Low phosphorus increases hepatic lipid deposition, oxidative stress and inflammatory response via Acetyl-CoA carboxylase-dependent manner in zebrafish liver cells.

Acetyl-CoA carboxylase (ACC) plays a regulatory role in both fatty acid synthesis and oxidation, controlling the process of lipid deposition in the liver. Given that existing studies have shown a close relationship between low phosphorus (P) and hepatic lipid deposition, this study was conducted to investigate whether ACC plays a crucial role in this relationship. Zebrafish liver cell line (ZFL) was incubated under low P medium (LP, P concentration: 0.77 mg/L) or adequate P medium (AP, P concentration: 35 mg/L) for 240 h. The results showed that, compared with AP-treated cells, LP-treated cells displayed elevated lipid accumulation, and reduced fatty acid ß-oxidation, ATP content, and mitochondrial mass. Furthermore, transcriptomics analysis revealed that LP-treated cells significantly increased lipid synthesis (Acetyl-CoA carboxylases (acc), Stearyl coenzyme A dehydrogenase (scd)) but decreased fatty acid ß-oxidation (Carnitine palmitoyltransferase I (cptI)) and (AMP-activated protein kinase (ampk)) mRNA levels compared to AP-treated cells. The phosphorylation of AMPK and ACC, and the protein expression of CPTI were significantly decreased in LP-treated cells compared with those in AP-treated cells. After 240 h of LP treatment, PF-05175157 (an ACC inhibitor) was supplemented in the LP treatment for an additional 12 h. PF-05175157-treated cells showed higher phosphorylation of ACC, higher protein expression of CPTI, and lower protein expression of FASN, lower TG content, enhanced fatty acid ß-oxidation, increased ATP content, and mitochondrial mass compared with LP-treated cells. PF-05175157 also relieved the LP-induced oxidative stress and inflammatory response. Overall, these findings suggest that ACC is a promising target for treating LP-induced elevation of lipid deposition in ZFL, and can alleviate oxidative stress and inflammatory response.

Nrf2 pathway in vegetable oil-induced inflammation of large yellow croaker (Larimichthys crocea).

This study was conducted to investigate the effects and regulation of dietary vegetable oil (VO, enriched with α-linolenic acid [ALA] and linoleic acid [LNA]) on the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) pathways in large yellow croaker. In vivo study showed that the VO diet significantly decreased the activity of antioxidant enzymes and antioxidant enzyme-related mRNA expression in the liver tissue, in comparison with the fish oil (FO) diet (P < 0.05). The suppression of antioxidant capacity might be due to the decrease of nuclear Nrf2 protein translocation, Nrf2 binding to antioxidant response element (ARE) sequences, and subsequently, antioxidant genes transcription as electrophoretic mobility shift assay (EMSA) and luciferase assay showed. VO-derivated ALA and LNA exerted a lower antioxidant capacity than FO-derivated DHA and EPA, characterized by significantly lower nucleus Nfr2 protein expression but significantly higher ROS production values in primary hepatocytes (P < 0.05). The pro-inflammatory genes (tumor necrosis factor α [TNFα] and interleukin 1ß [IL1ß]) expression was significantly higher in the liver tissue of fish fed the VO diet which might be due to the activation of the NF-κB pathway (P < 0.05). Knockdown of the Nrf2 gene negatively affected the anti-inflammatory effect of fatty acids by increasing the expression of TNFα and the IL1ß gene and nuclear p65 protein (P < 0.05). In general, the results indicated that dietary vegetable oil decreased antioxidant capacity but induced inflammatory responses through the Nrf2/NF-κB pathway.

High water temperature raised the requirements of methionine for spotted seabass (Lateolabrax maculatus).

