1459 results found
Laiman V, Lo Y-C, Chen H-C, et al., 2023, Data on lung and intestinal microbiome after air pollution exposure in ageing rats., Data Brief, Vol: 47
Air pollution has been linked to respiratory diseases, and urban air pollution can be attributed to a number of emission sources. The emitted particles and gases are the primary components of air pollution that enter the lungs during respiration. Particulate matter with an aerodynamic diameter of ≤ 2.5 µm (PM2.5) can deposit deep into the respiratory tract via inhalation and has been proposed as a causative agent for adverse respiratory health. In addition, the lung contains a diverse microbial community (microbiome) that maintains normal homeostasis and is significantly altered in a variety of pulmonary disorders. Air pollution, specifically PM2.5, has previously been shown to significantly alter the composition of the lower airway microbiome, which has been linked to decreased lung function in chronic obstructive pulmonary disease (COPD) patients. Surprisingly, the intestinal microbiome has also been implicated in the modulation of pulmonary inflammatory diseases. Therefore, dysbiosis of the lung and intestinal microbiomes pose significant negative effects on human health. This dataset describes the microbial community profiles of the lungs and intestines of ageing rats exposed to ambient unconcentrated traffic-related air pollution for three months. The whole-body exposure system was equipped with and without high efficiency particulate air (HEPA) filtration (gaseous vs. PM2.5 pollution). The data can provide valuable information on lung and intestinal microbiome changes, including that which was only found after traffic-related air pollution exposure.
Calderon AA, Dimond C, Choy DF, et al., 2023, Targeting interleukin-33 and thymic stromal lymphopoietin pathways for novel pulmonary therapeutics in asthma and COPD., Eur Respir Rev, Vol: 32
Interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP) are alarmins that are released upon airway epithelial injury from insults such as viruses and cigarette smoke, and play critical roles in the activation of immune cell populations such as mast cells, eosinophils and group 2 innate lymphoid cells. Both cytokines were previously understood to primarily drive type 2 (T2) inflammation, but there is emerging evidence for a role for these alarmins to additionally mediate non-T2 inflammation, with recent clinical trial data in asthma and COPD cohorts with non-T2 inflammation providing support. Currently available treatments for both COPD and asthma provide symptomatic relief with disease control, improving lung function and reducing exacerbation rates; however, there still remains an unmet need for further improving lung function and reducing exacerbations, particularly for those not responsive to currently available treatments. The epithelial cytokines/alarmins are involved in exacerbations; biologics targeting TSLP and IL-33 have been shown to reduce exacerbations in moderate-to-severe asthma, either in a broad population or in specific subgroups, respectively. For COPD, while there is clinical evidence for IL-33 blockade impacting exacerbations in COPD, clinical data from anti-TSLP therapies is awaited. Clinical data to date support an acceptable safety profile for patients with airway diseases for both anti-IL-33 and anti-TSLP antibodies in development. We examine the roles of IL-33 and TSLP, their potential use as drug targets, and the evidence for target patient populations for COPD and asthma, together with ongoing and future trials focused on these targets.
Chen X-Y, Chen K-Y, Feng P-H, et al., 2023, YAP-regulated type II alveolar epithelial cell differentiation mediated by human umbilical cord-derived mesenchymal stem cells in acute respiratory distress syndrome., Biomed Pharmacother, Vol: 159
Acute respiratory distress syndrome (ARDS) contributes to higher mortality worldwide. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have immunomodulatory and regenerative potential. However, the effects of hUC-MSCs as an ARDS treatment remain unclear. We investigated the role of hUC-MSCs in the differentiation of type II alveolar epithelial cells (AECII) by regulating Yes-associated protein (YAP) in ARDS. Male C57BL/6JNarl mice were intratracheally (i.t.) administered lipopolysaccharide (LPS) to induce an ARDS model, followed by a single intravenous (i.v.) dose of hUC-MSCs. hUC-MSCs improved pulmonary function, decreased inflammation on day 3, and mitigated lung injury by reducing the lung injury score and increasing lung aeration (%) in mice on day 7 (p < 0.05). hUC-MSCs inactivated YAP on AECII and facilitated cell differentiation by decreasing Pro-surfactant protein C (Pro-SPC) and galectin 3 (LGALS3) while increasing podoplanin (T1α) in lungs of mice (p < 0.05). In AECII MLE-12 cells, both coculture with hUC-MSCs after LPS exposure and the YAP inhibitor, verteporfin, reduced Pro-SPC and LGALS3, whereas the YAP inhibitor increased T1α expression (p < 0.05). In conclusion, hUC-MSCs ameliorated lung injury of ARDS and regulated YAP to facilitate AECII differentiation.
