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Journal articleKirk C, Kuederle A, Mico-Amigo ME, et al., 2024,
Mobilise-D insights to estimate real-world walking speed in multiple conditions with a wearable device (vol 14, 1754, 2024)
, SCIENTIFIC REPORTS, Vol: 14, ISSN: 2045-2322 -
Journal articleKermani NZ, Chung KF, Macis G, et al., 2024,
Radiomultiomics: quantitative CT clusters of severe asthma associated with multi-omics
, European Respiratory Journal, Vol: 64, ISSN: 0903-1936RationaleLung quantitative computed tomographic (qCT) severe asthma clusters have been reported, but their replication and underlying disease mechanisms are unknown. We identified and replicated qCT clusters of severe asthma in two independent asthma cohorts and determined their association with molecular pathways.MethodsWe used consensus clustering on qCT measurements of airway and lung CT scans, performed in 105 severe asthmatic adults from the U-BIOPRED cohort. The same qCT measurements were used to replicate qCT clusters in a subsample of the ATLANTIS asthma cohort (n=97). We performed integrated enrichment analysis using blood, sputum, bronchial biopsies, bronchial brushings and nasal brushings transcriptomics and blood and sputum proteomics to characterize radiomultiomic-associated clusters (RACs).ResultsqCT clusters and clinical features in U-BIOPRED were replicated in the matched ATLANTIS cohort. In the U-BIOPRED cohort, RAC1 (n=30) was predominantly female with elevated BMI, mild airflow limitation, normal qCT parameters and upregulation of the complement pathway. RAC2 (n=34) subjects had a lower degree of airflow limitation, airway wall thickness and dilatation, with upregulation of proliferative pathways, including neurotrophic receptor tyrosine kinase 2/tyrosine kinase receptor B (NTRK2/TRKB), and down-regulation of semaphorin pathways. RAC3 (n=41) showed increased lung attenuation area and air trapping, severe airflow limitation, hyperinflation, and upregulation of cytokine signaling and signaling by interleukin pathways, and matrix metallopeptidase 1, 2 and 9.ConclusionsU-BIOPRED severe asthma qCT clusters were replicated in a matched independent asthmatic cohort and associated with specific molecular pathways. Radiomultiomics might represent anovel strategy to identify new molecular pathways in asthma pathobiology.
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Journal articleWen Y, Chen Q, Wang H, et al., 2024,
Contribution of IL-17C-mediated macrophage polarization to Type 17 inflammation in neutrophilic asthma
, CELL COMMUNICATION AND SIGNALING, Vol: 22 -
Journal articleFinney L, Fenwick P, Kemp S, et al., 2024,
Impaired anti-viral immunity in frequent exacerbators of chronic obstructive pulmonary disease
, American Journal of Physiology: Lung Cellular and Molecular Physiology, ISSN: 1040-0605 -
Journal articleLee B, Man KKC, Wong E, et al., 2024,
Antidiabetic Medication and Asthma Attacks
, JAMA INTERNAL MEDICINE, ISSN: 2168-6106 -
Journal articleSilverberg JI, Mustapa MN, Reid F, et al., 2024,
Efficacy and safety of tozorakimab in moderate-to-severe atopic dermatitis: A Phase 2a randomized controlled trial (FRONTIER-2)
, JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, ISSN: 0926-9959 -
Journal articleRoche N, Usmani O, Franzini L, et al., 2024,
Pharmaceutical, Clinical, and Regulatory Challenges of Reformulating Pressurized Metered-Dose Inhalers to Reduce Their Environmental Impact
, JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, ISSN: 1941-2711 -
Journal articlePeltrini R, Cordell RL, Wilde M, et al., 2024,
Discovery and validation of a volatile signature of eosinophilic airway inflammation in asthma
, American Journal of Respiratory and Critical Care Medicine, Vol: 210, Pages: 1101-1112, ISSN: 1073-449XRationale: Volatile organic compounds (VOCs) in asthmatic breath may be associated with sputum eosinophilia. We developed a volatile biomarker-signature to predict sputum eosinophilia in asthma. Methods: VOCs emitted into the space above sputum samples (headspace) from severe asthmatics (n=36) were collected onto sorbent tubes and analysed using thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Elastic net regression identified stable VOCs associated with sputum eosinophilia ≥3% and generated a volatile biomarker signature. This VOC signature was validated in breath samples from: (I) acute asthmatics according to blood eosinophilia ≥0.3x109cells/L or sputum eosinophilia of ≥ 3% in the UK EMBER consortium (n=65) and U-BIOPRED-IMI consortium (n=42). Breath samples were collected onto sorbent tubes (EMBER) or Tedlar bags (U-BIOPRED) and analysed by gas-chromatography-mass spectrometry (GC×GC-MS -EMBER or GC-MS -U-BIOPRED). Main Results: The in vitro headspace identified 19 VOCs associated with sputum eosinophilia and the derived VOC signature yielded good diagnostic accuracy for sputum eosinophilia ≥ 3% in headspace (AUROC (95% CI) 0.90(0.80-0.99), p<0.0001), correlated inversely with sputum eosinophil % (rs= -0.71, p<0.0001) and outperformed FeNO (AUROC (95% CI) 0.61(0.35-0.86). Analysis of exhaled breath in replication cohorts yielded a VOC signature AUROC (95% CI) for acute asthma exacerbations of 0.89(0.76-1.0) (EMBER cohort) with sputum eosinophilia and 0.90(0.75-1.0) in U-BIOPRED - again outperforming FeNO in U-BIOPRED 0.62 (0.33-0.90). Conclusions: We have discovered and provided early-stage clinical validation of a volatile biomarker signature associated with eosinophilic airway inflammation. Further work is needed to translate our discovery using point of care clinical sensors.