This study evaluated the effects of dietary methionine level and rearing water temperature on growth, antioxidant capacity, methionine metabolism, and hepatocyte autophagy in spotted seabass (Lateolabrax maculatus). A factorial design was used with six methionine levels [0.64, 0.85, 1.11, 1.33, 1.58, and 1.76%] and two temperatures [moderate temperature (MT): 27 ℃, and high temperature (HT): 33 ℃]. The results revealed the significant effects of both dietary methionine level and water temperature on weight gain (WG) and feed efficiency (FE), and their interaction effect was found on WG (P < 0.05). In both water temperatures tested, fish WG increased with increasing methionine level up to 1.11% and decreased thereafter. The groups of fish reared at MT exhibited dramatically higher WG and FE than those kept at HT while an opposite trend was observed for feed intake. Liver antioxidant indices including reduced glutathione and malondialdehyde (MDA) concentrations, and catalase and superoxide dismutase (SOD) activities remarkably increased in the HT group compared to the MT group. Moreover, the lowest MDA concentration and the highest SOD activity were recorded at methionine levels between 1.11% and 0.85%, respectively, regardless of water temperatures. Expression of methionine metabolism-related key enzyme genes (mat2b, cbs, ms, and bhmt) in the liver was increased at moderate methionine levels, and higher expression levels were detected at MT compared to HT with the exception of ms gene relative expression. Relative expression of hepatocyte autophagy-related genes (pink1, atg5, mul1, foxo3) and hsp70 was upregulated by increasing methionine level up to a certain level and decreased thereafter and increasing water temperature led to significantly enhanced expression of hsp70. In summary, HT induced heat stress and reduced fish growth, and an appropriate dietary methionine level improved the antioxidant capacity and stress resistance of fish. A second-order polynomial regression analysis based on the WG suggested that the optimal dietary methionine level for maximum growth of spotted seabass is 1.22% of the diet at 27 ℃ and 1.26% of the diet at 33 ℃, then 1.37 g and 1.68 g dietary methionine intake is required for 100 g weight gain at 27 ℃ or 33 ℃, respectively.

Effects of dietary curcumin on growth, antioxidant capacity, fatty acid composition and expression of lipid metabolism-related genes of large yellow croaker fed a high-fat diet.

A 10-week feeding trial was conducted to investigate the effect of dietary curcumin (CC) on growth antioxidant responses, fatty acid composition, and expression of lipid metabolism-related genes of large yellow croaker fed a high-fat diet (HFD). Four diets (lipid level at 18 %) were formulated with different levels of curcumin (0, 0·02, 0·04 and 0·06 %). The best growth performance was found in the 0·04 % curcumin group, with the body and hepatic lipid levels lower than the control group (0 % CC). The content of TAG, total cholesterol and LDL-cholesterol was the least in the 0·06 % curcumin group. The lowest malondialdehyde and the highest superoxide dismutase, catalase and total antioxidant capacity were observed in the 0·04 % curcumin group. The 0·04 % curcumin group had higher expression of Δ6fad, elovl5 and elovl4 and showed higher hepatic n-6 and n-3 PUFA. Expression of ppara, cpt1, and aco was significantly increased, while expression of srebp1 and fas was dramatically decreased in curcumin groups compared with the control group. Overall, 0·04 % curcumin supplementation could mitigate the negative effects caused by HFD and promote growth via reducing hepatic lipid deposition, improving antioxidant activity and increasing PUFA of large yellow croaker. To conclude, abnormal hepatic lipid deposition was probably due to increased fatty acid oxidation and reduced de novo synthesis of fatty acids.

Effects of dietary terrestrial oils supplemented with L-carnitine on growth, antioxidant capacity, lipid metabolism and inflammation in large yellow croaker (Larimichthys crocea).

The present study was conducted to determine the effects of dietary terrestrial oils (TO) supplemented with L-carnitine on growth performance, biochemical and antioxidant response, lipid metabolism and inflammation in large yellow croaker (Larimichthys crocea). Three iso-nitrogenous and iso-lipidic experimental diets were formulated with FO (fish oil, the control group), 75% TO (75% FO was substituted by the oil mixture with equal amounts of soybean oil, linseed oil and pork lard) and 75% TOC (75% TO supplemented with 800 mg/kg L-carnitine), respectively. Compared to the control group, feed efficiency ratio and specific growth rate were significantly increased in fish fed diets with 75% TO and 75% TOC. Hepatic lipid content, serum triglyceride level, low-density lipoprotein-cholesterol level and the mRNA expression of pro-inflammatory genes (tnfα and ifnγ) were significantly increased in fish fed the diet with 75% TO compared to the control group. However, the supplementation of 800 mg/kg L-carnitine in the 75% TO diet repressed hepatic lipid content, serum low-density lipoprotein-cholesterol level and the mRNA expression of tnfα and ifnγ in fish compared to fish fed the diet with 75% TO. Total antioxidant capacity, the activity of superoxide dismutase, the mRNA expression of cpt-I and the activity of CPT-I were significantly increased in fish fed the diet with 75% TOC compared to 75% TO. In conclusion, these results suggested that the supplementation of 800 mg/kg L-carnitine in the diet with terrestrial oils mixture could increase growth, antioxidant capacity, fatty acid oxidation and decrease the expression of inflammatory genes in large yellow croaker.

