The association between PM2.5 concentration and the severity of acute asthmatic exacerbation in hospitalized children: A retrospective study in Chongqing, China.

BACKGROUND: Ambient PM2.5 is associated with asthma exacerbation. The association between the concentration of PM2.5 and the severity of asthma exacerbation has yet to be thoroughly clarified. The study aims to explore the association between the piror 30 days average concentration of PM2.5 and the severity of acute asthma exacerbation in hospitalized children. METHODS: A total of 269 children with acute exacerbation of asthma were enrolled and divided into three groups according to the PM2.5 exposure concentrations: group 1 (PM2.5: <37.5 µg/m3 ), group 2 (PM2.5: 37.5-75 µg/m3 ), group 3 (PM2.5: ≥75 µg/m3 ), respectively. The ordered logistic regression modeling was conducted to explore the influence of daily PM2.5 concentration on the clinical severity of children's asthma exacerbation. Multiple linear regression was conducted to explore the association between the concentration of PM2.5 and the length of stay in the hospital (LOS). We also conducted a receiver operating characteristic (ROC) curve analysis to explore the cutoff value of PM2.5 to predict the children's asthma exacerbation. RESULTS: There was no statistical difference among the three groups of children in gender, age, body mass index, ethnicity, the first diagnosis of asthma, allergic history, passive smoke exposure, or family history of asthma. There was a statistically significant difference in many hospitalization characteristics (p < 0.05) among the three groups of children. Significant differences were found in terms of accessory muscles of respiration (p = 0.005), respiratory failure (p = 0.012), low respiratory tract infectious (p = 0.020), and the severity of asthma exacerbation (p < 0.001) among the three groups. PM2.5 concentration was primarily positively correlated to neutrophile inflammation. The ordered multivariate logistic regression model showed that higher PM2.5 concentrations were significantly associated with greater odds of more severe asthma exacerbation in one and two-pollutant models. The adjusted odds ratio of severe asthma exacerbation was 1.029 (1.009, 1.049) in the one-pollutant model. The most significant odds ratio of severe asthma exacerbation was 1.050 (1.027, 1.073) when controlling NO2 in the two-pollutant models. Multiple linear regression showed that PM2.5 concentration was significantly associated with longer LOS in both one-pollutant and two-pollutant models. By performing ROC analysis, the average daily concentration of 44.5 µg/m3 of PM2.5 (AUC = 0.622, p = 0.002) provided the best performance to predict severe asthma of children exacerbation with a sensitivity of 59.2% and a specificity of 63.8%. CONCLUSION: The increased prior 30 days average concentration of PM2.5 was associated with greater asthma exacerbation severity and longer length of stay in the hospital of children with asthma exacerbation.

Serum CDC42 reflects the exacerbation risk and severity, Th1/2 cell imbalance and inflammation in asthmatic children.

Aim: To explore the clinical implication of serum CDC42 in asthmatic children. Materials & methods: Serum CDC42 from 80 asthmatic children experiencing exacerbation, 80 asthmatic children in remission and 40 healthy controls was detected by ELISA. Results: CDC42 was highest in asthmatic children experiencing exacerbation followed by asthmatic children in remission and healthy controls (p < 0.001). Among asthmatic children experiencing exacerbation, CDC42 positively correlated with exacerbation severity (p = 0.011), Th2 (p = 0.017), TNF-α (p < 0.001), IL-6 (p = 0.009) and IL-8 (p = 0.008) and negatively correlated with Th1/Th2 ratio (p = 0.028). In asthmatic children in remission, CDC42 correlated with lower Th1/Th2 ratio (p = 0.028) and higher TNF-α (p = 0.026). In healthy controls, CDC42 showed no correlation with Th1/2 or inflammatory cytokines. Conclusion: Circulating CDC42 reflects exacerbation risk, Th1/2 imbalance and inflammation in asthmatic children.

MiR-185-5p measurement assists in reflecting Th1/Th2 cell imbalance, inflammatory cytokine production, and exacerbation risk for childhood asthma.

