The Role of Biodiversity in the Development of Asthma and Allergic Sensitization: A State-of-the-Science Review.

BACKGROUND: Changes in land use and climate change have been reported to reduce biodiversity of both the environment and human microbiota. These reductions in biodiversity may lead to inadequate and unbalanced stimulation of immunoregulatory circuits and, ultimately, to clinical diseases, such as asthma and allergies. OBJECTIVE: We summarized available empirical evidence on the role of inner (gut, skin, and airways) and outer (air, soil, natural waters, plants, and animals) layers of biodiversity in the development of asthma, wheezing, and allergic sensitization. METHODS: We conducted a systematic search in SciVerse Scopus, PubMed MEDLINE, and Web of Science up to 5 March 2024 to identify relevant human studies assessing the relationships between inner and outer layers of biodiversity and the risk of asthma, wheezing, or allergic sensitization. The protocol was registered in PROSPERO (CRD42022381725). RESULTS: A total of 2,419 studies were screened and, after exclusions and a full-text review of 447 studies, 82 studies were included in the comprehensive, final review. Twenty-nine studies reported a protective effect of outer layer biodiversity in the development of asthma, wheezing, or allergic sensitization. There were also 16 studies suggesting an effect of outer layer biodiversity on increasing asthma, wheezing, or allergic sensitization. However, there was no clear evidence on the role of inner layer biodiversity in the development of asthma, wheezing, and allergic sensitization (13 studies reported a protective effect and 15 reported evidence of an increased risk). CONCLUSIONS: Based on the reviewed literature, a future systematic review could focus more specifically on outer layer biodiversity and asthma. It is unlikely that association with inner layer biodiversity would have enough evidence for systematic review. Based on this comprehensive review, there is a need for population-based longitudinal studies to identify critical periods of exposure in the life course into adulthood and to better understand mechanisms linking environmental exposures and changes in microbiome composition, diversity, and/or function to development of asthma and allergic sensitization. https://doi.org/10.1289/EHP13948.

Prenatal and early life exposure to air pollution and the risk of severe lower respiratory tract infections during early childhood: the Espoo Cohort Study.

BACKGROUND: There is inconsistent evidence of the effects of exposure to ambient air pollution on the occurrence of lower respiratory tract infections (LRTIs) in early childhood. We assessed the effects of individual-level prenatal and early life exposure to air pollutants on the risk of LRTIs in early life. METHODS: We studied 2568 members of the population-based Espoo Cohort Study born between 1984 and 1990 and living in 1991 in the City of Espoo, Finland. Exposure assessment was based on dispersion modelling and land-use regression for lifetime residential addresses. The outcome was a LRTI based on data from hospital registers. We applied Poisson regression to estimate the incidence rate ratio (IRR) of LTRIs, contrasting incidence rates in the exposure quartiles to the incidence rates in the first quartile. We used weighted quantile sum (WQS) regression to estimate the joint effect of the studied air pollutants. RESULTS: The risk of LRTIs during the first 2 years of life was significantly related to exposure to individual and multiple air pollutants, measured with the Multipollutant Index (MPI), including primarily sulphur dioxide (SO2), particulate matter with a dry diameter of up to 2.5 µm (PM2.5) and nitrogen dioxide (NO2) exposures in the first year of life, with an adjusted IRR of 1.72 per unit increase in MPI (95% CI 1.20 to 2.47). LRTIs were not related to prenatal exposure. CONCLUSIONS: We provide evidence that ambient air pollution exposure during the first year of life increases the risk of LRTIs during the first 2 years of life. SO2, PM2.5 and NO2 were found to contribute the highest weights on health effects.

Residential greenness during pregnancy and early life and development of asthma up to 27 years of age: The Espoo Cohort Study.

