High-dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase.

BACKGROUND: The same dosing schedule, 1000 SQ-U times three, with one-month intervals, have been evaluated in most trials of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis (AR). The present studies evaluated if a dose escalation in ILIT can enhance the clinical and immunological effects, without compromising safety. METHODS: Two randomized double-blind placebo-controlled trials of ILIT for grass pollen-induced AR were performed. The first included 29 patients that had recently ended 3 years of SCIT and the second contained 39 not previously vaccinated patients. An up-dosage of 1000-3000-10,000 (5000 + 5000 with 30 minutes apart) SQ-U with 1 month in between was evaluated. RESULTS: Doses up to 10,000 SQ-U were safe after recent SCIT. The combined symptom-medication scores (CSMS) were reduced by 31% and the grass-specific IgG4 levels in blood were doubled. In ILIT de novo, the two first patients that received active treatment developed serious adverse reactions at 5000 SQ-U. A modified up-dosing schedule; 1000-3000-3000 SQ-U appeared to be safe but failed to improve the CSMS. Flow cytometry analyses showed increased activation of lymph node-derived dendritic but not T cells. Quality of life and nasal provocation response did not improve in any study. CONCLUSION: Intralymphatic immunotherapy in high doses after SCIT appears to further reduce grass pollen-induced seasonal symptoms and may be considered as an add-on treatment for patients that do not reach full symptom control after SCIT. Up-dosing schedules de novo with three monthly injections that exceeds 3000 SQ-U should be avoided.

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.

Multidisciplinary approaches to identifying and managing global airways disease: Expert recommendations based on qualitative discussions.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma frequently co-exist and share pathologic features. Taking a "global" treatment approach benefits diagnosis and treatment of both, but care is often siloed by specialty: joined-up clinics are uncommon. Our objectives were to explore expert opinion to give practical suggestions to identify adults needing global airways care; enhance cross-specialty working; and widen knowledge to support diagnosis and management, integrate with existing care pathways, and supplement existing guidelines. Methods: Sixteen practicing physicians from northern Europe were invited for their national and/or international standing in treating asthma and/or chronic rhinosinusitis. Appreciative Inquiry techniques were used to guide their discussions. Results: Key themes arising were screening and referral, collaboration on management, awareness and education, and research. Provided are screening criteria and suggestions for specialist referrals, and pointers for physicians to optimize their knowledge of global airways disease. Collaborative working is underscored, and practical suggestions are given for multidisciplinary teamworking within global airways clinics. Research gaps are identified. Conclusion: This initiative provides practical suggestions for optimizing the care of adults with CRSwNP and asthma. Discussion of the role of allergy and drug exacerbations on these conditions, and care for patients with other global airways diseases were beyond scope; however, we expect some principles of our discussion will likely benefit patients with related conditions. The suggestions bridge asthma and CRSwNP management guidelines, envisioning interdisciplinary, global airway clinics relevant to various clinical settings. They highlight the value of joint screening for early recognition and referral of patients.

A preseason booster prolongs the increase of allergen specific IgG4 levels, after basic allergen intralymphatic immunotherapy, against grass pollen seasonal allergy.

BACKGROUND: Allergen specific IgG4 levels have been monitored as a surrogate marker for the tolerance inducing effect of subcutaneous immunotherapy (SCIT) in many studies. Its accuracy at group level has been well established, but IgG4 has not yet found its place in the daily care of immunotherapy patients. METHODS: Intralymphatic immunotherapy (ILIT) is a novel route for allergy vaccination against pollen allergy, where an ultrasound-guided injection of 1000 SQ-U Alutard is given directly into a groin lymph node. The suggested standard dosing so far has been one injection with 4 weeks in-between. In total 3000 SQ-U with the treatment completed in 2 months. IgG4 was measured with Immulite technique and rhinoconjunctivitis symptoms were estimated with daily online questionnaires. Mann-Whitney U-test and Wilcoxon Signed Rank test were applied for comparisons between groups and within groups, respectively. RESULTS: The present study demonstrates that a single, preseason ILIT booster of 1000 SQ-U Alutard 5-grasses®, re-increases the allergen specific timothy-IgG4 levels, in patients already treated with ILIT before the previous pollen season. It also shows the feasibility of the ILIT-route for allergy vaccination of rhinitis patients, with or without concomitant asthma, with low degree of side effects and reconfirms high and sustained patient satisfaction. CONCLUSIONS: It is tempting to suggest that the allergen specific IgG4 levels can be used to build an intuitive algorithm for future clinical guidance of ILIT patients.Trial registration Is Intralymphatic Allergen Immunotherapy Effective and Safe?, ClinicalTrials.gov Identifier NCT04210193. Registered 24 December 2019-Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT04210193?term=NCT04210193&draw=2&rank=1.

Capsaicin cough sensitivity in allergic asthmatic patients increases during the birch pollen season.

BACKGROUND: A change in neural responsiveness may occur as the result of allergic inflammation in the lower airways as well as in the upper airways. In the lower airways, capsaicin cough sensitivity is known to reflect sensory neural reactivity. OBJECTIVE: The aim of this study was to establish whether allergic inflammation changes airway neural sensory reactivity during prolonged allergen exposure. METHODS: Ten nonsmoking patients with birch pollen-allergic asthma performed a capsaicin inhalation challenge twice, once in the off-pollen season and once during the pollen season. The number of coughs and symptoms induced by capsaicin were recorded and compared with those of healthy control subjects. RESULTS: The response to capsaicin, expressed as number of coughs, increased in a dose-dependent manner during both tests. Before the season, the response was similar to that of healthy control subjects, but during the pollen season, the reactivity was significantly increased. Variations in forced expiratory volume in 1 second were not significant before and after each challenge, and values did not change during the pollen season as compared with the winter season. CONCLUSIONS: Sensory reactivity in allergic asthmatic patients may be increased during prolonged allergen exposure as during the pollen season. This finding suggests that allergic inflammation in the lower and/or upper airways may trigger neurogenic mechanisms of significant clinical importance.