Serum CC16 Research Articles

End tuberculosis strategy also requires initiation and integration of a national silicosis control program with the ongoing tuberculosis elimination activities: A review of the silicotuberculosis situation in India

Background: Earlier studies conducted by Indian researchers have demonstrated that the elimination of tuberculosis (TB) requires proactive control of silicosis, given India’s significant burden of silicosis and its common comorbidity, pulmonary TB, also known as silicotuberculosis. The TB Control Indian Health Authority saw human immunodeficiency virus infection, diabetes, and malnutrition, among others, as important risk factors for case findings, but overlooked the significance of silicosis. Silicotuberculosis control is often confronted with challenges of detecting microorganisms, uncertain treatment outcomes, a higher likelihood of mono-drug and multi-drug resistance, and increased mortality due to treatment failure. In addition, silicosis has a long latent period, typically 15 years or more, from the onset of silica dust exposure to the appearance of opacities on radiological examination, which is the conventional method of diagnosis of the condition. Objective and recommendation: Facing the aforementioned situation, scientists of the Indian Council of Medical Research-National Institute of Occupational Health have identified a useful biomarker, Club cell secretory protein 16 (CC-16) (a lung protein), that might serve as a surrogate marker for early detection of silicosis among silica dust-exposed workers. An added benefit of CC-16 is its ability to detect sub-radiological silicosis, which is recognized as a risk factor for TB and multi-drug-resistant TB. At present, two researchers have developed point-of-care devices for detecting silica-dust-induced lung damage using serum CC-16, to support its further application. Conclusion: The present review highlights possible mechanisms for the early detection of silicosis and silicotuberculosis by assessing several relevant research publications, and the findings suggest that a national silicosis control program, to be integrated with existing TB elimination activities for sustainable and improved outcomes, should be initiated.

Impact of metals exposure on lung function and serum club cell secretory protein among schoolchildren: A mixture and mediation analysis

Particulate matter (PM) and its harmful components are significant contributors to respiratory diseases and impaired lung function, especially in children. Club cell secretory protein (CC16) is a maker of lung epithelium or club cell injuries. To date, the relationship between metals related with PM and CC16 and lung function impairment has been overlooked in children. We enrolled 603 schoolchildren exposed to different levels of PM in China. We found per doubling increase, urinary thallium, and iron was associated with a 3.42 % (95 % CI: 0.01, 6.72) and 3.09 % (95 % CI: 0.55, 5.56) decrease of serum CC16, respectively, whereas urinary cadmium was associated with a 4.74 % (95 % CI: 1.29, 8.31) increase of serum CC16. The Bayesian kernel machine regression (BKMR) model confirmed these associations and showed a potential synergistic interaction between thallium and cadmium. Urinary metal mixtures were associated with lower CC16 when they were below the 35th percentile compared with their median. Serum CC16 mediated 11.47 % (95 % CI: 0.06, 45.00) of the association between urinary thallium and FEV1/FVC decline. The inverted U-shaped association with CC16 and the mediation role of CC16 on associations with lung function provide insight into the mechanisms underlying lung injury induced by metals related with PM.

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.

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..

Club cell protein (CC16) in serum as an effect marker for small airway epithelial damage caused by diesel exhaust and blasting fumes in potash mining

ObjectiveThe effect marker club cell protein (CC16) is secreted by the epithelium of the small respiratory tract into its lumen and passes into the blood. Increased amounts of CC16 in serum are observed during acute epithelial lung injury due to air pollutants. CC16 in serum was determined as part of this cross-sectional study in underground potash miners on acute and chronic health effects from exposures to diesel exhaust and blasting fumes.MethodsNitrogen oxides, carbon monoxide, and diesel particulate matter were measured in 672 workers at a German potash mining site on a person-by-person basis over an early shift or midday shift, together with CC16 serum concentrations before and after the respective shift. CC16 concentrations and CC16 shift-differences were evaluated with respect to personal exposure measurements and other quantitative variables by Spearman rank correlation coefficients. CC16 shift-differences were modeled using multiple linear regression. Above-ground workers as reference group were compared to the exposed underground workers.ResultsSerum concentrations of CC16 were influenced by personal characteristics such as age, smoking status, and renal function. Moreover, they showed a circadian rhythm. While no statistically significant effects of work-related exposure on CC16 concentrations were seen in never smokers, such effects were evident in current smokers.ConclusionThe small airways of current smokers appeared to be vulnerable to the combination of measured work-related exposures and individual exposure to smoking. Therefore, as health protection of smokers exposed to diesel exhaust and blasting fumes, smoking cessation is strongly recommended.

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.

