Tree pollen exposure is associated with reduced lung function in children.

BACKGROUND: Allergic disease is a recognized global epidemic and a significant cause of ill health and poor quality of life. The prevalence of pollen allergy is high throughout the world, and pollen exposure itself plays a role in emergency department presentations and hospitalizations for asthma. Lung function and airway inflammation are important measures of asthma activity and control. OBJECTIVE: To examine associations between exposure to multiple pollen types and lung function and markers of airway inflammation at 8 and 14 years of age, and to explore potential modification by residential greenness. METHODS: A cohort of high-risk children living in Sydney, Australia had spirometry and fractional exhaled nitric oxide (FeNO) measured at 8 and 14 years of age. Ambient pollen concentration on the day of lung function measurement and up to three days prior was used as the exposure measure. Residential greenness was derived from satellite imagery. We modelled the association between six pollen types and lung function and FeNO. We also assessed modifying effects of residential greenness. RESULTS: Casuarina, cypress and Pinus pollen in the air the day before measurement and 3 days prior respectively, were associated with reduced lung function in 8-year-olds. The pollen exposures were associated with decreases in FEV1 and FVC; however, the FEV1 /FVC ratio was not affected. Effect modification by greenness was not observed due to loss of power. CONCLUSIONS & CLINICAL RELEVANCE: Airborne tree pollen of cypress, Casuarina and Pinus and not grass in some regions may be detrimental to childhood lung function.

Food-dependent, exercise-induced anaphylaxis in a patient allergic to peach.

Determining the single factor that triggered anaphylactic shock can be challenging. We present an interesting case of a 25-year-old female patient with recurrent anaphylactic reactions developing after eating various foods, particularly in presence of co-factors of allergic reactions. Symptoms occurred after consumption of various kinds of foods - peach, pancakes with cottage cheese and fruit, a meal from a Chinese restaurant - all eaten on other occasions without symptoms. During diagnosis, skin prick tests were negative for all tested allergen extracts (both inhalatory and food) from Allergopharma. Prick by prick tests were positive for the peach - wheal diameter - 6 mm, nectarine - 4 mm (histamine 4 mm, negative control 0 mm). Increased levels of asIgE were found for allergens of peach (0.55 kU/L).Open challenge test with one mid-size peach combined with the physical exercise challenge test was positive. ImmunoCAP ISAC test indicated increased levels of IgE specific for the lipid transfer protein (LTP) for walnut (nJug r 3), peach (Pru p 3), wheat (rTri a 14) and plane tree (rPla a 3). The patient was diagnosed with food-dependent, exercise-induced anaphylaxis associated with an allergy to lipid transport proteins (LTPs).

Immunotherapy With the SQ Tree SLIT-tablet in Adults and Adolescents With Allergic Rhinoconjunctivitis.

PURPOSE: The SQ tree sublingual immunotherapy (SLIT)-tablet containing allergen extracts with the major allergen Bet v 1 from birch pollen is currently being developed for the treatment of tree pollen-induced allergic rhinitis/conjunctivitis with or without asthma. The aim of this Phase II trial was to investigate the dose-related efficacy and safety of the SQ tree SLIT-tablet. METHODS: This study was a randomized, parallel-group, double-blind, placebo-controlled, multi-national trial conducted in Europe. A total of 637 participants were randomized equally to receive placebo or treatment with the SQ tree SLIT-tablet in doses of 0.5, 1, 2, 4, 7, or 12 development units (DU). Treatment was initiated ~16 weeks before onset of the 2013 birch pollen season (BPS) and was continued throughout the BPS with a total duration of at least 6 months. During the BPS and tree pollen season (TPS), subjects assessed rhinoconjunctivitis symptoms and medication use on a daily basis in an electronic diary; weekly assessments of rhinoconjunctivitis quality of life were also made. FINDINGS: Analysis of the average daily symptom score during the BPS and the TPS showed that the difference between active treatment and placebo was statistically significant for the 7 DU group (BPS, P = 0.02; TPS, P = 0.03), with no clear dose-response relationship. All doses of the SQ tree SLIT-tablet induced changes from baseline in birch-specific IgE and IgG4 that were statistically significant compared with placebo at all time points assessed (P < 0.0001) with a clear dose-response relationship for birch specific IgG4. In general, the SQ tree SLIT-tablet was well tolerated, with the majority of treatment-related adverse events (≥95%) being mild or moderate in severity. The most frequently reported treatment-related adverse events were generally related to the sublingual administration of the tablet (ie, they occurred in the oral cavity). IMPLICATIONS: The results from this trial suggest that the SQ tree SLIT-tablet in doses up to 12 DU has a tolerability profile suitable for at-home administration. The immunomodulatory changes indicate a dose-response relationship, but clinical efficacy parameters were inconclusive, probably due to low pollen counts, emphasizing the importance of pollen exposure for the outcome of a pollen allergy immunotherapy trial. EudraCT no: 2012-000031-59.