Bai K-J, Liu W-T, Lin Y-C, et al., 2023, Ambient relative humidity-dependent obstructive sleep apnea severity in cold season: A case-control study., Sci Total Environ, Vol: 861
BACKGROUND: The objective of this study was to examine associations of daily averages and daily variations in ambient relative humidity (RH), temperature, and PM2.5 on the obstructive sleep apnea (OSA) severity. METHODS: A case-control study was conducted to retrospectively recruit 8628 subjects in a sleep center between January 2015 and December 2021, including 1307 control (apnea-hypopnea index (AHI) < 5 events/h), 3661 mild-to-moderate OSA (AHI of 5-30 events/h), and 3597 severe OSA subjects (AHI > 30 events/h). A logistic regression was used to examine the odds ratio (OR) of outcome variables (daily mean or difference in RH, temperature, and PM2.5 for 1, 7, and 30 days) with OSA severity (by the groups). Two-factor logistic regression models were conducted to examine the OR of RH with the daily mean or difference in temperature or PM2.5 with OSA severity. An exposure-response relationship analysis was conducted to examine the outcome variables with OSA severity in all, cold and warm seasons. RESULTS: We observed associations of mean PM2.5 and RH with respective increases of 0.04-0.08 and 0.01-0.03 events/h for the AHI in OSA patients. An increase in the daily difference of 1 % RH increased the AHI by 0.02-0.03 events/h in OSA patients. A daily PM2.5 decrease of 1 μg/m3 reduced the AHI by 0.03 events/h, whereas a daily decrease in the RH of 1 % reduced the AHI by 0.03-0.04 events/h. The two-factor model confirmed the most robust associations of ambient RH with AHI in OSA patients. The exposure-response relationship in temperature and RH showed obviously seasonal patterns with OSA severity. CONCLUSION: Short-term ambient variations in RH and PM2.5 were associated with changes in the AHI in OSA patients, especially RH in cold season. Reducing exposure to high ambient RH and PM2.5 levels may have protective effects on the AHI in OSA patients.
Wang R, Usmani OS, Chung KF, et al., 2023, Domiciliary Fractional Exhaled Nitric Oxide and Spirometry in Monitoring Asthma Control and Exacerbations., J Allergy Clin Immunol Pract
BACKGROUND: Domiciliary measurements of airflow obstruction and inflammation may assist healthcare teams and patients in determining asthma control and facilitate self-management. OBJECTIVE: To evaluate parameters derived from domiciliary spirometry and fractional exhaled nitric oxide (Feno) in monitoring asthma exacerbations and control. METHODS: Patients with asthma were provided with hand-held spirometry and Feno devices in addition to their usual asthma care. Patients were instructed to perform twice-daily measurements for 1 month. Daily symptoms and medication change were reported through a mobile health system. The Asthma Control Questionnaire was completed at the end of the monitoring period. RESULTS: One hundred patients had spirometry, of which 60 were given additional Feno devices. Compliance rates for twice-daily measurements were poor (median [interquartile range], 43% [25%-62%] for spirometry; 30% [3%-48%] for Feno); at least 15% of patients took little or no spirometry measurements and 40% rarely measured Feno. The coefficient of variation (CV) values in FEV1 and Feno were higher, and the mean % personal best FEV1 lower in those who had major exacerbations compared with those without (P < .05). Feno CV and FEV1 CV were associated with asthma exacerbation during the monitoring period (area under the receiver-operating characteristic curve, 0.79 and 0.74, respectively). Higher Feno CV also predicted poorer asthma control (area under the receiver-operating characteristic curve, 0.71) at the end of the monitoring period. CONCLUSIONS: Compliance with domiciliary spirometry and Feno varied widely among patients even in the setting of a research study. However, despite significant missing data, Feno and FEV1 were associated with asthma exacerbations and control, making these measurements potentially clinically valuable if used.
