Browsing by Subject "ALLERGY"

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  • Halonen, Jaana I.; Erhola, Marina; Furman, Eeva; Haahtela, Tari; Jousilahti, Pekka; Barouki, Robert; Bergman, Åke; Billo, Nils E.; Fuller, Richard; Haines, Andrew; Kogevinas, Manolis; Kolossa-Gehring, Marike; Krauze, Kinga; Lanki, Timo; Vicente, Joana Lobo; Messerli, Peter; Nieuwenhuijsen, Mark; Paloniemi, Riikka; Peters, Annette; Posch, Karl-Heinz; Timonen, Pekka; Vermeulen, Roel; Virtanen, Suvi M.; Bousquet, Jean; Antó, Josep M. (2021)
    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.
  • Kivisto, Juho E.; Dunder, Teija; Protudjer, Jennifer L. P.; Karjalainen, Jussi; Huhtala, Heini; Makela, Mika J. (2016)
  • Virkkula, P.; Penttilä, E.; Vento, S. I.; Myller, J.; Koskinen, A.; Hammaren-Malmi, S.; Laulajainen-Hongisto, A.; Hytönen, M.; Lilja, M.; Numminen, J.; Sillanpää, S.; Sahlman, J.; Toppila-Salmi, S. (2020)
    Background: Developing tools to identify chronic rhinosinusitis with nasal polyps (CRSwNP) patients requiring surgical treatment would help clinicians treat patients more effectively. The aim of this retrospective cross-sectional study was to identify cut-off values for eosinophil percentage, nasal polyps (NP), and Lund-Mackay (LM) scores that may predict the need for surgical treatment in Finnish CRSwNP patients. Methods: Data of CRSwNP patients (N = 378) undergoing consultation for ESS in 2001-19 were used. Data was collected from patient records and Lund-Mackay scores were determined from sinus computed tomography scans. The percentage of eosinophils was microscopically evaluated from the polyp samples available (n = 81). Associations were analyzed by Mann Whitney U test, and cut-off values by the area under the receiver operating characteristic curve (AUROC). Results: ESS was performed to 293 (77.5%) of patients. Polyp eosinophilia was associated significantly with ESS (p = 0.001), whereas peripheral blood eosinophil count, LM- score and endoscopic NP- score were not (p > 0.05). AUROC values (95% CI) for detecting those needing ESS were for polyp eosinophilia 0.71 (0.60-0.83), p = 0.001, for LM score 0.59 (0.50-0.67), p = 0.054; for NP score 0.56 (0.48-0.64), p = 0.17, and for blood eosinophil count 0.68 (0.46-0.90), p = 0.08. With the threshold value of polyp eosinophilia (>25%), the sensitivity and specificity were optimal for detecting the group needing ESS from the group not undergoing ESS. The cut-off value of blood eosinophil count (>0.26 x 10(9)/L) had relatively good, yet statistically insignificant (underpowered), predictive potential. Moderate cut-off values were found for endoscopic LM score (>= 14/24) and NP score (>= 4/8). Conclusions: Polyp eosinophilia (>25%) predicted ESS among Finnish hospital-level CRSwNP patients. A future challenge would be to find less invasive and cost-effective clinical factors predicting uncontrolled CRSwNP.
  • Karvala, Kirsi; Uitti, Jukka; Taponen, Saara; Luukkonen, Ritva; Lehtimäki, Lauri (2018)
    Objective: To study the association between perceptions of various triggers of asthma and employment status. Methods: A questionnaire was administered to all those adults living in the city of Tampere, Finland, who were entitled to special reimbursement for asthma medication by the Social Insurance Institution (n = 2613). The response rate was 79%. The study population (n = 1657) consisted of individuals who worked full-time (n = 967), were unemployed (n = 197), had all-cause work disability (n = 334), or were retired due to old age (n = 159). Given a list of potential asthma triggers, the respondents were asked how often (never/sometimes/often) the trigger caused or worsened their asthma symptoms during leisure time. Results: After adjusting for background variables (age, sex, smoking, and professional status), frequency of asthma symptoms, and the use of asthma medication during the last year, any individual trigger identified as asthma-relevant was associated with having work disability (vs. working full-time). The highest odds ratio (OR) was found for vehicle exhaust (OR 5.0, CI 2.2-11.4). We found similar but less consistent associations between asthma trigger perceptions and unemployment. No elevated ORs were found regarding asthma trigger perceptions for old-age retirement. Conclusions: Perceptions of asthma triggers are associated with all-cause work disability. Our findings suggest that asthmatics have excess trigger perceptions that are not explained by asthma alone. Asthmatics need to be informed that inaccurate trigger perceptions may develop, and how they are induced, because unnecessary trigger avoidance may interfere with work life.
