Bet v 1 triggers antiviral-type immune signalling in birch-pollen-allergic individuals.

BACKGROUND: In allergic patients, clinical symptoms caused by pollen remind of symptoms triggered by viral respiratory infections, which are also the main cause of asthmatic exacerbations. In patients sensitized to birch pollen, Bet v 1 is the major symptom-causing allergen. Immune mechanisms driving Bet v 1-related responses of human blood cells have not been fully characterized. OBJECTIVE: To characterize the immune response to Bet v 1 in peripheral blood in patients allergic to birch pollen. METHODS: The peripheral blood mononuclear cells of birch-allergic (n = 24) and non-allergic (n = 47) adolescents were stimulated ex-vivo followed by transcriptomic profiling. Systems-biology approaches were employed to decipher disease-relevant gene networks and deconvolution of associated cell populations. RESULTS: Solely in birch-allergic patients, co-expression analysis revealed activation of networks of innate immunity and antiviral signalling as the immediate response to Bet v 1 stimulation. Toll-like receptors and signal transducer transcription were the main drivers of gene expression patterns. Macrophages and dendritic cells were the main cell subsets responding to Bet v 1. CONCLUSIONS AND CLINICAL RELEVANCE: In birch-pollen-allergic patients, the activated innate immune networks seem to be, in part, the same as those activated during viral infections. This tendency of the immune system to read pollens as viruses may provide new insight to allergy prevention and treatment.

A call for urgent action to safeguard our planet and our health in line with the helsinki declaration.

In 2015, the Rockefeller Foundation-Lancet Commission launched a report introducing a novel approach called Planetary Health and proposed a concept, a strategy and a course of action. To discuss the concept of Planetary Health in the context of Europe, a conference entitled: "Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health" was held in Helsinki in December 2019. The conference participants concluded with a need for action to support Planetary Health during the 2020s. The Helsinki Declaration emphasizes the urgency to act as scientific evidence shows that human activities are causing climate change, biodiversity loss, land degradation, overuse of natural resources and pollution. They threaten the health and safety of human kind. Global, regional, national, local and individual initiatives are called for and multidisciplinary and multisectorial actions and measures are needed. A framework for an action plan is suggested that can be modified for local needs. Accordingly, a shift from fragmented approaches to policy and practice towards systematic actions will promote human health and health of the planet. Systems thinking will feed into conserving nature and biodiversity, and into halting climate change. The Planetary Health paradigm ‒ the health of human civilization and the state of natural systems on which it depends ‒ must become the driver for all policies.

The effects of climate change on respiratory allergy and asthma induced by pollen and mold allergens.

The impact of climate change on the environment, biosphere, and biodiversity has become more evident in the recent years. Human activities have increased atmospheric concentrations of carbon dioxide (CO2 ) and other greenhouse gases. Change in climate and the correlated global warming affects the quantity, intensity, and frequency of precipitation type as well as the frequency of extreme events such as heat waves, droughts, thunderstorms, floods, and hurricanes. Respiratory health can be particularly affected by climate change, which contributes to the development of allergic respiratory diseases and asthma. Pollen and mold allergens are able to trigger the release of pro-inflammatory and immunomodulatory mediators that accelerate the onset the IgE-mediated sensitization and of allergy. Allergy to pollen and pollen season at its beginning, in duration and intensity are altered by climate change. Studies showed that plants exhibit enhanced photosynthesis and reproductive effects and produce more pollen as a response to high atmospheric levels of carbon dioxide (CO2 ). Mold proliferation is increased by floods and rainy storms are responsible for severe asthma. Pollen and mold allergy is generally used to evaluate the interrelation between air pollution and allergic respiratory diseases, such as rhinitis and asthma. Thunderstorms during pollen seasons can cause exacerbation of respiratory allergy and asthma in patients with hay fever. A similar phenomenon is observed for molds. Measures to reduce greenhouse gas emissions can have positive health benefits.

The importance of the exposome and allostatic load in the planetary health paradigm.

