The impact of the EVLP on the lung microbiome and its inflammatory reaction.

The pulmonary microbiome has emerged as a significant factor in respiratory health and diseases. Despite the sterile conditions maintained during lung perfusion (EVLP), the use of antibiotics in the perfuse liquid can lead to dynamic changes in the lung microbiome. Here, we present the design of a study that aims to investigate the hypothesis that EVLP alters the lung microbiome and induces tissue inflammation.

Relationship between Respiratory Microbiome and Systemic Inflammatory Markers in COPD: A Pilot Study.

The respiratory microbiome may influence the development and progression of COPD by modulating local immune and inflammatory events. We aimed to investigate whether relative changes in respiratory bacterial abundance are also associated with systemic inflammation, and explore their relationship with the main clinical COPD phenotypes. Multiplex analysis of inflammatory markers and transcript eosinophil-related markers were analyzed on peripheral blood in a cohort of stable COPD patients (n = 72).

Exploring the Interplay between Cellular Senescence, Immunity, and Fibrosing Interstitial Lung Diseases: Challenges and Opportunities.

Fibrosing interstitial lung diseases (ILDs) are characterized by the gradual and irreversible accumulation of scar tissue in the lung parenchyma. The role of the immune response in the pathogenesis of pulmonary fibrosis remains unclear. In recent years, substantial advancements have been made in our comprehension of the pathobiology driving fibrosing ILDs, particularly concerning various age-related cellular disturbances and immune mechanisms believed to contribute to an inadequate response to stress and increased susceptibility to lung fibrosis.

Pathophysiology and genomics of bronchiectasis.

Bronchiectasis is a complex and heterogeneous inflammatory chronic respiratory disease with an unknown cause in around 30-40% of patients. The presence of airway infection together with chronic inflammation, airway mucociliary dysfunction and lung damage are key components of the vicious vortex model that better describes its pathophysiology. Although bronchiectasis research has significantly increased over the past years and different endotypes have been identified, there are still major gaps in the understanding of the pathophysiology.

Treatable traits in pre-COPD: Time to extend the treatable traits paradigm beyond established disease.

To date, the treatable traits (TTs) approach has been applied in the context of managing diagnosed diseases. TTs are clinical characteristics and risk factors that can be identified clinically and/or biologically, and that merit treatment if present. There has been an exponential increase in the uptake of this approach by both researchers and clinicians.

Lung Tissue Multilayer Network Analysis Uncovers the Molecular Heterogeneity of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. We hypothesized that the unbiased integration of different COPD lung omics using a novel multilayer approach might unravel mechanisms associated with clinical characteristics. We profiled mRNA, microRNA and methylome in lung tissue samples from 135 former smokers with COPD.

Lung-function trajectories: relevance and implementation in clinical practice.

Lung development starts in utero and continues during childhood through to adolescence, reaching its peak in early adulthood. This growth is followed by gradual decline due to physiological lung ageing. Lung-function development can be altered by several host and environmental factors during the life course.

Epigenome-Wide Association Studies of Chronic Obstructive Pulmonary Disease and Lung Function: A Systematic Review.

Chronic obstructive pulmonary disease (COPD) results from gene-environment interactions over the lifetime. These interactions are captured by epigenetic changes, such as DNA methylation. To systematically review the evidence form epigenome-wide association studies related to COPD and lung function.

Clinical relevance of lung function trajectory clusters in middle-aged and older adults.

Background: The determinants and health outcomes of lung function trajectories in adults among the general population are poorly understood. We aimed to identify and characterise clusters of lung function trajectories in adults aged ≥45 years.

Methods: Gaussian finite-mixture modelling was applied to baseline and annualised change of forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and FEV/FVC ratio z-scores in participants of the Rotterdam Study, a prospective population-based cohort study, with repeated spirometry (n=3884; mean±sd age 64.

From treatable traits to GETomics in airway disease: moving towards clinical practice.

The treatable traits approach represents a strategy for patient management. It is based on the identification of characteristics susceptible to treatments or predictive of treatment response in each individual patient. With the objective of accelerating progress in research and clinical practice relating to such a treatable traits approach, the Portraits event was convened in Barcelona, Spain, in November 2022.

Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype.

Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report that cellular senescence, and multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron.

Lung immune signatures define two groups of end-stage IPF patients.

Background: The role of the immune system in the pathobiology of Idiopathic Pulmonary Fibrosis (IPF) is controversial.

Methods: To investigate it, we calculated immune signatures with Gene Set Variation Analysis (GSVA) and applied them to the lung transcriptome followed by unbiased cluster analysis of GSVA immune-enrichment scores, in 109 IPF patients from the Lung Tissue Research Consortium (LTRC). Results were validated experimentally using cell-based methods (flow cytometry) in lung tissue of IPF patients from the University of Pittsburgh (n = 26).

Blood Immunophenotypes of Idiopathic Pulmonary Fibrosis: Relationship with Disease Severity and Progression.

(1) The role of the immune response in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remains controversial. We hypothesized that peripheral blood immune phenotypes will be different in IPF patients and may relate to the disease severity and progression. (2) Whole blood flow cytometry staining was performed at diagnosis in 32 IPF patients, and in 32 age- and smoking-matched healthy controls.

Similarity network fusion to identify phenotypes of small-for-gestational-age fetuses.

Fetal growth restriction (FGR) affects 5-10% of pregnancies, is the largest contributor to fetal death, and can have long-term consequences for the child. Implementation of a standard clinical classification system is hampered by the multiphenotypic spectrum of small fetuses with substantial differences in perinatal risks. Machine learning and multiomics data can potentially revolutionize clinical decision-making in FGR by identifying new phenotypes.

Phenotyping asthma with airflow obstruction in middle-aged and older adults: a CADSET clinical research collaboration.

Background: The prevalence and clinical profile of asthma with airflow obstruction (AO) remain uncertain. We aimed to phenotype AO in population- and clinic-based cohorts.

Methods: This cross-sectional multicohort study included adults ≥50 years from nine CADSET cohorts with spirometry data (N=69 789).