Investigation of serum surface active protein D and clara cell protein levels in workers exposed to silica dust in ferrous metal foundry

Objective: To investigate the levels of serum surface active protein D (SP-D) and clara cell protein (CCl6) in workers exposed to black silica dust, and analyze its influencing factors. Methods: From July to September 2021, 174 workers in 37 positions exposed to silica dust in 5 ferrous metal foundry were investigated by cross-sectional research method. The exposure concentration of silica dust workers was obtained through occupational health field investigation and detection, and the general situation of the study subjects was obtained through questionnaire survey and peripheral blood was collected. Double antigen sandwich enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of SP-D and CC16 in serum of workers. The mean values were compared by one-way ANOVA, and the influencing factors of SP-D and CC16 concentrations in serum were analyzed by ordered multiple logistic regression. Results: The time-weighted average concentration (C-TWA) of 174 workers exposed to silica dust (respirable dust) ranged from 0.09 mg/m(3)~3.58 mg/m(3), and the C-TWA overstandard rate of dust exposed workers was 32.18% (56/174) , with differences among workers in different positions (χ(2)=28.85, P<0.001) . The highest concentration of silica dust was (0.82±0.11) mg/m(3). Using C-TWA<50% OEL occupational exposure limit (OEL) as reference, serum SP-D concentration in workers with ≥50% OEL was increased (OR=4.95, 95%CI: 1.86~13.17, P=0.001) , while CC16 concentration was decreased (OR=0.15, 95%CI: 0.05~0.40, P<0.001) ; Serum CC16 concentration decreased in workers exposed to silica dust C-TWA≥OEL (OR=0.46, 95%CI: 0.28~0.98, P=0.043) . Compared with those with low occupational health literacy, the serum SP-D concentration of workers with high occupational health literacy decreased (OR=0.48, 95%CI: 0.25~0.92, P=0.027) and CC16 concentration increased (OR=2.09, 95%CI: 1.10-3.97, P=0.024) . Conclusion: When no abnormality was found in the physical examination of workers, the serum SP-D and CC16 concentration levels changed, and the change was related to the concentration of workers exposed to silica dust.

Effects of lifestyle and associated diseases on serum CC16 suggest complex interactions among metabolism, heart and lungs

IntroductionClara cell 16-kDa protein (CC16) is an anti-inflammatory, immunomodulatory secreted pulmonary protein with reduced serum concentrations in obesity according to recent data. ObjectiveStudies focused solely on bodyweight, which does not properly reflect obesity-associated implications of the metabolic and reno-cardio-vascular system. The purpose of this study was therefore to examine CC16 in a broad physiological context considering cardio-metabolic comorbidities of primary pulmonary diseases. MethodsCC16 was quantified in serum samples in a subset of the FoCus (N = 497) and two weight loss intervention cohorts (N = 99) using ELISA. Correlation and general linear regression analyses were applied to assess CC16 effects of lifestyle, gut microbiota, disease occurrence and treatment strategies. Importance and intercorrelation of determinants were validated using random forest algorithms. ResultsCC16 A38G gene mutation, smoking and low microbial diversity significantly decreased CC16. Pre-menopausal female displayed lower CC16 compared to post-menopausal female and male participants. Biological age and uricosuric medications increased CC16 (all p < 0.01). Adjusted linear regression revealed CC16 lowering effects of high waist-to-hip ratio (est. −11.19 [−19.4; −2.97], p = 7.99 × 10−3), severe obesity (est. −2.58 [−4.33; −0.82], p = 4.14 × 10−3) and hypertension (est. −4.31 [−7.5; −1.12], p = 8.48 × 10−3). ACEi/ARB medication (p = 2.5 × 10−2) and chronic heart failure (est. 4.69 [1.37; 8.02], p = 5.91 × 10−3) presented increasing effects on CC16. Mild associations of CC16 were observed with blood pressure, HOMA-IR and NT-proBNP, but not manifest hyperlipidemia, type 2 diabetes, diet quality and dietary weight loss intervention. ConclusionA role of metabolic and cardiovascular abnormalities in the regulation of CC16 and its modifiability by behavioral and pharmacological interventions is indicated. Alterations by ACEi/ARB and uricosurics could point towards regulatory axes comprising the renin-angiotensin-aldosterone system and purine metabolism. Findings altogether strengthen the importance of interactions among metabolism, heart and lungs.

