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.

Serum antibody response to periodontal pathogens and herpes simplex virus in relation to classic risk factors of cardiovascular disease.

BACKGROUND: Increasing evidence links chronic infections, especially burden of several infections, with increased risk for cardiovascular diseases (CVD). We studied joint immune response against two major periodontal pathogens and herpes simplex virus (HSV) in relation to established risk factors of CVD. METHODS: Serum antibody levels to HSV, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were determined by ELISA. The study included 1107 subjects, 734 from Finland and 373 from Russia. RESULTS: Combined antibody response to periodontal pathogens was associated inversely (OR, 95% CI) with high-density lipoprotein (HDL) cholesterol concentration (beta = 0.35; 0.20, 0.60; P < 0.001) and directly with HSV antibody quartiles: compared with the first quartile, ORs (95% CI) for quartiles 2-4 were 1.43 (0.88-2.32), 1.74 (1.07-2.82), and 1.89 (1.18-3.02), respectively (P for trend <0.001), after adjusting for age, gender, area, education, smoking, BMI, alcohol, triglycerides, and number of teeth. In linear regression analysis, the 3-pathogen antibody score (comprising antibody levels against periodontal pathogens and HSV) was inversely associated with HDL cholesterol concentration (beta = -0.067/1 mmol/l; -0.235, -0.018; P < 0.05). CONCLUSIONS: HSV infection may promote infection by periodontal pathogens. Furthermore, the infectious burden comprising HSV and periodontitis may increase the risk for CVD by clearly decreasing HDL cholesterol concentrations.

Infectious burden as a determinant of atopy-- a comparison between adults in Finnish and Russian Karelia.

BACKGROUND: Evidence of the influence of pathogen exposure on the development of atopy and atopic disease is not unequivocal. We investigated the association between markers of infections and occurrence of atopy among adults in eastern Finland and western Russia, two adjacent areas with profound differences in living conditions and lifestyles. METHODS: Randomly selected adults aged 25-54 years from Finland (n = 790) and from Russia (n = 387) participated in the study. Skin prick tests were performed to 11 common airborne allergens, and at least one positive prick reaction was considered to indicate atopy. Antibodies to different pathogens including hepatitis A virus (HAV), Helicobacter pylori, Toxoplasma gondii, herpes simplex virus (HSV), Chlamydia pneumoniae and the periodontal pathogens Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans were measured. RESULTS: In Finland 34.3% and in Russia 23.3% of the study population was atopic (p < 0.001). Seroprevalences to all these pathogens were significantly higher among the Russians. In multivariate logistic regression analysis, only H. pylori was inversely associated with atopy in Russia. A further stepwise analysis revealed that H. pylori alone can explain 32% of the difference in atopy between the countries, and T. gondii, A. actinomycetemcomitans, HSV and C. pneumoniae had a slightly additive effect, whereas, unexpectedly, seropositivity to HAV and, to a lesser extent, P. gingivalis had an opposite effect. The net result of the stepwise analysis showed that 44% of the difference in atopy between the countries could be explained by seropositivity to these seven pathogens. CONCLUSIONS: Seropositivity to select pathogens, particularly to H. pylori, could explain a substantial part of the difference in atopy prevalence between Finland and Russia. Exposure to HAV was not associated with protection against atopy in this adult population.

Growing disparities in atopy between the Finns and the Russians: a comparison of 2 generations.

