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.

Skin Physiology, Mucosal Functions, and Symptoms Are Modulated by Grass Pollen and Ozone Double Exposure in Allergic Patients.

INTRODUCTION: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under DE with pollen in grass pollen-allergic patients versus healthy controls. METHODS: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA2LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss as a parameter for epidermal barrier function. The subjects' general well-being, bronchial, nasal, and ocular symptoms were documented. RESULTS: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function and increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE duration. No relevant bronchial symptoms were recorded. CONCLUSION: Skin physiology and nasal mucosal symptoms are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose (time)-response relationship. The pH can be regarded as a possible modulatory mechanism.

Off-label Use of Oral Immunotherapy for Rhinoconjunctivitis and Asthma due to Grass Pollen: A Safe and Effective Alternative in Patients over 65 Years Old: A Series of Case Reports.

INTRODUCTION: Allergic rhinoconjunctivitis and asthma are the most common IgE-mediated diseases worldwide. Allergen-specific immunotherapy (AIT) is currently the only modifying treatment for these IgE-mediated diseases in both children and adults. Subcutaneous immunotherapy is widely used, but in patients over 65 years old, there may be an increased risk of adverse reactions and a worse response to treatment. Oral immunotherapy (OIT) has been proven to be effective and safe, but currently, in most countries, it has been licensed only for patients up to 65 years old based on its technical datasheet. So far, no studies on the efficacy and safety of this type of immunotherapy in patients older than 65 years old have been published. CASE PRESENTATION: We present four patients older than 65 years old with a diagnosis of moderate seasonal rhinoconjunctivitis and moderate-persistent seasonal pollen-induced asthma. Off-label use of oral immunotherapy (OIT) for grass pollen was prescribed due to the severity of their rhinoconjunctivitis symptoms and the worsening of asthma symptoms during the spring. Improvement in the rhinoconjunctivitis and asthma symptoms was reported by all patients since the first spring season and was maintained during the following two years of follow-up. There were no systemic reactions, and only two patients initially had self-limiting oral pruritus. CONCLUSION: Oral immunotherapy for pollens appears to be a convenient, effective, and safe option in older patients (>65 years) with comorbidities after a three-year treatment. This is, to the best of our knowledge, the first report on the off-label use of OIT in patients over 65 years old with symptoms of allergic rhinoconjunctivitis and asthma.

The role of short-term grass pollen exposure in food skin-prick test reactivity, food allergy, and eczema flares in children.

BACKGROUND: While the relationship between pollen and respiratory allergies is well-documented, the role of short-term pollen exposure in food allergy and eczema flares has not previously been explored. We aimed to investigate these associations in a population-based sample of children. METHODS: We investigated 1- (n = 1108) and 6-year-old (n = 675) children in the grass pollen season from the HealthNuts cohort. Grass pollen concentrations were considered on the day of testing (lag 0), up to three days before (lag 1-lag 3) and cumulatively (lag 0-3). Associations between grass pollen and food skin-prick test reactivity (SPT ≥ 2 mm at age 1 year and ≥ 3 mm at age 6 years), eczema flares, challenge-confirmed food allergy, reaction threshold to oral food challenges (OFC), and serum food-specific IgE levels were analyzed using either logistic or quantile regression models. Atopy and family history of allergic disease were considered as potent effect modifiers. RESULTS: Grass pollen at lag 0-3 (every 20 grains/m3 increase) was associated with an up to 1.2-fold increased odds of food SPT reactivity and eczema flares in 6-year-olds. In 1-year-olds, the associations were only observed for peanut in those with a family history of food allergy. Increasing grass pollen concentrations were associated with a lower reaction threshold to OFC and higher serum IgE levels in peanut-allergic 1-year-olds only. CONCLUSION: Increasing grass pollen concentration was associated with increased risk of food SPT reactivity and eczema flares in children. The associations in peanut-allergic infants may be related to immune activation and/or peanut and grass pollen cross-reactivity leading to a lower reaction threshold.

