scholarly journals Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation

2021 ◽  
pp. 2100142
Author(s):  
Maria Sparreman Mikus ◽  
Johan Kolmert ◽  
Lars I. Andersson ◽  
Jörgen Östling ◽  
Richard G. Knowles ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Biomarker Discovery ◽  
Oral Steroid ◽  
Chronic Obstructive ◽  
Complement Factor ◽  
Consensus Clustering ◽  
Obstructive Pulmonary Disease ◽  
Inflammatory Protein ◽  
Blood Neutrophils

RationaleAsthma phenotyping requires novel biomarker discovery.ObjectivesTo identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, chronic obstructive pulmonary disease (COPD) subjects and healthy controls (HC).MethodsAn antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HC in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a two-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED.ResultsIn U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HC. Ten proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, RANK, TGF-β1, and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, hsCRP, and BMI, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation.ConclusionsThe plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers, and validated several proteins with established involvement in the pathophysiology of severe asthma.

scholarly journals What are the barriers to the completion of a home-based rehabilitation programme for patients awaiting surgery for lung cancer: a prospective observational study

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e041907
Author(s):  
Heloise Catho ◽  
Sebastien Guigard ◽  
Anne-Claire Toffart ◽  
Gil Frey ◽  
Thibaut Chollier ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Observational Study ◽  
Prospective Observational Study ◽  
Living Alone ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Factors Associated ◽  
Home Based ◽  
Registration Number

ObjectivesHome-based rehabilitation programmes (H-RPs) could facilitate the implementation of pulmonary rehabilitation prior to resection for non-small cell lung cancer (NSCLC), but their feasibility has not been evaluated. The aim of this study was to identify determinants of non-completion of an H-RP and the factors associated with medical events occurring 30 days after hospital discharge.DesignA prospective observational study.InterventionAll patients with confirmed or suspected NSCLC were enrolled in a four-component H-RP prior to surgery: (i) smoking cessation, (ii) nutritional support, (iii) physiotherapy (at least one session/week) and (iv) home cycle-ergometry (at least three times/week).OutcomesThe H-RP was defined as ‘completed’ if the four components were performed before surgery.ResultsOut of 50 patients included, 42 underwent surgery (80% men; median age: 69 (IQR 25%–75%; 60–74) years; 64% Chronic Obstructive Pulmonary Disease (COPD); 29% type 2 diabetes). Twenty patients (48%) completed 100% of the programme. The median (IQR) duration of the H-RP was 32 (19; 46) days. Multivariate analysis showed polypharmacy (n=24) OR=12.2 (95% CI 2.0 to 74.2), living alone (n=8) (single vs couple) OR=21.5 (95% CI 1.4 to >100) and a long delay before starting the H-RP (n=18) OR=6.24 (95% CI 1.1 to 36.6) were independently associated with a risk of non-completion. In univariate analyses, factors associated with medical events at 30 days were H-RP non-completion, diabetes, polypharmacy, social precariousness and female sex.ConclusionFacing multiple comorbidities, living alone and a long delay before starting the rehabilitation increase the risk of not completing preoperative H-RP.Trial registration numberNCT03530059.

scholarly journals ILC2 Cells Promote Th2 Cell Differentiation in AECOPD Through Activated Notch-GATA3 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Jiang ◽  
Ren Cai ◽  
Jing Wang ◽  
Zheng Li ◽  
Dan Xu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Peripheral Blood ◽  
Culture Supernatant ◽  
Th2 Cells ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Protein Levels ◽  
Th2 Cell

This study is to investigate the capacity of type 2 innate lymphoid cells (ILC2s) in regulating the Th2 type adaptive immune response of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The study enrolled healthy people, stable chronic obstructive pulmonary disease (COPD) patients, and AECOPD patients. Flow cytometry was used to detect Th2 and ILC2 cells in the peripheral blood. In addition, ILC2s from the peripheral blood of AECOPD patients were stimulated with PBS, IL-33, Jagged1, DAPT, IL-33+Jagged1, IL-33+DAPT, and IL-33+Jagged-1+DAP in vitro. The levels of cytokines in the culture supernatant were detected by ELISA and the culture supernatant was used to culture CD4 + T cells. The mRNA and protein levels of Notch1, hes1, GATA3, RORα, and NF-κB of ILC2s were detected by real-time PCR and Western blot. The proportion of Th2 and ILC2s was significantly increased in the peripheral blood of AECOPD patients, alone with the increased Notch1, hes1, and GATA3 mRNA levels. In vitro results showed that the mRNA and protein levels of Notch1, hes1, GATA3 and NF-κB were significantly increased after stimulation with Notch agonist, meanwhile, the level of type 2 cytokines were increased in the supernatant of cells stimulated with Notch agonist, and significantly promoted differentiation of Th2 cells in vitro. Disruption of Notch pathway weakened GATA3 expression and cytokine production, and ultimately affected the differentiation of Th2 cells. In conclusion, our results suggest that ILC2s can promote Th2 cell differentiation in AECOPD via activated Notch-GATA3 signal pathway.

scholarly journals Diabetes mellitus type 2 in hospitalized patients with chronic obstructive pulmonary disease

2015 ◽  
Author(s):  
Evgeni Mekov ◽  
Yanina Slavova ◽  
Marianka Genova ◽  
Adelina Tsakova ◽  
Dimitar Kostadinov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Obstructive Pulmonary Disease ◽  
Hospital Stay ◽  
Pulmonary Disease ◽  
Smoking Status ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Bulgarian Population

