CC16 Levels Research Articles

Nasal effects of environmental tobacco smoke exposure in children with allergic rhinitis

ObjectivesTobacco smoke exposure is associated with inflammatory changes in the respiratory system including nasal mucosa. Our aim was to demonstrate nasal mucosal inflammation such as neutrophilic activation and epithelial permeability in patients with allergic rhinitis with exposure to environmental tobacco smoke (ETS) and reveal its effect on allergic rhinitis symptoms. MethodsWe enrolled 204 subjects with allergic rhinitis to this cross-sectional study. Sociodemographic and AR clinical characteristics were recorded. Urinary cotinine levels >50 ng/ml were defined as exposure to secondhand tobacco smoke. Club cell 16 (CC16) and myeloperoxidase (MPO) levels were measured in the nasal lavage fluid. Levels of these biomarkers and clinical severity were compared between ETS exposed and non-exposed children with AR. ResultsAmong 204 children enrolled, 53 (26 %) had ETS exposure. Mean age of the ETS exposed group was significantly higher than the unexposed group (12.1 ± 3.5 and 10.7 ± 3.6 years respectively, (p = 0.02). Similarly, T5SS score was significantly higher in ETS exposure group (9.3 vs 8.3, p = 0.03) but this significance was lost when corrected for age. Age and T5SS were inversely correlated with MPO levels (r = −0,24, p < 0.001 and r = −0,14, p = 0.04). Nasal lavage CC-16 and MPO levels were not found to be significantly different among subjects with and without ETS exposure (p = 0.13 and p = 0.26 respectively). ConclusionOur results demonstrated that ETS exposure is associated with more persistent AR in children. However, it is not related to severity or nasal lavage MPO or CC16 levels. Rhinitis symptoms beyond allergen period suggests isolated smoke exposure effect.

Diagnostic Value of Serum Clara Cell Secretory Protein Level in an Experimental Blunt Chest Trauma Model

Objective: Blunt chest trauma is a significant clinical problem leading to injury of the lungs that may be fatal. Experimental blunt chest trauma is well established in animal models. This study aimed to investigate whether Clara cell secretory protein (CC16) can be a biomarker in an experimentally created blunt chest trauma model. Material and Methods: A total of 30 rabbits were used in our study. A modified bilateral blunt thoracic trauma model was used to produce different levels of lung contusion. We divided the rabbits into four groups according to the energy level at which blunt thoracic trauma was applied. Blood samples were taken from the control and trauma groups to evaluate CC16 levels at 0, 12, and 24 hours. Results: The CC16 levels measured at the start of the experiment were significantly lower in the control and low-energy groups compared to the medium- and high-energy groups (p =.002). While there was a significant difference in CC16 levels measured at the 12th hour (p =.004), no significant difference was found among the groups at the 24th hour. Upon analyzing the change in CC16 levels over time within the groups, we observed that CC16 levels decreased from 0–12 hours and subsequently increased after the 12th hour. Histopathologically, we observed that the level of contusion increased in proportion to the severity of trauma across the different groups. Conclusion: With the designed platform, we created a reproducible experimental model of pulmonary contusion from blunt thoracic trauma in rabbits. Increased levels of CC16 following a lung contusion could serve as a foundation for clinical decision-making. Thus, CC16 has the potential to serve as a rapid and simple biochemical indicator for acute traumatic lung injury.

The predictive capacity of biomarkers for clinical pulmonary oedema in patients with severe falciparum malaria is low: a prospective observational study

