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Background: Numerous children present with early wheeze symptoms, yet solely a subgroup develops childhood asthma. Early identification of children at risk is key for clinical monitoring, timely patient-tailored treatment, and preventing chronic, severe sequelae. For early prediction of childhood asthma, we aimed to define an integrated risk score combining established risk factors with genome-wide molecular markers at birth, complemented by subsequent clinical symptoms/diagnoses (wheezing, atopic dermatitis, food allergy)., Methods: Three longitudinal birth cohorts (PAULINA/PAULCHEN, n = 190 + 93 = 283, PASTURE, n = 1133) were used to predict childhood asthma (age 5-11) including epidemiological characteristics and molecular markers: genotype, DNA methylation and mRNA expression (RNASeq/NanoString). Apparent (ap) and optimism-corrected (oc) performance (AUC/R2) was assessed leveraging evidence from independent studies (Naïve-Bayes approach) combined with high-dimensional logistic regression models (LASSO)., Results: Asthma prediction with epidemiological characteristics at birth (maternal asthma, sex, farm environment) yielded an ocAUC = 0.65. Inclusion of molecular markers as predictors resulted in an improvement in apparent prediction performance, however, for optimism-corrected performance only a moderate increase was observed (upto ocAUC = 0.68). The greatest discriminate power was reached by adding the first symptoms/diagnosis (up to ocAUC = 0.76; increase of 0.08, p = .002). Longitudinal analysis of selected mRNA expression in PASTURE (cord blood, 1, 4.5, 6 years) showed that expression at age six had the strongest association with asthma and correlation of genes getting larger over time (r = .59, p < .001, 4.5-6 years)., Conclusion: Applying epidemiological predictors alone showed moderate predictive abilities. Molecular markers from birth modestly improved prediction. Allergic symptoms/diagnoses enhanced the power of prediction, which is important for clinical practice and for the design of future studies with molecular markers., (© 2024 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Asthma is a common chronic disease characterised by variable respiratory symptoms and airflow limitation, affecting roughly 4%-10% of the adult population. Adult asthma is associated with higher all-cause mortality compared to individuals without asthma. In this study, we investigate the comorbidities that may affect the management of asthma., Methods: Total of 1648 adults with asthma and 3310 individuals without asthma aged 30-93 were matched with age, gender and area of residency, and followed from 1 January 1997 to 31 December 2013. Baseline information was collected with questionnaires 1997 and follow-up register data from the national discharge registry Finnish Institute for Health and Welfare. Data included diagnoses from outpatient care and day surgery of specialised health care, and data from inpatient care of specialised and primary health care. We included all main diagnoses that had at minimum 200 events and number of diagnoses based on their common appearance with adult asthma., Results: The mean follow-up time varied between 14.2 and 15.1 years, and age at the time of enrolment was 53.9 years for subjects without asthma and 54.4 years for patients with asthma. Chronic obstructive pulmonary disease was 10 times more common among asthmatics. Risk of acute rhinosinusitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis and vocal cord dysfunction was fourfold and risk of pneumonia, and chronic rhinosinusitis was 2.5 times more common among asthmatics. Sleep apnoea, gastro-oesophageal reflux disease, diabetes, allergic rhinitis and dysfunctional breathing were twofold and cataract nearly twofold higher in the asthmatic group. Adult asthma was also significantly associated with musculoskeletal diseases, incontinence and bronchiectasis., Conclusions: The most common and most severe comorbidity of adult asthma in this study was chronic obstructive pulmonary disease. Other common comorbidities of adult asthma include acute rhinosinusitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, allergic rhinitis, dysfunctional breathing, diabetes, pneumonia, sleep apnoea and gastro-oesophageal reflux disease., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: Sanna Toppila-Salmi reports consultancies for ALK-Abelló, AstraZeneca, ERT, GSK, Novartis, Sanofi, and Roche Products outside the submitted work, as well as grant of GSK outside the submitted work. All other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Phenotypes of adult asthma have been identified in previous studies but rarely in population-based settings., Objective: To identify clusters of adult-onset asthma in a Finnish population-based study on subjects born before 1967., Methods: We used population-based data from 1350 asthmatics with adult-onset asthma (Adult Asthma in Finland) from Finnish national registers. Twenty-eight covariates were selected based on literature. The number of covariates was reduced by using factor analysis before cluster analysis., Results: Five clusters (CLU1-CLU5) were identified, 3 clusters with late-onset adult asthma (onset ≥40 years) and 2 clusters with onset at earlier adulthood (<40 years). Subjects in CLU1 (n = 666) had late-onset asthma and were nonobese, symptomatic, and predominantly female with few respiratory infections during childhood. CLU2 (n = 36) consisted of subjects who had earlier-onset asthma, were predominantly female, obese with allergic asthma, and had recurrent respiratory infections. Subjects in CLU3 (n = 75) were nonobese, older, and predominantly men with late-onset asthma, smoking history, comorbidities, severe asthma, least allergic diseases, low education, many siblings, and childhood in rural areas. CLU4 (n = 218) was a late-onset cluster consisting of obese females with comorbidities, asthma symptoms, and low education level. Subjects in CLU5 (n = 260) had earlier onset asthma, were nonobese, and predominantly allergic females., Conclusions: Our population-based adult-onset asthma clusters take into account several critical factors such as obesity and smoking, and identified clusters that partially overlap with clusters identified in clinical settings. Results give us a more profound understanding of adult-onset asthma phenotypes and support personalized management., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of the study is to study functional impairment due to indoor air-related symptoms and associated characteristics., Methods: A questionnaire survey of a random sample of Finnish people aged 25 to 64 years. Analyses were done using multivariate multinomial logistic regression., Results: A total of 23.1% reported indoor air-related symptoms, 1.8% severe functional impairment due to symptoms, 5.3% moderate, 11.1% mild, and 4.9% reported no impairment. Those with severe functional impairment showed the strongest associations with comorbid diseases, for example, asthma and irritable bowel syndrome, perceived sensitivities to several environmental factors, like chemicals, and likelihood of having symptoms in multiple organs, while those with no or little functional impairment showed weak or even inverse associations. Similar results emerged with severity of indoor air-related symptoms., Conclusions: Individuals with indoor air-related symptoms are a very heterogeneous group. This should be better considered in future research and clinical practice., Competing Interests: Conflicts of interest: None declared., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Background: Although children can frequently experience a cough that affects their quality of life, few epidemiological studies have explored cough without a cold during childhood., Objectives: The objective of the study was to describe the latent class trajectories of cough from one to 10 years old and analyse their association with wheezing, atopy and allergic diseases., Methods: Questions about cough, wheeze and allergic diseases were asked at 1, 1.5, 2, 3, 4, 5, 6 and 10 years of age in the European prospective cohort of Protection against Allergy: STUdy in Rural Environment (PASTURE). Specific IgE assays were performed at 10 years of age. Questions regarding a cough without a cold were used to build a latent class model of cough over time., Results: Among the 961 children included in the study, apart from the never/infrequent trajectory (59.9%), eight trajectories of cough without a cold were identified: five grouped acute transient classes (24.1%), moderate transient (6.8%), late persistent (4.8%) and early persistent (4.4%). Compared with the never/infrequent trajectory, the other trajectories were significantly associated with wheezing, asthma and allergic rhinitis. For asthma, the strongest association was with the early persistent trajectory (OR a  = 31.00 [14.03-68.51]), which was inversely associated with farm environment (OR a  = 0.39 [0.19-0.77]) and had a high prevalence of cough triggers and unremitting wheeze. Late and early persistent trajectories were also associated with food allergy. Atopic sensitization was only associated with the late persistent trajectory., Conclusion: Late and early persistent coughs without a cold are positively associated with atopic respiratory diseases and food allergy. Children having recurrent cough without a cold with night cough and triggers would benefit from an asthma and allergy assessment. Growing up on a farm is associated with reduced early persistent cough., (© 2022 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Rationale: In murine models, microbial exposures induce protection from experimental allergic asthma through innate immunity. Objectives: Our aim was to assess the association of early life innate immunity with the development of asthma in children at risk. Methods: In the PASTURE farm birth cohort, innate T-helper cell type 2 (Th2), Th1, and Th17 cytokine expression at age 1 year was measured after stimulation of peripheral blood mononuclear cells with LPS in n  = 445 children. Children at risk of asthma were defined based on single-nucleotide polymorphisms at the 17q21 asthma gene locus. Specifically, we used the SNP rs7216389 in the GSDMB gene. Wheeze in the first year of life was assessed by weekly diaries and asthma by questionnaire at age 6 years. Measurements and Main Results: Not all cytokines were detectable in all children after LPS stimulation. When classifying detectability of cytokines by latent class analysis, carrying the 17q21 risk allele rs7216389 was associated with risk of wheeze only in the class with the lowest level of LPS-induced activation: odds ratio (OR), 1.89; 95% confidence interval [CI], 1.13-3.16; P  = 0.015. In contrast, in children with high cytokine activation after LPS stimulation, no association of the 17q21 risk allele with wheeze (OR, 0.63; 95% CI, 0.29-1.40; P  = 0.258, P  = 0.034 for interaction) or school-age asthma was observed. In these children, consumption of unprocessed cow's milk was associated with higher cytokine activation (OR, 3.37; 95% CI, 1.56-7.30; P  = 0.002), which was in part mediated by the gut microbiome. Conclusions: These findings suggest that within the 17q21 genotype, asthma risk can be mitigated by activated immune responses after innate stimulation, which is partly mediated by a gut-immune axis.

