Trafikk og astma. Betydning for utvikling og forverring av sykdom.

Transkript

1 Prevalence (%) Trafikk og astma. Betydning for utvikling og forverring av sykdom. Published Norwegian studies on asthma prevalence in childhood from ECA 16 years, Oslo 20 ECA, 10 years, Oslo Norland Norland Year

2 Life risk of asthma, diabetes and malignant diseases Lifetime risk (%) of developing chronic diseases from birth, comparing asthma(diamond data points) with diabetes (square data points) and all cancers (triangle datapoints) To T et al. Am J Respir Crit Care Med. 2010; 15;181(4): As the twig is bent, the tree inclines (Perhaps?) Burrows B, Taussig L. American Review of Respiratory Disease. 1980;122(6):

3 Lung function at birth and at 10 years of age and asthma at 10 years Barn med aktiv astma ved 10 års alder hadde lavere lungefunksjon ved 10 års alder, men også allerede ved fødsel Håland G, Lødrup Carlsen KC, Sandvik L, Devulapalli CS, Munthe-Kaas M, Pettersen M, Carlsen KH. Reduced lung function at birth increases risk of asthma at 10 years of age. N Engl J Med 2006 Oct 19;355(16): Lung function follows clinical entity Sears et al, NEJM 349:1414 (2003) 3

4 Childhood asthma and risk of COPD Men Women OR P verdi OR P verdi Childhood asthma 10,48 (6,10-18,03) <0,001 3,74 (1,55-9,02) 0,003 smoking status: Heavy smoker (>20 sig./day) 3,70 (2,05-6,69) <0,001 3,82 (2,04-7,13) <0,001 Svanes et al, Thorax : London, December 1952 UUS, KCLC- B. Brunekreef,

5 Luftforurensning fra trafikk: Mange bestanddeler Hovedkomponenter: 1. No x : Hovedsaklig NO 2 og NO. Kilde: Hovedsaklig dieselmotorer 2. Svevestøv: Trafikk: Forbrenningspartikler (<2.5 μm -finfraksjon) (diesel-ekshaust) Karbonkjerne med tilheftede metaller, organiske forbindelser som PAH, soppsporer, allergener og bakterierester. Slitasjepartikler (>2.5 μm -grovfraksjon) (vegslitasje piggdekk) Vedfyring (vinter), langtransporterte partikler 3. Polysykliske aromatiske hydrokarboner (PAH) PAH i luft: Flere hundre meget fettløselige, mange bundet til svevestøv. All ufullstendig forbrenning av organisk materiale: kilde for PAH. Viktigste kilder til denne type luftforurensning: aluminiumsverk, biltrafikk og fyring med olje og ved. Meterologiske forhold: Inversjon om vinteren: Kalde temperaturer, lite vind. Forurensningselementene er tyngre enn luft og legger seg over bykjernen. Trafikkforurensning: Små partikler ga r sammen. Store partikler bidrar til a rense luften for de minste partiklene: Elektronmikroskopi: Svevestøv fra Oslo. En stor og e n litt mindre mørk (tett) mineralpartikkel mot drueklaselignende aggregater av små forbrenningspartikler fra diesel- eksos. ELEKTRONMIKROSKOPI: ELLEN NAMORK, NASJONALT FOLKEHELSEINSTITUTT. 5

6 Comparison of land-use regression models for predicting spatial NO x contrasts over a three year period in Oslo, Norway Atmospheric Environment; 45, (21) 2011, Study area with forest and parks (green), water (blue) and road network (grey lines). High traffic roads are marked with thicker grey lines. Fixed monitoring stations are marked with red circles. Traffic locations are marked with blue squares, while background locations are marked with blue triangles. The co-located sampling with a fixed monitoring station is marked with a yellow circle. Scatter plots of NOx, NO2 and NO at the 69 sampling locations with the linear regression line (dotted line): (A) Comparison between measured concentrations in 2005 and 2008 (range R2 = ), (B) 2005-model predictions compared to 2008 measurements (range R2 = ), and (C) 2008-model predictions compared to 2005 measurements (range R2 = ). Outdoor air pollutants, including diesel exhaust and trafficassociated pollutants, represent a major risk for childhood immune dysfunction and allergic disease Two primary effects described: 1. Diesel exhaust act as an adjuvant enhancing the potency of allergen exposure. The clinically significant allergen threshold dose is reduced and/or produces more severe symptoms. 2. to alter the early-life immune system such that allergic responses are more likely. Diertert,R.R. et al, Birth Defects Res (Part B) 83: ,

