Holding a donor lung instantly educates. The delicate nature of the organ leads to an understanding of its vulnerability to the environment and, at the same time, revealing its perfect tissue architecture. Our lungs do gas exchange in the blood capillaries, nourishing the body with vital oxygen. Our lives depend on sufficient lung function, and research on lung disease contributes significantly to the advancement of medicine.
Since 1977 the James Hogg Lung Biobank (JHLB) has been collecting a growing inventory of donor lung tissue and associated clinical data. This collection has made a significant contribution to science and the diagnosis of lung disease contributing to over 700 research publications to date with a current average of 10 per year. The acquisition of new donor specimens is ongoing with approximately 12 donations per year. One example is idiopathic pulmonary fibrosis, a rare and fatal disease with limited treatment options to slow its progression. The JHLB tissue samples provided to researchers at the HLI in recent years have led to high impact scientific publications related to the early stages of chronic obstructive pulmonary disease (COPD) and lung fibrosis.
Patient confidentiality is paramount in biobanking and all donors are assigned a 4-digit identifier when donating so that no identifying information is ever used past the time of donation and all donors become anonymous. Since we are often asked, let me tell you where the lungs come from and what happens when they arrive at our biobank.
Our donor lungs are sourced from several locations both within Canada and internationally; one of the more recent sources is the International Institute for the Advancement of Medicine. This respected organization provides non-transplantable human organs and tissues for research. Our collaboration with this organization has led to the collection of healthy lungs free of disease; these specimens are essential for research as they provide a control to compare with cases of lung disease. One example of a recent lung donation was the case of a man suffering from idiopathic pulmonary fibrosis who made the selfless decision to donate at end of life.
Whenever the biobank is notified that a lung may be available, we begin our preparations for receiving the organ. We work together as a team and upon arrival, graduate students will prepare to culture cells lining the inner airways. To collect the cells, they will take brushings of the bronchus, the large airway the leads to the right or left lungs. The cells can be cultured in a dish, allowing them to divide and grow, so that we can use them for future experiments. These cells can potentially be used to model the human airway epithelium for evaluating novel drugs. After taking the brushings, the lung can be further examined and processed.
As I prepare for the next steps in the preservation of the lung, I have the oversight and advice of a research associate, an expert in respiratory research and image analysis, who can spot every fine detail of my technique. This process helps ensure everything is done with precision and accuracy resulting in an optimal specimen for future research. We air-inflate the lung to a specific pressure through the main bronchus to preserve the natural tissue architecture of the organ. The lung is then frozen over liquid nitrogen vapor in its inflated state to allow for a controlled rate of freezing to optimize its preservation. Each step in this process is carefully documented with images.
Once a lung is frozen it will be scanned by computed tomography (CT), which allows us to obtain a detailed 3D map of the entire donated lungs. This step is important as in most cases disease is heterogenous; there are sites of disease and spared normal tissue throughout the lung. Lung function, such as airflow and gas exchange, can vary significantly across different regions of the lung as well. Specific sites of disease activity or tissue sparing can be selected for research.
Donor lungs can be stored indefinitely in ultracold freezers but are usually processed into individual tissue samples collected at specific sites in the lung. These samples are collected with precision using procedures developed over years in our biobank. Frozen lungs are sectioned and then cylindrical core samples are collected at sites determined by software developed at HLI. The dimensions of the core sample are selected to accommodate taking a thin section for mounting on a microscope slide. By randomly sampling the locations to image, we add to the statistical significance of future findings. Shown below is an image of a core sample taken from a whole lung:
Some selected lung tissue core samples will be further processed into formalin-fixed paraffin-embedded tissue blocks. These tissue blocks can be stored indefinitely at room temperature with preserved tissue morphology and cellular details for future research. These techniques allow for a wide array of analysis to be done on a small sample of lung tissue including the tissue structure and cellular composition, gene expression and proteins present in the tissue. With the imaging previously done with the donor lung specific sites of disease can be selected for study.
Historically most of our specimens were collected from lung surgeries preformed at St. Paul’s Hospital between 1977 and 2007. The most common surgery historically was a lung cancer resection; these patients most often have an additional diagnosis of COPD. The JHLB has collected tissue and associated clinical data from over 3000 patients to date, including the whole spectrum of lung disease. Before their surgeries most patients underwent lung function testing at which time the patient would be given a detailed interview regarding their full occupational history and past exposures to potential lung toxins. This information has given us an invaluable database of occupational exposures related to lung disease.
The technology and tools available to researchers have advanced exponentially in the last decade. We often release tissue samples for analysis using technology which did not exist at the time the lung was donated! The donations being received today could very well be used for research in the future using technology which currently does not exist. Donor lung tissue can also play an important role in the development of new drugs and treatments by studying how they interact with human tissue before a clinical trial.
Over 48 years the James Hogg Lung Biobank has had the opportunity to acquire specimens from rare lung diseases, and accumulated significant cohorts for diverse research. Examples of these cohorts include IPF, acute respiratory distress syndrome, cystic fibrosis and fatal asthma. The patients and families thinking of others in donating their organ or tissue for research are making an incredibly important contribution that will inevitably save lives in the future. A lung donation from a single IPF patient like the one described earlier may not seem significant but it is a contribution to a larger cohort that will undoubtedly have a major impact on our understanding of the disease and contribute to the development of new treatments.