CC16 Concentrations Research Articles

CC16 as a Marker of COE-Induced the Early Change of Blood Composition of Coke Oven Workers

Objective: This project aims to enhance the occupational health insurance for coke oven workers. Methods: A total of 136 coke oven emissions workers and 61 oxygen plant workers were recruited to receive physical examinations. The coke oven emissions concentration at the workplace was measured by weighing method. The CC16 concentration was detected by enzyme-linked immunosorbent assay. Results: Logistic regression analysis revealed that exposure to coke oven emissions was correlated with CC16. Correlation analysis revealed that CC16 was related to some physical examination indicators. Multivariate general linear models showed that CC16 was indeed positively correlated with albumin after adjusting for confounding factors. Conclusions: Coke oven emissions affected multiple tissues and multiple systems. The blood system might be the earliest system affected and could be detected by the CC16 protein concentration.

Renal dysfunction reduces the diagnostic and prognostic value of serum CC16 for acute respiratory distress syndrome in intensive care patients

BackgroundContradictory results regarding changes in serum club cell protein 16 (CC16) levels in patients with acute respiratory distress syndrome (ARDS) have been reported, challenging the value of CC16 as a diagnostic and prognostic marker for ARDS. We have also observed increased serum CC16 levels in patients with renal dysfunction (RD). Therefore, the present study aimed to determine whether RD affects the diagnostic performance of CC16 for ARDS in intensive care unit (ICU) patients.MethodsWe measured serum CC16 concentrations in 479 ICU patients, who were categorized into six groups according to their diagnoses: control, acute kidney injury (AKI), chronic kidney disease (CKD), ARDS, ARDS+AKI, and ARDS+CKD. The sensitivity, specificity, and cutoff values for serum CC16 were assessed by receiver operating characteristic curve analysis.ResultsSerum CC16 concentrations were higher in the ARDS group than in the control group, and in ARDS patients with normal renal function, serum CC16 could identify ARDS and predict survival outcomes at 7 and 28 days. However, serum CC16 levels were similar among the ARDS+AKI, ARDS+CKD, AIK, and CKD groups. Consequently, in patients with AKI and/or CKD, the specificity of CC16 for diagnosing ARDS or ARDS+RD decreased from 86.62 to 2.82% or 81.70 to 2.12%, respectively. Consistently, the CC16 cutoff value of 11.57 ng/ml in patients with RD differed from the established values of 32.77–33.72 ng/ml with normal renal function. Moreover, the predictive value of CC16 for mortality in ARDS+RD patients was lost before 7 days but regained by 28 days.ConclusionRD reduces the diagnostic specificity, diagnostic cutoff value, and predictive value for 7-day mortality of serum CC16 for ARDS among ICU patients.

Reduced Serum Concentration of CC16 Is Associated with Severity of Chronic Obstructive Pulmonary Disease and Contributes to the Diagnosis and Assessment of the Disease.

BackgroundThe aim of this study was to reveal the correlations between serum concentration of Clara cell secretory protein (CC16) and clinical parameters of stable chronic obstructive pulmonary disease (COPD).Patients and MethodsSerum concentration of CC16 was determined by enzyme-linked immunosorbent assay (ELISA). The correlations between serum concentration of CC16 and clinical parameters was performed by linear correlation analysis and multiple linear regression analysis. The sensitivity and specificity of serum CC16 for differential diagnosis of COPD were determined by receiver operator characteristic curve (ROC).ResultsThe serum concentration of CC16 was down-regulated in stable COPD patients compared with healthy control group (p < 0.05). The decreased serum CC16 was negatively related to smoking (p < 0.05), GOLD grading (p < 0.005), mMRC score (p < 0.05) and medical history (p < 0.05) of patients, but positively correlated with pulmonary function (p < 0.05). The smoking, FEV1/FVC values, COPD grading and mMRC scores all affected the concentration of CC16 (p < 0.05). The decreased CC16 was an independent risk factor in the process of deterioration of lung function. The sensitivity and specificity of serum CC16 for identifying COPD reached to 65.3% and 75%.ConclusionDecreased serum concentration of CC16 correlated with the disease progression of COPD, suggesting that it can be used as an indicator contributing to the diagnosis and assessment of COPD.