Huang H-Y, Lo C-Y, Chung F-T, et al., 2023, Risk Factors for Influenza-Induced Exacerbations and Mortality in Non-Cystic Fibrosis Bronchiectasis., Viruses, Vol: 15
Influenza infection is a cause of exacerbations in patients with chronic pulmonary diseases. The aim of this study was to investigate the clinical outcomes and identify risk factors associated with hospitalization and mortality following influenza infection in adult patients with bronchiectasis. Using the Chang Gung Research Database, we identified patients with bronchiectasis and influenza-related infection (ICD-9-CM 487 and anti-viral medicine) between 2008 and 2017. The main outcomes were influenza-related hospitalization and in-hospital mortality rate. Eight hundred sixty-five patients with bronchiectasis and influenza infection were identified. Five hundred thirty-six (62%) patients with bronchiectasis were hospitalized for influenza-related infection and 118 (22%) patients had respiratory failure. Compared to the group only seen in clinic, the hospitalization group was older, with more male patients, a lower FEV1, higher bronchiectasis aetiology comorbidity index (BACI), and more acute exacerbations in the previous year. Co-infections were evident in 55.6% of hospitalized patients, mainly caused by Pseudomonas aeruginosa (15%), fungus (7%), and Klebsiella pneumoniae (6%). The respiratory failure group developed acute kidney injury (36% vs. 16%; p < 0.001), and shock (47% vs. 6%; p < 0.001) more often than influenza patients without respiratory failure. The overall mortality rate was 10.8% and the respiratory failure group exhibited significantly higher in-hospital mortality rates (27.1% vs. 6.2%; p < 0.001). Age, BACI, and previous exacerbations were independently associated with influenza-related hospitalization. Age, presence of shock, and low platelet counts were associated with increased hospital mortality. Influenza virus caused severe exacerbation in bronchiectasis, especially in those who were older and who had high BACI scores and previous exacerbations. A high risk of respiratory failure and mortality were observed in influenza-related hospit
Deng Z, Jin M, Ou C, et al., 2023, Eligibility of C-BIOPRED severe asthma cohort for type-2 biologic therapies., Chin Med J (Engl)
Wu X, Abubakar-Waziri H, Fang F, et al., 2023, Modeling for understanding of coronavirus disease-2019 (COVID-19) spread and design of an isolation room in a hospital, Physics of Fluids, Vol: 35, ISSN: 1070-6631
We have modeled the transmission of coronavirus 2019 in the isolation room of a patient suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the Royal Brompton Hospital in London. An adaptive mesh computational fluid dynamics model was used for simulation of three-dimensional spatial distribution of SARS-CoV-2 in the room. The modeling set-up is based on data collected in the room during the patient stay. Many numerical experiments have been carried out to provide an optimal design layout of the overall isolation room. Our focus has been on (1) the location of the air extractor and filtration rates, (2) the bed location of the patient, and (3) consideration of the health and safety of the staff working in the area.
