Farm Environment During Pregnancy and Childhood and Polysensitization at the Age of 31: Prospective Birth Cohort Study in Finland.

BACKGROUND AND OBJECTIVE: The farm environment, especially contact with farm animals in early childhood, may prevent allergic sensitization during adulthood. However, prospective associations between exposure to the farm environment and polysensitization have not been studied. Polysensitization is a risk factor for asthma and asthma-related morbidity. Objective: To investigate whether exposure to a farming environment in early childhood, especially exposure to animals, is associated with sensitization to specific allergens and polysensitization at the age of 31. METHODS: In a prospective birth cohort study, 5509 individuals born in northern Finland in 1966 underwent skin prick testing against birch, timothy, cat, and house dust mite at the age of 31. Prenatal exposure to the farming environment was documented at birth, whereas information on childhood exposure to pets was only collected retrospectively at the age of 31. Data were analyzed using logistic regression. RESULTS: Being born to a family with farm animals was associated with a reduced risk of sensitization to birch, timothy, and cat (adjusted odds ratio [aOR], 0.55 [95%CI, 0.43-0.70]; aOR, 0.62 [95%CI, 0.48-0.79]; aOR, 0.60 [95%CI, 0.47-0.75]) and polysensitization at the age of 31 (aOR, 0.62 [95%CI, 0.48-0.80]). The number of animal species present during childhood was dose-dependently associated with a reduced risk of sensitization to birch, timothy, and cat, as well as of polysensitization. No association was found with sensitization to house dust mite. CONCLUSIONS: Growing up on a farm and contact with higher numbers of animal species in childhood are associated with less frequent sensitization to birch, timothy, and cat allergens and polysensitization in adulthood, but not with sensitization to house dust mite.

Farm Environment During Pregnancy and Childhood and Polysensitization at the Age of 31: Prospective Birth Cohort Study in Finland

BACKGROUND: The farm environment, especially contact with farm animals in early childhood, may prevent allergic sensitization during adulthood. However, prospective associations between exposure to the farm environment and polysensitization have not been studied. Polysensitization is a risk factor for asthma and asthma-related morbidity. OBJECTIVE: To investigate whether exposure to a farming environment in early childhood, especially exposure to animals, is associated with sensitization to specific allergens and polysensitization at the age of 31. METHODS: In a prospective birth cohort study, 5509 individuals born in northern Finland in 1966 underwent skin prick testing against birch, timothy, cat, and house dust mite at the age of 31. Prenatal exposure to the farming environment was documented at birth, whereas information on childhood exposure to pets was only collected retrospectively at the age of 31. Data were analyzed using logistic regression. RESULTS: Being born to a family with farm animals was associated with a reduced risk of sensitization to birch, timothy, and cat (adjusted odds ratio [aOR], 0.55 [95%CI, 0.43-0.70]; aOR, 0.62 [95%CI, 0.48-0.79]; aOR, 0.60 [95%CI, 0.47-0.75]) and polysensitization at the age of 31 (aOR, 0.62 [95%CI, 0.48-0.80]). The number of animal species present during childhood was dose-dependently associated with a reduced risk of sensitization to birch, timothy, and cat, as well as of polysensitization. No association was found with sensitization to house dust mite. CONCLUSIONS: Growing up on a farm and contact with higher numbers of animal species in childhood are associated with less frequent sensitization to birch, timothy, and cat allergens and polysensitization in adulthood, but not with sensitization to house dust mite