Effect of replacement of dietary fish oil with four vegetable oils on prostaglandin E2 synthetic pathway and expression of inflammatory genes in marine fish Larimichthys crocea.

As a lipid mediator with important immune function, prostaglandin E2 (PGE2) has been widely studied in mammals, whereas its synthetic pathway and immune function in fish have yet to be fully studied. To investigate the regulation of PGE2 synthetic pathway and inflammatory genes expression by dietary different oils and the underlying relationship, a 10-week feeding experiment and an immune challenge were carried out in marine fish Larimichthys crocea. Replacement of dietary fish oil (FO) with four vegetable oils (VO), including soybean oil, linseed oil, palm oil, and olive oil, all reduced PGE2 levels, and the decrease of arachidonic acid (ARA, substrate for PGE2) could account for this decline. Meanwhile, the expression of PGE2 synthesis related genes was basically upregulated, which seemed to be a feedback regulation, but it cannot compensate the deficiency of ARA. In addition, mRNA expression of inflammatory genes, including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)α and interferon (IFN)γ was all upregulated in four VO groups compared with FO group, which was the opposite of PGE2 levels. To verify the inflammatory regulation of PGE2, an immune challenge was conducted, and PGE2 alleviated LPS-induced expression of inflammatory genes, including IL-6, TNFα and IFNγ, and the similar downregulation of toll-like receptor (TLR) genes expression revealed that TLR signaling pathway participated in the anti-inflammatory regulation of PGE2. In conclusion, replacement of dietary FO with four VO (lack of ARA) reduced the levels of PGE2 that could alleviate LPS-induced inflammatory genes expression via TLR signaling pathway, which could be one of the reasons that VO induced inflammation in marine fish.

Adipose tissue contributes to hepatic pro-inflammatory response when dietary fish oil is replaced by vegetable oil in large yellow croaker (Larimichthys crocea): An ex vivo study.

The shortage of fish oil (FO) leads to the extensive use of vegetable oil (VO) in marine fish diets. High replacement percentage of dietary FO by VO induced pro-inflammatory response of adipose tissue (AT) and liver tissue (LT) in large yellow croaker (Larimichthys crocea). Mammalian studies showed that the secretion of cytokines by AT affected the immune response of LT. To investigate whether or not the inflammation response of LT is related to AT in large yellow croaker, LT and AT cells from fish fed FO diet (FOL and FOA) and VO diet (VOL and VOA) were co-cultured in a trans-well system, which resulted in an assembly of the two cells types sharing the culture medium but being separated by the membrane of the insert. Co-culture of FOL and FOA was selected as the control group (FOL-FOA). Results indicated that, when compared with the control group, the expression of pro-inflammatory genes (toll like receptors [TLRs], tumour necrosis factor α [TNFα], interleukin 1ß [IL1ß], suppressor of cytokine signalling 3 [SOCS3] and cyclooxygenase 2 [COX2]) in FOL was significantly increased in the co-culture group of FOL and VOA (FOL-VOA), while the expression of anti-inflammatory genes (arginase I [ArgI] and transforming growth factor ß1 [TGFß1]) in FOL was significantly depressed. On the contrary, a significantly depressed expression of pro-inflammatory genes (TLRs, TNFα, IL1ß and COX2) and increased expression of anti-inflammatory genes (interleukin 10 [IL10]) in VOL was observed in the co-culture group of VOL and FOA (VOL-FOA) when compared with the co-culture group of VOL and VOA (VOL-VOA). The change of immune-related gene expressions in LT cells was attributed to nuclear factor κB (NF-κB) signalling since the expression of the p65 protein was observed to show a similar trend to the expression of pro-inflammatory genes. It is speculated that dietary VO increased the secretion of cytokines, which induced pro-inflammatory response in LT cells. These ex vivo results indicate that AT plays a vital role in LT pro-inflammatory response in fish fed VO diet.

