Sublingual immunotherapy improves bronchial epithelial antiviral resistance
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Key takeaways:
- Treatment improved bronchial epithelial expression of IFN-beta and IFN-lambda while decreasing IL-33.
- Allergy immunotherapy may improve outcomes among patients with house dust mite allergic asthma.
Sublingual immunotherapy for house dust mite allergic asthma improved bronchial epithelial antiviral resistance to viral infection, according to a study published in the American Journal of Respiratory and Critical Care Medicine.
These findings may explain why this treatment is effective in reducing exacerbations with allergic asthma, Christian Woehlk, MD, PhD, respiratory research unit, department of respiratory and infectious medicine, Bispebjerg Hospital, Copenhagen, Denmark, and colleagues wrote.
Also known as the VITAL study, the Effect of Allergen Immunotherapy on Anti-viral Immunity in Patients with Allergic Asthma study involved 20 adults who received house dust mite sublingual immunotherapy (HDM-SLIT) and 19 who received placebo, both for 24 weeks, with 18 patients completing the full protocol in each group.
At week 24, the treatment group had higher induction of interferon-beta (IFN-beta) after polyinosinic:polycytidylic acid (poly(I:C)) stimulation in response to HDM-SLIT compared with baseline at the gene (P = .009) and protein (P = .02) levels, but the placebo group did not.
Expression of type III IFN such as IFN-lambda followed a similar pattern after HDM-SLIT with higher induction in response to poly(I:C) (P = .03), the researchers said, but the placebo group did not experience this expression.
There was no significant difference in the relative increase in expression of IFN-beta and IFN-lambda between the groups, the researchers continued, but there was a trend in IFN-beta protein release.
Poly(I:C) stimulation also induced IL-33 expression in human bronchial epithelial cells (HBECs). This induction tended to decrease in the treatment group (P = .09) compared with baseline and significantly decrease compared with the placebo group.
Unstimulated HBECs had reduced IL-33 protein release in the treatment group compared with the placebo group as well (P = .009). But at week 24, there was no change in the expression of gene or protein thymic stromal lymphopoietin induced by poly(I:C) within or between the groups.
Compared with unstimulated cells, HBECs that were stimulated with poly(I:C) experienced increased concentrations of T2 cytokines IL-4, IL-13 and IL-10 at 24 hours, the researchers said, but there were no differences or changes within or between the groups.
Poly(I:C) stimulation also induced proinflammatory cytokines, including IL-8, tumor necrosis factor alpha (TNF-alpha), IL-6 and IL-1-beta. The placebo group did not experience any general alterations in this induction, the researchers said, but the treatment group experienced increased induction of IL-6 (P = .009) as well as TNF-alpha (P = .08) and IL-8 (P = .05).
Provoking doses of inhaled mannitol that caused a 15% reduction in FEV1 increased significantly in the treatment (P < .001) and placebo (P = .02) groups, the researchers said, but without any difference between the groups.
Before and after bronchodilator treatment, both groups experienced increased FEV1 as well, but without any differences between them. The researchers observed no changes in fractional exhaled nitric oxide either.
Both groups also experienced Asthma Control Questionnaire, Asthma Quality of Life Questionnaire, and Rhinoconjunctivitis Quality of Life Questionnaire score improvements as well, again without any differences between groups.
Furthermore, the treatment group experienced increases in total IgE (P < .001), IgE Dermatophagoides pteronyssinus (P < .001) and Dermatophagoides farinae (P < .001), in addition to blocking IgG and IgE-blocking factor.
The treatment group reported one patient with angioedema of the tongue or lips after treatment initiation and another who developed pleuritis and was admitted after bronchoscopy. In the placebo group, one patient developed pyelonephritis.
Overall, the researchers said, HDM-SLIT significantly enhanced the bronchial epithelial gene expression induced by poly(I:C) of IFN-beta, IFN-lambda and IL-6 in addition to the release of IFN-beta protein. Also, epithelial cells challenged with poly(I:C) experienced reduced IL-33 gene expression.
These findings indicate that HDM-SLIT enhances antiviral resistance IFNs, the researchers said, but has mixed responses pertaining to epithelial inflammatory tolerance to viral infection. Allergy immunotherapy may help prevent exacerbation and respiratory infections, the researchers concluded, among patients with HDM-allergic asthma.
Perspective
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Michael S. Blaiss, MD, FACAAI, FAAAAI
This study continues research showing the effects of allergen immunotherapy as a disease-modifying treatment for allergic asthma and rhinitis. It adds to our understanding of allergen immunotherapy’s action on mediators involved in viral infections in our atopic patients.
We know that viral infections are increased in atopic children and that they are a major source of asthma exacerbations. I am not surprised that this study found factors such as increases in gene expression of IFN-beta and IFN-lambda, which are protective against viral infection.
It is important to note that allergen immunotherapy was only evaluated after 24 weeks, which is a short time, so results may be better with longer use. Also, this was an adult study. We know that viral infections are a major trigger of asthma in children. We do not know if these results apply to children.
It is hard to single out allergen immunotherapy improvement in allergic asthma and rhinitis, as we are doing multiple approaches to improve our allergic asthma and rhinitis patients, including medications and avoidance procedures. Nevertheless, I do believe that allergen immunotherapy is playing a major role in preventing exacerbations, including ones from viruses.
We know that allergen immunotherapy is vastly underused in the allergic asthma and rhinitis population. This research is just another example of why more patients should be getting the benefit of this disease-modifying therapy.
We need studies in pediatric patients to confirm results seen in adults. We also need studies that look at longer durations of allergen immunotherapy to see if this leads to more resistance against viral infections. It would be important to do studies with bronchial provocation with viruses to see the total interaction of not only bronchial epithelial cells, but also the other mediators and cells in the lungs involved in inflammation. Will this show a more robust effect in viral infections?
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This was a very interesting study — and somewhat novel. In all, I see this as thought provoking, but not necessarily significant, and its clinical relevance is questionable.
I personally do not use any allergy immunotherapy with a goal of improving viral immunity in my asthmatics. However, immunotherapy as a treatment for rhinitis and asthma is standard of care in certain situations.
If this concept were actually shown to play out in patients in a clinical setting, it would improve care — meaning, if allergen immunotherapy (whether sublingual or subcutaneous) could decrease respiratory viral infections in patients with asthma, it would be important to better understand what this mode of therapy can do for patients.
It would be a harder study to do, but enrolling asthmatics in a double-blind study of allergen immunotherapy and then following over time to see if you can truly decrease respiratory viral infection frequency or severity would be a great next step.
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