ANTECEDENTES: El ambiente de granja, especialmente el contacto con animales de granja en la primera infancia, puede prevenir la sensibilización alérgica durante la edad adulta. Sin embargo, no se han estudiado las posibles asociaciones entre la exposición al entorno agrícola y la polisensibilización. La polisensibilización es un factor de riesgo para el asma y su morbilidad. OBJETIVO: Investigar si el entorno agrícola en la primera infancia, especialmente la exposición a animales, está asociado con la sensibilización a alérgenos específicos y la polisensibilización a la edad de 31 años. MÉTODOS: En un estudio prospectivo de cohorte de nacimiento, 5.509 sujetos nacidos en el norte de Finlandia en 1966 se sometieron a pruebas cutáneas a la edad de 31 años con abedul, hierba timotea, gato y ácaros del polvo doméstico. La exposición prenatal al ambiente agrícola se documentó al nacer, mientras que la información sobre la exposición infantil a las mascotas solo se recopiló retrospectivamente a la edad de 31 años. Se utilizó La regresión logística en los análisis estadísticos. RESULTADOS: Nacer en una familia con animales de granja se asoció con un menor riesgo de sensibilización frente a abedul, hierba timotea o gato (odds ratio ajustado, aOR = 0,55 [intervalo de confianza del 95% 0,43-0,70]; aOR = 0,62 [0,48-0,79] ; aOR = 0,60 [0,47-0,75]) y polisensibilización a la edad de 31 años (aOR = 0,62 [0,48-0,80]). La sensibilización frente a abedul, hierba timotea y gato, así como la polisensibilización, se asociaron de forma dependiente e inversa a la dosis con el número de especies animales presentes durante la infancia. No se encontró asociación con la sensibilización frente a los ácaros del polvo doméstico. CONCLUSIONES: Crecer en una granja y el contacto con un mayor número de especies animales en la infancia se asocia con una menor sensibilización frente al abedul, la hierba timotea, alérgenos de gato y polisensibilización en la edad adulta, pero no con sensibilización frente a los ácaros del polvo doméstico

Nasal mucosa and blood cell transcriptome profiles do not reflect respiratory symptoms associated with moisture damage.

Upper and lower respiratory symptoms and asthma are adverse health effects associated with moisture-damaged buildings. Quantitative measures to detect adverse health effects related to exposure to dampness and mold are needed. Here, we investigate differences in gene expression between occupants of moisture-damaged and reference buildings. Moisture-damaged (N = 11) and control (N = 5) buildings were evaluated for dampness and mold by trained inspectors. The transcriptomics cohort consisted of nasal brushings and peripheral blood mononuclear cells (PBMCs) from 86 teachers, with/without self-perceived respiratory symptoms. Subject categories comprised reference (R) and damaged (D) buildings with (S) or without (NS) symptoms, that is, R-S, R-NS, DS, and D-NS. Component analyses and k-means clustering of transcriptome profiles did not distinguish building status (R/D) or presence of respiratory symptoms (S/NS). Only one nasal mucosa gene (YBX3P1) exhibited a significant change in expression between D-S and D-NS. Nine other nasal mucosa genes were differentially expressed between R-S and D-S teachers. No differentially expressed genes were identified in PBMCs. We conclude that the observed mRNA differences provide very weak biological evidence for adverse health effects associated with subject occupancy of the specified moisture-damaged buildings. This emphasizes the need to evaluate all potential factors (including those not related to toxicity) influencing perceived/self-reported ill health in moisture-damaged buildings.

Diagnostic Accuracy of Symptoms, Endoscopy, and Imaging Signs of Chronic Rhinosinusitis Without Nasal Polyps Compared to Allergic Rhinitis.

Objectives The diagnosis of chronic rhinosinusitis without nasal polyps (CRSsNP) and distinguishing it from allergic rhinitis is difficult. Yet, early detection of CRSsNP is important to prevent progressive and severe chronic rhinosinusitis. Our aim was to compare diagnostic accuracy of symptoms, endoscopy, and imaging signs of CRSsNP and allergic rhinitis -only phenotypes. Setting Prospective controlled follow-up study. Participants Forty-two nonsmoking patients visiting tertiary care due to CRSsNP and 19 nonsmoking volunteer controls with allergic rhinitis filled a symptoms questionnaire and underwent nasal endoscopy off-seasonally. All CRSsNP patients underwent computed tomography scans of paranasal sinuses. All the allergic rhinitis control subjects and 14 of the CRSsNP patients underwent sinus magnetic resonance imaging. Results Radiologic Lund-Mackay score, duration of symptoms, visual analogue scale scores of symptoms, and Sinonasal Outcome Test 22 were significantly higher in the CRSsNP group compared to allergic rhinitis control group. These factors also correlated in part with each other. Endoscopic score did not correlate with other factors, nor did it differ between CRSsNP and allergic rhinitis groups. The highest area under curve value was demonstrated for visual analogue scale score of facial pain/pressure (0.93) and score ≥4/10 showed 60% sensitivity and 95% specificity for detecting CRSsNP group ( P < .001). Radiologic sign of obstructed osteomeatal complex showed 100% specificity and 38% sensitivity for detecting CRSsNP group ( P < .001). Conclusions CRSsNP phenotype could be primarily distinguished from allergic rhinitis by higher facial pain/pressure score and secondarily by radiologic sings of obstructed ostiomeatal complex and higher Lund-Mackay score. Endoscopic score has limited value in distinguishing CRSsNP from allergic rhinitis.

