To date, influenza epidemics have been considered suitable for use as a model for the COVID-19 epidemic, given that they are respiratory diseases with similar modes of transmission. However, data ...directly comparing the two diseases are scarce.
We did a nationwide retrospective cohort study using the French national administrative database (PMSI), which includes discharge summaries for all hospital admissions in France. All patients hospitalised for COVID-19 from March 1 to April 30, 2020, and all patients hospitalised for influenza between Dec 1, 2018, and Feb 28, 2019, were included. The diagnosis of COVID-19 (International Classification of Diseases 10th edition codes U07.10, U07.11, U07.12, U07.14, or U07.15) or influenza (J09, J10, or J11) comprised primary, related, or associated diagnosis. Comparisons of risk factors, clinical characteristics, and outcomes between patients hospitalised for COVID-19 and influenza were done, with data also stratified by age group.
89 530 patients with COVID-19 and 45 819 patients with influenza were hospitalised in France during the respective study periods. The median age of patients was 68 years (IQR 52-82) for COVID-19 and 71 years (34-84) for influenza. Patients with COVID-19 were more frequently obese or overweight, and more frequently had diabetes, hypertension, and dyslipidaemia than patients with influenza, whereas those with influenza more frequently had heart failure, chronic respiratory disease, cirrhosis, and deficiency anaemia. Patients admitted to hospital with COVID-19 more frequently developed acute respiratory failure, pulmonary embolism, septic shock, or haemorrhagic stroke than patients with influenza, but less frequently developed myocardial infarction or atrial fibrillation. In-hospital mortality was higher in patients with COVID-19 than in patients with influenza (15 104 16·9% of 89 530 vs 2640 5·8% of 45 819), with a relative risk of death of 2·9 (95% CI 2·8-3·0) and an age-standardised mortality ratio of 2·82. Of the patients hospitalised, the proportion of paediatric patients (<18 years) was smaller for COVID-19 than for influenza (1227 1·4% vs 8942 19·5%), but a larger proportion of patients younger than 5 years needed intensive care support for COVID-19 than for influenza (14 2·3% of 613 vs 65 0·9% of 6973). In adolescents (11-17 years), the in-hospital mortality was ten-times higher for COVID-19 than for influenza (five 1·1% of 458 vs one 0·1% of 804), and patients with COVID-19 were more frequently obese or overweight.
The presentation of patients with COVID-19 and seasonal influenza requiring hospitalisation differs considerably. Severe acute respiratory syndrome coronavirus 2 is likely to have a higher potential for respiratory pathogenicity, leading to more respiratory complications and to higher mortality. In children, although the rate of hospitalisation for COVID-19 appears to be lower than for influenza, in-hospital mortality is higher; however, low patient numbers limit this finding. These findings highlight the importance of appropriate preventive measures for COVID-19, as well as the need for a specific vaccine and treatment.
French National Research Agency.
Haemoptysis is a serious symptom with various aetiologies. Our aim was to define the aetiologies, outcomes and associations with lung cancer in the entire population of a high-income country.This ...retrospective multicentre study was based on the French nationwide hospital medical information database collected over 5 years (2008-2012). We analysed haemoptysis incidence, aetiologies, geographical and seasonal distribution and mortality. We studied recurrence, association with lung cancer and mortality in a 3-year follow-up analysis.Each year, ~15 000 adult patients (mean age 62 years, male/female ratio 2/1) were admitted for haemoptysis or had haemoptysis as a complication of their hospital stay, representing 0.2% of all hospitalised patients. Haemoptysis was cryptogenic in 50% of cases. The main aetiologies were respiratory infections (22%), lung cancer (17.4%), bronchiectasis (6.8%), pulmonary oedema (4.2%), anticoagulants (3.5%), tuberculosis (2.7%), pulmonary embolism (2.6%) and aspergillosis (1.1%). Among incident cases, the 3-year recurrence rate was 16.3%. Of the initial cryptogenic haemoptysis patients, 4% were diagnosed with lung cancer within 3 years. Mortality rates during the first stay and at 1 and 3 years were 9.2%, 21.6% and 27%, respectively.This is the first epidemiological study analysing haemoptysis and its outcomes in an entire population. Haemoptysis is a life-threatening symptom unveiling potentially life-threatening underlying conditions.
Heat shock proteins (HSPs), also known as stress proteins, constitute a complex network of proteins highly conversed across species that have been classified into different families according to ...their molecular weight: HSP110, HSP90, HSP70, HSP60, HSP40 and the small HSPs 1. Although they are mainly known for their chaperone and cytoprotective properties, HSPs also participate in the regulation of many cellular signalling processes 2. These proteins have been involved in various physiological as well as pathological conditions, including respiratory diseases such as asthma, chronic obstructive pulmonary disease, sarcoidosis or pulmonary hypertension pathogenesis. HSPs have been extensively studied in the cancer field thanks to their regulatory role for several proteins involved in carcinogenesis. Stress proteins are often overexpressed in cancer cells, promoting phenotypic hallmarks of cancer such as cellular reprogramming, sustaining proliferative signalling, supporting replicative immortality, evading growth suppressor or resistance to cell death. Therefore, several studies have focused on the potential use of HSP inhibitors concomitantly with chemotherapy in cancer patients 3, 4. In particular, HSP90 has emerged as an important target in cancer and besides 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), the first inhibitor targeting HSP90 tested in a clinical trial in 1999, several inhibitors targeting HSP90 have been developed and are now being tested in humans 5.
Since 2009, IPF patients across Europe are recruited into the eurIPFreg, providing epidemiological data and biomaterials for translational research.
The registry data are based on patient and ...physician baseline and follow-up questionnaires, comprising 1700 parameters. The mid- to long-term objectives of the registry are to provide clues for a better understanding of IPF phenotype sub-clusters, triggering factors and aggravating conditions, regional and environmental characteristics, and of disease behavior and management.
