GRIAC doing well in the ZonMW Open Competition grants

Marieke will investigate respiratory muscles in end-stage lung disease in the Re-MAP study, while Barbro will investigate if inhalable microplastics can contribute to the development of lung cancer.

Respiratory Muscles in end-stage lung disease: PAthophysiological Processes & clinical consequences (Re-MAP)

 In patients with chronic lung diseases, the role of respiratory muscle dysfunction has been underestimated. Also, current treatment options, like chronic NIV and lung transplantation (LTx), might also have deleterious effects on the respiratory muscles, and the mechanisms are poorly understood. Therefore in this exploratory study the objectives are to:

• Determine in vivo respiratory muscle function and progression of respiratory muscle dysfunction in end-stage COPD patients
• Establish the correlation between changes in the structure and contractility of respiratory myofibers and in vivo respiratory muscle function.
• Establish the effect of chronic NIV on structure and contractility of respiratory muscle fibers
• Determine whether the structure and contractility of respiratory muscles cells at the time of LTx predicts clinical recovery post-LTx.

The study will be an exploratory observational cohort study following patients on the LTx waiting list during the waiting period and afterwards until they showed functional recovery of respiratory muscle function.

We will assess clinical functioning of the respiratory muscles and relate and correlate these findings to in-vitro assessment of  individual respiratory myofibers, individual myofiber functioning (strength, calcium sensitivity, myofiber characteristics) and extracellular matrix characteristics, which will be retrieved from biopsies taken during LTx surgery.

The proposed collaboration of basic (AmsterdamUMC; UMCG) and clinical scientists (RadboudUMC; ErasmusMC; UMCG) offers a unique opportunity to combine non-invasive functional assessments of respiratory muscles with advanced pathophysiological analyses using tissue biopsies obtained from severe COPD patients during LTx.

Interrogating microplastics as an environmental driver of lung cancer origin

Microplastic pollution is an urgent global health issue, permeating our oceans, air, soil, and even living organisms. These particles, typically smaller than 5 millimeters, arise from sources like synthetic textiles and degraded plastics and have become widespread environmental contaminants. Their minute size facilitates easy inhalation or ingestion, leading to potential exposure with serious health implications, particularly concerning lung health. Research has identified microplastics in human lung tissue and in both indoor and outdoor air, with higher concentrations indoors. The health risks are concerning as inhaling microplastics is linked to respiratory problems and lung cancer in industrial workers and could thus possibly contribute to cancerous nodule formation.

This research project aligns with the ZonMw Open Competitie program's goals by addressing the overlooked connection between environmental contaminants, such as microplastics, and lung cancer. Our multidisciplinary approach will investigate how microplastics may disrupt lung cell function and promote cancer, focusing on the interactions between epithelial and immune cells within the lung microenvironment. Using cutting-edge organoid models and in vivo systems, we will explore the epigenetic and functional changes triggered by microplastics, aiming to identify biomarkers and therapeutic targets. This could significantly influence public health policy and oncology treatment strategies.

Collaboration between the Melgert lab's (RUG) expertise in microplastics and lung cell biology, TNO’s expertise in and provision of well-characterised PVC and nylon particles, and the Prekovic lab's (UMCU) strength in omics and cancer biology provides a unique opportunity to uncover the cellular mechanisms by which microplastics may drive lung cancer development. By integrating these complementary fields, the project addresses ZonMw's emphasis on innovative research and tackles a critical but underfunded area of lung cancer influenced by environmental factors. The anticipated findings could open new avenues for understanding and mitigating the environmental drivers of lung cancer.