Background: The influence of diet in early childhood on later allergic diseases is currently a highly debated research topic. We and others have suggested that an increased diet diversity in the first year of life has a protective effect on the development of allergic diseases., Objective: This follow-up study aimed to investigate associations between diet in the second year of life and later allergic diseases., Methods: A total of 1014 children from rural areas in 5 European countries (the Protection against Allergy: Study in Rural Environments or PASTURE birth cohort) were included. Information on feeding practices in their second year of life and allergic diseases were collected up to age 6 years. Multivariate logistic regressions were performed with different models considering reverse causality, such as excluding children with a positive sensitization to egg and those with a positive sensitization to cow's milk at the age of 1 year., Results: An increased food diversity score during the second year of life was negatively associated with the development of asthma. Consumption of dairy products and eggs in the second year of life found an inverse association with reported allergic outcomes. Consumption of butter was strongly associated with protection against asthma and food sensitization. Egg was inversely associated with atopic dermatitis (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.04-0.77). Yogurt and cow's milk were inversely associated with food allergy (OR for yogurt, 0.05; 95% CI, 0.01-0.55; OR for cow's milk, 0.31; 95% CI, 0.11-0.89)., Conclusion: Increased food diversity in the second year of life is inversely associated with the development of asthma, and consumption of dairy products might have a protective effect on allergic diseases., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: Many comorbidities are associated with adult asthma and may exacerbate the asthma burden of disease. This study aims to investigate the risk for major oral diseases or oral-manifesting diseases in asthmatic compared with non-asthmatic adults., Design: We conducted a population-based matched cohort study with a 13.8-year follow-up., Setting: A baseline questionnaire was completed by participants in 1997 and follow-up data were extracted from the national hospital discharge registry of the National Institute for Health and Welfare in Finland from 1997 to 2014., Participants: A total of 1394 adults with asthma were matched with 2398 adults without asthma based on sex, age and area of residence. Asthmatic adults were identified from the Drug Reimbursement Register of the Finnish Social Insurance Institution based on a special drug reimbursement right resulting from asthma. Participants without asthma were identified from the Population Register., Main Outcomes and Measures: Oral health-related primary diagnoses were retrieved using codes from the International Classification of Diseases, 10th edition and divided into groups of diseases. Cox's proportional hazards models stratified by matching unit and models matched and adjusted for pack-years, education level and body mass index (when possible) were used to evaluate the matched and further adjusted HRs for diseases comparing asthmatic and non-asthmatic cohorts., Results: Adult asthma was associated with a higher risk for any oral-manifesting disease (adjusted HR 1.41, 95% CI 1.11 to 1.80), herpes zoster (adjusted HR 6.18, 95% CI 1.21 to 31.6), benign tumours of the oral cavity and pharynx (matched HR 1.94, 95% CI 1.05 to 3.56) and dermatological diseases (pemphigus, pemphigoid, dermatitis herpetiformis, psoriasis and lichen planus, HR 1.67, 95% CI 1.01 to 2.78)., Conclusions: In this study, adult asthmatics experienced a higher risk for a major oral disease or oral-manifesting disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Exposure to indoor moisture damage and visible mold has been found to be associated with asthma and respiratory symptoms in several questionnaire-based studies by self-report. We aimed to define the prospective association between the early life exposure to residential moisture damage or mold and fractional exhaled nitric oxide (FeNO) and lung function parameters as objective markers for airway inflammation and asthma in 6-year-old children., Methods: Home inspections were performed in children's homes when infants were on average 5 months old. At age 6 years, data on FeNO (n = 322) as well as lung function (n = 216) measurements were collected. Logistic regression and generalized additive models were used for statistical analyses., Results: Early age major moisture damage and moisture damage or mold in the child's main living areas were significantly associated with increased FeNO levels (>75th percentile) at the age of 6 years (adjusted odds ratios, 95% confidence intervals, aOR (95% CI): 3.10 (1.35-7.07) and 3.16 (1.43-6.98), respectively. Effects were more pronounced in those who did not change residential address throughout the study period. For lung function, major structural damage within the whole home was associated with reduced FEV1 and FVC, but not with FEV1/FVC. No association with lung function was observed with early moisture damage or mold in the child's main living areas., Conclusion: These results underline the importance of prevention and remediation efforts of moisture and mold-damaged buildings in order to avoid harmful effects within the vulnerable phase of the infants and children's immunologic development., (© 2021 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The aim was to identify risk factors for severe adult-onset asthma., Methods: We used data from a population-based sample (Adult Asthma in Finland) of 1350 patients with adult-onset asthma (age range 31-93 years) from Finnish national registers. Severe asthma was defined as self-reported severe asthma and asthma symptoms causing much harm and regular impairment and ≥ 1 oral corticosteroid course/year or regular oral corticosteroids or waking up in the night due to asthma symptoms/wheezing ≥ a few times/month. Sixteen covariates covering several domains (personal characteristics, education, lifestyle, early-life factors, asthma characteristics and multiple morbidities) were selected based on the literature and were studied in association with severe asthma using logistic regressions., Results: The study population included 100 (7.4%) individuals with severe asthma. In a univariate analysis, severe asthma was associated with male sex, age, a low education level, no professional training, ever smoking, ≥ 2 siblings, ≥ 1 chronic comorbidity and non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) (p < 0.05), and trends for association (p < 0.2) were observed for severe childhood infection, the presence of chronic rhinosinusitis with nasal polyps, and being the 1st child. The 10 variables (being a 1st child was removed due to multicollinearity) were thus entered in a multivariate regression model, and severe asthma was significantly associated with male sex (OR [95% CI] = 1.96 [1.16-3.30]), ever smoking (1.98 [1.11-3.52]), chronic comorbidities (2.68 [1.35-5.31]), NERD (3.29 [1.75-6.19]), and ≥ 2 siblings (2.51 [1.17-5.41]). There was a dose-response effect of the total sum of these five factors on severe asthma (OR [95% CI] = 2.30 [1.81-2.93] for each one-unit increase in the score)., Conclusions: Male sex, smoking, NERD, comorbidities, and ≥ 2 siblings were independent risk factors for self-reported severe asthma. The effects of these factors seem to be cumulative; each additional risk factor gradually increases the risk of severe asthma.

