ABSTRACT
BACKGROUND: Fibrotic interstitial lung disease (fILD) is characterised primarily by impaired lung function and quality of life. The present study investigated whether oxygen therapy could improve exercise capacity among patients with fILD. METHODS: Previously published randomised controlled trials (RCTs) were surveyed. A systematic review and meta-analysis was conducted to evaluate the effectiveness of oxygen therapy in improving the exertional capacity of patients with fILD. The primary outcome was peripheral oxygen saturation (SpO2) during exercise. The effects of oxygen therapy on fatigue, dyspnoea, heart rate, and exercise duration or distance were also analysed. RESULTS: Fourteen RCTs involving 370 patients were included. Oxygen therapy improved SpO2 during exercise (mean difference, MD = 6.26 %), exercise duration (MD = 122.15 s), fatigue (standard mean difference, SMD = -0.30), and dyspnoea (MD = -0.75 Borg score units). High-flow oxygen systems tended to be more effective than low-flow systems in improving exercising SpO2, duration, fatigue, dyspnoea, and heart rate. High-flow nasal cannulas (HFNCs) yielded better outcomes regarding SpO2 and fatigue than did high-flow Venturi masks (MD = 1.60 % and MD = -1.19 Borg score units, respectively). No major adverse events were reported. CONCLUSION: The evidence from RCTs supports the short-term use of oxygen supplementation to improve SpO2, exercise capacity, fatigue, and dyspnoea among patients with fILD. Further analyses demonstrates that HFNCs yield more favourable outcomes, yet not reaching statistical significance except for improving SpO2 and fatigue. However, the long-term effects of oxygen therapy on quality of life and mortality remain unclear.
Subject(s)
Dyspnea , Exercise Tolerance , Lung Diseases, Interstitial , Oxygen Inhalation Therapy , Quality of Life , Randomized Controlled Trials as Topic , Humans , Oxygen Inhalation Therapy/methods , Exercise Tolerance/physiology , Lung Diseases, Interstitial/therapy , Lung Diseases, Interstitial/physiopathology , Dyspnea/therapy , Dyspnea/etiology , Oxygen Saturation , Fatigue/therapy , Fatigue/etiology , Male , Female , Heart Rate/physiology , Middle Aged , Treatment Outcome , AgedABSTRACT
BACKGROUND: Severe asthma, characterized by inflammation and airway remodeling, involves fibroblast differentiation into myofibroblasts expressing α-SMA. This process leads to the production of fibronectin and connective tissue growth factor (CTGF), driven by factors such as transforming growth factor (TGF)-ß. Furthermore, the persistent presence of myofibroblasts is associated with resistance to apoptosis and mitochondrial dysfunction. The chemokine (C-X3-C motif) ligand 1 (CX3CL1) plays a role in tissue fibrosis. However, it is currently unknown whether neutralization of CX3CL1 decreases TGF-ß-induced fibroblast differentiation and mitochondrial dysfunction in normal human lung fibroblasts (NHLFs). METHODS: CX3CL1/C-X3-C motif chemokine receptor 1 (CX3CR1), CX3CL1 was analyzed by immunofluorescence (IF) or immunohistochemical (IHC) staining of ovalbumin-challenged mice. CX3CL1 release was detected by ELISA. TGF-ß-induced CTGF, fibronectin, and α-SMA expression were evaluated in NHLFs following neutralization of CX3CL1 (TP213) treatment for the indicated times by Western blotting or IF staining. Mitochondrion function was detected by a JC-1 assay and seahorse assay. Cell apoptosis was observed by a terminal uridine nick-end labeling (TUNEL) assay. RESULTS: An increase in CX3CL1 expression was observed in lung tissues from mice with ovalbumin-induced asthma by IF staining. CX3CR1 was increased in the subepithelial layer of the airway by IHC staining. Moreover, CX3CR1 small interfering (si)RNA downregulated TGF-ß-induced CTGF and fibronectin expression in NHLFs. CX3CL1 induced CTGF and fibronectin expression in NHLFs. TGF-ß-induced CX3CL1 secretion from NHLFs. Furthermore, TP213 decreased TGF-ß-induced CTGF, fibronectin, and α-SMA expression in NHLFs. Mitochondrion-related differentially expressed genes (DEGs) were examined after CX3CL1 neutralization in TGF-ß-treated NHLFs. TP213 alleviated TGF-ß-induced mitochondrial dysfunction and apoptosis resistance in NHLFs. CX3CL1 induced p65, IκBα, and IKKα phosphorylation in a time-dependent manner. Furthermore, CX3CL1-induced fibronectin expression and JC-1 monomer were decreased by p65 siRNA. TP213 reduced TGF-ß-induced p65 and α-SMA expression in NHLFs. CONCLUSIONS: These findings suggest that neutralizing CX3CL1 attenuates lung fibroblast activation and mitochondrial dysfunction. Understanding the impacts of CX3CL1 neutralization on fibroblast mitochondrial function could contribute to the development of therapeutic strategies for managing airway remodeling in severe asthma.
