sFRP2 promotes airway inflammation and Th17/Treg imbalance in COPD via Wnt/β-catenin pathway.
Respir Physiol Neurobiol. 2019 Aug 17;:103282
Authors: Zhou M, Jiao L, Liu Y
Imbalance between inflammatory Th17 cells and immunosuppressive regulatory T cells (Treg) contributes to the progression of chronic obstructive pulmonary disease (COPD). We aims to investigate roles and mechanisms of secreted frizzled-related protein 2 (sFRP2) in airway inflammation and Th17/Treg differentiation in COPD. sFRP2 was significantly upregulated in the serum of patients with COPD and in human bronchial epithelial (HBE) cells that were exposed to cigarette smoke extract (CSE). sFRP2 was negatively correlated with FEV1/FVC. CSE increased IL-6 and TNF-α in HBE cells, which was reversed by sFRP2 silencing. CSE exposure elevated the percentage of Th17 in CD3+ CD8- cells while reduced the percentage of Treg in CD4+CD25+ cells. Knockdown of sFRP2 in peripheral blood mononuclear cells (PBMCs) attenuated Th17 differentiation and induced Treg differentiation. CSE suppressed the expression of β-catenin and Cyclin D1 in PBMCs while knockdown of sFRP2 markedly reversed the inhibitory effects of CSE. Wnt/β-catenin inhibition by Dickkopf-1 reversed the inhibitory effect of si-sFRP2 on the production of inflammatory cytokines and imbalance between Th17 and Treg cells caused by CSE. CSE induced sFRP2 potentiated airway inflammation and disturbed Th17/Treg homeostasis by inhibiting β-catenin.
PMID: 31430541 [PubMed - as supplied by publisher]
Prevalence and Treatment of Chronic Obstructive Pulmonary Disease (COPD) in the United States.
JAMA. 2019 Aug 20;322(7):602
Authors: Biener AI, Decker SL, Rohde F
PMID: 31429884 [PubMed - in process]
Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD.
Respir Res. 2019 Aug 20;20(1):190
Authors: Sidhaye VK, Holbrook JT, Burke A, Sudini KR, Sethi S, Criner GJ, Fahey JW, Berenson CS, Jacobs MR, Thimmulappa R, Wise RA, Biswal S
BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have high oxidative stress associated with the severity of the disease. Nuclear factor erythroid-2 related factor 2 (Nrf2)-directed stress response plays a critical role in the protection of lung cells to oxidative stress by upregulating antioxidant genes in response to tobacco smoke. There is a critical gap in our knowledge about Nrf-2 regulated genes in active smokers and former-smokers with COPD in different cell types from of lungs and surrogate peripheral tissues.
METHODS: We compared the expression of Nrf2 and six of its target genes in alveolar macrophages, nasal, and bronchial epithelium and peripheral blood mononuclear cells (PBMCs) in current and former smokers with COPD. We compared cell-type specific of Nrf2 and its target genes as well as markers of oxidative and inflammatory stress.
RESULTS: We enrolled 89 patients; expression all Nrf2 target gene measured were significantly higher in the bronchial epithelium from smokers compared to non-smokers. None were elevated in alveolar macrophages and only one was elevated in each of the other compartments.
CONCLUSION: Bronchial epithelium is the most responsive tissue for transcriptional activation of Nrf2 target genes in active smokers compared to former-smokers with COPD that correlated with oxidative stress and inflammatory markers. There were no consistent trends in gene expression in other cell types tested.
TRIAL REGISTRATION: Clinicaltrials.gov : NCT01335971.
PMID: 31429757 [PubMed - in process]
Are there specific clinical characteristics associated with physician's treatment choices in COPD?
Respir Res. 2019 Aug 20;20(1):189
Authors: Roche N, Antoniadis A, Hess D, Li PZ, Kelkel E, Leroy S, Pison C, Burgel PR, Aguilaniu B, COLIBRI COPD Research Group
BACKGROUND: The number of pharmacological agents and guidelines available for COPD has increased markedly but guidelines remain poorly followed. Understanding underlying clinical reasoning is challenging and could be informed by clinical characteristics associated with treatment prescriptions.
