Serum CC16 Research Articles

0061 Epidemiological study of lung inflammation and oxidative damage in indium tin oxide workers

ObjectivesIndium Tin Oxide (ITO) is widely used in many kinds of touch panels nowadays. Workers could expose to ITO particles from sintering granules, splashing, pulverisation, cutting, and grinding processes. This...

Association of serum Clara cell protein CC16 with respiratory infections and immune response to respiratory pathogens in elite athletes.

BackgroundRespiratory epithelium integrity impairment caused by intensive exercise may lead to exercise-induced bronchoconstriction. Clara cell protein (CC16) has anti-inflammatory properties and its serum level reflects changes in epithelium integrity and airway inflammation. This study aimed to investigate serum CC16 in elite athletes and to seek associations of CC16 with asthma or allergy, respiratory tract infections (RTIs) and immune response to respiratory pathogens.MethodsThe study was performed in 203 Olympic athletes. Control groups comprised 53 healthy subjects and 49 mild allergic asthmatics. Serum levels of CC16 and IgG against respiratory viruses and Mycoplasma pneumoniae were assessed. Allergy questionnaire for athletes was used to determine symptoms and exercise pattern. Current versions of ARIA and GINA guidelines were used when diagnosing allergic rhinitis and asthma, respectively.ResultsAsthma was diagnosed in 13.3% athletes, of whom 55.6% had concomitant allergic rhinitis. Allergic rhinitis without asthma was diagnosed in 14.8% of athletes. Mean CC16 concentration was significantly lower in athletes versus healthy controls and mild asthmatics. Athletes reporting frequent RTIs had significantly lower serum CC16 and the risk of frequent RTIs was more than 2-fold higher in athletes with low serum CC16 (defined as equal to or less than 4.99 ng/ml). Athletes had significantly higher anti-adenovirus IgG than healthy controls while only non-atopic athletes had anti-parainfluenza virus IgG significantly lower than controls. In all athletes weak correlation of serum CC16 and anti-parainfluenza virus IgG was present (R = 0.20, p < 0.01). In atopic athletes a weak positive correlations of CC16 with IgG specific for respiratory syncytial virus (R = 0.29, p = 0.009), parainfluenza virus (R = 0.31, p = 0.01) and adenovirus (R = 0.27, p = 0.02) were seen as well.ConclusionsRegular high-load exercise is associated with decrease in serum CC16 levels. Athletes with decreased CC16 are more susceptible to respiratory infections. Atopy may be an additional factor modifying susceptibility to infections in subjects performing regular high-load exercise.

Serum levels of club cell secretory protein (Clara) and short- and long-term exposure to particulate air pollution in adolescents

BackgroundStudies in populations have shown that particulate air pollution is associated with changes in lung function in adolescents. ObjectiveWe investigated the effect of short- and long-term exposure to particulate matter (PM10) on the pulmonary health of adolescents, using serum lung club cell secretory protein (Clara) (CC16) as a biomarker for respiratory epithelium integrity. MethodsWe measured serum CC16 in 825 adolescents (57% girls, mean age: 15years). Short-term and long-term exposure to ambient PM10 was estimated for each participant's home address using a kriging interpolation method. To explore the association between PM10 and serum CC16 we applied restricted cubic splines with 5 knots located at the 5th, 25th, 50th, 75th and 95th percentiles of the PM10 distribution. The explorative analyses showed a change in the slope of this association, after which a change-point analysis was performed. ResultsAfter adjustment for potential covariates, the analysis showed strong associations between PM10 concentrations, averaged over the week preceding the clinical examination, and serum CC16 levels. Each 5μg/m3 increase in mean PM10 concentration in the week before the clinical examination was associated with a substantial increase of 0.52μg/l (95% confidence interval: 0.31 to 0.73; p<0.0001) in serum CC16 levels. The association appears nonlinear with a flattening out of the slope at mean week PM10 levels above 37μg/m3. There was no evidence of an association between long-term exposure to PM10 and serum CC16 concentrations. ConclusionsOur findings suggest that short-term exposure to particulate air pollution may compromise the integrity of the lung epithelium and lead to increased epithelial barrier permeability in the lungs of adolescents, even at low concentrations.

Club cell protein 16 and disease progression in chronic obstructive pulmonary disease.