Kumar P, Zavala-Reyes JC, Kalaiarasan G, et al., 2023, Characteristics of fine and ultrafine aerosols in the London underground., Science of the Total Environment, Vol: 858, ISSN: 0048-9697
Underground railway systems are recognised spaces of increased personal pollution exposure. We studied the number-size distribution and physico-chemical characteristics of ultrafine (PM0.1), fine (PM0.1-2.5) and coarse (PM2.5-10) particles collected on a London underground platform. Particle number concentrations gradually increased throughout the day, with a maximum concentration between 18:00 h and 21:00 h (local time). There was a maximum decrease in mass for the PM2.5, PM2.5-10 and black carbon of 3.9, 4.5 and ~ 21-times, respectively, between operable (OpHrs) and non-operable (N-OpHrs) hours. Average PM10 (52 μg m-3) and PM2.5 (34 μg m-3) concentrations over the full data showed levels above the World Health Organization Air Quality Guidelines. Respiratory deposition doses of particle number and mass concentrations were calculated and found to be two- and four-times higher during OpHrs compared with N-OpHrs, reflecting events such as train arrival/departure during OpHrs. Organic compounds were composed of aromatic hydrocarbons and polycyclic aromatic hydrocarbons (PAHs) which are known to be harmful to health. Specific ratios of PAHs were identified for underground transport that may reflect an interaction between PAHs and fine particles. Scanning transmission electron microscopy (STEM) chemical maps of fine and ultrafine fractions show they are composed of Fe and O in the form of magnetite and nanosized mixtures of metals including Cr, Al, Ni and Mn. These findings, and the low air change rate (0.17 to 0.46 h-1), highlight the need to improve the ventilation conditions.
Cui Z-Y, Li Y-H, Liu Z, et al., 2023, The experience of tobacco withdrawal symptoms among current smokers and ex-smokers in the general population: Findings from nationwide China Health Literacy Survey during 2018-19, FRONTIERS IN PSYCHIATRY, Vol: 13, ISSN: 1664-0640
Edwards DA, Chung KF, 2023, Mouth breathing, dry air, and low water permeation promote upper airway inflammation, activate neural pathways and disrupt clearance by osmotic stresses originating in a water condensation layer above airway lining mucus, QRB Discovery
Respiratory disease and breathing abnormalities worsen with dehydration of the upper airways. We find that humidification of inhaled air occurs by evaporation of water over mucus lining the upper airways in such a way as to deliver an osmotic force on mucus, displacing it toward the epithelium. This displacement thins the periciliary layer of water beneath mucus while thickening topical water that is partially condensed from humid air on exhalation. With the rapid mouth breathing of dry air, this condensation layer, not previously reported while common to transpiring hydrogels in nature, can deliver an osmotic compressive force of up to around 100 cm H2O on underlying cilia, promoting ATP secretion and activating neural pathways. We derive expressions for the evolution of the thickness of the condensation layer, and its impact on cough frequency, inflammatory marker secretion, cilia beat frequency, and respiratory droplet generation. We compare our predictions with human clinical data from multiple published sources, and highlight the damaging impact of mouth breathing, dry air, and high minute volume on upper airway function. We predict the hypertonic (or hypotonic) saline mass required to reduce (or amplify) dysfunction by restoration (or deterioration) of the structure of ciliated and condensation water layers in the upper airways, and compare these predictions with published human clinical data. Preserving water balance in the upper airways appears critical in light of contemporary respiratory health challenges posed by the breathing of dirty and dry air.