High level of dietary olive oil decreased growth, increased liver lipid deposition and induced inflammation by activating the p38 MAPK and JNK pathways in large yellow croaker (Larimichthys crocea).

A feeding experiment was conducted to determine the effects of fish oil replaced by olive oil (OO) on growth performance, serum biochemical, antioxidant capacity and inflammatory response in large yellow croaker (Larimichthys crocea). Four iso-nitrogenous and iso-lipidic diets were formulated by replacing fish oil (FO) with 0% (the control group), 33.3%, 66.7% and 100% OO. Fish fed the diet with 100% OO had the lowest growth performance among dietary treatments. However, there were no significant differences in SGR and FI among fish fed diets with 0% (the control group), 33.3% and 66.7% OO (P > 0.05). As to morphological parameters, HSI was significantly increased in fish fed the diet with 100% OO than the control group (P < 0.05). Furthermore, the lipid content of the liver in fish fed the diet with 100% OO was significantly higher than the control group (P < 0.05). Fish fed the diet with 100% OO had the highest content of C18:1n-9 among dietary treatments. Serum total triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) levels and activity of serum alanine transaminase (ALT) were significantly increased in fish fed the diet with 100% OO compared with the control group (P < 0.05). Meanwhile, dietary OO decreased the activity of superoxide dismutase (SOD) and the total antioxidant capacity (T-AOC) in fish fed diets with increasing dietary OO levels. However, the content of malondialdehyde (MDA) was significantly increased in fish fed the diet with 100% OO compared with the control group (P < 0.05). The expression of pro-inflammatory genes, COX-2, IL-1ß and TNFα, were significantly increased in the liver of fish fed the diet with 100% OO compared with the control group (P < 0.05), which was probably due to the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathways and Jun N-terminal kinase (JNK) as the increased protein ratio of p-p38 MAPK to p38 MAPK and p-JNK to JNK. These results suggested that high level of dietary OO decreased the growth performance and antioxidant capacity but induced inflammation via the activation of p38 MAPK and JNK pathways in large yellow croaker.

High percentage of dietary palm oil suppressed growth and antioxidant capacity and induced the inflammation by activation of TLR-NF-κB signaling pathway in large yellow croaker (Larimichthys crocea).

A 70-day feeding trial was conducted to investigate the effects of dietary fish oil (FO) replaced by palm oil (PO) on growth, biochemical and antioxidant response as well as inflammatory response in the liver of large yellow croaker (initial weight 15.87 ±â€¯0.14 g). Four iso-proteic and iso-lipidic experimental diets were formulated with 0% (the control group), 33.3%, 66.7% and 100% FO replaced by PO. Fish fed the diet with 100% PO showed significantly lower growth performance than the control group. As expected, the contents of C16:0, C18:1n-9 and C18:2n-6 were increased with increasing dietary PO levels. There were remarkable increases in total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels in fish fed the diet with 100% PO compared to the control group. Moreover, dietary PO significantly increased activities of plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) in fish fed the diet with 100% PO compared to the control group. The total antioxidant capacity (T-AOC) and the activity of catalase (CAT) in plasma were significantly decreased in fish fed the diet with 100% PO compared to the control group, and meanwhile no significant differences were found in T-AOC and CAT activity in fish fed diets with no more than 66.7% PO. Fish fed the diet with 100% PO exerted significantly higher toll like receptors (TLRs) and myeloid differentiation factor (MyD88) mRNA expression levels than the control group. The IFNγ, IL-1ß and TNFα mRNA expressions were increased with increasing dietary PO levels. The increase of pro-inflammatory gene expression may be due to the activation of NF-κB signaling as the ratio of nucleus p65 to total p65 protein was elevated with the increase of dietary PO levels. These results showed that relatively higher PO levels in diets suppressed the growth and antioxidant capacity as well as induced the inflammatory response by activating TLR-NF-κB signaling pathway in juvenile large yellow croaker.

Palmitic acid activates NLRP3 inflammasome through NF-κB and AMPK-mitophagy-ROS pathways to induce IL-1ß production in large yellow croaker (Larimichthys crocea).