BackgroundPulmonary oedema is a feared and difficult to predict complication of severe malaria that can emerge after start of antimalarial treatment. Proinflammatory mediators are thought to play a central role in its pathogenesis.MethodsAn exploratory study was conducted to evaluate the predictive capacity of biomarkers for development of clinical pulmonary oedema in patients with severe falciparum malaria at two hospitals in Bangladesh. Plasma concentrations of interleukin-6 (IL-6), IL-8, tumour necrosis factor (TNF), soluble Receptor of Advanced Glycation End-products (sRAGE), surfactant protein-D (SP-D), club cell secretory protein (CC16), and Krebs von den Lungen-6 (KL-6) on admission were compared with healthy controls. Correlations between these biomarker and plasma lactate and Plasmodium falciparum histidine-rich protein 2 (PfHRP2) levels were evaluated. Receiver Operating Characteristic (ROC) curves were constructed to assess the predictive capacity for clinical pulmonary oedema of the biomarkers of interest.ResultsOf 106 screened patients with falciparum malaria, 56 were classified as having severe malaria with a mortality rate of 29%. Nine (16%) patients developed clinical pulmonary oedema after admission. Plasma levels of the biomarkers of interest were higher in patients compared to healthy controls. IL-6, IL-8, TNF, sRAGE, and CC16 levels correlated well with plasma PfHRP2 levels (rs = 0.39; P = 0.004, rs = 0.43; P = 0.001, rs = 0.54; P < 0.001, rs = 0.44; P < 0.001, rs = 0.43; P = 0.001, respectively). Furthermore, IL-6 and IL-8 levels correlated well with plasma lactate levels (rs = 0.37; P = 0.005, rs = 0.47; P < 0.001, respectively). None of the biomarkers of interest had predictive capacity for development of clinical pulmonary oedema.ConclusionsIL-6, IL-8, TNF, sRAGE, SP-D, CC16 and KL-6 cannot be used in predicting clinical pulmonary oedema in severe malaria patients.

Application value of P-selectin and Clara cell secretory protein 16 expression in children with severe adenovirus pneumonia.

This study investigated the roles of P-selectin and Clara cell secretory protein 16 (CC16) levels in the pathogenesis of severe adenovirus (ADV) pneumonia in children and evaluated their ability to predict disease. Fifty-one children (age, 1-5 years) with ADV pneumonia who were admitted to Xiamen Children's Hospital were included in this study and divided into the mild group (24 patients) and severe group (27 patients). A control group comprising healthy children of the same age who underwent routine physical examinations during the same period (30 patients) was also included. The univariate analysis demonstrated that the levels of the white blood cell count and C-reactive protein, procalcitonin, d-dimer, and P-selectin were increased in a severe group compared with a mild group, while CC16 levels were significantly decreased (p < 0.05). The logistic regression analysis revealed that P-selectin and CC16 levels were independent risk factors for severe ADV pneumonia in children. The areas under the ROC curves suggested that P-selectin and CC16 exhibited high predictive value for severe ADV pneumonia. P-selectin values more than 898.58 pg/mL and CC16 values less than 11.355 ng/mL predicted severe ADV pneumonia. P-selectin and CC16 levels are correlated with the severity of ADV pneumonia in children.

Study association of urinary Club Cell Protein with air pollution-related pulmonary function compromised among children

BackgroundChildhood exposure to air pollution exacerbates respiratory conditions and even carries deleterious effects on lung functions in adulthood. It is desirable to establish a non-invasive screening test for children to predict early lung insult with air pollution exposure. The association between serum club cell protein (CC16) and obstructive airway diseases is known, but the same is not explored with air-pollution-related lung insult and pulmonary function test (PFT) parameters. AimTo investigate the association between urinary CC16 and PFT parameters in children exposed to differing levels of air pollution. MethodsThis cross-sectional study recruited 107 children from critically-polluted area (CPA) and 96 age-sex-matched children from non-polluted area (NPA). PFT and urinary CC16 were determined with standard techniques. Air quality parameters were estimated with adherence to National Ambient Air Quality Standards (NAAQS). ResultsCPA was observed with 2.5 times poorer Air-Quality-Index compared to NPA. Urinary CC16 levels of children were four-fold higher in CPA compared to NPA (p < 0.001). CPA children were significantly deprived in PFT parameters [FVC(L)-1.86 v/s 2.02, p = 0.01; FEV1(L/s)-1.71 v/s 1.86, p = 0.01 & PEFR(L/s)- 3.25 v/s 3.69, p < 0.001]. While adjusted for physiological parameters, urinary CC16 observed with significant negative association with PFT parameters (FVC: β = −0.02, p=0.03; FEV1: β = −0.03, p=0.001 & FEF25–75 %: β = −0.05, p=0.04). ConclusionThe significant decline in lung function parameters and elevated urinary CC16 levels among children in polluted areas underscore the need for further research to validate urinary CC16 as a reliable screening tool for respiratory health monitoring among children.

