ICS/LABA Combined With Subcutaneous Immunotherapy Modulates the Th17/Treg Imbalance in Asthmatic Children.

Rationale: The imbalance of T helper (Th17) cell and regulatory T (Treg) cell are involved in allergic asthma pathogenesis. We hypothesized that ICS/LABA could modulate the Th17/Treg imbalance and that subcutaneous immunotherapy (SCIT) could coordinate with ICS/LABA to rebalance the dysfunction of Th17/Treg. Methods: Thirty house dust mites (HDM) allergic asthmatic children and fifteen healthy control subjects were enrolled in this study. Fifteen asthmatic children were treated by ICS/LABA powder inhalation, while the other fifteen asthmatic children were treated by ICS/LABA powder inhalation combined with HDM-SCIT. Asthmatic subjects were followed up for 6 months, but 2 asthmatics treated with ICS/LABA were lost to follow-up. Flow cytometry was used to determine the proportions of Th17 and Treg in CD4+ T cells from peripheral blood mononuclear cells (PBMCs). Serum levels of IL-17A and IL-10 were assessed by ELISA. Result: ICS/LABA treatment significantly reduced the percentage of Th17 cells (1.252 ± 0.134% vs. 2.567 ± 0.386%), serum IL-17A (49.42 ± 2.643 pg/ml vs. 66.75 ± 3.442 pg/ml) and Th17/Treg ratio (0.194 ± 0.025 vs. 0.439 ± 0.072) compared to baseline (P<0.01). The ICS/LABA+HDM-SCIT treatment group showed similar reduction in the percentage of Th17 cells (1.11 ± 0.114% vs. 2.654 ± 0.276%), serum IL-17A (49.23 ± 2.131 pg/ml vs. 66.41 ± 2.616 pg/ml) and the Th17/Treg ratio (0.133 ± 0.015 vs. 0.4193 ± 0.050) (P<0.01). ICS/LABA+HDM-SCIT treatment group demonstrated elevated Treg percentages (8.483 ± 0.408% vs. 6.549 ± 0.299%) and serum IL-10 levels (127.4 ± 4.423 pg/ml vs. 93.15 ± 4.046 pg/ml), resulting in a lower Th17/Treg ratio than the ICS/LABA group. Conclusion: ICS/LABA treatment regulates Th17/Treg imbalance mainly by mitigating Th17-induced inflammation in asthma patients. The addition of SCIT further enhanced such effect by upregulating Treg cells.

Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: Results from the REACT study, a retrospective cohort study.

BACKGROUND: Allergen immunotherapy (AIT) is the only causal treatment for respiratory allergy. Long-term real-life effectiveness of AIT remains to be demonstrated beyond the evidence from randomised controlled trials (RCTs). METHODS: REACT (Real world effectiveness in allergy immunotherapy) is a retrospective cohort study using claims data between 2007 and 2017. Study eligibility was a confirmed diagnosis of allergic rhinitis (AR), with or without asthma, and AIT. To ensure comparable groups, AIT-treated subjects were propensity score matched 1:1 with control subjects, using characteristic and potential confounding variables. Outcomes were analysed as within (pre vs post AIT) and between (AIT vs control) group differences across 9 years of follow-up (ClinicalTrial.gov: NCT04125888). FINDINGS: 46,024 AIT-treated subjects were matched with control subjects and 14,614 were included in the pre-existing asthma cohort. AIT-treated subjects were 29·5 (16·3) years and 53% were male. Compared to pre-index year, AIT was consistently associated with greater reductions compared to control subjects in AR and asthma prescriptions, including both asthma controller and reliever prescriptions. Additionally, the AIT group had significantly greater likelihood of stepping down asthma treatment (P <0·0001). In addition to the reduction in asthma treatment in the AIT group, a greater reduction in severe asthma exacerbations was demonstrated (P<0·05). Reductions in pneumonia with antibiotic prescriptions, hospitalisations, and duration of inpatients stays were all in favour of AIT. INTERPRETATION: The study extends the existing RCT evidence for AIT by demonstrating longer-term and sustained effectiveness of AIT in the real world. Additionally, in patients with concurrent asthma, AIT was associated with reduced likelihood of asthma exacerbations and pneumonia. FUNDING: The study was funded by ALK A/S.

Oral immunotherapy for peanut allergy: The con argument.

BACKGROUND: In some countries of the world, peanut allergy represents an important source of anaphylactic reactions. Traditionally treated with the avoidance of responsible allergens, this condition can also be targeted by oral peanut immunotherapy. METHODS: In this study, we review the beneficial and side effects of currently available forms of peanut oral immunotherapy (POIT). We report the discussions resulting from the publication of a meta-analysis that brought to light the downsides of oral immunotherapy for peanuts. RESULTS: In some clinical situations, the risk-benefit ratio can favor peanut oral immunotherapy over avoidance. In many other situations, this is not the case. The decision must be based on the values and preferences of clinicians and patients. Those not ready to accept serious adverse effects from POIT are likely to continue the elimination diet; those motivated to achieving desensitization, and prepared to accept serious adverse effects, may choose to undergo POIT. CONCLUSIONS: Without being prejudiced against peanut oral immunotherapy, we indicate the possible evolution of treatment for this condition is in a rapidly evolving broader scenario. Among the future options, sublingual immunotherapy, parenteral immunotherapy with modified allergens, transcutaneous immunotherapy, and the use of biologics will become important options.