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).

Determining the minimal important differences in the RQLQ score with grass and tree allergy immunotherapy versus placebo in adults with moderate-to-severe allergy.

BACKGROUND: Pollen from grasses and trees can trigger allergic rhinitis (AR), where the symptoms and associated consequences can negatively affect quality of life (QoL). The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) is frequently used in clinical trials of AR to assess QoL. To help interpret RQLQ data, the minimal important difference (MID) can be used to assess whether a mean difference in QoL between treatment groups is clinically meaningful. In seasonal allergy, an MID differs according to the allergen, pollen exposure, symptom severity, patient age and treatment; the same MID cannot be applied to all scenarios. METHODS: Using data from four Phase III clinical trials of SQ sublingual immunotherapy-tablets in adults with moderate-to-severe allergy, between-group MIDs were derived for the RQLQ in grass pollen allergy (during the peak [n = 501] and entire [n = 514] pollen seasons), and in tree pollen allergy (during the birch [n = 516] and tree [n = 518] pollen seasons), using anchor-based methodology, supported by distribution-based methods. RESULTS: For grass pollen allergy, anchor-based derived between-group MIDs were 0.22 for the entire pollen season (n = 343) and 0.10 for the peak pollen season (n = 335). For tree pollen allergy, anchor-based derived between-group MIDs were 0.26 for the tree pollen season (n = 306) and 0.16 for the birch pollen season (n = 305) (representative of peak season). Distribution-based derived MIDs were supportive of the anchor-based values. CONCLUSIONS: This analysis has derived between-group MIDs specific to the trial populations evaluated and to the conditions under which the data were obtained, and highlights the need for a range of MIDs to reflect the unique nature of seasonal allergic disease.

Grass pollen sensitization in dogs in Paraná, Brazil: comparison between percutaneous and intradermal testing / [Sensibilização a polens em cães no Paraná, Brasil: comparação entre o teste percutâneo e o teste intradérmico]

Canine atopic dermatitis is an inflammatory, genetic, pruritic and chronic dermatosis that affects between 10 and 30% of dogs and one of the most important allergens is grass pollen. The objective of this study was to evaluate the sensitization to grass pollen allergens in dogs with canine atopic dermatitis and to compare intradermal skin test (IDT) with percutaneous test (PT). For this study, ten healthy dogs and 39 dogs with atopic dermatitis were tested. Dogs were submitted to IDT and PT for Lolium multiflorum, Cynodon dactylon and Paspalum notatum. The IDT and PT tests were compared using the Proportion Test. All healthy dogs were negative to both tests. Ten atopic dogs (25.6%) responded positively to the PT and none were positive in IDT. C. dactylon, L. multiflorum and P. notatum were responsible for positive reactions in 70%, 70% and 30% of positive dogs, respectively. The number of positive reactions in PT were statistically higher than IDT (P<0.05). In conclusion, grass pollen can be important source of allergens for dogs in Paraná state (Brazil) and the PT showed higher sensitization to grass pollen in dogs with atopic dermatitis than IDT.(AU)

A dermatite atópica canina é uma dermatose inflamatória, genética, prurítica e crônica que afeta entre 10% e 30% dos cães, e um dos alérgenos mais importantes são os polens de gramíneas. O objetivo deste estudo é avaliar a sensibilização a alérgenos de polens de gramíneas em cães com dermatite atópica e comparar o teste intradérmico (TID) com o teste percutâneo (TP). Para o estudo, 10 cães hígidos e 39 cães com dermatite atópica foram testados. Estes foram submetidos ao TID e ao TP para Lolium multiflorum, Cynodon dactylon e Paspalum notatum. TID e TP foram comparados usando-se o teste de proporção. Todos os cães hígidos foram negativos em ambos os testes. Dez cães atópicos (25,6%) responderam positivamente ao TP e nenhum ao TID. C. dactylon, L. multiflorum e P. notatum foram responsáveis por reações positivas de 70%, 70% e 30% dos cães positivos, respectivamente. O número de reações positivas no TP foi estatisticamente maior que no TID (P<0,05). Foi concluído que os polens de gramíneas podem ser importantes fontes de alérgenos para cães no estado do Paraná (Brasil) e que o TP mostrou maior sensibilização a polens em cães com dermatite atópica que o TID.(AU)

The Effect of Broccoli Sprout Extract on Seasonal Grass Pollen-Induced Allergic Rhinitis.

