Quality over quantity: the importance of collecting relevant samples to understand complex diseases

Extract

Whole transcriptional studies investigating COPD have provided important insights into the development and progression of this complex disease. These have ranged from transcriptome studies on easily accessible samples like blood, induced sputum and nasal epithelial brushes [1], to those that are more invasive and difficult to collect, such as bronchial biopsies and brushes [2, 3], or lung tissue [4, 5], which usually requires tissue derived from transplant donors or lung cancer resection. Lung tissue is considered one of the most relevant samples to COPD due to the nature and location of parenchymal tissue destruction. However, the heterogeneity of the disease, not only between patients but also within a single individual, makes interpretation of the results more difficult. In the article by Feng et al. [6] in the current issue of the European Respiratory Journal, the authors show that the loss of terminal bronchioles in COPD occurs in so-called “hot spots”, which are areas with a linear mean intercept between 500 and 1000 µm. Transcriptional profiling of lung tissue from these hot spots using “regional transcriptomics” identified an 11 gene signature associated with upregulation of IFNG signalling, co-stimulatory immune checkpoint genes, and genes related to the inflammasome pathway. Regional transcriptomics is a method where multiple samples are taken from the same patient, and matching histology is collected from samples that are sequenced. This method allows for histological features to be linked to transcriptomic profiles and potentially helps to identify the genes and mechanism behind these features (figure 1a).