The biodiversity hypothesis of allergy : The interrelations between the skin microbiota, allergic diseases and exposure to microbes in residential environments

Biodiversity on earth is threatened and already drastically decreased due to anthropogenic actions. The ravenous utilization of natural resources has reached the point of payback in the forms of climate change, diseased crops, and disturbed water cycles. Obviously, these changes influence wellbeing of mankind. Besides these measurable problems, an invisible world, which covers all surfaces on earth, is altering. Loss of diversity in macroscopic organisms is repeated at the level of micro-organisms, many of which may have disappeared before ever described. The human body is a lively ecosystem hosting millions of microbial organisms, which together form the microbiota. These bacterial, viral, fungal, and other microscopic residents are faced with our immune system, challenging their survival. However, the relationship between the host and the residents is often not hostile, but in most cases reciprocal. Actually, the human immune system has partly shared the responsibility of immune-regulation with commensals. This evolved dependency between human and microbial residents highlights that several health problems may arise if this ancient collaboration is disturbed. Indeed, numerous inflammatory diseases coincide with disturbed host microbiota. These diseases, such as allergies, asthma, inflammatory bowel disease, and cancers, have increased rapidly since recent modernization of human habitats and lifestyle. Still, in traditional farming and hunter-gatherer communities allergies are almost absent. The biodiversity hypothesis, which is the concept tested in this thesis, suggest that change in the invisible world can seriously increase morbidity in human populations. This hypothesis states that the destruction of natural environments has altered our contact with microbial world, which can disturb our immune function, potentially leading to the development of inflammatory diseases. In this thesis, the emphasis is on the effect of exposure to environmental microbes, via the living environment and lifestyle, on health; central factors suggested by the biodiversity hypothesis. The key results from four separate projects, which are based on new datasets, are following. (I) Skin microbiota differs between rural and urban newborns and children. In teenagers this difference disappears, probably due to lifestyle-related changes. (II) Children who attend to nature-oriented outdoor-daycares have considerably more diverse skin microbiota than children in other daycares. However, their life differs in many ways from that of other children, indicating also the importance of lifestyle. (III) In the canine model, the prevalence of allergies is clearly lower in rural environments, also when the effect of dog-breed is controlled. Finally, (IV) the exposure to environmental microbes in residential environment, and through lifestyle, are concurrently related to the skin microbiota and allergies in the canine model. This thesis suggests the importance of living environment and lifestyle, which jointly influence the individual’s contact with environmental microbes, for health. Therefore, the human living environments, and the residing biodiversity in those, can either promote or disrupt human health. Currently, accumulating evidence projects that exposure to green environments, farms, children and animals, basically to all factors that increase microbial exposure directly or indirectly, are beneficial for human health. My thesis adds to this by showing interrelations between microbial exposure, microbiota and allergies. Therefore, people, especially children, and their fellow-animals, should increase their contact with diverse environments and lifeforms in order to support both microbial and immunological balance in their bodies. Finally, natural environments provide yet again one more invaluable ecosystem service, which should be recognized and protected

Luonnon monimuotoisuus edistää kansanterveyttä

Vertaisarvioitu.Luonnon monimuotoisuus tarkoittaa kaikkea elävän luonnon vaihtelua niin elinympäristöjen, lajien kuin yksilöidenkin välillä. Viime vuosien tutkimus on osoittanut, että luonnon monimuotoisuus voi suojata ihmistä sekä tarttuvilta että tarttumattomilta sairauksilta. Ympäristössämme se suojaa uusien tartuntatautien kehittymiseltä ja toisaalta altistaa mikrobeille, jotka tukevat immuunijärjestelmän toimintaa. Luonnon monimuotoisuuden nopea köyhtyminen uhkaakin suoraan ihmisen hyvinvointia. Pohdimme, miten kaupungistuvassa yhteiskunnassa voidaan turvata altistuminen hyville mikrobeille ja samalla suojautua haitallisilta taudinaiheuttajilta. Nykytiedon valossa luonnon monimuotoisuuden ylläpitämisellä voidaan tukea sairauksia ehkäisevää lääketiedettä ja kansanterveystyötä.Peer reviewe