Previous studies have suggested that living close to green spaces has protective health effects, but potential effects on asthma are contradictory. We investigated the association between the amount of greenness in the residential area during pregnancy and early life and development of asthma in the first 27 years of life. The study population included all 2568 members of the Espoo Cohort Study, Finland. We calculated individual-level exposure to green space measured as cumulative Normalized Difference Vegetation Index (cumNDVI in unit-months) within 300 m of the participant's residence during pregnancy and the first two years of life in both spring and summer seasons. The onset of asthma was assessed using information from the baseline and follow-up surveys. Exposure to residential greenness in the spring season during pregnancy was associated with an increased risk of asthma up to 6 years of age, with an adjusted hazard ratio (aHR) of 3.72 (95% confidence interval (CI): 1.11, 12.47) per 1 unit increase in cumNDVI. Increased greenness in the summer during pregnancy associated with asthma up to 6 years, with an aHR of 1.41 (95% CI: 0.85, 2.32). The effect was found to be related to increased greenness particularly during the third trimester of pregnancy, with an aHR of 2.37 (95% CI: 1.36, 4.14) per 1 unit increase of cumNDVI. These associations were weaker at the ages of 12 and 27 years. No association was found between NDVI in the first two years of life and the development of asthma. Our findings provide novel evidence that exposure to greenness during pregnancy increases the risk of developing asthma. The adverse effects were strongest for the prenatal greenness in the spring season and in the third trimester of pregnancy. Both the season and trimester of exposure to greenness are critical in the development of asthma.

Effect of cold winters on the risk of new asthma: a case-crossover study in Finland.

BACKGROUND: Cold weather increases respiratory symptoms and provokes exacerbations of asthma, but there are no previous studies on its role in the aetiology of asthma. OBJECTIVE: We tested the hypothesis that a cold winter increases the risk of developing asthma during the following 1 to 2 years. METHODS: We conducted a case-crossover study of 315 newly diagnosed cases of asthma from the population-based Espoo Cohort Study from birth to the age of 27 years. The hazard period constituted 3 winter months preceding the onset of asthma and bidirectional reference periods of 1 year before hazard period and 1 year after onset of asthma. Exposure constituted average ambient temperature during the winter months of December, January and February. The outcome of interest was new doctor-diagnosed asthma. The measure of effect was OR of asthma estimated by conditional logistic regression analysis. RESULTS: The average winter temperature for the study period from winter 1983 to 2010 was -4.4°C (range -10.7 to 0.4). A 1°C decrease in the average winter temperature predicted a 7% increase in the risk of new asthma (OR=1.07, 95% CI 1.02 to 1.13). A cold winter with an average temperature below the climate normal value (-4.5°C; period 1981-2010) increased the risk of new asthma by 41% during the following year (OR: 1.41; 95% CI 1.04 to 1.90). CONCLUSIONS: This case-crossover study provides original evidence that a cold winter with below normal average temperatures increases the risk of developing new asthma during the following 1 to 2 years.

Occupation and occurrence of respiratory infections among adults with newly diagnosed asthma.

BACKGROUND: Work environments are potential areas for spreading respiratory infections. We hypothesized that certain occupations increase susceptibility to respiratory infections among adults with asthma. Our objective was to compare the occurrence of respiratory infections among different occupations in adults with newly diagnosed asthma. METHODS: We analysed a study population of 492 working-age adults with newly diagnosed asthma who were living in the geographically defined Pirkanmaa Area in Southern Finland during a population-based Finnish Environment and Asthma Study (FEAS). The determinant of interest was occupation at the time of diagnosis of asthma. We assessed potential relations between occupation and occurrence of both upper and lower respiratory tract infections during the past 12 months. The measures of effect were incidence rate ratio (IRR) and risk ratio (RR) adjusted for age, gender, and smoking habits. Professionals, clerks, and administrative personnel formed the reference group. RESULTS: The mean number of common colds in the study population was 1.85 (95% CI 1.70, 2.00) infections in the last 12 months. The following occupational groups showed increased risk of common colds: forestry and related workers (aIRR 2.20, 95% CI 1.15-4.23) and construction and mining (aIRR 1.67, 95% CI 1.14-2.44). The risk of lower respiratory tract infections was increased in the following groups: glass, ceramic, and mineral workers (aRR 3.82, 95% CI 2.54-5.74), fur and leather workers (aRR 2.06, 95% CI 1.01-4.20) and metal workers (aRR 1.80, 95% CI 1.04-3.10). CONCLUSIONS: We provide evidence that the occurrence of respiratory infections is related to certain occupations.