Club (Clara) cell protein 16 (CC-16) is a protein that is synthesized predominantly in the lungs and is detectable in serum. Its expression decreases with lung injury and smoking, and is thus a marker of bronchial cell dysfunction. To evaluate the possibility of using serum CC-16 as a biomarker for disease progression in chronic obstructive pulmonary disease (COPD). We measured serum CC-16 levels from 4,724 subjects with mild-to-moderate airflow limitation in the Lung Health Study. Using a linear regression model, we determined the relationship of serum CC-16 concentrations to decline in lung function over 9 years. In addition, to determine whether CC-16 plays a major role in the pathogenesis of mild COPD, we exposed CC-16-deficient (-/-) mice to 6 months of cigarette smoke. Reduced serum concentrations of CC-16 were associated with accelerated decline in FEV1 over 9 years (P < 0.0001), and this association persisted after adjustments for age, sex, race, smoking status, airway reactivity, body mass index, and baseline FEV1 (P = 0.0002). However, CC-16(-/-) mice did not demonstrate an enhanced risk of emphysema or small airway remodeling in response to cigarette smoke. Serum CC-16 is associated with disease progression, and may assist in the identification of "rapid progressors." However, the absence of CC-16 does not appear to modify the risk of cigarette-related COPD in mice.

Serum concentrations of club cell secretory protein (Clara) and cancer mortality in adults: a population-based, prospective cohort study

Club cell secretory protein (Clara) (CC16) is produced mainly by bronchiolar club cells and has been shown to have protective effects against airway inflammation and oxidative stress from cigarette smoking and related carcinogens. The goal of this study was to establish whether serum CC16 concentrations predict all-cause and cancer-specific mortality in adults. We used data from the population-based Tucson Epidemiological Study of Airway Obstructive Diseases (TESAOD), a prospective cohort study of respiratory health initiated in Tucson, AZ, USA, in 1972, that recruited a multistage stratified cluster sample of non-Hispanic white households. We measured serum CC16 concentrations in cryopreserved serum samples and reviewed vital status up to Jan 1, 2011, through contact with next of kin, collection of death certificates, and searches of the National Death Index. Our primary analysis was the relation of baseline serum CC16 to all-cause mortality or cause-specific mortality risk, analysed by adjusted Cox proportional hazards models. 1086 TESAOD participants aged 21-70 years at enrolment were eligible for inclusion. Of these, 653 (60%) had died by 2011, and cause of death was ascertained for 649 (99%). When adjusted for sex, age, education, body-mass index, smoking and pack-years, and baseline levels of lung function, serum CC16 concentrations at baseline were inversely associated with mortality risk over the study follow-up. Mortality risk increased for each 1-SD decrease in CC16 (adjusted hazard ratio [HR] 1·16 [95% CI 1·06-1·26]; p=0·0007). For cause-specific mortality, each 1-SD decrease in serum CC16 was associated with an increased risk of dying of cancer (adjusted HR 1·41 [1·19-1·67]; p<0·0001). In the subset of smokers, the corresponding adjusted HR for mortality by lung cancer was 1·52 (1·14-2·03; p=0·004). Serum CC16 concentrations can predict mortality risk in the general adult population. The excess risk associated with lower CC16 concentrations is predominantly driven by cancer, particularly lung cancer. National Heart, Lung, and Blood Institute.

Serum levels of Clara cell protein and short- and long-term exposure to particulate air pollution in adolescents

Background: Studies in populations have shown that particulate air pollution is associated with changes in lung function in adolescents. Objective: We investigated the effect of short- and long-term exposure to particulate matter (PM10) on pulmonary health of adolescents, using serum lung Clara cell protein (CC16) as a biomarker for respiratory epithelium integrity. Methods: We measured serum CC16 in 825 adolescents (57% girls, mean age: 15 years). Short-term and long-term exposure to ambient PM10 was estimated for each participant’s home address using a kriging interpolation method. To explore the relationship between PM10 and serum CC16 we applied restricted cubic splines with 5 knots located at the 5th, 25th, 50th, 75th and 95th percentiles of the PM10 distribution. Results: After adjustment for potential covariates, the analysis showed strong associations between PM10 concentrations during a preceding week and serum CC16 levels. An increase from 20 to 30 µg/m³ in mean PM10 in the week before clinical examination was associated with a substantial increase of 0.93 µg/l (0.14 to 1.17, p=0.021) in serum CC16 levels. The association flattens at higher concentrations (mean week averages of more than 30 µg/m³). There was no evidence of an association between long-term exposure to PM10 and serum CC16 concentrations. Conclusions: Our findings suggest that short-term exposure to particulate air pollution may compromise the integrity of the lung epithelium and lead to increased epithelial barrier permeability in the lungs of adolescents, even at low concentrations.