Patients exposed to pollutants are more likely to suffer from allergic rhinitis and may benefit from antioxidant treatment. Our study determined if patients diagnosed with grass-induced allergic rhinitis could benefit from broccoli sprout extract (BSE) supplementation. In total, 47 patients were confirmed with grass-induced allergic rhinitis and randomized to one of four groups: group 1 (nasal steroid spray + BSE), group 2 (nasal steroid spray + placebo tablet), group 3 (saline nasal spray + BSE) and group 4 (saline nasal spray + placebo tablet). Peak Nasal Inspiratory Flow (PNIF), Total Nasal Symptoms Scores (TNSS) and nasal mucus cytokine levels were analyzed in samples collected before and after the 3-week intervention. Comparing before and after the intervention, PNIF improved significantly when comparing Groups 1 and 2, vs. placebo, at various time points (p ≤ 0.05 at 5, 15, 60 and 240 min) following nasal challenge, while TNSS was only statistically significant at 5 (p = 0.03), 15 (p = 0.057) and 30 (p = 0.05) minutes. There were no statistically significant differences in various cytokine markers before and after the intervention. Combining nasal corticosteroid with BSE led to the most significant improvement in objective measures.

Correcting fresh grass allowance for rejected patches due to excreta in intensive grazing systems for dairy cows.

Dairy farms with intensive grazing systems combine grazing with supplemental feeding, which can be challenging because an incorrect balance between fresh grass allowance and feed supplementation results in inefficient use of the pasture, lower feed efficiency, and potential decreases in animal production. When estimating fresh grass allowance, we currently do not correct for the formation of rejected patches (RP) surrounding excreta, which can lead to overestimation of the potential fresh grass intake and hampers optimal grazing. In this study, therefore, we aim to quantify the formation of RP in intensive grazing systems and improve the quantification of fresh grass allowance. To do so, we studied 2 grazing systems (i.e., compartmented continuous grazing and strip grazing) that differ in key grazing characteristics, such as pre- and post-grazing heights and period of regrowth. The experiment was performed from April to October in 2016 and 2017 with 60 dairy cows at a fixed stocking rate of 7.5 cows/ha. Average pre-grazing grass height was measured with a rising plate meter. To quantify the formation of RP after grazing, individual grass height measurements were conducted after grazing and classified as RP or not, based on visual assessment. Our analysis showed that the average percentage of grassland covered with RP increased from around 22% at the end of May to around 43% at the end of July/beginning of August, and these percentages do not differ across grazing systems. The percentage of grassland covered with RP should be subtracted from the total grazed area to better estimate true fresh grass allowance.

New toxicity testing of PQ grass allergy immunotherapy to support product development.

PQ Grass represents an allergen-specific immunotherapy for pre-seasonal treatment of patients with seasonal allergic rhinitis (or rhinoconjunctivitis) with or without mild-to-moderate bronchial asthma. It consists of a native pollen extract for 13 grass species, chemically modified with glutaraldehyde, and adsorbed to l-tyrosine in a microcrystalline form with addition of the adjuvant Monophosphoryl Lipid A (MPL® ). Previous non-clinical safety testing, including rat repeat dose toxicity in adult and juvenile animals, rat reproductive toxicity and rabbit local tolerance studies showed no safety findings of concern. A new Good Laboratory Practice compliant rat subcutaneous repeat dose toxicity study to evaluate a higher clinical dose and modified posology (once every 2 weeks for 13 weeks) showed no signs of toxicity. As seen in previous studies, relatively minor, immunostimulatory effects were seen such as reversible increased white cell count (notably neutrophils), increased globulin level (resulting in decreased A/G ratio) and increased fibrinogen as well as minor dose site reaction in the form of inflammatory cell infiltrate. These findings are likely due to the immunostimulatory nature of MPL and/or the presence of l-tyrosine within the adjuvanted vaccine. This new toxicity study with PQ Grass therefore supports longer posology with higher dose levels.

