Long-term exposure to air pollution from road traffic and lung function in children and adolescents

Lung function in early life is an important predictor of peak lung function and later decline in adults. However, lung development may also be influenced by factors later in childhood and adolescence. Identification of susceptible periods and modifiable factors affecting lung development already during infancy and childhood could help promote respiratory health later in life. The overall aim of this thesis was to investigate potential environmental determinants of lung function in children and adolescents, with particular focus on exposure to traffic-related air pollution. The papers in this thesis were based on the BAMSE study, a longitudinal population-based birth cohort of children followed until adolescence. The parents of all children born in predefined urban and suburban areas of Stockholm County between February 1994 and November 1996 were invited to enroll their children. Symptoms of allergy-related disease, life-style factors and major exposures were assessed from questionnaires filled out at the ages of 1, 2, 4, 8, 12 and 16 years. Lung function was measured using spirometry at 8 and 16 years of age, with the addition of impulse oscillometry at age 16 years. The assessment of individual long-term exposure to traffic-related air pollution was based on dispersion modeling, using emission inventories and data on road traffic, meteorological conditions and topography, at relevant geographical locations. Time-weighted annual averages of nitrogen oxides (NOx) and particulate matter with an aerodynamic diameter of less than 10 μm (PM10) were assessed over the life course. The influence of long-term exposure to traffic-related air pollution on lung function at 8 and 16 years of age was assessed, including life course analyses. Pollution exposure during the first year of life, but none of the other time periods examined, was significantly associated with reduced lung function at 8 and 16 years of age. No associations were observed for the change in lung function between the two time points for any of the time windows explored. This suggests that exposure in early life influences early lung growth and that lung function thereafter tracks with age. In addition, we observed that air pollution during the first year of life was associated with small but significant increase of small airways resistance. Associations appeared stronger in subjects with asthma at 16 years. Exposure to air pollution and other environmental factors was investigated in relation to lung function growth between childhood and adolescence, using quantile regression on the 10th, 50th and 90th percentiles, corresponding to low, median, and high lung function growth. Out of 20 examined variables, birth weight, asthma heredity and environmental tobacco smoke exposure in infancy were the only independent predictors of lung function growth. In summary, exposure to traffic-related air pollution during infancy was associated with decreased lung function, including in the small airways, in childhood and adolescence. Air pollution and other environmental factors assessed after infancy had little impact on lung function growth, supporting the notion of a susceptible period early in life with tracking of lung function thereafter

Comparative effectiveness of initial computed tomography and invasive coronary angiography in women and men with stable chest pain and suspected coronary artery disease: multicentre randomised trial

To assess the comparative effectiveness of computed tomography and invasive coronary angiography in women and men with stable chest pain suspected to be caused by coronary artery disease

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: A meta-analysis of 150 000 European children

BACKGROUND: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. METHODS: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. RESULTS: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. CONCLUSIONS: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections