronchoscopy). The primary outcome was the change in interferon (IFN)-β gene expression in human bronchial epithelial cells at week 24. The full study protocol was completed by 18 patients in both groups.
Human bronchial epithelial cells obtained before treatment had a similar response to the poly(I:C) in the placebo and HDM-SLIT groups regarding type I and III IFNs expression. The induction at week 24 of IFN-β (type I IFN) after poly(I:C) stimulation was greater in response to HDM-SLIT therapy vs baseline at the gene (P =.009) and protein (P =.020) level and was not observed in the placebo group. The pattern was similar for type III IFN (IFN-λ) expression, with a greater induction in response to poly(I:C) occurring after HDM-SLIT (P =.030) that was not found in the placebo group.
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Overall, these findings support the use of allergen immunotherapy for the prevention of exacerbation and respiratory infections in patients with HDM-allergic asthma and warrant further investigations of allergen immunotherapy in patients with seasonal allergic asthma.
Stimulation with poly(I:C) induced IL-33 expression in HBECs obtained before treatment. The induction of IL-33 gene expression tended to be reduced in the HDM-SLIT arm (P =.09) vs baseline and was significantly decreased vs the placebo group. IL-33 protein release decreased (P =.009) in unstimulated human bronchial epithelial cells from HDM-SLIT vs placebo.
Poly(I:C) stimulation induced the pro-inflammatory cytokines interleukin (IL)-8, tumor necrosis factor-α, IL-6, and IL-1β. The induction did not change in the placebo group, although HDM-SLIT increased the induction of interleukin-6 (P =.009), as well as tumor necrosis factor-α (P =.08) and IL-8 (P =.05) in HBECs stimulated with poly(I:C).
Serious adverse events (SAEs) were observed in 2 patients in the HDM-SLIT group — 1 participant had angioedema of the tongue and lips and 1 had pleuritis and was hospitalized following bronchoscopy. In the placebo group, 1 SAE was observed owing to pyelonephritis.
The study is limited by the lack of consideration of several factors that could affect the antiviral response of airway epithelial cells.
“Overall, these findings support the use of allergen immunotherapy for the prevention of exacerbation and respiratory infections in patients with HDM-allergic asthma and warrant further investigations of allergen immunotherapy in patients with seasonal allergic asthma,” stated the researchers.
Disclosure: This research has been supported in part by ALK Abelló A/s, and Pharmaxis Ltd. Please see the original reference for a full list of disclosures.
