Limited beneficial effects of systemic steroids when added to standard of care treatment of seasonal allergic rhinitis.

Intramuscular injections with methylprednisolone treating allergic rhinitis (AR) have a long history. Modern guidelines are designed to dissuade this treatment, but it´s frequently used, especially in primary care. This despite of concern for side effects and lack of modern placebo-controlled studies. This study was designed to evaluate if methylprednisolone, could significantly improve symptoms of birch pollen induced AR and reduce the concomitant use of standard of care medication. Forty-two patients with birch pollen induced AR were randomized to treatment with methylprednisolone (80 mg) or placebo (NaCl 0.9%). Daily symptom- and medication scores was registered for 3 weeks. Quality of life questionnaires Sino-nasal Outcome Test-22 (SNOT-22) and Juniper Rhinoconjunctivitis Quality of Life Questionaire (Juniper RQLQ) were registered at trial start and at the end of the 3 weeks period. The combined symptom- and medication scores indicate that the methylprednisolone treated group [mean Area Under the Curve (AUC) 37.1 (SD 16.2 (95% CI 29.9-44.6))] was significantly better off than the placebo group [mean AUC 49.1 (SD 10.1 (95% CI 44.5-53.7))], p = 0.008. No significant difference between the groups were found in the SNOT-22 and Juniper RQLQ analysis. Registered side effects were few and mild. The limited beneficial effects of systemic steroids when added to standard of care in combination of its potential risk for side effects, speaks against its use for treatment of severe seasonal allergic rhinitis. The lack of difference in quality-of-life further underscores this result.

Designing an automatic pollen monitoring network for direct usage of observations to reconstruct the concentration fields.

We consider several approaches to a design of a regional-to-continent-scale automatic pollen monitoring network in Europe. Practical challenges related to the arrangement of such a network limit the range of possible solutions. A hierarchical network is discussed, highlighting the necessity of a few reference sites that follow an extended observations protocol and have corresponding capabilities. Several theoretically rigorous approaches to a network design have been developed so far. However, before starting the process, a network purpose, a criterion of its performance, and a concept of the data usage should be formalized. For atmospheric composition monitoring, developments follow one of the two concepts: a network for direct representation of concentration fields and a network for model-based data assimilation, inverse problem solution, and forecasting. The current paper demonstrates the first approach, whereas the inverse problems are considered in a follow-up paper. We discuss the approaches for the network design from theoretical and practical standpoints, formulate criteria for the network optimality, and consider practical constraints for an automatic pollen network. An application of the methodology is demonstrated for a prominent example of Germany's pollen monitoring network. The multi-step method includes (i) the network representativeness and (ii) redundancy evaluation followed by (iii) fidelity evaluation and improvement using synthetic data.

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.

Cognitive dysfunction and quality of life during pollen season in children with seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis often gives rise to impaired quality of life and is believed to also affect cognitive function. We aimed to examine whether cognitive functions were impaired during grass pollen season in symptomatic allergic children and to relate the degree of impairment to quality of life and biomarkers related to stress and inflammation. METHODS: Forty-three grass pollen-allergic children (age 8-17 years) with non-satisfactory effect of medication (antihistamines and nasal steroids daily) during previous seasons were included. In addition, 26 matched non-allergic children were included as controls. Both groups performed cognitive tests (CANTAB) and completed Quality of Life questionnaires outside and during the pollen season. Blood samples were collected and analyzed for stress and inflammatory biomarkers. Pollen level was measured daily. RESULTS: Impaired cognitive function was found in spatial working memory, where the allergic group made more errors compared to the non-allergic group during pollen season, but not off-season. No significant differences could be seen between the allergic group and the controls in the other tests investigating visual memory or attention. Quality of health questionnaires revealed more symptoms and impaired quality of life in allergic compared to non-allergic children, and increased symptoms in allergic children were associated with longer reaction time for simple movement during pollen season. No differences in stress or inflammatory biomarkers could be found between the groups. CONCLUSION: Cognitive function was affected during pollen season in pollen-allergic children, and the more symptoms the allergic children had, the longer the reaction time in the cognitive tests.