Significance of changes of serum Clara cell secretory protein 16, pulmonary surfactant protein A in newborn infants with acute lung injury/acute respiratory distress syndrome

Objective To investigate the effect of serum Clara cell secretory protein 16 (CC16), pulmonary surfactant protein A(SP-A) in diagnosis of acute lung injury (ALI)/acute respiratory distress syndrome(ARDS) in newborn infants. Methods Fifty ALI/ARDS newborn infants in Zhuhai People's Hospital between 2011 Sep.and Dec.2012 were selected as treatment group(ALI group including 35 cases, ARDS group including 15 cases), 50 healthy newborns were selected as healthy control group.The changes of serum CC16, SP-A were detected by enzyme-linked immuno sorbent assay and were compared in the 3 groups. Results 1.Serum CC16 in ALI group and ARDS group were (34.19±1.09) mg/L, (55.28±0.82) mg/L, respectively, which were significantly higher than that in healthy control group [(12.67±1.10) mg/L](all P<0.05), and there was significant difference between ALI group and ARDS group(P<0.05).2.Serum SP-A in ALI group and ARDS group were(56.78±3.48) mg/L, (70.23±5.14) mg/L respectively, which were significantly higher than that in healthy control group [(22.10±3.32) mg/L](all P<0.05), and there was significant difference between ALI group and ARDS group(P<0.05). Conclusion Serum CC16, SP-A can be effective parameter for early monitoring ALI/ARDS in newborn infants. Key words: Acute lung injury; Acute respiratory distress syndrome; Newborn infant

Effect of therapeutic arsenic exposure on pulmonary function

Arsenic-contaminated drinking water has been associated with respiratory diseases and lung function impairment. Oral arsenic trioxide (ATO) is a standard treatment for acute promyelocytic leukaemia. This study aimed to explore the effect of therapeutic exposure to arsenic on lung function. This was a case-control cross-sectional study on patients with haematological malignancies with or without exposure to ATO. Full lung function tests and serum Clara cell protein 16 (CC16) were measured. There were 57 cases (arsenic exposed) and 57 matched controls (arsenic non-exposed) recruited. Among cases, the median duration of ATO exposure was 519 (194-1259) days. The mean FEV(1)/FVC ratio, FEV(1) (% predicted), and RV/TLC (%), as well as % subjects with FEV(1)/FVC below lower limits of normal (LLN), were similar in the two groups with or without arsenic exposure. However the mean TLC (% predicted) and DLCO/VA were significantly higher in arsenic-exposed versus non-exposed group (p = 0.01 and p = 0.008 respectively). There were mildly reduced FEV(1)/FVC ratio and FEF(25-75) (% predicted), largely within normal limits, among high level arsenic exposure compared with non-exposure (p = 0.01 and p = 0.05 respectively). Serum CC16 was comparable among both arsenic exposed and non-exposed groups. Therapeutic use of oral ATO for a median of around 1.5 years was not associated with clinically significant lung function impairment.

Oxidative DNA damage and inflammatory responses in cultured human cells and in humans exposed to traffic-related particles