BACKGROUND AND OBJECTIVE: Western lifestyle has consistently been associated with the current asthma and atopy epidemics. We examined the occurrence and risk factors of atopy among schoolchildren and their mothers in 2 geographically adjacent areas with fundamental differences in living conditions and lifestyles. METHODS: A population-based study of 2 generations was carried out in eastern Finland and in western Russia. Randomly selected schoolchildren aged 7 to 16 years (367 in Finland and 446 in Russia) and their mothers (365 and 437, respectively) were enrolled. Data were obtained by using a modified International Study of Asthma and Allergies in Childhood questionnaire and by performing skin prick tests against 14 common airborne and food allergens. RESULTS: In children a 4-fold higher risk for atopy (> or =1 positive prick test result) was found in Finland compared with Russia. Sensitization rates in Finland were generally higher among children compared with those of their mothers, whereas in Russia the opposite trends emerged. Parental farming in early life (<1 year) in Finland (odds ratio [OR], 0.53; 95% CI, 0.28-0.99) and in Russia (OR, 0.47; 95% CI, 0.22-1.03) and currently in Finland (OR, 0.45; 95% CI, 0.22-0.91) conferred protection against atopy. Having pets, dogs in Finland (OR, 0.57; 95% CI, 0.35-0.95) and cats in Russia (OR, 0.43; 95% CI, 0.24-0.80), in early life was also inversely associated with atopy. CONCLUSION: Atopy was several-fold more common in Finland compared with in Russia, and disparities in sensitization rates between the countries have further increased during these generations. The similarity of explanatory variables of atopy in both countries suggests that determinants of atopy are shared, at least in similar geoclimatic conditions.

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.

Characterization of a common susceptibility locus for asthma-related traits.

Susceptibility to asthma depends on variation at an unknown number of genetic loci. To identify susceptibility genes on chromosome 7p, we adopted a hierarchical genotyping design, leading to the identification of a 133-kilobase risk-conferring segment containing two genes. One of these coded for an orphan G protein-coupled receptor named GPRA (G protein-coupled receptor for asthma susceptibility), which showed distinct distribution of protein isoforms between bronchial biopsies from healthy and asthmatic individuals. In three cohorts from Finland and Canada, single nucleotide polymorphism-tagged haplotypes associated with high serum immunoglobulin E or asthma. The murine ortholog of GPRA was up-regulated in a mouse model of ovalbumin-induced inflammation. Together, these data implicate GPRA in the pathogenesis of atopy and asthma.

Physical map of an asthma susceptibility locus in 7p15-p14 and an association study of TCRG.

Chromosome 7p15-p14 showed genome-wide significant linkage to asthma related traits among the Finnish and French-Canadian families. As an essential step toward cloning the susceptibility gene, a detailed physical map of the region is needed. In this study we report a dense set of carefully tested, new microsatellite markers for fine mapping embedded in a continuous, easy-to-read, physical map of the region that includes the known genes and putative transcripts. Even though susceptibility genes for asthma are difficult to predict from a multitude of unknown genes mapped to the region, TCRG encoding the gamma-chain of the heterodimeric gamma/delta T cell receptor is a potential candidate. We present linkage and association results for TCRG in two independent Finnish family sets by using four highly polymorphic microsatellites spanning 169 kb across the locus. Linkage results confirmed our previous findings, but our study did not provide any evidence on behalf of a strong association of TCRG with either high serum total Immunoglobulin (IgE) level or asthma. Our results suggest that some other known or yet unidentified gene in the linkage region is the true asthma susceptibility gene.

Allergic diseases, skin prick test responses, and IgE levels in North Karelia, Finland, and the Republic of Karelia, Russia.

BACKGROUND: There is growing evidence to show that atopic diseases are more common in Western Europe than in the former socialist countries of Eastern Europe. OBJECTIVE: The aim of this study was to assess whether a similar difference exists between the most eastern province of Finland and a neighboring western district of Russia. METHODS: A random sample of 25- to 54-year-old subjects was taken from the population registers in the North Karelia Province in eastern Finland and from the Pitkäranta district across the border in the western part of Russia. Participants filled out a questionnaire on atopic and allergic symptoms and participated in a clinical study, which included skin prick tests with 11 airborne allergens and IgE measurements. RESULTS: Self-reported hay fever, allergic eye symptoms, atopic eczema, and asthma were much more common in Finland than in Russia. In Finland 34.2% and in Russia 21.8% had at least one positive skin prick test reaction. In Finland 21.5% but in Russia only 15.8% had at least one elevated allergen-specific IgE value of the 5 values measured. From 6% to 47% of the differences in self-reported symptoms between the countries were explained by atopy, as measured by means of skin prick testing or specific IgE values. CONCLUSIONS: A major difference in clinical allergic diseases and signs of symptoms was observed between the 2 geographically adjacent areas. This suggests that the difference in clinical allergy and atopic disposition is related to the differences in lifestyle and environmental factors.