Club cell protein 16 as a biomarker for early detection of silicosis.

Background & objectives:Clinically silicosis is diagnosed by chest X-ray showing specific opacities along with history of silica dust exposure. Diagnosis is invariably made at an advanced or end stage when it is irreversible. Moreover, silicosis patients are susceptible to develop tuberculosis. Therefore, a suitable biomarker for early detection of silicosis is needed. This study evaluated the suitability of club cell protein (CC16) as a biomarker for early detection of silicosis.Methods:This pilot study included 121 individuals from X-ray-confirmed/advanced silicosis, moderate silica dust-exposed workers and healthy controls from western India. CC16 levels were quantified in serum samples through ELISA. Sensitivity and specificity of CC16 values at different cut-off points were calculated in both non-smokers and smokers.Results:Serum CC16 level was significantly (P<0.01) decreased in X-ray confirmed advanced silicosis patients (4.7±3.07 ng/ml) followed by moderately exposed workers (10.2±1.77 ng/ml) as compared to healthy non-exposed individuals (16.7±3.81 ng/ml). Tobacco smoking also caused a significant decrease of serum CC16 concentration in both healthy (10.2±1.12 ng/ml) and advanced silicosis workers (2.6±2.28 ng/ml) compared to non-smokers. Sensitivity and specificity of CC16 values were also found to be ≥83 per cent for screening all categories of individuals.Interpretation & conclusions:Because of high sensitivity and specificity, serum CC16 could be used as predictive biomarker for suspicion and early detection of silicosis, which would help in reducing/delaying premature deaths caused by silicosis. It would also control silicotuberculosis additionally.

Plasma CC16 mediates the associations between urinary metals and fractional exhaled nitric oxide: A cross-sectional study

Exposure to environmental metals has been reported to be associated with airway inflammation. Fractional exhaled nitric oxide (FeNO) is an important inflammatory biomarker of the airway. However, the associations between metal exposures and FeNO change and the underlying mechanisms remain unclear. To investigate the associations between urinary metals and FeNO, and the potential role of Club cell secretory protein (CC16), a lung epithelial biomarker, in these associations. We conducted a cross-sectional study from the Wuhan-Zhuhai cohort and measured eight urinary metals, plasma CC16 and FeNO among 3067 subjects by using inductively coupled plasma-mass spectrometry, enzyme-linked immunosorbent assay kit and Nano Coulomb Nitric Oxide Analyzer, respectively. Mixed linear models were used to quantify dose-relationships between urinary metals and FeNO, as well as urinary metals and plasma CC16. The potential role of plasma CC16 in the associations between urinary metals and FeNO was estimated using mediationanalyses. After adjusting for covariates, one percent increase in urinary vanadium, nickel or antimony was associated with a respective 6.60% (95% CI: 3.52%, 9.68%), 2.18% (0.45%, 3.91%), 4.87% (1.47%, 8.27%) increase in FeNO level. The adverse associations were much stronger among participants with low concentration of plasma CC16 than those with high CC16 level. Moreover, plasma CC16 decreased monotonically with increasing quartiles of urinary vanadium, nickel or antimony. Mediation analyses found that CC16 mediated the associations between urinary metals and FeNO by 5.64%, 39.06% and 25.18% for vanadium, nickel and antimony respectively. CC16 plays an important role in airway inflammation. General population with lower plasma CC16 concentration is more likely to suffer from airway inflammation when exposed to high levels of vanadium, nickel or antimony.