Pollen exposure weakens innate defense against respiratory viruses.

BACKGROUND: Hundreds of plant species release their pollen into the air every year during early spring. During that period, pollen allergic as well as non-allergic patients frequently present to doctors with severe respiratory tract infections. Our objective was therefore to assess whether pollen may interfere with antiviral immunity. METHODS: We combined data from real-life human exposure cohorts, a mouse model and human cell culture to test our hypothesis. RESULTS: Pollen significantly diminished interferon-λ and pro-inflammatory chemokine responses of airway epithelia to rhinovirus and viral mimics and decreased nuclear translocation of interferon regulatory factors. In mice infected with respiratory syncytial virus, co-exposure to pollen caused attenuated antiviral gene expression and increased pulmonary viral titers. In non-allergic human volunteers, nasal symptoms were positively correlated with airborne birch pollen abundance, and nasal birch pollen challenge led to downregulation of type I and -III interferons in nasal mucosa. In a large patient cohort, numbers of rhinoviruspositive cases were correlated with airborne birch pollen concentrations. CONCLUSION: The ability of pollen to suppress innate antiviral immunity, independent of allergy, suggests that high-risk population groups should avoid extensive outdoor activities when pollen and respiratory virus seasons coincide.

Oak pollen seasonality and severity across Europe and modelling the season start using a generalized phenological model.

Oak pollen seasons are relatively unexplored in large parts of Europe despite producing allergens and being a common tree in both continental and northern parts. Many studies are concentrated only on the Iberian Peninsula. In this study, the seasonal pattern of oak pollen in Europe was analysed using 10 observation sites, ranging from Spain to Sweden. The magnitude of peaks and annual pollen integral together with season-length were studied and substantially higher pollen levels and longer seasons were found in Spain. Two northern sites in Denmark and Sweden showed high oak pollen peaks together with two sites in Spain and United Kingdom. The study also tested four common definitions of season start and applied a generalized phenological model for computing the start of the pollen season. The most accurate definition for a European-wide description of the observed oak pollen start was when the cumulative daily average pollen count reached 50 grains per cubic meter. For the modelling of the start a thermal time method based on Growing Degree Day (GDD) was implemented, utilizing daily temperatures and a generalized approach to identify model parameters applicable to all included sites. GDD values varied between sites and generally followed a decreasing gradient from south to north, with some exceptions. Modelled onsets with base temperatures below 7 °C matched well with observed onsets and 76% of the predictions differed ≤4 days compared to observed onsets when using a base temperature of 2 °C. Base temperatures above 7 °C frequently predicted onsets differing >1 week from the observed. This general approach can be extended to a larger area where pollen observations are non-existent. The presented work will increase the understanding of oak pollen variation in Europe and provide knowledge of its phenology, which is a critical aspect both for modelling purposes on large-scale and assessing the human exposure to oak allergens.

Pollen Lipids Can Play a Role in Allergic Airway Inflammation.

In seed plants, pollen grains carry the male gametes to female structures. They are frequent in the ambient air, and cause airway inflammation in one out of four persons in the population. This was traditionally attributed to soluble glycoproteins, leaking into the nasal mucosa or the conjunctiva, and able to bind antibodies. It is now more and more recognized that also other immunomodulating compounds are present. Lipids bind to Toll-like and PPARγ receptors belonging to antigen-presenting cells in the mammal immune system, activate invariant Natural Killer T-cells, and are able to induce a Type 2 reaction in effector cells. They may also mimic lipid mediators from mammal mast cells. Pollen grains have a rich lipodome of their own. Among the lipids that have been associated with an atopic reaction are saturated and unsaturated fatty acids, glycophospholipids, sphingolipids, sterols, and oxylipids, as well as lipopolysaccharides from the microbiome on the pollen surface. Lipids can be ligands to allergenic proteins.

A statistical model for predicting the inter-annual variability of birch pollen abundance in Northern and North-Eastern Europe.

