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Purpose To estimate susceptibility to smoking among never-smoking youth globally and identify factors associated with such behavior. Methods Cross-sectional data for 168 countries were obtained from the Global Youth Tobacco Survey. Simple and multiple logistic regression analyses were conducted. Frequencies and proportions for descriptive statistics, and adjusted odds ratios with 95% confidence intervals for logistic regression models were reported. Results Approximately 12.5% of never-smoking youth worldwide were susceptible to smoking worldwide, of which 7.2% were males and 5.3% were females. Compared with youth in the Americas, those in other WHO regions were associated with decreased susceptibility to smoking. Regardless of gender, exposure to parental or peer smoking, secondhand smoke inside or outside home, and tobacco industry promotion was associated with increased smoking susceptibility. In contrast, support for smoke-free policies and school antismoking education was associated with decreased susceptibility to smoking among females. Moreover, exposure to antismoking media messages was associated with increased susceptibility to smoking among never-smoking youth. Conclusions Approximately 1 in 8 never-smoking youth worldwide was found to be susceptible to smoking. A comprehensive approach involving parental and peer education, smoke-free policies, ban on tobacco advertising and promotions, and antismoking education in schools should be developed by policy makers and public health professionals to protect never-smoking youth from being susceptible to smoking and transforming into future regular smokers.

No / Background  Interleukin (IL)-33 is a member of the IL-1 family and has been implicated in Th2-driven allergic diseases such as atopic dermatitis (AD) and asthma. The principal Th2 cytokine IL-4, found highly expressed in acute allergic eczema, is known to downregulate human β-defensin 2 (hBD2) expression in human keratinocytes and this is associated with superinfection in patients with AD. Objectives  To investigate the effect of IL-33 on the expression of hBD2 in human keratinocytes. Methods  hBD2 production by stimulated keratinocytes was measured by enzyme-linked immunosorbent assay. Results  Our results showed that serum is a very potent inducer of hBD2 and 2·5% human serum was much more potent in inducing hBD2 than 20 ng mL−1 of tumour necrosis factor-α. Interestingly, serum from patients with AD showed an impaired ability to induce hBD2 in normal keratinocytes. IL-33 significantly downregulated serum-induced hBD2. The downregulatory capacity of IL-33 was found to be 1·5- to 2-fold weaker compared with IL-4. Conclusions  Our data suggest that IL-33 can significantly contribute to the decreased expression of hBD2 in acute eczematous reaction clinically characterized by spongiosis and oozing – thus indicative for contact of the epidermis with serum components.

Background: Vitamin D is known to be associated with inflammatory diseases, but its relationship with allergic diseases is unclear. The study objective is to determine the association of serum vitamin D levels and markers of wheeze, asthma and atopy. Methods: Data (n = 9,463) on serum vitamin D levels and atopy were obtained from 2005-2006 National Health and Nutrition Examination Survey. Serum vitamin D level was categorized into four groups: Normal (≥30ng/ml), Insufficient (21-29ng/ml), Deficient (11-20ng/ml) and Severely Deficient (≤10ng/ml). Atopy was defined as at least 1 positive allergen-specific IgE level measured for a panel of 5 common aeroallergens- cat, dog, house dust mite, cock roach and Alternaria species. Doctor-diagnosed asthma and wheeze in the previous 12 months were assessed by means of questionnaire. Multivariable logistic regression analyses were conducted to investigate the association of serum vitamin D with wheeze, asthma and atopy adjusting for age, sex, race, smoking, outdoor physical activity, body mass index and poverty income ratio. Results: Overall, 15%, 14% and 28% of subjects had wheeze, asthma and atopy, respectively. Approximately 21% had normal serum vitamin D levels, while 35%, 28% and 5% had insufficient, deficient and severely deficient levels. Compared to subjects with normal vitamin D levels, those with insufficient, deficient and severely deficient levels had increased relative odds of wheeze and atopy with highest adjusted estimates in subjects with severe vitamin D deficiency (adjusted odds ratio [OR] 2.31, 95% Confidence Interval [CI] 1.73-3.10 for wheeze; OR 1.49, 95% CI 1.17-1.89 for atopy). Conclusion: Low serum vitamin D levels were found to be associated with wheeze and atopy. Findings contribute to ongoing efforts to understanding the role of vitamin D in atopic diseases.