  • Koskinen, Jyri-Pekka; Kiviranta, Hannu; Vartiainen, Erkki; Jousilahti, Pekka; Vlasoff, Tiina; von Hertzen, Leena; Mäkelä, Mika; Laatikainen, Tiina; Haahtela, Tari (2016)
    Background: Atopic allergy is much more common in Finnish compared with Russian Karelia, although these areas are geographically and genetically close. To explore the role of environmental chemicals on the atopy difference a random sample of 200 individuals, 25 atopic and 25 non-atopic school-aged children and their mothers, were studied. Atopy was defined as having at least one positive skin prick test response to 14 common inhalant and food allergens tested. Concentrations of 11 common environmental pollutants were measured in blood samples. Results: Overall, the chemical levels were much higher in Russia than in Finland, except for 2,2', 4,4'-tetra-bromodiphenyl ether (BDE47). In Finland but not in Russia, the atopic children had higher concentrations of polychlorinated biphenyls and 1,1-Dichloro-2,2-bis-(p-chlorophenyl)-ethylene (DDE) than the non-atopic children. In Russia but not in Finland, the atopic mothers had higher DDE concentrations than the non-atopic mothers. Conclusions: Higher concentrations of common environmental chemicals were measured in Russian compared with Finnish Karelian children and mothers. The chemicals did not explain the higher prevalence of atopy on the Finnish side.
  • the TRIGR Invest; Virtanen, Suvi M.; Cuthbertson, David; Nucci, Anita M.; Hyytinen, Mila; Salonen, Marja; Savilahti, Erkki; Knip, Mikael (2021)
    The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) tested the hypothesis whether extensively hydrolyzed casein-based versus regular cow's milk-based infant formula reduces the risk of type 1 diabetes. We describe dietary compliance in the trial in terms of study formula intake, feeding of nonrecommended foods, and serum cow's milk antibody concentration reflecting intake of cow's milk protein among 2,159 eligible newborn infants with a biological first-degree relative affected by type 1 diabetes and with HLA-conferred susceptibility to type 1 diabetes. The participating infants were introduced to the study formula feeding at the median age of 15 days with a median duration of study formula use of 63 days. During the intervention, 80% of the infants received study formula. Of these, 57% received study formula for at least 2 months. On average, 45.5 l of study formula were used per infant. Only 13% of the population had received a nonrecommended food by the age of 6 months. The dietary compliance was similar in the intervention and control arm. The reported cow's milk consumption by the families matched very well with measured serum casein IgA and IgG antibody concentration. To conclude, good compliance was observed in this randomized infant feeding trial. Compliance varied between the regions and those infants who were breastfed for a longer period of time had a shorter exposure to the study formula. High dietary compliance in infant feeding trial is necessary to allow accurate interpretation of study results.