Asthma and Respiratory Infections From Birth to Young Adulthood.

We applied data from a population-based prospective study, the Espoo Cohort Study (n = 2,568), to identify the potential susceptibility of persons with asthma to respiratory tract infections (RTIs). Information on the occurrence of asthma and both upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs) was collected with a questionnaire at baseline and at the 6-year and 20-year follow-up studies, and from the Finnish national health registries. We estimated age- and sex-specific incidence rate differences (IRDs) and incidence rate ratios (IRRs) by applying negative binomial regression. Meta-regression was used to summarize the age-specific IRRs from childhood to 27 years of age. Individuals with asthma at any age during the follow-up period had increased risks of both URTIs (adjusted IRD = 72.6 (95% confidence interval (CI): 50.6, 94.7) per 100 person-years; adjusted IRR = 1.27 (95% CI: 1.20, 1.35)) and LRTIs (adjusted IRD = 25.5 (95% CI: 17.9, 33.1); adjusted IRR = 2.87 (95% CI: 2.33, 3.53)) from childhood to young adulthood. In young adulthood, the association between asthma and URTIs was stronger in women than in men, while such an association was not detected for LRTIs. This analysis provides strong evidence that persons with asthma experience more RTIs from preschool age to young adulthood than do those without asthma. Thus, they constitute a susceptible population for RTIs. Women with asthma are at especially high risk.

Maternal antibiotic use and infections during pregnancy and offspring asthma: the Norwegian Mother, Father and Child Cohort Study and a nationwide register cohort.

Maternal antibiotic use during pregnancy has been linked to asthma risk in children, but the role of underlying infections remains unclear. We investigated the association of maternal antibiotic use and infections during pregnancy with offspring risk of asthma. We used two population-based cohorts: the Norwegian Mother, Father and Child Cohort Study (MoBa) (n = 53 417) and a register-based cohort (n = 417 548). Asthma was defined based on dispensed asthma medications at 7 and 13 years from the Norwegian Prescription Database. Self-reported information on antibiotic use and infections during pregnancy was available in MoBa, while registrations of dispensed prescriptions were used to classify use of antibiotics in the register-based cohort. Maternal antibiotic use during pregnancy was associated with asthma at 7 in both cohorts (adjusted risk ratio (aRR) 1.23, 95% CI 1.11-1.37 in MoBa and 1.21, 1.16-1.25 in the register cohort) and asthma at 13 in the register cohort (1.13, 1.03-1.23) after adjusting for maternal characteristics. In MoBa, the estimate was attenuated after adjusting for infections during pregnancy. Maternal lower and upper respiratory tract infections (aRR 1.30, 95% CI 1.07-1.57 and 1.19, 1.09-1.30, respectively) and urinary tract infections (1.26, 1.11-1.42) showed associations with asthma at 7. Register cohort also showed an increased risk of asthma in relation to maternal antibiotics before and after pregnancy. Our findings suggest that both maternal antibiotics and infections during pregnancy have a role in the risk of offspring asthma. However, results from the register cohort suggest that the effect of antibiotics may reflect the shared underlying susceptibility.

ERS International Congress 2020: highlights from the Epidemiology and Environment Assembly.

In this article, early career members of the Epidemiology and Environment Assembly of the European Respiratory Society (ERS) summarise a selection of five sessions from the ERS 2020 Virtual International Congress. The topics covered include risk factors for chronic respiratory diseases over the life course, from early life origins to occupational exposures in adulthood, and the interplay between these risk factors, including gene-environment interactions. Novel results were also presented on smoking prevention and potential risks of vaping. Finally, the challenges and opportunities for epidemiological and environmental research brought by the coronavirus disease 2019 (COVID-19) pandemic were a major topic of this year's congress.

Short-term prenatal exposure to ambient air pollution and risk of preterm birth - A population-based cohort study in Finland.

