RESUMO
NMDA receptor-dependent long-term depression (LTD) in the hippocampus is a well-known form of synaptic plasticity that has been linked to different cognitive functions. Although the underlying mechanisms remain unclear, this form of LTD cannot be induced by low-frequency stimulation (LFS) in adult mice. In this study, we found that LFS-induced LTD was not easily induced in adult animals and was age dependent. Interestingly, the level of the 5-HT1A receptor was correspondingly increased and exhibited an inverse correlation with the magnitude of LFS-LTD during development. Knockout or pharmacological inhibition of the 5-HT1A receptor reversed impaired LFS-LTD in adult mice (P60), while activation or inhibition of this receptor disturbed or enhanced LFS-LTD in adolescent mice (P21), respectively. Furthermore, the astrocytic 5-HT1A receptor in the hippocampus predominantly mediated age-dependent LFS-LTD through enhancing GABAergic neurotransmission. Finally, fear memory extinction differed among the above conditions. These observations enrich our knowledge of LTD at the cellular level and suggest a therapeutic approach for LTD-related psychiatric disorders.
RESUMO
Objectives: The aim of this study is to estimate the excess mortality burden of influenza virus infection in China from 2012 to 2021, with a concurrent analysis of its associated disease manifestations. Methods: Laboratory surveillance data on influenza, relevant population demographics, and mortality records, including cause of death data in China, spanning the years 2012 to 2021, were incorporated into a comprehensive analysis. A negative binomial regression model was utilized to calculate the excess mortality rate associated with influenza, taking into consideration factors such as year, subtype, and cause of death. Results: There was no evidence to indicate a correlation between malignant neoplasms and any subtype of influenza, despite the examination of the effect of influenza on the mortality burden of eight diseases. A total of 327,520 samples testing positive for influenza virus were isolated between 2012 and 2021, with a significant decrease in the positivity rate observed during the periods of 2012-2013 and 2019-2020. China experienced an average annual influenza-associated excess deaths of 201721.78 and an average annual excess mortality rate of 14.53 per 100,000 people during the research period. Among the causes of mortality that were examined, respiratory and circulatory diseases (R&C) accounted for the most significant proportion (58.50%). Fatalities attributed to respiratory and circulatory diseases exhibited discernible temporal patterns, whereas deaths attributable to other causes were dispersed over the course of the year. Conclusion: Theoretically, the contribution of these disease types to excess influenza-related fatalities can serve as a foundation for early warning and targeted influenza surveillance. Additionally, it is possible to assess the costs of prevention and control measures and the public health repercussions of epidemics with greater precision.
Assuntos
Causas de Morte , Influenza Humana , Humanos , Influenza Humana/mortalidade , Influenza Humana/epidemiologia , China/epidemiologia , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Pré-Escolar , Adolescente , Criança , Lactente , Idoso , Adulto Jovem , Vigilância da PopulaçãoRESUMO
BACKGROUND AND AIMS: Recent evidence suggests that insulin resistance affects asthma outcomes; however, the effect of the homeostatic measure of insulin resistance (HOMA-IR) on airway inflammation and asthma exacerbations (AEs) is poorly understood. OBJECTIVES: To analyze the relationship between HOMA-IR and clinical and inflammatory characteristics in patients with asthma, and the association between HOMA-IR and asthma exacerbations (AEs) in the following year. METHODS: A prospective cohort study recruited participants with asthma, who were classified into the HOMA-IRhigh group and HOMA-IRlow group based on the cutoff value of 3.80 for HOMA-IR and were observed within 12 months. We evaluated the clinical and inflammatory features, and a 1-year follow-up was conducted to study the exacerbations. A negative binomial regression model was used to analyze the association between HOMA-IR and AEs. RESULTS: Compared with the patients in the HOMA-IRlow group (n = 564), patients in the HOMA-IRhigh group (n = 61) had higher levels of BMI, higher waist circumference and waist/hip ratio, higher triglycerides, lower cholesterol high-density lipoproteins (HDL), more neutrophils in the peripheral blood, and elevated IL-5 levels in the induced sputum. Furthermore, patients in the HOMA-IRhigh group had a significantly increased risk for moderate-to-severe AEs (adjusted incidence rate ratio (aIRR) = 2.26, 95% confidence interval (CI) = [1.38, 3.70]), severe AEs (aIRR = 2.42, 95% CI = [1.26, 4.67]), hospitalization(aIRR = 2.54, 95% CI = [1.20, 5.38]), and emergency visits (aIRR = 3.04, 95% CI = [1.80, 8.53]). CONCLUSION: HOMA-IR was associated with asthma-related clinical features, and airway inflammation, as well as being an independent risk factor for future AEs. Therefore, insulin resistance may have important implications for managing asthma as a potential treatable trait.
