Browsing by Subject "CHILDHOOD ASTHMA"

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  • Haahtela, Tari (2019)
    Biodiversity hypothesis states that contact with natural environments enriches the human microbiome, promotes immune balance and protects from allergy and inflammatory disorders. We are protected by two nested layers of biodiversity, microbiota of the outer layer (soil, natural waters, plants, animals) and inner layer (gut, skin, airways). The latter inhabits our body and is colonized from the outer layer. Explosion of human populations along with cultural evolution is profoundly changing our environment and lifestyle. Adaptive immunoregulatory circuits and dynamic homeostasis are at stake in the newly emerged urban surroundings. In allergy, and chronic inflammatory disorders in general, exploring the determinants of immunotolerance is the key for prevention and more effective treatment. Loss of immunoprotective factors, derived from nature, is a new kind of health risk poorly acknowledged until recently. The paradigm change has been implemented in the Finnish allergy programme (2008-2018), which emphasized tolerance instead of avoidance. The first results are promising, as allergy burden has started to reduce. The rapidly urbanizing world is facing serious biodiversity loss with global warming, which are interconnected. Biodiversity hypothesis of health and disease has societal impact, for example, on city planning, food and energy production and nature conservation. It has also a message for individuals for health and well-being: take nature close, to touch, eat, breathe, experience and enjoy. Biodiverse natural environments are dependent on planetary health, which should be a priority also among health professionals.
  • Pakkasela, Johanna; Ilmarinen, Pinja; Honkamäki, Jasmin; Tuomisto, Leena E.; Andersen, Heidi; Piirilä, Päivi; Hisinger-Mölkänen, Hanna; Sovijärvi, Anssi; Backman, Helena; Lundbäck, Bo; Rönmark, Eva; Kankaanranta, Hannu; Lehtimäki, Lauri (2020)
    Background Onset of allergic asthma has a strong association with childhood but only a few studies have analyzed incidence of asthma from childhood to late adulthood in relation to allergy. The purpose of the study was to assess age-specific incidence of allergic and non-allergic asthma. Methods Questionnaires were sent to 8000 randomly selected recipients aged 20-69 years in Finland in 2016. The response rate was 52.3% (n = 4173). The questionnaire included questions on e.g. atopic status, asthma and age at asthma diagnosis. Asthma was classified allergic if also a physician-diagnosed allergic rhinitis was reported. Results The prevalence of physician-diagnosed asthma and allergic rhinitis were 11.2 and 17.8%, respectively. Of the 445 responders with physician-diagnosed asthma, 52% were classified as allergic and 48% as non-allergic. Median ages at diagnosis of allergic and non-allergic asthma were 19 and 35 years, respectively. Among subjects with asthma diagnosis at ages 0-9, 10-19, 20-29, 30-39, 40-49, 50-59 and 60-69 years, 70, 62, 58, 53, 38, 19 and 33%, respectively, were allergic. For non-allergic asthma, the incidence rate was lowest in children and young adults (0.7/1000/year). It increased after middle age and was highest in older age groups (2.4/1000/year in 50-59 years old). Conclusions The incidence of allergic asthma is highest in early childhood and steadily decreases with advancing age, while the incidence of non-allergic asthma is low until it peaks in late adulthood. After approximately 40 years of age, most of the new cases of asthma are non-allergic.