Higher mortality of adults with asthma: A 15-year follow-up of a population-based cohort.

BACKGROUND: Higher all-cause mortality in asthmatics has been shown previously. Polysensitization is associated with higher morbidity among asthmatic children, and allergic rhinitis and/or allergic conjunctivitis (AR/AC) are associated with higher morbidity in adult asthmatics. Little is known about the effect of AR/AC and other factors on mortality among adult asthmatics. The aim was to study mortality and its risk factors in adults with and without asthma. METHODS: We randomly selected 1648 asthmatics with age over 30 years from national registers and matched the asthma sample with one or two controls. Baseline information was obtained by a questionnaire in 1997, and the study population was linked with the death certificate information of Statistics Finland from 1997 to 2013. Overall and cause-specific survival between the groups was compared in several adjusted models. RESULTS: During a mean follow-up period of 15.6 years, 221 deaths among 1052 asthma patients and 335 deaths among 1889 nonasthmatics were observed. Cardiovascular diseases were the main cause of death in both groups. Asthma was associated with increased all-cause mortality (adjusted HR 1.25; 95% CI 1.05-1.49, P = .011) as well as mortality from chronic obstructive pulmonary disease (HR 12.0, 4.18-34.2, P < .001) and malignant neoplasms of respiratory organs (HR 2.33, 1.25-4.42, P = .008). Among asthmatics, smoking was associated with increased all-cause mortality, and self-reported AR/AC was associated with decreased mortality. Among nonasthmatics, smoking, and obesity were associated with increased all-cause mortality, whereas female gender showed an association with a decreased risk. CONCLUSIONS: Increased mortality among adult asthmatics was largely explained by the development of COPD, malignant respiratory tract neoplasms, and cardiovascular diseases. Smoking cessation is important for reduction in total mortality in both asthmatic and nonasthmatic adults. AR/AC was associated with decreased mortality only in asthmatics. Thus, studies in other populations of larger size are needed to explore further the nature of this association.

Early age exposure to moisture damage and systemic inflammation at the age of 6 years.

Cross-sectional studies have shown that exposure to indoor moisture damage and mold may be associated with subclinical inflammation. Our aim was to determine whether early age exposure to moisture damage or mold is prospectively associated with subclinical systemic inflammation or with immune responsiveness in later childhood. Home inspections were performed in children's homes in the first year of life. At age 6 years, subclinical systemic inflammation was measured by serum C-reactive protein (CRP) and blood leukocytes and immune responsiveness by ex vivo production of interleukin 1-beta (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α) in whole blood cultures without stimulation or after 24 hours stimulation with phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG) in 251-270 children. Moisture damage in child's main living areas in infancy was not significantly associated with elevated levels of CRP or leukocytes at 6 years. In contrast, there was some suggestion for an effect on immune responsiveness, as moisture damage with visible mold was positively associated with LPS-stimulated production of TNF-α and minor moisture damage was inversely associated with PI-stimulated IL-1ß. While early life exposure to mold damage may have some influence on later immune responsiveness, it does not seem to increase subclinical systemic inflammation in later life.

Microbial growth in building material samples and occupants' health in severely moisture-damaged homes.

