Regenerating the lung – a multidisciplinary approach to combat COPD?

Overview

COPD is a progressive pulmonary disorder, especially amongst the elderly, presenting with largely irreversible airflow limitation, a result of chronic bronchitis and/or irreversible damage of the lung tissue (emphysema). COPD is the third leading cause of death worldwide. It affects more than 400-600 million people globally, killing over three million people per year, with no curative therapy currently available. The staggering socio-economic burden that comes with COPD treatment is now surpassing any other disease. Among 23 EU member states, the average prevalence is 15-20%, which increases with age. COPD is a heterogeneous disease encompassing multiple organs beyond the lungs. Both pulmonary and extrapulmonary pathology cause a high clinical and societal burden. COPD has long been considered a disease of smoking, but only a fraction of exposed individuals develop the disease, and 25-40% of COPD patients have never smoked. Ample evidence suggests vulnerability for COPD development stems from (epi)genetic risk factors and interaction with environmental exposure across the life course, as early as in childhood, aging of the global population, and poor dietary quality intake combined with sedentary behaviour. A major hurdle remains the identification of different disease endotypes, early detection and cellular and molecular mechanisms of early disease development. Despite the heterogeneity of the disease, diagnostic approaches have not markedly changed in decades and patients are not stratified according to condition, explaining therapy and clinical trial failure. To change this, we need a better understanding of pathophysiological mechanisms.

Here, a major chance lies in the international collaboration of basic, translational and clinical researchers, which is so far not well organized. To change this, a group of researchers, including the two seminar chairs, and spearheaded by Önder Yildirim, have recently established an international Advanced COPD Research Network.

The network´s primary focus is the advancement of translational COPD research by discussing ongoing projects, cutting-edge human in vitro models, state-of-the art systems biology approaches and clinical cohorts. By fostering new collaborations and ideas to transform our understanding of COPD, we aim to ignite novel research directions and therapeutic avenues thereby paving the way to eliminate COPD.

The network identified key areas for future COPD research that align with current priority topics of Assembly 3 (‘Cellular plasticity in lung regeneration’ ; ‘cell-cell interactions in lung physiology and disease’; ‘immune metabolic changes in lung disease’, ‘state of the art models to answer clinical questions’); Assembly 5 (priority topics: ‘No cell is an island – clinical implications of immunological crosstalk in the lung’); Assembly 7 (priority topics: ‘Prematurity related lung diseases’); Assembly 1 (Priority topics: ‘Functional lung imaging); and Assembly 14 (Priority topics: ‘Advances in thoracic imaging’).

The four key areas of the network are:

1. Endotyping of COPD cohorts
2. Systems biology
3. Immunity
4. Repair and regeneration

The goal of the COPD network is to contribute to regenerating COPD lungs, which is why key area four is focused on understanding the impaired repair and regeneration capacity. Imbalanced immunity likely impacts regenerative capacity, a novel concept which is of special interest to the network and will be a focus of this research seminar. We believe that the combination of expertise in the four different key areas will enable novel pathomechanistic understanding of the disease thereby facilitating the development of precision medicine approaches to cure COPD.

To initiate the necessary collaborations, we have started monthly online meetings with COPD researchers around the globe (134 participants). The kick-off meeting was 28 April, 2022, followed by 12 additional meetings consisting of two scientific presentations and discussions about further network development. The participants represent 12 different countries and encompass both early as well as senior researchers with backgrounds in biology, medicine, systems medicine, pharmacology, toxicology and epidemiology. To date, a total of three in-person meetings have been organised at the annual meetings of the European Respiratory Society (ERS) and American Thoracic Society, that were very well attended. In October 2023, the first COPD iNet symposium took place in Munich, addressing all four key areas. While those meetings generated initial ideas for novel joined avenues in COPD research, participants expressed the desire to organize longer in-person meetings to get a chance to establish personal connections and discuss key questions of regenerative approaches in COPD research in depth.

The proposed research seminar is supported by Assembly 1, 3, 5, 7 and 14, and will be critical in achieving this and bringing the network to the next level. One of the aims of this research seminar is to enhance the active interaction between clinical and basic/translational researchers with complimentary expertise in regeneration. The research seminar will include up-to-date cutting edge approaches to model COPD in all of the sessions. During this in-person research seminar, we aim to define key questions for the next years of COPD research as well as further steps for the Advanced COPD Network to develop.  

Objectives

The seminar aims to bring together experts from different disciplines (clinicians, epidemiologists, biologists, pharmacologists, pathologists), both members and non-members of the Advanced COPD Research Network to:

• Identify knowledge gaps in COPD research approached from a multidisciplinary perspective, focusing on regeneration.
• Define novel key questions on translational COPD research focusing on early disease pathogenesis and disease phenotypes/endotypes to enable regeneration.
• Strengthen and expand the existing COPD Research Network among leading global experts and early-career rising stars to support researchers at many levels.

Outcomes

• A state-of-the-art review article in the European Respiratory Journal, written by a group of early-career researchers attending the seminar under the guidance of experienced COPD researchers.
• A second educational-focused review for publication in Breath with a focus on residents in respiratory medicine written by clinical early-career researcher members, with the support of experienced researchers.
• A follow-up webinar on the ERS respiratory channel, organized by the research seminar chairs.
• The expansion of the Advanced COPD Research Network.