  • PASTURE EFRAIM Study Grp; Metzler, Stefanie; Frei, Remo; Schmausser-Hechfellner, Elisabeth; Pekkanen, Juha; Karvonen, Anne M.; Kirjavainen, Pirkka V.; Roduit, Caroline (2019)
    Background: Allergies are a serious public health issue, and prevalences are rising worldwide. The role of antibiotics in the development of allergies has repeatedly been discussed, as results remain inconsistent. The aim of this study was to investigate the association between pre-and post-natal antibiotic exposure and subsequent development of allergies (atopic dermatitis, food allergy, asthma, atopic sensitization and allergic rhinitis). Methods: A total of 1080 children who participated in a European birth cohort study (PASTURE) were included in this analysis. Data on antibiotic exposure during pregnancy and/or first year of life and allergic diseases were collected by questionnaires from pregnancy up to 6 years of age and analysed by performing logistic regressions. To take into account reverse causation, we included models, where children with diagnosis or symptoms of the respective disease in the first year of life were excluded. Results: Antibiotic exposure in utero was significantly and positively associated with atopic dermatitis and food allergy. The strongest effect was on diseases with onset within the first year of life (for atopic dermatitis: aOR 1.66, 95% CI 1.11-2.48 and for food allergy: aOR 3.01, 95% CI 1.22-7.47). Antibiotics in the first year of life were positively associated with atopic dermatitis up to 4 years (aOR 2.73, 95% CI 1.66-4.49) and also suggested a dose-response relationship. A tendency was observed with asthma between 3 and 6 years (aOR 1.65, 95% CI 0.95-2.86). Conclusions: Our findings show positive associations between exposure to antibiotics and allergies, mainly atopic dermatitis and food allergy within the first year of life, after prenatal exposure, and atopic dermatitis and asthma after post-natal exposure to antibiotics in children born in rural settings.
  • Honkamäki, Jasmin; Piirilä, Päivi; Hisinger-Mölkänen, Hanna; Tuomisto, Leena E.; Andersen, Heidi; Huhtala, Heini; Sovijärvi, Anssi; Lindqvist, Ari; Backman, Helena; Lundbäck, Bo; Rönmark, Eva; Lehtimäki, Lauri; Pallasaho, Paula; Ilmarinen, Pinja; Kankaanranta, Hannu (2021)
    BACKGROUND: Child-onset asthma is known to remit with high probability, but remission in adult-onset asthma is seem-ingly less frequent. Reports of the association between remission and asthma age of onset up to late adulthood are scarce. OBJECTIVE: To evaluate the association between asthma remission, age at diagnosis and gender, and assess risk factors of nonremission. METHODS: In 2016, a random sample of 16,000 subjects aged 20 to 69 years from Helsinki and Western Finland were sent a FinEsS questionnaire. Physician-diagnosed asthma was catego-rized by age at diagnosis to early-(0-11 years), intermediate-(12-39 years), and late-diagnosed (40-69 years) asthma. Asthma remission was defined by not having had asthma symptoms and not having used asthma medication in the past 12 months. RESULTS: Totally, 8199 (51.5%) responded, and 879 reported physician-diagnosed asthma. Remission was most common in early-diagnosed (30.2%), followed by intermediate-diagnosed (17.9%), and least common in late-diagnosed asthma (5.0%) (P < .001), and the median times from diagnosis were 27, 18.5, and 10 years, respectively. In males, the corresponding remission rates were 36.7%, 20.0%, and 3.4%, and in females, 20.4%, 16.6%, and 5.9% (gender difference P < .001). In multivariable binary logistic regression analysis, signifi-cant risk factors of asthma nonremission were intermediate (odds ratio [OR] = 2.15, 95% confidence interval: 1.373.36) and late diagnosis (OR = 11.06, 4.82-25.37) compared with early diagnosis, chronic obstructive pulmonary disease (COPD) (OR = 5.56, 1.26-24.49), allergic rhinitis (OR = 2.28, 1.50-3.46), and family history of asthma (OR = 1.86, 1.22-2.85). Results were similar after excluding COPD. CONCLUSION: Remission was rare in adults diagnosed with asthma after age 40 years in both genders. Late-diagnosed asthma was the most significant independent risk factor for nonremission. (C) 2020 American Academy of Allergy, Asthma & Immunology
  • Twardziok, Monika; Schroder, Paul C.; Krusche, Johanna; Casaca, Vera I.; Illi, Sabina; Bock, Andreas; Loss, Georg J.; Kabesch, Michael; Toncheva, Antoaneta A.; Roduit, Caroline; Depner, Martin; Genuneit, Jon; Renz, Harald; Roponen, Marjut; Weber, Juliane; Braun-Fahrlander, Charlotte; Riedler, Josef; Lauener, Roger; Vuitton, Dominique Angele; Dalphin, Jean-Charles; Pekkanen, Juha; von Mutius, Erika; Schaub, Bianca; PASTURE Study Grp; Hyvarinen, Anne; Karvonen, Anne M.; Kirjavainen, Pirkka V.; Remes, Sami; Kaulek, Vincent; Dalphin, Marie-Laure; Ege, Markus; Pfefferle, Petra I.; Doekes, Gert (2017)
