Scientific interest:
• The pathogenesis of childhood asthma
• Early intervention strategies to prevent childhood asthma
• Smart data to improve human and planetary health
Major scientific achievements
“Wheezy” studies:
I started my current main research topics, “the role of respiratory virus infections in the pathogenesis of childhood asthma” and “early intervention strategies in the prevention of childhood asthma” with Vinku study in 2000 (Vinku is a nick name for ”wheeze” in Finnish). I was supervised by prof. Olli Ruuskanen, University of Turku, and during my post doct studies in 2005-2007 by prof. James Gern, University of Wisconsin. The Vinku study series has made many significant findings on the impact of formerly known and newly discovered respiratory virus infections, especially rhinovirus infections, in children as well as on factors associated with and interventions preventing pathogenesis of asthma in children. We are first to show that we can influence natural course of asthma by identifying high risk children and providing them with effective early intervention (i.e. 30% less asthma at school-age in two independent trials).
Tonsil research:
Tonsils are the first contact point with respiratory pathogens and allergens. Tonsils have gained interest as a direct in vivo model to investigate local lymphoid tissue in relation to infection, allergy, age and various exposures. Our tonsil research was initiated in 2008 after fruitful discussions with prof. Cezmi Akdis, University of Zürich, who also supervised the studies. The project has produced interesting pathogenetic findings such as identification of functional FOXP3+ Treg cells, triggers of breaking allergen-specific T cell tolerance to allergens and virus infection associated immune responses lymph node level.
Human and planetary health:
I have integrated 6G Future Sustainable Society project and the problem named non-communicable diseases (NCDs) which cause the highest public health burden in the world and account for 70% of all deaths. They include obesity, cardiovascular diseases, diabetes, cancer, depression etc. NCDs have steadily increased since 1960s. Our main aim in the GUIDE study is to GUIDe and Engage for healthier lifestyle and improved planetary health with a human-centric approach supported by AI, data and platforms. Specific aims: 1. Preventing NCDs; 2. Halting biodiversity loss; 3. Increasing quality of life; 4. Economic scalability, replicability and sustainability; 5. Resolving regulatory, ownership and technical problems. A key common denominator in NCDs is the inflammatory process strongly influenced by lifestyle and environment (physical inactivity, unhealthy diet, loss of contact to nature and social exclusion). Major changes are warranted in human behavior (learning and motivation). To make preventive health care effective, smart infrastructure should deliver the right message, at the right time, and in the right way. 5/6G enables collecting and corresponding contextual and environmental data by equal terms.
Rationale of research
“Wheezy” studies:
The main idea in my research is to use modern virus and bacterial detection combined to immunology and long-term outcome as a tool to understand early pathogenesis of asthma. Although chronic childhood asthma is mainly atopic, using only atopy-based markers is not sufficient in early identification high asthma-risk children since atopy markers become feasible too slowly even in hospitalized wheezing children – hardly seen during the first year of life. However, susceptibility to common respiratory infections manifesting as more severe lower airway illness, tells as about compromised antivirus defense and/or initiating chronic inflammatory condition of the airways. By using viral (or microbial) markers, we can detect high asthma-risk children early, already during infancy, even at the time of the first wheeze, understand the early pathogenesis of asthma and design better early intervention strategies. Vinku and Vinku2 trials have shown that targeting first-time wheezing children with rhinovirus infection, especially those with high virus genome loads, with a 3-day course of oral corticosteroid has decreased the development of childhood asthma by 30%. Key issue appears to be the early identification and effective anti-inflammatory treatment. Interestingly, all those with high rhinovirus load receiving placebo developed new wheezing episode within 100 days, and needed regular asthma control medication within 14 months. Decreasing the incidence of asthma even by 10% would produce appr. 80 mil. eur annual savings in Finland alone. Thus, this would currently the most effective secondary prevention approach against asthma.
Tonsil research:
During last decade, our awareness on the interaction between respiratory virus infections, bacterial colonization, allergen exposure and immunopathogenesis atopic asthma have markedly expanded. Currently, we are on the first steps in understanding their interplay in pediatric patients. The challenge is to develop effective and safe early immunomodulatory approach to prevent atopy and asthma. Our tonsil research has lifted the investigation of peripheral blood mononuclear cell to local immune tissue level, tonsils. Furthermore, we have performed clinical interventions before removing tonsils. So far, our in vivo tonsil models have worked effectively and provided many new aspects of immune system functions.
Human and planetary health:
NCDs are the number one killer in the world. Decreasing NCDs in the mutual aim of EU, UN and WHO. The anticipated impact of GUIDE is enormous. The accomplishment of ‘the change’ will improve personal and planetary health, e.g. the annual costs of NCDs in EU are €115 bil; even a decrease of 1% will help to save >1 bil in EU area alone. My “wheezy” study mainly focus on the secondary prevention of asthma. However, GUIDE takes additional step and focuses on primary prevention of asthma and many other NCDs. Most common NCDs in children after allergic diseases (upto 45% depending on disease) are obesity (20-30% depending on gender) and mental disorders (1-25% depending on disease).