Studies on marine fish showed that vegetable oils substituted for excessive fish oil increased interleukin-1ß (IL-1ß) production. However, whether the nucleotide-binding oligomerization domain, leucine-rich repeat-containing family, pyrin domain-containing-3 (NLRP3) inflammasome has a substantial role in fatty acid-induced IL-1ß production in fish remains unclear. The associated specific mechanism is also unknown. In this study, nlrp3, caspase-1 and apoptosis-associated speck-like protein containing a CARD (asc) were successfully cloned, and NLRP3 inflammasome consisted of NLRP3, caspase-1 and ASC in large yellow croaker. Primary hepatocytes of fish incubated with palmitic acid (PA) exhibited the highest expression of pro-inflammatory genes (il-1ß and tnfα) and NLRP3 inflammasome related genes (nlrp3, caspase-1 and asc), caspase-1 activity and IL-1ß production among different treatments. Furthermore, PA-induced NLRP3 inflammasome activation was confirmed to require two signals: the first signal was that PA promoted the NF-κB (P65) protein into the nucleus, and NF-κB increased NLRP3 promoter activity and nlrp3 transcription. The second signal was that PA inhibited AMPK phosphorylation and decreased mitophagy by inhibiting the expression of PINK and parkin proteins, thereby damaging the mitochondria that could not be effectively cleared. Mitochondrial damage generated excessive amounts of reactive oxygen species, which activated the NLRP3 inflammasome and then induced caspase-1 activity and IL-1ß production. Therefore, excessive dietary PA activated NLRP3 inflammasome through NF-κB and AMPK-mitophagy-ROS pathways to induce IL-1ß production, thereby leading to inflammation in fish.

Effects of Dietary Supplementation of Bile Acids on Growth, Glucose Metabolism, and Intestinal Health of Spotted Seabass (Lateolabrax maculatus).

An 8-week feeding trial was performed to investigate the effects of dietary bile acids on growth, glucose metabolism, and intestinal health in spotted seabass (Lateolabrax maculatus) reared at high temperatures (33 °C). The fish (20.09 ± 1.12 g) were fed diets supplemented with bile acids: 0 (Con), 400 (BA400), 800 (BA800), and 1200 (BA1200) mg/kg, respectively. The results showed that the growth was promoted in fish at the BA800 treatment compared with the control (p < 0.05). Increased enzyme activities and transcripts of gluconeogenesis in the liver were observed, whereas decreased enzyme activities and transcripts of glycolysis, as well as glycogen content, were shown in the BA800 treatment (p < 0.05). The transcripts of bile acid receptors fxr in the liver were up-regulated in the BA800 treatment (p < 0.05). A bile acid supplementation of 800 mg/kg improved the morphological structure in the intestine. Meanwhile, intestinal antioxidant physiology and activities of lipase and trypsin were enhanced in the BA800 treatment. The transcripts of genes and immunofluorescence intensity related to pro-inflammation cytokines (il-1ß, il-8, and tnf-α) were inhibited, while those of genes related to anti-inflammation (il-10 and tgf-ß) were induced in the BA800 treatment. Furthermore, transcripts of genes related to the NF-κB pathway in the intestine (nfκb, ikkα, ikkß, and ikbα1) were down-regulated in the BA800 treatment. This study demonstrates that a dietary bile acid supplementation of 800 mg/kg could promote growth, improve glucose metabolism in the liver, and enhance intestinal health by increasing digestive enzyme activity and antioxidant capacity and inhibiting inflammatory response in L. maculatus.

Pulmonary embolism and left renal vein thrombosis extending into the inferior vena cava associated with nephrotic syndrome: A case report.

Nephrotic syndrome (NS) had serious complications due to hypercoagulable state in both various venous and arteries which could lead thromboembolic events. we described a case of a 41-year-old man who presented with pulmonary artery thrombosis and was diagnosed with NS. Early diagnosis and management of nephrotic syndrome may prevent the occurrence of venous thromboembolism (VTE).

Short version of the smartphone addiction scale: Measurement invariance across gender.

The Smartphone Addiction Scale Short Version (SAS-SV) has been widely used in research, but little is known about the measurement invariance across gender. The current study measured SAS-SV invariance between male and female college students in a sample of 1112 participants. Single- and multiple-group confirmatory factor analyses (CFAs) of smartphone addiction symptom ratings were conducted using R program with RStudio. SAS-SV was psychometrically robust in measuring the severity of smartphone addiction among college students, as well as the gender-based invariance. The differences in SAS-SV between male and female participants were likely to represent true gender differences, and meaningful comparisons could be made.