The burden of chronic rhinosinusitis with nasal polyps and its relation to asthma in Finland

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is commonly associated with asthma. Treatment of CRSwNP includes intranasal and systemic corticosteroids, with non-responsive patients commonly considered for endoscopic sinus surgery (ESS). This nationwide register-based study evaluated the incidence, prevalence, and treatment burden of CRSwNP in Finland, and their association with the presence and severity of comorbid asthma. Methods Electronic health records of patients diagnosed with CRSwNP between 1.1.2012 and 31.12.2018 in Finnish specialty and primary care were included in the study. The patients were divided into subgroups based on presence, severity, and control of asthma: no asthma, mild to moderate asthma, severe controlled asthma, and severe uncontrolled asthma. A mean cumulative count of ESS was calculated over time per subgroup. Results The prevalence of CRSwNP increased from 602.2 to 856.7 patients per 100,000 population between years 2012 and 2019 (p < 0.001). A total of 18,563 patients (59.9% male) had incident CRSwNP between 2012 and 2019, with 27% having asthma, 6% having severe asthma, and 1.5% having severe uncontrolled asthma. In the no asthma, severe controlled asthma, and severe uncontrolled asthma subgroups, systemic corticosteroids were used by 54.1%, 94.9% and 99.3% (p < 0.001), respectively, while the ESS count 3 years post diagnosis was 0.49, 0.68 and 0.80, respectively. Conclusions The prevalence of CRSwNP showed a significant increase in the recent decade in Finland. Comorbid asthma, and in particular severe asthma, increased the probability of receiving systemic corticosteroids and undergoing ESS. Thus, improved management of CRSwNP in patients with comorbid asthma is urgently needed.Peer reviewe

Urban environment predisposes dogs and their owners to allergic symptoms

Our companion-animals, dogs, suffer increasingly from non-communicable diseases, analogous to those common in humans, such as allergic manifestations. In humans, living in rural environments is associated with lower risk of allergic diseases. Our aim was to explore whether a similar pattern can be found in dogs, using a nation-wide survey in Finland (n = 5722). We characterised the land-use around dog's home at the time of birth as well as around its current home, and described several lifestyle factors. The severity of owner-reported allergic symptoms in dogs was estimated with a comprehensive set of questions, developed by experts of canine dermatology. Also, the prevalence of diagnosed allergies in dog owners was recorded. The results indicate that allergic symptoms are more prevalent in urban environments both in dog owners and in dogs (accounting the effect of dog breed). Several factors related to rural living, such as bigger family size and regular contact with farm animals and other pets, were also protective against allergic symptoms in dogs. Interestingly, allergic dogs were more likely to have allergic owners than healthy dogs were. Therefore, we suggest that the mutual presence of allergic symptoms in both species indicates common underlying causal factors of allergic diseases.Peer reviewe

Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients

Abstract Background Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported. Methods To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo. Associations with P < 1 × 10− 5 were further tested in two independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 183) and Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 180). We also tested the genome-wide significant single nucleotide polymorphism (SNP) for association with left ventricular hypertrophy in GENRES. Results In GENRES GWAS, rs4905794 near BCL11B achieved genome-wide significance (β = − 4.8%, P = 9.6 × 10− 9 for systolic and β = − 4.3%, P = 2.2 × 10− 6 for diastolic night-to-day BP ratio). Seven additional SNPs in five loci had P values < 1 × 10− 5. The association of rs4905794 did not significantly replicate, even though in DYNAMIC the effect was in the same direction (β = − 0.8%, P = 0.4 for systolic and β = − 1.6%, P = 0.13 for diastolic night-to-day BP ratio). In GENRES, the associations remained significant even during administration of four different antihypertensive drugs. In separate analysis in GENRES, rs4905794 was associated with echocardiographic left ventricular mass (β = − 7.6 g/m2, P = 0.02). Conclusions rs4905794 near BCL11B showed evidence for association with nocturnal BP dipping. It also associated with left ventricular mass in GENRES. Combined with earlier data, our results provide support to the idea that BCL11B could play a role in cardiovascular pathophysiology