Pollen exposure at birth and adolescent lung function, and modification by residential greenness.

BACKGROUND: Exposure to high levels of pollen in infancy is a risk factor for allergic respiratory diseases in later childhood, but effects on lung function are not fully understood. We aim to examine associations between grass pollen exposure in the first months of life and lung function at 12 and 18 years, and explore potential modification. METHODS: Using the Melbourne Atopy Cohort Study, a birth cohort of children with a family history of allergic diseases, we modeled the association between cumulative grass pollen exposure up to 3 months after birth, on FEV1 , FVC, and FEV1 /FVC ratio at 12 and 18 years. We also assessed modifying effects of residential greenness levels (derived from satellite imagery), asthma, and early life sensitization to ryegrass. RESULTS: Grass pollen exposure in the first 7 days was associated with a reduction in FEV1 (-15.5 mL; 95% CI: -27.6, -3.3 per doubling of pollen count) and FVC (-20.8 mL; -35.4, -6.1) at 12 years, but not at 18 years. Increase in cumulative grass pollen exposure up to 3 months was negatively associated with FVC at 12 and 18. Exposure to high residential greenness modified the association at 18 years. CONCLUSION: Early exposure to grass pollen was associated with decreased lung function in children and adolescents. Targeted interventions for pollen avoidance strategies that take into account local topography could be implemented alongside other clinical interventions such as immunotherapy.

Coeliac disease.

Coeliac disease is an immune-mediated enteropathy against dietary gluten present in wheat, rye and barley and is one of the most common lifelong food-related disorders worldwide. Coeliac disease is also considered to be a systemic disorder characterized by a variable combination of gluten-related signs and symptoms and disease-specific antibodies in addition to enteropathy. The ingestion of gluten leads to the generation of harmful gluten peptides, which, in predisposed individuals, can induce adaptive and innate immune responses. The clinical presentation is extremely variable; patients may have severe gastrointestinal symptoms and malabsorption, extraintestinal symptoms or have no symptoms at all. Owing to the multifaceted clinical presentation, diagnosis remains a challenge and coeliac disease is heavily underdiagnosed. The diagnosis of coeliac disease is achieved by combining coeliac disease serology and small intestinal mucosal histology during a gluten-containing diet. Currently, the only effective treatment for coeliac disease is a lifelong strict gluten-free diet; however, the diet is restrictive and gluten is difficult to avoid. Optimizing diagnosis and care in coeliac disease requires continuous research and education of both patients and health-care professionals.

Human exposure to airborne pollen and relationships with symptoms and immune responses: Indoors versus outdoors, circadian patterns and meteorological effects in alpine and urban environments.

Pollen exposure is a major cause of respiratory allergies worldwide. However, it is unclear how everyday exposure is related to symptoms and how allergic patients may be affected spatially and temporally. Hence, we investigated the relationship of pollen, symptoms and immune responses under a controlled regime of 'high-low-moderate' pollen exposure in urban versus alpine environment. The research was conducted in 2016 in two locations in Germany: urban Augsburg (494 m) and Schneefernerhaus (UFS) on Zugspitze mountain (2656 m). Monitoring of airborne pollen took place using Hirst-type volumetric traps. On UFS, both indoor and outdoor samples were taken. Grass pollen allergic human volunteers were monitored daily during the peak of the grass pollen season, in Augsburg, on UFS, then again in Augsburg. Nasal biosamples were obtained throughout the study to investigate immune responses. All symptoms decreased significantly during the stay on UFS and remained low even after the return to Augsburg. The same was observed for nasal total IgE and IgM levels and for nasal type 2 cytokines and chemokines. Augsburg showed higher pollen concentrations than those on UFS. At all sites, pollen were present throughout each day, but were more abundant in Augsburg during morning. On UFS, outdoor pollen levels were up to 6-fold higher than those indoors. Nasal, ocular and pulmonary symptoms correlated with current and previous days' pollen concentrations and relative humidity. Stays in low-exposure environments during the peak pollen season can be an efficient means of reducing allergic symptoms and immune responses. However, in alpine environments, even occasional pollen exposure during short intervals may still trigger symptoms because of the additional environmental stress posed onto allergics. This highlights the need for the consideration of additional environmental factors, apart from symptom diaries and immune responses, so as to efficiently predict high-risk allergy periods.

