A 5-Year Open-Label Follow-up of a Randomized Double-Blind Placebo-Controlled Trial of Intralymphatic Immunotherapy for Birch and Grass Allergy Reveals Long-term Beneficial Effects.

BACKGROUND: Intralymphatic immunotherapy (ILIT) is a novel, faster alternative to conventional allergen immunotherapy (AIT). Few previous studies have evaluated its long-term effects. The objective of the present study was to complete a 5-year follow-up of a randomized double-blind placebo-controlled trial of ILIT for a combination of birch and grass allergens. METHODS: Fifty-eight patients with allergic rhinitis were treated with either placebo or a combination of ALK Alutard Birch and Grass 1000 SQ-U administered in 3 intralymphatic injections at 1-month intervals. A year after the vaccination, the symptoms induced by nasal provocation were significantly reduced. After 5-6 years, 20 out of 26 actively treated patients were followed up with a nasal provocation test (NPT) and seasonal registration of the combined symptom and medications score (CSMS), IgE and IgG4 levels in blood, and immunological markers in blood and lymph nodes and compared with 13 unvaccinated controls. RESULTS: The reduction in the NPT response with ILIT at year 1 could not be convincingly reproduced at year 5. The new CSMS scores were markedly lower among the previously treated patients than among the control group. Furthermore, grass-specific IgG4 was increased, grass-specific IgE decreased, FcεR1 on basophils was reduced, and the fraction of memory T-cells in lymph nodes increased. CONCLUSION: The combination of seasonal clinical data and immunological parameters supports the notion of a long-lasting effect of ILIT. These data support the concept of ILIT as a good alternative to traditional AIT in pollen-induced allergic rhinitis.

A 5-Year Open-Label Follow-up of a Randomized Double-Blind Placebo-Controlled Trial of Intralymphatic Immunotherapy for Birch and Grass Allergy Reveals Long-term Beneficial Effects

Background: Intralymphatic immunotherapy (ILIT) is a novel, faster alternative to conventional allergen immunotherapy (AIT). Few previous studies have evaluated its long-term effects. The objective of the present study was to complete a 5-year follow-up of a randomized double-blind placebo-controlled trial of ILIT for a combination of birch and grass allergens. Methods: Fifty-eight patients with allergic rhinitis were treated with either placebo or a combination of ALK Alutard Birch and Grass 1000 SQ-U administered in 3 intralymphatic injections at 1-month intervals. A year after the vaccination, the symptoms induced by nasal provocation were significantly reduced. After 5-6 years, 20 out of 26 actively treated patients were followed up with a nasal provocation test (NPT) and seasonal registration of the combined symptom and medications score (CSMS), IgE and IgG4 levels in blood, and immunological markers in blood and lymph nodes and compared with 13 unvaccinated controls. Results: The reduction in the NPT response with ILIT at year 1 could not be convincingly reproduced at year 5. The new CSMS scores were markedly lower among the previously treated patients than among the control group. Furthermore, grass-specific IgG4 was increased, grass-specific IgE decreased, FcεR1 on basophils was reduced, and the fraction of memory T-cells in lymph nodes increased. Conclusion: The combination of seasonal clinical data and immunological parameters supports the notion of a long-lasting effect of ILIT. These data support the concept of ILIT as a good alternative to traditional AIT in pollen-induced allergic rhinitis (AU)