Cobalt exposure and pulmonary function reduction in chronic obstructive pulmonary disease patients: the mediating role of club cell secretory protein

BackgroundCobalt (Co) is a metal which is widely used in the industrial production. The previous studies found the toxic effects of environmental Co exposure on multiple organs. However, the correlation of blood Co concentration with lung function was inconsistent in patients with chronic obstructive pulmonary disease (COPD).MethodsAll 771 stable COPD patients were recruited. Peripheral blood and clinical information were collected. The levels of blood Co and serum CC16 were measured.ResultsCross-sectional study suggested that the level of blood Co was inversely and dose-dependently related to lung function parameters. Each 1 ppm elevation of blood Co was related to 0.598 L decline in FVC, 0.465 L decline in FEV1, 6.540% decline in FEV1/FVC%, and 14.013% decline in FEV1%, respectively. Moreover, higher age, enrolled in winter, current-smoking, higher smoking amount, and inhaled corticosteroids prominently exacerbated the negative correlation between blood Co and lung function. Besides, serum CC16 content was gradually reduced with blood Co elevation in COPD patients. Besides, serum CC16 was positively correlated with lung function, and inversely related to blood Co. Additionally, decreased CC16 substantially mediated 11.45% and 6.37% Co-triggered downregulations in FEV1 and FEV1%, respectively.ConclusionBlood Co elevation is closely related to the reductions of pulmonary function and serum CC16. CC16 exerts a significantly mediating role of Co-related to pulmonary function decrease among COPD patients.

Extracellular Vesicle-Encapsulated microRNAs and Respiratory Health Among American Indian Participants in the Strong Heart Study

American Indian populations have experienced marked disparities in respiratory disease burden. Extracellular vesicle-encapsulated microRNAs (EV-miRNAs) are a novel class of biomarkers that may improve recognition of lung damage in indigenous populations in the United States. Are plasma EV-miRNAs viable biomarkers of respiratory health in American Indian populations? The Strong Heart Study is a prospective cohort study that enrolled American Indian patients aged 45 to 74 years. EV-miRNA expression was measured in plasma (1993-1995). Respiratory health outcomes, including prebronchodilator FEV1, FVC, and respiratory symptom burden, were ascertained in the same study visit. Club cell secretory protein (CC-16), an antiinflammatory pneumoprotein implicated in COPD pathogenesis, was measured in serum. Linear and logistic regression were used for statistical analyses. Biological pathway analyses were used to elucidate gene targets of significant EV-miRNAs. Among 853 American Indian adults, three EV-miRNAs were associated with FEV1, four EV-miRNAs were associated with FVC, and one EV-miRNA was associated with FEV1/FVC (P< .05). Increased miR-1294 expression was associated with higher odds of airflow limitation (OR, 1.29; 95%CI, 1.07-1.55), whereas increased expression of miR-1294 (OR, 1.32; 95%CI, 1.07-1.63) and miR-532-5p (OR, 1.57; 95%CI, 1.02-2.40) was associated with higher odds of restriction. Increased miR-451a expression was associated with lower odds of exertional dyspnea (OR, 0.71; 95%CI, 0.59-0.85). Twenty-two EV-miRNAs were associated with serum CC-16 levels (q< 0.05), suggesting that EV-miRNAs may play a role in the pathway linking CC-16 to COPD pathogenesis. A pathway analysis showed key EV-miRNAs targeted biological pathways that modulate inflammation, immunity, and structural integrity in the lungs. Circulating EV-miRNAs are novel mechanistic biomarkers of respiratory health and may facilitate the early detection and treatment of lung damage in American Indian populations that have been disproportionately affected by chronic lung diseases.

Detection of serum CC16 by a rapid and ultrasensitive magnetic chemiluminescence immunoassay for lung disease diagnosis.

It has been reported that serum Clara cell secreted protein 16 (CC16) is a potential biomarker for lung injury diseases, but currently, there is no other method that is faster, more accurate, or more sensitive being applied in clinical practice apart from ELISA. The current study was designed to established a magnetic nanoparticles chemiluminescence immunoassay (MNPs-CLIA) for highly sensitive automated detection of serum Clara cell secretory protein 16 (CC16), and validated its diagnostic performance for lung disease. The study included the expression of CC16 recombinant protein, the preparation and screening of its monoclonal antibody (MAb), as well as the construction, optimization and analytical evaluation of the MNPs-CLIA method. The clinical application value of this method was investigated by detecting CC16 level in 296 serum samples. The linear range of the MNPs-CLIA assay system was 0.2-50 ng/mL, and the limit of detection was 0.037 ng/mL. Performance parameters such as specificity, recovery rate, and precision can meet the industry standards of invitro diagnostic reagents. The established method reveals consistent results with ELISA (R2=0.9962) currently used clinically, and it also exhibits satisfactory diagnostic efficacy of silicosis, chronic obstructive pulmonary disease (COPD), and pulmonary sarcoidosis, with areas under the curve (AUC) of 0.9748, 0.8428 and 0.9128, respectively. Our established MNPs-CLIA method has the advantages of automation, high throughput, rapidity, and simplicity, and can be promoted for widely popularized in clinical applications. MNPs-CLIA detection of serum CC16 has efficient diagnostic potentiality for predicting and diagnosing lung diseases.