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Journal articleKhamas SS, Van Dijk Y, Abdel-Aziz MI, et al., 2024,
Exhaled Volatile Organic Compounds for Asthma Control Classification in Children with Moderate to Severe Asthma Results from the SysPharmPediA Study
, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 210, Pages: 1091-1100, ISSN: 1073-449X -
Journal articleLough G, Bosnic-Anticevich S, Roche N, et al., 2024,
Patient and Provider Perspectives Driving Inhaler Choice Optimizing Sustainable Health Care
, CHEST, Vol: 166, Pages: 934-937, ISSN: 0012-3692 -
Journal articleJun H, Park JY, Oh J-Y, et al., 2024,
Exploring Traits Associated With Central Sensitization Features in Patients With Chronic Cough
, ALLERGY ASTHMA & IMMUNOLOGY RESEARCH, Vol: 16, Pages: 690-700, ISSN: 2092-7355 -
Journal articleZhu J, Edwards MR, Message SD, et al., 2024,
Cilomilast Modulates Rhinovirus-Induced Airway Epithelial ICAM-1 Expression and IL-6, CXCL8 and CCL5 Production
, PHARMACEUTICALS, Vol: 17 -
Conference paperLee B, Wong E, Tan T, et al., 2024,
Effectiveness of Metformin in Preventing Asthma Exacerbations: A Self-Controlled Case Series and Inverse Propensity Score Weighting Analysis
, Publisher: WILEY, Pages: 104-104, ISSN: 1053-8569 -
Journal articlevan Boven JFM, Yorgancioglu A, Roche N, et al., 2024,
Ensuring availability of respiratory medicines in times of European drug shortages
, EUROPEAN RESPIRATORY JOURNAL, Vol: 64, ISSN: 0903-1936 -
Journal articlePatel B, Mumby S, Johnson N, et al., 2024,
A randomized control trial evaluating the advice of a physiological-model/digital twin-based decision support system on mechanical ventilation in patients with acute respiratory distress syndrome
, Frontiers in Medicine, Vol: 11, ISSN: 2296-858XBackground: Acute respiratory distress syndrome (ARDS) is highly heterogeneous, both in its clinical presentation and in the patient’s physiological responses to changes in mechanical ventilator settings, such as PEEP. This study investigates the clinical efficacy of a physiological model-based ventilatory decision support system (DSS) to personalize ventilator therapy in ARDS patients.Methods: This international, multicenter, randomized, open-label study enrolled patients with ARDS during the COVID-19 pandemic. Patients were randomized to either receive active advice from the DSS (intervention) or standard care without DSS advice (control). The primary outcome was to detect a reduction in average driving pressure between groups. Secondary outcomes included several clinically relevant measures of respiratory physiology, ventilator-free days, time from control mode to support mode, number of changes in ventilator settings per day, percentage of time in control and support mode ventilation, ventilation- and device-related adverse events, and the number of times the advice was followed.Results: A total of 95 patients were randomized in this study. The DSS showed no significant effect on average driving pressure between groups. However, patients in the intervention arm had a statistically improved oxygenation index when in support mode ventilation (−1.41, 95% CI: −2.76, −0.08; p = 0.0370). Additionally, the ventilatory ratio significantly improved in the intervention arm for patients in control mode ventilation (−0.63, 95% CI: −1.08, −0.17, p = 0.0068). The application of the DSS led to a significantly increased number of ventilator changes for pressure settings and respiratory frequency.Conclusion: The use of a physiological model-based decision support system for providing advice on mechanical ventilation in patients with COVID-19 and non-COVID-19 ARDS showed no significant difference in driving pre
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Journal articleMessaoud-Nacer Y, Culerier E, Rose S, et al., 2024,
STING-dependent induction of neutrophilic asthma exacerbation in response to house dust mite
, ALLERGY, ISSN: 0105-4538 -
Book chapterHassibi S, Donnelly L, 2024,
Macrophage Dysfunction in Respiratory Disease.