  • Kirjavainen, Pirkka V.; Karvonen, Anne M.; Adams, Rachel I.; Täubel, Martin; Roponen, Marjut; Tuoresmäki, Pauli; Loss, Georg; Jayaprakash, Balamuralikrishna; Depner, Martin; Ege, Markus Johannes; Renz, Harald; Pfefferle, Petra Ina; Schaub, Bianca; Lauener, Roger; Hyvärinen, Anne; Knight, Rob; Heederik, Dick J. J.; von Mutius, Erika; Pekkanen, Juha (2019)
    Asthma prevalence has increased in epidemic proportions with urbanization, but growing up on traditional farms offers protection even today(1). The asthma-protective effect of farms appears to be associated with rich home dust microbiota(2,3), which could be used to model a health-promoting indoor microbiome. Here we show by modeling differences in house dust microbiota composition between farm and non-farm homes of Finnish birth cohorts(4) that in children who grow up in non-farm homes, asthma risk decreases as the similarity of their home bacterial microbiota composition to that of farm homes increases. The protective microbiota had a low abundance of Streptococcaceae relative to outdoor-associated bacterial taxa. The protective effect was independent of richness and total bacterial load and was associated with reduced proinflammatory cytokine responses against bacterial cell wall components ex vivo. We were able to reproduce these findings in a study among rural German children(2) and showed that children living in German non-farm homes with an indoor microbiota more similar to Finnish farm homes have decreased asthma risk. The indoor dust microbiota composition appears to be a definable, reproducible predictor of asthma risk and a potential modifiable target for asthma prevention.
  • Ramasamy, Adaikalavan; Kuokkanen, Mikko; Vedantam, Sailaja; Gajdos, Zofia K.; Alves, Alexessander Couto; Lyon, Helen N.; Ferreira, Manuel A. R.; Strachan, David P.; Zhao, Jing Hua; Abramson, Michael J.; Brown, Matthew A.; Coin, Lachlan; Dharmage, Shyamali C.; Duffy, David L.; Haahtela, Tari; Heath, Andrew C.; Janson, Christer; Kahonen, Mika; Khaw, Kay-Tee; Laitinen, Jaana; Le Souef, Peter; Lehtimaki, Terho; Madden, Pamela A. F.; Marks, Guy B.; Martin, Nicholas G.; Matheson, Melanie C.; Palmer, Cameron D.; Palotie, Aarno; Pouta, Anneli; Robertson, Colin F.; Viikari, Jorma; Widen, Elisabeth; Wjst, Matthias; Jarvis, Deborah L.; Montgomery, Grant W.; Thompson, Philip J.; Wareham, Nick; Eriksson, Johan; Jousilahti, Pekka; Laitinen, Tarja; Pekkanen, Juha; Raitakari, Olli T.; O'Connor, George T.; Salomaa, Veikko; Jarvelin, Marjo-Riitta; Hirschhorn, Joel N.; Australian Asthma Genetics (2012)
  • Loo, Evelyn Xiu Ling; Lau, Hui Xing; Suaini, Noor Hidayatul Aini; Wong, Lydia Su Yin; Goh, Anne Eng Neo; Teoh, Oon Hoe; Van Bever, Hugo P. S.; Shek, Lynette Pei-chi; Lee, Bee Wah; Tan, Kok Hian; Godfrey, Keith M.; Eriksson, Johan Gunnar; Chong, Yap Seng; Tham, Elizabeth Huiwen (2021)
  • Tanno, Luciana K.; Haahtela, Tari; Calderon, Moises A.; Cruz, Alvaro; Demoly, Pascal; Joint Allergy Academies (2017)
    Asthma and allergic diseases can start in childhood and persist throughout life, but could also be manifested later, at any time for still misunderstood reasons. They are major chronic multifactorial respiratory diseases, for which prevention, early diagnosis and treatment is recognized as a priority for the Europe's public health policy and the United Nations. Given that allergy triggers (including infections, rapid urbanization leading to loss in biodiversity, pollution and climate changes) are not expected to change in a foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies. Currently there are good treatments for asthma, several risk factors are known (e.g., allergies, rhinitis, tobacco smoke) and tools to control the disease have been developed. However, we are still uncertain how to prevent patients from developing asthma and allergic diseases. In this paper, we list the positive and negative experiences in this field as well as analyze the missing links in the process. This critical analysis will be the basis of setting-up an effective program for prevention and making, a process labeled as "implementation gaps". (C) 2017 Elsevier Ltd. All rights reserved.