There is no commonly approved approach to detect and quantify the health-relevant microbial exposure in moisture-damaged buildings. In 39 single-family homes with severe moisture damage, we studied whether concentrations of viable microbes in building material samples are associated with health among 71 adults and 68 children, and assessed with symptoms questionnaires, exhaled NO, and peak expiratory flow (PEF) variability. Symptoms were grouped into three scores: upper respiratory symptoms, lower respiratory symptoms, and general symptoms. The homes were divided into three groups based on viable counts of fungi, actinomycetes, and total bacteria cultivated from building material samples. Highest group of actinomycete counts was associated with more general symptoms, worse perceived health, and higher daily PEF variability (aOR 12.51; 1.10-141.90 as compared to the lowest group) among adults, and with an increase in lower respiratory symptoms in children, but the confidence intervals were wide. We observed significant associations of fungal counts and total microbial score with worse perceived health in adults. No associations with exhaled NO were observed.

Microbial characteristics in homes of asthmatic and non-asthmatic adults in the ECRHS cohort.

Microbial exposures in homes of asthmatic adults have been rarely investigated; specificities and implications for respiratory health are not well understood. The objectives of this study were to investigate associations of microbial levels with asthma status, asthma symptoms, bronchial hyperresponsiveness (BHR), and atopy. Mattress dust samples of 199 asthmatics and 198 control subjects from 7 European countries participating in the European Community Respiratory Health Survey II study were analyzed for fungal and bacterial cell wall components and individual taxa. We observed trends for protective associations of higher levels of mostly bacterial markers. Increased levels of muramic acid, a cell wall component predominant in Gram-positive bacteria, tended to be inversely associated with asthma (OR's for different quartiles: II 0.71 [0.39-1.30], III 0.44 [0.23-0.82], and IV 0.60 [0.31-1.18] P for trend .07) and with asthma score (P for trend .06) and with atopy (P for trend .02). These associations were more pronounced in northern Europe. This study among adults across Europe supports a potential protective effect of Gram-positive bacteria in mattress dust and points out that this may be more pronounced in areas where microbial exposure levels are generally lower.

Birth decade affects the sensitization pattern and asthma risk in Finnish adult population.

We have previously shown that sensitizations to several types of allergens distinguish subjects with and without adult-onset asthma in Finland. The aim was to analyze how age affects sensitization and asthma risk. We used previous population-based case-control data (N=456) from Finnish adult asthma patients with one or two matched controls. Asthma was diagnosed based on a typical history of asthmatic symptoms and lung function tests. Allergic sensitization was determined by skin prick test (SPT) to 17 aeroallergens. Information on demographics was obtained by a questionnaire. Sensitization to more than one allergen type and the number of positive SPT reactions associated with younger age and asthma. Atopic subjects aged 65 and above were characterized by sensitization to only one to two allergens, with very few animal danders and without an association with asthma. Multiple sensitizations and animal dander sensitization are more common among Finnish asthmatic adults aged under 56 than among older asthmatics. Cohort studies are needed to understand timing of host-environmental interactions behind this.

Analyzing symptom data in indoor air questionnaires for primary schools.

Questionnaires on symptoms and perceived quality of indoor environment are used to assess indoor environment problems, but mainly among adults. The aim of this article was to explore best ways to analyze and report such symptom data, as part of a project to develop a parent-administered indoor air questionnaire for primary school pupils. Indoor air questionnaire with 25 questions on child's symptoms in the last 4 weeks was sent to parents in five primary schools with indoor air problems and in five control schools. About 83% of parents (N=1470) in case schools and 82% (N=805) in control schools returned the questionnaire. In two schools, 351 (52%) parents answered the questionnaire twice with a 2-week interval. Based on prevalence of symptoms, their test-retest repeatability (ICC), and on principal component analysis (PCA), the number of symptoms was reduced to 17 and six symptoms scores were developed. Six variants of these six symptom scores were then formed and their ability to rank schools compared. Four symptom scores (respiratory, lower respiratory, eye, and general symptoms) analyzed dichotomized maintained sufficiently well the diversity of symptom data and captured the between-school differences in symptom prevalence, when compared to more complex and numerous scores.

Skin prick tests and specific IgE in 10-year-old children: Agreement and association with allergic diseases.