Particulate pollution is a major public health concern because epidemiological studies have demonstrated that exposure to particles is associated with respiratory diseases and lung cancer. Diesel exhaust particles (DEP), which is classified as a human carcinogen (IARC, 2012), are considered a major contributor to traffic-related particulate matter (PM) in urban areas. DEP consists of various compounds, including PAHs and metals which are the principal components that contribute to the toxicity of PM. The present study aimed to investigate effects of PM on induction of oxidative DNA damage and inflammation by using lymphocytes in vitro and in human exposed to PM in the environment. Human lymphoblasts (RPMI 1788) were treated with DEP (SRM 2975) at various concentrations (25-100 μg/ml) to compare the extent of responses with alveolar epithelial cells (A549). ROS generation was determined in each cell cycle phase of DEP-treated cells in order to investigate the influence of the cell cycle stage on induction of oxidative stress. The oxidative DNA damage was determined by measurement of 8-hydroxy-deoxyguanosine (8-OHdG) whereas the inflammatory responses were determined by mRNA expression of interleukin-6 and -8 (IL-6 and IL-8), Clara cell protein (CC16), and lung surfactant protein-A (SP-A). The results showed that RPMI 1788 and A549 cells had a similar pattern of dose-dependent responses to DEP in terms of particle uptake, ROS generation with highest level found in G2/M phase, 8-OHdG formation, and induction of IL-6 and IL-8 expression. The human study was conducted in 51 healthy subjects residing in traffic-congested areas. The effects of exposure to PM2.5 and particle-bound PAHs and toxic metals on the levels of 8-OHdG in lymphocyte DNA, IL-8 expression in lymphocytes, and serum CC16 were evaluated. 8-OHdG levels correlated with the exposure levels of PM2.5 (P<0.01) and PAHs (P<0.05), but this was not the case with IL-8. Serum CC16 showed significantly negative correlations with B[a]P equivalent (P<0.05) levels, but positive correlation with Pb (P<0.05). In conclusion, a similar pattern of the dose-dependent responses to DEP in the lymphoblasts and lung cells suggests that circulating lymphocytes could be used as a surrogate for assessing PM-induced oxidative DNA damage and inflammatory responses in the lung. Human exposure to PM leads to oxidative DNA damage whereas PM-induced inflammation was not conclusive and should be further investigated.

Clara Cell Protein and Myeloperoxidase Levels in Serum of Subjects after Exposure to Fire Smoke

Fire smoke inhalation is a well-recognized aetiological factor of airway injuries. The objective of this study was evaluation of Clara cell protein (CC16) and myeloperoxidase (MPO) concentrations in serum of patients after exposure to uncontrolled fire smoke. The study group consisted of 40 consecutive patients admitted to the Toxicology Unit after exposure to fire smoke. CC16 and MPO concentrations in their serum samples was measured on the day of admission to hospital and rechecked at the 2nd day and on the day of discharge. Patients also underwent routine toxicological diagnostic procedures applied in case of exposures, such as carboxyhaemoglobin (COHb) levels and blood lactate and urinary thiocyanate concentrations. The same diagnostic tests were performed in the control group consisting of 10 healthy subjects not exposed to fire smoke. The average concentration of CC16 in the serum of subjects exposed to toxic factors was significantly higher at the day of admission in comparison with the respective values recorded on the 2nd day and on the day of discharge. The mean level of CC16 in the serum of the exposed group was also significantly higher than that in the control group. Tests for MPO concentrations in the serum did not reveal any significant changes in patients exposed to fire smoke. As indicated, acute exposure to smoke induces injury at the alveolar level, which results in a transient increase of CC16 in serum of exposed subjects.

Clara cell protein 16

Clara cell protein 16 (CC16) has recently gained acceptance as a blood biomarker for detecting direct and indirect lung injury. Although the early elevation of CC16 serum levels has been shown to correlate with pulmonary damage in patients with multiple injuries, the subsequent time course of CC16 serum levels has not been investigated in these patients. Fifty-eight patients with multiple injuries, 32 with severe thoracic injury, and 12 healthy volunteers were enrolled in this study. CC16 serum levels were measured at the time they were admitted to the trauma ward "time 0" and subsequently until day 14 using the enzyme-linked immunosorbent assay technique. The correlation between CC16 serum levels and severe lung injury, onset of nosocomial pneumonia, acute respiratory distress syndrome or acute lung injury, and organ failure was measured. In addition, areas under the receiver operating characteristic curve were calculated (p < 0.05 = significant). In patients with lung injury, initial "time 0" median CC16 values were significantly elevated (11.2 ng/mL) compared with patients without severe thoracic injury (6.9 ng/mL) and controls (6.3 ng/mL). The observed elevation in serum CC16 declined to control values within 12 to 24 hours after trauma unless patients secondarily developed pneumonia. In the latter patients, median CC16 serum levels were significantly elevated (14.5 ng/mL) at the onset of pneumonia compared with their levels (7.3 ng/mL) 1 day before. In contrast, no secondary elevation in CC16 serum levels was observed in patients without severe lung injury within the same 24-hour period. The area under the receiver operating characteristic curve for serum CC16 and pneumonia was 0.79 (0.62-0.97; p = 0.0011). Our results confirm the previously described association between initial elevation in CC16 serum levels and severe thoracic injury in patients with multiple injuries. In addition, we found that the initial elevation in CC16 serum levels declines to control values within the first day after trauma and that a secondary elevation indicates respiratory complications. Diagnostic study, level II.

Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 6: 6-day randomized clinical trial of a menthol cigarette in Japan

A randomized, controlled, open-label, parallel-group, single-center study to determine biomarkers of exposure to 12 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke, excretion of mutagenic material in urine, and serum Clara cell 16-kDa protein (CC16) in 102 male and female Japanese subjects who smoked Marlboro Ultra Lights Menthol cigarettes (M4JM; 4mg tar and 0.3mg nicotine) at baseline. Subjects were randomized to continue smoking M4JM, or switch to smoking either the Electrically Heated Cigarette Smoking System menthol cigarette (EHCSS-K6M; 5mg tar and 0.3mg nicotine) or the Lark One menthol cigarette (Lark1M; 1mg tar and 0.1mg nicotine), or to no-smoking. The mean decreases from baseline to Day 5/6 were statistically significant (p⩽0.05) for exposure to 10 of 12 cigarette smoke HPHC including the primary endpoint (carbon monoxide) and urinary excretion of mutagenic material in the EHCSS-K6M group (−12.3% to −83.4%). Smaller, but statistically significant reductions (p⩽0.05) occurred in the Lark1M group (−3.3% to −35.2%), with the exception of urinary mutagens. The largest mean reductions (all p⩽0.05) in exposure to cigarette smoke HPHC and excretion of mutagenic material occurred in the no-smoking group (−1.4% to −93.6%). Serum CC16, an indicator of lung epithelial injury, was not significantly different between groups.

Swimming pool attendance and respiratory symptoms and allergies among Dutch children

ObjectivesTo describe associations among swimming, respiratory health, allergen sensitisation and Clara cell protein 16 (CC16) levels in Dutch schoolchildren. Trichloramine levels in swimming pool air were determined to assess potential...

Evaluation of a Common Variant of the Gene Encoding Clara Cell 10 kd Protein (CC10) as a Candidate Determinant for Asthma Severity and Steroid Responsiveness Among Chinese Children

Objective. The gene (SCGB1A1) encoding Clara cell 10-kDa protein (CC10), a steroid-inducible immune modulator, is a candidate gene for asthma, but the evidence is equivocal. The potential influence of a common variant on asthma severity and serum CC10 levels during acute exacerbation and after corticosteroid treatment in Chinese case–control children and its functional relevance was investigated. Methods. Genotyping of a non-coding variant G+38A was performed in 489 children, of whom 277 had asthma with varying severity, and 212 healthy controls. Associations were tested for asthma, asthma severity, and responsiveness to steroid treatment. The transcriptional activity of this variant was examined in a Clara-like cell line (H358) using transient transfection assays. Results. Significant association was observed for the combined GA and AA genotypes of the CC10 G+38A variant and an increased risk of asthma [odds ratio (OR), 2.62, p < .001]. This association was correlated with asthma severity (moderate: OR, 2.85, p < .001; near-fatal: OR, 4.81, p < .001). Also, patients with the GA and AA genotypes showed significantly lower serum CC10 (p < .01) and provocation concentration causing a 20% fall (PC20) in forced expiratory volume in 1 s (FEV1) (p < .0001) when compared with those with the GG. After glucocorticoid treatment, the CC10 levels were significantly increased in asthmatic patients with GG (p < .0001), but not those with the GA and AA genotypes. Moreover, a lower dexamethasone-induced reporter (luciferase) activity was observed for H358 cells transiently transfected with the G38A risk allele (A) compared with wild-type allele (G). Conclusions. These findings suggest that the CC10 G+38A variant may contribute to the severity of asthma and lower level of steroid responsiveness.