Effectiveness and safety of a glutaraldehyde-modified, L-tyrosine-adsorbed and monophosphoryl lipid A-Adjuvanted allergen immunotherapy in patients with allergic asthma sensitized to olive pollen: A retrospective, controlled real-world study.

BACKGROUND: Allergy to olive pollen is one of the primary causes of allergic asthma in Spain. Even though allergen immunotherapy (AIT) has shown clinical benefits in patients sensitized to different allergens, studies in asthmatic patients sensitized to olive pollen are insufficient. OBJECTIVE: To assess the effectiveness and safety of an ultra-short course of AIT with an L-tyrosine-adsorbed and monophosphoryl lipid A-adjuvanted olive pollen and olive/grass pollen extract (Pollinex Quattro®) in patients with allergic asthma in the real-world setting. METHODS: Retrospective, controlled study including patients with asthma, with and without allergic rhinitis, caused by sensitization to olive pollen from 11 centers in Spain. Patients received out-of-season (October-March) treatment with AIT in addition to their pharmacological treatment (active group) or pharmacological treatment (control group). Effectiveness variables, including unscheduled visits to the healthcare center, emergency room admissions, symptoms of asthma and rhinitis (following GEMA and ARIA classifications, respectively), and use of medication to treat asthma and rhinitis during the subsequent pollen season were compared between treatment groups. RESULTS: Of 131 study patients, 42 were treated with their usual asthma medication (control group) and 89 were treated with AIT (active group), either Pollinex Quattro® 100% olive pollen (n = 43, 48.3%) or 50% olive pollen/50% grass pollen (n = 46, 51.7%). Patients' demographic and clinical characteristics were similar between groups. The mean (SD) number of unscheduled visits to a healthcare center and emergency room admissions due to allergy symptoms was 2.19 (1.40) and 0.43 (0.63) in the control group, and 1.09 (1.25) and 0.11 (0.51) in the active group (P = 0.001 and P = 0.006, respectively). Severity and control of asthma symptoms remained unchanged (P = 0.347 and P = 0.179, respectively), rhinitis type improved (P = 0.025), and severity remained unchanged in the active compared to the control group. The use of short-acting beta-agonists and inhaled corticosteroids to treat asthma symptoms decreased in the active vs. the control group (P = 0.001 and P = 0.031, respectively). Twelve (13.5%) and two (2.2%) patients in the active group experienced local adverse reactions (edema, swelling, erythema, hives, pruritus, and heat), and systemic adverse reactions (hypertensive crisis and low-grade fever) to AIT, respectively; none was serious. CONCLUSION: AIT with Pollinex Quattro® specific for olive pollen and olive/grass pollens resulted in reduced visits to the healthcare center and emergency room and the use of asthma medication during the pollen season, indicating that this treatment was safe and effective in treating asthma in patients sensitized to these pollens.

Success factors for adherence in hyposensitization.

For the success of an immunotherapy regimen, adherence is a major success factor. The goal of our study was to identify the factors that positively and negatively influence patient compliance, and to create strategies to improve it. Four questionnaires were designed for different patient groups: A - after immunotherapy; B - during immunotherapy; C - before immunotherapy; D - no experience with immunotherapy. From March to October 2008, 790 questionnaires were collected. For the first group, questionnaire A was answered by 272 patients. Of these, 15.8% had dropped out of immunotherapy. Women had higher dropout rates than men (16.8% vs. 12.3%). The following aspects of immunotherapy were viewed by the patients as negative: time consuming (69.5%), adverse reactions (62.5%), insufficient patient information (53.7%), no change in use of symptomatic medication (33.8%) and no change in symptoms (60.7%). Despite the mentioned drawbacks, 74% of all patients would still recommend allergen immunotherapy. Questionnaire B was completed by 281 patients. In this group, 8.7% had already considered dropping out. The following unfavourable aspects were identified: time consuming (66.2%), adverse reactions (61.9%), insufficient patient information (54.8%), no change in symptoms (51.2%) and use of symptomatic medication (47.0%). Despite this, up to 95.4% of all patients would recommend immunotherapy. Questionnaire C was filled-out by 55 patients. The following reasons were rated by the patients as "important" or "very important" for the decision to start hyposensitization: long-lasting symptom alleviation (100%), few adverse reactions (98.2%), comprehensive patient information (96.3%), easy integration into daily routine (89.1%), re-assessment of therapy by doctor (83.3%) and reduced need for symptomatic medication (81.8%). Questionnaire D was filled in by 182 participants. 89% had already heard the term hyposensitization before. Their general knowledge regarding this therapy was average (3.23 on a scale of 1 - 6; where 1 = optimum). Long-lasting symptom alleviation (99.5%), comprehensive patient information (97.8%), easy integration into daily routine (96.1%), reduced symptomatic medication use (92.6%) and re-assessment by doctor (88.8%) were considered "very important" or "important" characters in the desired immunotherapy regime. Adherence to the hyposensitization schedule is essential for its success. The treating doctor should aim at choosing the right therapy and working out an individualized patient treatment plan. Equally important is providing information to the patient throughout the duration of the treatment. The doctor should assist the patient to create an optimized time schedule to help make the therapy less time-consuming.

Current opinion and review on peanut oral immunotherapy.

In the last decade, peanut oral immunotherapy research has shown promise as an alternative treatment to avoidance in peanut-allergic patients. Research has not only focused on desensitization, but also on immunologic changes and sustained-tolerance. This article reviews the current literature and the historical background of oral immunotherapy as well as immune mechanisms in oral immunotherapy and other therapies being explored in food allergic individuals.