Ultrafine CB-induced small airway obstruction in CB-exposed workers and mice

The potential threat of superfine carbon black (CB) particles to human health has received attention, but there are few human toxicological data available. The purpose of this study was to investigate the relationships between serum CC16 and SP-A with small airway related pulmonary functions in CB workers. Ninety-nine male CB packers and 115 non-CB-exposed healthy male workers were recruited. Serum CC16 and/or SP-A and pulmonary function tests were evaluated, and the relationship between them were also analyzed. To further assess pulmonary damage induced by CB particles in target organs, an animal inhalation exposure study was conducted. Male C57BL/6 mice were exposed to 15 and 30 mg/m3 CB for 6 h per day for 28 days. Levels of CC16 and SP-A were evaluated by ELISA and immunohistochemical staining (IHC). The results showed a 20% decreased in median CC16 and a 15% increase in median SP-A among CB-exposed workers. FEV1%, FEV/FVC, MMEF%, FEF25%, and FEF75% were also decreased in CB-exposed workers (P < 0.05). A significant positive correlation was observed between serum CC16 concentration and FEV1/FVC, although a negative correlation was found between serum SP-A concentration and FEV1/FVC. Serum CC16 was significantly reduced by 72% in mice with high CB-exposure, and serum SPA was 1.65x and 1.17x higher than CB-unexposed control mice in low and high CB-exposed mice, respectively. Lung CC16 and serum CC16 levels were positively correlated in mice (P = 0.024). Long-term exposure to ultrafine CB particles is associated with a decrease in CC16 and an increase in SP-A in the peripheral blood of CB-exposed workers. In conclusion, superfine CB particles have the potential to cause small airway obstruction.

Pneumoproteins in Offshore Drill Floor Workers.

The aim was to assess pneumoproteins and a certain biomarker of systemic inflammation in drill floor workers exposed to airborne contaminants generated during drilling offshore, taking into consideration serum biomarkers of smoking, such as nicotine (S-Nico) and cotinine. Blood samples of club cell protein 16 (CC-16), surfactant protein D (SP-D) and C-reactive protein (CRP) were collected before and after a 14-day work period from 65 drill floor workers and 65 referents. Air samples of oil mist, drilling mud components and elemental carbon were collected in person. The drill floor workers were exposed to a median air concentration of 0.18 mg/m3 of oil mist and 0.14 mg/m3 of airborne mud particles. There were no differences in the concentrations of CC-16 and SP-D across the 14-day work period and no difference between drill floor workers and referents at baseline after adjusting for differences in sampling time and smoking. CRP decreased across the work period. There was a strong association between the CC-16 concentrations and the time of sampling. Current smokers with S-Nico > detection limit (DL) had a statistically significantly lower CC-16 concentration, while smokers with S-Nico < DL had CC-16 concentrations similar to that of the non-smokers. Fourteen days of work offshore had no effect on serum pneumoprotein and CRP concentrations. However, the time of blood sampling was observed to have a strong effect on the measured concentrations of CC-16. The effect of current smoking on the CC-16 concentrations appears to be dependent on the S-Nico concentrations.

Clara cells protein, prolactin and transcription factors of protein NF-ĸB and c-Jun/AP-1 levels in rats inhaled to stainless steel welding dust and its soluble form.

Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese, and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. Bronchiolar epithelium Clara cells/club cells, coordinate these inflammatory responses. Clara cells secretory protein (CC16) with ant-inflammatory role. The pulmonary toxicity of welding dust (WD) was assessed for Wistar rats exposed to 60 mg/m3 of respirable-size welding dust (mean diameter 1.17 μm for 1 and 2 weeks (6 h/day, 5 days/week)) or the aerosols of soluble form (SWD) in the nose-only exposure chambers. Additionally the effect of antiinflammatory betaine supplementation was assessed. Clara cells secretory protein, differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase - LDH) activities were determined in bronchoalveolar lavage fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) and prolactin concentrations were assessed in serum. Histopathology examination of lung, brain, liver, kidney, spleen was done. Additionally slices of brain and lung were exanimated in laser ablation inductively coupled plasma mass spectrometry. Both WD and SWD exposure evoked large bronchiolar infiltration shoved in histopathology examination. In this study, TBARS inversely correlated with a significant decrease of CC16 concentration that occurred after instillation of both WD and SWD indicating decreased anti- inflammatory potential in the lung. In WD exposed rats prolactin correlated with nuclear factor-kappa B (NF-κB), LDH, TBARS and serum levels Cr, Ni and inversely with c-Jun. In SWD exposed rats prolactin correlated with CC16 indicated effect of prolactin on the population of epithelial cells. In the current study, deleterious effects of repeated inhalation stainless steel welding dust form on club (Clara) cell secretory protein (CC16) were demonstrated. Clara cells secretory protein relation with prolactin in exposed rats to welding dust were shown and explored whether the NF-κB and c-Jun/activator protein 1 related pathway was involved. Int J Occup Med Environ Health 2018;31(5):613-632.