The paper suggests a methodology for predicting next-year seasonal pollen index (SPI, a sum of daily-mean pollen concentrations) over large regions and demonstrates its performance for birch in Northern and North-Eastern Europe. A statistical model is constructed using meteorological, geophysical and biological characteristics of the previous year). A cluster analysis of multi-annual data of European Aeroallergen Network (EAN) revealed several large regions in Europe, where the observed SPI exhibits similar patterns of the multi-annual variability. We built the model for the northern cluster of stations, which covers Finland, Sweden, Baltic States, part of Belarus, and, probably, Russia and Norway, where the lack of data did not allow for conclusive analysis. The constructed model was capable of predicting the SPI with correlation coefficient reaching up to 0.9 for some stations, odds ratio is infinitely high for 50% of sites inside the region and the fraction of prediction falling within factor of 2 from observations, stays within 40-70%. In particular, model successfully reproduced both the bi-annual cycle of the SPI and years when this cycle breaks down.

The relationship between birch pollen, air pollution and weather types and their effect on antihistamine purchase in two Swedish cities.

Exposure to elevated air pollution levels can aggravate pollen allergy symptoms. The aim of this study was to investigate the relationships between airborne birch (Betula) pollen, urban air pollutants NO2, O3 and PM10 and their effects on antihistamine demand in Gothenburg and Malmö, Sweden, 2006-2012. Further, the influence of large-scale weather pattern on pollen-/pollution-related risk, using Lamb weather types (LWTs), was analysed. Daily LWTs were obtained by comparing the atmospheric pressure over a 16-point grid system over southern Sweden (scale ~3000 km). They include two non-directional types, cyclonic (C) and anticyclonic (A) and eight directional types depending on the wind direction (N, NE, E…). Birch pollen levels were exceptionally high under LWTs E and SE in both cities. Furthermore, LWTs with dry and moderately calm meteorological character (A, NE, E, SE) were associated with strongly elevated air pollution (NO2 and PM10) in Gothenburg. For most weather situations in both cities, simultaneously high birch pollen together with high air pollution had larger over-the-counter (OTC) sales of antihistamines than situations with high birch pollen alone. LWTs NE, E, SE and S had the highest OTC sales in both cities. In Gothenburg, the city with a higher load of both birch pollen and air pollution, the higher OTC sales were especially obvious and indicate an increased effect on allergic symptoms from air pollution. Furthermore, Gothenburg LWTs A, NE, E and SE were associated with high pollen and air pollution levels and thus classified as high-risk weather types. In Malmö, corresponding high-risk LWTs were NE, E, SE and S. Furthermore, occurrence of high pollen and air pollutants as well as OTC sales correlated strongly with vapour pressure deficit and temperature in Gothenburg (much less so in Malmö). This provides evidence that the combination of meteorological properties associated with LWTs can explain high levels of birch pollen and air pollution. Our study shows that LWTs represent a useful tool for integrated daily air quality forecasting/warning.

A nasally applied cellulose powder in seasonal allergic rhinitis in adults with grass pollen allergy: a double-blind, randomized, placebo-controlled, parallel-group study.

BACKGROUND: A nasally applied cellulose powder is increasingly used in many countries as a remedy for allergic rhinitis. In 2009, a 4-week study in birch pollen-allergic children showed a reduction in nasal symptoms. The best effect occurred on days with lower pollen counts. The present study in grass pollen-allergic adults used the same basic design. METHODS: In May 2013, a double-blind, placebo-controlled study was conducted in 108 patients with allergic rhinitis due to grass pollen (18-40 years of age). SMS on mobile phones were used as reminders of treatment and reporting of symptom scores. RESULTS: We found significant reductions in severity scores for sneezing, runny nose, stuffy nose and symptoms from eyes and lower airways, both separately and together (all p < 0.001). Reflective opinion of effect and guess on treatment at follow-up visits (both p < 0.001) confirmed a high efficacy. No clinically significant adverse effects were reported. CONCLUSIONS: The product provided significant protection against all seasonal allergic rhinitis symptoms from both upper and lower airways during the grass pollen season in an adult population. The magnitude and scope of efficacy support the use of the product as an early choice in the treatment of allergic rhinitis.