METHODS: To determine whether COPD treatment choices by respiratory physicians correspond to specific patients' features, this study was performed in 1171 patients who had complete treatment and clinical characterisation data. Multiple statistical models were applied to explain five treatment categories: A: no COPD treatment or short-acting bronchodilator(s) only; B: one long-acting bronchodilator (beta2 agonist, LABA or anticholinergic agent, LAMA); C: LABA+LAMA; D: a LABA or LAMA + inhaled corticosteroid (ICS); E: triple therapy (LABA+LAMA+ICS).
RESULTS: Mean FEV1 was 60% predicted. Triple therapy was prescribed to 32.9% (treatment category E) of patients and 29.8% received a combination of two treatments (treatment categories C or D); ICS-containing regimen were present for 44% of patients altogether. Single or dual bronchodilation were less frequently used (treatment categories B and C: 19% each). While lung function was associated with all treatment decisions, exacerbation history, scores of clinical impact and gender were associated with the prescription of > 1 maintenance treatment. Statistical models could predict treatment decisions with a < 35% error rate.
CONCLUSION: In COPD, contrary to what has been previously reported in some studies, treatment choices by respiratory physicians appear rather rational since they can be largely explained by the patients' characteristics proposed to guide them in most recommendations.
PMID: 31429756 [PubMed - in process]
Technology-Enabled Self-Monitoring of Chronic Obstructive Pulmonary Disease With or Without Asynchronous Remote Monitoring: Protocol for a Randomized Controlled Trial.
JMIR Res Protoc. 2019 Aug 19;8(8):e13920
Authors: Stamenova V, Yang R, Engel K, Liang K, van Lieshout F, Lalingo E, Cheung A, Erwood A, Radina M, Greenwald A, Agarwal P, Sidhu A, Bhatia RS, Shaw J, Shafai R, Bhattacharyya O
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality worldwide. Reducing the number of COPD exacerbations is an important patient outcome and a major cost-saving approach. Both technology-enabled self-monitoring (SM) and remote monitoring (RM) programs have the potential to reduce exacerbations, but they have not been directly compared with each other. As RM is a more resource-intensive strategy, it is important to understand whether it is more effective than SM.
OBJECTIVE: The objective of this study is to evaluate the impact of SM and RM on self-management behaviors, COPD disease knowledge, and respiratory status relative to standard care (SC).
METHODS: This was a 3-arm open-label randomized controlled trial comparing SM, RM, and SC completed in an outpatient COPD clinic in a community hospital. Patients in the SM and RM groups recorded their vital signs (oxygen, blood pressure, temperature, and weight) and symptoms with the Cloud DX platform every day and were provided with a COPD action plan. Patients in the RM group also received access to a respiratory therapist (RT). The RT monitored their vital signs intermittently and contacted them when their vitals varied outside of predetermined thresholds. The RT also contacted patients once a week irrespective of their vital signs or symptoms. All patients were randomized to 1 of the 3 groups and assessed at baseline and 3 and 6 months after program initiation. The primary outcome was the Partners in Health scale, which measures self-management skills. Secondary outcomes included the St. George's Respiratory Questionnaire, Bristol COPD Knowledge Questionnaire, COPD Assessment Test, and modified-Medical Research Council Breathlessness Scale. Patients were also asked to self-report on health system usage.
RESULTS: A total of 122 patients participated in the study, 40 in the SC, 41 in the SM, and 41 in the RM groups. Out of those patients, 7 in the SC, 5 in the SM, and 6 in the RM groups did not complete the study. There were no significant differences in the rates of study completion among the groups (P=.80).
CONCLUSIONS: Both SM and RM have shown promise in reducing acute care utilization and exacerbation frequencies. As far as we are aware, no studies to date have directly compared technology-enabled self-management with RM programs in COPD patients. We believe that this study will be an important contribution to the literature.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03741855; https://clinicaltrials.gov/ct2/show/NCT03741855.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13920.
PMID: 31429418 [PubMed]