Serum CC16 Research Articles

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.

The effect of physical preparedness levels on serum levels of CC16, SP-D and lung function in endurance runners

Summary Objectives Endurance runners are exposed to respiratory damages due to extreme endurance exercises. Increasing CC16 and SP-D in the bloodstream is a sign of respiratory tract damage. The purpose of this pilot study was to investigate the effect of physical preparedness levels on serum CC16 and SP-D levels and lung function. Equipment and methods Ten healthy male elite runners and ten healthy male recreational runners were recruited based on the inclusion and exclusion criteria. Lung permeability [Surfactant protein D (SP-D), the Clara cell secretory protein (CC16) in serum and CC16/SP-D ratio] and lung function (FEV1, FVC and FEV1/FVC ratio) were measured before and after endurance session of running with an intensity of 80% to 85% maximum heart rate for 30 minutes. Comparisons were performed by RM-ANCOVA. Results Serum CC-16 and SP-D levels, and CC16/SP-D ratio increased significantly with time (P = 0.05). However, FEV1, FVC, FEV1/FVC ratio decreased significantly with time (P ≤ 0.05). Also, the interaction of group × time and between group changes was not significant for FEV1, FVC, FEV1/FVC ratio (P > 0.05). Based on the results of this study, physical preparedness levels have no effect on the release of CC16, SP-D, CC16/SP-D ratio and lung function. Further large-scale studies are needed to confirm these findings.

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.

Urinary club cell protein 16 (CC16): Utility of its assay during acute bronchiolitis.

Acute bronchiolitis is responsible for high morbidity in infants. Club cell protein 16 kDa (CC16) is a major pneumoprotein secreted by club cells of the bronchial epithelium and eliminated by the renal pathway. CC16 seems to be a biomarker of epithelial damage in asthma. However, its value as a marker of acute bronchiolitis severity and later recurrent wheezing are uncertain, especially the value of its urinary assay for this purpose. A prospective, observational, analytical study was conducted at Clermont‐Ferrand University Hospital to correlate serum CC16 level with clinical severity of bronchiolitis in hospitalized infants aged less than 1 year. We analyzed correlations between serum and urinary CC16, CC16 levels and Wainwright score, immediate morbidity due to bronchiolitis, causal viruses, and recurrent wheezing 1 year after inclusion. In 166 infants, serum CC16 did not correlate with acute bronchiolitis severity (P = .49), but urinary CC16 did (P < .001). In multivariate analysis, urinary CC16 correlated mainly with urinary retinol binding protein (RBP; r = 0.70; P < .001). The logCC16u/logRBPu ratio correlated significantly with severity (P = .02). CC16 levels were not correlated with recurrent wheezing at 1 year. Urinary CC16 could be a useful biomarker in acute bronchiolitis for specific indications. This noninvasive assay would be particularly useful in the young infant population. Several factors must be taken into account in its interpretation, mainly tubular function. Further studies are needed to assess these factors.

The effects of long-term exposure to silica dust on serum CC16 and KL-6 levels

Objective: To investigate the effects of long-term exposure to silica dust on serum CC16 and KL-6 levels. Methods: The patients with stage I silicosis who were hospitalized in our hospital from April 2016 to April 2017 were treated as silicosis group. The silica dust exposed workers without silicosis who were taken the physical examination in our hospital were taken as a dust-exposed group. The healthy control group comes from in the same period of community physical examination did not touch the dust. The levels of CC16 and KL-6 in serum of all subjects were determined by enzyme-linked immunosorbent assay (ELISA) , and the levels of CC16 and KL-6 in serum were compared in three groups. Results: Compared with the control group, the serum levels of CC16 in the silicosis group (P<0.01) and the dust-exposed group (P<0.01) were significantly lower. Compared with the control group, the level of serum KL-6 in the silicosis group was significantly decreased (P<0.01) compared with the control group, while the level of KL-6 in the serum of the dust-exposed group was significantly increased (P<0.01) . The ROC area of CC16 for diagnosis of silicosis was 0.92 (P<0.01) , with a sensitivity of 81.37%, specificity of 92.63% and Kappa value of 0.74. Conclusion: Long-term exposure to silica dust may lead to a decrease in serum CC16 levels. Reduced serum CC16 levels may be useful in identifying the diagnosis of silicosis.