Association Between Seasonal Allergic Rhinitis and Air Pollution, Meteorological Factors, and Grass Pollen Counts in Madrid (1996 and 2009).

OBJECTIVE: The aim of this study was to assess the relationship between meteorological and pollution-related variables and the symptoms of patients with seasonal allergic rhinitis due to sensitization to grass pollen during 2 different time periods in Madrid, Spain. METHODS: Between March 23 and December 31 in 1996 and 2009, we carried out a daily count of grass pollen grains (Burkard spore trap) and recorded the rhinitis symptom scores in 2 groups of patients with a history of seasonal allergic rhinitis (n=25 in 1996 and n=23 in 2009). Descriptive statistics of the same variables during the study periods were recorded. Associations between variables were assessed using the paired-samples Wilcoxon test and categorical principal component analysis (CatPCA, SPSS24 package). RESULTS: The mean symptom score was low in 1996 and moderate in 2009. The 1996 and 2009 CatPCA analysis explained around 66.4% and 70.5% of the variance, respectively. The strongest relationships in 1996 were between symptoms and grass pollen counts (R=0.55) and between temperature and ozone (R=0.63). In 2009, the association between temperature and pollution-related variables was even stronger than in 1996 (ozone [R=0.53] and PM10 [R=0.34], with a positive sign in both cases). CONCLUSIONS: The effect of temperature and pollution (mainly ozone, even at lower atmospheric concentrations than in established guidelines for effects on health) may have contributed to the higher seasonal allergic rhinitis symptom score recorded in 2009.

Beta-Expansin of Bermuda, Johnson, and Para grass pollens, is a major cross-reactive allergen for Allergic Rhinitis patients in subtropical climate.

BACKGROUND: Subtropical grass pollens of Bermuda (BGP), Johnson (JGP), and Para or buffalo grass (PGP), are common causes of pollen allergies in warm climate area. Allergic rhinitis (AR) patients had positive skin prick test (SPT) to extract of these 3 grass pollens. However, no allergenic proteins of 3 grass pollens have never been studied. OBJECTIVE: To identify major allergens of BGP, JGP, and PGP in Thai grass pollen-allergic patients and to examine their sIgE cross-reactivity. METHODS: Serum of nine AR patients with positive SPT to at least 2 of 3 studied pollens were collected. Based on availability, only ImmunoCAP of BGP and JGP were available to determine a level of sIgE. Profiles of sIgE bound proteins from BGP, JGP, and PGP, were obtained by immunoblot. Major IgE bound protein was identified by liquid chromatography-tandem mass spectrophotometry (LC-MS/MS). Cross-reactivity of purified major allergen of the 3 grass pollens was determined by inhibition of sIgE in both ELISA and immunoblot. RESULTS: AR patients who have positive SPT to extract of BGP, JGP, and PGP, were 9, 8, and 6, respectively. Positive sIgE (> 0.35 kUA/L) to BGP and JGP were found in 9 and 8 patients, respectively. Eight profiles of IgE bound proteins of the 3 grass pollens showed 29-30 kDa pollen protein as major allergen and was identified as beta-expansin (ExpB). Moreover, purified ExpB of the 3 grass pollens cross-inhibited serum sIgE. CONCLUSION: ~30 kDa ExpB of BGP, JGP, and PGP, is major cross-reactive allergen for AR Thai patients.