7 Diesel Exhaust and Asthma: Hypotheses and Molecular Mechanisms of Action Pandya et al: Environ Health Perspect 110(suppl 1): (2002). DEPs: Abundant evidence cause biologic responses that are related to asthma. associated with the inflammatory and immune responses involved in asthma? underlying molecular mechanisms DEPs alone may IgE, trigger eosinophil degranulation stimulate release of cytokines and chemokines. play a role in unleashing the cytotoxic effects of free radicals in the airways. All: produce airway inflammation, bronchial smooth muscle contraction, serum leakage, and mucus production, thereby resulting in the clinical symptoms of asthma. appear to have a far greater impact as an adjuvant with allergens than it has alone. Luftforurensning diesel eksos (DE) DE årsak til opp til % av partikler med median str. 10 µm i London 14 voksne atopisk astma Daglig IHGCS ( mcg) 1 t. Eksponering til diesel Nordenhåll et al, Eur Resp J

8 Residential Outdoor Air Pollution and Lung Function in Schoolchildren : spirometry performed in year-old children who had lived in Oslo, Norway, since birth. Outdoor air pollution exposure for each child assessed by the EPISODE dispersion model, calculating hourly concentrations of NO2, PM10, PM 2.5 Early and lifetime exposures to outdoor air pollution were associated with reduced PEFR and reduced FEF25 and FEF50, especially in girls. One interquartile increase of lifetime exposure to NO2, PM10, and PM2.5 was associated with change in adjusted PEFR of, respectively, 79 ml/s (95% CI 128 to 31), 66 ml/s (110 to 23), and 58 ml/s (94 to 21). Oftedal,B. et al, Epidemiology 2008;19: ) Epigenetikk Hvordan miljøet direkte påvirker våre gener Høye nivåer av CD14 beskytter mot allergi utvikling Nivåer styres bl.a. av eksponering for infeksjoner og gener. DNA i gener kan inaktiveres ved metylering. Dette kan skyldes miljøpåvirkning I Miljø barne astma undersøkelsen øker metylering fra fødsel til 2 års alder og videre til 10 års alder. Kan være årsaksfaktor til den økte allergiforekomst Methylation of CPG islands of CD14 genes Munthe-Kaas MC et al. J Allergy Clin Immunol Jun;125(6):

9 Methylation (%) Methylation (%) Inhaled Diesel Exhaust Particles and Allergen Exposure Alter Methylation of T Helper Genes and IgE Production In Vivo BALB/c mice were exposed to a 3-week course of inhaled DEP exposure while undergoing intranasal sensitization to A. fumigatus. Total IgE production was increased following intranasal sensitization A. fumigatus. IgE production was augmented further following combined exposure to A. fumigatus and DEP exposure. Inhaled DEP exposure and intranasal A. fumigatus induced hypermethylation at CpG245, CpG253, CpG2205 sites of the IFNg promoter and hypomethylation at CpG2408 of the IL-4 promoter. Altered methylation of promoters correlated significantly with changes in IgE levels. Liu J. et al. TOXICOLOGICAL SCIENCES 102(1), (2008) Level of IFN-c methylation correlates with IgE production. Methylation level at each CpG site was plotted versus IgE level among mice that underwent sensitization to A. fumigatus in the absence or presence of DEP exposure. *p < 0.05 two tailed, Rank order correlation; **p < 0.05 one tailed, Rank order correlation. Maternal Exposure to Polycyclic Aromatic Hydrocarbons and 5 -CpG Methylation of Interferon-γ in Cord White Blood Cells Methylation status of the IFNγ promoter was evaluated in cord white blood cells from 53 participants in the Columbia Center for Children s Environmental Health cohort. Maternal PAH exposure was estimated by personal air monitoring during pregnancy. Methylation percent versus PAH in region 1 Maternal exposure to PAHs was associated with promoter hypermethylation of IFNγ in cord blood DNA from cohort children. Methylation percent versus PAH in region 2 Tang W-y et al. Environ Health Perspect 120: (2012) 9

10 Exercising in Hyde Park vs Oxford Street McCreanor J. et al New Engl J Med 2007;357: adults: mild or moderate asthma walked for 2 hours on Oxford Street and, on a separate occasion, in a nearby park (Hyde Park) in a randomized manner. The exposure was significantly higher to fine particles (<2.5 μm), ultrafine particles, elemental carbon, and NO2 on Oxford Street than in Hyde Park. Walking for 2 hours on Oxford Street induced asymptomatic but consistent reductions in FEV1 (up to 6.1%) and FVC (up to 5.4%), significantly larger than after Hyde Park (P = 0.04 and P = 0.01), Asthma in exercising children exposed to ozone: a cohort study 3535 children with no history of asthma, recruited from schools in 12 communities in so-cal, followed for up to 5 years. 265 children reported new asthma diagnosis. Children participated in sports with high metabolic indices, (basketball, football, soccer, swimming, and tennis), low metabolic indices, (baseball, softball, and volleyball), and other sports. 3 (n=16) 2 (n=14) 1 (n=36) 0 (n=55) High PM communities. Relative risk for new asthma according to number of team sports RR (95% C.I.) 10