RESUMO
BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) combined with portal and hepatic vein cancerous thrombosis is poor, for unresectable patients the combination of targeted therapy and immune therapy was the first-line recommended treatment for advanced HCC, with a median survival time of only about 2.7-6 months. In this case report, we present the case of a patient with portal and hepatic vein cancerous thrombosis who achieved pathologic complete response after conversion therapy. CASE SUMMARY: In our center, a patient with giant HCC combined with portal vein tumor thrombus and hepatic vein tumor thrombus was treated with transcatheter arterial chemoembolization (TACE), radiotherapy, targeted therapy and immunotherapy, and was continuously given icaritin soft capsules for oral regulation. After 7 months of conversion therapy, the patient's tumor shrank and the tumor thrombus subsided significantly. The pathology of surgical resection was in complete remission, and there was no progression in the postoperative follow-up for 7 months, which provided a basis for the future strategy of combined conversion therapy. CONCLUSION: In this case, atezolizumab, bevacizumab, icaritin soft capsules combined with radiotherapy and TACE had a good effect. For patients with hepatocellular carcinoma combined with hepatic vein/inferior vena cava tumor thrombus, adopting a high-intensity, multimodal proactive strategy under the guidance of multidisciplinary team (MDT) is an important attempt to break through the current treatment dilemma.
RESUMO
Purpose: This study aimed to investigate the alteration trends and overlaps of positive features in benign and malignant thyroid nodules of different sizes based on the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS). Patients and Methods: 1337 patients with 1558 thyroid nodules were retrospectively recruited from November 2021 to December 2023. These nodules were divided into three groups according to maximum diameter: A (≤10 mm), B (10-20 mm), and C (≥20 mm). C-TIRADS positive features were compared between benign and malignant thyroid nodules of different sizes. In addition, the trends of positive features with changes in nodule size among malignant thyroid nodules were analyzed. Results: The incidence of positive features in malignant thyroid nodules was higher than that in benign. As benign nodules grow, the incidence of all positive features showed a linear decreasing trend (Z values were 72.103, 101.081, 17.344, 33.909, and 129.304, P values < 0.001). With the size of malignant thyroid nodules increased, vertical orientation, solid, marked hypoechogenicity, and ill-defined/irregular margins/extrathyroidal extension showed a linear decreasing trend (Z = 148.854, 135.378, 8.590, and 69.239, respectively; P values < 0.05), while suspicious microcalcifications showed a linear increasing trend (Z = 34.699, P<0.001). In terms of overlapping characteristics, group A had a significantly higher overlapping rate than the other two groups, and the overlapping rate of solid indicators remained the highest among all three groups (P < 0.05). Conclusion: Differences in positive features were observed between thyroid nodules of different sizes. Except for suspicious microcalcifications, the incidence of other four positive features decreased with increasing nodule size. In addition, a negative correlation was observed between the overlap rate and nodule size. These results may provide a basis for sonographers to upgrade or downgrade thyroid nodules based on their own experience.
RESUMO
Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.
