Another step in COPD-endotyping:transcriptomic profiling of the host and respiratory microbiome

The work presented in this thesis comprises various chapters applyinggene expression profiling in bronchial biopsy and sputum samples for the molecularcharacterization of COPD patients. Based on these results, various conclusions canbe drawn: (1) RNA-Seq allows to study expression profiles of genes in much higherdetail compared to microarrays, but available microarray datasets could still beutilized to study bulk tissue deconvolution in lung biopsies, without the need to resequence samples. (2) Smoke-induced changes in the transcriptome of the bronchialmucus barrier might be reversible after 1-year smoking cessation in healthy andCOPD patients. (3) The sputum gene signature PRISE suggests that eosinophils andmacrophages as innate effector cells are associated with the likelihood to exacerbatein COPD patients after ICS withdrawal. PRISE might also be a better predictor forICS-response in COPD patients, compared to eosinophilia, however, this hypothesisneeds to be validated in independent cohorts. (4) The sputum microbiome exhibitsa promising potential to contribute to endotyping in COPD, but still faces importantlimitations and challenges on its path to becoming an important biomarker. (5)Investigating the microbiome in bronchial biopsy samples in stable COPD patientsusing RNA-seq, yields ultra-low levels of microbial biomass, indicating that otherlung specimens might be preferable to study the viable respiratory microbiome