Inflammatory imbalance in tracheal aspirate of very preterm newborns is associated with airway obstruction and lung function deficiencies at school age: a cohort study

ObjectiveA low expression of club cell secretory protein (CC16) and high levels of proinflammatory cytokines at preterm birth are associated with airway inflammation and more severe neonatal lung disease. The...

The effects of robot-assisted laparoscopic surgery with Trendelenburg position on short-term postoperative respiratory diaphragmatic function

ObjectiveTo study how Pneumoperitoneum under Trendelenburg position for robot-assisted laparoscopic surgery impact the perioperative respiratory parameters, diagrammatic function, etc.MethodsPatients undergoing robot-assisted laparoscopic surgery in the Trendelenburg position and patients undergoing general surgery in the supine position were selected. The subjects were divided into two groups according to the type of surgery: robot-assisted surgery group and general surgery group. ① Respiratory parameters such as lung compliance, oxygenation index, and airway pressure were recorded at 5 min after intubation, 1 and 2 h after pneumoperitoneum. ② Diaphragm excursion (DE) and diaphragm thickening fraction (DTF) were recorded before entering the operating room (T1), immediately after extubation (T2), 10 min after extubation (T3), and upon leaving the postanesthesia care unit (T4). ③ Peripheral venous blood (5 ml) was collected before surgery and 30 min after extubation and was analyzed by enzyme-linked immunosorbent assay to determine the serum concentration of Clara cell secretory protein 16 (CC16) and surfactant protein D (SP-D).Result① Compared with the general surgery group (N = 42), the robot-assisted surgery group (N = 46) presented a significantly higher airway pressure and lower lung compliance during the surgery(P < 0.001). ② In the robot-assisted surgery group, the DE significantly decreased after surgery (P < 0.001), which persisted until patients were discharged from the PACU (P < 0.001), whereas the DTF only showed a transient decrease postoperatively (P < 0.001) and returned to its preoperative levels at discharge (P = 0.115). In the general surgery group, the DE showed a transient decrease after surgery(P = 0.011) which recovered to the preoperative levels at discharge (P = 1). No significant difference in the DTF was observed among T1, T2, T3, and T4. ③ Both the general and robot-assisted surgery reduced the postoperative serum levels of SP-D (P < 0.05), while the robot-assisted surgery increased the postoperative levels of CC16 (P < 0.001).ConclusionRobot-assisted laparoscopic surgery significantly impairs postoperative diaphragm function, which does not recover to preoperative levels at PACU discharge. Elevated levels of serum CC16 after surgery suggest potential lung injury. The adverse effects may be attributed to the prolonged Trendelenburg position and pneumoperitoneum during laparoscopic surgery.

Pneumoprotein CC16 in the Umbilical Cord Blood of Preterm Neonates.