Assuntos
Hidrocefalia , AVC Isquêmico , Tuberculose Meníngea , Humanos , Adulto , Tuberculose Meníngea/complicações , Tuberculose Meníngea/epidemiologia , Tuberculose Meníngea/tratamento farmacológico , AVC Isquêmico/complicações , Fatores de Risco , Inflamação/complicações , Hidrocefalia/complicaçõesRESUMO
BACKGROUND: Age is a significant risk factor of diabetes mellitus (DM). With the develop of population aging, the incidence of DM remains increasing. Understanding the epidemiology of DM among elderly individuals in a certain area contributes to the DM interventions for the local elderly individuals with high risk of DM. AIM: To explore the prevalence of DM among elderly individuals in the Lugu community and analyze the related risk factors to provide a valid scientific basis for the health management of elderly individuals. METHODS: A total of 4816 elderly people who came to the community for physical examination were retrospectively analyzed. The prevalence of DM among the elderly was calculated. The individuals were divided into a DM group and a non-DM group according to the diagnosis of DM to compare the differences in diastolic blood pressure (DBP) and systolic blood pressure (SBP), fasting blood glucose, body mass index (BMI), waist-to-hip ratio (WHR) and incidence of hypertension (HT), coronary heart disease (CHD), and chronic kidney disease (CKD). RESULTS: DM was diagnosed in 32.70% of the 4816 elderly people. The BMI of the DM group (25.16 ± 3.35) was greater than that of the non-DM group (24.61 ± 3.78). The WHR was 0.90 ± 0.04 in the non-DM group and 0.90 ± 0.03 in the DM group, with no significant difference. The left SBP and SBP in the DM group were 137.9 mmHg ± 11.92 mmHg and 69.95 mmHg ± 7.75 mmHg, respectively, while they were 126.6 mmHg ± 12.44 mmHg and 71.15 mmHg ± 12.55 mmHg, respectively, in the non-DM group. These findings indicate higher SBP and lower DBP in DM patients than in those without DM. In the DM group, 1274 patients were diagnosed with HT, accounting for 80.89%. Among the 3241 non-DM patients, 1743 (53.78%) were hypertensive and 1498 (46.22%) were nonhypertensive. The DM group had more cases of HT than did the non-DM group. There were more patients with CHD or CKD in the DM group than in the non-DM group. There were more patients who drank alcohol more frequently (≥ 3 times) in the DM group than in the non-DM group. CONCLUSION: Older adults in the Lugu community are at a greater risk of DM. In elderly individuals, DM is closely related to high BMI and HT, CHD, and CKD. Physical examinations should be actively carried out for elderly people to determine their BMI, SBP, DBP, and other signs, and sufficient attention should be given to abnormalities in the above signs before further diagnosis.
Assuntos
Neuregulina-1 , Transdução de Sinais , Isolamento Social , Animais , Isolamento Social/psicologia , Neuregulina-1/metabolismo , Neuregulina-1/genética , Transtorno Autístico/psicologia , Transtorno Autístico/fisiopatologia , Complexo Nuclear Corticomedial/metabolismo , Humanos , Adolescente , Camundongos , Masculino , Tonsila do Cerebelo/metabolismoRESUMO
BACKGROUND: At present, there is no unified and effective treatment for extreme corrosive esophageal stenosis (CES) with esophagotracheal fistula (ETF). This case had extreme and severe esophageal stenosis (ES) and ETF after ingesting an enzyme-based chemical detergent, resulting in a serious pulmonary infection and severe malnutrition. Upper gastrointestinal imaging showed that he had an ETF, and endoscopy showed that he had extreme and severe esophageal stricture. This case was complex and difficult to treat. According to the domestic and foreign literature, there is no universal treatment that is low-risk. CASE SUMMARY: A patient came to our hospital with extreme ES, an ETF, and severe malnutrition complicated with pulmonary tuberculosis 1 mo after the consumption of an enzyme-based detergent. The ES was serious, and the endoscope was unable to pass through the esophagus. We treated him by endoscopic incision method (EIM), esophageal stent placement (ESP), and endoscopic balloon dilation (EBD) by using the bronchoscope and gastroscope. This treatment not only closed the ETF, but also expanded the esophagus, with minimal trauma, greatly reducing the pain of the patient. According to the literature, there are no similar reported cases. CONCLUSION: We report, for the first time, a patient with extreme CES complicated with ETF, where the endoscope could not be passed through his esophagus but he could be examined by bronchoscopy and treated by EIM, ESP, and EBD.