Antecedentes: La inmunoterapia intralinfática (ILIT) se ha propuesto como una alternativa novedosa y rápida frente a la inmunoterapia convencional con alérgenos (AIT). Muy pocos estudios han evaluado sus efectos a largo plazo. El objetivo del estudio fue completar un seguimiento de 5 años de un ensayo aleatorizado, doble ciego, controlado con placebo, previamente realizado, de ILIT con una combinación de alérgenos de abedul y gramíneas. Métodos: 58 pacientes con rinitis alérgica fueron tratados con placebo o una combinación de ALK Alutard Birch and Grass 1000 SQ-U, mediante tres inyecciones intralinfáticas administradas con intervalos de un mes. Un año después de la vacunación, los síntomas inducidos por provocación nasal se redujeron significativamente. Entre 5 y 6 años más tarde, 20 de los 26 pacientes tratados activamente fueron evaluados mediante nueva prueba de provocación nasal (NPT), registro estacional de la puntuación combinada de síntomas y consumo de medicamentos (CSMS), niveles de IgE e IgG4 en sangre y marcadores inmunológicos en sangre y ganglios linfáticos y en comparación con los observados en los 13 controles no vacunados. Resultados: La reducción inducida por ILIT en la respuesta de NPT observada en el primer año no se reprodujo de manera significativa en el quinto año. Las nuevas puntuaciones de CSMS fueron notablemente más bajas entre los pacientes previamente tratados que en el grupo de control. Además, aumentó la IgG4 específica frente gramíneas, disminuyó la IgE específica frente a gramíneas, se redujo la expresión del FcεR1 en los basófilos y aumentó la cantidad de células T de memoria en los ganglios linfáticos. Conclusión: La combinación de datos clínicos y parámetros inmunológicos respalda la noción de un efecto duradero de ILIT. Estos datos respaldan el concepto de ILIT como una buena alternativa a la AIT tradicional en la rinitis alérgica inducida por polen (AU)

Oropharyngeal squamous cell carcinoma induces an innate systemic inflammation, affected by the size of the tumour and the lymph node spread.

OBJECTIVES: Inflammation is known to be associated with the progression of cancer. The study was designed to characterise the systemic inflammation in patients with oropharyngeal squamous cell carcinoma (OPSCC) and investigate its relation to tumour size, ability to metastasise and HPV status. MATERIALS AND METHODS: Blood was obtained from 58 patients with OPSCC and 90 healthy controls and analysed with leucocyte differential count. RESULTS: The patients with OPSCC displayed an increased number of neutrophils and monocytes, whereas the lymphocytes were suppressed compared to the healthy controls. The neutrophils-to-lymphocyte ratio (NLR) and the monocyte-to-lymphocyte ratio (MLR) were calculated, and patients with large tumours exhibited high NLR and MLR. Further, patients with regional lymph node spread displayed a low NLR and MLR. Patients with HPV-positive tumours (n = 48) had a lower NLR than the patients (n = 8) with HPV-negative tumours. CONCLUSION: This study demonstrates that patients with OPSCC have an increased systemic inflammation that is affected by the HPV status, the size of the tumour and lymph node spread.

Timing-dependent effects of restraint stress on eosinophilic airway inflammation in mice.

BACKGROUND: Chronic stress has been proposed to aggravate allergic inflammation, whereas acute stress may have functional beneficial effects. The aim of this study was to investigate the influence of timing of single short restraint stress (RST) in a model of eosinophilic airway inflammation. METHODS: The airways of ovalbumin (OVA)-sensitized mice were exposed to an intranasal OVA challenge. RST was applied in two different ways; either 2 h before (pre-stress) or after (post-stress) the OVA challenge, respectively, or as a combination of stress before and after (double-stress) the OVA challenge. One group of mice was also treated with metyrapone (ME) prior to a pre-stress challenge. The inflammatory cell response was evaluated in bronchoalveolar lavage fluid (BALF), lung and nasal tissue, as well as bone marrow. RESULT: RST applied prior to the OVA challenge (pre-stress) inhibited OVA-induced airway inflammation in BALF and lung tissue, and reduced nasal histopathology compared to unstressed mice. Given as post-stress or double-stress, RST did not affect the inflammation in BALF, lungs or nasal tissue. Pre-treatment with ME prevented the pre-challenge stress evoked decrease in inflammation in BALF and lungs. CONCLUSION: Effects of RST on eosinophilic airway inflammation appear to be strongly dependent on timing and, as could be judged from the ME inhibition pattern, also corticosterone dependent. Hypothalamic-pituitary-adrenal axis activation probably influences eosinophilic inflammation through specific sequences of compartmental activation and thereby timing effects are evident on cellular recruitment pattern during the allergic reaction.