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

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