Lung diseases that generally present with mucus obstruction and chronic airway inflammation, such as cystic fibrosis and COPD, could be triggered by the epigenetic reprogramming of airway macrophages (AM). A recent study led by a team of researchers from German Cancer Research Center (DKFZ) and German Center for Lung Research (DZL) at Heidelberg in Germany has for the first time identified that epigenetically controlled, differentially regulated pathways and transcription factors are involved in inflammatory responses and macrophage polarization. The mechanistic link of mucus obstruction and chronic airway inflammation in these lung diseases were not fully understood till now.  The new study, published in Nature on November 11, showed that mucostasis induces epigenetic reprogramming of airway macrophages, leading to changes favoring tissue damage and disease progression. Further research targeting these new findings can lead to novel therapeutic approaches in patients suffering from muco-obstructive lung diseases.