In 1980, Jonas Salk (1914-1995) encouraged professionals in anthropology and related disciplines to consider the interconnections between "planetary health," sociocultural changes associated with technological advances, and the biology of human health. The concept of planetary health emphasizes that human health is intricately connected to the health of natural systems within the Earth's biosphere; experts in physiological anthropology have illuminated some of the mechanisms by which experiences in natural environments (or the built environment) can promote or detract from health. For example, shinrin-yoku and related research (which first emerged from Japan in the 1990s) helped set in motion international studies that have since examined physiological responses to time spent in natural and/or urban environments. However, in order to advance such findings into planetary health discourse, it will be necessary to further understand how these biological responses (inflammation and the collective of allostatic load) are connected to psychological constructs such as nature relatedness, and pro-social/environmental attitudes and behaviors. The exposome refers to total environmental exposures-detrimental and beneficial-that can help predict biological responses of the organism to environment over time. Advances in "omics" techniques-metagenomics, proteomics, metabolomics-and systems biology are allowing researchers to gain unprecedented insight into the physiological ramifications of human behavior. Objective markers of stress physiology and microbiome research may help illuminate the personal, public, and planetary health consequences of "extinction of experience." At the same time, planetary health as an emerging multidisciplinary concept will be strengthened by input from the perspectives of physiological anthropology.

Dietary intake of α-linolenic acid and low ratio of n-6:n-3 PUFA are associated with decreased exhaled NO and improved asthma control.

As recently described, adherence to the Mediterranean diet is associated with improved asthma control. However, evidence of how specific nutrients such as fatty acids and antioxidants may affect this relationship remains largely unknown. We aimed to examine the association between dietary intake of fatty acids and antioxidants and asthma control. A cross-sectional study was developed in 174 asthmatics, mean age of 40 (SD 15) years. Dietary intake was obtained by a FFQ, and nutritional content was calculated using Food Processor Plus™ software (ESHA Research, Inc., Salem, OR, USA). Good asthma control was defined by the combination of forced expiratory volume during the first second, exhaled NO (eNO) and Asthma Control Questionnaire (ACQ) score (control: forced expiratory volume in the first second ≥80 %; eNO ≤35 ppb; ACQ <1·0, scale 0-6 score). Multiple linear and logistic regression models were performed to analyse the associations between nutrients and asthma outcomes, adjusting for confounders. A high n-6:n-3 PUFA ratio predicted high eNO, whereas high intakes of n-3 PUFA, a-linolenic acid (ALA) and SFA were associated with low eNO. Odds for controlled asthma improved along with an increased intake of n-3 PUFA (OR 0·14, 95% CI 0·04, 0·45; P for trend=0·001), SFA (OR 0·36, 95% CI 0·13, 0·97; P for trend=0·047) and ALA (OR 0·18, 95% CI 0·06, 0·58; P for trend=0·005). A high n-6:n-3 PUFA ratio increased the odds for uncontrolled asthma (OR 3·69, 95% CI 1·37, 9·94; P for trend=0·009), after adjusting for energy intake, sex, age, education and use of inhaled corticosteroids. Higher intakes of n-3 PUFA, ALA and SFA were associated with good asthma control, while the risk for uncontrolled asthma increased with a higher n-6:n-3 PUFA ratio. The present results introduce a protective effect of ALA in asthma control, independent of marine n-3 fatty acids, and provide a rationale to dietary intervention studies in asthma.

Montelukast is not effective in controlling allergic symptoms outside the airways: a randomised double-blind placebo-controlled crossover study.

BACKGROUND: Subjects with atopic syndrome often perceive symptoms from various organs. A single drug that acts on all the syndrome's manifestations would be the ideal treatment. The role of montelukast, a cysteinyl-leukotriene receptor antagonist, is established in treating allergic rhinitis and asthma, but its ability to alleviate atopic symptoms outside the airways is controversial. Our aim was to assess if montelukast could be used to treat all the various symptoms seen in subjects with atopic syndrome. METHODS: A randomised, double-blind, placebo-controlled crossover study on the effect of montelukast in atopic syndrome was conducted during the 2007 pollen season. Forty-five pollen-sensitised subjects who had allergic symptoms from both the upper and lower airways and allergic symptoms outside the airways (conjunctivitis, oral symptoms, eczema and/or urticaria) were recruited. The primary outcome parameter was the allergic symptoms, which were assessed using a questionnaire. Secondary outcome parameters were lower-airway inflammation (exhaled nitric oxide) and the need for rescue medication (inhaled beta2-agonists and oral antihistamines). RESULTS: There were no differences between montelukast and placebo treatments in allergic symptoms, in exhaled NO concentration or in the need for oral antihistamines. The need for inhaled beta2-agonists was significantly lower during montelukast treatment. CONCLUSIONS: Montelukast was not effective in treating allergic symptoms outside the airways in subjects suffering from different manifestations of the atopic syndrome. Based on the current results, montelukast should not be recommended as a general drug to treat all the symptoms of atopic syndrome, but it should be considered as a drug for asthma and rhinitis.