BACKGROUND: Accurate assessment of atopic sensitization is pivotal to clinical practice and research. Skin prick test (SPT) and specific IgE (sIgE) are often used interchangeably. Some studies have suggested a disagreement between these two methods, and little is known about their association with allergic diseases. The aims of our study were to evaluate agreement between SPT and sIgE, and to compare their association with allergic diseases in 10-year-old children. METHODS: Skin prick test, sIgE measurements, and assessment of allergic diseases were performed in children aged 10 years in the Protection against Allergy: STUdy in Rural Environments (PASTURE) cohort. The agreement between SPT and sIgE was assessed by Cohen's kappa coefficient with different cutoff values. RESULTS: Skin prick tests and sIgE were performed in 529 children. The highest agreement (κ=.44) was found with a cutoff value of 3 and 5 mm for SPT, and 3.5 IU/mL for sIgE. The area under the curve (AUC) obtained with SPT was not significantly different from that obtained with sIgE. For asthma and hay fever, SPT (cutoff value at 3 mm) had a significantly higher specificity (P<.0001) than sIgE (cutoff value at 0.35 IU/mL) and the specificity was not different between both tests (P=.1088). CONCLUSION: Skin prick test and sIgE display moderate agreement, but have a similar AUC for allergic diseases. At the cutoff value of 3 mm for SPT and 0.35 IU/mL for sIgE, SPT has a higher specificity for asthma and hay fever than sIgE without difference for sensitivity.

The associations of indoor environment and psychosocial factors on the subjective evaluation of Indoor Air Quality among lower secondary school students: a multilevel analysis.

Subjective evaluation of Indoor Air Quality (subjective IAQ) reflects both building-related and psychosocial factors, but their associations have rarely been studied other than on the individual level in occupational settings and their interactions have not been assessed. Therefore, we studied whether schools' observed indoor air problems and psychosocial factors are associated with subjective IAQ and their potential interactions. The analysis was performed with a nationwide sample (N = 195 schools/26946 students) using multilevel modeling. Two datasets were merged: (i) survey data from students, including information on schools' psychosocial environment and subjective IAQ, and (ii) data from school principals, including information on observed indoor air problems. On the student level, school-related stress, poor teacher-student relationship, and whether the student did not easily receive help from school personnel, were significantly associated with poor subjective IAQ. On the school level, observed indoor air problem (standardized ß = -0.43) and poor teacher-student relationship (standardized ß = -0.22) were significant predictors of poor subjective IAQ. In addition, school-related stress was associated with poor subjective IAQ, but only in schools without observed indoor air problem (standardized ß = -0.44).

School attendance and daily respiratory symptoms in children: influence of moisture damage.

We investigated the effect of weekends and school holidays on the daily frequency and severity of respiratory and other symptoms among children attending schools with (index) or without (reference) moisture damage in Spain, the Netherlands, and Finland. Throughout 1 year, parents of 419 children with a respiratory condition attending index (n=15) or reference (n=10) primary schools completed three symptom diaries. We assessed associations between lower respiratory tract, upper respiratory tract or allergy, and other symptom scores and school day, weekend, or summer holiday using mixed regression models stratified by country and moisture damage. We evaluated interactions between moisture damage and type of day. We combined country-specific estimates (incidence rate ratios [IRRs] and 95% confidence interval [CI]) in meta-analyses. Symptom scores were lower during weekends and holiday. Lower respiratory tract symptoms were statistically significantly less common during holiday with strongest effect in index schools (IRR=0.7; CI=0.6-0.8). Reporting of other symptoms was more reduced during holiday in index (IRR=0.6; CI=0.4-0.9) than in reference (IRR=0.95; CI=0.8-1.2) schools (interaction P<.01). In conclusion, symptoms were less frequent and/or severe during summer holiday and weekends. This pattern was stronger among children attending moisture-damaged schools, suggesting potential improvement in moisture damage-related symptoms during school breaks.

A switch in regulatory T cells through farm exposure during immune maturation in childhood.