A higher diversity of food items introduced in the first year of life has been inversely related to subsequent development of asthma. In the current analysis, we applied latent class analysis (LCA) to systematically assess feeding patterns and to relate them to asthma risk at school age. PASTURE (N=1133) and LUKAS2 (N=228) are prospective birth cohort studies designed to evaluate protective and risk factors for atopic diseases, including dietary patterns. Feeding practices were reported by parents in monthly diaries between the 4 th and 12 th month of life. For 17 common food items parents indicated frequency of feeding during the last 4 weeks in 4 categories. The resulting 153 ordinal variables were entered in a LCA. The intestinal microbiome was assessed at the age of 12 months by 16S rRNA sequencing. Data on feeding practice with at least one reported time point was available in 1042 of the 1133 recruited children. Best LCA model fit was achieved by the 4-class solution. One class showed an elevated risk of asthma at age 6 as compared to the other classes (adjusted odds ratio (aOR): 8.47, 95% CI 2.52-28.56, p = 0.001) and was characterized by daily meat consumption and rare consumption of milk and yoghurt. A refined LCA restricted to meat, milk, and yoghurt confirmed the asthma risk effect of a particular class in PASTURE and independently in LUKAS2, which we thus termed unbalanced meat consumption (UMC). The effect of UMC was particularly strong for non-atopic asthma and asthma irrespectively of early bronchitis (aOR: 17.0, 95% CI 5.2-56.1, p < 0.001). UMC fostered growth of iron scavenging bacteria such as Acinetobacter (aOR: 1.28, 95% CI 1.00-1.63, p = 0.048), which was also related to asthma (aOR: 1.55, 95% CI 1.18-2.03, p = 0.001). When reconstructing bacterial metabolic pathways from 16S rRNA sequencing data, biosynthesis of siderophore group nonribosomal peptides emerged as top hit (aOR: 1.58, 95% CI 1.13-2.19, p = 0.007). By a data-driven approach we found a pattern of overly meat consumption at the expense of other protein sources to confer risk of asthma. Microbiome analysis of fecal samples pointed towards overgrowth of iron-dependent bacteria and bacterial iron metabolism as a potential explanation., Competing Interests: EvM reports to have received personal fees from PharmaVentures, OM Pharma, Springer-Verlag, Elsevier, Peptinnovate, Turun Yliopisto, Tampereen Yliopisto, Helsingin Yliopisto, European Respiratory Society, Deutsche Pharmazeutische Gesellschaft, Massachusetts Medical Society, the Chinese University of Hong Kong, European Commission, Boehringer Ingelheim, Universiteit Utrecht Faculteit Diergeneeskunde, Universität Salzburg, Georg Thieme Verlag, Japanese Society of Pediatric Allergy and Clinical Immunology, Nestlé Deutschland and HiPP, outside of the submitted work, and has received funding and research support from FrieslandCampina. In addition, EvM has patent LU101064 (Barn dust extract for the prevention and treatment of diseases) pending, royalties paid to ProtectImmun for patent EP2361632 (Specific environmental bacteria for the protection from and/or the treatment of allergic, chronic inflammatory and/or autoimmune disorders, granted on 19 March 2014), and patents EP1411977 (Composition containing bacterial antigens used for the prophylaxis and the treatment of allergic diseases, granted on 18 April 2007), EP1637147 (Stable dust extract for allergy protection, granted on 10 December 2008), and EP 1964570 (Pharmaceutical compound to protect against allergies and inflammatory diseases, granted on 21 November 2012) licensed to ProtectImmun. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hose, Pagani, Karvonen, Kirjavainen, Roduit, Genuneit, Schmaußer-Hechfellner, Depner, Frei, Lauener, Riedler, Schaub, Fuchs, von Mutius, Divaret-Chauveau, Pekkanen and Ege.)

Growing up on a farm is associated with an asthma-protective effect, but the mechanisms underlying this effect are largely unknown. In the Protection against Allergy: Study in Rural Environments (PASTURE) birth cohort, we modeled maturation using 16S rRNA sequence data of the human gut microbiome in infants from 2 to 12 months of age. The estimated microbiome age (EMA) in 12-month-old infants was associated with previous farm exposure (β = 0.27 (0.12-0.43), P = 0.001, n = 618) and reduced risk of asthma at school age (odds ratio (OR) = 0.72 (0.56-0.93), P = 0.011). EMA mediated the protective farm effect by 19%. In a nested case-control sample (n = 138), we found inverse associations of asthma with the measured level of fecal butyrate (OR = 0.28 (0.09-0.91), P = 0.034), bacterial taxa that predict butyrate production (OR = 0.38 (0.17-0.84), P = 0.017) and the relative abundance of the gene encoding butyryl-coenzyme A (CoA):acetate-CoA-transferase, a major enzyme in butyrate metabolism (OR = 0.43 (0.19-0.97), P = 0.042). The gut microbiome may contribute to asthma protection through metabolites, supporting the concept of a gut-lung axis in humans.

Rationale: Environmental tobacco smoke (ETS) exposure increases asthma risk in children. There is limited knowledge of prenatal ETS for adult-onset asthma., Objectives: To determine the association between prenatal ETS and adult onset asthma., Measurements and Main Results: The questionnaire and clinical data of 5200 people, free of physician-diagnosed asthma by 31 years of age, who were included in the Northern Finland Birth Cohort 1966 Study was used. The association of maternal smoking during the last 3 months of pregnancy with onset of physician-diagnosed asthma and with lung function in adult offspring was studied using adjusted multivariate regression analyses. The cumulative incidence of physician-diagnosed asthma between the ages of 31 and 46 years was 5.1% among men and 8.8% among women. Gestational smoke exposure was associated with adult-onset asthma among offspring (adjusted OR 1.54, 95% CI 1.04-2.29), namely among offspring who reported either past non-diagnosed asthma (OR 9.63, 95% CI 2.28-40.67) or past cough with wheeze (3.21, 95% CI 1.71-6.05). A significant association was detected between gestational smoke exposure and the offspring's forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) ratio at 31 years of age. In offspring with the haplotype rs11702779-AA of RUNX1 , gestational smoke exposure was associated with adult-onset asthma (5.53, 95% CI 2.11-14.52, adjusted p-value for interaction 0.10)., Conclusion: Maternal smoking during pregnancy is associated with the cumulative incidence of asthma in offspring between the ages of 31 and 46 years. The association was accentuated in offspring who at age 31, reported having past respiratory problems and/or who had haplotype rs11702779-AA. A reduction in FEV 1 /FVC ratio was also observed at age 31 years in offspring with gestational smoke exposure. These results could reflect the early vulnerability of offspring's airways to ETS and its putative long-term effects., Competing Interests: Conflict of interest: S. Toppila-Salmi has been a consultant for Mylan Laboratories Ltd, ERT Ltd and Roche Products Ltd, outside the submitted work. Conflict of interest: A.T. Luukkainen has nothing to disclose. Conflict of interest: B. Xu has nothing to disclose. Conflict of interest: J. Lampi has nothing to disclose. Conflict of interest: J. Auvinen has nothing to disclose. Conflict of interest: K. Dhaygude has nothing to disclose. Conflict of interest: M-R. Järvelin has nothing to disclose. Conflict of interest: J. Pekkanen has nothing to disclose., (Copyright ©ERS 2020.)