Pneumoproteins and markers of inflammation and platelet activation in the blood of grain dust exposed workers

Purpose: To investigate if blood biomarkers could indicate early signs of lung damage or cardiovascular risk due to exposure to grain dust.Materials and methods: Pneumoproteins and markers of inflammation and platelet activation were analysed in blood samples of 102 grain elevator and compound feed mill workers. Differences between exposed (n = 67) and controls (n = 35), and associations with exposure measurements and respiratory health were investigated by multiple linear regression analyses.Results: Concentrations of CC-16 and IL-6 were higher in exposed workers compared with controls (p < 0.001 for both), whereas fibrinogen was lower (p = 0.005). Concentrations of CRP, TNF-α, sCD40L and sP-selectin were similar in both groups. Serum CC-16 was significantly higher in workers with farm childhood, regardless of exposure. The impact of farm childhood on CC-16 interacted with smoking. None of the biomarkers were associated with exposure measurements or any of the tested respiratory health parameters.Conclusion: Dust exposure induced inflammatory and anti-inflammatory reactions, but did not induce systemic inflammation and had no effect on platelet activation. No cause–effect relationship could be established in spite of relatively high exposure levels, particularly to endotoxin. Whether increased serum CC-16 is an early sign of lung damage or a reversible defense reaction remains unclear.

Club cell secretory protein (CC16) in gastric fluid at birth and subsequent lung disease in preterm infants.

Club cell secretory protein (CC16) probably has a role in protecting the lung from inflammation. To evaluate if low levels of CC16 in gastric fluid at birth, reflecting low levels of CC16 in the lung, would be associated with lung inflammation and respiratory morbidity. A study of 64 infants with mean gestational age 26.1 weeks. CC16 was analyzed in gastric fluid at birth. CC16, pro-inflammatory cytokines, and MMP-9 were analyzed in tracheal aspirate within 24 h from birth. CC16 in gastric fluid increased with gestational age (P = 0.033). Lower concentrations of CC16 in gastric fluid at birth were associated with higher concentrations of IL-1β (P = 0.028), TNF-α (P = 0.034), and MMP-9 (P = 0.015) in tracheal aspirate. Infants who needed mechanical ventilation at 24 and 72 h of age had lower CC16 in gastric fluid than those not ventilated at these ages (P = 0.011 and P = 0.024, respectively). Lower CC16 in gastric fluid was associated with higher FiO2 at 6 h (P = 0.009), higher PaCO2 at 24 h (P = 0.03), more ventilator days (P = 0.012) and more days with supplemental oxygen (P = 0.03). Infants who had either died or were still treated with supplemental oxygen at 36 weeks postmenstrual age had lower CC16 in gastric fluid than infants with none of these outcomes (P = 0.049). A low CC16 concentration in gastric fluid at birth was associated with increased inflammation in the trachea within the first 24 h of life and with more need for respiratory support in the neonatal period.

Burnt sugarcane harvesting work: effects on pulmonary and systemic inflammatory markers

