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

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-ß 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).

Allergen immunotherapy effectively reduces the risk of exacerbations and lower respiratory tract infections in both seasonal and perennial allergic asthma: a nationwide epidemiological study.

BACKGROUND: Allergic asthma is associated with increased risk of respiratory tract infections and exacerbations. It remains unclear whether this susceptibility is conditioned by seasonal or by perennial allergy. AIM: To investigate perennial allergy compared with seasonal allergy as a risk factor for lower respiratory tract infections and exacerbations in asthma and whether this risk can be reduced by allergen immunotherapy (AIT). METHODOLOGY: This is a prospective register-based nationwide study of 18-44-year-olds treated with AIT during 1995-2014. Based on the type of AIT and use of anti-asthmatic drugs, patients were subdivided into two groups: perennial allergic asthma (PAA) versus seasonal allergic asthma (SAA). Data on antibiotics against lower respiratory tract infections (LRTI) and oral corticosteroids for exacerbations were analysed before starting AIT (baseline) and 3 years after completing AIT (follow-up). RESULTS: We identified 2688 patients with asthma treated with AIT, of whom 1249 had PAA and 1439 had SAA. At baseline, patients with SAA had more exacerbations (23.8% versus 16.5%, p≤0.001), but there were no differences in LRTI. During the 3-year follow-up, we observed a highly significant reduction of exacerbations with an average decrease of 57% in PAA and 74% in SAA. In addition, we observed a significant reduction of LRTI in both PAA and SAA: 17% and 20% decrease, respectively. CONCLUSION: AIT effectively reduced the risk of exacerbations and lower respiratory tract infections in both seasonal and perennial allergic asthma. Perennial allergy is seemingly not a stronger risk factor for respiratory infections and exacerbations than seasonal allergy.

Allergic asthma is associated with increased risk of infections requiring antibiotics.

BACKGROUND: Viral infection and allergy have been identified as major risk factors for exacerbation in asthma, especially in the presence of both. However, whether patients with allergic asthma are more susceptible to respiratory infections requiring antibiotics remains unknown. OBJECTIVE: To investigate allergy as a risk factor for respiratory infections requiring antibiotics based on register data from a nationwide population of patients with asthma. METHODS: A register-based prospective follow-up study was performed using the Danish prescription database. In the inclusion period from 2010 through 2011, we identified patients with allergic asthma 18 to 44 years old. Patients were investigated during the follow-up period from 2012 through 2013, depending on their prescription drug use of antiallergic medication and antibiotics. Odds ratios were adjusted for age, sex, asthma severity, education, and urban vs rural residence. RESULTS: In a nationwide population we identified 60,415 patients with asthma. Based on prescriptions fillings for antiallergic medication, patients were subdivided into (1) nonallergic asthma (n = 35,334, 51.5%) and (2) allergic asthma (n = 25,081, 48.5%). Allergic asthma was associated with an increased risk of filling at least 2 antibiotic prescriptions per year compared with nonallergic asthma (odds ratio 1.28, 95% confidence interval 1.24-1.33, P < .0001). Interestingly, a subgroup analysis showed a protective effect of immunotherapy against the risk of requiring antibiotics (odds ratio 0.76, 95% confidence interval 0.66-0.87, P = .0001). CONCLUSION: Patients with allergic asthma have an increased risk of being prescribed antibiotics for respiratory infections compared with those with nonallergic asthma. Treatment with allergen immunotherapy appears to have a protective effect against this risk.