Long-term safety and impact on infection rates of postnatal probiotic and prebiotic (synbiotic) treatment: randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Live probiotic bacteria and dietary prebiotic oligosaccharides (together termed synbiotics) increasingly are being used in infancy, but evidence of long-term safety is lacking. In a randomized, placebo-controlled, double-blind trial, we studied the safety and long-term effects of feeding synbiotics to newborn infants. METHODS: Between November 2000 and March 2003, pregnant mothers carrying infants at high risk for allergy were randomly assigned to receive a mixture of 4 probiotic species (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99, and Propionibacterium freudenreichii ssp shermanii) or a placebo for 4 weeks before delivery. Their infants received the same probiotics with 0.8 g of galactooligosaccharides, or a placebo, daily for 6 months after birth. Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3, 6, and 24 months and from questionnaires at ages 3, 6, 12, and 24 months. Growth data were collected at each time point. RESULTS: Of the 1018 eligible infants, 925 completed the 2-year follow-up assessment. Infants in both groups grew normally. We observed no difference in neonatal morbidity, feeding-related behaviors (such as infantile colic), or serious adverse events between the study groups. During the 6-month intervention, antibiotics were prescribed less often in the synbiotic group than in the placebo group (23% vs 28%). Throughout the follow-up period, respiratory infections occurred less frequently in the synbiotic group (geometric mean: 3.7 vs 4.2 infections). CONCLUSION: Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life.

Allergy in marathon runners and effect of Lactobacillus GG supplementation on allergic inflammatory markers.

OBJECTIVE: We studied the prevalence of asthma and allergy in non-elite marathon runners and investigated the effects of probiotic supplementation on allergic inflammatory markers. METHODS: Asthma and allergies were surveyed by questionnaire, and blood eosinophils, serum eosinophil cationic protein (ECP), total IgE, and Phadiatop were measured in 141 Finnish marathon runners who took part in the Helsinki City Marathon. They were also randomized to receive either Lactobacillus GG (LGG) or placebo during the 3 months of the pollen season prior to the marathon. RESULTS: Lifetime prevalence of physician-diagnosed asthma was 4.3% (six out of 139 athletes), of allergic rhinitis 17.3% (24/139), of food allergy 5.0% (7/139), and of atopic eczema 4.3% (6/139). Prevalence of atopy was 31% (35/112), and 21% (24/112) of the athletes were sensitized to birch pollen. Asthma or allergy medication was used by 20% (28/139) of the athletes. During pollen season, serum ECP increased significantly in all athletes, and total IgE and Phadiatop in atopics. The marathon induced a significant eosinopenia but had no effect on serum ECP or total IgE. No differences in changes were seen between groups receiving LGG or placebo. CONCLUSION: Non-elite marathon runners have asthma and allergies similar to Finnish general population. LGG supplementation did not prevent the increase of allergic markers during the pollen season, or the eosinopenia induced by the marathon.

Asthma, airway inflammation and treatment in elite athletes.