RESUMO
BACKGROUND: Clinical heterogeneity may exist within asthma subtypes defined by inflammatory markers. However, the heterogeneity of neutrophilic asthma (NA) remains largely unexplored. OBJECTIVE: To explore potential clusters and the stability of NA. METHODS: Participants with NA from the Australasian Severe Asthma Network underwent a multidimensional assessment. They were then asked to participate in a 12-month longitudinal cohort study. We explored potential clusters using a hierarchical cluster analysis and validated the differential future risk of asthma exacerbations in the identified clusters. A decision tree analysis was developed to predict cluster assignments. Finally, the stability of prespecified clusters was examined within 1 month. RESULTS: Three clusters were identified in 149 patients with NA. Cluster 1 (n = 99; 66.4%) was characterized by female-predominant nonsmokers with well-controlled NA, cluster 2 (n = 16; 10.7%) by individuals with comorbid anxiety/depressive symptoms with poorly controlled NA, and cluster 3 by older male smokers with late-onset NA. Cluster 2 had a greater proportion of participants with severe exacerbations (P = .005), hospitalization (P = .010), and unscheduled visits (P = .013) and a higher number of emergency room visits (P = .039) than that of the other two clusters. The decision tree assigned 92.6% of participants correctly. Most participants (87.5%; n = 7) in cluster 2 had a stable NA phenotype, whereas participants of clusters 1 and 3 had variable phenotypes. CONCLUSIONS: We identified three clinical clusters of NA, in which cluster 2 represents an uncontrolled and stable NA subtype with an elevated risk of exacerbations. These findings have clinical implications for the management of NA.
Assuntos
Asma , Humanos , Estudos Longitudinais , Asma/diagnóstico , Fenótipo , Comorbidade , Análise por ConglomeradosRESUMO
Background: Older adults with asthma have the greatest burden and worst outcomes, and there is increasing evidence that chronic cough (CC) is associated with asthma severity and poor prognosis. However, the clinical characteristics of older adult patients with both asthma and CC remain largely unknown. Methods: Participants with stable asthma underwent two cough assessments within 3â months to define the presence of CC. Patients were divided into four groups based on CC and age (cut-off ≥60â years). Multidimensional assessment was performed at baseline, followed by a 12-month follow-up to investigate asthma exacerbations. Logistic regression models were used to explore the interaction effect of CC and age on asthma control and exacerbations. Results: In total, 310 adult patients were prospectively recruited and divided into four groups: older CC group (n=46), older non-CC group (n=20), younger CC group (n=112) and younger non-CC group (n=132). Compared with the younger non-CC group, the older CC group had worse asthma control and quality of life and increased airflow obstruction. The older CC group showed an increase in moderate-to-severe exacerbations during the 12-month follow-up. There was a significant interaction effect of CC and ageing on the increased moderate-to-severe exacerbations (adjusted risk ratio 2.36, 95% CI 1.47-3.30). Conclusion: Older asthma patients with CC have worse clinical outcomes, including worse asthma control and quality of life, increased airway obstruction and more frequent moderate-to-severe exacerbations, which can be partly explained by the interaction between CC and ageing.