Background: Childhood asthma prevalence is significantly greater in urban areas compared with rural/farm environments. Murine studies have shown that TNF-α-induced protein 3 (TNFAIP3; A20), an anti-inflammatory regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, mediates environmentally induced asthma protection., Objective: We aimed to determine the role of TNFAIP3 for asthma development in childhood and the immunomodulatory effects of environmental factors., Methods: In a representative selection of 250 of 2168 children from 2 prospective birth cohorts and 2 cross-sectional studies, we analyzed blood cells of healthy and asthmatic children from urban and rural/farm environments from Europe and China. PBMCs were stimulated ex vivo with dust from "asthma-protective" farms or LPS. NF-κB signaling-related gene and protein expression was assessed in PBMCs and multiplex gene expression assays (NanoString Technologies) in isolated dendritic cells of schoolchildren and in cord blood mononuclear cells from newborns., Results: Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased, whereas proinflammatory Toll-like receptor 4 expression was increased in urban asthmatic patients (P < .05), reflecting their increased inflammatory status. Ex vivo farm dust or LPS stimulation restored TNFAIP3 expression to healthy levels in asthmatic patients and shifted NF-κB signaling-associated gene expression toward an anti-inflammatory state (P < .001). Farm/rural children had lower expression, indicating tolerance induction by continuous environmental exposure. Newborns with asthma at school age had reduced TNFAIP3 expression at birth, suggesting TNFAIP3 as a possible biomarker predicting subsequent asthma., Conclusion: Our data indicate TNFAIP3 as a key regulator during childhood asthma development and its environmentally mediated protection. Because environmental dust exposure conferred the anti-inflammatory effects, it might represent a promising future agent for asthma prevention and treatment., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The aim was to study the association between allergic multimorbidity and adult-onset asthma considering the number of allergic diseases and the age effect., Methods: We used population-based data from Finnish national registers including 1205 adults over 30 years of age with recently diagnosed asthma (age range: 30-93), matched for gender, age, and living region with one or two controls (n = 2050). Allergic rhinitis (AR), allergic conjunctivitis (AC), and allergic dermatitis (AD) were defined from self-completed questionnaire. Conditional logistic regression adjusted on potential confounders (smoking, growing in countryside, childhood hospitalized infection/pneumonia, parental asthma/allergy, parental smoking, education level, professional training, number of siblings, and birth order) was applied to estimate the asthma risk associated with allergic multimorbidity., Results: A total of 1118 cases with asthma and 1772 matched controls were included [mean (SD, min-max) 53 (11, 31-71) years, 37% men)]. AR, AC, and AD were reported by 50.2%, 39.6%, and 33.8%, respectively, among subjects with asthma and 26.1%, 20.0%, and 23.5%, respectively, among controls. Compared to nonatopics, adult-onset asthma increased with the number of allergic diseases; adjusted OR for asthma [95% CI] associated with 1, 2, and 3 allergic diseases was 1.95 [1.52-2.49], 2.87 [2.19-3.77], and 4.26 [3.07-5.90], respectively. The association between adult-onset asthma and ≥ 1 allergic multimorbidity decreased with increasing age (3.52 [2.51-4.94], 2.44 [1.74-3.42], and 1.68 [1.04-2.71]) in subjects < 50 years, 50-62 years, and > 62 years, respectively (p for age*≥1 allergic multimorbidity interaction, 0.002)., Conclusions: Adult-onset asthma was positively associated with the number of allergic diseases, and this association decreases with age., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Childhood asthma is often preceded by early wheeze. Usually, wheezing episodes are recorded retrospectively, which may induce recall bias., Aims and Objectives: The aim of this study was to investigate true-positive recall of parent-reported wheeze at 1 year of age, its determinants, and its implications for asthma and lung function at 6 years of age., Methods: The PASTURE (Protection Against Allergy-Study in Rural Environments) study followed 880 children from rural areas in 5 European countries from birth to age 6 years. Wheeze symptoms in the first year were asked weekly. At age 6, parent-reported asthma diagnosis was ascertained and lung function measurements were conducted. Correct parental recall of wheeze episodes at the end of the first year was assessed for associations with lung function, asthma, and the asthma risk locus on chromosome 17q21., Results: Parents correctly recalled wheeze after the first year in 54% of wheezers. This true-positive recall was determined by number of episodes, timing of the last wheeze episode, and parental asthma. Independently from these determinants, true-positive recall predicted asthma at age 6 years (odds ratio 4.54, 95% confidence interval (CI) [1.75-14.16]) and impaired lung function (β = -0.62, 95% CI [-1.12; -0.13], P-value = .02). Associations were stronger in children with asthma risk SNPs on chromosome 17q21., Conclusion: Correct parental recall of wheezing episodes may reflect clinical relevance of early wheeze and its impact on subsequent asthma and lung function impairment. Questions tailored to parental perception of wheezing episodes may further enhance asthma prediction., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

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 > |0.4|) 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., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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.

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., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Dietary changes are suggested to play a role in the increasing prevalence of allergic diseases and asthma. Short-chain fatty acids (SCFAs) are metabolites present in certain foods and are produced by microbes in the gut following fermentation of fibers. SCFAs have been shown to have anti-inflammatory properties in animal models. Our objective was to investigate the potential role of SCFAs in the prevention of allergy and asthma., Methods: We analyzed SCFA levels by high-performance liquid chromatography (HPLC) in fecal samples from 301 one-year-old children from a birth cohort and examined their association with early life exposures, especially diet, and allergy and asthma later in life. Data on exposures and allergic diseases were collected by questionnaires. In addition, we treated mice with SCFAs to examine their effect on allergic airway inflammation., Results: Significant associations between the levels of SCFAs and the infant's diet were identified. Children with the highest levels of butyrate and propionate (≥95th percentile) in feces at the age of one year had significantly less atopic sensitization and were less likely to have asthma between 3 and 6 years. Children with the highest levels of butyrate were also less likely to have a reported diagnosis of food allergy or allergic rhinitis. Oral administration of SCFAs to mice significantly reduced the severity of allergic airway inflammation., Conclusion: Our results suggest that strategies to increase SCFA levels could be a new dietary preventive option for allergic diseases in children., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objectives: Chronic cough is linked to various long-standing risk factors like asthma, chronic rhinitis and oesophageal reflux disease. On the contrary, acute and subacute cough are usually considered to be caused by acute respiratory infections. Little is known about the possible long-standing risk factors for acute and subacute cough. In this study, we have identified the long-standing risk factors for acute, subacute and chronic cough in order to identify the risk factors specifically associated with chronic cough., Design: A comprehensive 80-item questionnaire was sent via email to the participants., Setting: A community-based study to all public service employees of two towns in central Finland., Participants: There were 13 980 employees, of them 3697 responded (26.4%). Among the responders, there were 199 subjects with current daily acute cough (duration <3 weeks, prevalence 5.4%), 126 subjects with current daily subacute cough (duration 3-8 weeks, prevalence 3.4%) and 267 subjects with current daily chronic cough (duration >8 weeks, prevalence 7.2%)., Primary Outcome Measures: The risk factors that associated with each cough subtype. The subjects without any cough formed the reference group., Results: Several risk factors were associated with both short and long cough subtypes namely family history of chronic cough, moisture damage exposure and number of reported somatic symptoms. Furthermore, allergy was associated with acute and subacute cough. Current asthma and chronic rhinitis were associated with subacute and chronic cough. Oesophageal reflux disease and advanced age were associated with chronic cough., Conclusions: The specific risk factors for chronic cough were oesophageal reflux disease and advanced age. Acute and subacute cough should not be regarded merely as symptoms of acute respiratory infections but possible manifestations of long-standing risk factors. A new risk factor for all cough types was family history of chronic cough., Competing Interests: Competing interests: AML reports grants from Kuopion Hengityssäätiö Foundation, grants from Hengityssairauksien Tutkimussäätiö, during the conduct of the study; personal fees from Orion, Boehringer-Ingelheim, Roche to visit international scientific meetings , outside the submitted work. HOK reports grants from Kuopion Hengityssäätiö Foundation, grants from Hengityssairauksien Tutkimussäätiö, during the conduct of the study; personal fees from Mundipharma, Orion Pharma, Oy, Eli Lilly Finland, Boehringer Ingelheim Finland as payments for giving scientific lectures in gatherings organised by medical companies, personal fees from Takeda Leiras, Boehringer Ingelheim and Mundipharma to visit international scientific meetings, other from owning shares of Orion Pharma worth €25 000, outside the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: We aimed to determine whether maternal hemoglobin levels or anemia during pregnancy are associated with the development of asthma among offspring., Methods: Data were retrieved from the birth register database of Kuopio University Hospital between 1989 and 2007 (n = 38 381). Hemoglobin levels were measured during three trimesters of pregnancy and anemia was defined according to the World Health Organization criteria. The prevalence of asthma was determined from the register of reimbursement for medication for asthma at the Finnish Social Security Institution. Cox proportional hazard regression analysis was performed to evaluate the possible associations between prenatal factors and development of asthma ever., Results: A total of 8198 (21.4%) women had anemia at some stage of pregnancy. Mild maternal anemia during the first trimester was associated with an increased risk of asthma among male offspring (adjusted hazard ratio, 1.46; 95% confidence interval, 1.11-1.94) compared with those with normal maternal hemoglobin levels. This finding remained significant also after applying the Bonferroni correction., Conclusion: Male offspring with maternal anemia during the first trimester of pregnancy had significantly more asthma ever than the offspring of women with normal hemoglobin levels during pregnancy. These findings were not strong but suggest possible sex-specific effects of maternal health on prenatal programming and future risk of asthma., (© 2018 Japan Society of Obstetrics and Gynecology.)