Kole TM, Vanden Berghe E, Kraft M, et al., 2023, Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study., The Lancet Respiratory Medicine, Vol: 11, Pages: 55-64, ISSN: 2213-2600
BACKGROUND: Persistent airflow limitation (PAL) occurs in a subset of patients with asthma. Previous studies on PAL in asthma have included relatively small populations, mostly restricted to severe asthma, or have no included longitudinal data. The aim of this post-hoc analysis was to investigate the determinants, clinical implications, and outcome of PAL in patients with asthma who were included in the ATLANTIS study. METHODS: In this post-hoc analysis of the ATLANTIS study, we assessed the prevalence, clinical characteristics, and implications of PAL across the full range of asthma severity. The study population included patients aged 18-65 years who had been diagnosed with asthma at least 6 months before inclusion. We defined PAL as a post-bronchodilator FEV1/forced vital capacity (FVC) of less than the lower limit of normal at recruitment. Asthma severity was defined according to the Global Initiative for Asthma. We used Mann-Whitney U test, t test, or χ2 test to analyse differences in baseline characteristics between patients with and without PAL. Logistic regression was used for multivariable analysis of the associations between PAL and baseline data. Cox regression was used to analyse risk of exacerbation in relation to PAL, and a linear mixed-effects model was used to analyse change in FEV1 over time in patients with versus patients without PAL. Results were validated in the U-BIOPRED cohort. FINDINGS: Between June 30, 2014 and March 3, 2017, 773 patients were enrolled in the ATLANTIS study of whom 760 (98%) had post-bronchodilator FEV1/FVC data available. Of the included patients with available data, mean age was 44 years (SD 13), 441 (58%) of 760 were women, 578 (76%) were never-smokers, and 248 (33%) had PAL. PAL was not only present in patients with severe asthma, but also in 21 (16%) of 133 patients with GINA step 1 and 24 (29%) of 83 patients with GINA step 2. PAL was independently associated with older age at baseline (46 years in PAL group vs 43
Rattu A, Khaleva E, Brightling C, et al., 2022, Identifying and appraising outcome measures for severe asthma: a systematic review., Eur Respir J
BACKGROUND: Valid outcome measures are imperative to evaluate treatment response, yet the suitability of existing endpoints for severe asthma is unclear. This review aimed to identify outcome measures for severe asthma and appraise the quality of their measurement properties. METHODS: A literature search was performed to identify "candidate" outcome measures published between 2018-2020 (PROSPERO, CRD42020204437). A modified Delphi exercise was conducted to select "key" outcome measures within healthcare professional, patient, pharmaceutical, and regulatory stakeholder groups. Initial validation studies for "key" measures were rated against modified quality criteria from COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN). The evidence was discussed at multi-stakeholder meetings to ratify "priority" outcome measures. Subsequently, four bibliographic databases were searched from inception to identify development and validation studies for these endpoints. Two reviewers screened records, extracted data, assessed their methodological quality, and graded the evidence according to COSMIN. RESULTS: 96 outcome measures were identified as "candidates", 55 as "key", and 24 as "priority" for severe asthma; including clinical, healthcare utilisation, quality of life, asthma control, and composite. 32 studies reported measurement properties of 17 "priority" endpoints from the latter three domains. Only SAQ and C-ACT were developed with input from severe asthma patients. The certainty of evidence was "low" to "very low" for most "priority" endpoints across all measurement properties, and none fulfilled all quality standards. CONCLUSION: Only two outcome measures had robust developmental data for severe asthma. This review informed development of core outcome measures sets for severe asthma.
Do AR, An J, Jo J, et al., 2022, A genome-wide association study implicates the pleiotropic effect of NMUR2 on asthma and COPD, Scientific Reports, Vol: 12, ISSN: 2045-2322
Asthma and chronic obstructive pulmonary disease (COPD) are two distinct diseases that are associated with chronic inflammation. They share common features in terms of their advanced stages and genetic factors. This study aimed to identify novel genes underlying both asthma and COPD using genome-wide association study (GWAS) to differentiate between the two diseases. We performed a GWAS of asthma and COPD in 7828 Koreans from three hospitals. In addition, we investigated genetic correlations. The UK Biobank dataset was used for the replication studies. We found that rs2961757, located near neuromedin U receptor 2 (NMUR2) on chromosome 5, was genome-wide significant ([Formula: see text] = 0.44, P-valueAsthma-COPD = 3.41 × 10-8), and significant results were replicated with the UK Biobank data ([Formula: see text] = 0.04, P-valueAsthma-COPD = 0.0431). A positive genetic correlation was observed between asthma and COPD (39.8% in the Korean dataset and 49.8% in the UK Biobank dataset). In this study, 40-45% of the genetic effects were common to asthma and COPD. Moreover, NMUR2 increases the risk of asthma development and suppresses COPD development. This indicates that NMUR2 allows for better differentiation of both diseases, which can facilitate tailored medical therapy.