Exposure to disinfection by-products in swimming pools and biomarkers of genotoxicity and respiratory damage – The PISCINA2 Study

BackgroundSwimming in pools is a healthy activity that entails exposure to disinfection by-products (DBPs), some of which are irritant and genotoxic. ObjectivesWe evaluated exposure to DBPs during swimming in a chlorinated pool and the association with short-term changes in genotoxicity and lung epithelium permeability biomarkers. MethodsNon-smoker adults (N = 116) swimming 40 min in an indoor pool were included. We measured a range of biomarkers before and at different times after swimming: trihalomethanes (THMs) in exhaled breath (5 min), trichloroacetic acid (TCAA) in urine (30 min), micronuclei in lymphocytes (1 h), serum club cell protein (CC16) (1 h), urine mutagenicity (2 h) and micronuclei in reticulocytes (4 days in a subset, N = 19). Several DBPs in water and trichloramine in air were measured, and physical activity was extensively assessed. We estimated interactions with polymorphisms in genes related to DBP metabolism. ResultsMedian level of chloroform, brominated and total THMs in water was 37.3, 9.5 and 48.5, μg/L, respectively, and trichloramine in air was 472.6 μg/m3. Median exhaled chloroform, brominated and total THMs increased after swimming by 10.9, 2.6 and 13.4, μg/m3, respectively. Creatinine-adjusted urinary TCAA increased by 3.1 μmol/mol. Micronuclei in lymphocytes and reticulocytes, urine mutagenicity and serum CC16 levels remained unchanged after swimming. Spearman correlation coefficients showed no association between DBP exposure and micronuclei in lymphocytes, urine mutagenicity and CC16. Moderate associations were observed for micronuclei in reticulocytes and DBP exposure. ConclusionsThe unchanged levels of the short-term effect biomarkers after swimming and null associations with personal estimates of exposure to DBPs suggest no measurable effect on genotoxicity in lymphocytes, urine mutagenicity and lung epithelium permeability at the observed exposure levels. The moderate associations with micronuclei in reticulocytes require cautious interpretation given the reduced sample size.

Blood Biomarkers of Sensitization and Asthma.

Biomarkers are essential to determine different phenotypes of childhood asthma, and for the prediction of response to treatments. In young preschool children with asthma, aeroallergen sensitization, and blood eosinophil count of 300/μL or greater may identify those who can benefit from the daily use of inhaled corticosteroids (ICS). We propose that every preschool child who is considered for ICS treatment should have these two features measured as a minimum before a decision is made on the commencement of long-term preventive treatment. In practice, IgE-mediated sensitization should be considered as a quantifiable variable, i.e., we should use the titer of sIgE antibodies or the size of skin prick test response. A number of other blood biomarkers may prove useful (e.g., allergen-specific IgG/IgE antibody ratios amongst sensitized individuals, component-resolved diagnostics which measures sIgE response to a large number of allergenic molecules, assessment of immune responses to viruses, level of serum CC16, etc.), but it remains unclear whether these can be translated into clinically useful tests. Going forward, a more integrated approach which takes into account multiple domains of asthma, from the pattern of symptoms and blood biomarkers to genetic risk and lung function measures, is needed if we are to move toward a stratified approach to asthma management.

Serum Clara Cell Protein (CC16) Levels and Multi-Detector Computed Tomography–Based Volumetric Assessment of Lung Parenchymal Injury in Isolated Blunt Thoracic Trauma Patients: a Prospective Observational Study

Numerous studies have been done for markers of lung injury especially in animal models and it remains relatively unexplored whether these biomarkers clinically correlate with the outcome of patients or with the extent of lung parenchymal injury as deduced by MDCT. This prospective study was conducted to assess the serum level of Clara cell secretory protein (CC16) and volume of the uninvolved lung by MDCT and to ascertain the correlation between levels of CC16 with the volume of the injured lung in the clinical outcome of patients of blunt thoracic trauma. Serum CC16 levels and mean uninvolved lung volumes of both lungs were compared in between groups of eventless recovery, need for mechanical ventilation and mortality with p value < 0.05 considered to be significant. Sixty-two patients of blunt chest trauma, age range from 18 to 60 years, were evaluated in our study. Out of them, 43 (69%) were male. Higher level (more than 100 ng/mL) of serum Clara cell protein was associated with the requirement of ventilator and mortality. Total mean uninvolved lung volume of 1075.71 ± 327.5 and 2329.23 ± 776.01 was significantly associated with the requirement of mechanical ventilation and eventless recovery of patients respectively. A mild negative correlation (− 0.4) between the remaining volume of the lung after injury and serum Clara cell protein levels were also noted. Serum CC16 levels may obviate the need of MDCT in the selected group of patients and thereby avoiding its radiation hazards.