Highly trained athletes are repeatedly and strongly exposed to cold air during winter training and to many inhalant irritants and allergens all year round. Asthma occurs most commonly in athletes engaging in endurance events such as cross-country skiing, swimming, or long-distance running. As well as the type of training, a major risk factor is atopic disposition. A mixed type of eosinophilic and neutrophilic airway inflammation has been shown to affect elite swimmers, ice-hockey players, and cross-country skiers. The inflammation may represent a form of repeated thermal, mechanical, or osmotic airway trauma resulting in a healing or remodelling process. Elite athletes commonly use antiasthma drugs to treat exercise-induced bronchial symptoms. Only a few controlled studies have been conducted on the effects of antiasthma drugs on asthma symptoms, bronchial hyperresponsiveness and airway inflammation in elite athletes. Inhaled beta(2)-adrenoceptor agonists are effective against exercise-induced bronchospasm. In contrast, airway inflammation, bronchial hyperresponsiveness and symptoms have responded poorly to inhaled corticosteroids and leukotriene antagonists. As discontinuing high-level exercise has proved effective in reducing eosinophilic airway inflammation, exercise or training should be restricted in athletes having troublesome symptoms and sputum eosinophilia. Switching training to less irritating environments should be considered whenever possible. It appears to be difficult to change the 'natural course' of asthma in athletes by anti-inflammatory treatment.

IgE reactivity pattern to timothy and birch pollen allergens in Finnish and Russian Karelia.

BACKGROUND: Little is known about differences in IgE reactivity patterns to individual allergens in random populations. We studied the IgE reactivity profile to individual recombinant (r) and native (n) allergens in sera from subjects sensitized to timothy and/or birch pollen living in Finnish and Russian Karelia. METHODS: Sera from IgE-sensitized adults were obtained from an epidemiological study on a random sample of 1,177 subjects. The IgE reactivity to pollen extracts and eight timothy (rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4) and three birch pollen allergens (rBet v 1, 2 and 4) were analyzed with UniCAP. RESULTS: The levels of IgE antibodies to timothy and birch pollen were higher in Finnish (median 5.2, range 0.35 to >100 kUA/l,) than in Russian Karelia (median 1.8 kUA/l, range 0.43-25.2 kUA/l, p <0.01). There was a significantly higher prevalence of IgE reactivity to three timothy pollen allergens in Finnish (n=57) than in Russian Karelia (n=12): rPhl p 2, 28 vs. 0%; rPhl p 5, 60 vs. 0%; rPhl p 6, 47 vs. 0%. The prevalence of IgE reactivity to the birch pollen allergens was similar in the two populations. IgE reactivity to rPhl p 2, 5, 6 and 11 was associated with hay fever symptoms. The timothy-pollen-specific serum IgE levels and the numbers of IgE reactivities to individual allergens correlated significantly (rs=0.87, p <0.0001). CONCLUSIONS: The data indicate that timothy- and birch pollen-specific IgE levels are higher in Finnish compared to Russian Karelia. This is reflected in wider IgE reactivity to individual timothy pollen allergens in Finnish Karelia, including the major allergen Phl p 5, and increased pollen allergy.

Direct in vivo monitoring of acute allergic reactions in human conjunctiva.

Immediate allergic reactions are initiated by allergen-induced, specific IgE-mediated mast cell degranulation and involve leukocyte recruitment into the inflamed site. We compared conjunctival signs, symptoms, and in vivo leukocyte rolling and extravasation into sites of inflammation in five patients allergic to birch pollen and in 10 nonallergic controls who received a challenge to birch allergen or histamine. Both the specific allergen in allergic patients and histamine, both in patients and in healthy controls, induced symptoms and signs of an immediate allergic reaction together with leukocyte rolling within the conjunctival blood vessels. However, only allergen, not histamine, caused leukocyte extravasation into the site of inflammation in the allergic patients. Allergen also increased expression of endothelial P-selectin in conjunctival vessels and slowed the rolling of leukocytes which is required for their extravasation from blood circulation into the target tissue. Finally, i.v. heparin strongly reduced the number of slowly rolling cells during allergen- or histamine-induced reactions and this can probably hinder the leukocyte extravasation after allergen exposure. These findings suggest that slow rolling is required for leukocyte extravasation in acute allergic reactions, and it can be inhibited by heparin in vivo in therapeutically relevant conditions.

IgE-mediated allergy to fungal allergens in Finland with special reference to Alternaria alternata and Cladosporium herbarum.