McGarvey L, Smith JA, Morice A, et al., 2022, A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 2b Trial of P2X3 Receptor Antagonist Sivopixant for Refractory or Unexplained Chronic Cough, LUNG, ISSN: 0341-2040
- Author Web Link
- Citations: 1
Kumar P, Kalaiarasan G, Bhagat RK, et al., 2022, Active air monitoring for understanding the ventilation and infection risks of SARS-CoV-2 transmission in public indoor spaces, Atmosphere, Vol: 13, Pages: 1-24, ISSN: 2073-4433
Indoor, airborne, transmission of SARS-CoV-2 is a key infection route. We monitored fourteen different indoor spaces in order to assess the risk of SARS-CoV-2 transmission. PM2.5 and CO2 concentrations were simultaneously monitored in order to understand aerosol exposure and ventilation conditions. Average PM2.5 concentrations were highest in the underground station (261 ± 62.8 μgm−3), followed by outpatient and emergency rooms in hospitals located near major arterial roads (38.6 ± 20.4 μgm−3), the respiratory wards, medical day units and intensive care units recorded concentrations in the range of 5.9 to 1.1 μgm−3. Mean CO2 levels across all sites did not exceed 1000 ppm, the respiratory ward (788 ± 61 ppm) and the pub (bar) (744 ± 136 ppm) due to high occupancy. The estimated air change rates implied that there is sufficient ventilation in these spaces to manage increased levels of occupancy. The infection probability in the medical day unit of hospital 3, was 1.6-times and 2.2-times higher than the emergency and outpatient waiting rooms in hospitals 4 and 5, respectively. The temperature and relative humidity recorded at most sites was below 27 °C, and 40% and, in sites with high footfall and limited air exchange, such as the hospital medical day unit, indicate a high risk of airborne SARS-CoV-2 transmission.
Chung Y-L, Laiman V, Tsao P-N, et al., 2022, Diesel exhaust particles inhibit lung branching morphogenesis via the YAP/TAZ pathway, SCIENCE OF THE TOTAL ENVIRONMENT, Vol: 861, ISSN: 0048-9697
Faiz A, Pavlidis S, Kuo C-H, et al., 2022, Th2 high and mast cell gene signatures are associated with corticosteroid sensitivity in COPD, THORAX, ISSN: 0040-6376
- Author Web Link
- Citations: 1
Thorsen J, Stokholm J, Rasmussen MA, et al., 2022, Asthma and Wheeze Severity and the Oropharyngeal Microbiota in Children and Adolescents., Ann Am Thorac Soc, Vol: 19, Pages: 2031-2043
Rationale: There is a major unmet need for improving the care of children and adolescents with severe asthma and wheeze. Identifying factors contributing to disease severity may lead to improved diagnostics, biomarkers, or therapies. The airway microbiota may be such a key factor. Objectives: To compare the oropharyngeal airway microbiota of children and adolescents with severe and mild/moderate asthma/wheeze. Methods: Oropharyngeal swab samples from school-age and preschool children in the European U-BIOPRED (Unbiased BIOmarkers in the PREDiction of respiratory disease outcomes) multicenter study of severe asthma, all receiving severity-appropriate treatment, were examined using 16S ribosomal RNA gene sequencing. Bacterial taxa were defined as amplicon sequence variants. Results: We analyzed 241 samples from four cohorts: A) 86 school-age children with severe asthma; B) 39 school-age children with mild/moderate asthma; C) 65 preschool children with severe wheeze; and D) 51 preschool children with mild/moderate wheeze. The most common bacteria were Streptococcus (mean relative abundance, 33.5%), Veillonella (10.3%), Haemophilus (7.0%), Prevotella (5.9%), and Rothia (5.5%). Age group (school-age vs. preschool) was associated with the microbiota in β-diversity analysis (F = 3.32, P = 0.011) and in a differential abundance analysis (28 significant amplicon sequence variants). Among all children, we found no significant difference in the microbiota between children with severe and mild/moderate asthma/wheeze in univariable β-diversity analysis (F = 1.99, P = 0.08, N = 241), but a significant difference in a multivariable model (F = 2.66, P = 0.035), including the number of exacerbations in the previous year. Age was also significant when expressed as a microbial maturity score (Spearman Rho, 0.39; P = 4.6 × 10-10); however, t
