Effects of air pollution and greenness on asthma and allergy — over time and across generations
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Background: The prevalence of asthma and allergies have increased in the last decades, likely due to complex interaction of genes and environmental factors; however, causal pathways are still far from understood. Environmental factors like air pollution and greenness play a part, but the impact of relatively low levels of air pollution and greenness on the development of asthma and allergies throughout the lifespan and across generations has not been elucidated. When studying intergenerational risk factors, the use of reports on asthma across generations is essential. Before using such reports, however, it is important to validate them. Objectives: I) To determine the agreement between parental and offspring asthma reports in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study, and identify predictors of disagreement. II) To investigate the risk of adult asthma, rhinitis and low lung function after lifelong exposure to air pollution and greenness. III) To investigate the associations between parental childhood exposure to air pollution and greenness in relation to their future offspring asthma and rhinitis, and assess if the associations were direct effects or if they were mediated through parental asthma, pregnancy exposure to greenness/air pollution and offspring own exposure. Material and methods: I) Asthma reports from 6752 offspring and their 5907 parents from the RHINESSA study regarding themselves and each other were analysed. Cohen’s kappa, sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated to determine agreement. The participant’s own answers regarding themselves were defined as the gold standard. Logistic regression analyses were performed to identify predictors for disagreement. II) and III) Individual annual mean residential exposures to nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), black carbon (BC), ozone (O3) and greenness (normalized difference vegetation index (NDVI)) were calculated and averaged across the following susceptibility windows: Paper II (N = 3428): 0-10 years, 10-18 years, from birth until age of diagnosis, lifetime and year before study participation. Paper III (N = 1106 parents, 1949 offspring): parents 0-18 years and offspring 0-10 years. In paper II, logistic regression was performed for the outcomes asthma attack, rhinitis and impaired lung function (below lower limit of normal (LLN: z-score <1.64 SD)), while conditional logistic regression with a matched case-control design was performed for asthma (ever/allergic/non-allergic). In paper III, logistic regression and mediation analyses were performed for the outcomes offspring asthma and rhinitis. Results: I) Agreement of parental reports of offspring early (<10 years) and late (>10 years) onset asthma was good and moderate, respectively (Cohen’s kappa 0.72 and 0.46). Agreement of offspring reports of maternal and paternal asthma was good (Cohen’s kappa 0.69 and 0.68). For both parents and offspring, the most common disagreement was to report no asthma in asthmatic relatives rather than to report asthma in non-asthmatic relatives. Current smokers (odds ratio (OR) 1.46 95% confidence interval (CI) 1.05, 2.02) and fathers (OR 1.31 95% CI 1.08, 1.59) were more likely to report offspring asthma incorrectly. Offspring wheeze was associated with reporting parental asthma incorrectly (OR 1.60 95% CI 1.21, 2.11). II) Exposures to NO2, PM10 and O3 were associated with increased risk for asthma attacks (range ORs 1.29 to 2.25). Exposures to PM2.5 and O3 increased the risk for low lung function, in particular forced expiratory volume in one second (FEV1) (range ORs 2.65 to 4.21). Increased NDVI was associated with lower FEV1 and forced vital capacity (FVC) in all susceptibility windows (range ORs 1.39 to 1.74). III) Maternal exposures to PM2.5 and PM10 was associated with higher offspring asthma risk (OR 2.23 95% CI 1.32, 3.78; OR 2.27, 95% CI 1.36, 3.80) and paternal high BC exposure was associated with lower offspring asthma risk (OR 0.31, 95% CI 0.11, 0.87). Risk for rhinitis increased for offspring of fathers with medium O3 exposure (OR 4.15, 95%CI 1.28, 13.50) and mothers with high PM10 exposure (OR 2.66, 95% CI 1.19, 5.91). The effect of maternal PM10 exposure on offspring asthma was direct, while it for rhinitis was mediated through exposures in pregnancy and offspring’s own exposures. Paternal O3 exposure had a direct effect on offspring rhinitis. Conclusions: I) Agreement of self-reported asthma across generations in the RHINESSA study showed moderate to good agreement, although with some risk of under-report. II) Lifelong air pollution exposure was associated with asthma attacks, rhinitis and low lung function. Exposure to greenness was associated with low lung function. III) Parental air pollution exposures in their childhood were associated with increased risk of asthma and rhinitis in future offspring. Consequences: Exposure to air pollution and greenness impact numerous people. Further research is warranted to entirely understand the complex underlying interactions between air pollution and greenness and respiratory health. However, results from this PhD project suggest that existing air pollution limit values may be too high, and that exposures below the upper limit values may have harmful health effects. From a public health perspective, one should continuously strive for cleaner air, not only for today’s population, but also for the next generations.
Består avPaper I: Kuiper IN, Svanes C, Benediktsdottir B, Bertelsen RJ, Bråbäck L, Dharmage SC, Holm M, Janson C, Jögi R, Malinovschi A, Matheson M, Moratalla JM, Real FG, Sánchez-Ramos JL, Schlünssen V, Timm S, Johannessen A. Agreement in reporting of asthma by parents or offspring – the RHINESSA generation study. BMC Pulmonary Medicine (2018) 18:122. The article is available at: https://hdl.handle.net/1956/19661
Paper II: Kuiper IN, Markevych I, Accordini S, Bertelsen RJ, Bråbäck L, Christensen JH, Forsberg B, Halvorsen T, Heinrich J, Hertel O, Hoek G, Holm M, de Hoogh K, Janson C, Malinovschi A, Marcon A, Nilsen RM, Sigsgaard T, Svanes C, Johannessen A. Lifelong exposure to air pollution and greenness in relation to asthma, rhinitis and lung function in adulthood. Env Int (2021) 146, 106219. The submitted version is available in the thesis file. The published version is available at: https://doi.org/10.1016/j.envint.2020.106219
Paper III: Kuiper IN, Markevych I, Accordini S, Bertelsen RJ, Bråbäck L, Christensen JH, Forsberg B, Halvorsen T, Heinrich J, Hertel O, Hoek G, Holm M, de Hoogh K, Malinovschi A, Marcon A, Sigsgaard T, Svanes C, Johannessen A. Associations of preconception exposure to air pollution and greenness with offspring asthma and hay fever. Int. J. Environ. Res. Public Health 2020, 17, 5828. The article is available in the thesis file. The article is also available at: https://doi.org/10.3390/ijerph17165828