Diabetes mellitus (DM) affects 2-37% of patients with chronic obstructive pulmonary disease (COPD), with results being highly variable between studies. DM may also correlate with disease characteristics.The aim of this study was to examine the prevalence of DM and its correlation with comorbidities and COPD characteristics in patients with COPD admitted for exacerbation. 152 patients were studied for presence of DM. All of them were also assessed for vitamin D status and metabolic syndrome (MS). Data were gathered for smoking status and exacerbations during the last year. All patients completed CAT (COPD assessment test) and mMRC (Modified Medical Research Council Dyspnea scale) questionnaires and underwent spirometry. Duration of current hospital stay was recorded. 13.2% (20/152) of patients are taking medications for DM. Additional 21.7% (33/152) have newly discovered DM and 30.9% (47/152) have prediabetes. Only 34.2% of the studied patients do not have DM or prediabetes. 37% (40/108) of males have DM vs. 29,5% (13/44) of females (p=0.379). The prevalence of DM in this study is significantly higher when compared to an unselected Bulgarian population (12,8% in subjects over 45 years). 91% of patients with newly discovered diabetes had glycated hemoglobin (HbA1c)≥6,5% suggesting prolonged hyperglycemia. There is a correlation between the presence of DM and MS (p=0.008). The presence of DM is associated with more severe exacerbations (hospitalizations) during the previous year (p=0.003) and a longer hospital stay (p=0.006). DM is not associated with reduced quality of life and worse pulmonary function. The patients with COPD admitted for exacerbation are at great risk for impaired glucose metabolism which is associated with worse COPD characteristics. The majority of the patients in this study are unaware of having DM.

scholarly journals Asthma‐chronic obstructive pulmonary disease overlap: A clinical entity?

2020 ◽  
Vol 3 (1) ◽  
pp. 2-8
Author(s):  
Robert A. Wise
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Middle Age ◽  
Clinical Manifestations ◽  
Normal Lung ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Neutrophilic Inflammation ◽  
Normal Lung Function

Asthma and COPD are easily recognizable clinical entities in their characteristic presentations. Asthma is an early-onset disorder characterized by Type 2, eosinophil-predominant, inflammation of the airways and is associated with atopy. COPD presents in middle age and is characterized by neutrophilic inflammation of the airways and is associated with cigarette smoking or biomass fuel exposure. Between exacerbations, asthma typically has normal lung function whereas COPD has incompletely reversible lung function. Approximately one in five patients with either of these disorders will show some features of both COPD and Asthma. This overlap is far more common than can be accounted for by chance concurrence of two common diseases. There are likely genetic and environmental susceptibilities to both disorders, but there is no single pathobiological mechanism that identifies all such overlap patients. Most likely there are numerous predispositions that lead to Asthma-COPD overlap that may be grounded in early childhood or even pre-natal events. Thus, Asthma-COPD overlap is best considered a family of diseases with overlapping clinical manifestations. The future elucidation of these different pathways to Asthma-COPD overlap, in conjunction with highly targeted therapies will aid clinicians in treating these patients.

scholarly journals Eosinophil-derived IL-13 promotes emphysema

2019 ◽  
Vol 53 (5) ◽  
pp. 1801291 ◽  
Author(s):  
Alfred D. Doyle ◽  
Manali Mukherjee ◽  
William E. LeSuer ◽  
Tyler B. Bittner ◽  
Saif M. Pasha ◽  
...  
Keyword(s):  
Mouse Model ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Chronic Type ◽  
Obstructive Pulmonary Disease ◽  
Lung Eosinophilia

The inflammatory responses in chronic airway diseases leading to emphysema are not fully defined. We hypothesised that lung eosinophilia contributes to airspace enlargement in a mouse model and to emphysema in patients with chronic obstructive pulmonary disease (COPD).A transgenic mouse model of chronic type 2 pulmonary inflammation (I5/hE2) was used to examine eosinophil-dependent mechanisms leading to airspace enlargement. Human sputum samples were collected for translational studies examining eosinophilia and matrix metalloprotease (MMP)-12 levels in patients with chronic airways disease.Airspace enlargement was identified in I5/hE2 mice and was dependent on eosinophils. Examination of I5/hE2 bronchoalveolar lavage identified elevated MMP-12, a mediator of emphysema. We showed, in vitro, that eosinophil-derived interleukin (IL)-13 promoted alveolar macrophage MMP-12 production. Airspace enlargement in I5/hE2 mice was dependent on MMP-12 and eosinophil-derived IL-4/13. Consistent with this, MMP-12 was elevated in patients with sputum eosinophilia and computed tomography evidence of emphysema, and also negatively correlated with forced expiratory volume in 1 s.A mouse model of chronic type 2 pulmonary inflammation exhibited airspace enlargement dependent on MMP-12 and eosinophil-derived IL-4/13. In chronic airways disease patients, lung eosinophilia was associated with elevated MMP-12 levels, which was a predictor of emphysema. These findings suggest an underappreciated mechanism by which eosinophils contribute to the pathologies associated with asthma and COPD.

Use of inhaled corticosteroids and the risk of developing type 2 diabetes in patients with chronic obstructive pulmonary disease

2020 ◽  
Vol 22 (8) ◽  
pp. 1348-1356
Author(s):  
Mohamad Isam Saeed ◽  
Josefin Eklöf ◽  
Imane Achir ◽  
Pradeesh Sivapalan ◽  
Howraman Meteran ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease
Sign in / Sign up

Export Citation Format

Share Document