Background: Questionnaires can be used to assess perceived indoor air quality and symptoms in schools. Questionnaires for primary school aged children have traditionally been parent-administered, but self-administered questionnaires would be easier to administer and may yield as good, if not better, information. Our aim was to compare the repeatability of self- and parent-administered indoor air questionnaires designed for primary school aged pupils., Methods: Indoor air questionnaire with questions on child's symptoms and perceived indoor air quality in schools was sent to parents of pupils aged 7-12 years in two schools and again after two weeks. Slightly modified version of the questionnaire was administered to pupils aged 9-12 years in another two schools and repeated after a week. 351 (52%) parents and 319 pupils (86%) answered both the first and the second questionnaire. Test-retest repeatability was assessed with intra-class correlation (ICC) and Cohen's kappa coefficients (k)., Results: Test-retest repeatability was generally between 0.4-0.7 (ICC; k) in both self- and parent-administered questionnaire. In majority of the questions on symptoms and perceived indoor air quality test-retest repeatability was at the same level or slightly better in self-administered compared to parent-administered questionnaire. Agreement of self- and parent administered questionnaires was generally < 0.4 (ICC; k) in reported symptoms and 0.4-0.6 (ICC; k) in perceived indoor air quality., Conclusions: Children aged 9-12 years can give as, or even more, repeatable information about their respiratory symptoms and perceived indoor air quality than their parents. Therefore, it may be possible to use self-administered questionnaires in future studies also with children.

Both protective and adverse effects of indoor microbial exposure on asthma have been reported, but mostly in children. To date, no study in adults has used non-targeted methods for detection of indoor bacteria followed by quantitative confirmation.A cross-sectional study of 198 asthmatic and 199 controls was conducted within the European Community Respiratory Health Survey (ECRHS) II. DNA was extracted from mattress dust for bacterial analysis using denaturing gradient gel electrophoresis (DGGE). Selected bands were sequenced and associations with asthma confirmed with four quantitative PCR (qPCR) assays.15 out of 37 bands detected with DGGE, which had at least a suggestive association (p<0.25) with asthma, were sequenced. Of the four targeted qPCRs, Clostridium cluster XI confirmed the protective association with asthma. The association was dose dependent (aOR 0.43 (95% CI 0.22-0.84) for the fourth versus first quartile, p for trend 0.009) and independent of other microbial markers. Few significant associations were observed for the three other qPCRs used.In this large international study, the level of Clostridium cluster XI was independently associated with a lower risk of prevalent asthma. Results suggest the importance of environmental bacteria also in adult asthma, but need to be confirmed in future studies., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2018.)

Rationale: Asthma is characterised by inflammation and reversible airway obstruction. However, these features are not always closely related. Fluctuations of daily lung function contain information on asthma phenotypes, exacerbation risk and response to long-acting β-agonists., Objectives: In search of subgroups of asthmatic participants with specific lung functional features, we developed and validated a novel clustering approach to asthma phenotyping, which exploits the information contained within the fluctuating behaviour of twice-daily lung function measurements., Methods: Forced expiratory volume during the first second (FEV 1 ) and peak expiratory flow (PEF) were prospectively measured over 4 weeks in 696 healthy and asthmatic school children (Protection Against Allergy - Study in Rural Environments (PASTURE)/EFRAIM cohort), and over 1 year in 138 asthmatic adults with mild-to-moderate or severe asthma (Pan-European Longitudinal Assessment of Clinical Course and BIOmarkers in Severe Chronic AIRway Disease (BIOAIR) cohort). Using enrichment analysis, we explored whether the method identifies clinically meaningful, distinct clusters of participants with different lung functional fluctuation patterns., Measurements and Main Results: In the PASTURE/EFRAIM dataset, we found four distinct clusters. Two clusters were enriched in children with well-known clinical characteristics of asthma. In cluster 3, children from a farming environment predominated, whereas cluster 4 mainly consisted of healthy controls. About 79% of cluster 3 carried the asthma-risk allele rs7216389 of the 17q21 locus. In the BIOAIR dataset, we found two distinct clusters clearly discriminating between individuals with mild-to-moderate and severe asthma., Conclusions: Our method identified dynamic functional asthma and healthy phenotypes, partly independent of atopy and inflammation but related to genetic markers on the 17q21 locus. The method can be used for disease phenotyping and possibly endotyping. It may identify participants with specific functional abnormalities, potentially needing a different therapeutic approach., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Living on a farm has repeatedly been shown to protect children from asthma and allergies. A major factor involved in this effect is consumption of unprocessed cow's milk obtained directly from a farm. However, this phenomenon has never been shown in a longitudinal design, and the responsible milk components are still unknown., Objectives: We sought to assess the asthma-protective effect of unprocessed cow's milk consumption in a birth cohort and to determine whether the differences in the fatty acid (FA) composition of unprocessed farm milk and industrially processed milk contributed to this effect., Methods: The Protection Against Allergy-Study in Rural Environments (PASTURE) study followed 1133 children living in rural areas in 5 European countries from birth to age 6 years. In 934 children milk consumption was assessed by using yearly questionnaires, and samples of the "usually" consumed milk and serum samples of the children were collected at age 4 years. Doctor-diagnosed asthma was parent reported at age 6 years. In a nested case-control study of 35 asthmatic and 49 nonasthmatic children, 42 FAs were quantified in milk samples., Results: The risk of asthma at 6 years of age was reduced by previous consumption of unprocessed farm milk compared with shop milk (adjusted odds ratio for consumption at 4 years, 0.26; 95% CI, 0.10-0.67). Part of the effect was explained by the higher fat content of farm milk, particularly the higher levels of ω-3 polyunsaturated FAs (adjusted odds ratio, 0.29; 95% CI, 0.11-0.81)., Conclusion: Continuous farm milk consumption in childhood protects against asthma at school age partially by means of higher intake of ω-3 polyunsaturated FAs, which are precursors of anti-inflammatory mediators., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Rationale: Growing up on a farm protects from childhood asthma and early wheeze. Virus-triggered wheeze in infancy predicts asthma in individuals with a genetic asthma risk associated with chromosome 17q21., Objectives: To test environmental determinants of infections and wheeze in the first year of life, potential modifications of these associations by 17q21, and the implications for different trajectories of wheeze., Methods: We followed 983 children in rural areas of Europe from birth until age 6 years. Symptoms of wheeze, rhinitis, fever, and environmental exposures were documented with weekly diaries during year 1. Asthma at age 6 was defined as ever having a reported doctor's diagnosis. Single-nucleotide polymorphisms related to ORMDL3 (rs8076131) and GSDMB (rs7216389, rs2290400) at 17q21 were genotyped., Measurements and Main Results: Early wheeze was positively associated with presence of older siblings among carriers of known asthma risk alleles at 17q21 (e.g., rs8076131) (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.16-2.01). Exposure to farm animal sheds was inversely related to wheeze (aOR, 0.44; 95% CI, 0.33-0.60). Both effects were similarly observed in children with transient wheeze up to age 3 years without subsequent development of asthma (aOR, 1.71 [95% CI, 1.09-2.67]; and aOR, 0.48 [95% CI, 0.30-0.76], respectively)., Conclusions: These findings suggest that the chromosome 17q21 locus relates to episodes of acute airway obstruction common to both transient wheeze and asthma. The previously identified asthma risk alleles are the ones susceptible to environmental influences. Thus, this gene-environment interaction reveals two faces of 17q21: The same genotype constitutes genetic risk and allows for environmental protection, thereby providing options for prospective prevention strategies.

