Atmen: Luftschadstoffe und Gesundheit – Teil III

Zusammenfassung

Der dritte Teil des DGP-Positionspapiers stellt den aktuellen Wissensstand zu bislang weniger untersuchten Gesundheitsgefährdungen durch Luftschadstoffe vor: gestörte Glukosetoleranz und Diabetes sowie neurodegenerative Erkrankungen und neurokognitive Entwicklung bei Kindern. Weiterhin wird die Bedeutung einer Exposition während der Schwangerschaft für Mutter und Kind beschrieben und abschließend in die derzeit diskutierten Mechanismen zur Erklärung der unterschiedlichen adversen Effekte von Luftschadstoffen eingeführt.

Verschiedene, sich oft ergänzende Pathomechanismen bilden die Grundlage für die unterschiedlichen, durch Luftschadstoffe bedingten Gesundheitseffekte. Oxidativer Stress und eine subklinische entzündliche Reaktion in der Lunge, aber auch auf systemischer Ebene („low-grade systemic inflammation“), stehen dabei im Mittelpunkt. Diese begünstigen sekundäre Veränderungen im Organismus wie vaskuläre oder metabolische Prozesse und können darüber hinaus zu epigenetischen Effekten oder zur „Neuroinflammation“ führen. Die Bedeutung von löslichen, systemisch verfügbaren Partikelbestandteilen aber auch die Translokation von ultrafeinen Partikeln aus der Lunge über die Blutbahn in sekundäre Zielorgane wie Leber, Gehirn oder den Fötus wird dabei intensiv diskutiert.

Diabetes mellitus ist eine der häufigsten chronischen Erkrankungen weltweit, mit einer Prävalenz von knapp 14 % in Deutschland. Bei dem mit großem Abstand häufigeren Typ 2-Diabetes mellitus spielen Lebensstilfaktoren bei der Genese eine wesentliche Rolle. Toxikologische und epidemiologische Studien legen darüber hinaus nahe, dass auch eine langfristige Luftschadstoffbelastung zu einem erhöhten Risiko v. a. für den Typ 2-Diabetes beitragen kann. Zusätzliche Hinweise für eine ursächliche Rolle liefern Studien zur Glukoseregulation, der Insulinsensitivität und dem Schwangerschaftsdiabetes. Ergebnisse experimenteller Studien unterstützen diese Zusammenhänge und zeigen plausible biologische Mechanismen auf. Jedoch sind zur Stärkung der gegenwärtigen Evidenz prospektive Studien mit Berücksichtigung multipler Lebensstil- und Umweltfaktoren wie Grünflächen oder Lärm und einer präziseren individuellen Abschätzung der Schadstoffbelastung notwendig.

Mit der Altersentwicklung in der Bevölkerung nimmt die Krankheitslast durch neurodegenerative Erkrankungen zu. Erste Studien weisen auf einen möglichen Beitrag durch Luftschadstoffe, v. a. durch Feinstaub, hin. So wird in einigen Studien bei einer erhöhten Schadstoffbelastung eine Abnahme der neurokognitiven Leistungsfähigkeit im Erwachsenenalter und ein erhöhtes Risiko für eine Demenz oder eine Alzheimer-Erkrankung beobachtet, jedoch sind die Studien in Bezug auf Design, Expositionsabschätzung und Gesundheitseffekt noch inhomogen und die Studienergebnisse insgesamt gesehen noch inkonsistent. In Bezug auf die neurokognitive Entwicklung im Kindesalter beschreiben erste Studien einen Zusammenhang zwischen dem Grad der Luftverschmutzung, z. B. an der Schule, und einer verzögerten kognitiven Entwicklung.

Auch wenn die Evidenz für die verschiedenen biologischen Endpunkte während der Schwangerschaft noch sehr heterogen ist, weisen die Studien insgesamt auf einen negativen Einfluss der Luftschadstoffe auf den mütterlichen und fetalen Organismus hin. Die stärkste Evidenz liegt für ein verringertes Geburtsgewicht im Zusammenhang mit erhöhten Luftschadstoffen vor, allerdings mit relativ niedriger Effektgröße von im Mittel nur wenigen Gramm. Darüber hinaus kommt es zu einer erhöhten Häufigkeit von zu geringem Geburtsgewicht (< 2500 g). Eine mögliche Beeinflussung des mütterlichen Organismus durch die Schadstoffbelastung wird durch ein erhöhtes Risiko für Schwangerschaftsbluthochdruck und Präeklampsie verdeutlicht. Der Einfluss einer intrauterinen Exposition auf die frühkindliche Lungenfunktion und die Entstehung allergischer Erkrankungen ist derzeit nicht eindeutig, für diese Endpunkte fällt auch die Differenzierung zwischen intrauterinen und postnatalen Effekten in epidemiologischen Studien schwer.

Abstract

The third part of the DGP statement introduces the current body of knowledge on less studied health outcomes associated with exposure to ambient air pollution: the negative impact on metabolism leading to impaired glucose tolerance and diabetes as well as contribution to the development of neurodegenerative disorders and delayed cognitive function in children. Furthermore, prenatal exposure and adverse effects on mother and child are addressed. Finally, the currently discussed biological mechanisms underlying various health effects associated with exposure to air pollution are described.

Differing, but often complementary biological mechanisms create the basis for the diverse health outcomes caused by air pollution. Oxidative stress and a subclinical inflammatory response in the lungs and on a systemic level (“low-grade systemic inflammation”) are considered to be key mechanisms. They promote secondary alterations in the body, such as vascular or metabolic processes, and may also result in the currently studied epigenetic phenomena or neuroinflammation. In this context, the health significance of soluble particulate matter and the role of ultrafine particles translocated across biological membranes into blood vessel and transported via the circulation to secondary target organs, such as liver, brain or the fetus, are intensively discussed.

Diabetes is one of the leading chronic diseases worldwide, with a prevalence of almost 14 % in Germany. Although lifestyle factors are the main causes, current evidence suggests that long-term exposure to air pollution may additionally increase the risk for type 2 diabetes. Supporting evidence for a causal role of air pollution is provided by studies addressing the regulation of the blood glucose levels in metabolically healthy participants, insulin sensitivity, or pregnancy-related diabetes. Experimental studies provide further support for plausible biological mechanisms. However, prospective studies are needed to gain more evidence, taking multiple lifestyle and environmental factors, such as green space and noise, and an improved individual exposure assessment into account.

The aging population has an increased risk of neurodegenerative diseases. First studies point towards a contribution of chronic exposure to air pollution, specifically by particulate matter. Several studies report its association with decreased neurocognitive capacity or an increased prevalence of dementia or Alzheimer’s disease in adults. However, the studies are inhomogeneous regarding design, exposure and outcome, leading to inconsistent results. With respect to the influence on neurocognitive development of children, first studies suggest an association between the level of air pollution, e. g. at school, and delayed cognitive development.

Even though the evidence for the different biological endpoints during pregnancy is still heterogeneous, the studies generally point towards an adverse impact of air pollution on the maternal and fetal organisms. The strongest evidence exists for low birth weight, with small effect sizes of only some grams, and for a higher incidence of reduced birth weight (< 2500 g). An increased risk for gestational hypertension and preeclampsia underscores the possible impact of exposure to air pollution on the maternal organism. However, the current body of evidence does not yet allow a final conclusion on the influence of intrauterine exposure to air pollution regarding early childhood lung function and development of allergies, particularly in light of the fact that it is hard to distinguish in epidemiological studies between the effects of pre- and postnatal exposure.

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