    Several studies report an important role of CD8(+) cytotoxic T-cells in atopy. Farm children show protection against atopy development, partly explained by CD4(+) T-cell subtypes. Additional effects of CD8(+) T-cells are unknown being investigated in this study within the PASTURE/EFRAIM birth cohort in PBMCs from farming and non-farming 6-year-old (N = 76) German children. CD3(+) CD8(+) CD25(+) T-cells were analyzed by flow cytometry. Genotyping of 17q21 locus-SNPs associated with childhood asthma was performed. No differences in CD8(+) T-cell subsets were seen between farmers and non-farmers regardless of asthma. Among farm children, asthmatics displayed increased CD3(+) CD8(low)(CD25(+)) T-cells compared to non-asthmatics. Asthmatic farm children exhibited a lower PI-induced stimulatory capacity of CD3(+) CD8(low)(CD25(+)) cells and a lower IFN-gamma secretion than non-asthmatic farm children. Among farm children with GSDMB and ORMDL3 risk alleles, asthmatics displayed higher CD3(+) CD8(low) cells than non-asthmatics. Our data indicates a specific role of CD8(low) T-cells in asthmatic farm children. (C) 2017 Elsevier Inc. All rights reserved.
  • Wisgrill, Lukas; Fyhrquist, Nanna; Ndika, Joseph; Paalanen, Laura; Berger, Angelika; Laatikainen, Tiina; Karisola, Piia; Haahtela, Tari; Alenius, Harri (2022)
    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.
  • Koivusaari, Katariina; Syrjala, Essi; Niinistö, Sari; Ahonen, Suvi; Åkerlund, Mari; Korhonen, Tuuli E.; Toppari, Jorma; Ilonen, Jorma; Kaila, Minna; Knip, Mikael; Alatossava, Tapani; Veijola, Riitta; Virtanen, Suvi M. (2022)
    Background Consumption of unprocessed cow's milk has been associated with a lower risk of childhood asthma and/or atopy. Not much is known about differently processed milk products. We aimed to study the association between the consumption of differently processed milk products and asthma risk in a Finnish birth cohort. Methods We included 3053 children from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study. Asthma and its subtypes were assessed at the age of 5 years, and food consumption by food records, at the age of 3 and 6 months and 1, 2, 3, 4, and 5 years. We used conventional and processing (heat treatment and homogenization)-based classifications for milk products. The data were analyzed using a joint model for longitudinal and time-to-event data. Results At the age of 5 years, 184 (6.0%) children had asthma, of whom 101 (54.9%) were atopic, 75 (40.8%) were nonatopic, and eight (4.3%) could not be categorized. Consumption of infant formulas [adjusted hazard ratio (95% confidence intervals) 1.15 (1.07, 1.23), p < .001] and strongly heat-treated milk products [1.06 (1.01, 1.10), p = .01] was associated with the risk of all asthma. Consumption of all cow's milk products [1.09 (1.03, 1.15), p = .003], nonfermented milk products [1.08 (1.02, 1.14), p = .008], infant formulas [1.23 (1.13, 1.34), p < .001], and strongly heat-treated milk products [1.08 (1.02, 1.15), p = .006] was associated with nonatopic asthma risk. All these associations remained statistically significant after multiple testing correction. Conclusions High consumption of infant formula and other strongly heat-treated milk products may be associated with the development of asthma.
  • Garn, Holger; Bahn, Sabine; Baune, Bernhard T.; Binder, Elisabeth B.; Bisgaard, Hans; Chatila, Talal A.; Chavakis, Triantafyllos; Culmsee, Carsten; Dannlowski, Udo; Gay, Steffen; Gern, James; Haahtela, Tari; Kircher, Tilo; Mueller-Ladner, Ulf; Neurath, Markus F.; Preissner, Klaus T.; Reinhardt, Christoph; Rook, Graham; Russell, Shannon; Schmeck, Bernd; Stappenbeck, Thaddeus; Steinhoff, Ulrich; van Os, Jim; Weiss, Scott; Zemlin, Michael; Renz, Harald (2016)
    Recent research indicates that chronic inflammatory diseases, including allergies and autoimmune and neuropsychiatric diseases, share common pathways of cellular and molecular dysregulation. It was the aim of the International von-Behring-Rontgen Symposium (October 16-18, 2014, in Marburg, Germany) to discuss recent developments in this field. These include a concept of biodiversity; the contribution of urbanization, lifestyle factors, and nutrition (eg, vitamin D); and new mechanisms of metabolic and immune dysregulation, such as extracellular and intracellular RNAs and cellular and mitochondrial stress. Epigenetic mechanisms contribute further to altered gene expression and therefore to the development of chronic inflammation. These novel findings provide the foundation for further development of preventive and therapeutic strategies.