BACKGROUND: MicroRNA (miR)-185-5p participates in the pathology of asthma by regulating immune imbalance, inflammation, periostin synthesis, and smooth muscle contraction. This study intended to explore the dysregulation of miR-185p and its correlation with T-helper (Th)1, Th2 cells, and inflammatory cytokines in childhood asthma. METHODS: In 150 childhood asthma patients and 30 healthy controls (HCs), miR-185-5p from peripheral blood mononuclear cells was detected using reverse transcription-quantitative polymerase chain reaction, Th cells from peripheral blood samples were detected using flow cytometry, inflammatory cytokines from serum samples were detected using enzyme-linked immunosorbent assay. RESULTS: MiR-185-5p was increased in childhood asthma patients versus HCs [median (interquartile range (IQR)): 2.315 (1.770-3.855) versus 1.005 (0.655-1.520)] (P < 0.001). Meanwhile, miR-185-5p was negatively associated with Th1 cells (P = 0.035) but positively correlated with Th2 cells (P = 0.006) and IL-4 (P = 0.003) in childhood asthma patients; however, miR-185-5p was not linked to Th1 cells, Th2 cells, IFN-γ, or IL-4 in HCs (all P > 0.05). In addition, miR-185-5p was positively related to TNF-α (P < 0.001), IL-1ß (P = 0.015), and IL-6 (P = 0.008) in childhood asthma patients, miR-185-5p was only linked to TNF-α (P = 0.040) but not IL-1ß or IL-6 (both P > 0.05) in HCs. Moreover, miR-185-5p was increased in exacerbated childhood asthma patients versus remissive patients [median (IQR): 3.170 (2.070-4.905) versus 1.900 (1.525-2.615)] (P < 0.001). Besides, miR-185-5p was highest in patients with severe exacerbation followed by patients with moderate exacerbation, and lowest in patients with mild exacerbation (P = 0.010). CONCLUSION: MiR-185-5p is associated with imbalanced Th1/Th2 cells, increased inflammatory cytokines along with elevated exacerbation risk, and severity in childhood asthma patients.

MiR-185-5p measurement assists in reflecting Th1/Th2 cell imbalance, inflammatory cytokine production, and exacerbation risk for childhood asthma

Background: MicroRNA (miR)-185-5p participates in the pathology of asthma by regulating immune imbalance, inflammation, periostin synthesis, and smooth muscle contraction. This study intended to explore the dysregulation of miR-185p and its correlation with T-helper (Th)1, Th2 cells, and inflammatory cytokines in childhood asthma. Methods: In 150 childhood asthma patients and 30 healthy controls (HCs), miR-185-5p from peripheral blood mononuclear cells was detected using reverse transcription-quantitative polymerase chain reaction, Th cells from peripheral blood samples were detected using flow cytometry, inflammatory cytokines from serum samples were detected using enzyme-linked immunosorbent assay. Results: MiR-185-5p was increased in childhood asthma patients versus HCs [median (interquartile range (IQR)): 2.315 (1.770–3.855) versus 1.005 (0.655–1.520)] (P < 0.001). Meanwhile, miR-185-5p was negatively associated with Th1 cells (P = 0.035) but positively correlated with Th2 cells (P = 0.006) and IL-4 (P = 0.003) in childhood asthma patients; however, miR-185-5p was not linked to Th1 cells, Th2 cells, IFN-γ, or IL-4 in HCs (all P > 0.05). In addition, miR-185-5p was positively related to TNF-α (P < 0.001), IL-1β (P = 0.015), and IL-6 (P = 0.008) in childhood asthma patients, miR-185-5p was only linked to TNF-α (P = 0.040) but not IL-1β or IL-6 (both P > 0.05) in HCs. Moreover, miR-185-5p was increased in exacerbated childhood asthma patients versus remissive patients [median (IQR): 3.170 (2.070–4.905) versus 1.900 (1.525–2.615)] (P < 0.001). Besides, miR-185-5p was highest in patients with severe exacerbation followed by patients with moderate exacerbation, and lowest in patients with mild exacerbation (P = 0.010). Conclusion: MiR-185-5p is associated with imbalanced Th1/Th2 cells, increased inflammatory cytokines along with elevated exacerbation risk, and severity in childhood asthma patients (AU)

Short- and Long-Term Impact of Prior Chronic Obstructive Pulmonary Disease Exacerbations on Healthcare Resource Utilization and Related Costs: An Observational Study (SHERLOCK).

The observational retrospective cohort Study on HEalthcare Resource utiLization (HCRU) related to exacerbatiOns in patients with COPD (SHERLOCK; D5980R00014) evaluated exacerbation-related HCRU and costs using the U.K. National Health Service Greater Glasgow and Clyde Health Board data. Patients (≥40 years) with COPD were stratified by exacerbations one year before the index date: Group A (none), B (1 moderate), C (1 severe) and D (≥2 moderate and/or severe). All-cause and COPD-related HCRU and costs were assessed over 36 months. Adjusted rate ratios (RRs) or relative costs versus Group A were estimated using generalized linear models with appropriate distributions and link functions. The study included 22 462 patients (Group A, n = 7788; B, n = 5151; C, n = 250 and D, n = 9273). At 12 months, RRs (95% CI) versus Group A for all-cause and COPD-related HCRU, respectively, were highest in Groups C (1.28 [1.18, 1.39] and 1.18 [1.09, 1.29]) and D (1.26 [1.23, 1.28] and 1.29 [1.26, 1.31]). General practitioner and outpatient visits, and general ward stays/days accounted for the greatest COPD-related HCRU. All-cause and COPD-related relative costs (95% CI) versus Group A at 12 months, respectively, were 1.03 (0.94, 1.12) and 1.06 (0.99, 1.13) in Group B; 1.47 (1.07, 2.01) and 1.54 (1.20, 1.97) in Group C; 1.47 (1.36, 1.58) and 1.63 (1.54, 1.73) in Group D. Increased HCRU and costs in patients with exacerbation histories persisted at 36 months, demonstrating the sustained impact of exacerbations. The study suggests the importance of management and prevention of exacerbations through intervention optimization and budgeting by payers for exacerbation-related costs.