BACKGROUND: Alternaria alternata and Cladosporium herbarum are common fungi in outdoor environments, but their clinical significance has not been elucidated in Finland. OBJECTIVE: To evaluate the prevalence of IgE-mediated allergy and clinical outcomes caused by sensitization to fungal allergens in patients with suspected allergy. METHODS: Skin prick tests (SPTs) were performed with C. herbarum in 6,376 patients and also with A. alternata in 1,504 of these patients. SPTs were repeated in 40 patients who showed a positive reaction to either allergen using commercial and in-house extracts. The association of SPT with allergen-specific IgE antibodies in serum was evaluated. Seven patients also underwent a conjunctival challenge test with these fungal allergens. RESULTS: The prevalence of positive SPT results to A. alternata and C. herbarum was low (2.8% and 2.7%, respectively). Among the 40 patients, atopic eczema/dermatitis syndrome was found in 58%, asthma in 44%, and rhinitis in 31%. Most of the patients displayed SPT reactions also to several other fungal allergens, and 75% to 80% showed a positive SPT reaction to allergens of pet animals or pollens. Four patients had a positive reaction to A. alternata and 6 to C. herbarum in the conjunctival challenge test. CONCLUSION: In the Finnish population with allergic symptoms, IgE-mediated sensitization to 2 common fungal allergens was rare and of minor clinical importance. SPT reactions to fungi are mostly observed in patients with multiple sensitivity to various allergens.

Different IgE reactivity profiles in birch pollen-sensitive patients from six European populations revealed by recombinant allergens: an imprint of local sensitization.

BACKGROUND: Sensitivity to birch pollen allergens is a common feature among European patients with seasonal pollen allergy. In this in vitro study, we examined the specific serum IgE binding profiles to individual birch pollen allergens in birch-sensitive patients from six European populations. METHODS: The study included 242 patients from Finland, Sweden, Austria, France, Switzerland and Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. Their sera were analyzed for specific IgE reactivity to individual birch pollen allergens (recombinant Bet v 1, Bet v 2 and Bet v 4) and natural birch pollen extract using Pharmacia CAP System and immunoblotting. RESULTS: Almost all Finnish, Swedish and Austrian sera contained IgE specific for Bet v 1 (>or=98%). Bet v 1-specific IgE antibodies were found in 90% of the French sera, and in 65 and 62% of the sera from Switzerland and Italy, respectively. Few Finnish (2%) and Swedish (12%) patients had IgE to Bet v 2, while Bet v 2 reactivity was more common in the other populations (20-43%). Reactivity to Bet v 4 was rare in all populations (5-11%) except for the Italian patients, in whom 3 of 11 sera were positive (27%). The immunoblot results supported the specific IgE profiles obtained with Pharmacia CAP System showing a broader IgE reactivity profile in patients from central and southern Europe as compared to northern Europe. CONCLUSION: Component-resolved allergy diagnosis with recombinant allergens reveals that the IgE reactivity profiles to individual birch pollen allergens vary between European populations. This observation may be explained by sensitization to different allergen sources and will have an impact on allergen-specific prevention and therapy strategies.

Omalizumab and the immune system: an overview of preclinical and clinical data.

OBJECTIVE: This review discusses the role of immunoglobulin (Ig)E in allergic disease, inhibition of IgE with omalizumab, and the consequences of IgE inhibition (both clinically and in terms of the effect on the immune system). DATA SOURCES: Relevant publications obtained from a literature review. STUDY SELECTION: Relevant publications on IgE, allergic disease, and anti-IgE were critically evaluated. RESULTS: IgE plays a key role in allergic diseases such as allergic asthma and allergic rhinitis. Its role in healthy individuals is less well defined. Treatment of allergic asthma and rhinitis with omalizumab, a humanized monoclonal anti-IgE antibody, causes a marked reduction in circulating free IgE levels. This has been shown to reduce symptoms and decrease the need for other medication in patients with these allergic diseases. Anti-IgE treatment with omalizumab did not cause any of the complications that might, in theory, be expected to result from reduction in circulating free IgE, such as adverse effects upon the immune system or other body systems. CONCLUSIONS: The limited clinical data currently available suggest that this novel method of treatment for allergic asthma and rhinitis seems to be both effective and well tolerated in clinical use.