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

Woehlk, Christian ; Ramu, Sangeetha LU ; Sverrild, Asger ; Nieto-Fontarigo, Juan José LU ; Vázquez-Mera, Sara ; Cerps, Samuel LU ; Pulga, Alexis ; Andreasson, Louise Munkholm ; Eriksen, Lise Lotte and Dyhre-Petersen, Nanna , et al. (2023) In American Journal of Respiratory and Critical Care Medicine 207(9). p.1161-1170
Abstract

Rationale: Allergic asthma is linked to impaired bronchial epithelial secretion of IFNs, which may be causally linked to the increased risk of viral exacerbations. We have previously shown that allergen immunotherapy (AIT) effectively reduces asthma exacerbations and prevents respiratory infections requiring antibiotics; however, whether AIT alters antiviral immunity is still unknown. Objectives: To investigate the effect of house dust mite sublingual AIT (HDM-SLIT) on bronchial epithelial antiviral and inflammatory responses in patients with allergic asthma. Methods: In this double-blind, randomized controlled trial (VITAL [The Effect of Allergen Immunotherapy on Anti-viral Immunity in Patients with Allergic Asthma]), adult patients... (More)

Rationale: Allergic asthma is linked to impaired bronchial epithelial secretion of IFNs, which may be causally linked to the increased risk of viral exacerbations. We have previously shown that allergen immunotherapy (AIT) effectively reduces asthma exacerbations and prevents respiratory infections requiring antibiotics; however, whether AIT alters antiviral immunity is still unknown. Objectives: To investigate the effect of house dust mite sublingual AIT (HDM-SLIT) on bronchial epithelial antiviral and inflammatory responses in patients with allergic asthma. Methods: In this double-blind, randomized controlled trial (VITAL [The Effect of Allergen Immunotherapy on Anti-viral Immunity in Patients with Allergic Asthma]), adult patients with HDM allergic asthma received HDM-SLIT 12-SQ or placebo for 24 weeks. Bronchoscopy was performed at baseline and at Week 24, which included sampling for human bronchial epithelial cells. Human bronchial epithelial cells were cultured at baseline and at Week 24 and stimulated with the viral mimic polyinosinic:polycytidylic acid (poly(I:C)). mRNA expression was quantified using qRT-PCR, and protein concentrations were measured using multiplex ELISA. Measurements and Main Results: Thirty-nine patients were randomized to HDM-SLIT (n = 20) or placebo (n = 19). HDM-SLIT resulted in increased polyinosinic:polycytidylic acid-induced expression of IFN-β at both the gene (P = 0.009) and protein (P = 0.02) levels. IFN-λ gene expression was also increased (P = 0.03), whereas IL-33 tended to be decreased (P = 0.09). On the other hand, proinflammatory cytokines IL-6 (P = 0.009) and TNF-α (tumor necrosis factor-α) (P = 0.08) increased compared with baseline in the HDM-SLIT group. There were no significant changes in TSLP (thymic stromal lymphopoietin), IL-4, IL-13, and IL-10. Conclusions: HDM-SLIT improves bronchial epithelial antiviral resistance to viral infection. These results potentially explain the efficacy of HDM-SLIT in reducing exacerbations in allergic asthma. Clinical trial registered with www.clinicaltrials.gov (NCT04100902).

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
airway resistance, allergen immunotherapy, allergic asthma, antiviral immunity, bronchial epithelium
in
American Journal of Respiratory and Critical Care Medicine
volume
207
issue
9
pages
10 pages
publisher
American Thoracic Society
external identifiers
  • pmid:36701676
  • scopus:85159254100
ISSN
1535-4970
DOI
10.1164/rccm.202209-1708OC
language
English
LU publication?
yes
id
b6b69648-201b-44a9-bd63-f41d68403603
date added to LUP
2023-08-10 14:42:50
date last changed
2024-04-20 01:21:06
@article{b6b69648-201b-44a9-bd63-f41d68403603,
  abstract     = {{<p>Rationale: Allergic asthma is linked to impaired bronchial epithelial secretion of IFNs, which may be causally linked to the increased risk of viral exacerbations. We have previously shown that allergen immunotherapy (AIT) effectively reduces asthma exacerbations and prevents respiratory infections requiring antibiotics; however, whether AIT alters antiviral immunity is still unknown. Objectives: To investigate the effect of house dust mite sublingual AIT (HDM-SLIT) on bronchial epithelial antiviral and inflammatory responses in patients with allergic asthma. Methods: In this double-blind, randomized controlled trial (VITAL [The Effect of Allergen Immunotherapy on Anti-viral Immunity in Patients with Allergic Asthma]), adult patients with HDM allergic asthma received HDM-SLIT 12-SQ or placebo for 24 weeks. Bronchoscopy was performed at baseline and at Week 24, which included sampling for human bronchial epithelial cells. Human bronchial epithelial cells were cultured at baseline and at Week 24 and stimulated with the viral mimic polyinosinic:polycytidylic acid (poly(I:C)). mRNA expression was quantified using qRT-PCR, and protein concentrations were measured using multiplex ELISA. Measurements and Main Results: Thirty-nine patients were randomized to HDM-SLIT (n = 20) or placebo (n = 19). HDM-SLIT resulted in increased polyinosinic:polycytidylic acid-induced expression of IFN-β at both the gene (P = 0.009) and protein (P = 0.02) levels. IFN-λ gene expression was also increased (P = 0.03), whereas IL-33 tended to be decreased (P = 0.09). On the other hand, proinflammatory cytokines IL-6 (P = 0.009) and TNF-α (tumor necrosis factor-α) (P = 0.08) increased compared with baseline in the HDM-SLIT group. There were no significant changes in TSLP (thymic stromal lymphopoietin), IL-4, IL-13, and IL-10. Conclusions: HDM-SLIT improves bronchial epithelial antiviral resistance to viral infection. These results potentially explain the efficacy of HDM-SLIT in reducing exacerbations in allergic asthma. Clinical trial registered with www.clinicaltrials.gov (NCT04100902).</p>}},
  author       = {{Woehlk, Christian and Ramu, Sangeetha and Sverrild, Asger and Nieto-Fontarigo, Juan José and Vázquez-Mera, Sara and Cerps, Samuel and Pulga, Alexis and Andreasson, Louise Munkholm and Eriksen, Lise Lotte and Dyhre-Petersen, Nanna and Menzel, Mandy and Klein, Ditte K. and Hansen, Susanne and Uller, Lena and Porsbjerg, Celeste}},
  issn         = {{1535-4970}},
  keywords     = {{airway resistance; allergen immunotherapy; allergic asthma; antiviral immunity; bronchial epithelium}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{9}},
  pages        = {{1161--1170}},
  publisher    = {{American Thoracic Society}},
  series       = {{American Journal of Respiratory and Critical Care Medicine}},
  title        = {{Allergen Immunotherapy Enhances Airway Epithelial Antiviral Immunity in Patients with Allergic Asthma (VITAL Study) : A Double-Blind Randomized Controlled Trial}},
  url          = {{http://dx.doi.org/10.1164/rccm.202209-1708OC}},
  doi          = {{10.1164/rccm.202209-1708OC}},
  volume       = {{207}},
  year         = {{2023}},
}