How to hit the allergy target: A critical appraisal of intralymphatic immunotherapy with practical recommendations on ultrasound-guided injections.

BACKGROUND: Intralymphatic immunotherapy (ILIT) represents a promising novel approach treating allergic diseases. However, no standardized procedures or recommendations have been established or reported, despite the recognized fact that treatment efficacy relies on the ability to inject the allergen intranodally. OBJECTIVE: We aim to provide a critical appraisal of ILIT as a method of allergen immunotherapy and to deliver practical recommendations for accurate ILIT. METHODS: One hundred and seventy-three ILIT injections were performed in 28 (47%) women and 32 (53%) men with median age of 29 years (21-59). The injections were ultrasound-guided and recorded for retrospective analysis with respect to injection location, needle visibility, medication release, and patient characteristics. RESULTS: The results show that the correct positioning of the needle within the lymph node (LN) was most critical. If the whole length of the needle bevel was not inserted into the LN, substance backflush into the interstitium was observed. Selecting a more superficial LN and inserting the needle at a smaller angle towards the LN significantly improved needle visibility in the ultrasound. Longitudinal results showed that continuous practice significantly correlated with improved needle visibility and more accurate ILIT injections. CONCLUSION: Based on our results and practical experience, we propose several recommendations for LN selection and the correct handling of ultrasound probe and needle. We are confident that ILIT standardization and training will be important as to meet the goals of good safety and efficacy of ILIT.

Intralymphatic immunotherapy with birch and grass pollen extracts. A randomized double-blind placebo-controlled clinical trial.

INTRODUCTION: There is a need to evaluate the safety and efficacy of intralymphatic immunotherapy (ILIT) for inducing tolerance in patients with allergic rhinitis. METHODS: Thirty-seven patients with seasonal allergic symptoms to birch and grass pollen and skin prick test >3 mm and/or IgE to birch and timothy >0.35 kU/L were randomized to either ILIT, with three doses of 0.1 mL of birch pollen and 5-grass pollen allergen extracts on aluminium hydroxide (10,000 SQ-U/ml; ALK-Abelló) or placebo using ultrasound-guided intralymphatic injections at monthly intervals. Daily combined symptom medical score and rhinoconjunctivitis total symptom score were recorded during the peak pollen seasons the year before and after treatment. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were recorded annually starting 2 years after treatment. Circulating proportions of T helper cell subsets and allergen-induced cytokine and chemokine production were analysed using flow cytometry and ELISA. RESULTS: There were no differences between the groups related to daily combined symptom medical score the year before and after treatment. Two years after ILIT (after unblinding), the actively treated group reported significantly fewer symptoms, lower medication use and improved quality of life than did the placebo group. After the pollen seasons the year after ILIT, T regulatory cell frequencies and grass-induced IFN-γ levels increased only in the actively treated group. CONCLUSION: In this randomized controlled trial, ILIT with birch and grass pollen extract was safe and accompanied by immunological changes. Further studies are required to confirm or refute the efficacy of the treatment.

The effect of the COVID-19 pandemic on severe asthma care in Europe: will care change for good?

Background: The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods: In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results: 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions: Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.

Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen.

INTRODUCTION: There is a need for a fast, efficient and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective. METHODS: Patients with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml, ALK-Abelló), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production were analysed by flow cytometry and Luminex. RESULTS: The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased 3 years after treatment. CONCLUSIONS: Intralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective and may be associated with bystander immune modulatory responses. CLINICAL TRIAL REGISTRATION: EudraCT (2013-004726-28).

HealthSWEDE: costs with sublingual immunotherapy-a Swedish questionnaire study.

BACKGROUND: The aim of this cross-sectional survey was to compare the health-economic consequences for allergic rhinitis (AR) patients treated with sublingual Immunotherapy (SLIT) in terms of direct and indirect costs with a reference population of patients receiving standard of care pharmacological therapy. METHODS: Primary objective was to analyse the health-economic consequences of SLIT for grass pollen allergy in Sweden vs reference group waiting for subcutaneous immunotherapy (SCIT). A questionnaire was mailed to two groups of AR patients. RESULTS: The questionnaire was distributed to 548 patients, 307 with SLIT and 241 in reference group (waiting for SCIT). Response rate was 53.8%. Mean annual costs were higher for reference patients than SLIT group; € 3907 (SD 4268) vs € 2084 (SD 1623) p < 0.001. Mean annual direct cost was higher for SLIT-patients, € 1191 (SD 465) than for reference, € 751 (SD 589) p < 0.001. Mean annual indirect costs for combined absenteeism and presenteeism were lower for patients treated with SLIT, € 912 (SD 1530), than for reference, € 3346 (SD 4120) p < 0.001, with presenteeism as main driver. CONCLUSIONS: SLIT seems to be a cost-beneficial way to treat seasonal AR. This information might be used to guide future recommendations.

Intralymphatic Immunotherapy: Update and Unmet Needs.

Allergen-specific immunotherapy (AIT) is the only allergy treatment that confers long-term symptom amelioration for patients suffering from allergy. The most frequently used allergen application route is subcutaneous injection (SCIT), commonly taken as the gold standard, followed by sublingual (SLIT) or oral (OIT) application of allergen preparations. This is an up-to-date review of the clinical evidence for a novel route of allergen application, i.e., directly into lymph nodes - intralymphatic immunotherapy (ILIT). The major advantages of ILIT over the current AIT approaches are its short duration and the low allergen doses administered. The whole treatment consists of merely 3 ultrasound-guided injections into inguinal lymph nodes 1 month apart. While the number of patients included in randomised controlled trials is still limited, the clinical results for ILIT are encouraging, but more clinical trials are needed, as well as more preclinical work for optimising formulations.

[When and how to step down asthma treatment]. / Många överbehandlas med astmamedicin - Algoritm för nedtrappning av astmaläkemedel är ett hjälpmedel för att uppnå optimal behandling.

Swedish asthma guidelines recommend treating asthma with the lowest effective dose possible. These recommendations are both hard to follow and seldom considered enough in asthma care today. As an example, combination therapy with inhaled corticosteroids (ICS) and long acting beta agonists (LABA) should only be considered if asthma control is not achieved with low to medium dose ICS daily. However, the Swedish National Board of Health and Welfare estimates that 120 000 asthma patients are overmedicated with combination therapy. Guidelines are clear in instructions of when and how to step up asthma treatment, while instructions for stepping down are not that obvious. In this article, we present an asthma treatment algorithm for step 1-3 in adults for use in clinical practice (Fig. 1), where stepping down asthma treatment is considered as an alternative. Included are also instructions of how to step down asthma treatment (Fig. 2). We conclude that stepping down is possible to do in a safe way in certain patient groups while maintaining asthma control. If possible risks are taken into consideration, stepping down asthma treatment can be done in every clinical setting.

Expert Nordic perspectives on the potential of novel inhalers to overcome unmet needs in the management of obstructive lung disease.

The effective self-management of obstructive lung disease is dependent upon the patient achieving good inhaler technique. However, many current inhalers are complicated to use, which may lead to handling difficulties. These difficulties can cause clinically relevant errors, whereby pharmacotherapy fails to achieve adequate lung deposition and therapeutic effect. In this report, the potential of novel inhaler devices to overcome unmet needs in the management of obstructive lung disease is considered by a panel of Nordic experts. The panel concludes that innovative inhalers can contribute to good disease management and better use of healthcare resources.