Objective: To evaluate the effects of burnt sugarcane harvesting on the plasmatic and urinary concentrations of the club cell secretory protein (CC16) and inflammatory systemic biomarkers in a group of sugarcane cutters.Methods: Seventy-eight sugar cane workers were evaluated. The plasmatic and urinary concentrations of CC16, a pulmonary damage marker and inflammatory systemic biomarkers were collected at three time points: before, three months after and six months after the onset of the burnt sugarcane harvesting period. All evaluations were performed at ∼7 am, before the daily work shift. In the three-month evaluation, a post-work shift assessment (acute effect) was also performed.Results: The age of the workers was 37.9 ± 11.0 years. The PM2.5 concentrations were 27.0 (23.0–33.0) and 101.0 (31.0–139.5) µg/m3 in the pre harvest and harvest periods, respectively (p < .001). Burnt sugarcane harvesting was associated with a reduction, throughout the work during burnt sugarcane harvesting (subchronic effect), in plasmatic and urinary CC16 concentrations. Acutely, there was a decrease in plasmatic concentrations. There were acute and subchronic increases in inflammatory markers (neutrophils, monocytes) and muscle damage markers (CK and LDH) and a decrease in red blood cells.Conclusions: Harvesting of burnt sugarcane was associated with acute and subchronic reductions in the plasmatic and urinary concentrations of CC16 protein and changes in systemic inflammatory markers.

Reduced serum club cell protein as a pulmonary damage marker for chronic fine particulate matter exposure in Chinese population

BackgroundExposure to fine particulate matter (PM2.5) pollution is associated with increased morbidity and mortality from respiratory diseases. However, few population-based studies have been conducted to assess the alterations in circulating pulmonary proteins due to long-term PM2.5 exposure. MethodsWe designed a two-stage study. In the first stage (training set), we assessed the associations between PM2.5 exposure and levels of pulmonary damage markers (CC16, SP-A and SP-D) and lung function in a coke oven emission (COE) cohort with 558 coke plant workers and 210 controls. In the second stage (validation set), significant initial findings were validated by an independent diesel engine exhaust (DEE) cohort with 50 DEE exposed workers and 50 controls. ResultsSerum CC16 levels decreased in a dose response manner in association with both external and internal PM2.5 exposures in the two cohorts. In the training set, serum CC16 levels decreased with increasing duration of occupational PM2.5 exposure history. An interquartile range (IQR) (122.0μg/m3) increase in PM2.5 was associated with a 5.76% decrease in serum CC16 levels, whereas an IQR (1.06μmol/mol creatinine) increase in urinary 1-hydroxypyrene (1-OHP) concentration was associated with a 5.36% decrease in serum CC16 levels in the COE cohort. In the validation set, the concentration of serum CC16 in the PM2.5 exposed group was 22.42% lower than that of the controls and an IQR (1.24μmol/mol creatinine) increase in urinary 1-OHP concentration was associated with a 12.24% decrease in serum CC16 levels in the DEE cohort. ConclusionsSerum CC16 levels may be a sensitive marker for pulmonary damage in populations with high PM2.5 exposure.

Urinary polycyclic aromatic hydrocarbon metabolites, Club cell secretory protein and lung function

BackgroundExposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with lung function decline. However, the underlying mechanisms for the association remain unclear. ObjectivesTo explore potential role of a lung epithelial biomarker, Club cell secretory protein (CC16), in associations between PAH exposures and lung function decline. MethodsWe investigated 3384 adults from the Wuhan-Zhuhai cohort, and followed up at three years after first examination. Linear mixed models was used to quantify dose-response relationships between urinary monohydroxylated PAH metabolites (OH-PAHs) and lung function, as well as OH-PAHs and plasma CC16. Mediation analysis was conducted to investigate role of CC16 in the association between OH-PAHs and lung function. We also estimated the relationships between OH-PAHs and lung function change in three years among participants with different levels of CC16. ResultsEach 1-unit increase of log-transformed total urinary high and low molecular weight OH-PAHs (∑HMW OH-PAH and ∑LMW OH-PAHs) were associated with a 22.59 and 25.25ml reduction of FEV1 respectively, while∑HMW OH-PAH was associated with a 30.38ml reduction of FVC. Moreover, these negative associations between OH-PAHs and lung function levels were significant only among low CC16 group (<15.83ng/ml). CC16 concentration decreased monotonically with increased high molecular weight OH-PAHs (∑HMW OH-PAHs) when ∑HMW OH-PAH concentration was over 0.67μg/mmol Cr. CC16 mediated 22.13% of the association between ∑HMW OH-PAH and FVC among individuals with higher ∑HMW OH-PAH. After three years of follow-up, subjects with low level of plasma CC16 had a significant decline of FVC when exposed to high level of ∑HMW OH-PAH. ConclusionsCC16 play an important role in the association between high molecular weight PAHs and FVC. Individuals with low plasma CC16 level might suffer a decline in lung function when exposed to high level of high molecular weight PAHs.