SERUM CLARA CELL PROTEIN (CC16) IN RELATION TO PULMONARY FUNCTIONS AMONG WORKERS EXPOSED TO NAPHTHALENE IN PVC MANUFACTURE

AbstractIntroduction: Naphthalene is a harmful environmental tox reduced in serum and/or airway lining fluid of patients with COPD, asthma, bronchopulmonary dysplasia, silicosis, and post-transplant rejection. Aim of work: This study was done to evaluate the use of serum CC16 level as a biological marker for occupational respiratory diseases in relation to pulmonary function tests among workers exposed to naphthalene in polyvinyl chloride (PVC) manufacture. Material and methods: The study included 33 exposed workers and 33 control subjects. The study groups were subjected to full history taking, clinical examination and pulmonary function testing. Serum levels of CC16 and naphthalene levels measured for both groups. Results: Pulmonary functions parameters (FVC, FEV1, FEV1/FVC, FEF 25%, FEF 50%, FEF 75%), were significantly decreased in the exposed group compared to the control and indicated obstructive ventilatory impairment among the exposed workers. Serum naphthalene was significantly higher, while serum CC16 was significantly lower among the exposed group compared to the control. Exposed smokers exhibited the highest serum naphthalene and the lowest serum CC16 among all study groups. The duration of naphthalene exposure positively correlated with the serum level of naphthalene and negatively correlated with pulmonary functions and the serum level of CC16. Also serum level of CC16 correlated negatively with the serum naphthalene level and smoking index.Conclusion: Occupational exposure to naphthalene in PVC manufacture is associated with obstructive ventilatory impairment, with corresponding decrease in the serumlevel of Clara cell protein (CC16), which can be used as a biomarker for respiratory system affection among workers exposed to naphthalene.

Association between Early Acute Respiratory Distress Syndrome after Living-Donor Liver Transplantation and Perioperative Serum Biomarkers: The Role of Club Cell Protein 16.

Background Acute respiratory distress syndrome (ARDS) after living-donor liver transplantation (LDLT) is not uncommon, but it lacks the biomarkers for early detection. Club cell protein 16 (CC16), high-motility group box 1 protein (HMGB1), interleukin-1β (IL-1β), and IL-10 have been reported as relevant to the development of ARDS. However, they have not been investigated during LDLT. Methods Seventy-three consecutive recipients undergoing LDLT were enrolled and received the same perioperative care plan. Perioperative serum CC16, HMGB1, IL-1β, and IL-10 levels were measured at the pretransplant state, 30 minutes after reperfusion, postoperative day 1 (POD1), and POD3. ARDS was diagnosed according to the 2012 Berlin definition. Results Of the 73 recipients, 13 developed ARDS with significantly longer durations of mechanical ventilation and intensive care unit stay. Serum CC16 levels on POD1 increased significantly from the pretransplant state in the ARDS group but not in the non-ARDS group. Pretransplant serum CC16 levels were also higher in the ARDS group. The area under the receiver operating characteristic curves for POD1 serum CC16 levels used to discriminate ARDS was 0.803 (95% confidence interval: 0.679 to 0.895; p < 0.001). By comparison, HMGB1, IL-1β, and IL-10 were not associated with ARDS after LDLT. Conclusion The higher pretransplant serum CC16 level and its increased level on POD1 were associated with the development of early ARDS after LDLT. This trial is registered with NCT01936545, 27 August 2013.

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.

Decreased serum club cell secretory protein in asthma and chronic obstructive pulmonary disease overlap: a pilot study.

PurposeImprovement in the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO), and identification of biomarkers for phenotype recognition will encourage good patient care by providing optimal therapy. We investigated club cell secretory protein (CC-16), a protective and anti-inflammatory mediator, as a new candidate biomarker for diagnosing ACO.Patients and methodsWe performed a multicenter cohort study. A total of 107 patients were divided into three groups – asthma, COPD, and ACO – according to the Spanish guidelines algorithm, and enrolled into the study. Serum CC-16 levels were measured using commercial ELISA kits.ResultsSerum CC-16 levels were the lowest in patients with ACO. Low serum CC-16 levels were a significant marker for the ACO even after adjustment for age, sex, and smoking intensity. Serum CC-16 levels were positively correlated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25%–75% of FVC, FEV1/FVC, vital capacity, and diffusing capacity of the lung for carbon monoxide, and were negatively correlated with smoking amount (pack-years), bronchodilator response, fractional residual capacity, residual volume, and number of exacerbations per year. FEV1 and serum CC-16 levels were significantly lower in patients with frequent exacerbations.ConclusionSerum CC-16 has the potential to be a biomarker for ACO diagnosis and also treat frequent exacerbations in patients with chronic inflammatory airway diseases.

