Neutrophils are important in the pathophysiology of coronavirus disease 2019 (COVID-19), but the molecular changes contributing to altered neutrophil phenotypes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We used quantitative mass spectrometry-based proteomics to explore neutrophil phenotypes immediately following acute SARS-CoV-2 infection and during recovery.
Prospective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May to December 2020). Patients were enrolled within 96 h of admission, with longitudinal sampling up to 29 days. Control groups comprised non-COVID-19 acute lower respiratory tract infection (LRTI) and age-matched noninfected controls. Neutrophils were isolated from peripheral blood and analysed using mass spectrometry. COVID-19 severity and recovery were defined using the World Health Organization ordinal scale.
Neutrophil proteomes from 84 COVID-19 patients were compared to those from 91 LRTI and 42 control participants. 5800 neutrophil proteins were identified, with >1700 proteins significantly changed in neutrophils from COVID-19 patients compared to noninfected controls. Neutrophils from COVID-19 patients initially all demonstrated a strong interferon signature, but this signature rapidly declined in patients with severe disease. Severe disease was associated with increased abundance of proteins involved in metabolism, immunosuppression and pattern recognition, while delayed recovery from COVID-19 was associated with decreased granule components and reduced abundance of metabolic proteins, chemokine and leukotriene receptors, integrins and inhibitory receptors.
SARS-CoV-2 infection results in the sustained presence of circulating neutrophils with distinct proteomes suggesting altered metabolic and immunosuppressive profiles and altered capacities to respond to migratory signals and cues from other immune cells, pathogens or cytokines.
Pulmonary embolism (PE) is a condition in which thrombus, usually embolised from the veins of the pelvis or lower limbs, obstructs the pulmonary arterial vascular bed. The incidence of PE is estimated at 60–70 per 100 000 per year [1] with a 1-year mortality of 15% [2, 3]. In survivors, patency of the pulmonary vasculature is restored, in most patients, within the first few months [4]. However, pulmonary emboli may not resolve and patients may also develop a chronic obstructing microvasculopathy [5, 6].
]]>Our objective was to investigate the effect of a day-long exposure to high altitude on peak exercise capacity and safety in stable patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).
In a randomised controlled crossover trial, stable patients with PAH or distal CTEPH without resting hypoxaemia at low altitude performed two incremental exercise tests to exhaustion: one after 3–5 h at high altitude (2500 m) and one at low altitude (470 m).
In 27 patients with PAH/CTEPH (44% females, mean±
Among predominantly low-risk patients with stable PAH/CTEPH, cycling exercise during the first day at 2500 m was well tolerated, but peak exercise capacity, blood oxygenation and ventilatory efficiency were lower compared with 470 m.
Prognosis and disease severity in cystic fibrosis (CF) are linked to declining lung function. To characterise lung function by the number of adults in countries with different levels of Gross National Income (GNI), data from the European Cystic Fibrosis Society Patient Registry were utilised.
Annual data including age, forced expiratory volume in 1 s (FEV1), anthropometry, genotype, respiratory cultures and CF-related diabetes (CFRD) were retrieved between 2011 and 2021. All countries were stratified into GNI per capita to reflect differences within Europe.
A consistent improvement in FEV1 % pred and survival was observed among the 47 621 people with CF (pwCF), including subjects with chronic Pseudomonas aeruginosa infection, CFRD and/or undernutrition. Mean values of FEV1 % pred changed from 85% to 94.2% for children and from 63.6% to 74.7% for adults. FEV1 % pred further increased among those carrying the F508del mutation in 2021, when elexacaftor/tezacaftor/ivacaftor was available. The number of adult pwCF increased from 13 312 in 2011 to 21 168 in 2021, showing a 60% increase. PwCF living in European lower income countries did not demonstrate a significant annual increase in FEV1 % pred or in the number of adults.
This pan-European analysis demonstrates a consistent improvement in FEV1 % pred, number of adult pwCF and survival over the last decade only in European higher and middle income countries. Urgent action is needed in the lower income countries where such improvement was not observed. The notable improvement observed in pwCF carrying the F508del mutation emphasises the need to develop treatments for all CF mutations.
The enzyme leukotriene A4 hydrolase (LTA4H) is classically known for its epoxide hydrolase activity that converts leukotriene A4 (LTA4) to the neutrophil chemoattractant LTB4 [1]. In 2010, our group published a study in Science that demonstrated that during an influenza model of acute airway inflammation, LTA4H was released from cells to degrade proline-glycine-proline (PGP), a non-canonical CXCR1 and -2 agonist of polymorphonuclear neutrophil (PMN) recruitment and activation [2], thereby attenuating PMN inflammation [3].