High Baseline Serum Clara Cell 16 kDa Predicts Subsequent Lung Disease Worsening in Systemic Sclerosis.

Clara cell secretory protein (CC16) is a sensitive marker of bronchial epithelial cell damage. The CC16 serum level is elevated in patients with pulmonary fibrosis, but its predictive value on lung disease progression has not yet been studied. We aimed to assess the value of serum CC16 concentration in predicting lung disease deterioration in patients with systemic sclerosis (SSc). We prospectively analyzed and followed 106 patients with SSc during a 4-year period for the risk of developing combined deleterious event, defined as a 10% decrease in total lung capacity or forced vital capacity from baseline, or death, according to serum CC16 at inclusion. Receiver-operating characteristic (ROC) curve analysis was performed for prediction of events during the first 2 years after inclusion. Cumulative risks of combined events were computed by Kaplan-Meier analysis. The best cutoff level of serum CC16 for prediction of a combined event was 33 ng/ml, with 76% sensitivity and 65% specificity (area under the ROC curve: 0.71, 95% CI 0.61-0.81, p < 0.0001). Progression of lung disease evaluated by a mean time-to-event differed between patients with high baseline serum CC16 (42.8 mos, 36.3-49.3) and those with low serum CC16 (56.3 mos, 50.9-61.7; log-rank test, p < 0.001). After adjustment for age, duration of disease, clinical and lung function measures, the risk of combined event occurrence in patients with high serum CC16 was significantly higher than in those with low CC16 (HR 2.9, 1.2-6.75, p < 0.05). High baseline serum CC16 predicts lung disease worsening in patients with SSc.

Eosinophil Chemokines and Clara Cell Protein 16 Production in Nasal Mucosa of Patients with Persistent Allergic Rhinitis.

Eotaxin-2 and regulated on activation normal T cell expressed and secreted (RANTES) are involved in the eosinophil trafficking in patients with persistent allergic rhinitis (PAR). Clara cell protein 16 (CC16) is an anti-inflammatory protein mainly produced by the epithelial non-ciliated Clara cells. The aim of this study was to investigate the production of CC16 and chemokines eotaxin-2 and RANTES in nasal mucosa of patients with PAR. Twenty-one PAR patients and 20 healthy participants were included. CC16, eotaxin-2, and RANTES concentrations were measured in nasal secretions. PAR patients were administered fluticasone furoate nasal spray (220 μg daily for 14 days). We performed nasal cytology, symptom score assessment, and inflammatory mediator detection before and after the therapy. The level of CC16 in patients with PAR was lower than in the healthy subjects (p=0.023). The eosinophil counts and local concentrations of eotaxin-2 and RANTES were higher in patients with PAR in comparison with controls (p=0.008, p=0.001, p=0.031, respectively). We also found a negative correlation between the CC16 and eotaxin-2 levels in nasal secretions of PAR patients (r=-0.492, p=0.023). After corticosteroid therapy, the patients with PAR had lower nasal symptoms, eosinophil counts, eotaxin-2, and RANTES levels and higher levels of CC16 (p<0.001 for all parameters). Our results suggest the presence of a negative correlation in production of CC16 and eotaxin-2 in nasal mucosa of patients with PAR. Intranasal corticosteroids have a suppressive effect on mucosal eosinophilic inflammation and a stimulating effect on local CC16 production.

Clinical study on the changes of lung-specific proteins: CC16 after lung contusion.