Objectives: Farming as an occupation is considered a risk factor for asthma and reduced lung function. By contrast, living on a farm during infancy has been reported to be associated with lower risk of asthma in adulthood. However, little is known about the association between farming environment during infancy and lung function in adulthood. We aimed to study the prospective longitudinal association between farming environment during infancy and lung function in adulthood., Design: A prospective birth cohort study., Setting: Northern Finland., Participants: 5666 participants born in 1966 were followed up at the age of 31 years., Primary Outcome Measures: Spirometry at the age of 31 years., Results: To be born into a farmer's family was associated with higher forced expiratory volume in 1 s (FEV1) (36 mL; 95% CI 6 to 67 mL) and forced vital capacity (FVC) (40 mL; 95% CI 5 to 75 mL) at the age of 31 years. Contact with farm animals during infancy was associated with higher FEV1. No associations were seen with FEV1/FVC (FEV1/FVC ratio). Having dogs in childhood revealed similar associations. There was a suggestive dose-dependent association with the number of animal species during childhood and higher FEV1 and FVC at adulthood, especially among women., Conclusions: Farming environment in early life may have a positive impact on lung function in adulthood., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Excess moisture and visible mold are associated with increased risk of asthma. Only a few studies have performed detailed home visits to characterize the extent and location of moisture damage and mold growth., Methods: Structured home inspections were performed in a birth cohort study when the children were 5 months old (on average). Children (N = 398) were followed up to the age of 6 years. Specific immunoglobulin E concentrations were determined at 6 years., Results: Moisture damage and mold at an early age in the child's main living areas (but not in bathrooms or other interior spaces) were associated with the risk of developing physician-diagnosed asthma ever, persistent asthma, and respiratory symptoms during the first 6 years. Associations with asthma ever were strongest for moisture damage with visible mold in the child's bedroom (adjusted odds ratio: 4.82 [95% confidence interval: 1.29-18.02]) and in the living room (adjusted odds ratio: 7.51 [95% confidence interval: 1.49-37.83]). Associations with asthma ever were stronger in the earlier part of the follow-up and among atopic children. No consistent associations were found between moisture damage with or without visible mold and atopic sensitization., Conclusions: Moisture damage and mold in early infancy in the child's main living areas were associated with asthma development. Atopic children may be more susceptible to the effects of moisture damage and mold., (Copyright © 2015 by the American Academy of Pediatrics.)

Background: Recently, the bacterial diversity of the intestinal flora and the diversity of various environmental factors during infancy have been linked to the development of allergies in childhood. Food is an important environmental exposure, but the role of food diversity in the development of asthma and allergies in childhood is poorly defined., Objective: We studied the associations between food diversity during the first year of life and the development of asthma and allergies by age 5 years., Methods: In a Finnish birth cohort we analyzed data on 3142 consecutively born children. We studied food diversity at 3, 4, 6, and 12 months of age. Asthma, wheeze, atopic eczema, and allergic rhinitis were measured by using the International Study of Asthma and Allergies in Childhood questionnaire at age 5 years., Results: By 3 and 4 months of age, food diversity was not associated with any of the allergic end points. By 6 months of age, less food diversity was associated with increased risk of allergic rhinitis but not with the other end points. By 12 months of age, less food diversity was associated with increased risk of any asthma, atopic asthma, wheeze, and allergic rhinitis., Conclusion: Less food diversity during the first year of life might increase the risk of asthma and allergies in childhood. The mechanisms for this association are unclear, but increased dietary antigen exposure might contribute to this link., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells., Objective: We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant., Methods: From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4(+)CD25(+) forkhead box protein 3 (FOXP3)(+) (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis., Results: Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4(+)CD25(+), FOXP3(+) T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells., Conclusions: Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Rationale: Clinical and epidemiologic approaches have identified two distinct sets of classifications for asthma and wheeze phenotypes., Objectives: To compare epidemiologic phenotype definitions identified by latent class analysis (LCA) with clinical phenotypes based on patient histories, diagnostic work-up, and treatment responses. To relate phenotypes to genetic and environmental determinants as well as diagnostic and treatment-related parameters., Methods: LCA was performed in an international multicenter birth cohort based on yearly questions about current wheeze until age 6 years. Associations of wheeze classes and clinical phenotypes with asthma-related characteristics such as atopy, lung function, fraction of exhaled nitric oxide, and medication use were calculated using regression models., Measurements and Main Results: LCA identified five classes, which verified the clinically defined wheeze phenotypes with high sensitivity and specificity; the respective receiver operating characteristics curves displayed an area under the curve ranging from 84% (frequent wheeze) to 85% (asthma diagnosis) and 87% (unremitting wheeze) to 97% (recurrent unremitting wheeze). Recurrent unremitting wheeze was the most specific and unremitting wheeze at least once the most sensitive definition. The latter identified a subgroup of children with decreased lung function, increased genetic risk, and in utero smoke exposure (ODDS RATIO, 2.03; 95% CONFIDENCE INTERVAL, 1.12-3.68; P = 0.0191), but without established asthma diagnosis and treatment., Conclusions: Clinical phenotypes were well supported by LCA analysis. The hypothesis-free LCA phenotypes were a useful reference for comparing clinical phenotypes. Thereby, we identified children with clinically conspicuous but undiagnosed disease. Because of their high area under the curve values, clinical phenotypes such as (recurrent) unremitting wheeze emerged as promising alternative asthma definitions for epidemiologic studies.

Objective: To evaluate the association between maternal fecundity factors and time to pregnancy and risk of asthma in offspring., Design: Retrospective observational hospital-based birth cohort study., Setting: A university-based obstetrics and gynecology department., Patient(s): A total of 40,914 women, who delivered between 1989 and 2007, were linked with the register for asthma reimbursement (n = 2,577) for their offspring. Fecundity factors were recorded during pregnancy. Logistic regression analyses were used., Intervention(s): None., Main Outcome Measure(s): Asthma among offspring., Result(s): The risk of asthma was significantly increased if the mother had any infertility problems (adjusted odds ratio [adjusted OR] 1.39, 95% confidence interval [CI] 1.19-1.63), medical infertility treatment (aOR 1.43, 95% CI 1.13-1.80), or any infertility treatment (aOR 1.50, 95% CI 1.26-1.79). The risk of asthma among offspring was also higher among mothers who had more than two miscarriages (aOR 1.25, 95% CI 1.04-1.51) and time to pregnancy over 3 months (aOR 1.25, 95% CI 1.07-1.45)., Conclusion(s): These findings suggest that maternal subfertility exposes offspring to an increased risk of asthma., Clinical Trial Registration Number: The study is registered in Kuopio University Hospital register (TUTKI): ID 5302448., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Emerging evidence questions current recommendations on the timing of infant feeding for the prevention of childhood allergies. The evidence for asthma is inconclusive., Objective: We sought to investigate the associations between the duration of breast-feeding and timing of introduction of complementary foods and the development of asthma and allergies by the age of 5 years., Methods: Data were analyzed for 3781 consecutively born children. The dietary exposures were categorized into thirds and analyzed as time-dependent variables. Asthma, allergic rhinitis, and atopic eczema end points were assessed by using the International Study of Asthma and Allergies in Childhood questionnaire, whereas IgE antibodies were analyzed from serum samples at the age of 5 years. Cox proportional hazard and logistic regressions were used for the analyses., Results: The median duration of exclusive and total breast-feeding was 1.4 months (interquartile range, 0.2-3.5 months) and 7.0 months (interquartile range, 4.0-11.0 months), respectively. Total breast-feeding of 9.5 months or less was associated with an increased risk of nonatopic asthma. Introduction of wheat, rye, oats, or barley at 5 to 5.5 months was inversely associated with asthma and allergic rhinitis, whereas introduction of other cereals at less than 4.5 months increased the risk of atopic eczema. Introduction of egg at 11 months or less was inversely associated with asthma, allergic rhinitis, and atopic sensitization, whereas introduction of fish at 9 months or less was inversely associated with allergic rhinitis and atopic sensitization., Conclusion: Early introduction of wheat, rye, oats, and barley cereals; fish; and egg (respective to the timing of introduction of each food) seems to decrease the risk of asthma, allergic rhinitis, and atopic sensitization in childhood. Longer duration of total breast-feeding, rather than its exclusivity, was protective against the development of nonatopic but not atopic asthma, suggesting a potential differing effect of breast-feeding on different asthma phenotypes., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Particulate matter air pollution has been associated with adverse health effects. The fraction of ambient particles that are mainly responsible for the observed health effects is still a matter of controversy. Better characterization of the health relevant particle fraction will have major implications for air quality policy since it will determine which sources should be controlled.The RUPIOH study, an EU-funded multicentre study, was designed to examine the distribution of various ambient particle metrics in four European cities (Amsterdam, Athens, Birmingham, Helsinki) and assess their health effects in participants with asthma or COPD, based on a detailed exposure assessment. In this paper the association of central site measurements with respiratory symptoms and restriction of activities is examined., Methods: At each centre a panel of participants with either asthma or COPD recorded respiratory symptoms and restriction of activities in a diary for six months. Exposure assessment included simultaneous measurements of coarse, fine and ultrafine particles at a central site. Data on gaseous pollutants were also collected. The associations of the 24-hour average concentrations of air pollution indices with the health outcomes were assessed in a hierarchical modelling approach. A city specific analysis controlling for potential confounders was followed by a meta-analysis to provide overall effect estimates., Results: A 10 μg/m3 increase in previous day coarse particles concentrations was positively associated with most symptoms (an increase of 0.6 to 0.7% in average) and limitation in walking (OR= 1.076, 95% CI: 1.026-1.128). Same day, previous day and previous two days ozone concentrations were positively associated with cough (OR= 1.061, 95% CI: 1.013-1.111; OR= 1.049, 95% CI: 1.016-1.083 and OR= 1.059, 95% CI: 1.027-1.091, respectively). No consistent associations were observed between fine particle concentrations, nitrogen dioxide and respiratory health effects. As for particle number concentrations negative association (mostly non-significant at the nominal level) was observed with most symptoms whilst the positive association with limitation of activities did not reach the nominal level of significance., Conclusions: The observed associations with coarse particles are in agreement with the findings of toxicological studies. Together they suggest it is prudent to regulate also coarse particles in addition to fine particles.

