Publications by authors named "Manuela Funke-Chambour"

Background: Acute respiratory distress syndrome (ARDS) causes high mortality and has no specific pharmacological treatment. Scarcity of drugs against ARDS is in part due to the lack of models for ARDS. As raised serum heme levels are associated with higher mortality in patients with ARDS, we hypothesised that circulating heme contributes to ARDS pathology and can induce lung injury resembling human disease.

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Background: The coronavirus disease 2019 (COVID-19) outbreak revealed the susceptibility of elderly patients to respiratory virus infections, showing cell senescence or subclinical persistent inflammatory profiles and favoring the development of severe pneumonia.

Methods: In our study, we evaluated the potential influence of lung aging on the efficiency of replication of influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as determining the pro-inflammatory and antiviral responses of the distal lung tissue.

Results: Using precision-cut lung slices (PCLS) from donors of different ages, we found that pandemic H1N1 and avian H5N1 IAV replicated in the lung parenchyma with high efficacy.

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Background: Advances in the field of genetics of interstitial lung diseases (ILDs) have led to the recent consensus statements made by expert groups. International standards for genetic testing in ILD have not yet been established. We aimed to examine current real-world strategies employed by pulmonologists working with familial ILD.

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Introduction: Fibrotic cocktail (FC) is a combination of pro-fibrotic and pro-inflammatory mediators that induces early fibrotic changes in organotypic lung models. We hypothesised that transforming growth factor beta 1 (TGF-β1) alone induces a pro-fibrotic effect similar to FC. Our aim was to compare the pro-fibrotic effects of TGF-β1 with FC in human precision-cut lung slices (PCLS).

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In 2015, around 4400 individuals received a diagnosis of lung cancer, and Switzerland recorded approximately 3200 deaths related to lung cancer. Advances in detection, such as lung cancer screening and improved treatments, have led to increased identification of early-stage lung cancer and higher chances of long-term survival. This progress has introduced new considerations in imaging, emphasising non-invasive diagnosis and characterisation techniques like radiomics.

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Antifibrotic therapy with nintedanib is the clinical mainstay in the treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, provides quantitative insights into organ-scale pathophysiology, generating digital disease fingerprints. Here, we performed an integrative analysis of radiomic and proteomic profiles (radioproteomics) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to nintedanib in (experimental) fibrosing ILD.

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Background: Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process.

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Objectives: We aimed to assess the available evidence for corticosteroids in fibrotic interstitial lung disease (fILD) to inform the randomised embedded multifactorial adaptive platform ILD.

Design: Systematic review and meta-analysis.

Data Sources: We searched Embase, Medline, Cochrane CENTRAL and Web of Science databases from inception to April 17 2023.

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Pulmonary fibrosis (PF) encompasses a spectrum of chronic lung diseases that progressively impact the interstitium, resulting in compromised gas exchange, breathlessness, diminished quality of life (QoL), and ultimately respiratory failure and mortality. Various diseases can cause PF, with their underlying causes primarily affecting the lung interstitium, leading to their referral as interstitial lung diseases (ILDs). The current understanding is that PF arises from abnormal wound healing processes triggered by various factors specific to each disease, leading to excessive inflammation and fibrosis.

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Article Synopsis
  • High bacterial load in lung microbiota is linked to the progression of idiopathic pulmonary fibrosis (IPF), and azithromycin (AZT), a macrolide antibiotic, may influence lung microbiota positively in IPF patients.
  • A study involving 24 adults with IPF revealed that a 3-month AZT treatment significantly reduced community diversity in lung microbiota and changed the relationship between upper and lower airway microbiota.
  • Results indicated that AZT led to lasting alterations in the microbiota diversity and composition, affecting how the upper and lower airways interacted over time.
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  • Patients recovering from severe COVID-19 exhibited poorer lung function compared to those with non-severe cases after 12 months, specifically in measures like diffusion capacity and lung capacity.
  • While overall lung function improved for both groups over the year, the gap in lung performance between severe and non-severe cases narrowed over time.
  • Chest CT scans showed a correlation between lingering lung function issues and radiological abnormalities, with some patterns worsening even as other abnormalities reduced.
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  • The Omicron-BA.1 variant of concern became the dominant strain globally in early 2022, prompting the need for extensive research using primary cell cultures and animal models to understand its characteristics compared to the Delta variant.* -
  • In laboratory studies, Omicron-BA.1 showed increased early replication in human nasal cells but less replication in bronchial cells; however, in animal models like hamsters and ferrets, Delta variant remained more dominant.* -
  • The research revealed that the spike gene from Omicron-BA.1 leads to lower replication and pathogenicity in certain mice, while also indicating that this variant may escape immune responses generated by mRNA vaccines, contributing to its dominance over other variants.*
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Patients with progressive fibrosing interstitial lung diseases (fILD) have increased morbidity and mortality. Lung fibrosis can be associated with lung cancer. The pathogenesis of both diseases shows similarities, although not all mechanisms are understood.