, Monocytes and Macrophages in Development, Regeneration, and Disease, Editors: Kloc, Kubiak, Halasa, Publisher: Springer, Pages: 239-256, ISBN: 978-3-031-65944-7Our understanding of the origin, phenotype, and function of pulmonary macrophages has evolved over recent years. The use of lineage tracing and single-cell RNA sequencing has led to a greater understanding of how these cells regulate homeostasis in the lung. The primary function of alveolar macrophages is to clear any inhaled particles or pathogens and they as well as tissue-resident cells also play a role in the clearance of apoptotic cells and the resolution of inflammation. Lung diseases affect over half a billion people globally and are attributable to 7% of all deaths each year. The common diseases are chronic obstructive pulmonary disease (COPD) and asthma but others that contribute to this statistic include cystic fibrosis and idiopathic pulmonary fibrosis (IPF). Macrophages are aberrant in all these diseases with a reduced phagocytic capacity and a high proinflammatory phenotype with changes to their capacity to resolve inflammation. The pathways leading to these macrophage dysfunctions differ with disease and may relate to the specific lung environment in each condition. However, there are clear changes in metabolic profiles and mitochondrial activity in many of these conditions that contribute to a change in macrophage phenotype towards a more proinflammatory, less homeostatic cell. Understanding the mechanisms that drive these changes will allow for more targeted therapies for the treatment of these long-term and debilitating conditions..
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Journal articleHopkinson N, Agrawal S, Thakar R, et al., 2024,
Achieving a smoke-free country—a best buy for the UK chancellor
, BMJ: British Medical Journal, Vol: 387, ISSN: 0959-535X -
Journal articleWiseman DJ, Thwaites RS, Ritchie AI, et al., 2024,
Respiratory syncytial virus-related community COPD exacerbations and novel diagnostics: a binational prospective cohort study
, American Journal of Respiratory and Critical Care Medicine, Vol: 210, Pages: 994-1001, ISSN: 1073-449XRATIONALE: Respiratory syncytial virus (RSV) is a common global respiratory virus increasingly recognized as a major pathogen in frail older adults and as a cause of chronic obstructive pulmonary disease (COPD) exacerbations. There is no single test for RSV in adults with acceptable diagnostic accuracy. Trials of RSV vaccines have recently shown excellent safety and efficacy against RSV in older adults; defining the frequency of RSV-related community infections and COPD exacerbations is important for vaccine deployment decisions. OBJECTIVES: This prospective study aimed to establish the frequency of outpatient-managed RSV-related exacerbations of COPD in two well-characterized patient cohorts using a combination of diagnostic methods. METHODS: Participants were recruited at specialist clinics in London, UK and Groningen, NL from 2017 and observed for three consecutive RSV seasons, during exacerbations and at least twice yearly. RSV infections were detected by reverse transcription-polymerase chain reaction (RT-PCR) and serologic testing. MEASUREMENTS AND MAIN RESULTS: 377 patients with COPD attended 1,999 clinic visits and reported 310 exacerbations. There were 27 RSV-related exacerbations (8·7% of total); of these, seven were detected only on PCR, 16 only on serology and 4 by both methods. Increases in RSV specific N-protein antibody were as sensitive as antibody to pre-F or post-F for serodiagnosis of RSV related exacerbations. CONCLUSIONS: RSV is associated with 8.7% of outpatient managed COPD exacerbations in this study. Antibodies to RSV-N protein may have diagnostic value, potentially important in a vaccinated population. The introduction of vaccines that prevent RSV is expected to benefit patients with COPD. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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Journal articleAbubakar-Waziri H, Edwards DA, Bhandu Bhatta D, et al., 2024,
Inhaled alkaline hypertonic divalent salts reduce refractory chronic cough frequency
, ERJ Open Research, Vol: 10, ISSN: 2312-0541Background. Treatment of chronic cough remains a challenge. We hypothesized that inhaled alkaline hypertonic divalent salts (alkaline HDS) might provide relief for refractory chronic cough by laryngeal and tracheal hydration.Methods. We conducted an exploratory, single-blinded, nasal-saline-controlled study in 12 refractory chronic cough patients to examine cough-suppression efficacy of an alkaline HDS composition (SC001) at pH 8 or pH 9 administered by nasal inhalation. As control, we used nasal saline with the same hand-held pump spray aerosol device. Each subject was monitored continuously using a digital cough monitor watch for one week of baseline, one week of control treatment, and one week of active treatment.Results. Baseline daily cough rates ranged from 4 to 34 coughs/hour with mean visual analog score 65±17 pre- and post-baseline testing. Control-adjusted efficacy of cough rate reduction ranged from 15% (p=0.015) (from Day 1) to 23% (p=0.002) (from Day 3). Control-adjusted efficacy was highest with SC001 pH 9 (n=5), ranging from 25% (p=0.03) (from Day 1) to 35% (p=0.02) (from Day 3), and lowest for SC001 pH 8 (n=7), ranging from 9% (p=0.08) (from Day 1) to 16% (p=0.02) (from Day 3). Hourly cough counts and VAS correlated for baseline (r=0.254, p-value=0.02) and control (r=0.299, p-value=0.007) monitoring weeks. Treatment improved this correlation (r=0.434, p-value=0.00006). No adverse events were reported.Conclusions. Alkaline (pH 9) HDS aerosol is a promising treatment for refractory chronic cough and should be further evaluated.
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