Background: The high prevalence of children's asthma symptoms, worldwide, is unexplained. We examined the relation between maternal pre-pregnancy weight and body mass index (BMI), and asthma symptoms in adolescents., Methods: Data from 6945 adolescents born within the Northern Finland Birth Cohort 1986 were used. Prospective antenatal and birth outcome data, including maternal pre-pregnancy weight and BMI, and asthma symptoms in adolescent offspring at age 15-16 years, were employed. Logistic regression analyses were performed to examine the associations between relevant prenatal factors and asthma symptoms during adolescence., Results: Current wheeze (within the past year) was reported by 10.6% of adolescents, and physician-diagnosed asthma by 6.0%. High maternal pre-pregnancy BMI was a significant predictor of wheeze in the adolescents (increase per kilogram per square metre unit; 2.7%, 95% CI 0.9 to 4.4 for ever wheeze; 3.5%, 95% CI 1.3 to 5.8 for current wheeze), and adjusting for potential confounders further increased the risk (2.8%, 95% CI 0.5 to 5.1; 4.7%, 95% CI 1.9 to 7.7, respectively). High maternal pre-pregnancy weight, in the top tertile, also significantly increased the odds of current wheeze in the adolescent by 20% (95% CI 4 to 39), and adjusting for potential confounders further increased the risk (OR=1.52, 95% CI 1.19 to 1.95). Results were similar for current asthma. Furthermore, these significant associations were observed only among adolescents without parental history of atopy but not among those with parental history of atopy., Conclusions: The association demonstrated here between maternal pre-pregnancy overweight and obesity, and asthma symptoms in adolescents suggests that increase in asthma may be partly related to the rapid rise in obesity in recent years.

There is a need to better define phenotypes of asthma. However, many studies have data available only on asthma and atopy, so they are often used to define ‘atopic’ and ‘non-atopic’ asthma. We discuss and illustrate the problems of analyzing such outcomes. We used the 31 year follow-up of the Northern Finland Birth Cohort 1966 (n=5,429). ‘Atopic asthma’ and ‘non-atopic asthma’ were defined based on presence or absence of atopy (any skin prick test ≥3 mm) at age 31. Gender and ownership of cat in childhood were used as risk factors. Simple calculations on hypothetical datasets were used to support the conclusions. ‘Atopic asthma’ and ‘non-atopic asthma’, are not well separated disease entities. The association of a risk factor with ‘atopic asthma’ and ‘non-atopic asthma’ is determined both by its association with asthma and with atopy. E.g. if a risk factor is not associated with asthma, but is protective for atopy, this will produce a protective association with ‘atopic asthma’, but an opposite association with ‘non-atopic asthma’. This is the result from the typical analysis, which uses all non-asthmatics as the comparison group. Valid results, unconfounded by atopy, can be gained by comparing asthmatics to nonasthmatics separately among atopics and non-atopics, i.e. by doing the analysis stratified by atopy. If data only on asthma and atopy are available, asthma and atopy should be analyzed at first as separate outcomes. If atopic and nonatopic asthma are used as additional outcomes, valid results can be gained by stratifying the analysis by atopy.

Rationale: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies., Objectives: To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations., Methods: The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P<5 x 10(-8)) and three variants reported as suggestive (P<5× 10(-7)). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever., Main Results: We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4 × 10(-9)). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (P(Stage1+Stage2) = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (P(Stage1+Stage2) = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status., Conclusions: Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.

Background: Valid identification of childhood asthma at the population level for epidemiological purposes remains a challenge. We aimed at validating the Finnish version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire based on parental-reported childhood asthma., Materials and Methods: The ISAAC questionnaire has been validated against anti-asthmatic medication reimbursement data of the Finnish Social Insurance Institution, being the gold standard, among 2236 5-year-old consecutively born children (1996-2004) carrying human leukocyte antigen (HLA)-conferred susceptibility to type 1 diabetes. Two combined questionnaire questions (any wheezing symptom or use of asthma medication during the preceding 12 months plus ever asthma; any wheezing symptom or use of asthma medication during the preceding 12 months plus ever doctor-diagnosed asthma) were validated against valid reimbursement with purchase of at least one anti-asthmatic medication during a 12-month period. The validity of the questionnaire was estimated as the sensitivity, specificity, positive predictive value, negative predictive value, and Youden's index., Results: The sensitivity 0.98 [95% confidence interval (CI) = 0.92-0.99]; specificity 0.98 (95% CI = 0.97-0.98); negative predictive value 1.00 (95% CI = 1.00-1.00); and Youden's index 0.96 (95% CI = 0.96-0.96) were the same for each of the two sets of combined questions. The positive predictive value for the first combined question was 0.63 (95% CI = 0.55-0.71), while it was 0.64 (95% CI = 0.57-0.72) for the second combined question., Conclusion: The Finnish ISAAC questionnaire was highly valid and is an acceptable instrument for the survey of the prevalence of parental-reported childhood asthma for epidemiological purposes., (© 2010 Blackwell Publishing Ltd.)

Aim: There is a need for markers of Th1 and Th2 imbalance in diseases such as asthma. CD30 is an activation marker of Th2 cells, and importance of Th1 marker CD26 was recently found in adult asthma. We studied whether serum-soluble CD30 (sCD30) or serum-soluble CD26 (sCD26) could support early diagnosis of asthma in children at school age., Methods: sCD26 and sCD30 were measured in 34 children with clinically confirmed asthma, 31 with possible asthma and in 147 controls. In addition, the associations of flow volume spirometry, methacholine inhalation challenge and free running test results with serum sCD26 or sCD30 were analysed., Results: Serum sCD30 was significantly higher in children with confirmed asthma (mean 91.5 IU/mL, SD 23.0) than in the controls (78.8 IU/mL, 25.9; p = 0.042). No significant differences were found in serum sCD26 levels between the groups. There was a negative correlation of mean mid expiratory flow values with serum sCD26 (r = -0.22, p = 0.0018). Neither methacholine inhalation challenge nor free running test results were associated with serum sCD26 or sCD30., Conclusion: Serum sCD30 was higher in children with asthma. However, marked overlap in serum sCD30 between asthmatic and healthy children limits the usefulness of sCD30 as a diagnostic marker of asthma., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Background: Health effects of ozone have been observed in numerous studies. However, analyses of more cause-specific morbidity or mortality outcomes have rarely been performed. A study was undertaken to determine the short-term associations of ozone with cause-specific cardiorespiratory mortality and morbidity by age groups., Methods: Daily levels of ozone were measured at a background measurement station in 1998-2004 in Helsinki, Finland. All analyses were a priori restricted to the warm season. Daily cause-specific cardiorespiratory mortality and hospital admissions were studied in elderly people (> or =65 years) and adults (15-64 years) and associations between ozone and asthma emergency room visits in children (<15 years) were analysed. All models were adjusted for PM(2.5) and Poisson regression was used for the analyses., Results: There was a positive association between ozone and admissions for asthma-chronic obstructive pulmonary disease (COPD) in elderly people (9.6%; 95% CI 2.0% to 17.8% at 0-day lag for 25 microg/m(3) increase in ozone). Consistent associations were also found between ozone and asthma emergency room visits in children (12.6%; 95% CI 0.8% to 25.1%, 0-day lag). There was a suggestion of an association between ozone and admissions for arrhythmia among elderly people (6.4%; 95% CI 0.63% to 12.5%, 1-day lag), which was slightly confounded by PM(2.5)., Conclusions: Positive associations were found for ambient ozone with asthma visits among children and with pooled asthma/COPD admissions among elderly people. The evidence for a positive association between ozone and cardiovascular health was weaker.