RESUMO
Purpose: To compare the diagnostic value of the Thyroid Imaging Reporting and Data System (TI-RADS) of the American College of Radiology (ACR) versus the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) scoring and classification system for elderly thyroid cancers. Patients and Methods: A total of 512 nodules from 465 patients aged ≥60 with surgical pathology-proven thyroid nodules were enrolled in our study. The ultrasound features of thyroid nodules were independently evaluated by the ACR TI-RADS and C-TIRADS classification systems, and the receiver operating characteristic curve (ROC) was plotted. The optimal cut-off values of the ACR TI-RADS and C-TIRADS scoring and classification systems for diagnosing elderly thyroid nodules were estimated, and the diagnostic efficacy was analyzed. Results: The ACR TI-RADS and C-TIRADS scores and classifications of thyroid cancers were both higher than benign nodules (both P < 0.05). The area under the curve (AUC) of ACR TI-RADS and C-TIRADS scoring and classification systems were 0.861, 0.897, 0.879, and 0.900, respectively, and the AUC of the scoring system was greater than the classification system for both criteria. When the Youden index was the highest, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the ACR TI-RADS scoring and classification systems were consistent, ie, they were 89.66%, 41.70%, 89.93%, and 59.00%, respectively; the sensitivity, specificity, PPV, and NPV of the C-TIRADS scoring and classification systems were also consistent, ie, they were 88.71%, 44.26%, 90.23%, 59.69%, respectively. The diagnostic efficacy between the two systems was not statistically significant. Conclusion: ACR TI-RADS and C-TIRADS systems had relatively high diagnostic efficacy for elderly thyroid cancer. The diagnostic efficiency of the scoring systems of ACR TI-RADS and C-TIRADS were higher than the classification systems. In addition, the two systems had high clinical practical values, while there is still a significant risk of missed diagnosis.
RESUMO
Purpose: To explore the diagnostic value of positive features in the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) for thyroid nodules of different sizes. Patients and Methods: A total of 1864 patients with 2347 thyroid nodules were selected from January 2021 to December 2022 and assessed according to C-TIRADS. According to the maximum diameter, nodules were divided into the A1 group (≤10 mm), A2 group (>10 mm,<20 mm), and A3 group (≥20 mm). With surgical pathology as the golden standard, the receiver operating characteristic curves (ROC) were constructed, and each group's area under the curve (AUC) was calculated. The diagnostic value of positive features in C-TIRADS for different sizes of thyroid nodules was analyzed. Results: In all groups, malignant thyroid nodules had a higher incidence of positive features than benign nodules (P < 0.05). In A1 group, the diagnostic efficiency of C-TIRADS positive features for thyroid nodules was vertical orientation> ill-defined/irregular margin or extrathyroidal extension> solid composition> markedly hypoechoic> microcalcifications. The AUCs were 0.718, 0.675, 0.609, 0.558, and 0.581, respectively. In A2 group, the diagnostic efficacy of each positive features for thyroid nodules was ill-defined/irregular margins or extra-thyroid invasion> solid composition> microcalcifications> markedly hypoechoic> vertical orientation. The AUCs were 0.854, 0.730, 0.719, 0.670, and 0.609, respectively. In A3 group, the diagnostic efficacy of each positive features for thyroid nodules was ill-defined/irregular margin or extrathyroidal extension> microcalcifications> solid composition> vertical orientation> markedly hypoechoic. The AUCs were 0.847, 0.778, 0.767, 0.584, and 0.560, respectively. Conclusion: C-TIRADS positive features exhibited different diagnostic efficacy for thyroid nodules of various sizes, especially for thyroid nodules ≤10 mm, for which all positive features had low diagnostic efficacy.
RESUMO
Natriuretic peptides, which are produced by the heart, bind to natriuretic peptide receptor A (NPR1 encoded by natriuretic peptide receptor 1 gene) and cause vasodilation and natriuresis. Thus, they serve an important role in regulating blood pressure. In the present study, microinjection of CRISPR associated protein 9/single guide RNA into fertilized C57BL/6N mouse eggs was performed to generate filial generation zero (F0) Npr1 knockout homozygous mice (Npr1-/-). F0 mice mated with wild-type (WT) mice to obtain F1 Npr1 knockout heterozygous mice with stable heredity (Npr1+/-). F1 self-hybridization was used to expand the population of heterozygous mice (Npr1+/-). The present study performed echocardiography to investigate the impact of NPR1 gene knockdown on cardiac function. Compared with those in the WT group (C57BL/6N male mice), the left ventricular ejection fraction, myocardial contractility and renal sodium and potassium excretion and creatinine-clearance rates were decreased, indicating that Npr1 knockdown induced cardiac and renal dysfunction. In addition, expression of serum glucocorticoid-regulated kinase 1 (SGK1) increased significantly compared with that in WT mice. However, glucocorticoids (dexamethasone) upregulated NPR1 and inhibited SGK1 and alleviated cardiac and renal dysfunction caused by Npr1 gene heterozygosity. SGK1 inhibitor GSK650394 ameliorate cardiorenal syndrome by suppressing SGK1. Briefly, glucocorticoids inhibited SGK1 by upregulating NPR1, thereby ameliorating cardiorenal impairment caused by Npr1 gene heterozygosity. The present findings provided novel insight into the understanding of cardiorenal syndrome and suggested that glucocorticoids targeting the NPR1/SGK1 pathway may be a potential therapeutic target to treat cardiorenal syndrome.