Levels of Clara cell secretory protein and surfactant protein A in municipal solid waste management workers in Ibadan, Southwest Nigeria

Toxic pneumonitis and related respiratory symptoms are common among waste management workers (WMWs). Products of different cellular responses following exposure to toxic components of wastes can lead to the production of a variety of biomolecules. There is a growing recognition of the importance of biomarkers in risk assessment and a strong advocacy for their determination and use as indicators of health and safety. This study assessed the prevalence of respiratory symptoms and the relevance of pulmonary surfactant protein A (SP-A) and Clara cell 16 protein (CC16) as indicators of occupational inhalation exposure to toxic substances and irritants in WMW. A total of 172 subjects consisting of 112 WMWs and 60 Non-WMWs were recruited by purposive sampling. Data on socio-economic and work-related symptoms were collected using structured questionnaire. CC16 and SP-A were determined by ELISA in serum samples. Clinical history reveals a slightly higher prevalence of respiratory symptoms in WMWs relative to control subjects. Increased permeability of the lung-blood barrier, characterized by significant elevation of serum SP-A and serum CC16, was associated with respiratory symptoms in WMWs. Steady increases in SP-A and CC16, respectively, in relation to occupational duration were observed in WMWs relative to control. Receiver operating characteristic curve and multivariate analyses revealed SP-A and CC16 as important lung biomarkers for assessing sub-clinical effects of occupational exposure. Our data suggest SP-A and CC16 may be relevant indicators for assessing occupational inhalation exposure to toxic substances and irritants among WMWs.

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.

Retracted: Predictive Value of Serum Markers SFRP1 and CC16 in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

[This retracts the article DOI: 10.1155/2022/6488935.].

Potential consequences of screening of occupational silica dust exposed workers for early detection of silicosis/silico-tuberculosis using a novel biomarker, club cell protein-16, with possible intervention by repurposing metformin

Earlier, a study conducted by the Indian Council of Medical Research – National Institute of Occupational Health (ICMR-NIOH), India, evidenced that CC16 may be used as a proxy marker and screening tool for early detection and progression of silica-induced lung damage. Once CC16 indicates early silicosis, it needs to be confirmed by chest radiography. Next, ICMR-NIOH and ICMR-National Institute of Virology (ICMR-NIV) jointly developed a semi-quantitative and point-of-care CC16 detection kit using lateral flow immune chromatography. The said test can be done from one drop of blood collected through a finger prick. All trained peripheral healthcare workers can screen the silica dust-exposed workers periodically, under the national silicosis control program. Once early silicosis is detected, their sputum may be examined periodically by CB-NAAT/True-NAT for early detection of silicotuberculosis. The serum CC-16 detection kit is the first of its kind for early detection of silicosis through periodic screening, which is approved by the Indian Council of Medical Research, Ministry of Health, Govt. of India. Unless silicosis is controlled, elimination of TB appears to be difficult in India as there is a huge burden of silicosis including sub-radiological silicosis in India and considering the fact that silicosis is a stronger risk factor for lung tuberculosis due to its progressive declining effect of lung immunity. Since occupational silica dust exposure facilitates progressive fibrosis of lung tissue, a clinical trial using metformin may be the need of the day as animal experiments have already shown metformin's anti-fibroblastic effect in silica-induced animals.

Club cell secretory protein 16 is a potential biomarker for silica-induced pulmonary fibrosis

This study was conducted to investigate the changes of Club cell protein 16 (CC16) and surfactant protein D (SP-D) levels in serum and bronchoalveolar lavage fluid (BALF) in silicotic rats and to explore their potential as early biomarkers for silicosis. Pulmonary fibrosis models of rats were constructed by exposing them to silica particles. BALF and serum were collected to determine CC16 and SP-D levels using enzyme-linked immunosorbent assay (ELISA) at different times after the exposure. Hydroxyproline (HYP) level in BALF and CC16 level in the lung tissues were also measured immunohistochemistrially. The BALF levels of CC16 decreased from 49.65 to 38.02 ng/mg after the rats were exposed to silica for 3 and 28 days, which were all significantly lower as compared with the controls (P<0.05), where the levels remained barely changed during the same period (61.27 to 56.76 ng/mg). The serum CC16 also showed a similar decrease from 9.8 ng/ml to 8.78 ng/ml during the period, while in the controls, the serum CC16 levels remained constantly between 11.04 and 10.96 ng/ml. The levels of SP-D in the serum of silica-exposed rats did not decrease as compared with the controls and BALF SP-D presented a parabolic curve change with silica exposure. Immunohistochemical examinations showed that the lung Club cells were severely damaged and CC16 expression was obviously decreased after silica exposure. BALF HYP level was higher in silica-exposed rats than in control only when the exposure was at 50 mg/ml. Our work demonstrates that expressions of CC16 and SP-D are pulmonary tissue-specific and CC16 expression is down-regulated as a result of silica-exposure. The significant relationship between CC16 and silica dose indicates that CC16 may be exploited as an early biomarker to assess silica-induced pulmonary fibrosis.

