1. Long-term exposure to air pollution and asthma hospitalisations in older adults: a cohort study Zorana Jovanovic Andersen 27.09.2011 ERS Conflict of interest disclosure ‘I have no, real or perceived, conflicts of interest that relate to this presentation’

2. Asthma  Chronic inflammatory disease of the airways, characterized by variable and recurring symptoms, reversible airflow obstruction, hyperresponsiveness, bronchospasm.

3. Background  The prevalence of asthma in older adults is 6-10% in high- income countries, and increasing, including Denmark, where increase in the severity is also documented  The economic burden associated with hospital care, medications, and years of work lost is projected to escalate with increasing numbers of older people with asthma due to enhanced longevity

4. Background: Asthma & Air Pollution  Short-term exposure to elevated air pollution linked to exacerbation of asthma symptoms (wheezing, coughing, breathlessness) in children and adults, leading to asthma hospitalizations  More studies in children than adults: long-term exposure to air pollution in early life linked to development of asthma  Limited evidence in adults: does long-time/lifetime exposure to air pollution increases risk of asthma development in adult life?

5. Background: Asthma & Air Pollution Limitations: - asthma incidence and prevalence based on self-reports of asthma - losely defined onset, recall/info bias - short air pollution exposure windows

6. Aim of this study  We studied the association between traffic-related air pollution levels for up to 35 years at the residence and the risk for hospital admission for asthma in an elderly Danish cohort  We tested for an effect modification by lifestyle, education, and co-morbid conditions

7. Methods - Cohort  Danish Diet, Cancer and Health cohort  57 053 subjects, Copenhagen and Aarhus  Interviewed in 1993-1997 (baseline)  Age 50-65 years  Linkage to Central Population Registry and Danish Address Database - residential address history (1971)  Linkage to Danish National Patient Register (1979):  first-admission for asthma (ICD-10: J45-46), between baseline (1993-1997) and 27 June 2006  co-morbidities defined as hospitalizations for COPD (J40-44), ischemic heart disease (I20-25), and stroke (I60-63)

8. Methods – Air Pollution Exposure  AirGIS dispersion model, sum of: 1) regional background, 2) urban background, & 3) street level contribution  Input for AirGIS model  Street/building geometry  Street network and traffic data  Meteorology GIS Maps building height, street width, open sector Traffic counts, emission factors, density, speed, types, variation patterns over time

9. Methods – Air Pollution Exposure  AirGIS Model output:  Annual mean NO 2 /NO x concentrations at individual address Flow and dispersion inside a street canyon

10. Methods – Statistical Model  Cox proportional hazards model, left truncation at age at baseline, and right censoring at age at hospital admission for asthma, death, emigration, or 27 June 2006  NO 2 time-dependent variables, log transformed, mean since 1971 until asthma/censoring, estimates per IQR  Confounders: sex, smoking (status, intensity, duration, ETS), occupational exposures, BMI, educational level, fruit consumption  Effect modification: interaction term, Wald-test  Spline (rcs) in R, for dose-repsonse curve

11. Results: Study Population CohortAsthma 57 053 -571 cancer before baseline -962 missing address or geocode -1 236 missing address -589 missing info on covariates Original Cohort 53 695 Study Population977 (1.9%) 53 143 Asthma-free821 (1.5%) 552 Previous Asthma176 (31.9%)

12. Outcome: Asthma Hospitalization  Objective measure of asthma onset, nationwide register  Not marker of disease onset, but hallmark of asthma progression to a more severe stage or exacerbation  Traditionally confirmed by objective measurements of lung function and reversible airflow obstruction in Danish hospitals  The specificity of asthma as high as 0.98  Underestimates real asthma burden

13. Results: Descriptive Statistics

14. Results: Exposure to Air Pollution Median NO 2 for cohort 15.2 µg/m 3 and for asthmatics (n=977) 16.4 µg/m 3

15. Results: Main Analysis Excluding 452 subjects with prior COPD admissions: 1.11 (1.02-1.21) 1.10 (1.01-1.21) 1.29 (1.03-1.60)

16. Results: Effect Modification

17. Results: dose-response

18. Conclusions  The risk for asthma hospitalization in this elderly cohort was significantly positively associated with increasing levels of NO 2 assessed over 35 years at their residences  The risk for new asthma hospitalizations about 10% per IQR  The risk was most pronounced for people with a previous asthma 41% per IQR or COPD hospitalization 31% per IQR.

19. Limitation  No data on atopy, allergy, or familial history of asthma, important risk factors for asthma and potential effect modifiers  Lack of work address, activity pattern, indoor air pollution sources, which could have imporved air pollution exposure assesment

20. Acknowledgements  Thorax