We examined the impact of perinatal factors on cord serum club cell protein (CC16) and the association of CC16 with mechanical ventilation and bronchopulmonary dysplasia (BPD) in preterm neonates. A retrospective cohort study including 60 neonates born with gestational age (GA) < 34 weeks. The impact of categorical perinatal factors on cord blood levels of CC16 was examined with univariate and multivariate regression analyses. In neonates with GA < 32 weeks, cord blood CC16 concentrations were significantly lower compared to neonates with GA between 320/7 and 336/7 weeks (5.4 ± 2.5 compared to 7.6 ± 2.9 ng/mL, p = 0.039). Neonates with prolonged rupture of membranes had significantly lower CC16 compared to those without prolonged rupture of membranes (4.0 ± 1.9 compared to 7.2 ± 2.2, p < 0.001). Finally, neonates with BPD had significantly lower CC16, compared to neonates without BPD (4.2 ± 2.1 compared to 7.0 ± 2.2 ng/mL, p = 0.004).Prolonged rupture of membranes was significantly negatively associated with CC16 (b = -2.67, 95% confidence interval [CI] -0.49 to -4.85, p = 0.017), after adjusting for GA (b = 0.23, 95% CI 0.03-0.42, p = 0.022), mode of conception, and mode of delivery. Finally, higher CC16 levels were significantly inversely associated with BPD (odds ratio = 0.33, 95% CI 0.12-0.88, p = 0.028), after adjusting for GA (b = 0.27, 95% CI 0.09-0.78, p = 0.015), and birth weight. Prolonged rupture of membranes was significantly negatively associated with cord serum CC16, after adjusting for GA, conception, and delivery mode, and CC16 was significantly inversely associated with BPD, after adjusting for GA and birth weight. · Neonates with prolonged rupture of membranes had lower CC16 levels.. · CC16 was significantly negatively associated with BPD.. · CC16 could be a biomarker of lung injury and BPD..

Associations of Serum Clara Cell Protein 16 with Severity and Prognosis in Adults with Community-Acquired Pneumonia.

Clara cell protein 16 (CC16) has multiple functions, including antioxidant, anti-inflammatory, and immune regulation properties. Nevertheless, the concrete function of CC16 in adult patients with community-acquired pneumonia (CAP) remained blurred. A total of 541 adult patients with CAP were recruited on admission. Peripheral blood specimens, clinical parameters, and demographic characteristics were collected. The concentration of serum CC16 was evaluated through ELISA. The relationships between serum CC16 and clinical parameters were appraised by Spearman or Pearson correlative analyses. The correlations of serum CC16 with severity and prognosis were assessed using linear or logistic regression models. The level of CC16 was gradually decreased across with the elevated severity scores system of CAP. After treatment, the level of serum CC16 was upregulated. Correlative analyses found that serum CC16 was negatively related to inflammatory cytokines. Additionally, multivariate linear and logistic regression models revealed that serum CC16 was inversely associated with severity scores system. In addition, reduced serum CC16 on admission elevated the risks of vasoactive agent usage, ICU admission, and death during hospitalization. We observed an almost discriminatory ability for severity and death between serum CC16 and severity scores system, and were all obviously elevated compared to routine inflammatory and infectious markers. There are substantially inverse correlations between serum CC16 level on admission with severity scores and poorly prognostic outcomes, indicating that CC16 is involved in the pathophysiological process of CAP. This study is helpful for establishing the potential application of serum CC16 in risk evaluation and targeted treatment.

Значення васкулярної молекули клітинної адгезії-1 та білка CC16 при бронхіоліті в дітей раннього віку

Given the severity of the course of bronchiolitis in young children, especially with a burdened allergic history, the search for biomarkers for early diagnosis and prognosis of the disease is urgent. Purpose - to substantiate the expediency of determining the levels of VCAM-1 and CC16 in blood serum in bronchiolitis in young children. Material and methods. The main group consisted of 34 children with bronchiolitis without a serious allergic history. The comparison group included 33 children who suffered from bronchiolitis and had a severe allergic history. The control group consisted of 25 conditionally healthy children. The clinical and laboratory examination consisted in determining the levels of VCAM-1 and CC16 in blood serum using the immunoenzymatic method. Results. The level of VCAM-1 in blood serum was established (55.5±1.12 ng/ml) in the children of the main group, while in the children of the comparison group the average value (164.9±1.1 ng/ml) of this indicator was 3 times higher, (AOR=3; 95% CI: 1.48-6.12; p&lt;0.05). In children of the control group, the average level of VCAM-1 in blood serum was (41.6±1.32 ng/ml). Analysis of the average level of CC16 protein in blood serum revealed its significant increase in children of the main group (41.2±1.24 ng/ml) compared to the indicator of children with bronchiolitis with a severe allergic history (22.8±1.64 ng/ml ml), (AOR=1.6; 95% CI: 0.8-3.2; p&lt;0.05). In children of the control group, the average value of the CC16 protein was within the reference values (16.2±2.43 ng/ml). Conclusions. In young children with bronchiolitis, it is advisable to determine the level of CC16 and VCAM-1 protein in blood serum. It was found that the level of SS16 protein in blood serum was significantly lower in children with a severe allergic history compared to children without a severe allergic history. On the other hand, regarding the level of VCAM-1 in blood serum, its value was significantly increased in the majority of children with severe allergic history. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

PCV-VG combined individualized PEEP determination in one-lung ventilated patients with PEEP step change direction: A randomized controlled trial.

