Protective Mechanisms of the Airways in COPD: New Insights into Environmental Resilience

COPD is one of the most common lung diseases worldwide and is strongly linked to environmental factors. Identifying new protective mechanisms against environmental nanoparticles could be crucial for developing targeted therapies and prevention strategies. A research team led by scientists from the German Center for Lung Research (DZL) at the Comprehensive Pneumology Center Munich (CPC-M) has gained important new insights into the effects of pollution on the airways and their role in chronic obstructive pulmonary disease (COPD). The research sheds light on previously poorly understood protective mechanisms of the airways against environmental nanoparticles, both in healthy and diseased individuals.

The bronchial epithelium, which lines the bronchi, is responsible for the self-cleaning of the airways. Ciliated cells with fine hair-like structures and mucus-producing cells ensure that foreign particles are transported out of the airways. This so-called bronchial epithelium forms an essential barrier against the entry of toxic substances into the airways. Environmental pollutants burden the epithelium and impair lung health, especially in individuals with COPD, where the regenerative capacity of the epithelium is already depleted.

A team led by DZL scientists PD Dr. Anne Hilgendorff and Dr. Mircea Gabriel Stoleriu has for the first time documented how common environmental pollutants affect the function and regeneration of the bronchial epithelium. They analyzed cells from the bronchi of patients with advanced COPD (COPD-IV), early-stage disease (COPD-II), and healthy individuals. The cells were exposed to carbon and zinc oxide nanoparticles and then characterized with numerous tests.

The researchers found that cells from healthy individuals were significantly more damaged by the nanoparticles than cells from patients with severe COPD. Even at higher doses of pollutants, cells from COPD patients remained better protected.

More Mucus and Fewer Cilia

Further investigations revealed that the bronchial epithelium of patients with advanced COPD contains cell types that produce more mucus and have fewer cilia. These changes make the cells more resilient to the nanoparticles. Similar changes were already observed in patients at an early stage of COPD when exposed to cigarette smoke.

Significantly Altered Gene Activity in Precursor Cells

In so-called basal cells of patients with advanced COPD, certain genes are more active than in the basal cells of healthy individuals. Basal cells are located deep in the epithelium and can develop into specialized cells, such as ciliated cells or mucus-producing goblet cells. The altered gene activity was particularly evident in precursor cells of specialized airway cell types.

The researchers conclude that the stage-specific gene changes observed in COPD influence the composition of cells in the bronchial epithelium and could regulate protective mechanisms against pollution in COPD patients. The new findings provide valuable information for the development of treatment and prevention strategies and represent a significant advance in the understanding of COPD.

Original Publication: Stoleriu MG, Ansari M, Strunz M, et al. COPD basal cells are primed towards secretory to multiciliated cell imbalance driving increased resilience to environmental stressors. Thorax. 2024;79(6):524-537. Published 2024 May 20. doi: 10.1136/thorax-2022-219958.