Efficacy of Ultrasound-Guided Thoracic Paravertebral Block on Postoperative Quality of Recovery in Patients Undergoing Percutaneous Nephrolithotomy: A Randomized Double-Blind Placebo-Controlled Trial.

Purpose: This study aimed to examine the effectiveness of ultrasound-guided thoracic paravertebral block on postoperative quality of recovery in patients undergoing percutaneous nephrolithotomy. Patients and Methods: In this randomized, double-blind, placebo-controlled trial, we enrolled patients scheduled for unilateral percutaneous nephrolithotomy. Patients were randomly allocated to receive thoracic paravertebral block either with 20 mL of 0.5% ropivacaine (PVB group) or an equal volume of saline (control group). The primary outcome was the quality of patient recovery at 24 h postoperatively, assessed using the 15-item Quality of Recovery scale. The secondary outcomes included the area under the curve of pain scores over time, time to first rescue analgesia, and postoperative 24 h morphine consumption. Results: We analyzed the data of 70 recruited participants. The median Quality of Recovery-15 score at 24 h postoperatively was 127 (interquartile range, 117-133) in the PVB group, which was significantly higher than 114 (interquartile range, 109-122) in the control group, with a median difference of 10 points (95% confidence interval, 5-14; P<0.001). The area under the curve of pain scores over time was lower in patients receiving thoracic PVB than in those receiving saline block (P<0.001). The median time to first rescue analgesia in the PVB group (10.8 h, interquartile range 7.1-22.8 h) was longer than that in the control group (1.9 h, interquartile range 0.5-4.3 h) (P<0.001). Similarly, the median postoperative 24-hour morphine consumption was nearly half as low in the PVB group as in the control group (P<0.001). The occurrence of postoperative nausea and vomiting, and pruritus were significantly higher in the control group (P=0.016 and P=0.023, respectively). Conclusion: Preoperative ultrasound-guided single injection of thoracic paravertebral block with ropivacaine improved the postoperative quality of recovery and analgesia in patients undergoing percutaneous nephrolithotomy.

Physiological Response of Spotted Seabass (Lateolabrax maculatus) to Different Dietary Available Phosphorus Levels and Water Temperature: Changes in Growth, Lipid Metabolism, Antioxidant Status and Intestinal Microbiota.

A 10-week growth experiment was conducted to assess the physiological response of spotted seabass (Lateolabrax maculatus) raised at moderate (27 °C) and high temperatures (33 °C) to different dietary available phosphorus (P) levels. Five diets with available P levels of 0.35, 0.55, 0.71, 0.82 and 0.92% were formulated, respectively. A water temperature of 33 °C significantly decreased growth performance and feed utilization, and increased oxidative stress and lipid deposition of spotted seabass compared with 27 °C. A second-order polynomial regression analysis based on weight gain (WG) showed that the available P requirement of spotted seabass raised at 27 °C and 33 °C was 0.72% and 0.78%, respectively. The addition of 0.71-0.82% P to the diet improved the growth performance, feed utilization, and antioxidant capacity of spotted seabass and alleviated the excessive lipid deposition compared with the low-P diet (0.35% P). Moreover, the addition of 0.71-0.92% P to diets increased the diversity of intestinal microbiota and the relative abundance of Lactococcus lactis and decreased the relative abundance of Plesiomonas compared with the low-P diet. Thus, dietary supplementation with 0.71-0.82% P improved the growth performance, antioxidant capacity and microbial composition of spotted seabass, and alleviated the disturbance of lipid metabolism caused by high temperature or low-P diet.

The future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease in various GOLD groups: a focus on the GOLD 2017 and GOLD 2023 reports.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report revised the combined assessment, merged the C and D groups into the E group, and revised the initial inhalation therapy recommendation. OBJECTIVES: This study aimed to analyze the future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease (COPD) in various groups based on the GOLD 2017 and GOLD 2023 reports. DESIGN: This is a multicenter and retrospective study. METHODS: Stable COPD patients from the database setup by 12 hospitals were enrolled. The patients were divided into Groups A, B, C, D, and E according to the GOLD 2017 and GOLD 2023 reports. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting ß2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS subgroups. Data on exacerbation and death during 1 year of follow-up were collected. RESULTS: A total of 4623 patients were classified into Group A (15.0%), Group B (37.8%), Group C (7.3%), Group D (39.9%), and Group E (47.2%). The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies in Groups A and C. Patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS in Groups B, D, and E. The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies after combining Groups A with C. CONCLUSION: Patients in Group A should be recommended to undergo mono-LAMA, while patients in Groups B and E should be recommended treatment with LABA + LAMA, which is consistent with the GOLD 2023 report. However, it is worth considering merging Groups A and C into a single group and recommending mono-LAMA as the initial inhalation therapy.