Subject(s)
Apoptosis , CX3C Chemokine Receptor 1 , Cell Differentiation , Chemokine CX3CL1 , Connective Tissue Growth Factor , Fibroblasts , Fibronectins , Mitochondria , Pulmonary Fibrosis , Transforming Growth Factor beta , Chemokine CX3CL1/metabolism , Chemokine CX3CL1/genetics , Animals , Mitochondria/metabolism , Mitochondria/drug effects , Mitochondria/pathology , Humans , Connective Tissue Growth Factor/metabolism , Connective Tissue Growth Factor/genetics , Cell Differentiation/drug effects , Apoptosis/drug effects , Fibroblasts/metabolism , Fibroblasts/drug effects , Fibroblasts/pathology , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Transforming Growth Factor beta/metabolism , CX3C Chemokine Receptor 1/metabolism , CX3C Chemokine Receptor 1/genetics , Fibronectins/metabolism , Mice , Actins/metabolism , Lung/pathology , Lung/metabolism , NF-kappa B/metabolism , Signal Transduction , Asthma/metabolism , Asthma/pathology , Disease Models, Animal , Cells, Cultured , Myofibroblasts/metabolism , Myofibroblasts/pathology , Myofibroblasts/drug effects , OvalbuminABSTRACT
OBJECTIVE: Cancer-related fatigue (CRF) is a common side effect in cancer patients, possibly due to disrupted circadian rhythms. While bright light therapy (BLT) is known to modulate circadian rhythms, its role in mitigating CRF remains unclear. This study examined the impact of BLT on CRF and other related symptoms. METHODS: PubMed, Embase, Cochrane Library, and SCOPUS databases were searched. The trials were selected according to the PRISMA guidelines. The severity and quality of CRF and related symptoms were investigated in post-BLT intervention. RESULTS: Twelve trials involving 691 were included. BLT significantly reduced CRF (SMD = -0.92, 95% CI: -1.45 to -0.40, p < 0.00001, I2 = 90%) and insomnia (SMD = -2.80, 95% CI: -4.61 to -0.98, I2 = 0%). Subgroup analyzes were performed based on various factors including light illuminance and intervention duration. BLT was found to be effective in both preventing and treating CRF, though it did not significantly enhance sleep quality, depression, and quality of life (QoL). CONCLUSION: BLT is a promising intervention for managing CRF in cancer patients. Its efficacy in improving sleep quality, and insomnia, reducing depression, and enhancing QoL requires further exploration. A 4-week BLT intervention with ≥10,000 lx is recommended for preventing and treating CRF, with longer or less intense interventions also showing effectiveness. Otherwise, BLT exhibited minimal adverse effects.
Subject(s)
Neoplasms , Sleep Initiation and Maintenance Disorders , Humans , Depression/therapy , Quality of Life , Sleep Initiation and Maintenance Disorders/etiology , Sleep Initiation and Maintenance Disorders/therapy , Randomized Controlled Trials as Topic , Neoplasms/complications , Neoplasms/therapy , Phototherapy , Fatigue/etiology , Fatigue/therapyABSTRACT
BACKGROUND: Airway fibrosis is one of the pathological characteristics of severe asthma. Transforming growth factor (TGF)-ß has been known to promote epithelial-mesenchymal transition formation and to play a role in the progression of tissue fibrosis. Cellular communication network factor 2 (CCN2) and fibronectin (FN) are well-known markers of EMT and fibrosis. However, whether AREG is involved in TGF-ß-induced CCN2 and FN expression in human lung epithelial cells is unknown. METHODS: AREG and FN were analyzed by immunofluorescence staining on ovalbumin-challenged mice. CCN2 and FN expression were evaluated in human lung epithelial (A459) cells following TGF or AREG treatment for the indicated times. Secreted AREG from A549 cells was detected by ELISA. Cell migration was observed by a wound healing assay. Chromatin immunoprecipitation was used to detect the c-Jun binding to the CCN2 promoter. RESULTS: AREG and FN expression colocalized in lung tissues from mice with ovalbumin-induced asthma by immunofluorescence staining. Moreover, TGF-ß caused the release of AREG from A549 cells into the medium. Smad3 siRNA down-regulated AREG expression. AREG also stimulated CCN2 and FN expression, JNK and c-Jun phosphorylation, and cell migration in A549 cells. AREG small interfering (si) RNA inhibited TGF-ß-induced expression of CCN2, FN, and cell migration. Furthermore, AREG-induced CCN2 and FN expression were inhibited by EGFR siRNA, a JNK inhibitor (SP600125), and an activator protein-1 (AP-1) inhibitor (curcumin). EGFR siRNA attenuated AREG-induced JNK and c-Jun phosphorylation. Moreover, SP600125 downregulated AREG-induced c-Jun phosphorylation. CONCLUSION: These results suggested that AREG mediates the TGF-ß-induced EMT in human lung epithelial cells through EGFR/JNK/AP-1 activation. Understanding the role of AREG in the EMT could foster the development of therapeutic strategies for airway remodeling in severe asthma.