14:45 NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IN SCHIZOPHRENIA: READY FOR PRACTICE OR A GOOD START? A META-ANALYSIS

Recently, there have been some reports that schizophrenia is accompanied by an immune-inflammatory response, characterized by increased secretion of interleukin-6 (IL-6), soluble IL-2 receptor (sIL-2) and lower plasma levels of CC16 (Clara cell protein), an endogenous anti-cytokine. It was shown that clozapine, an atypical antipsychotic drug, may increase the plasma levels of sIL-2R and pro-inflammatory cytokines. This study was carried out in order to examine serum IL-6, IL-6R, CC16, IL-1R antagonist (IL-1RA), transferrin receptor (TfR) and sCD8 antigen, both before and after treatment with clozapine in schizophrenic subjects versus normal controls. Schizophrenic patients showed significantly higher plasma IL-6R and IL-1RA and lower plasma CC16 than normal controls. Treatment with clozapine significantly increased plasma sCD8, IL-6, CC16 and IL-1RA concentrations. The clozapine-induced increments in plasma IL-6 and CC16 appeared during the first 2 weeks of treatment, whereas the increases in plasma sCD8 and IL-1RA appeared after 5 weeks. Clozapine appears to have complex in vivo immunomodulatory effects.

An Oral Inhibitor of p38 MAP Kinase Reduces Plasma Fibrinogen in Patients With Chronic Obstructive Pulmonary Disease

The aims were to determine the effect of an oral inhibitor of the signaling mediator p38 mitogen-activated protein kinase (GW856553, losmapimod) on sputum neutrophils, pulmonary function, and blood biomarkers of inflammation in chronic obstructive pulmonary disease (COPD). Three hundred and two individuals with GOLD stage II COPD were randomized to oral losmapimod 7.5 mg twice daily, inhaled salmeterol/fluticasone propionate 50 µg/500 µg combination (SFC), or placebo in a 12-week, randomized, double-blind, double-dummy study (MKI102428/NCT00642148). Neither losmapimod nor SFC had an effect on the primary end point of sputum neutrophils. Losmapimod was well tolerated and reduced plasma fibrinogen by 11% (-0.4 g/L, ratio of effect of losmapimod/placebo 0.89; 95% confidence interval, 0.83-0.96; P = .002) with nonsignificant reductions in interleukin-6, interleukin-8, and C-reactive protein. There was evidence of improvement in hyperinflation with losmapimod compared with placebo (overall P = .02). Inhaled SFC significantly improved lung function and reduced serum CC-16 (ratio of effect of SFC/placebo 0.87; 95% confidence interval, 0.82-0.93; P < .001). It was concluded that oral losmapimod significantly reduced plasma fibrinogen in patients with COPD.

Circulating Levels of Clara Cell Protein 16 But Not Surfactant Protein D Identify and Quantify Lung Damage in Patients With Multiple Injuries

Almost 60% of all patients with severe multiple injuries sustain severe chest trauma with aggravating effect on morbidity and mortality. Diagnosis of lung contusion is performed by early posttraumatic multislice computed tomography. Because this diagnostic procedure requires time, resources, and exposure to radiation, a noninvasive approach with easy follow-up measurements is warranted. Serum levels of Clara cell protein 16 (CC16) and surfactant protein D as lung-specific biomarkers were obtained on admission from 104 patients with multiple injuries using enzyme-linked immunosorbent assay technique. Patients were divided into those with severe lung injury ([LI]; n = 68) and without LI (NLI; n = 36). Nonsmoking healthy volunteers served as controls. In addition, volume of lung contusions were calculated planimetrically on serial multislice computed tomography scans obtained after admission. Factors influencing CC16 serum levels were determined in uni- and multivariate analyses, and Spearman rank coefficients were calculated for correlations. Patients with LI showed a significant (p < 0.05) elevation of median CC16 levels (10.2 ng/mL) compared with NLI patients (5.4 ng/mL) and controls (5.2 ng/mL). Serum CC16 levels correlated with the volume of lung contusions (r = 0.78, p < 0.0001) and were not influenced by overall injury severity, age, gender, or preclinical ventilation. In contrast, circulating surfactant protein D levels were not associated with the presence of LI or the extent of lung contusions. Our results advocate CC16 as a potential biomarker for LI in severely injured patients because of its high correlation with the volume of contused lung parenchyma. Therefore, this parameter may allow a specified initial treatment of patients with multiple injuries.