RESUMO
BACKGROUND: A few studies have explored the association between short sleep duration and worse asthma outcomes in patients with self-reported asthma; however, all of them were cross-sectional. OBJECTIVES: To investigate the association between self-reported sleep duration and asthma-related clinical and inflammatory characteristics and whether sleep duration is associated with asthma exacerbations (AEs) in the following year. METHODS: A prospective cohort study consecutively recruited participants with asthma, who were classified into short (n = 58), normal (n = 380), and long (n = 84) sleep duration groups. We investigated the clinical and inflammatory characteristics and exacerbations within a 1-year follow-up. RESULTS: Patients with short sleep duration were older and had significantly lower total IgE and FeNO levels and higher airway inflammation, characterized by increased levels of IL-6 and TNF-α in sputum than those of patients with normal sleep duration. Furthermore, they had a significantly increased risk for poorly controlled asthma (adjusted odds ratio = 2.741; 95% CI, 1.379-5.447; P = .004) and moderate to severe AEs (adjusted incidence rate ratio = 1.798; 95% CI, 1.098-2.942; P = .020). CONCLUSIONS: Short sleep duration was associated with non-type 2 inflammation and is an independent risk factor for future AEs. Therefore, as a potentially treatable trait, sleep duration may have clinical implications for asthma management.
Assuntos
Asma , Privação do Sono , Humanos , Autorrelato , Estudos Prospectivos , Asma/epidemiologia , Inflamação/epidemiologiaRESUMO
BACKGROUND: Dyslipidemia has been widely documented to be associated with cardiovascular disease, and recent studies have found an association with asthma prevalence. However, longitudinal studies investigating the relationships between dyslipidemia, asthma phenotypes, and future asthma exacerbations (AEs) are lacking. OBJECTIVE: To investigate the relationships between dyslipidemia, asthma phenotypes, and AEs. METHODS: This study used an observational cohort study design with a 12-month follow-up. All subjects underwent serum lipid measurement, and they were then classified into 2 groups: the normal-lipidemia group and the dyslipidemia group. Demographic and clinical information and details regarding pulmonary function and asthma phenotypes at baseline were collected. All patients were followed up regularly to assess AEs. Associations of dyslipidemia with airway obstruction and asthma phenotypes were assessed at baseline, whereas dyslipidemia and AEs were assessed longitudinally. RESULTS: A total of 477 patients with asthma were consecutively enrolled in this study. At baseline, the dyslipidemia group (n = 218) had a higher proportion of uncontrolled asthma, defined by the 6-item Asthma Control Questionnaire score (≥1.5). Furthermore, dyslipidemia was associated with severe asthma, nonallergic asthma, asthma with fixed airflow limitation, and older adult asthma phenotypes at baseline. In addition, dyslipidemia was associated with increased frequencies of severe AEs and moderate to severe AEs during the 12-month follow-up. In sensitivity analyses, after excluding the patients who were receiving statins, results did not differ significantly from those of the main analysis. CONCLUSIONS: We identified the clinical relevance of dyslipidemia, which is associated with specific asthma phenotypes and increased AEs, independent of other components of metabolic syndrome. These findings highlight the importance of considering dyslipidemia as an "extrapulmonary trait" in asthma management.