Clinical characteristics and risk of all-cause mortality in low education patients with chronic obstructive pulmonary disease in the Chinese population.

Background: Education levels play a critical role in the development of chronic obstructive pulmonary disease (COPD), which mainly affects the elderly, who generally have a low level of education in China. We aimed to investigate the association between education level and COPD clinical characteristics and outcomes, especially the effects of education level on the all-cause mortality of COPD in the Chinese population. Methods: We retrieved data collected between December 2016 and June 2020 in the RealDTC, an ongoing multicenter, real-world study on the status of diagnosis and treatment of COPD. The patients were classified into low- and high-education groups. We extracted data on demographics, pulmonary function, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, modified Medical Research Council (mMRC) scores, COPD Assessment Test (CAT) scores, exacerbation history, therapy, and comorbidities, and on mortality during three years of follow-up. Results: We included 4098 patients with COPD, of whom 3258 (79.5%) were of low education. This group had higher ages, CAT scores, mMRC scores, and numbers of exacerbations, as well as a greater proportion of females, never smokers, biofuel exposure, and GOLD grade 3. Logistic regression showed that being aged ≥65 years, being female, having biofuel exposure, having CAT scores of 20-29, and having ≥2 exacerbations were independently associated with having low education (P < 0.05). Furthermore, low-education COPD patients had a higher cumulative mortality risk during three years of follow-up than their high-education counterparts (hazard ratio (HR) = 1.75; 95% confidence interval (CI) = 1.17-2.61, P = 0.006). Conclusions: Low-education COPD patients, who accounted for most of our sample, had a higher symptom burden, risk of exacerbation, and risk of all-cause mortality. Clinicians attending COPD patients should be more attentive of individuals with low education levels.

Clinical-functional characteristics and risk of exacerbation and mortality among more symptomatic patients with chronic obstructive pulmonary disease: a retrospective cohort study.

OBJECTIVES: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 classified chronic obstructive pulmonary disease (COPD) patients into more and less symptomatic groups. This study aimed to analyze the clinical characteristics, risk of future exacerbation and mortality among patients in more symptomatic group. DESIGN: A retrospective cohort study. SETTING: Data were obtained from patients enrolled in a database setup by Second Xiangya Hospital of Central South University. PARTICIPANTS: 1729 stable COPD patients listed from September 2017 to December 2019 in the database. The patients were classified into more and less symptomatic groups based on GOLD 2017 report. OUTCOMES: All patients were followed up for 18 months. We collected baseline data and recorded the number of exacerbations and mortality during follow-up. RESULTS: The more symptomatic patients were older, had higher Clinical COPD Questionnaire (CCQ) scores, more severe airflow limitation and higher number of exacerbations and hospitalizations in the past year (P < 0.05). Logistic regression showed that having more symptoms correlated with the CCQ scores and exacerbations in the past year (P < 0.05). After patients were followed up, there were higher numbers of exacerbations, hospitalizations and mortality rates in more symptomatic patients (P < 0.05). The multivariate model showed that age more than 65 years (OR = 2.047, 95% CI = 1.020-4.107) and COPD assessment test scores more than 30 (OR = 2.609, 95% CI = 1.339-5.085) were independent risk factors for mortality, whereas current smoker (OR = 1.565, 95% CI = 1.052-2.328), modified Medical Research Council scores (OR = 1.274, 95% CI = 1.073-1.512) and exacerbations in the past year (OR = 1.061, 95% CI = 1.013-1.112) were independent risk factors for exacerbation in more symptomatic patients (P < 0.05). CONCLUSIONS: More symptomatic COPD patients have worse outcomes. In addition, several independent risk factors for exacerbation and mortality were identified. Therefore, clinicians should be aware of these risk factors and take them into account during interventions.

The clinical characteristics and treatment response of patients with chronic obstructive pulmonary disease with low body mass index.

