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Bergen Respiratory Research Group

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Chronic lung diseases including COPD, asthma, interstitial lung disease, and lung cancer afflict over 20% of the adult population, leading to massive morbidity and mortality and is presenting a considerable health challenge.

The high prevalence of chronic lung diseases is a recent development. Although COPD has a clear cause in tobacco smoking, only 25% of smokers develop COPD, and the majority of ex-smokers will continue their disease progression after quitting. The current high prevalence of asthma is a phenomenon starting in the latter half of the 20th Century. Allergies were first described in the medical literature as late as 1903. Sarcoidosis was first described at the end of the 19th century, and in line with other ILDs, the prevalence appears to be increasing.

It has long been recognized that there is some element of systemic inflammation involved for nearly all the chronic lung diseases. Inflammatory markers are increased in the systemic circulation in afflicted patients. Looking at lung and airways biopsies from patients with different chronic lung diseases compared with healthy controls; three findings are striking:

1) There is invariably an element of local inflammation.

2) The inflammation varies distinctly for the different disease entities.

3) The inflammation resembles immune responses to different microorganisms.

High-throughput 16S rDNA sequencing has now consistently shown the presence of a diverse low-biomass bacterial microbiome in the lungs, contrary to the standard belief pre-2010 that the lower airways were sterile. Our research has proven the existence also of a fungal lower airway microbiome. The role of these microbiomes is yet unknown; however the immune system must control commensal microorganisms, and commensals must adapt to its host to survive. If bacteria or fungi not recognized by the immune system as beneficial get to dominate over time, persistent and harmful inflammation may follow.

We are researching the lower airways microbiome and its relation to chronic lung disease. Whereas other studies often employ indirect measurements of the lower airways - prone to contamination, we focus on true sampling of the lower airways with bronchoscopy.

Since 2013, at the outpatient clinic at the Department of Thoracic Medicine, Haukeland University Hospital, we have conducted the MicroCOPD study (249 participants) and the MicroILD study (70 participants) and started the pilot phase of the MicroLC study in August 2023. We have to date performed over 400 bronchoscopies with true lower airways sampling.

We have performed 16S rDNA, ITS and WGS sequencing, either in-house, or with our partners at Sequentia Biotech. Our protocols for sampling, DNA extraction and 16S rDNA sequencing are published.

Data from the MicroCOPD has so far led to three published PhD theses from: Martinsen, Drengenes,

Leiten.

We have a wealth of data available, and several PhD students and postdocs now work on data from these studies.