Persistent regulatory T-cell response 2 years after 3 years of grass tablet SLIT: Links to reduced eosinophil counts, sIgE levels, and clinical benefit.

BACKGROUND: In the first 2 years of grass tablet sublingual immunotherapy treatment, we have previously demonstrated a progressive development of a regulatory T-cell response, which was preceded by an early decrease in the frequency of both IL-4+ cells and sIgE levels. A progressive increase in sIgG4 levels and FAB blockage were also found. METHODS: By monitoring immunological kinetics during 3 years of active treatment + 2 years of follow-up, we aimed to identify key immunological parameters that could explain sustained clinical benefit of grass tablet sublingual immunotherapy. RESULTS: Thirty patients completed the 5-year clinical trial protocol. Although individual responses were heterogeneous, reduction in both sIgE and circulating IL-4+ cells compared to the initial 1- to 4-month peak was maintained throughout the 3-year treatment period and for 2 years after discontinuation. Meanwhile, after a 2-year increase in sIgG4, the levels were stabilized during the third year and decreased post-therapy. FAB inhibition remained significantly inhibited throughout the study compared to preimmunotherapy in 83% of patients. A sustained regulatory T-cell response, after IT cessation, occurs in two-thirds of the patients. There was a statistical association between this regulatory response, the maintenance of lower eosinophil counts during grass pollen seasons, and sIgE titers lower than before immunotherapy treatment, and the latter were significantly associated with clinical response. CONCLUSION: Our results suggest that the immunological mechanisms underlying the sustained response after 2 years of cessation of immunotherapy (3-year treatment period) are linked to the acquisition and maintenance of a regulatory T-cell response.

Association between seasonal allergic rhinitis and air pollution, meteorological factors, and grass pollen counts in Madrid (1996 and 2009)

OBJECTIVE: The aim of this study was to assess the relationship between meteorological and pollution-related variables and the symptoms of patients with seasonal allergic rhinitis due to sensitization to grass pollen during 2 different time periods in Madrid, Spain. METHODS: Between March 23 and December 31 in 1996 and 2009, we carried out a daily count of grass pollen grains (Burkard spore trap) and recorded the rhinitis symptom scores in 2 groups of patients with a history of seasonal allergic rhinitis (n=25 in 1996 and n=23 in 2009). Descriptive statistics of the same variables during the study periods were recorded. Associations between variables were assessed using the paired-samples Wilcoxon test and categorical principal component analysis (CatPCA, SPSS24 package). RESULTS: The mean symptom score was low in 1996 and moderate in 2009. The 1996 and 2009 CatPCA analysis explained around 66.4% and 70.5% of the variance, respectively. The strongest relationships in 1996 were between symptoms and grass pollen counts (R=0.55) and between temperature and ozone (R=0.63). In 2009, the association between temperature and pollution-related variables was even stronger than in 1996 (ozone [R=0.53] and PM10 [R=0.34], with a positive sign in both cases). CONCLUSIONS: The effect of temperature and pollution (mainly ozone, even at lower atmospheric concentrations than in established guidelines for effects on health) may have contributed to the higher seasonal allergic rhinitis symptom score recorded in 2009

INTRODUCCIÓN: El objetivo de este estudio fue evaluar las relaciones de las variables meteorológicas y contaminantes en los síntomas de los pacientes con rinitis alérgica estacional con sensibilización al polen de gramíneas durante dos períodos diferentes en Madrid. MÉTODOS: Durante el período del 23 de marzo al 31 de diciembre de 1996 y 2009, se realizó un recuento diario de granos de polen de gramíneas (Burkard spore trap) y puntuación de síntomas de rinitis en dos grupos de pacientes (n = 25 en 1996 y n = 23 en 2009) con historia de rinitis alérgica estacional. Para describir cómo se relacionan las variables, se realizaron estadísticas descriptivas de las mismas variables en los períodos de estudio de 1996 y 2009, contraste no paramétrico pareado de Wilcoxon y un análisis de componentes principales (CatPCA, SPSS24). RESULTADOS: El valor medio de la puntuación de síntomas en 1996 fue bajo y en 2009 moderado. El análisis CatPCA de 1996 y 2009 explica aproximadamente el 66,4% y el 70,5% de la varianza, respectivamente. La relación más fuerte en 1996 fue entre los síntomas y los recuentos de polen de gramíneas (R = 0,55), la temperatura y el O3 (R = 0,63). En 2009, la relación entre la temperatura y las variables de contaminación fue incluso mayor que en el período de 1996: O3 (R = 0,53) y con PM10 (R = 0,34), en ambos casos con un signo positivo. CONCLUSIONES: El efecto de la temperatura y la contaminación (principalmente O3, incluso a concentraciones atmosféricas más bajas que las pautas establecidas sobre sus efectos en la salud), podría contribuir a la mayor puntuación de síntomas de rinitis alérgica estacional observada en 2009

Positivity rates of in vitro inhalant/respiratory and food allergy tests in the northern midwestern United States.

Rates of allergy-test positivity vary by country and by regions within countries. Several studies have looked at allergy test results to determine the most common allergens. Many of these studies have been based on surveys or on studies of small numbers of tests. Positivity rates for allergy tests are poorly defined in the northern midwestern region of the United States. We conducted a study to identify the rates of positive allergy tests for both inhalant/respiratory allergens and food allergens in the upper Midwest. We extracted from our laboratory database the results of all test samples sent for one of eight allergen panels that had been analyzed between Sept. 1, 2014, and Sept. 1, 2015. All testing was performed at The Cleveland Clinic with the Phadia ImmunoCAP system. The percentage of positive tests, the distribution of the most frequently positive tests, and the class of in vitro responses were identified. A total of 148,628 test results for 63 different allergens were identified. Of the 125,190 tests for inhalant/respiratory allergens, the most frequently positive were dog dander (24% of tests), cat dander (23%), dust mites (23% for both Dermatophagoides pteronyssinus and Dermatophagoides farinae), and June grass (21%). Of the 23,438 food tests, the most frequently positive test results were for milk (18%), peanut (17%), wheat (16%), and egg white (15%). Most of the results fell into classes 1 through 3, although there was still a notable number of very high responses (class 5 and 6). These findings suggest that there is wide variability in the positivity of in vitro allergy tests and that the likelihood of a positive result in screening panels can be estimated. Evaluating such rates will help identify the most and least common allergens and will help to cost-effectively refine allergy screening panels.

New European Academy of Allergy and Clinical Immunology definition on pollen season mirrors symptom load for grass and birch pollen-induced allergic rhinitis.

BACKGROUND: The use of allergen immunotherapy (AIT) for allergic rhinitis and its clinical efficacy in clinical trials depends on the effective determination of pollen allergen exposure time periods. We evaluate pollen data from Germany to examine the new definitions on pollen season and peak pollen period start and end as proposed by the European Academy of Allergy and Clinical Immunology (EAACI) in a recently published Position Paper. The aim was to demonstrate the ability of these definitions to mirror symptom loads for grass and birch pollen-induced allergic rhinitis based on real-life data. METHODS: Data coming from four pollen monitoring stations in the Berlin and Brandenburg area in Germany and for 3 years (2014-2016) were used to investigate the correlation of season definitions, birch and grass pollen counts and total nasal symptom and mediation scores as reported by patients in "Patients Hay fever Diaries" (PHDs). After the identification of pollen periods on the basis of the EACCI criteria, a statistical analysis was employed, followed by a detailed graphical investigation. RESULTS: The analysis revealed that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to symptom loads for grass and birch pollen-induced allergic rhinitis reported by patients in PHDs. CONCLUSION: Based on our analysis, the validity of the EAACI definitions on pollen season is confirmed. Their use is recommended in future clinical trials on AIT as well as in daily routine for optimal patient care.