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Article Synopsis
  • * In laboratory tests, DHEA showed the ability to lower pro-fibrotic markers without being toxic, and it influenced cell growth by changing the cell cycle and reducing G6PD activity.
  • * Low levels of DHEAS in patients with idiopathic pulmonary fibrosis and other fibrotic ILDs were linked to worse lung function and increased risk of early mortality, suggesting that DHEAS could serve as a potential biomarker for disease severity.
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Introduction: Post-COVID-19 syndrome affects approximately 10-25% of people suffering from COVID-19 infection, irrespective of initial COVID-19 severity. Fatigue is one of the major symptoms, occurring in 30-90% of people with post-COVID-19 syndrome. This study aims at describing factors associated with fatigue in people with Post-COVID-19 seen in our newly established Post-Covid clinic.

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Background: The Clinical Frailty Scale (CFS) is increasingly used for clinical decision making in acute care but little is known about frailty after COVID-19.

Objectives: To investigate frailty and the CFS for post-COVID-19 follow-up.

Methods: This prospective multicentre cohort study included COVID-19 survivors aged ≥50 years presenting for a follow-up visit ≥3 months after the acute illness.

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: Fibrosis in pulmonary Langerhans cell histiocytosis (PLCH) histologically comprises a central scar with septal strands and associated airspace enlargement that produce an octopus-like appearance. The purpose of this study was to identify the octopus sign on high-resolution computed tomography (HRCT) images to determine its frequency and distribution across stages of the disease. : Fifty-seven patients with confirmed PLCH were included.

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  • A study investigated the immediate impacts of electronic nicotine delivery systems (ENDS) and tobacco smoke on lung ventilation and perfusion using functional MRI and lung function tests, involving 44 healthy adults.
  • Results showed that lung perfusion decreased after END exposure but showed no significant change for tobacco smokers, while ENDS users experienced a slight increase in perfusion post-exposure.
  • The research highlights the need for more evidence on the short-term effects of ENDS versus tobacco smoke on lung function.
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Article Synopsis
  • - Sarcoidosis is a systemic inflammatory disease marked by granulomas that form due to unknown triggers in individuals with a genetic predisposition, affecting various organs with symptoms that can vary widely.
  • - The disease activates both the innate and adaptive immune systems, with the lungs, lymph nodes, skin, and eyes being the most commonly affected areas, while severe complications can involve the heart, kidneys, and nervous system, leading to higher morbidity levels.
  • - Treatment varies based on the severity and persistence of symptoms, ranging from topical therapies for mild cases to long-term immunosuppressive drugs for severe cases, requiring a multidisciplinary approach to manage organ-specific involvement and overall patient care.
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Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe complication associated with a high mortality. However, evidence and guidance on management is sparse. The aim of this international survey was to assess differences in prevention, diagnostic and treatment strategies for AE-IPF in specialised and non-specialised ILD centres worldwide.

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Introduction: Emerging evidence suggests that long-term pulmonary symptoms and functional impairment occurs in a proportion of individuals following SARS-CoV-2 infection. Although the proportion of affected patients remains to be determined, physicians are increasingly being confronted with patients reporting respiratory symptoms and impairment beyond the acute phase of COVID-19. In face of limited evidence, the Swiss Society for Pulmonology established a working group to address this area of unmet need and formulated diagnostic and treatment recommendations for the care of patients with pulmonary long COVID (LC).

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