Outdoor pollen is a trigger of child and adolescent asthma emergency department presentations: A systematic review and meta-analysis.

BACKGROUND: In the context of increased asthma exacerbations associated with climatic changes such as thunderstorm asthma, interest in establishing the link between pollen exposure and asthma hospital admissions has intensified. Here, we systematically reviewed and performed a meta-analysis of studies on pollen and emergency department (ED) attendance. METHODS: A search for studies with appropriate search strategy in MEDLINE, EMBASE, Web of Science and CINAHL was conducted. Each study was assessed for quality and risk of bias. The available evidence was summarized both qualitatively and meta-analysed using random-effects models when moderate heterogeneity was observed. RESULTS: Fourteen studies were included. The pollen taxa investigated differed between studies, allowing meta-analysis only of the effect of grass pollen. A statistically significant increase in the percentage change in the mean number of asthma ED presentations (MPC) (pooled results from 3 studies) was observed for an increase in 10 grass pollen grains per cubic metre of exposure 1.88% (95% CI = 0.94%, 2.82%). Time series studies showed positive correlations between pollen concentrations and ED presentations. Age-stratified studies found strongest associations in children aged 5-17 years old. CONCLUSION: Exposure to ambient grass pollen is an important trigger for childhood asthma exacerbations requiring ED attendance. As pollen exposure is increasingly a problem especially in relation to thunderstorm asthma, studies with uniform measures of pollen and similar analytical methods are necessary to fully understand its impact on human health.

First allergenic pollen monitoring in Bucharest and results of three years collaboration with European aerobiology specialists.

INTRODUCTION: Respiratory allergies induced by allergenic plants pollen represent an important public health problem with increasing prevalence and severity. Aerobiologic study of allergenic pollens is performed in many countries on regular basis and correlated with health data from allergists in the frame of national aerobiology networks. Romania has no aerobiology network and pollen measurements have been done between 1999-2012 in West region only. In the frame of COST Action called Sustainable management of Ambrosia artemisiifolia in Europe (SMARTER FA 1203), three years collaboration with Reseau National de Surveillance Aerobiologique (RNSA) from France and the first pollen monitoring center in Bucharest were established.The aim of this paper is to present results of first pollen monitoring in Bucharest, activities of Romanian SMARTER group and collaboration with European aerobiology specialists. MATERIAL AND METHOD: We used a Hirst-type pollen trap placed on the roof of the Research Center from "Colentina" Clinical Hospital and the pollen monitoring method based on European Aeroallergen Network (EAN) standardized requirements. Monthly results during the pollen seasons 2014-2016 were sent to RNSA and EAN and posted on the European pollen information site. RESULTS: We found high amounts of allergenic pollen, mainly grasses from May to September and Ambrosia artemisiifolia during September. Conlcusions. We concluded that SMARTER offered access to aerobiology training, improved multidisciplinary collaboration and perspectives to further develop national and international projects. More coordinated efforts to develop national aerobiology network and to recuperate the gap comparing to other European countries in the field of aerobiology and respiratory allergology are needed.