Serum dual-specificity phosphatase 1 reflects decreased exacerbation risk, correlates with less advanced exacerbation severity and lower inflammatory cytokines in children with asthma.

BACKGROUND: It is as fact that dual-specificity phosphatase 1 (DUSP1) regulates the T cell activation, pro-allergic response, and inflammation to engage with the pathogenesis of asthma, but its clinical role in children with asthma is unclear. The present study aimed to explore the expression of DUSP1, its association with exacerbation risk, severity, and inflammatory cytokines in children with asthma. METHOD: Around 52 children with asthma-exacerbation, 50 children in asthma-remission, and 50 healthy children were chosen for the study. The serum levels of DUSP1, as well as tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-17 were detected by the enzyme-linked immunosorbent assay. RESULTS: The levels of DUSP1 was the highest in healthy children (median (IQR)=34.305 (25.892- 43.693) ng/mL), the second highest in children in asthma-remission (median (IQR)=21.471 (18.581-27.934) ng/mL), and the lowest in children with asthma-exacerbation (median (IQR)=13.982 (7.901-21.624) ng/mL) (P<0.001). At the same time, DUSP1 was also related to decreased asthma risk with area under curve (AUC) (95%CI) of 0.847 (0.780-0.914), and correlated with its lower exacerbation risk with AUC (95%CI) of 0.755 (0.661-0.849). Besides, DUSP1 was negatively linked with exacerbation severity (rs =-0.338, P=0.014), immunoglobulin E (rs =-0.277, P=0.047), TNF-α (rs =-0.423, P=0.002), IL-1ß (rs =-0.389, P=0.004), and IL-17 (rs =-0.293, P=0.035), but not related with other disease features in children with asthma-exacerbation. Meanwhile, DUSP1 was only negatively associated with TNF-α (rs=-0.300, P=0.034) and IL-1ß (rs =-0.309, P=0.029) in children in asthma-remission. However, no correlation was found in DUSP1 with inflammatory cytokines or other disease features in healthy children (all P>0.05). CONCLUSION: DUSP1 reflects the reduced exacerbation risk, and associates with lower exacerbation severity and inflammatory cytokines in children with asthma-exacerbation; it also associates with inflammatory cytokines in children in asthma-remission. These findings suggest that DUSP1 may help to improve the management of asthmatic children.

Serum dual-specificity phosphatase 1 reflects decreased exacerbation risk, correlates with less advanced exacerbation severity and lower inflammatory cytokines in children with asthma

Background It is as fact that dual-specificity phosphatase 1 (DUSP1) regulates the T cell activation, pro-allergic response, and inflammation to engage with the pathogenesis of asthma, but its clinical role in children with asthma is unclear. The present study aimed to explore the expression of DUSP1, its association with exacerbation risk, severity, and inflammatory cytokines in children with asthma. Method Around 52 children with asthma-exacerbation, 50 children in asthma-remission, and 50 healthy children were chosen for the study. The serum levels of DUSP1, as well as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 were detected by the enzyme-linked immunosorbent assay. Results The levels of DUSP1 was the highest in healthy children (median (IQR)=34.305 (25.892– 43.693) ng/mL), the second highest in children in asthma-remission (median (IQR)=21.471 (18.581–27.934) ng/mL), and the lowest in children with asthma-exacerbation (median (IQR)=13.982 (7.901–21.624) ng/mL) (P<0.001). At the same time, DUSP1 was also related to decreased asthma risk with area under curve (AUC) (95%CI) of 0.847 (0.780–0.914), and correlated with its lower exacerbation risk with AUC (95%CI) of 0.755 (0.661–0.849). Besides, DUSP1 was negatively linked with exacerbation severity (rs=–0.338, P=0.014), immunoglobulin E (rs=-0.277, P=0.047), TNF-α (rs=-0.423, P=0.002), IL-1β (rs=-0.389, P=0.004), and IL-17 (rs=-0.293, P=0.035), but not related with other disease features in children with asthma-exacerbation. Meanwhile, DUSP1 was only negatively associated with TNF-α (rs=-0.300, P=0.034) and IL-1β (rs=-0.309, P=0.029) in children in asthma-remission. However, no correlation was found in DUSP1 with inflammatory cytokines or other disease features in healthy children (all P>0.05). Conclusion DUSP1 reflects the reduced exacerbation risk, and associates with lower (AU)