Grass pollen allergy in children and adolescents-symptoms, health related quality of life and the value of pollen prognosis.

INTRODUCTION: An association between pollen count (Poaceae) and symptoms is well known, but to a lesser degree the importance of priming and lag effects. Also, threshold levels for changes in symptom severity need to be validated. The present study aims to investigate the relationship between pollen counts, symptoms and health related quality of life (HRQL), and to validate thresholds levels, useful in public pollen warnings. MATERIAL AND METHODS: Children aged 7-18 with grass pollen allergy filled out a symptom diary during the pollen season for nose, eyes and lung symptoms, as well as a HRQL questionnaire every week. Pollen counts were monitored using a volumetric spore trap. RESULTS: 89 (91%) of the included 98 children completed the study. There was a clear association between pollen count, symptom severity and HRQL during the whole pollen season, but no difference in this respect between early and late pollen season. There was a lag effect of 1-3 days after pollen exposure except for lung symptoms. We found only two threshold levels, at 30 and 80 pollen grains/m(3) for the total symptom score, not three as is used today. The nose and eyes reacted to low doses, but for the lung symptoms, symptom strength did hardly change until 50 pollen grains/m(3). CONCLUSION: Grass pollen has an effect on symptoms and HRQL, lasting up to 5 days after exposure. Symptoms from the lungs appear to have higher threshold levels than the eyes and the nose. Overall symptom severity does not appear to change during the course of season. Threshold levels need to be revised. We suggest a traffic light model for public pollen warnings directed to children, where green signifies "no problem", yellow signifies "can be problems, especially if you are highly sensitive" and red signifies "alert - take action".

Quality of life in children and adolescents with respiratory allergy, assessed with a generic and disease-specific instrument.

INTRODUCTION: Respiratory allergic disorders like rhinitis and asthma are common conditions that not only affect target organs, but complicate the daily life of affected children and adolescents. OBJECTIVES: The aim of this study was to investigate the QoL (quality of life) in children with grass pollen allergy in and out of grass pollen season. METHODS: We used the Pediatric Allergic Disease Quality of Life Questionnaire (PADQLQ), a disease-specific questionnaire including both asthma and rhinitis symptoms. We also used the DISABKIDS (a European project which aims at enhancing the quality of life and the independence of children with chronic health conditions and their families) questionnaire, a generic questionnaire covering non-organ-specific effects of disease. RESULTS: Ninety-eight children 7­18 years old with grass pollen allergy were included. Eighty-nine children (91%) completed the study. The QoL was significantly decreased during pollen season assessed both with DISABKIDS and PADQLQ. The correlation between the questionnaires was 0.73. Not only the physical domain score (P = 0.00093) but also the emotional domain score (P = 0.034) was significantly lowered. Children with multiple manifestations (asthma and rhinitis) had lower QoL than children with rhinitis alone (P = 0.01). Multiple regression analysis showed a highly significant impact on QoL for symptoms from nose, eyes and lungs. They were equally important (standardized coefficient 047, 0.47 and 0.46, respectively). CONCLUSION: The QoL in children and adolescents with respiratory allergy deteriorates during pollen season. This was shown both with generic (DISABKIDS) and disease-specific instrument (PADQLQ).

Interactions of physical, chemical, and biological weather calling for an integrated approach to assessment, forecasting, and communication of air quality.

This article reviews interactions and health impacts of physical, chemical, and biological weather. Interactions and synergistic effects between the three types of weather call for integrated assessment, forecasting, and communication of air quality. Today's air quality legislation falls short of addressing air quality degradation by biological weather, despite increasing evidence for the feasibility of both mitigation and adaptation policy options. In comparison with the existing capabilities for physical and chemical weather, the monitoring of biological weather is lacking stable operational agreements and resources. Furthermore, integrated effects of physical, chemical, and biological weather suggest a critical review of air quality management practices. Additional research is required to improve the coupled modeling of physical, chemical, and biological weather as well as the assessment and communication of integrated air quality. Findings from several recent COST Actions underline the importance of an increased dialog between scientists from the fields of meteorology, air quality, aerobiology, health, and policy makers.