11 Living in proximity to major traffic roads and asthma, employing GIS Cohort studis PIAMA, The Netherlands (Brauer M et al, Europe Respir J : 2007; 29: ). Birth cohort of 3538 children at 4 years of age. Using GIS systems. Address were estimated by land-use regression models. High-traffic roads within 250 m, major road within 50m and housing density within 300m for home address at birth) could explain 73, 81 and 85% of the variability in annual average PM2.5, soot and NO2, respectively. One IQR increase in NO2 (10.6m g/m3 ) associated with a 19% [95% CI), ] and 28% (95% CI, ) increased risk of wheeze and doctor-diagnosed asthma PIAMA, The Netherlands at 8 years, 3,863 children: Gehring U et al, Am J Respir Crit Care Medl 181. pp , 2010 Individual exposures to NO2, PM2.5, and soot at the birth. PM2.5 levels were associated with a significant increase in incidence of asthma (OR, 1.28;95% CI, ), prevalence of asthma (OR, 1.26; 95% CI, ), and prevalence of asthma symptoms (OR, 1.15; 95% CI, ). Findings were similar for NO2 and soot. Associations were stronger for children who had not moved since birth. Positive associations with hay fever were found in nonmovers South California, 4762 children, 5-7 years old: McConnell R. et al, Environ Health Perspect 2010; 118 (7): Cohort of 2,497 kindergarten children followed for 3 years. Traffic-related pollution exposure based on a line source dispersion model of traffic volume, distance from home and school, and local meteorology. Regional ambient ozone, nitrogen dioxide (NO2), and particulate matter measured continuously at one central site monitor in each of 13 study communities. Asthma risk increased with modeled traffic-related pollution exposure from roadways near homes [Hazard ratio (HR) 1.51; 95% confidence interval (CI), ] and near schools (HR 1.45; 95% CI, ). Ambient NO2 measured at a central site in each community was also associated with increased risk (HR 2.18; 95% CI, ). Effect of exposure to traffic on lung development from 10 to 18 years of age: a cohort study Gauderman WJ et al, Lancet 2007; 369: children from10-18 years participated from 12 So-Cal communities. Yearly lung-function. Children living within 500 m of a motorway had deficits in 8-year growth of FEV1: 81 ml, p=0.01 and MMEF: 127 ml/s, p=0.03, compared with children living at least 1500 m from a freeway. Pronounced deficits in lung function at age 18 years for those living within 500 m of a freeway, with mean %pred. 97.0% for FEV1 (p=0.013, relative to >1500 m and 93.4% for MMEF (p=0.006). 11

12 Norsk vs svensk eksponering for NO2. B. Forsberg 1997 (svart strek: daglig irriterende luftforurensning.): Bo-område I storby, sterkt trafikkert, beboere Bo-område, lite til middels trafikkert, beboere Scenarios for development of traffic air pollution in Oslo ; NO 2 μg/m 3. Bidrag fra dieselbiler og mulige tiltak. Sundvor I. et al, Norsk Institutt for Luftforskning OR 62/2011 ISBN: (trykt) (elektronisk) NILU 12

13 Impact of Changes in Transportation and Commuting Behaviors During the 1996 summer Olympic Games in Atlanta on Air Quality and Childhood Asthma Friedman MS et al, JAMA. 2001;285(7): Ecological study comparing 17 days of Olympic Games to a baseline period 4 weeks before and after the Olympics, Children 1-16 years. During the Olympic Games, number of asthma acute care events decreased 41.6% (4.23 vs 2.47 daily events) in the Georgia Medicaid claims file, 44.1% (1.36 vs 0.76 daily events) in a health maintenance organization database, 11.1% (4.77 vs 4.24 daily events) in 2 pediatric emergency departments, and 19.1% (2.04 vs 1.65 daily hospitalizations) in the Georgia Hospital Discharge Database. Peak daily ozone concentrations decreased 27.9%, from 81.3 ppb during the baseline period to 58.6 ppb during the Olympic Games (P<.001). Peak weekday morning traffic counts dropped 22.5% (P<.001). Traffic counts were significantly correlated with that day's peak ozone concentration (average r = 0.36 for all 4 roads examined). Air pollution in Beijing during the Olympics 2008 PM10 Data from BBC 300 PM10 Beijing 250 PM10 = Particles below 10 μm WHO rec. 0 13

14 Those who do not make time for exercise will eventually have to make time for illness The Earl of Derby,