Characterization of a Major Allergen from Mongolian Oak, Quercus mongolica, a Dominant Species of Oak in Korea.

BACKGROUND: Oaks are the most common trees in Korean forests, and Mongolian oak, Quercus mongolica, is the dominant species. However, no allergen has been characterized from Mongolian oak. In this study, we tried to characterize a major allergen from Mongolian oak. METHODS: A molecule homologous to pathogenesis-related 10 (PR-10)-like protein, Que m 1, was cloned by RT-PCR. Its recombinant protein, along with Que a 1, an allergen from white oak (Q. alba), was produced. The allergenicity and diagnostic value of recombinant Que m 1, Que a 1, and Bet v 1 proteins were compared by ELISA using sera from oak-sensitized subjects. A basophil activation test was also performed using CD63 expression as an activation marker. RESULTS: Que m 1 sequence shares 57.5-96.2% amino acid sequence identity with PR-10-like allergens from various plants. Specific IgE to recombinant Que m 1, Que a 1, and Bet v 1 were detected in 92.0, 74.0, and 38.0% of 50 serum samples from Korean tree pollinosis patients. Recombinant Que m 1 was able to inhibit IgE reactivity to Que a 1 and Bet v 1, indicating its strong cross-reactivity. The activation patterns of basophils from 5 patients were similar in terms of the CD63 expression and protein concentration of challenged Bet v 1 and Que m 1. CONCLUSIONS: A major allergen, Que m 1, was cloned, and its recombinant protein was produced from Mongolian oak, a dominant species in Korea. Recombinant Que m 1 is potentially useful for the diagnosis and treatment of tree pollinosis in Korea.

Tolerability of the SQ Tree SLIT Tablet in Adults.

PURPOSE: The tree pollen sublingual immunotherapy (SLIT)-tablet (ALK, Denmark) is being developed for the treatment of tree pollen induced allergic rhinitis with or without conjunctivitis. The objective of this Phase I trial was to investigate the tolerability and acceptable dose range of the SQ tree SLIT-tablet in adults with allergic rhinoconjunctivitis. METHODS: The trial was a randomized, double-blind, placebo-controlled, dose escalation Phase I trial that included 70 adults (aged 19-61 years) with birch pollen-induced rhinoconjunctivitis with or without mild to moderate asthma. The trial included 6 different dosage groups that were randomized 3:1 to active treatment or placebo once daily for 28 days. Adverse events (AEs) were coded in the Medical Dictionary for Regulatory Activities by medically qualified personnel. Immunologic assessments included IgE and IgE-blocking factor. FINDINGS: Most (96%) reported AEs were mild, and only 5 severe events (0.2%) were reported. The most frequently reported investigational medicinal product-related AEs were oral pruritus, ear pruritus, mouth edema, sensation of foreign body, throat irritation, pharyngolaryngeal pain, dry throat, tongue blistering, eye pruritus, and headache. The trial included doses ranging from 1 to 24 development units (DU), and the mean number of investigational medicinal product-related AEs per participant was highest in the 24 DU group. The 12 and 24 DU doses induced statistically significant changes from baseline compared with placebo in birch specific IgE and IgE-blocking factor. IMPLICATIONS: The trial found that doses up to 12 DU of the SQ tree SLIT tablet have a tolerability profile suitable for at-home administration. An immunomodulatory effect was found for all doses included in the trial, and doses up to 12 DU were thus chosen for further clinical development of the SQ tree SLIT tablet. EudraCT identifier: 2007-003234-42.

Determination of irritant threshold concentrations of multiple tree, grass, weed and mould allergens for intradermal testing of horses residing in the southern USA.