This paper describes baseline data of 525 IPF subjects recruited from 11/2009 until 10/2016. IPF patients had a mean age of 68.1 years, and seeked medical advice due to insidious dyspnea (90.1%), fatigue (69.2%), and dry coughing (53.2%). A surgical lung biopsy was performed in 32% in 2009, but in only 8% of the cases in 2016, possibly due to increased numbers of cryobiopsy. At the time of inclusion in the eurIPFreg, FVC was 68.4% ± 22.6% of predicted value, DLco ranged at 42.1% ± 17.8% of predicted value (mean value ± SD). Signs of pulmonary hypertension were found in 16.8%. Steroids, immunosuppressants and N-Acetylcysteine declined since 2009, and were replaced by antifibrotics, under which patients showed improved survival (p = 0.001).
Our data provide important insights into baseline characteristics, diagnostic and management changes as well as outcome data in European IPF patients over time.
The eurIPFreg and eurIPFbank are listed in ClinicalTrials.gov( NCT02951416 ).
Purpose of review
Pleuroparenchymal fibroelastosis (PPFE) is a clinico-radiologic-pathologic interstitial lung disease (ILD) characterized by fibrosis that has upper lobe and subpleural predominance, ...involving both the visceral pleura and the subjacent subpleural lung parenchyma, and comprises dense fibroelastic changes with prominent elastosis of the alveolar walls together with fibrous thickening of the visceral pleura. The goal of this review is to summarize the state-of-the-art understanding in PPFE.
Recent findings
PPFE was described in an increasing number of conditions. The course of disease is heterogeneous. Idiopathic PPFE, cases associated with telomerase-related gene mutations, cases related to a history of chemotherapy, and cases combining PPFE with a pattern of usual interstitial pneumonia, may have a particularly poor prognosis. Well-conducted retrospective studies identified marked PPFE features in approximately 10% of patients with idiopathic pulmonary fibrosis, 11% of patients with systemic sclerosis-associated ILD, 6.5% of patients with rheumatoid arthritis-associated ILD, and 23% of patients with hypersensitivity pneumonitis. Drug therapy has not been evaluated prospectively. A small retrospective study suggests that nintedanib may slow disease progression. However, whether the efficacy of antifibrotics is comparable in PPFE and in other forms of progressive pulmonary fibrosis warrants further evaluation.
Summary
Accumulating data indicate that PPFE features are associated with poor prognosis in fibrosing ILDs. Further research on the management of PPFE is warranted.
Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the lung parenchyma, causing significant morbidity and mortality 1, 2. The therapeutic options in IPF are limited to only two recently ...approved drugs, pirfenidone and nintedanib, which have been shown to slow progression but are not able to stop or reverse the disease 3, 4. Better pathophysiological knowledge is needed to develop new therapeutic strategies in IPF. The current understanding of the disease is that fibroblastic foci, characterised by accumulation of myofibroblasts and overlying “activated” epithelium, represent “hot zones” of the disease and drivers of abnormal extracellular matrix (ECM) accumulation 5. Transforming growth factor (TGF)-β1 is a key cytokine involved in the process of fibrogenesis. TGF-β1 causes myofibroblast proliferation and differentiation and increases the synthesis of collagen, fibronectin and many other ECM components 5. The TGF-β1 signalling pathways are complex and occur essentially through serine/threonine kinase receptors, TGF-β receptors type I and II (TGF-βRI and TGF-βRII). TGF-βRII is constitutively active and activates TGF-βRI via phosphorylation upon ligand binding 6. The cytoplasmic proteins Smad2 and Smad3 predominantly mediate signals from activated TGF-β1 receptors. Activation of Smad2 and Smad3 via phosphorylation makes them bind to Smad4, promoting translocation to the nucleus where numerous TGF-β1-responsive genes are activated. TGF-β1 pathways are undoubtedly very promising but also challenging targets to treat fibrosis and in particular IPF.
Heat shock proteins (HSPs) are chaperones that catalyze the proper folding of nascent proteins and the refolding of denatured proteins. The ubiquitin-proteasome system is an error-checking system ...that directs improperly folded proteins for destruction. A coordinated interaction between the HSPs (renaturation) and the proteasome (degradation) must exist to assure protein quality control mechanisms. Although it still remains unknown how the decision of folding vs. degradation is taken, many pieces of evidence demonstrate that HSPs interact directly or indirectly with the proteasome, assuring quite selectively the proteasomal degradation of certain proteins under stress conditions. In this review, we will describe the different data that demonstrate a role for HSP90, HSP70, HSP27, and áB-crystallin in the partitioning of proteins to either one of these pathways, referred as protein triage.
Experimental models are critical for the understanding of lung health and disease and are indispensable for drug development. However, the pathogenetic and clinical relevance of the models is often ...unclear. Further, the use of animals in biomedical research is controversial from an ethical perspective.The objective of this task force was to issue a statement with research recommendations about lung disease models by facilitating in-depth discussions between respiratory scientists, and to provide an overview of the literature on the available models. Focus was put on their specific benefits and limitations. This will result in more efficient use of resources and greater reduction in the numbers of animals employed, thereby enhancing the ethical standards and translational capacity of experimental research.The task force statement addresses general issues of experimental research (ethics, species, sex, age,
and
models, gene editing). The statement also includes research recommendations on modelling asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung infections, acute lung injury and pulmonary hypertension.The task force stressed the importance of using multiple models to strengthen validity of results, the need to increase the availability of human tissues and the importance of standard operating procedures and data quality.
COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. ...The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19).
Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared.
COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1β concentrations.
CXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach.
ClinicalTrials.gov, NCT03955887.
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