The efficacy of pressure-controlled volume-guaranteed ventilation (PCV-VG) combined with a gradient-directional change in positive end-expiratory pressure (PEEP) during one-lung ventilation (OLV) in patients who underwent thoracoscopic surgery was investigated. Ninety patients were randomly divided into the PC (PCV-VG + 5 cm H2 O fixed PEEP), PI (PCV-VG + incremental PEEP titration), and PD (PCV-VG + decremental PEEP titration) groups. Hemodynamic (heart rate [HR] and mean arterial pressure [MAP]), respiratory mechanics (Ppeak , Pmean, and Cdyn), and arterial blood gas (pH, PaCO2 , PaO2 , and PaO2 /FiO2 ) indices were evaluated at T1 (10 min of two-lung ventilation [TLV]), T2 (10 min of OLV), and T3 (10 min of recovery, TLV). Enzyme-linked immunosorbent assay was performed to detect neutrophil elastase (NE), clara cell secretory protein (CC16), and interleukin-8 (IL-8) levels at T1 and T3. At T2 and T3 , Ppeak was lower in the PI and PD groups than in the PC group, while Pmean and Cdyn were higher than in the PC group. Ppeak in the PD group was lower than that in the PI group; however, Pmean was higher at T2 and T3 (P < 0.05). At T2 , PaO2 and PaO2 /FiO2 were higher, but PaO2 /FiO2 and VD /VT were lower in the PD and PI groups than in the PC group (P < 0.05). NE, CC16, IL-6, and IL-8 levels were elevated in all three groups at T3 , but the PI and PD groups had lower levels than the PC group (P < 0.05). The incidences of postoperative pulmonary complications (PPCs) and surgical intensive care unit hospitalizations in the PD and PI groups were much lower. Gradient-directed altered PEEP titration could improve respiratory mechanics, arterial blood gases, and inflammatory responses and reduce the incidence of PPCs in patients undergoing thoracoscopic surgery.

Correlation of Serum Clara Cell Secretory Protein 16, Plasma Fibrinogen and Serum Amyloid A with the Severity of Acute Exacerbated COPD and Their Combination in Prognosis Assessment.

Chronic obstructive pulmonary disease (COPD) has tremendous detrimental effects on patients' quality of life, lung function, disease progression and socioeconomic burden. This study aimed to investigate new serum biomarkers for COPD detection. Three recently emerging biomarkers, including Clara cell secretory protein⁃16 (CC16), plasma fibrinogen (FIB) and serum amyloid A (SAA), were investigated for their potential in stratifying the severity of COPD. A total of 220 patients with AECOPD were recruited. Multivariate logistical regression was used to analyze odds ratios of an array of characteristic of patients, including age, global initiative for chronic obstructive lung disease (GOLD), diabetes mellitus, heart diseases, PaCO2, CC16, FIB, and SAA. Correlations of CC16, FIB and SAA levels to each other, GOLD, and PaCO2 were also measured using Spearman correlation. Receiver operating characteristic (ROC)/curve analysis was used to assess sensitivity and specificity of CC16, FIB, SAA and the combination of the three markers in identifying AECOPD patients with poor prognosis. Our data suggested that age, GOLD, diabetes mellitus, heart diseases, PaCO2, CC16, FIB, and SAA are all significant risk factors for poor prognosis of AECOPD. CC16, FIB and SAA were positively correlated to each other and to GOLD and PaCO2 levels. CC16, FIB and SAA all had a high sensitivity and specificity in identifying patients with a poor prognosis. CC16, FIB and SAA are new markers with potentially high predictive value in AECOPD. Our data support further development of these biomarkers to improve clinical management of AECOPD through providing more accurate prognosis of AECOPD patients that enable timely adjustment of treatment plans.