BACKGROUND: Farm exposure protects against development of allergies early in life. At 4.5 years, protection against asthma by farm-milk exposure was partially mediated by regulatory T cells (Tregs). The aim of this study was to investigate the critical time window of the 'asthma-protective' farm effect via Tregs during childhood immune maturation. METHODS: Tregs were assessed longitudinally at 4.5 and 6 years in 111 children (56 farm and 55 reference children) from the PASTURE/EFRAIM birth cohort (flow cytometry). Peripheral blood mononuclear cells were cultured unstimulated (U), with phorbol 12-myristate 13-acetate/ionomycin (PI) or lipopolysaccharide (LPS), and stained for Tregs (CD4+ CD25high FOXP3upper20% ). mRNA expression of Treg/Th1/Th2/Th17-associated cell markers was measured ex vivo. Suppressive capacity of Tregs on effector cells and cytokines was assessed. Detailed questionnaires assessing farm exposures and clinical phenotypes from birth until age 6 years were answered by the parents. RESULTS: Treg percentage before and after stimulation and FOXP3mRNA expression ex vivo decreased from age 4.5 to 6 years (P(U,LPS) < 0.001; P(PI) = 0.051; P(FOXP3) < 0.001). High vs low farm-milk and animal-stable exposure was associated with decreased LPS-stimulated Treg percentage at age 6 years (P(LPS) = 0.045). Elevated LPS-stimulated-Treg percentage at age 6 was associated with increased risk of asthma (aOR = 11.29, CI: 0.96-132.28, P = 0.053). Tregs from asthmatics vs nonasthmatics suppressed IFN-γ (P = 0.015) and IL-9 (P = 0.023) less efficiently. mRNA expression of Th1/Th2/Th17-associated cell markers decreased between 4.5 and 6 years (P < 0.001). CONCLUSIONS: Tregs at the age of 6 years were decreased with farm exposure and increased within asthmatics, opposite to age 4.5 years. This immunological switch defines a critical 'time window' for Treg-mediated asthma protection via environmental exposure before age 6 years.

Inflammatory potential in relation to the microbial content of settled dust samples collected from moisture-damaged and reference schools: results of HITEA study.

Aiming to identify factors causing the adverse health effects associated with moisture-damaged indoor environments, we analyzed immunotoxicological potential of settled dust from moisture-damaged and reference schools in relation to their microbiological composition. Mouse RAW264.7 macrophages were exposed to settled dust samples (n = 25) collected from moisture-damaged and reference schools in Spain, the Netherlands, and Finland. After exposure, we analyzed production of inflammatory markers [nitric oxide (NO), tumor necrosis factor-α (TNF-)α, interleukin (IL)-6, and macrophage inflammatory protein (MIP)2] as well as mitochondrial activity, viability, apoptosis, and cell cycle arrest. Furthermore, particle counts, concentration of selected microbial groups as well as chemical markers such as ergosterol, 3-hydroxy fatty acids, muramic acid, endotoxins, and glucans were measured as markers of exposure. Dust from moisture-damaged schools in Spain and the Netherlands induced stronger immunotoxicological responses compared to samples from reference schools; the responses to Finnish samples were generally lower with no difference between the schools. In multivariate analysis, IL-6 and apoptosis responses were most strongly associated with moisture status of the school. The measured responses correlated with several microbial markers and numbers of particles, but the most important predictor of the immunotoxicological potential of settled dust was muramic acid concentration, a marker of Gram-positive bacteria.

Moisture damage in home associates with systemic inflammation in children.

This study investigated the association between confirmed moisture damage in homes and systemic subclinical inflammation in children. Home inspections were performed in homes of 291 children at the age of 6 years. Subclinical inflammation at the age of 6 years was assessed by measuring the circulating levels of C-reactive protein (CRP) and leukocytes in peripheral blood and fractional exhaled nitric oxide (FeNO). Proinflammatory cytokines interleukin (IL)-1ß and IL-6 and tumor necrosis factor (TNF)-α were measured in unstimulated, and in phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG)-stimulated whole blood. Major moisture damage in the child's main living areas (living room, kitchen, or child's bedroom) and moisture damage with mold in the bathroom were associated with increased levels of CRP and stimulated production of several proinflammatory cytokines. There were no significant associations between moisture damage/visible mold and leukocyte or FeNO values. The results suggest that moisture damage or mold in home may be associated with increased systemic subclinical inflammation and proinflammatory cytokine responsiveness.

Circulating Dendritic Cells, Farm Exposure and Asthma at Early Age.