Association of serum CC16 levels with eosinophilic inflammation and respiratory dysfunction in severe asthma

BackgroundThere are knowledge gaps in the potential role of Club cell 16-kDa secretory protein (CC16) in severe asthma phenotypes and type 2 inflammation, as well as the longitudinal effect of CC16 on pulmonary function tests and exacerbation risk in epidemiological studies. Objective and methodsTo assess whether serum CC16 is associated with eosinophilic inflammation in patients with severe asthma. We also examined the effect of this protein on the annual decline in forced expiratory volume in the first second (FEV1) and the risk of exacerbation using a longitudinal approach. We recruited 127 patients with severe asthma from 30 hospitals/pulmonary clinics in Hokkaido, Japan. The least square means and standard error were calculated for T-helper 2 (Th2) biomarkers and pulmonary function test across CC16 tertiles at baseline. We did the same for asthma exacerbation and annual decline in FEV1 with 3 and 5 years’ follow-up, respectively. ResultsWe found that serum CC16 was inversely associated with sputum eosinophils and blood periostin in a dose-response manner. Baseline CC16 and FEV1/forced vital capacity ratio were positively associated in adjusted models (p for trend = 0.008). Patients with the lowest tertile of serum CC16 levels at baseline had a −14.3 mL decline in FEV1 than those with the highest tertile over 5 years of follow-up (p for trend = 0.031, fully adjusted model). We did not find any association of CC16 with exacerbation risk. ConclusionPatients with severe asthma with lower circulatory CC16 had enhanced eosinophilic inflammation with rapid FEV1 decline over time.

Brief Research Report: Serum clara cell 16 kDa protein levels are increased in patients hospitalized for severe SARS-CoV-2 or sepsis infection.

BackgroundClara cell 16 kDa protein (CC16) is a secretory protein primarily expressed in epithelial cells in the lungs. Previous studies show that CC16 exerts anti-inflammatory and immune-modulatory properties in both acute and chronic pulmonary diseases. However, despite the evidence of CC16’s high biomarker potential, evaluation of its role in infectious diseases is yet very limited.MethodsSerum CC16 concentrations were measured by ELISA and assessed in two different types of severe infections. Using a case-control study design, patients treated for either severe SARS-CoV-2 or severe non-pulmonary sepsis infection were compared to age- and sex-matched healthy human subjects.ResultsSerum CC16 was significantly increased in both types of infection (SARS-CoV-2: 96.22 ± 129.01 ng/ml vs. healthy controls: 14.05 ± 7.48 ng/ml, p = 0.022; sepsis: 35.37 ± 28.10 ng/ml vs. healthy controls: 15.25 ± 7.51 ng/ml, p = 0.032) but there were no distinct differences between infections with and without pulmonary focus (p = 0.089). Furthermore, CC16 serum levels were positively correlated to disease duration and inversely to the platelet count in severe SARS-CoV-2 infection.ConclusionsIncreased CC16 serum levels in both SARS-CoV-2 and sepsis reinforce the high potential as a biomarker for epithelial cell damage and bronchoalveolar−blood barrier leakage in pulmonary as well as non-pulmonary infectious diseases.

CC16 ROLE IN BRONCHIOLITIS IN YOUNG CHILDREN

Introduction. CC16 protein is secreted by Club epithelial cells of the bronchioles, maintains homeostasis of theairway epithelium and has anti-inflammatory effects in the lungs. It is important to study the level of CC16 proteinin the serum in order to understand the integrity of the bronchial epithelium and the development of bronchialdysfunction in young children with bronchiolitis.Aim of the study. Analysis of blood serum CC16 concentration in younger bronchiolitis patients.Material and methods. We clinically examined 70 young children. The main group consisted of 35 non-allergicbronchiolitis patients. The comparison group included 25 young bronchiolitis patients with a history of allergies.The control group comprised 10 conditionally healthy children. The average age of patients was 8.4 ± 1.6 months,6.2 ± 1.4, and 6.4 ± 1.2 months in the main, comparison, and control group, accordingly. The complex of clinicaland-laboratory examination of children included CC16 serum tests. Serum CC16 content was determined by enzymelinked immunosorbent assay according to the “Human CC16 ELISA Kit”.Results of the study. It should be noted that the most main group patients (22 (62.8 ± 6.4%) of all examined) hadelevated CC16 readings. Whereas in the comparison group we did not find an increase in CC16 protein in any case.In contrast, 13 (51.8 ± 14.4%) children with bronchiolitis with a history of allergy had a decrease in CC16 protein,which may be a sign of endothelial dysfunction (p = 0.01).The study showed that young non-allergic bronchiolitis patients had the mean CC16 (38.9 ± 4.5 ng/ml) significantlyhigher than those with a history of allergies (22.9 ± 3.3 ng/ml), (OR=1,667; 0,854 - 3,250 95% CI; p &lt; 0,05). Thecontrol group patients had the mean CC16 within the reference interval (14.2 ± 2.12 ng/ml).Conclusions. In young children, elevated CC16 may be considered a marker of respiratory failure in bronchiolitispatients. Bronchiolitis patients with a history of allergies had statistically significantly lower serum CC16 levels thanthose in children without a history of allergies.