  • Korpelainen, Helena; Pietiläinen, Maria (2017)
    In the present study, we conducted DNA metabarcoding (the nuclear ITS2 region) for indoor fungal samples originating from two nursery schools with a suspected mould problem (sampling before and after renovation), from two university buildings, and from an old farmhouse. Good-quality sequences were obtained, and the results showed that DNA metabarcoding provides high resolution in fungal identification. The pooled proportions of sequences representing filamentous ascomycetes, filamentous basidiomycetes, yeasts, and other fungi equalled 62.3%, 8.0%, 28.3%, and 1.4%, respectively, and the total number of fungal genera found during the study was 585. When comparing fungal diversities and taxonomic composition between different types of buildings, no obvious pattern was detected. The average pairwise values of Sorensen(Chao) indices that were used to compare similarities for taxon composition between samples among the samples from the two university buildings, two nurseries, and farmhouse equaled 0.693, 0.736, 0.852, 0.928, and 0.981, respectively, while the mean similarity index for all samples was 0.864. We discovered that making explicit conclusions on the relationship between the indoor air quality and mycoflora is complicated by the lack of appropriate indicators for air quality and by the occurrence of wide spatial and temporal changes in diversity and compositions among samples.
  • Reinius, Lovisa E.; Gref, Anna; Saaf, Annika; Acevedo, Nathalie; Joerink, Maaike; Kupczyk, Maciej; D'Amato, Mauro; Bergstroem, Anna; Melen, Erik; Scheynius, Annika; Dahlen, Sven-Erik; Pershagen, Goran; Soderhall, Cilla; Kere, Juha; BIOAIR Study Grp (2013)
  • Kere, Maura; Gruzieva, Olena; Ullemar, Vilhelmina; Söderhäll, Cilla; Greco, Dario; Kull, Inger; Bergström, Anna; Pershagen, Göran; Almqvist, Catarina; Melén, Erik (2020)
  • Merid, Simon Kebede; Novoloaca, Alexei; Sharp, Gemma C.; Kupers, Leanne K.; Kho, Alvin T.; Roy, Ritu; Gao, Lu; Annesi-Maesano, Isabella; Jain, Pooja; Plusquin, Michelle; Kogevinas, Manolis; Allard, Catherine; Vehmeijer, Florianne O.; Kazmi, Nabila; Salas, Lucas A.; Rezwan, Faisal I.; Zhang, Hongmei; Sebert, Sylvain; Czamara, Darina; Rifas-Shiman, Sheryl L.; Melton, Phillip E.; Lawlor, Debbie A.; Pershagen, Goran; Breton, Carrie V.; Huen, Karen; Baiz, Nour; Gagliardi, Luigi; Nawrot, Tim S.; Corpeleijn, Eva; Perron, Patrice; Duijts, Liesbeth; Nohr, Ellen Aagaard; Bustamante, Mariona; Ewart, Susan L.; Karmaus, Wilfried; Zhao, Shanshan; Page, Christian M.; Herceg, Zdenko; Jarvelin, Marjo-Riitta; Lahti, Jari; Baccarelli, Andrea A.; Anderson, Denise; Kachroo, Priyadarshini; Relton, Caroline L.; Bergstrom, Anna; Eskenazi, Brenda; Soomro, Munawar Hussain; Vineis, Paolo; Snieder, Harold; Bouchard, Luigi; Jaddoe, Vincent W.; Sorensen, Thorkild I. A.; Vrijheid, Martine; Arshad, S. Hasan; Holloway, John W.; Haberg, Siri E.; Magnus, Per; Dwyer, Terence; Binder, Elisabeth B.; DeMeo, Dawn L.; Vonk, Judith M.; Newnham, John; Tantisira, Kelan G.; Kull, Inger; Wiemels, Joseph L.; Heude, Barbara; Sunyer, Jordi; Nystad, Wenche; Munthe-Kaas, Monica C.; Raikkonen, Katri; Oken, Emily; Huang, Rae-Chi; Weiss, Scott T.; Anto, Josep Maria; Bousquet, Jean; Kumar, Ashish; Soderhall, Cilla; Almqvist, Catarina; Cardenas, Andres; Gruzieva, Olena; Xu, Cheng-Jian; Reese, Sarah E.; Kere, Juha; Brodin, Petter; Solomon, Olivia; Wielscher, Matthias; Holland, Nina; Ghantous, Akram; Hivert, Marie-France; Felix, Janine F.; Koppelman, Gerard H.; London, Stephanie J.; Melen, Erik (2020)
    Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P <1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
  • 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.