The evidence of the effect of the age at introduction of new foods during infancy on the development of asthma and allergic rhinitis is inconsistent and scarce. We set out to study these associations. A prospective birth cohort of infants with increased HLA-DQB1-conferred risk for type 1 diabetes was recruited in 1996-2000. The families completed at home a record on the age at introduction of new foods. Persistent asthma and allergic rhinitis were assessed at the age of 5 years with an International Study of Asthma and Allergies in Childhood-type questionnaire. The Cox proportional hazards regression analyses were adjusted for parental asthma and allergic diseases, and several perinatal and sociodemographical factors. Out of the 1293 children, 77 (6.0 %) developed persistent asthma; and out of the 1288 children, 185 (14.4 %) developed allergic rhinitis by the age of 5 years. Early age at introduction of oats was associated with a reduced risk of persistent asthma (hazard ratio (HR; 95 % CI) for the first and mid-tertiles compared with the latest tertile was 0.36 (0.15, 0.85) and 0.37 (0.22, 0.62), respectively, P < 0.001). Early age at introduction of fish was dose dependently associated with a decreased risk of allergic rhinitis (HR (95 % CI) for the first and mid-tertiles compared with the latest tertile was 0.34 (0.22, 0.54) and 0.45 (0.28, 0.70), respectively, P < 0.001). The present finding that age at introduction of oats is inversely and independently associated with development of persistent asthma is novel. We confirmed the earlier observation that the age at introduction of fish is inversely related to the risk of allergic rhinitis. Clinical implications remain to be determined.

Background: Markers for microbial groups are commonly measured in house dust samples to assess indoor exposure to microbes in studies on asthma and allergy. However, little is known about the sources of different microbes. A better understanding of the nature and origin of microbes present in the immediate environment of human beings is crucial if one wants to elucidate protective as well as adverse effects on human health., Objective: To determine the extent to which the bacterial composition of mattress and floor dust reflects the presence of the human body in relation to other environmental sources., Methods: House dust and skin surface swab samples of occupants in 4 homes were collected and analyzed for their bacterial content, using a culture-independent methodology. Bacterial sequences analyzed from the different house dusts and skin surface swabs represented random samples of bacteria present in a given sample. Highly similar sequences were grouped to assess biodiversity and to draw conclusions about the sources of bacteria., Results: The bacterial flora in the house dust samples was found to be highly diverse and dominated by gram-positive bacteria. To a considerable extent, the presence of different bacterial groups was attributed to human sources. In the individuals' mattress dust samples, 69% to 88% of the bacterial sequences analyzed were associated with human origins. The respective percentages for the individual floor dusts ranged from 45% to 55%., Conclusion: Our study indicates that human-derived bacteria account for a large part of the mainly gram-positive bacterial content in house dust.

Objectives: Most previous studies on the association between moisture or mold problems in the home and respiratory symptoms in children were cross-sectional and based on self-reported exposure. The aim of this study was to evaluate the impact of objectively observed moisture damage and visible mold in the homes on early-life respiratory morbidity and atopic sensitization in a birth cohort., Methods: Building inspection was performed by building engineers in the homes of 396 children, and the children were followed up with questionnaires from birth to the age of 18 months. Specific immunoglobulin E levels were measured at the age of 1 year., Results: Doctor-diagnosed wheezing was associated with the severity of moisture damage in the kitchen and with visible mold in the main living area and especially in the bedroom of the child. The risk for parent-reported wheezing apart from cold increased with the severity of moisture damage in the kitchen. Moisture damage in the bathrooms or other interior spaces had no significant association with wheezing. No significant associations were observed for other end points, such as cough, or respiratory infections. There was a suggestion for an increased risk for sensitization to cat dander linked with moisture and mold exposure., Conclusions: This birth-cohort study supports previous observations that moisture mold problems in the kitchen and in the main living area increase the risk for wheezing in early childhood. The results underline the importance of assessing separately the health effects of moisture and mold problems in different areas of the home.

Background: Microbial colonization of the airways and intestine during birth might have an effect on the risk of asthma and allergic diseases later in life., Objective: We sought to evaluate the association between intrauterine microbial growth at the time of delivery and the development of asthma and allergic sensitization among offspring., Methods: Intrauterine bacterial culture results were recorded at the time of cesarean delivery of 460 children who were born at Kuopio University Hospital during 1990-1992. When the children reached the age of 15 to 17 years, self-administered questionnaires were sent to the mothers, and 382 of the children were also examined by using skin prick tests., Results: Intrauterine growth of potential pathogenic anaerobic bacteria and Streptococcus species at birth was associated with an increased risk of doctor-diagnosed asthma ever (odds ratio [OR], 4.51 [95% CI, 1.56-13.0]; OR, 2.53 [95% CI, 1.19-5.38]) and doctor-diagnosed current asthma (OR, 7.34 [95% CI, 2.44-22.03]; OR, 3.37 [95% CI, 1.46-7.76]) at the age of 15 to 17 years compared with the risk seen in subjects with negative microbial cultures. These findings remained significant also after applying the Bonferroni correction. No significant association after the Bonferroni correction was detected between intrauterine microbial growth and allergic sensitization among offspring., Conclusion: The results of this study indicated that specific intrauterine microbial growth at the time of birth might increase the risk of asthma among offspring through inflammatory mechanisms. These results indicate new potential targets for future studies on the effects of maternal vaginal microflora and intrauterine infection in the development of asthma among children.

Background: The aim of the present study was to evaluate the prevalence of sensitization to molds and to house dust mites (HDM) in pre-school children with newly-diagnosed asthma., Methods: From 1996 to 2000, 122 children 1 to 6 years of age with fresh asthma treated in the Kuopio University Hospital, Kuopio, Finland, were recruited in the study; 94% attended. Skin prick tests were performed to common inhalant allergens and to 10 molds. The homes were surveyed for moisture damage., Results: A majority of the houses had signs of dampness and moisture. One-third of the children reacted to inhalant allergens. There were 11 positive reactions to molds in five children who all reacted to at least one animal dander or seasonal pollen. Aspergillus fumigatus, Botrytis cinerea, and Cladosporium herbarum were the most common mold allergens. There were only two children with positive reactions to HDM, and none of them reacted to molds. No associations were found between the presence or degree of moisture problems at home and mold or HDM allergy., Conclusion: Sensitization to molds seems to play only a minor role in pre-school children with newly-diagnosed asthma in a northern climate where the incidences of mold and HDM allergies are rather low.

The authors assessed determinants of ergosterol, 3-OH fatty acids (FAs), and viable microbes in vacuum cleaner dust, and investigated the association between these microbial markers and childhood asthma. The authors studied the homes of 36 children who were new cases of childhood asthma and the homes of 36 controls. Home characteristics explained 34% to 44% of the variation in levels of different microbial groups. Determinants of 3-OH FAs were a lower level of cleanliness, having a fireplace, having livestock, and moisture damage; determinants of viable bacteria were the level of home repair needed and the material used in the building frame of the home. Ergosterol was associated with the presence of livestock and the practice of cleaning rugs outside; viable fungi was associated with the material used in the building frame, visible mold, and the practice of cleaning rugs outside. Exposure to mesophilic actinomycetes was nonsignificantly associated with risk of asthma. The authors concluded that the variation of microbial levels in dust could be explained relatively well by home characteristics, and suggested that exposure to mesophilic actinomycetes may increase the risk of new asthma.