  • Karvonen, Anne M.; Kirjavainen, Pirkka V.; Täubel, Martin; Jayaprakash, Balamuralikrishna; Adams, Rachel I.; Sordillo, Joanne E.; Gold, Diane R.; Hyvärinen, Anne; Remes, Sami; von Mutius, Erika; Pekkanen, Juha (2019)
    Background: Early-life indoor bacterial exposure is associated with the risk of asthma, but the roles of specific bacterial genera are poorly understood. Objective: We sought to determine whether individual bacterial genera in indoor microbiota predict the development of asthma. Methods: Dust samples from living rooms were collected at 2 months of age. The dust microbiota was characterized by using Illumina MiSeq sequencing amplicons of the bacterial 16S ribosomal RNA gene. Children (n = 373) were followed up for ever asthma until the age of 10.5 years. Results: Richness was inversely associated with asthma after adjustments (P = .03). The phylogenetic microbiota composition in asthmatics patients' homes was characteristically different from that in nonasthmatic subjects' homes (P = .02, weighted UniFrac, adjusted association, permutational multivariate analysis of variance, PERMANOVA-S). The first 2 axis scores of principal coordinate analysis of the weighted UniFrac distance matrix were inversely associated with asthma. Of 658 genera detected in the dust samples, the relative abundances of 41 genera correlated (r > vertical bar 0.4 vertical bar) with one of these axes. Lactococcus genus was a risk factor for asthma (adjusted odds ratio, 1.36 [95% CI, 1.13-1.63] per interquartile range change). The abundance of 12 bacterial genera (mostly from the Actinomycetales order) was associated with lower asthma risk (P <.10), although not independently of each other. The sum relative abundance of these 12 intercorrelated genera was significantly protective and explained the majority of the association of richness with less asthma. Conclusion: Our data confirm that phylogenetic differences in the microbiota of infants' homes are associated with subsequent asthma risk and suggest that communities of selected bacteria are more strongly linked to asthma protection than individual bacterial taxa or mere richness.
  • Kluger, Nicolas (2021)
    Tattoos are not mentioned as a source of exposure to nickel. Traces of nickel are, however, almost inevitably found in tattoo inks as impurities and sometimes in tattooed skin. Whether nickel in tattoos has any health consequence is debated. We performed a narrative review of what is currently known about this topic. Today, nickel is frequently detected in inks, but at highly variable levels. It appears to be at higher concentrations in green, blue, and sometimes brown and violet inks. Only nickel allergy in tattooed individuals and nickel-associated tattoo ink allergy are addressed in the literature. Reports of tattoo ink allergy related to nickel are rare and heterogenous. Authors often neglect possible implications of other metals or dyes. A positive patch test is not enough to confirm the role of nickel in a reaction observed after tattooing. We found no report of any systemic complication attributed to nickel from tattoos. The Council of Europe ResAP(2008)1 bans the presence of nickel at high levels in tattoo inks, which is a safety net for individuals with nickel allergy. Large epidemiologic case-control studies with systematic biopsies on normal and inflamed tattoos and patch testing would help to understand the role of nickel in tattoo ink allergies.
  • Holm, Matilda; Saraswat, Mayank; Joenväärä, Sakari; Seppo, Antti; Looney, R. John M.; Tohmola, Tiialotta; Renkonen, Jutta; Renkonen, Risto; Järvinen, Kirsi (2022)
    The prevalence of allergic diseases and asthma is increasing rapidly worldwide, with environmental and lifestyle behaviors implicated as a reason. Epidemiological studies have shown that children who grow up on farms are at lower risk of developing childhood atopic disease, indicating the presence of a protective "farm effect". The Old Order Mennonite (OOM) community in Upstate New York have traditional, agrarian lifestyles, a low rate of atopic disease, and long periods of exclusive breastfeeding. Human milk proteins are heavily glycosylated, although there is a paucity of studies investigating the milk glycoproteome. In this study, we have used quantitative glycoproteomics to compare the N-glycoprotein profiles of 54 milk samples from Rochester urban/suburban and OOM mothers, two populations with different lifestyles, exposures, and risk of atopic disease. We also compared N-glycoprotein profiles according to the presence or absence of atopic disease in the mothers and, separately, the children. We identified 79 N-glycopeptides from 15 different proteins and found that proteins including immunoglobulin A1, polymeric immunoglobulin receptor, and lactotransferrin displayed significant glycan heterogeneity. We found that the abundances of 38 glycopeptides differed significantly between Rochester and OOM mothers and also identified four glycopeptides with significantly different abundances between all comparisons. These four glycopeptides may be associated with the development of atopic disease. The findings of this study suggest that the differential glycosylation of milk proteins could be linked to atopic disease.