BACKGROUND: Previous studies have provided evidence that prenatal exposure to low-level air pollution increases the risk of preterm birth (PTB), but the findings of the effects of short-term exposure have been inconclusive. Moreover, there is little knowledge on potential synergistic effects of different combinations of air pollutants. OBJECTIVES: To assess independent and joint effects of prenatal exposure to air pollutants during the week prior to the delivery on the risk of PTB. METHODS: The study population included 2568 members of the Espoo Cohort Study, living in the City of Espoo, Finland, born between 1984 and 1990. We assessed individual-level prenatal exposure to ambient air pollutants of interest based on maternal residential addresses, while taking into account their residential mobility. We used both regional-to-city-scale dispersion modelling and land-use regression-based method to estimates the pollutant concentrations. We contrasted the risk of PTB in the highest quartile (Q4) of exposure to the lower exposure quartiles (Q1-Q3) during the specific periods of pregnancy. We applied Poisson regression analysis to estimate the adjusted risk ratios (RRs) with their 95% confidence intervals (CI), adjusting for season of birth, maternal age, sex of the baby, family's socioeconomic status, maternal smoking, and exposure to environmental tobacco smoke during pregnancy, single parenthood, and exposure to other air pollutants (this in multi-pollutant models). RESULTS: The risk of PTB was related to exposures to PM2.5, PM10 and NO2 during the week prior to the delivery with adjusted RRs of 1.67 (95%CI: 1.14, 2.46), 1.60 (95% CI: 1.09, 2.34) and 1.65 (95% CI: 1.14, 2.37), from three-pollutant models respectively. There were no significant joint effects for these different air pollutants (during the week prior to the delivery). CONCLUSION: Our results provide evidence that exposure to fairly low-level air pollution may trigger PTB, but synergistic effects of different pollutants are not likely.

Is the Association of Early Day Care Attendance with Childhood Asthma Explained by Underlying Susceptibility?

BACKGROUND: Previous studies of early day care attendance and asthma development are inconsistent, which may be explained by inadequate control of confounding and effect modification. We examined the effect of early day care on the risk of asthma taking into account the underlying susceptibility to asthma. METHODS: The study included 55,404 children participating in the Norwegian Mother, Father and Child Cohort Study. Asthma at age 7 was defined by dispensed asthma medications in the Norwegian Prescription Database. We defined a disease risk score (DRS) to account for an underlying susceptibility to asthma including a range of hereditary and nonhereditary predictors of asthma. We assessed confounding and modifying effects of DRS on the association between day care and asthma. RESULTS: Day care before 18 months was associated with a lower risk of asthma by age 7 (adjusted risk ratio [RR] = 0.85; 95% confidence interval [CI] = 0.78, 0.92) when compared with home care. DRS modified the estimated effect of day care on asthma risk. Among the 80% of children with DRS between 0.03 and 0.16, day care was associated with a reduced asthma risk (RRs between 0.79 and 0.87), whereas among 0.5% of children with a high DRS (above 0.28), estimated effect of day care on asthma increased gradually (RR for the highest DRS 2.2; 1.0-4.9). CONCLUSIONS: In our study, among most children, early day care was associated with reduced asthma risk at 7 years, and increased risk in a small group of children with very high underlying susceptibility to asthma.

Dental caries is associated with lower respiratory tract infections: A population-based cohort study.

INTRODUCTION: Dental caries and respiratory tract infections are among the most common infectious diseases worldwide and they both are appearing in the respiratory system. However, their relations are still unclear. This study investigated the association of dental caries on the risk of lower respiratory tract infections (LRTI) in young adulthood. METHODS: The study population consisted of 1,592 Finnish young adults participating in the 20-year follow-up of The Espoo Cohort Study. The information on the occurrence of LRTIs (pneumonia or acute bronchitis) during the preceding 12 months was based on the follow-up questionnaire and the National Hospital Discharge Register. Lifelong caries on permanent teeth was defined as a self-reported number of filled teeth (FT). The risk ratios (RR) of LRTIs with 95% confidence intervals (CI) were estimated using Poisson regression models. RESULTS: High FT number was associated with an increased occurrence of LRTIs with an adjusted RR of 1.24 per interquartile range (IQR) of FT (95% CI 1.06-1.44). The risk of LRTIs increased according to the increasing number of FTs, being highest among those subjects with 10 or more filled teeth (adjusted RR 2.30; 1.27-4.17). Family's socioeconomic status or smoking did not modify the effect. CONCLUSIONS: Our results suggest that dental caries increases the risk of LRTIs. We did not find any significant effect modification by shared determinants of caries and LRTIs. However, it is possible, that common risk factors might explain at least partly the observed relation between FT and LRTIs or that the causality is bidirectional.