  • Laulajainen-Hongisto, Anu; Lyly, Annina; Hanif, Tanzeela; Dhaygude, Kishor; Kankainen, Matti; Renkonen, Risto; Donner, Kati; Mattila, Pirkko; Jartti, Tuomas; Bousquet, Jean; Kauppi, Paula; Toppila-Salmi, Sanna (2020)
    Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p <10(-8)) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR-associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p <0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p <0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.
  • Haahtela, T.; Laatikainen, T.; Alenius, H.; Auvinen, P.; Fyhrquist, N.; Hanski, I.; von Hertzen, L.; Jousilahti, P.; Kosunen, T. U.; Markelova, O.; Mäkelä, M. J.; Pantelejev, V.; Uhanov, M.; Zilber, E.; Vartiainen, E. (2015)
    The Finnish and Russian Karelia are adjacent areas in northern Europe, socio-economically distinct but geoclimatically similar. The Karelia Allergy Study was commenced in 1998 to characterize the allergy profiles in the two areas. Allergy prevalence had increased in Finland since the early 1960s, but the situation in Russia was unknown. The key finding was that allergic symptoms and diseases were systematically more common in Finnish children and adults than in their Russian counterparts. For example, in the early 2000s, hay fever in school children was almost non-existent in Russian Karelia, and only 2% were sensitized to birch pollen compared with 27% in Finnish Karelia. Adult birth cohorts showed that among those born in the 1940s, the sensitization to pollens and pets was at the same low level in both countries, but among younger generation born in the late 1970s, the difference was already manifold. Seropositivity to some pathogens, microbial content in house dust and drinking water seemed to confer allergy protection in Russia. In subsequent studies, it became apparent that on the Finnish side, healthy children had a more biodiverse living environment as well as greater diversity of certain bacterial classes on their skin than atopic children. Abundance of skin commensals, especially Acinetobacter (gammaproteobacteria), associated with anti-inflammatory gene expression in blood leucocytes. In vivo experiments with the mouse model demonstrated that intradermally applied Acinetobacter protected against atopic sensitization and lung inflammation. These observations support the notion that the epidemic of allergy and asthma results from reduced exposure to natural environments with rich microbiota, changed diet and sedentary lifestyle. Genetic studies have confirmed strong influence of lifestyle and environment. With our results from the Karelia study, a 10-year National Allergy Programme was started in 2008 to combat the epidemic in Finland.