]]>Over half of all cases of obstructive sleep apnoea (OSA) are classified as supine-related OSA; however, the pathological endotype during supine position is not fully understood. This study aims to investigate the endotypic traits of supine-predominant OSA and explore the variations in endotypic traits between the supine and lateral positions.
We prospectively recruited 689 adult patients with OSA from a single sleep centre between April 2020 and December 2022. Endotypic traits, namely arousal threshold, collapsibility, loop gain and upper airway muscle compensation, were retrieved from polysomnographic signals. We identified spOSA by a supine to non-supine apnoea–hypopnoea index (AHI) ratio >2. We cross-sectionally compared demographic and endotypic traits between supine-predominant OSA and non-positional OSA and examined the associations between supine-predominant OSA and endotypic traits. Additionally, we compared the changes in endotypic traits between supine and lateral positions in patients with supine-predominant OSA and non-positional OSA.
In our study sample, 75.8% of patients were identified as having supine-predominant OSA. Compared to non-positional OSA, supine-predominant OSA was associated with low collapsibility (β= –3.46 %eupnoea, 95% CI –5.93– –1.00 %eupnoea) and reduced compensation (β= –6.79 %eupnoea, 95% CI –10.60– –2.99 %eupnoea). When transitioning from the lateral to supine position, patients with supine-predominant OSA had a substantial decrease in compensation compared to those with non-positional OSA (–11.98 versus –6.28 %eupnoea).
Supine-predominant OSA is the prevalent phenotype of OSA in Asian patients. Inadequate upper airway compensation appears to be a crucial underlying pathology in patients with supine-predominant OSA.
We read with great interest the article by B
Altitude exposure is generally considered to be contraindicated in pulmonary arterial hypertension (PAH), out of concern that (hypobaric) hypoxic pulmonary vasoconstriction (HPV) might further increase pulmonary vascular resistance (PVR) and worsen right heart failure [1]. This notion is mentioned in the guidelines of the European Society of Cardiology (ESC) and European Respiratory Society (ERS), who provide a recommendation against the travel to altitude of >1500 m without supplemental oxygen [2, 3].
]]>From the influenza pandemic of 1918–1919 to the most recent COVID-19 pandemic, respiratory infections remain a leading cause of mortality worldwide [1, 2]. Concurrently, the development of high-throughput omics technologies has revolutionised research about host responses to known and emerging respiratory pathogens [3], accelerating our understanding of highly prevalent pulmonary diseases [4]. Notably, omics technology-based characterisation of pathogens and host pathophysiology have critically supported diagnostic and therapeutic global health efforts during both the influenza A H1N1 and SARS-CoV-2 pandemics [5–7]. Nonetheless, elucidation of key immune response mechanisms and development of host-targeted therapeutics remain important unrealised research and clinical priorities in the global fight against lower respiratory tract infections (LTRIs) [8, 9].
]]>We read with interest the paper by H
We thank Y. Li and co-workers for their interest in the European Respiratory Society/European Society of Thoracic Surgeons statement on the management of pleural infection, recently published in the European Respiratory Journal [1]. Our interpretation of their correspondence is that they have misunderstood "IPC" to denote a standard chest drain or tube used, with a well-established evidence base, in the acute management of pleural infection [2]. This is also sometimes referred to as an intercostal catheter or an intercostal drain. In the statement, IPC refers specifically to "indwelling pleural catheter", and the abbreviation is introduced on first mention in the relevant paragraph [1]. The preceding sections discussing acute management refer to "chest tube drainage". We apologise if this was not clear.
]]>For many years now, the pulmonary hypertension community has been trying to narrow down on the true incidence of chronic thromboembolic pulmonary hypertension (CTEPH) following pulmonary embolism. The study by D
Cystic fibrosis (CF) is one of the most common autosomal recessive genetic conditions that causes progressive lung disease and premature death [1]. Median survival worldwide is estimated to be around 50 years, but there is variation between countries [2–4]. Reasons for this variation are complex, and include genetic factors such as cystic fibrosis transmembrane conductance regulator (CFTR) genetic mutations in the population [5], as well as non-genetic factors such as access to lung transplantation and socioeconomic status (SES) [4].
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