Assuntos
Asma , Dislipidemias , Humanos , Estudos Prospectivos , Asma/epidemiologia , Pulmão , Estudos Longitudinais , Dislipidemias/epidemiologiaRESUMO
BACKGROUND: Emerging evidence suggests that aging affects asthma outcomes, but the mechanism remains largely unexplored. OBJECTIVE: To explore age-related clinical characteristics, inflammatory features, phenotypes, and treatment response in asthma. METHODS: This was a prospective cohort study of asthmatic patients with a 12-month follow-up in a real-world setting. Clinical inflammatory and phenotypic characteristics, future risk for exacerbations, and treatment response were assessed across different age groups (young was defined as age 18 to 39 years; middle-aged, 40 to 64 years; and elderly, 65 years or older). RESULTS: Compared with young (n = 106) and middle-aged (n = 179) asthmatic patients, elderly patients (n = 55) had worse airway obstruction, more comorbidities including chronic obstructive pulmonary disease and diabetes, less atopy, and lower levels of IgE and FeNO, and were more likely to have late-onset and fixed airflow obstruction asthma and a reduced risk for having type 2 profile asthma. Levels of IFN-gamma, IL-17A, and IL-8 in induced sputum were significantly increased in elderly asthmatic patients (all P < .05). Path analysis indicated that age directly and significantly led to future exacerbations in asthma, partially mediated by an upregulation of airway IFN-gamma. Moreover, elderly patients with asthma had a reduced treatment response (improvement in FEV1 of 12% or greater, or 200 mL, and a reduction in Borg scores of 1 or greater) (adjusted odds ratio = 0.11; 95% CI, 0.02-0.52; and adjusted odds ratio = 0.12; 95% CI, 0.03-0.49, respectively). CONCLUSIONS: This study confirms that asthma in the elderly population represents a specific phenotype and indicates that aging can influence asthma in terms of clinical characteristics, inflammatory features, exacerbations, and treatment response.
Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Idoso , Humanos , Estudos Prospectivos , Asma/tratamento farmacológico , Asma/epidemiologia , Fenótipo , Pulmão , EscarroRESUMO
Background: The prevalence and prognostic significance of malnutrition risk remain unclear in Chinese patients with pulmonary tuberculosis. Therefore, we aimed to investigate the malnutrition risk in Chinese patients and explore the relationship between malnutrition risk and follow-up outcomes. Methods: We conducted a hospital-based cohort study from January 2020 to December 2020. Malnutrition risks were evaluated using nutritional scales, including the Nutritional Risk Screening 2002 (NRS-2002), the controlling nutritional status score (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index (PNI). The primary outcome was all-cause mortality at a one-year follow-up. Malnutrition risk was calculated, and the relationship between malnutrition and follow-up outcomes was analyzed. We assessed the performance of malnutrition risks to predict clinical outcomes in prognostic models. Results: A total of 1,075 patients were included. According to NRS-2002, CONUT, GNRI, and PNI, 818 (76.09%), 954 (88.74%), 682 (63.44%), and 364 (33.86%) patients were at risk of malnutrition, respectively. Before 1-year follow-up, a total of 99 patients (9.2%) had died. After adjustment for risk factors, the association between severe malnutrition in CONUT (HR = 4.78, 95% CI: 1.14-20.11, P = 0.033), GNRI (HR = 3.53, 95% CI: 1.70-7.34, P = 0.001), or PNI (HR = 2.94, 95% CI: 1.76-4.88, P < 0.001) and death before 1-year follow-up remained significant. The addition of the nutritional scales to prognostic models improved death prediction, as validated by the integrated discrimination index (all P-values of <0.05). Conclusion: Malnutrition in patients with pulmonary tuberculosis was associated with an increased risk of all-cause death in the long-term follow-up. Our findings provided evidence for the use of admission nutrition screening in patients with pulmonary tuberculosis.