  • Malmström, Kristiina; Lohi, Jouko; Sajantila, Antti; Jahnsen, Frode L.; Kajosaari, Merja; Sarna, Seppo; Makela, Mika J. (2017)
    Background: Thickening of reticular basement membrane, increased airway smooth muscle mass and eosinophilic inflammation are found in adult fatal asthma. At the present study the histopathology of fatal paediatric and adolescent asthma is evaluated. Methods: Post-mortem lung autopsies from 12 fatal asthma cases and 8 non-asthmatic control subjects were examined. Thickness of reticular basement membrane (RBM) and percentage of airway smooth muscle (ASM%) mass area were measured and inflammatory cells were counted. Patient records were reviewed for clinical history. Results: The age range of the cases was from 0.9 to 19.5 years, eight were males and five had received inhaled corticosteroids. Thickened RBM was detected in majority of the cases without any correlation to treatment delay, age at onset of symptoms or diagnosis. In the large airways ASM was clearly increased in one third of the cases whereas the median ASM% did not differ from that in healthy controls (14.0% vs. 14.0%). In small airways no increase of ASM was found, instead mucous plugs were seen in fatal asthma. The number of eosinophils, plasmacytoid dendritic cells, macrophages, and B-cells were significantly increased in fatal asthma cases compared with controls and the two latter correlated with the length of the fatal exacerbation. Conclusions: The findings highlight the strong presence of eosinophils and mucous plugs even in small airways in children and adolescents with fatal asthma. Thickened RBM was obvious in majority of the patients. Contrary to our hypothesis, increased ASM% was detected in only one third of the patients.
  • Haahtela, Tari; Alenius, Harri; Lehtimäki, Jenni; Sinkkonen, Aki; Fyhrquist, Nanna; Hyöty, Heikki; Ruokolainen, Lasse; Mäkelä, Mika J. (2021)
    Increase of allergic conditions has occurred at the same pace with the Great Acceleration, which stands for the rapid growth rate of human activities upon earth from 1950s. Changes of environment and lifestyle along with escalating urbanization are acknowledged as the main underlying causes. Secondary (tertiary) prevention for better disease control has advanced considerably with innovations for oral immunotherapy and effective treatment of inflammation with corticosteroids, calcineurin inhibitors, and biological medications. Patients are less disabled than before. However, primary prevention has remained a dilemma. Factors predicting allergy and asthma risk have proven complex: Risk factors increase the risk, while protective factors counteract them. Interaction of human body with environmental biodiversity with micro-organisms and biogenic compounds as well as the central role of epigenetic adaptation in immune homeostasis have given new insight. Allergic diseases are good indicators of the twisted relation to environment. In various non-communicable diseases, the protective mode of the immune system indicates low-grade inflammation without apparent cause. Giving microbes, pro- and prebiotics, has shown some promise in prevention and treatment. The real-world public health programme in Finland (2008-2018) emphasized nature relatedness and protective factors for immunological resilience, instead of avoidance. The nationwide action mitigated the allergy burden, but in the lack of controls, primary preventive effect remains to be proven. The first results of controlled biodiversity interventions are promising. In the fast urbanizing world, new approaches are called for allergy prevention, which also has a major cost saving potential.
  • 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.
  • Burman, Janne; Malmberg, Leo Pekka; Remes, Sami; Jartti, Tuomas; Pelkonen, Anna S.; Makela, Mika J. (2021)
    Background: Separating individuals with viral-induced wheezing from those with asthma is challenging, and there are no guidelines for children under 6 years of age. Impulse oscillometry, however, is feasible in 4-year-old children. Objective: To explore the use of impulse oscillometry in diagnosing and monitoring asthma in young children and evaluating treatment response to inhaled corticosteroid (ICS). Methods: A total of 42 children (median age 5.3 years, range 4.0-7.9 years) with physician-diagnosed asthma and lability in oscillometry were followed for 6 months after initiation of ICS treatment. All children performed the 6-minute free-running test and impulse oscillometry at 3 time points. After the baseline, they attended a second visit when they had achieved good asthma control and a third visit approximately 60 days after the second visit. A positive ICS response was defined as having greater than 19 points in asthma control test and no hyperreactivity on the third visit. Results: In total, 38 of 42 children responded to ICS treatment. Exercise-induced increases of resistance at 5 Hz decreased after ICS treatment (61% vs 18% vs 13.5%, P < .001), and running distance during the 6-minute test was lengthened (800 m vs 850 m vs 850 m, P = .001). Significant improvements in childhood asthma control scores occurred between the baseline and subsequent visits (21 vs 24 vs 24, P < .001) and acute physicians' visits for respiratory symptoms (1, (0-6) vs 0, (0-2), P = .001). Similar profiles were observed in children without aeroallergen sensitization and among those under 5 years of age. Conclusion: Impulse oscillometry is a useful tool in diagnosing asthma and monitoring lung function in young children. (C) 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc.
  • 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.