  • Ottman, Noora; Ruokolainen, Lasse; Suomalainen, Alina; Sinkko, Hanna; Karisola, Piia; Lehtimaki, Jenni; Lehto, Maili; Hanski, Ilkka; Alenius, Harri; Fyhrquist, Nanna (2019)
    Background: Sufficient exposure to natural environments, in particular soil and its microbes, has been suggested to be protective against allergies. Objective: We aim at gaining more direct evidence of the environment-microbiota-health axis by studying the colonization of gut microbiota in mice after exposure to soil and by examining immune status in both a steady-state situation and during allergic inflammation. Methods: The gastrointestinal microbiota of mice housed on clean bedding or in contact with soil was analyzed by using 16S rRNA gene sequencing, and the data were combined with immune parameters measured in the gut mucosa, lung tissue, and serum samples. Results: We observed marked differences in the small intestinal and fecal microbiota composition between mice housed on clean bedding or in contact with soil, with a higher proportion of Bacteroidetes relative to Firmicutes in the soil group. The housing environment also influenced mouse intestinal gene expression, as shown by upregulated expression of the immunoregulatory markers IL-10, forkhead box P3, and cytotoxic T lymphocyte-associated protein 4 in the soil group. Importantly, using the murine asthma model, we found that exposure to soil polarizes the immune system toward T(H)1 and a higher level of anti-inflammatory signaling, alleviating T(H)2-ype allergic responses. The inflammatory status of the mice had a marked influence on the composition of the gut microbiota, suggesting bidirectional communication along the gut-lung axis. Conclusion: Our results provide evidence of the role of environmentally acquired microbes in alleviating against T(H)2-driven inflammation, which relates to allergic diseases.
  • Hui, Nan; Parajuli, Anirudra; Puhakka, Riikka; Grönroos, Mira; Roslund, Marja; Vari, Heli; Selonen, Ville A. O.; Yan, Guoyang; Siter, Nathan; Nurminen, Noora; Oikarinen, Sami; Laitinen, Olli; Rajaniemi, Juho; Hyöty, Heikki; Sinkkonen, Aki (2019)
    An agricultural environment and exposure to diverse environmental microbiota has been suggested to confer protection against immune-mediated disorders. As an agricultural environment may have a protective role, it is crucial to determine whether the limiting factors in the transfer of environmental microbiota indoors are the same in the agricultural and urban environments. We explored how sampling month, garden diversity and animal ownership affected the indoor-transfer of environmental microbial community. We collected litter from standardized doormats used for 2 weeks in June and August 2015 and February 2016 and identified bacterial phylotypes using 16S rRNA Illumina MiSeq sequencing. In February, the diversity and richness of the whole bacterial community and the relative abundance of environment-associated taxa were reduced, whereas human-associated taxa and genera containing opportunistic pathogens were enriched in the doormats. In summer, the relative abundances of several taxa associated previously with beneficial health effects were higher, particularly in agricultural areas. Surprisingly, the importance of vegetation on doormat microbiota was more observable in February, which may have resulted from snow cover that prevented contact with microbes in soil. Animal ownership increased the prevalence of genera Bacteroides and Acinetobacter in rural doormats. These findings underline the roles of season, living environment and lifestyle in the temporal variations in the environmental microbial community carried indoors. As reduced contact with diverse microbiota is a potential reason for immune system dysfunction, the results may have important implications in the etiology of immune-mediated, non-communicable diseases.