The aim of the present study was to examine the clinical value of continuously monitoring serum CC16 levels in diagnosing pulmonary contusion, estimating its severity degree and predicting disease progression. Thirty-one acute trauma patients with lung contusion diagnosed by chest computed tomography (CT) were included, and chest CT was re-examined on day 1, 3 and 7 after injury. Calculating all the contusion volume by the Siemens syngo volume calculation program, complications such as pleural effusion or atelectasis were observed and recorded. ELISA was employed to measure the levels of CC16 in all the patients for seven days, and another 15 serum samples were obtained from healthy volunteers to provide the reference value. Correlation analysis was further conducted for the CC16 levels and pulmonary contusion volume and its variations. Serum concentrations of CC16 in all the lung contusion patients were significantly higher than those in the controls, and reached a peak value on the first day. However, the contusion damage area shown in CT gradually increased with the occurrence of atelectasis and pleural effusion. The maximum volume of lung contusion had a positive correlation to the initial and average concentrations of CC16, and changes in the contusion volume were positively correlated with the initial concentration. The increased concentration of CC16 after lung contusion is an important reference for diagnosis, and may portend the possibility of further progress, while continuously monitoring CC16 serum levels in patients may provide the basis for clinical decision-making.

Personal exposure to fine particulate matter, lung function and serum club cell secretory protein (Clara)

BackgroundThe underlying mechanisms about the association between ambient fine particulate matter (PM2.5) and lung function were unclear. Few epidemiological studies have evaluated the potential mediating effects of serum club cell secretory protein (Clara) (CC16), a biomarker of pulmonary epithelium integrity. ObjectivesTo evaluate the short-term effect of personal PM2.5 exposure on lung function and to explore the potential mediating role of CC16 in this effect. MethodsWe enrolled 36 healthy, nonsmoking college students for a panel study in Shanghai, China from December 17, 2014 to July 11, 2015. We measured personal and real-time exposure to PM2.5 for 72 h preceding each of four rounds of health examinations, including lung function test and serum CC16 measurement. We used linear mixed-effect models to examine the effects of PM2.5 on lung function and CC16 over various lag times. Furthermore, we analyzed the mediating effect of CC16 in the association between PM2.5 and lung function. ResultsAverage PM2.5 exposure ranged from 36 to 52 μg/m3 across different lag periods. PM2.5 exposure was negatively associated with lung function and positively associated with serum CC16 concentration. The effect of PM2.5 on CC16 occurred earlier than that on lung function. For instance, an interquartile range (IQR) increase in 0–2 h average exposure to PM2.5 was significantly associated with a 4.84% increase in serum CC16; and an IQR increase in 3–6 h average exposure to PM2.5 was significantly associated with a 1.08% decrease in 1-sec forced expiratory volume. These effects lasted up to 24 h after exposure. Increased serum CC16 contributed 3.9%–36.3% of the association between PM2.5 and impaired lung function. ConclusionsAcute exposure to PM2.5 might induce an immediate decrease in lung function by virtue of the loss of pulmonary epithelium integrity.

Arsenic exposure alters lung function and airway inflammation in children: A cohort study in rural Bangladesh

Exposure to arsenic has been associated with increased risk of reduced lung function in adults, but the adverse impacts in early life are unclear. We aim to examine whether prenatal and childhood arsenic exposure is associated with reduced lung function and increased airway inflammation in school-aged children. Children born in the MINIMat cohort in rural Bangladesh were evaluated at 9years of age (n=540). Arsenic exposure was assessed in urine (U-As) that was collected from mothers during early pregnancy and their children aged 4.5 and 9years. In the 9-year-old children, lung function was assessed using spirometry and airway inflammation was assessed by the NIOX MINO system. C-reactive protein (CRP) and Clara cell secretory protein (CC16) concentrations were measured in plasma by immunoassays. The U-As concentrations in 9-year-old children were lower (median 53μg/l) compared to their mothers (median 76μg/l). Maternal U-As (log2 transformed) was inversely associated with forced vital capacity (FVC) and forced expiratory volume at 1s (FEV1) (β=−12; 95% CI: −22, −1.5; p=0.031 and β=−12; 95% CI: −22, −1.9; p=0.023, respectively) in all children, and the associations were stronger in boys and among children with adequate height and weight, as well as among those whose mothers had higher percentages of methylarsonic acid (MMA) and lower percentages of dimethylarsinic acid (DMA). U-As (log2 transformed) at 4.5 and 9years was positively associated with fractional exhaled nitric oxide (FENO) concentrations in boys (β=0.89; 95% CI: 0.13, 1.66; p=0.022 and β=0.88; 95% CI: 0.16, 1.61; p=0.017, respectively) but not in girls. Increased CC16 concentrations were associated with higher lung function indices. In conclusion, our findings suggest that prenatal arsenic exposure is related to impaired lung function, while childhood exposure may increase airway inflammation, particularly in boys.