Radiographic geometry and clinical glenohumeral range of motion after reverse shoulder athroplasty, a retrospective cohort study

BackgroundThe range of motion (ROM) in reverse shoulder arthroplasty (RSA), is mechanically limited by the surrounding bony obstacles especially in abduction and rotation planes. However, the clinical effect of implant positioning, prosthesis design, and individual differences in bone morphology, on ROM is obscure. The aim of this study was to investigate the correlation between radiographic geometry and clinical glenohumeral (GH) ROM after RSA.MethodsRSA patients operated at Turku University Hospital during 2007–2013 were called for radiological and clinical follow-up. Pre- and postoperative true anteroposterior radiographs were obtained and the positioning of the center of rotation (COR) in relation to the surrounding bony structures was measured. Active and passive shoulder and GH abduction, flexion, internal and external rotation ROM were measured with goniometer. The Constant score (CS) and pain visual analogue scale (VAS) were recorded. The correlation between the radiographically measured parameters and the active and passive ROM and clinical outcome was statistically analyzed.Results91 shoulders were available for analyses with a mean follow-up of 38.7 months ± SD 20 (range 12–83) months. 77% of the patients were female, the mean age was 73 (SD 9) years. The mean angle between the line of supraspinatus fossa, and the line between COR and lateral edge of the acromion (α-angle) was 127° (SD 14) and the mean angle between the lines from lateral edge of the acromion to COR, and from there to the superior edge of the greater tubercle (β-angle) was 54° (SD 11). The mean active shoulder flexion at follow-up was 118° (SD 26), abduction 104° (SD 32), external rotation 41° (SD 22), internal rotation 77° (SD 21). The mean passive GH flexion was 80° (SD 19), abduction 67° (SD 15), external rotation 31° (SD 16) and internal rotation 34° (SD 14). The mean Constant score at follow-up was 53 (SD 18) and pain VAS 2 (SD 3). The positioning of the radiographically measured COR did not statistically significantly correlate with the ROM or clinical outcome scores.ConclusionsPostoperative radiographically measured two-dimensional geometry and positioning of the COR does not significantly correlate with the glenohumeral range of motion or clinical results after RSA.</p

Preventing biodiversity loss with ecological restoration

Restoration of watersheds, wetlands, and forests is a way to compensate for the human-caused damage on biodiversity. Halting biodiversity loss is essential for safeguarding ecosystems and human well-being. A key to successful restoration is targeting large enough landscape units. For example, planning at a catchment level can ensure that a forest drainage conducted upstream does not threaten the condition of the waterbodies downstream

Scrutiny of the CHRNA5-CHRNA3-CHRNB4 smoking behavior locus reveals a novel association with alcohol use in a Finnish population based study

The CHRNA5-CHRNA3-CHRNB4 gene cluster on chromosome 15q25.1 encoding the cholinergic nicotinic receptor subunits is robustly associated with smoking behavior and nicotine dependence. Only a few studies to date have examined the locus with alcohol related traits and found evidence of association with alcohol abuse and dependence. Our main goal was to examine the role of three intensively studied single nucleotide polymorphisms, rs16969968, rs578776 and rs588765, tagging three distinct loci, in alcohol use. Our sample was drawn from two independent Finnish population-based surveys, the National FINRISK Study and the Health 2000 (Health Examination) Survey. The combined sample included a total of 32,592 adult Finns (54% women) of whom 8,356 were assessed for cigarettes per day (CPD). Data on alcohol use were available for 31,812 individuals. We detected a novel association between rs588765 and alcohol use defined as abstainers and low-frequency drinkers versus drinkers (OR=1.15, p=0.00007). Additionally, we provide precise estimates of strength of the association between the three loci and smoking quantity in a very large population based sample. As a conclusion, our results provide further evidence for the nicotine-specific role of rs16969968 (locus 1). Further, our data suggest that the effect of rs588765 (locus 3) may be specific to alcohol use as the effect is seen also in never smokers