BACKGROUND: Appropriate allergen threshold concentrations (TCs) for intradermal testing (IDT) have not been established in horses for many pollen and mould allergens. OBJECTIVES: To determine the TCs in non-allergic horses and describe the frequency of late phase reactions for 26 allergens, including trees, grasses, weeds and moulds in horses residing in the southern Unites States. ANIMALS: Twenty four clinically normal horses in the southern United States. METHODS: Threshold concentrations for different allergens were determined using IDT subjective measurements at 30 minutes. Delayed reactions were evaluated at 4 and 24 h. RESULTS: Threshold concentrations (all PNU/mL) were established for eight tree allergens (black willow 1,000, box elder 1,000, live oak 1,000, pecan 2,000, white ash 4,000, red oak 4,000, red mulberry 2,000 and green ash 2,000); two grass allergens (Johnson grass 250 PNU/mL and Kentucky blue grass 500 PNU/mL); two weeds (carelessweed 1,000 PNU/mL, great ragweed 500 PNU/mL) and one mould (Curvularia 8,000 PNU/mL). The TC was not determined due to excessive reactivity at the lowest concentration tested (1,000 PNU/mL) for bahia and perennial rye grass. Eleven other allergens did not meet the criteria to establish a TC when evaluated at 30 min due to lack of positive reactions. Multiple allergens caused positive reactions in ≥10% of horses at 4 h. Reactions at 24 h were rare with the exception of one horse. CONCLUSIONS AND CLINICAL IMPORTANCE: This study identified intradermal TC for multiple pollen and mould allergens in horses. These values may prove useful for optimizing allergen concentrations for IDT of allergic horses.

Is the ISAC 112 Microarray Useful in the Diagnosis of Pollinosis in Spain?

BACKGROUND: Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population. METHODS: Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay. RESULTS: The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type. CONCLUSIONS: The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap.

The clinical significance of the pollen calendar of the Western Thrace/northeast Greece region in allergic rhinitis.

BACKGROUND: There are major differences in the clinical pattern of allergic rhinitis (AR) patients among countries, reflecting local aerobiological conditions. We analyzed the correlation between airborne pollen concentrations of the Western Thrace/northeast (NE) Greece region with symptoms scores in AR patients. The above data is the first provided for the Mediterranean climate of Greece and reflects the clinical significance of pollen calendar in everyday clinical practice. METHODS: An annual pollen calendar of the most important outdoor aeroallergens (grasses, trees, and weeds) was developed, using a Burkard volumetric spore trap. A total of 168 AR patients were studied and asked to evaluate their symptoms and main seasonal appearance. Sensitization prevalence to pollen species was detected by skin prick tests. Symptoms were evaluated by Total 5 Symptoms Score (T5SS) and correlated to aerobiological data. RESULTS: As far as the pollen calendar is concerned, the highest total percentages of pollens were recorded for olive (24.02% of total), oak (13.74%), grasses (9.08%), and cypress (7.63%). Regarding patients' sensitivities, the most prevalent ones were to grasses (56.0%), olive (43.5%), wall pellitory (24.4%), and cypress (16.7%) antigens. A strong significant correlation between total pollen counts and patients' T5SS (r = 0.874, p < 0.001) was observed. Moreover, strong significant correlations between T5SS and pollen counts were also found for the most prevalent species, including grasses, olive, and Parietaria allergens (r = 0.627, p = 0.029; r = 0.695, p = 0.012; and r = 0.656, p = 0.021, respectively). CONCLUSION: Patients' symptoms scores were found to be significantly correlated to pollen counts. Given data are important for the management of AR patients who live in similar Mediterranean climate conditions.

[Sensitization to Casuarina equisetifolia and Pinus spp pollen in patients with allergic rhinitis and asthma in Mexico City]. / Sensibilización al polen de Casuarina equisetifolia y Pinus spp en pacientes con rinitis alérgica y asma en la Ciudad de México.