Song W-J, Chung KF, 2022, Cough Focused Series: progress in understanding and management of chronic cough., J Thorac Dis, Vol: 14, Pages: 5073-5074, ISSN: 2072-1439
Mazzone SB, Satia I, McGarvey L, et al., 2022, Chronic cough and cough hypersensitivity: from mechanistic insights to novel antitussives., Lancet Respir Med, Vol: 10, Pages: 1113-1115
Chung KF, Birring SS, Morice AH, et al., 2022, Tackling the neuropathic cough of idiopathic pulmonary fibrosis (IPF): more needs to be done, Lung: an international journal on lungs, airways and breathing, Vol: 200, Pages: 673-675, ISSN: 0341-2040
Up to 80% of patients with idiopathic pulmonary fibrosis (IPF) suffer from a chronic cough, which may be the first symptom of the disease. Cough has been reported to be an independent predictor of disease progression  and is associated with reduced quality of life (QoL), because from the patients’ point of view, it causes physical and emotional distress with chest pain, hoarse voice, incontinence, and sleep disturbance [2, 3]. In addition, cough QoL scores have been independently associated with a higher risk of hospitalisation, lung transplantation and death at 1 year . Therefore, control of cough in IPF remains an important priority.
Allam VSRR, Pavlidis S, Liu G, et al., 2022, Macrophage migration inhibitory factor promotes glucocorticoid resistance of neutrophilic inflammation in a murine model of severe asthma, Thorax, ISSN: 0040-6376
Background: Severe neutrophilic asthma is resistant to treatment with glucocorticoids. The immunomodulatory protein macrophage migration inhibitory factor (MIF) promotes neutrophil recruitment to the lung and antagonises responses to glucocorticoids. We hypothesised that MIF promotes glucocorticoid resistance of neutrophilic inflammation in severe asthma.Methods: We examined whether sputum MIF protein correlated with clinical and molecular characteristics of severe neutrophilic asthma in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. We also investigated whether MIF regulates neutrophilic inflammation and glucocorticoid responsiveness in a murine model of severe asthma in vivo.Results: MIF protein levels positively correlated with the number of exacerbations in the previous year, sputum neutrophils and oral corticosteroid use across all U-BIOPRED subjects. Further analysis of MIF protein expression according to U-BIOPRED-defined transcriptomic-associated clusters (TACs) revealed increased MIF protein and a corresponding decrease in annexin-A1 protein in TAC2, which is most closely associated with airway neutrophilia and NLRP3 inflammasome activation. In a murine model of severe asthma, treatment with the MIF antagonist ISO-1 significantly inhibited neutrophilic inflammation and increased glucocorticoid responsiveness. Coimmunoprecipitation studies using lung tissue lysates demonstrated that MIF directly interacts with and cleaves annexin-A1, potentially reducing its biological activity.Conclusion: Our data suggest that MIF promotes glucocorticoid-resistance of neutrophilic inflammation by reducing the biological activity of annexin-A1, a potent glucocorticoid-regulated protein that inhibits neutrophil accumulation at sites of inflammation. This represents a previously unrecognised role for MIF in the regulation of inflammation and points to MIF as a potential therapeutic target for the management of severe neutrophilic
Wang R, Usmani OS, Chung KF, et al., 2022, DOMICILIARY FRACTIONAL EXHALED NITRIC OXIDE AND SPIROMETRY IN PREDICTING ASTHMA CONTROL AND EXACERBATIONS, Publisher: BMJ PUBLISHING GROUP, Pages: A73-A74, ISSN: 0040-6376