Synergistic effects of prenatal exposure to fine particulate matter (PM2.5) and ozone (O3) on the risk of preterm birth: A population-based cohort study.

BACKGROUND: There is some evidence that prenatal exposure to low-level air pollution increases the risk of preterm birth (PTB), but little is known about synergistic effects of different pollutants. OBJECTIVES: We assessed the independent and joint effects of prenatal exposure to air pollution during the entire duration of pregnancy. METHODS: The study population consisted of the 2568 members of the Espoo Cohort Study, born between 1984 and 1990, and living in the City of Espoo, Finland. We assessed individual-level prenatal exposure to ambient air pollutants of interest at all the residential addresses from conception to birth. The pollutant concentrations were estimated both by using regional-to-city-scale dispersion modelling and land-use regression-based method. We applied Poisson regression analysis to estimate the adjusted risk ratios (RRs) with their 95% confidence intervals (CI) by comparing the risk of PTB among babies with the highest quartile (Q4) of exposure during the entire duration of pregnancy with those with the lower exposure quartiles (Q1-Q3). We adjusted for season of birth, maternal age, sex of the baby, family's socioeconomic status, maternal smoking during pregnancy, maternal exposure to environmental tobacco smoke during pregnancy, single parenthood, and exposure to other air pollutants (only in multi-pollutant models) in the analysis. RESULTS: In a multi-pollutant model estimating the effects of exposure during entire pregnancy, the adjusted RR was 1.37 (95% CI: 0.85, 2.23) for PM2.5 and 1.64 (95% CI: 1.15, 2.35) for O3. The joint effect of PM2.5 and O3 was substantially higher, an adjusted RR of 3.63 (95% CI: 2.16, 6.10), than what would have been expected from their independent effects (0.99 for PM2.5 and 1.34 for O3). The relative risk due to interaction (RERI) was 2.30 (95% CI: 0.95, 4.57). DISCUSSION: Our results strengthen the evidence that exposure to fairly low-level air pollution during pregnancy increases the risk of PTB. We provide novel observations indicating that individual air pollutants such as PM2.5 and O3 may act synergistically potentiating each other's adverse effects.

Early Respiratory Infections and Dental Caries in the First 27 Years of Life: A Population-Based Cohort Study.

Early-life respiratory tract infections (RTIs) and dental caries are among the most common infectious diseases worldwide. The relations between early RTIs and development of caries in permanent teeth have not been studied earlier. We assessed childhood RTIs as potential predictors of caries in young adulthood in a 20-year prospective population-based cohort study (The Espoo Cohort Study). Information on lower respiratory tract infections (LRTIs) that had required hospitalization was retrieved from the National Hospital Discharge Registry (n = 1623). Additional information on LRTIs and upper RTIs (URTIs) was assessed based on the questionnaire reports that covered the preceding 12 months. Caries was measured as the number of teeth with fillings (i.e. filled teeth, FT) reported in the 20-year follow-up questionnaire. The absolute and relative excess numbers of FT were estimated applying negative binomial regression. The mean number of FT in young adulthood was 1.4 greater among subjects who had experienced LRTIs requiring hospitalization before the age of 2 years (SD 4.8) compared to those without any such infections (SD 3.4), and the adjusted relative excess number of FT was 1.5 (95% CI 1.0-2.2). LRTIs up to 7 years were associated with an absolute increase of 0.9 in the mean FT number, the adjusted relative excess being 1.3 (1.0-1.8). Also the questionnaire-based LRTIs (adjusted relative excess 1.3; 95% CI 0.9-1.8) and URTIs (adjusted relative excess 1.4, 1.0-1.8) before the age of 2 years predicted higher occurrence of FT. Findings suggest that early RTIs have a role in the development of dental caries in permanent teeth.