BACKGROUND: Pollinosis studies at Mexico City have found a considerable amount of Casuarina equisetifolia and Pinus spp pollen, its sensitization frequency is unknown. In Mexico, some allergens are not considered related to asthma or allergic rhinitis, even though reports in other countries have been demonstrated their relevance as aeroallergens. OBJECTIVE: To estimate the frequency of sensitization to Casuarina equisetifolia and Pinus spp pollen. PATIENTS AND METHOD: A transversal, descriptive trial was done at Hospital General de Mexico. Previous informed consent 142 patients with allergic rhinitis and asthma, 3 to 55 years old, were included to the study. A complete clinical evaluation, laboratory tests and skin prick tests were performed. RESULTS: We included 142 patients, 44 children (64% males) and 98 adults (73% females). We found that 8 (18.18%) children and 35 (35.7%) adults had a positive skin prick test to Casuarina equisetifolia. None of the patients included in the study had a positive skin prick test to Pinus spp. CONCLUSIONS: Sensitization to Casuarina equisetifolia is as important as other pollens found in Mexico City. These results suggest that it should be included when skin prick tests are performed. Pinus spp pollen is considered an aeroallergen in European countries but we did not corroborate sensitization in our population.

ANTECEDENTES: los estudios de polinosis efectuados en la Ciudad de México han encontrado una cantidad importante de polen de Casuarina equisetifolia y Pinus spp, la frecuencia de sensibilización a estos pólenes se desconoce. Estos alergenos no se han relacionado con asma bronquial o rinitis alérgica en México, a pesar de que estudios efectuados en otros países han demostrado su relevancia como aeroalergenos. OBJETIVO: determinar la frecuencia de sensibilización al polen de Casuarina equisetifolia y Pinus spp. PACIENTES Y MÉTODO: estudio transversal, descriptivo, efectuado en el servicio de Alergia e Inmunología Clínica del Hospital General de México. Previo consentimiento informado, se incluyeron 142 pacientes de 3 a 55 años de edad con diagnóstico de rinitis alérgica, asma o ambas. Se les realizó historia clínica completa, estudios de laboratorio, gabinete y pruebas cutáneas por punción. RESULTADOS: de los 142 pacientes, se incluyeron 44 niños (64% de sexo masculino) y 98 adultos (73% de sexo femenino). Se encontró que 8 (18.1%) niños y 35 (35.7%) adultos tuvieron reacción positiva en la prueba cutánea para Casuarina equisetifolia. Ninguno de los pacientes incluidos en el estudio tuvo reacción positiva a la prueba cutánea para Pinus spp. La frecuencia de sensibilización a Casuarina equisetifolia fue ligeramente menor a la de otros pólenes frecuentemente encontrados en la Ciudad de México. CONCLUSIONES: la sensibilización al polen de Casuarina equisetifolia es tan importante como la de otros pólenes encontrados en la Ciudad de México. Con estos resultados se sugiere que este polen se incluya en la práctica de pruebas cutáneas. El polen de Pinus spp es un aeroalergeno en países europeos. Sin embargo, en nuestra población no corroboramos la sensibilización al mismo.

Recombinant allergens for pollen immunotherapy.

Specific immunotherapy (IT) represents the only potentially curative therapeutic intervention of allergic diseases capable of suppressing allergy-associated symptoms not only during treatment, but also after its cessation. Presently, IT is performed with allergen extracts, which represent a heterogeneous mixture of allergenic, as well as nonallergenic, compounds of a given allergen source. To overcome many of the problems associated with extract-based IT, strategies based on the use of recombinant allergens or derivatives thereof have been developed. This review focuses on recombinant technologies to produce allergy therapeuticals, especially for allergies caused by tree, grass and weed pollen, as they are among the most prevalent allergic disorders affecting the population of industrialized societies. The reduction of IgE-binding of recombinant allergen derivatives appears to be mandatory to increase the safety profile of vaccine candidates. Moreover, increased immunogenicity is expected to reduce the dosage regimes of the presently cumbersome treatment. In this regard, it has been convincingly demonstrated in animal models that hypoallergenic molecules can be engineered to harbor inherent antiallergenic immunologic properties. Thus, strategies to modulate the allergenic and immunogenic properties of recombinant allergens will be discussed in detail. In recent years, several successful clinical studies using recombinant wild-type or hypoallergens as active ingredients have been published and, currently, novel treatment forms with higher safety and efficacy profiles are under investigation in clinical trials. These recent developments are summarized and discussed.