Effect of dexmedetomidine on acute lung injury in patients undergoing retroperitoneal laparoscopic surgery

Objective To investigate the effect of dexmedetomidine on acute lung injury in the patients undergoing retroperitoneal laparoscopic surgery. Methods Forty patients of both sexes, aged 18-60 yr, weighing 50-80 kg, of American Society of Anesthesiologist physical statusⅠor Ⅱ, scheduled for elective retroperitoneal laparoscopic partial nephrectomy, were divided into either control group(group C, n=20)or dexmedetomidine group(group Dex, n=20)using a random number table.At 10 min before induction of anesthesia, dexmedetomidine was injected intravenously in a loading dose of 1.0 μg/kg, followed by an infusion of 0.5 μg·kg-1·h-1 throughout surgery in group Dex, and the equal volume of normal saline was given instead in group C. The patients were placed in lateral position after anesthesia, and CO2 pneumoperitoneum was induced with an intra-abdominal pressure of 12 mmHg.Before induction of anesthesia(T0), at 60 and 120 min of pneumoperitoneum(T1, 2), and at 15 and 60 min after deflation(T3, 4), peripheral venous blood samples were taken for determination of serum malondialdehyde(MDA), tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6)and Clara cell 16-kDa secretory protein(CC16)concentrations by enzyme-linked immunosorbent assay. Results Compared with the baseline at T0, the serum MDA, TNF-α, IL-6 and CC16 concentrations were significantly increased at T1-4 in group C, and the serum MDA concentrations at T3, 4, serum TNF-α and IL-6 concentrations at T1-4 and serum concentrations of CC16 at T2-4 were significantly increased in group Dex(P<0.05). Compared with group C, the serum MDA, TNF-α, and CC16 concentrations at T2-4 and serum IL-6 concentrations at T1-4 were significantly decreased in group Dex(P<0.05). Conclusion Dexmedetomidine can reduce acute lung injury in the patients undergoing retroperitoneal laparoscopic surgery. Key words: Dexmedetomidine; Pneumoperitoneum, artificial; Respiratory distress syndrome, adult

Global DNA hypomethylation has no impact on lung function or serum inflammatory and fibrosis cytokines in asbestos-exposed population.

To examine the effect of asbestos exposure on global DNA methylation and determine whether lung function and inflammatory and fibrosis biomarkers are correlated with the methylation state. A total of 26 healthy subjects without asbestos exposure (Group 1), 47 healthy subjects with exposure (Group 2), and 52 subjects with benign asbestos-related disorders (ARDs) (Group 3) participated in this cross-sectional study. Blood global 5-methylcytosine (5mC) and serum TNF-α, collagen IV, CCL5 and CC16 concentrations were analyzed using enzyme-linked immunosorbent assay-like assays. Spirometric maneuvers were performed to assess lung function. Decreased 5mC levels were observed in Groups 2 and 3 compared to Group 1, irrespective of lung function (p < 0.01). There was no significant change in 5mC between Groups 2 and 3. Overall, 5mC was negatively correlated with CCL5 and collagen IV (p < 0.05), but no significant inverse relationship was found between 5mC and CCL5 or collagen IV in each group. Additionally, both 5mC and CC16 were inversely associated with FEV1/FVC% (p = 0.001, adjusted R 2 = 0.145) for non-smokers, and consistently significant inverse relationships were found between CC16 and FEV1/FVC%, independent of asbestos exposure. Asbestos exposure causes global DNA hypomethylation. DNA hypomethylation has no influence on serum biomarkers and lung function in asbestos-exposed population with or without pleural and pulmonary parenchymal abnormalities.