Relation between serum CC16 levels and asthma predictive index in pre-schoolers with recurrent wheezing

BackgroundLow levels of serum CC16 were reported in asthmatic adults, but the studies on children were scarce and conflicting. The aim of this study was to compare serum CC16 levels in pre-school children with recurrent wheezing assessed using an asthma predictive index (API). MethodsWe performed a case-control study based on API, with all enrolled pre-school children who had recurrent wheezing episodes (>3 episodes/last year confirmed by a physician) and had presented at one paediatric clinic in Santiago, Chile. The population was divided according to stringent API criteria into positive or negative. ResultsIn a one-year period, 60 pre-schoolers were enrolled. After excluding 12, 48 pre-schoolers remained (27 males, age range from 24 to 71 months) and completed the study; 34 were API positive and 14 were API negative. There were no significant differences in demographics between groups. The level of serum CC16 levels for pre-schoolers with a positive API and negative API were (median 9.2 [7.1–11.5] and 9.4 [5.5–10], p=0.26, respectively). The area under the curve for the serum CC16 levels to predict a positive API was 0.6, 95% CI [0.43–0.77], p=0.3. A correlation between serum CC16 levels and age was found (r=0.36 [0.07–0.59], p=0.01], but not between serum CC16 levels and peripheral eosinophils blood. ConclusionThere was no evidence that serum CC16 levels played a role in recurrent wheezing and a positive API in pre-school children. More studies are needed to confirm this finding.

Club cell protein 16 (Cc16) deficiency increases inflamm-aging in the lungs of mice.

Low serum CC16 levels are associated with accelerated lung function decline in human population studies, but it is not known whether low serum CC16 levels contribute to lung function decline, or are an epiphenomenon. We tested the hypothesis that unchallenged Cc16 −/− mice develop accelerated rates of pulmonary function test abnormalities and pulmonary pathologies over time compared with unchallenged WT mice. Respiratory mechanics, airspace enlargement, and small airway fibrosis were measured in unchallenged wild‐type (WT) versus Cc16 −/− mice over 6–18 months of age. Lung leukocyte counts and lung levels of metalloproteinases (Mmps), cytokines, oxidative stress, cellular senescence markers (p19 and p21), and lung cell apoptosis, and serum C‐reactive protein (CRP) levels were measured in age‐matched WT versus Cc16 −/− mice. Unchallenged Cc16 −/− mice developed greater increases in lung compliance, airspace enlargement, and small airway fibrosis than age‐matched WT mice over 6–18 months of age. Cc16 −/− mice had greater: (1) lung leukocyte counts; (2) lung levels of Ccl2, Ccl‐5, interleukin‐10, Mmp‐2, and Mmp‐9; (3) pulmonary oxidative stress levels, (4) alveolar septal cell apoptosis and staining for p16 and p21; and (5) serum CRP levels. Unchallenged Cc16 −/− mice had greater nuclear factor‐κB (NF‐κB) activation in their lungs than age‐matched WT mice, but similar lung levels of secretory phospholipase‐A2 activity. Cc16 deficiency in mice leads spontaneously to an accelerated lung aging phenotype with exaggerated pulmonary inflammation and COPD‐like lung pathologies associated with increased activation of NF‐ κB in the lung. CC16 augmentation strategies may reduce lung aging in CC16‐deficient individuals.

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.

CC16 levels correlate with cigarette smoke exposure in bronchial epithelial cells and with lung function decline in smokers

BackgroundClub cell protein-16 (CC16) expression has been associated with smoking-related lung function decline. The study hypothesis was that CC16 expression in both serum and bronchial epithelium is associated with lung function decline in smokers, and exposure to cigarette smoke will lead to reduction in CC16 expression in bronchial epithelial cells.MethodsIn a cohort of community-based male Chinese subjects recruited for lung function test in 2000, we reassessed their lung function ten years later and measured serum levels of CC16. CC16 expression was further assayed in bronchial epithelium from endobronchial biopsies taken from an independent cohort of subjects undergoing autofluorescence bronchoscopy, and tested for correlation between CC16 immunostaining intensity and lung function. In an in-vitro model, bronchial epithelial cells were exposed to cigarette smoke extract (CSE), and the expression levels of CC16 were measured in bronchial epithelial cells before and after exposure to CSE.ResultsThere was a significant association between FEV1 decline and serum CC16 levels in smokers. Expression of CC16 in bronchial epithelium showed significant correlation with FEV1/FVC. Bronchial epithelial cells showed significant decrease in CC16 expression after exposure to CSE, followed by a subsequent rise in CC16 expression upon removal of CSE.ConclusionsResults of these clinical and laboratory investigations suggested that low serum CC16 was associated with smoking-related decline in lung function, demonstrated the first time in a Chinese cohort. The data also lend support to the putative role of CC16 in protection against smoking-related bronchial epithelial damage.( word count: 243)US clinical trial registryNCT01185652, first posted 20 August, 2010.

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.

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.

The Comparison of Serum Inflammatory Biomarkers and CC-16 Between Bronchiectasis and COPD

The Comparison of Serum Inflammatory Biomarkers and CC-16 Between Bronchiectasis and COPD

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.