Laiman V, Lo Y-C, Chen H-C, et al., 2022, Effects of antibiotics and metals on lung and intestinal microbiome dysbiosis after sub-chronic lower-level exposure of air pollution in ageing rats, ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, Vol: 246, ISSN: 0147-6513
Khaleva E, Rattu A, Brightling C, et al., 2022, Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)., Eur Respir J
BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies. METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria. RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately). CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
Hsiao T-C, Han C-L, Yang T-T, et al., 2022, Importance of surface charge of soot nanoparticles in determining inhalation toxicity in mice, ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH, ISSN: 0944-1344
Frankenberg Garcia J, Rogers A, Mak J, et al., 2022, Mitochondrial transfer regulates bioenergetics in healthy and COPD airway smooth muscle, American Journal of Respiratory Cell and Molecular Biology, Vol: 67, Pages: 471-481, ISSN: 1044-1549
Mitochondrial dysfunction has been reported in chronic obstructive pulmonary disease (COPD). Transfer of mitochondria from mesenchymal stem cells to airway smooth muscle cells (ASMCs) can attenuate oxidative stress-induced mitochondrial damage. It is not known whether mitochondrial transfer can occur between structural cells in the lungs or what role this may have in modulating bioenergetics and cellular function in healthy and COPD airways. Here, we show that ASMCs from both healthy ex-smokers and subjects with COPD can exchange mitochondria, a process that happens, at least partly, via extracellular vesicles. Exposure to cigarette smoke induces mitochondrial dysfunction and leads to an increase in the donation of mitochondria by ASMCs, suggesting that the latter may be a stress response mechanism. Healthy ex-smoker ASMCs that receive mitochondria show increases in mitochondrial biogenesis and respiration and a reduction in cell proliferation, irrespective of whether the mitochondria are transferred from healthy ex-smoker or COPD ASMCs. Our data indicate that mitochondrial transfer between structural cells is a homeostatic mechanism for the regulation of bioenergetics and cellular function within the airways and may represent an endogenous mechanism for reversing the functional consequences of mitochondrial dysfunction in diseases such as COPD.
Phillips T, Heaney CE, Benmoufok E, et al., 2022, Multi-Output Regression with Generative Adversarial Networks (MOR-GANs), Applied Sciences, Vol: 12, Pages: 1-24, ISSN: 2076-3417
Regression modelling has always been a key process in unlocking the relationships betweenindependent and dependent variables that are held within data. In recent years, machine learninghas uncovered new insights in many fields, providing predictions to previously unsolved problems.Generative Adversarial Networks (GANs) have been widely applied to image processing producinggood results, however, these methods have not often been applied to non-image data. Seeing thepowerful generative capabilities of the GANs, we explore their use, here, as a regression method. Inparticular, we explore the use of the Wasserstein GAN (WGAN) as a multi-output regression method.The resulting method we call Multi-Output Regression GANs (MOR-GANs) and its performanceis compared to a Gaussian Process Regression method (GPR) - a commonly used non-parametricregression method that has been well tested on small datasets with noisy responses. The WGANregression model performs well for all types of datasets and exhibits substantial improvements overthe performance of the GPR for certain types of datasets, demonstrating the flexibility of the GAN asa model for regression.
Zhou J, Yi F, Wu F, et al., 2022, Characteristics of different asthma phenotypes associated with cough: a prospective, multicenter survey in China, RESPIRATORY RESEARCH, Vol: 23
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