Background: This study aimed to analyze the clinical characteristics and treatment response of patients with chronic obstructive pulmonary disease (COPD) with low body mass index (BMI). Methods: In this cross-sectional study, we enrolled patients with stable COPD from the database setup by the Second Xiangya Hospital of Central South University. We classified the patients into three groups based on BMI: low-BMI (<18.5 kg/m2), normal-BMI (≥18.5 and <24.0 kg/m2), and high-BMI (≥24 kg/m2) groups. We defined clinically important deterioration (CID) as a COPD Assessment Test (CAT) score increase of ≥2 and minimum clinically important difference (MCID) as a CAT score decrease of ≥2 during 6 months of follow-up. We recorded the number of exacerbations and mortality during 1 year of follow-up. Results: A total of 910 COPD patients were included with 144 (15.8%) patients in low-BMI, 475 (52.2%) in normal-BMI, and 291 (32.0%) in high-BMI groups. Patients with low BMI had worse pulmonary function, higher symptom scores, and exacerbations in the past year compared with normal- and high-BMI groups (p < 0.05). Logistic regression analysis revealed that age, Global Initiative for Chronic Obstructive Lung Disease grades 3 and 4, and hospitalizations in the past year were independent risk factors for patients with low BMI (p < 0.05). After 1 year of follow-up, patients with low BMI had higher mortality and number of hospitalizations. Patients with low BMI were more likely to attain CID and less likely to attain MCID compared with patients with high BMI (p < 0.05). In addition, patients with low BMI treated with long-acting ß2-agonist (LABA)+long-acting muscarinic antagonist (LAMA) and LABA+LAMA+inhaled corticosteroid (ICS) were more likely to attain MCID than those treated with LABA+ICS and LAMA (p < 0.05). Conclusion: COPD patients with low BMI had worse pulmonary function, higher symptom scores, and higher risk of future hospitalizations and mortality and were less likely to attain MCID and more likely to attain CID. It is worth noting that patients with low BMI treated with LABA+LAMA and LABA+LAMA+ICS were more likely to attain MCID than those treated with LABA+ICS and LAMA.

The clinical characteristics and outcomes of different inhaled therapies in chronic obstructive pulmonary disease patients with frequent cough.

BACKGROUND: Cough is a common symptom in patients with chronic obstructive pulmonary disease (COPD). Patients with cough may exhibit various clinical characteristics and experience varying outcomes based on inhaled therapies they receive. OBJECTIVES: This study aimed to explore the clinical characteristics and outcomes of various inhaled therapies in COPD patients with frequent cough. METHODS: This was a multicenter, prospective cohort study. Of these patients, the median cough score in COPD assessment test (CAT) was two. Patients were classified into frequent cough group if they scored two or over in the first item of CAT and infrequent cough group otherwise. Patients with frequent cough were then divided into long-acting antimuscarinic (LAMA), long-acting beta2-agonist (LABA)/LAMA, inhaled corticosteroids (ICS)/LABA and ICS/LABA/LAMA groups. Minimum clinically important difference (MCID) (CAT scores decreased ≥2 from baseline) and the improvement of cough (cough score decreased ≥1 from baseline) were collected in the six-month follow-up. Frequent exacerbations (experiencing at least two exacerbations) were collected in the one-year follow-up. RESULTS: Of 906 patients, 581 (64.1%) patients reported frequent cough at the initial visit. Frequent cough was associated with the current smokers and CAT scores (p < 0.05). The MCID showed no significant difference between frequent cough and infrequent cough groups in the follow-up. More patients with frequent cough experienced future frequent exacerbations compared to those with infrequent cough. After receiving inhaled therapies, 62% of patients with frequent cough got the cough improved. More patients with frequent cough treated with LABA/LAMA or ICS/LABA/LAMA attained MCID and fewer experienced exacerbations than those treated with LAMA or ICS/LABA (p < 0.05). The change in cough score showed no difference among various inhaled therapies in patients with frequent cough. CONCLUSION: COPD patients with frequent cough were related to current smokers and higher CAT scores. These patients had a higher incidence of frequent exacerbations than those with infrequent cough. Patients with frequent cough who were treated with LABA/LAMA or ICS/LABA/LAMA were more likely to attain MCID and at a lower risk of exacerbation than those treated with LAMA or ICS/LABA.