Early Respiratory Infections and the Development of Asthma in the First 27 Years of Life.

Previous studies have provided contradictory evidence on the role of early childhood respiratory infections in the development of asthma and other allergic diseases during childhood. We investigated early-life respiratory infections as predictors of the development of asthma in a 20-year prospective cohort study (the Espoo Cohort Study, 1991-2011). Information on upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs) was collected with a parent-administered baseline questionnaire covering the preceding 12 months (part 1; n = 2,228), and information on LRTIs leading to hospitalization was obtained from the National Hospital Discharge Registry (part 2; n = 2,568). The incidence of asthma was assessed on the basis of 6-year and 20-year follow-up questionnaires. Adjusted hazard ratios were estimated using Cox proportional hazards models. Both URTIs (adjusted hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.22, 2.19) and LRTIs (adjusted HR = 2.11, 95% CI: 1.48, 3.00) in early childhood were strong predictors of asthma incidence up to young adulthood (ages 20-27 years). A declining age trend was present for both URTIs (P-trend < 0.01) and LRTIs (P-trend < 0.001). In part 2 of our analysis, a significant risk of asthma was found in relation to LRTIs requiring hospitalization (adjusted HR = 1.93, 95% CI: 1.10, 3.38). The results provide new evidence that respiratory tract infections in early life predict the development of asthma through childhood to young adulthood.

Allergic diseases and asthma in the family predict the persistence and onset-age of asthma: a prospective cohort study.

BACKGROUND: Family history of asthma and other allergic diseases have been linked to the risk of childhood asthma previously, but little is known about their effect on the age-of-onset and persistency of asthma until young adulthood. METHODS: We assessed the effect of the family history of asthma and allergic diseases on persistent vs. transient, and early- vs. late-onset persistent asthma in The Espoo Cohort Study 1991-2011, a population-based cohort study of 1623 subjects (follow-up rate 63.2%). The determinants were any family history (any parent or sibling); maternal; paternal; siblings only; parents only; and both siblings and parents. Analyses were conducted separately for asthma and allergic diseases while taking the other disease into account as a confounding factor. The outcomes were persistent, transient, early-onset persistent (<13 years) and late-onset persistent asthma. Adjusted risk ratios (RR) were calculated applying Poisson regression. Q-statistics were used to assess heterogeneity between RRs. RESULTS: Family history was associated with the different subtypes but the magnitude of effect varied quantitatively. Any family history of asthma was a stronger determinant of persistent (adjusted RR = 2.82, 95% CI 1.99-4.00) than transient asthma (1.65, 1.03-2.65) (heterogeneity: P = 0.07) and on early-onset than late-onset persistent asthma. Also any family history of allergic diseases was a stronger determinant of persistent and early-onset asthma. The impact of paternal asthma continued to young adulthood (early-onset: 3.33, 1.57-7.06 vs. late-onset 2.04, 0.75-5.52) while the influence of maternal asthma decreased with age (Early-onset 3.94, 2.11-7.36 vs. Late-onset 0.88, 0.28-2.81). Paternal allergic diseases did not follow the pattern of paternal asthma, since they showed no association with late-onset asthma. Also the effect estimates for other subtypes were lower than in other hereditary groups (persistent 1.29, 0.75-2.22 vs. transient 1.20, 0.67-2.15 and early-onset 1.86, 0.95-3.64 vs. late-onset 0.64, 0.22-1.80). CONCLUSIONS: Family history of asthma and allergic diseases are strong determinants of asthma, but the magnitude of effect varies according to the hereditary group so that some subtypes have a stronger hereditary component, and others may be more strongly related to environmental exposures. Our results provide useful information for assessing the prognosis of asthma based on a thorough family history.