The role of O3 exposure and physical activity status on redox state, inflammation, and pulmonary toxicity of young men: A cross-sectional study

The exposure to traffic-related air pollutants, such as NO2 and O3, are associated with detrimental health effects, becoming one of the greatest public health issues worldwide. Exercising in polluted environments could result in harmful outcomes for health and may blunt the physiological adaptations of exercise training. This study aimed to investigate the influence of physical activity and O3 exposure on redox status, an inflammatory marker, response to stress, and pulmonary toxicity of healthy young individuals. We performed a cross-sectional study with 100 individuals that, based on their exposure to O3 and physical fitness (PF) level, were distributed in four groups: Low PF + Low O3; Low PF + High O3; High PF + Low O3; High PF + High O3. We evaluated personal exposure to NO2 and O3, physical activity level, variables of oxidative stress (SOD, ROS, CAT, GSH, TBARS), pulmonary toxicity (CC16), and inflammatory mediators (IL-1β, IL-4, IL-6, IL-10, TNF-α, HSP70). Spearman correlation test to check the association among the variables was used and to compare groups we used one-way ANOVA followed by Bonferroni's post hoc and Kruskal Wallis test followed by Dunn's post hoc. O3 levels correlated with physical activity (r = 0.25; p = 0.01) but not with age or markers of body composition (p > 0.05). The individuals with high physical fitness that were less exposed to O3 presented higher CAT activity (p < 0.001), lower TBARS (p < 0.01) and IL-1β concentrations (p < 0.01), higher IL-6 (p < 0.05) and IL-10 concentrations (p < 0.05), lower IL-6:1L-10 ratio (p < 0.05), lower CC16 levels (p < 0.05), and higher HSP70 concentration (p < 0.05). Physical activity could result in higher exposure to O3 that could partially blunt some exercise adaptations, while high physical fitness improved the antioxidant defense system, systemic inflammatory mediators, and pulmonary toxicity.

Quercetin-Induced Enhancement of Nasal Epithelial Cells' Ability to Produce Clara Cell 10-kD Protein In Vitro and In Vivo.

Background: Quercetin, a polyphenolic flavonoid found in various plants and foods, is known to have antioxidant, antiviral and anticancer effects. Although quercetin is well known to exert anti-inflammatory and anti-allergic effects, the precise mechanisms by which quercetin favorably modifies the clinical status of allergic diseases, such as allergic rhinitis (AR), remain unclear. The present study examined whether quercetin could modulate the production of the endogenous anti-inflammatory molecule, Clara cell 10-kD protein (CC10), in vitro and in vivo. Methods: Human nasal epithelial cells (1 × 105 cells/mL) were stimulated with 20 ng/mL of tumor necrosis factor-alpha (TNF) in the presence of quercetin for 24 h. CC10 levels in culture supernatants were examined by ELISA. Sprague Dawley rats were sensitised with toluene 2,4-diisocyanate (TDI) by intranasal instillation of 10% TDI in ethyl acetate at a volume of 5.0 μL once daily for five days. This sensitisation procedure was repeated after an interval of two days. The rats were treated with different dosages of quercetin once daily for five days starting on the 5th day following the second sensitization. Nasal allergy-like symptoms induced by the bilateral application of 5.0 μL of 10% TDI were assessed by counting sneezing and nasal-rubbing behaviours for 10 min immediately after the TDI nasal challenge. The levels of CC10 in nasal lavage fluids obtained 6 h after TDI nasal challenge were examined using ELISA. Results: The treatment of cells with low doses of quercetin (<2.5 μM) scarcely affected TNF-induced CC10 production from nasal epithelial cells. However, the ability of nasal epithelial cells to produce CC10 after TNF stimulation significantly increased on treatment with quercetin doses (>5.0 μM). The oral administration of quercetin (>25 mg/kg) for five days significantly increased the CC10 content in nasal lavage fluids and attenuated the nasal symptoms induced by the TDI nasal challenge. Conclusions: Quercetin inhibits AR development by increasing the ability of nasal epithelial cells to produce CC10.

Role of club cell 16-kDa secretory protein in asthmatic airways.