  • Hisinger-Mölkänen, Hanna; Pallasaho, Paula; Haahtela, Tari; Lindqvist, Ari; Sovijärvi, Anssi; Piirilä, Päivi (2019)
    Background: Mortality and hospitalization due to asthma have decreased in many European countries, but asthma symptoms still cause a lot of morbidity and costs. Objectives: We evaluated prevalence trends of asthma, asthma symptoms and allergic rhinoconjunctivitis in adults aged 20-69 years during a 20-year period from 1996 to 2016 in the city of Helsinki, the capital of Finland. Methods: Three cross-sectional postal surveys were conducted in random population samples 10 years apart. In 1996, 2006 and 2016, a total of 6062 (response rate 75.9%), 2449 (61.9%) and 4026 subjects (50.3%) took part, respectively. Results: In all responders, the prevalence of physician-diagnosed asthma was 6.6% in 1996, 10% in 2006 and 10.9% in 2016. The prevalence increased from 1996 to 2006, but stabilized from 2006 to 2016, both in men and women and in smokers and non-smokers. The prevalence of current asthma (8.5% in 2006 and 8.8% in 2016) and of asthma with rhinoconjunctivitis (7.6% in 2006 and 7.5% in 2016) remained also at the same level. Allergic rhinoconjunctivitis decreased significantly from 2006 (42.7%) to 2016 (39.0%, p=0.004). Those with physician diagnosed asthma reported significantly less symptoms in 2016 compared to 2006 and 1996, although there was no change in smoking habits or medication use. Young asthmatics (20-29 years) without rhinoconjunctivitis reported least symptoms. Conclusion: Previously observed increase of physician-diagnosed asthma prevalence in adults seems to be levelling off in Helsinki, and patients have fewer symptoms than 20 years ago. In addition, allergic rhinoconjunctivitis is less frequent than 10 years earlier. (247 words).
  • Nuutinen, Mikko; Lyly, Annina; Virkkula, Paula; Hytönen, Maija; Saarentaus, Elmo; Mäkitie, Antti; Palotie, Aarno; Torkki, Paulus; Haukka, Jari; Toppila-Salmi, Sanna (2022)
    Background The aim was to evaluate the relative proportion of Non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD) and other comorbidities, and their impact on the burden of outpatient visits due to allergic rhinitis (AR), non-allergic rhinitis (NAR), acute rhinosinusitis (ARS), and chronic rhinosinusitis with nasal polyps (CRSwNP) and without (CRSsNP). Methods We used hospital registry data of a random sample of 5080 rhinitis/rhinosinusitis patients diagnosed during 2005-2019. International Statistical Classification of Diseases and Related Health Problems (ICD10) diagnoses, visits, and other factors were collected from electronic health records by using information extraction and data processing methods. Cox's proportional hazards model was used for modeling the time to the next outpatient visit. Results The mean (+/- standard deviation) age of the population was 33.6 (+/- 20.7) years and 56.1% were female. The relative proportion of AR, NAR, ARS, CRSsNP and CRSwNP, were 33.5%, 27.5%, 27.2%, 20.7%, and 10.9%, respectively. The most common other comorbidities were asthma (44.4%), other chronic respiratory diseases (38.5%), musculoskeletal diseases (38.4%), and cardiovascular diseases (35.7%). Non-steroidal anti-inflammatory drug exacerbated respiratory disease existed in 3.9% of all patients, and 17.7% of the CRSwNP group. The relative proportion of subjects having 1, 2, 3 and >= 4 other diseases were 18.0%, 17.6%, 17.0%, 37.0%, respectively. All diseases except AR, ARS, and mouth breathing, were associated with a high frequency of outpatient visits. Conclusions Our results revealed a high relative proportion of NERD and other comorbidities, which affect the burden of outpatient visits and hence confirm the socioeconomic impact of upper airway diseases.