La marche atopique désigne la progression séquentielle des maladies atopiques, en particulier l’apparition d’asthme chez les enfants précédée par celle d’une dermatite atopique (DA) sévère chez les nourrissons. De plus, l’asthme est influencé par le degré de sévérité de la DA, qui pourrait ainsi être considérée comme la porte d’entrée pour le développement ultérieur d’une inflammation allergique des voies aériennes.Mon travail de thèse a consisté à déterminer l’implication de la cytokine TSLP produite par les kératinocytes pendant la marche atopique et implication de la cytokine TSLP pendant le développement de la DA. Pour atteindre ces objectifs, j’ai utilisé des modèles murins de maladies atopiques, en combinaison avec plusieurs lignées de souris génétiquement modifiées.Dans la première partie de mon travail de thèse, nous avons montré que la production de la cytokine TSLP dans les kératinocytes est un facteur nécessaire, non seulement pour l’inflammation cutanée, mais aussi pour générer une réponse immunitaire systémique à l’allergène.Dans la deuxième partie de mon travail de thèse, nous avons montré que la cytokine TSLP induise un recrutement de basophiles d’une façon innée, suite d’une augmentation de ce recrutement induit par l'immunité adaptative. De plus, nous avons montré que la réponse de type “Th2” induit par la cytokine TSLP ce le résultat de une coopération coordonnée de cellules dendritiques, de cellules T CD4+ et de basophiles. Des études cliniques sont nécessaires pour déterminer si l’inhibition de l’expression de la cytokine TSLP et/ou son activité pendant une DA peut réduire l’inflammation cutanée et prévenir la sensibilisation aux allergènes. / Atopic march refers to the natural history of allergic diseases, which is characterized by a typical sequence of sensitization and manifestation of symptoms in different tissues. Commonly, the clinical manifestation of atopic dermatitis (AD) appears in the early life and precedes the development of airway allergic diseases. AD has been proposed as an entry point for subsequent atopic diseases.The objective of my thesis was to better understand the role of TSLP in the atopic march and the cascade events initiated by TSLP in vivo in the development of AD. To reach my thesis objectives we used mouse models of atopic diseases in combination with various deficient-mouse lines.In the first part of this work, using a atopic march mouse model developed during my PhD work, we demonstrated that keratinocytic TSLP is essentially required not only for the development of allergic skin inflammation, but also for the generation of the allergen-specific immune response. In the second part of this work, using a cytokine TSLP-induced AD mouse model (topical MC903 treatment), we demonstrated that skin TSLP induces an early innate recruitment of basophils in the skin, followed by a late recruitment involving adaptive immunity. In addition, we demonstrate that TSLP-induced Th2 response requires an orchestrated cooperation of dendritic cells, CD4+ T cells and basophils.This work provide new knowledge in the cellular and molecular mechanisms implicated in atopic diseases involving TSLP and should provide new insight for the development of therapeutic options of these diseases.

Abstract Little is known about a) the differences in allergic and respiratory diseases between the Finnish and Russian populations, and the environmental factors associated with those differences, and b) exposure to pollen grains indoors and the efficiency of penetration of pollen from outdoor to indoor air. This thesis is based on a cross-sectional population-based epidemiological study conducted in Imatra (Finland) and Svetogorsk (Russia) in 2003 and a rotorod-type-sampler-based pollen study conducted in the province of South Karelia (Finland) between 2003 and 2004. The prevalence of allergic diseases was higher among Finnish than Russian schoolchildren. The symptoms among allergic children were more severe, and the occurrence of respiratory infections was in general more frequent in Russia than in Finland. In the logistic regression analyses the risk of asthma was particularly related to high maternal smoking exposure, and the risk of the common cold was related to high combined parental smoking during infancy (adjusted OR 1.83, 95% CI 1.06–3.17) in Finnish children. Among Russian