Club cell 16-kDa secretory protein (CC16) is a pneumoprotein and functions as an anti-inflammatory or antioxidant protein. However, altered levels of serum CC16 as well as their effect on airways inflammation have not been fully evaluated. We recruited 63 adult asthmatics on maintenance medications and 61 healthy controls (HCs). The asthmatic subjects were divided into two groups according to the result of bronchodilator responsiveness (BDR) test: the present BDR (n = 17) and absent BDR (n = 46) groups. Serum CC16 levels were measured by ELISA. As an in vitro study, the effect of Dermatophagoides pteronyssinus antigen 1 (Der p1) on the production of CC16 in airways epithelial cells (AECs) according to a time-dependent manner was assessed; the effects of CC16 protein on oxidative stress system, airways inflammation and remodelling were tested. Serum CC16 levels showed significantly higher in the asthmatics than in the HCs (p < .001) with a positive correlation with FEV1 % (r = .352, p = .005). The present BDR group had significantly lower levels of serum CC16, FEV1 % and MMEF%, but showed higher level of FeNO than the absent BDR group. Serum CC16 levels (below 496.0 ng/mL) could discriminate the present BDR group from the absent BDR group (area under the curve = 0.74, p = .004). In vitro testing demonstrated that Der p1 exposure significantly induced CC16 release from AECs for 1 h, which was progressively decreased after 6 h and followed by MMP-9 and TIMP-1 production. These findings were associated with oxidant/antioxidant disequilibrium and restored by CC16 treatment (but not dexamethasone). Decreased CC16 production contributes to persistent airways inflammation and lung function decline. CC16 may be a potential biomarker for asthmatics with BDR.

Inflammatory mediators in nasal secretions of patients with nasal polyposis with and without aspirin sensitivity.

The aim of this cross-sectional study was to compare the levels of inflammatory mediators in nasal secretions in patients with aspirin-exacerbated respiratory disease (AERD) and in those with nasal polyposis (NP) without aspirin-sensitivity and to correlate nasal fluid mediator concentrations with clinical parameters of the disease. A total of 30 patients with AERD, 30 chronic rhinosinusitis (CRS) with NP patients without aspirin sensitivity (CRSwNP), and 30 control subjects without inflammation of the nasal mucosa (C), selected for surgical treatment entered the study. The total nasal symptom score (TNSS), endoscopic score (ES), and Lund-Mackay score (LMS), were evaluated. The concentrations of eosinophil cationic protein (ECP), tryptase, heat shock protein 70 (HSP70), substance P and Clara cell protein 16 (CC16) were determined in nasal secretions. Higher concentrations of ECP, tryptase, and HSP70 were measured in the AERD patients than in the CRSwNP patients and the C group (p < .001; p < .001, respectively for all mediators). However, levels of CC16 were higher in the C group than in the AERD and CRSwNP groups (p < .001; p < .001, respectively). A positive correlation between the TNSS and CC16 and a negative one between CC16 and tryptase levels were found in the C group. The CRSwNP group showed positive correlations between ECP, HSP70, and tryptase and negative correlations between substance P, ES, and LMS, as well as between CC16 and tryptase levels. In the AERD group, we found a positive correlation between HSP70 and ECP levels and a negative correlation between the TNSS and CC16 concentration. The obtained results indicate the increased production of mediators of eosinophil and mast cell function, and the decreased production of biomarker of respiratory epithelial function in AERD patients. Clinical and biochemical parameters correlate in different ways in the AERD and CRSwNP patients.

Validation of Prognostic Club Cell Secretory Protein (CC16) Cut-point in an Independent ALTA Cohort.

Club cell secretory protein (CC16) has demonstrated utility as a lung-specific biomarker in predicting mortality in acute respiratory distress syndrome (ARDS). These findings have been observed in pre-clinical trials and a re-analysis of a large, randomized controlled trial of ARDS (Fluid and Catheter Treatment Trial (FACTT)). The purpose of this study was to validate previous findings by evaluating CC16 level as a mortality predictor in patients from the albuterol to treat acute lung injury (ALTA) trial. In this secondary biomarker analysis, plasma CC16 level was measured from 100 ALTA subjects using enzyme-linked immunosorbent assay (ELISA). The rate of mortality was assessed in patients with high (⩾45 ng/mL) versus low CC16 (<45 ng/mL) levels. This cut-off level was applied based on our previous analysis from FACTT trial. Significance was assessed using Kaplan-Meier curves and a log-rank test. Subjects were an average of 50 years old and 46% of them were females. Patients with high CC16 levels had higher 90-day mortality compared to those with low CC16 levels, (37.73% vs 8.95%, P < .001). Other clinical outcomes including ICU-free days, ventilator-free days, and organ failure free days were significantly different between the groups (All P < .05). In this validation study, we demonstrated that ARDS patients with high plasma CC16 concentration had a higher mortality rate than those with low CC16 levels, confirming previous findings that CC16 levels are associated with ARDS mortality.