  • Krusche, Johanna; Twardziok, Monika; Rehbach, Katharina; Böck, Andreas; Tsang, Miranda S.; Schröder, Paul C.; Kumbrink, Jörg; Kirchner, Thomas; Xing, Yuhan; Riedler, Josef; Dalphin, Jean-Charles; Pekkanen, Juha; Lauener, Roger; Roponen, Marjut; Li, Jing; Wong, Chun K.; Wong, Gary W.K.; Schaub, Bianca; Ege, Markus; Depner, Martin; Illi, Sabina; Loss, Georg J.; Renz, Harald; Pfefferle, Petra I.; Kabesch, Michael; Genuneit, Jon; Karvonen, Anne M.; Hyvärinen, Anne; Kirjavainen, Pirkka V.; Remes, Sami; Braun-Fahrländer, Charlotte; Roduit, Caroline; Frei, Remo; Kaulek, Vincent; Dalphin, Marie-Laure; Divaret-Chauveau, Amandine; Doekes, Gert (2019)
    Background: Childhood asthma prevalence is significantly greater in urban areas compared with rural/farm environments. Murine studies have shown that TNF-alpha-induced protein 3 (TNFAIP3; A20), an anti-inflammatory regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) signaling, mediates environmentally induced asthma protection. Objective: We aimed to determine the role of TNFAIP3 for asthma development in childhood and the immunomodulatory effects of environmental factors. Methods: In a representative selection of 250 of 2168 children from 2 prospective birth cohorts and 2 cross-sectional studies, we analyzed blood cells of healthy and asthmatic children from urban and rural/farm environments from Europe and China. PBMCs were stimulated ex vivo with dust from "asthma-protective'' farms or LPS. NF-kappa B signaling-related gene and protein expression was assessed in PBMCs and multiplex gene expression assays (NanoString Technologies) in isolated dendritic cells of schoolchildren and in cord blood mononuclear cells from newborns. Results: Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased, whereas proinflammatory Toll-like receptor 4 expression was increased in urban asthmatic patients (P <.05), reflecting their increased inflammatory status. Ex vivo farm dust or LPS stimulation restored TNFAIP3 expression to healthy levels in asthmatic patients and shifted NF-kappa B signaling-associated gene expression toward an anti-inflammatory state (P <.001). Farm/rural children had lower expression, indicating tolerance induction by continuous environmental exposure. Newborns with asthma at school age had reduced TNFAIP3 expression at birth, suggesting TNFAIP3 as a possible biomarker predicting subsequent asthma. Conclusion: Our data indicate TNFAIP3 as a key regulator during childhood asthma development and its environmentally mediated protection. Because environmental dust exposure conferred the anti-inflammatory effects, it might represent a promising future agent for asthma prevention and treatment.
  • Parajuli, Anirudra; Grönroos, Mira; Siter, Nathan; Puhakka, Riikka; Vari, Heli K.; Roslund, Marja; Jumpponen, Ari; Nurminen, Noora; Laitinen, Olli H.; Hyöty, Heikki; Rajaniemi, Juho; Sinkkonen, Aki Tapio (2018)
    Expanding urbanization is a major factor behind rapidly declining biodiversity. It has been proposed that in urbanized societies, the rarity of contact with diverse environmental microbiota negatively impacts immune function and ultimately increases the risk for allergies and other immune-mediated disorders. Surprisingly, the basic assumption that urbanization reduces exposure to environmental microbiota and its transfer indoors has rarely been examined. We investigated if the land use type around Finnish homes affects the diversity, richness, and abundance of bacterial communities indoors. Debris deposited on standardized doormats was collected in 30 rural and 26 urban households in and near the city of Lahti, Finland, in August 2015. Debris was weighed, bacterial community composition determined by high throughput sequencing of bacterial 16S ribosomal RNA (rRNA) gene on the Illumina MiSeq platform, and the percentage of four different land use types (i.e., built area, forest, transitional, and open area) within 200 m and 2000 m radiuses from each household was characterized. The quantity of doormat debris was inversely correlated with coverage of built area. The diversity of total bacterial, Proteobacterial, Actinobacterial, Bacteroidetes, and Firmicutes communities decreased as the percentage of built area increased. Their richness followed the same pattern except for Firmicutes for which no association was observed. The relative abundance of Proteobacteria and particularly Gammaproteobacteria increased, whereas that of Actinobacteria decreased with increasing built area. Neither Phylum Firmicutes nor Bacteroidetes varied with coverage of built area. Additionally, the relative abundance of potentially pathogenic bacterial families and genera increased as the percentage of built area increased. Interestingly, having domestic animals (including pets) only altered the association between the richness of Gammaproteobacteria and diversity of Firmicutes with the built area coverage suggesting that animal ownership minimally affects transfer of environmental microbiota indoors from the living environment. These results support the hypothesis that people living in densely built areas are less exposed to diverse environmental microbiota than people living in more sparsely built areas.