children, allergic conjunctivitis was related to maternal smoking, while the common cold was inversely related to paternal and parental smoking (0.60, 0.37–0.98 and 0.31, 0.11–0.83, respectively) during the study period. The risk of asthma was inversely related to any indoor dog-keeping in Finland (0.35, 0.13–0.95), whereas in Russia the risk of asthma was increased in relation to combined indoor cat exposure during infancy and the study period (4.56, 1.10–18.91). The concentrations of pollen grains decreased from abundant (0–855 pollen grains per cubic meter, pg/m3) to low (0–3 pg/m3), when moving from outdoors to indoors and further. The differences in diseases and symptoms in these two closely related populations could be ascribed to differences in culture, exposures, diagnostic criteria and treatment. The concentrations of pollen in indoor air during the flowering period were mostly on a level high enough to cause reactions in only the most sensitive subjects. The results suggest that more efforts should be directed to reducing parental smoking, to studying the role and effects of nationally different animal exposures in childhood, and to assessing the importance of different penetration routes of pollen grains. / Tiivistelmä Suomen ja Venäjän välisistä allergioiden ja hengitystietulehdusten esiintymiseroista ja esiintymiseen vaikuttavista ympäristötekijöistä tiedetään varsin vähän. Myös tutkimuksia siitepölyille altistumisesta sisätiloissa ja siitepölyjen tunkeutumiskyvystä ulkoilmasta sisäilmaan on niukasti. Tutkimus yhdistää sekä lääketieteellisen että luonnontieteellisen tutkimusalan tutkimustraditiot sekä atooppisten sairauksien ja/tai hengitystietulehdusten tärkeimpien määrittäjien tarkastelun yhdeksi tutkimuskokonaisuudeksi. Väestö- ja kyselylomakepohjainen poikkileikkaustutkimus toteutettiin Suomen ja Venäjän rajan molemmin puolin sijaitsevissa Imatran ja Svetogorskin kaupungeissa vuonna 2003. Tutkimusväestö koostui 512 suomalaisesta ja 581 venäläisestä 7–16-vuotiaasta koululaisesta (osallistumisaste 79 %). Rotorod-tyyppisen keräimen käyttöön perustuva siitepölytutkimus toteutettiin erilaisissa ulko- ja sisätiloissa Lappeenrannan ja Imatran kaupungeissa, Rautjärven kunnassa ja valtatie 6:lla vuosina 2003 ja 2004. Atooppisten sairauksien esiintyvyys oli runsaampaa suomalaisten koululaisten keskuudessa. Sitä vastoin allergisten lasten kokemat oireet olivat voimakkaampia ja hengitystietulehdusten esiintyvyys oli runsaampaa venäläisten koululaisten keskuudessa. Astmariski kytkeytyi erityisesti äidin runsaalle tupakoinnille altistumiseen raskauden (vakioitu OR 3.51, 95 % luottamusväli 1.00–12.3), ensimmäisen elinvuoden (3.34, 1.23–9.07) ja tutkimuksen aikana (3.27, 1.26–8.48). Nuhakuumeen riski oli suurentunut suomalaisten koululaisten keskuudessa, jotka olivat altistuneet molempien vanhempien runsaalle tupakoinnille ensimmäisen elinvuoden aikana (1.83, 1.06–3.17). Äidin tupakoinnille ensimmäisen elinvuoden (4.53, 1.49–13.8) ja tutkimuksen aikana (2.82, 1.07–7.44) altistuneilla venäläisillä oli suurentunut allergisen silmän sidekalvotulehduksen riski. Tutkimuksen aikainen isän ja vanhempien tupakointi vähensi nuhakuumeen riskiä (0.60, 0.37–0.98; 0.31, 0.11–0.83) Venäjällä. Suomessa koiranpito sisätiloissa vähensi astmariskiä (0.35, 0.13–0.95), vastaavasti Venäjällä raskauden jälkeinen sisätiloissa tapahtuva kissa-altistus lisäsi koululaisten astmariskiä (4.56, 1.10–18.91). Siitepölyjen pitoisuudet pienenivät siirryttäessä ulkoa (0–855 siitepölyhiukkasta ilmakuutiossa; sp/m3) sisätiloihin (0–17 sp/m3). Ympäristöaltisteisiin ja sairauden ennusteeseen vaikuttavat sekä kansallinen kulttuuri ja vakiintuneet tavat, että erot diagnosointikriteereissä, yleisessä tautitietoisuudessa ja lääkkeiden saatavuudessa. Näin ollen altisteiden voimakkuus ja kesto sekä terveysvaikutukset voivat vaihdella merkittävästi lähellä toisiaan sijaitsevien alueiden välillä. Siitepölypitoisuudet sisätiloissa olivat pääosin tasolla, jolle altistuminen aiheuttaa oireita vain kaikkein herkimmille allergisille. Tutkimuksen tulosten mukaan lisää voimavaroja tulisi suunnata passiiviselle tupakoinnille altistumisen vähentämiseen erityisesti yksilökehityksellisesti herkkien varhaisvaiheiden aikana, kansallisten eläinaltistuserojen terveysvaikutusten selvittämiseen sekä siitepölyjen erilaisten kulkeutumisreittien merkityksen tutkimiseen.