Action plan
My Vinku and tonsil study series are already running in University of Turku since years 2000 and 2008, respectively. From Oulu, I will bring GUIDE and SynAir-G to Turku.
• INSTAR is a Nordic 8-center trial (N=280) repeating Vinku and Vinku2 study design (systemic corticosteroid intervention for the first-time wheezing rhinovirus-positive hospitalized children) in a big sample size hoping to confirm earlier findings and to get a new treatment indication in bronchiolitis guidelines. The recruitment started 2019 in Turku University Hospital, patients will be followed until school-age. Currently, we have 80 randomized children. In addition to clinical trial, study has multidisciplinary approach to investigate the pathogenesis of asthma by analyzing genetic, epigenetic, immunologic, microbiologic, physiologic, environmental and quality of life data.
• Vinku3 is based on a standard “wheezy” questionnaires collected from pediatric infectious diseases ward, Turku University Hospital, in 1980-2014 (appr. n=3500). Adding these into clinical follow-up, microbiologic, allergy test, environmental and possibly genetic data, we will get one of the heaviest data set focusing early severe wheezing and long-term asthma outcome. The data will allow us to test many questions related to early risk factors of asthma and identification future asthmatics early.
• Pooling of Vinku, Vinku2 and MARC-30Fin “wheezy” cohorts creates prospective N=650 carefully characterized and investigated (virus, allergy and clinical characteristics) data-set of which e.g. 240 have been randomized to receive prednisolone vs placebo at the first severe wheezing episode, 160 cases have genome wide SNP data, 110 cases have stimulated (7 stimulants, acute and convalescent phases) PBMC data for immunologic outcome (61 plex cytokine panel), and genome-wide RNAseq data is from 70 cases. The follow-up extents to 10-16 years, and includes 100% follow-up from national Kela registry for drug purchase, time of asthma diagnosis. INSTAR follows same study design and can be added in to this Vinku pool.
• Biodiversity hypothesis is rapidly evolving and we have also extended our studies to collect detailed geographic data for all our wheezy cohorts: Vinku, Vinku2, MARC30Fin, INSTAR and Vinku3 (appr. n=4500).
Tonsil research is currently investigating genome-wide RNA expression in relation to microbiome, allergy and exposure. Then, we will move to analyze our intervention data produced by immunotherapy products and live attenuated nasal cavity vaccine in collaboration with University of Zürich. We have data and samples of 522 tonsils.
To improve human and planetary health, our action and the crucial method is to develope GUIDE, a proactive and responsive human-centric approach that comprises intelligent use of mydata/contextual data and AI on platforms that 1. combines all data in the holistic and AI-responsive manner (sensor/app, questionnaire, geographic, environmental, register data); 2. GUIDes and Engages to healthier personal lifestyle with persuasive technologies (nutrition, exercise, social support) and environmental awareness (nature contact); 3. enables translational research to support innovation, novel solutions on merged data and governance. GUIDE connects (but is not limited) to Nature step to health, a regional 10-year health program, in Lahti 2022-2032 (of note, Lahti is my previous home town). The program is based on the EU’s Green Capital Year of 2021 and aims to create a future community plan for well-being for people and planet. GUIDE involves all Finnish Universities with associated University Hospitals and Finnish Institute for Health and Welfare (THL). The research networks are already established. The ethics permission and hospital permissions have been achieved. We are currently in the implementation phase. GUIDE will be curried out in Turku, Lahti and Oulu and aim to get > 37.000 participants.
SynAir-G
(Disrupting Noxious Synergies of Indoor Air Pollutants and their Impact in Childhood Health and Wellbeing, using Advanced Intelligent Multisensing and Green Interventions) is an EU project. In the context of the European Green Deal, on May 12, 2021, the European Commission adopted the Zero Pollution Action Plan aiming to reduce pollution to levels no longer harmful to health and natural ecosystems. People spend most of their time indoors, where pollutant composition and concentration can be considerably different. In SynAir-G, we hypothesize that major indoor air effects on respiratory, immune, and mental health are modulated by synergistic interactions between biological and chemical pollutants. Clinical samples and context data will be collected from 800 pupils/5 schools from Turku area in a two-year study period. Study started in 10/2022.
IDEAL is a indoor air quality and health cluster of 6 EU projects. Since indoor air call resulted 6 very similar projects, EU demanded synergistic actions and cluster activities. IDEAL will combine data from InChildHealth, INQUIRE, K-HEALTHinAIR, LEARN, TwinAir and SynAir-G in four working groups (guidelines, sensors, health outcomes, in vitro models). Clinical data will be analyzed in four levels: disease data (symptoms, severity, acute/chronic illnesses, drug usage/costs.), health data (wellness, fitness, QoL, success), 3. context data (general/big environmental data) and specific research data. Consortium started in 10/2022.