Assuntos
Desnutrição , Tuberculose Pulmonar , Humanos , Idoso , Prognóstico , Estudos de Coortes , Prevalência , Estudos Retrospectivos , Desnutrição/epidemiologia , Hospitais , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/epidemiologiaRESUMO
OBJECTIVE: Endogenous adenosine 5'-monophosphate (AMP), acetylcholine (ACh), and histamine (HA) are known to be important in bronchial contraction, but their clinical relevance to asthma is poorly understood. We aimed to quantify endogenous AMP, ACh, and HA in induced sputum samples and explore their relationships with asthma control and exacerbations. METHODS: 20 healthy subjects and 112 asthmatics underwent clinical assessment, sputum induction, and blood sampling. The level of asthma control was determined by the asthma control test (ACT) questionnaire. Asthma exacerbation was evaluated according to the criteria of the American Thoracic Society/European Respiratory Society. Levels of AMP, ACh, and HA in sputum were measured by liquid chromatography coupled to tandem mass spectrometry. IL-ß, IL-4, IL-5, IL-6, IL-8, IL-13, IL-17A, TNF-α, IFN-γ, and macrophage-derived chemokine (MDC) were also measured. RESULTS: Compared to healthy controls, asthmatics had higher levels of HA, lower levels of ACh, and similar levels of AMP in induced sputum samples. Compared to controlled asthma (n = 54), uncontrolled asthma (n = 58) showed higher AMP levels (P = 0.002), but similar HA and ACh levels. AMP was negatively correlated with ACT scores (r = - 0.348) and asthma quality of life questionnaire scores (r = - 0.188) and positively correlated with blood monocytes percentage (r = 0.195), sputum MDC (r = 0.214), and IL-6 levels (r = 0.196). Furthermore, AMP was associated with an increased risk of exacerbations in the preceding year. CONCLUSION: Endogenous AMP, but not ACh or HA, was associated with asthma control, quality of life, and exacerbations in the previous year, which indicates that AMP could be a clinically useful biomarker of asthma.
Assuntos
Asma , Interleucina-17 , Acetilcolina , Adenosina , Monofosfato de Adenosina , Biomarcadores , Quimiocina CCL22 , Histamina , Humanos , Interleucina-13 , Interleucina-4 , Interleucina-5 , Interleucina-6 , Interleucina-8/análise , Controle de Qualidade , Qualidade de Vida , Escarro , Fator de Necrose Tumoral alfaRESUMO
PURPOSE: The molecular links between metabolism and inflammation that drive different inflammatory phenotypes in asthma are poorly understood. We aimed to identify the metabolic signatures and underlying molecular pathways of different inflammatory asthma phenotypes. METHODS: In the discovery set (n = 119), untargeted ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to characterize the induced sputum metabolic profiles of asthmatic patients with different inflammatory phenotypes using orthogonal partial least-squares discriminant analysis (OPLS-DA), and pathway topology enrichment analysis. In the validation set (n = 114), differential metabolites were selected to perform targeted quantification. Correlations between targeted metabolites and clinical indices in asthmatic patients were analyzed. Logistic and negative binomial regression models were established to assess the association between metabolites and severe asthma exacerbations. RESULTS: Seventy-seven differential metabolites were identified in the discovery set. Pathway topology analysis uncovered that histidine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism as well as phenylalanine, tyrosine and tryptophan biosynthesis were involved in the pathogenesis of different asthma phenotypes. In the validation set, 24 targeted quantification metabolites were significantly expressed between asthma inflammatory phenotypes. Finally, adenosine 5'-monophosphate (adjusted relative risk [adj RR] = 1.000; 95% confidence interval [CI] = 1.000-1.000; P = 0.050), allantoin (adj RR = 1.000; 95% CI = 1.000-1.000; P = 0.043) and nicotinamide (adj RR = 1.001; 95% CI = 1.000-1.002; P = 0.021) were demonstrated to predict severe asthma exacerbation rates. CONCLUSIONS: Different inflammatory asthma phenotypes have specific metabolic profiles in induced sputum. The potential metabolic signatures may identify therapeutic targets in different inflammatory asthma phenotypes.