Farm environment has been shown to protect from childhood asthma. Underlying immunological mechanisms are not clear yet, including the role of dendritic cells (DCs). The aim was to explore whether asthma and farm exposures are associated with the proportions and functional properties of DCs from 4.5-year-old children in a subgroup of the Finnish PASTURE birth cohort study. Myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and CD86 expression on mDCs ex vivo (n = 100) identified from peripheral blood mononuclear cells (PBMCs) were analysed using flow cytometry. MDCs and production of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) by mDCs were analysed after 5 h in vitro stimulation with lipopolysaccharide (LPS) (n = 88). Prenatal and current farm exposures (farming, stables, hay barn and farm milk) were assessed from questionnaires. Asthma at age 6 years was defined as a doctor's diagnosis and symptoms; atopic sensitization was defined by antigen-specific IgE measurements. Asthma was positively associated with CD86 expression on mDCs ex vivo [adjusted odds ratio (aOR) 4.83, 95% confidence interval (CI) 1.51-15.4] and inversely with IL-6 production in mDCs after in vitro stimulation with LPS (aOR 0.19, 95% CI 0.04-0.82). In vitro stimulation with LPS resulted in lower percentage of mDCs in the farm PBMC cultures as compared to non-farm PBMC cultures. Our results suggest an association between childhood asthma and functional properties of DCs. Farm exposure may have immunomodulatory effects by decreasing mDC proportions.

Exposure to a farm environment is associated with T helper 1 and regulatory cytokines at age 4.5 years.

BACKGROUND: Farm exposure has been shown to protect from childhood asthma and allergic diseases, but underlying immunological mechanisms are not clear yet. OBJECTIVE: To explore whether farming lifestyle determines cytokine profile of peripheral blood mononuclear cells (PBMCs) of 4.5-year-old children (n = 88) from the Finnish PASTURE birth cohort study. METHODS: We analysed regulatory (IL-10, IL-2), T helper 1 (Th1)-associated (IL-12, IFN-γ), inflammatory (IL-1ß, TNF, CXCL8) and Th2-associated (IL-13) cytokines in unstimulated PBMCs and after a short-term (5 h) stimulation with lipopolysaccharide (LPS). Specific farm exposures (stables, hay barn, farm milk) at age 4 years were assessed from questionnaires. RESULTS: The unstimulated PBMCs of farm children produced more IL-10 (GMR 1.22, P = 0.032), IL-12 (GMR 1.24, P = 0.012) and IFN-γ (GMR 1.24, P = 0.024) than those of non-farm children. Also, specific farm exposures were associated with higher spontaneous production of cytokines. The number of specific farm exposures tended to be dose dependently associated with higher spontaneous production of IFN-γ (test for trends, P = 0.013) and lower LPS-induced production of TNF (test for trends, P = 0.025). CONCLUSION AND CLINICAL RELEVANCE: Farming lifestyle seemed to be associated with increased spontaneous production of Th1 and regulatory cytokines. Decreased TNF responses to short-term LPS stimulation in farm-exposed children may imply tolerogenic immune mechanisms. These novel findings might contribute to the asthma and allergy protection in farm environment.

Microbial secondary metabolites in homes in association with moisture damage and asthma.

We aimed to characterize the presence of microbial secondary metabolites in homes and their association with moisture damage, mold, and asthma development. Living room floor dust was analyzed by LC-MS/MS for 333 secondary metabolites from 93 homes of 1-year-old children. Moisture damage was present in 15 living rooms. At 6 years, 8 children had active and 15 lifetime doctor-diagnosed asthma. The median number of different metabolites per house was 17 (range 8-29) and median sum load 65 (4-865) ng/m(2) . Overall 42 different metabolites were detected. The number of metabolites present tended to be higher in homes with mold odor or moisture damage. The higher sum loads and number of metabolites with loads over 10 ng/m(2) were associated with lower prevalence of active asthma at 6 years (aOR 0.06 (95% CI <0.001-0.96) and 0.05 (<0.001-0.56), respectively). None of the individual metabolites, which presence tended (P < 0.2) to be increased by moisture damage or mold, were associated with increased risk of asthma. Microbial secondary metabolites are ubiquitously present in home floor dust. Moisture damage and mold tend to increase their numbers and amount. There was no evidence indicating that the secondary metabolites determined would explain the association between moisture damage, mold, and the development of asthma.