Biomarkers of early respiratory effects in smoking adolescents

Noninvasive biomarkers can be used to evaluate airways damage caused by tobacco smoke, but studies so far have only involved adult smokers. In this study, we evaluated whether such biomarkers can detect early respiratory effects in adolescents passively or actively exposed to tobacco smoke. In a cross-sectional study of 845 adolescents (mean age 16 yrs), we measured exhaled nitric oxide (NO) and various epithelial markers in nasal lavage fluid (NALF) and serum, including Clara cell protein (CC16) and surfactant protein (SP)-D. Information about smoking habits and potential confounders was collected by questionnaire. Four groups of equal size (n = 36), of nonsmokers, passive smokers, light smokers (<5 cigarettes · day(-1), median 0.08 pack-yrs) and heavy smokers (≥ 5 cigarettes · day(-1), median 0.35 pack-yrs), were matched using an automated procedure. The levels of exhaled NO and of CC16 in NALF were significantly decreased in the group of heavy smokers. A trend towards lower levels of CC16 in NALF was observed in passive smokers. There were no significant changes in serum CC16 and SP-D, which suggests that the deep lung epithelium had not yet been affected by smoking. In conclusion, tobacco smoke can cause early changes in the airways of adolescents with a cumulative smoking history of <1 pack-yr.

The CC16 A38G polymorphism is associated with the development of asthma in children with allergic rhinitis

Although asthma and allergic rhinitis (AR) are considered to be one syndrome, many questions remain unanswered. Why do some AR patients develop asthma but others do not, and which factors play a role in the development of asthma that have so far not been clearly elucidated. We hypothesize that children with AR who have the Clara cell secretory protein (CC16, secretoglobin 1A1) 38A/38A genotype (rs3741240) have an increased likelihood of developing asthma. The study sample included 117 children, with AR, but no asthma diagnosed within the following 5 years, as the control group. Cases group (n=202) included age- and gender-matched children with AR first, and asthma developed 3-5 years later, as the study group. The CC16 genotype was determined by PCR and Sau96I restriction digestion of PCR products. The serum CC16 levels were measured by ELISA. Total serum IgE, allergen specific IgE, eosinophil count and pulmonary function were also measured. In children with rhinitis who develop asthma, the frequencies of the AA genotype were significantly higher than those who did not develop asthma [odds ratio (OR)=2.527; 95% confidence interval (CI)=1.571-4.065; P<0.01]. Serum CC16 levels in the children with rhinitis who develop asthma and carry the AA genotype were significantly lower than those who carry the non-AA genotype and those who did not develop asthma. Results of this study suggest that CC16 38A/38A genotype plays a role in the development of early asthma in children with AR. Early identification of rhinitis children at risk may assist in designing preventative approach to asthma development.

Pooling Data on Pools: Genotoxicity of Chemicals in Indoor Swimming Pools

Disinfection by-products (DBPs) form in swimming pool water from reactions between disinfectants such as chlorine and organic matter such as sweat, skin cells, and urine. A new study described in a set of three articles provides the first comprehensive characterization of DBPs in an indoor pool environment and offers initial evidence of cellular-level effects of these chemicals in swimmers in an indoor chlorinated pool [EHP 118(11):1523–1530; Richardson et al.; EHP 118(11):1531–1537, Kogevinas et al.; EHP 118(11):1538–1544, Font-Ribera et al.]. The authors assessed short-term changes in 49 healthy adults after they swam for 40 minutes in a public indoor chlorinated pool. They observed increases in two biomarkers of genotoxicity relative to the concentration of brominated trihalomethanes (THMs) in exhaled breath, which were used as a proxy of the swimmers’ total DBP exposures. Those biomarkers were micronuclei in blood lymphocytes (which have been associated with cancer risk in healthy subjects) and urine mutagenicity (a biomarker of exposure to genotoxic agents). The team also took detailed measurements of THMs in air around the pool and in exhaled breath of the swimmers before and after swimming. The investigators measured several biomarkers of respiratory effects after swimming and found changes in only one—a slight increase in serum CC16, which suggests an increase in lung epithelium permeability. However, they found no evidence that DBP exposure affected lung function. The research team identified more than 100 DBPs in the water of the chlorinated pool as well as another indoor pool disinfected with bromine. Some of these compounds had never been reported previously in swimming pool water and/or chlorinated drinking water. In vitro assays showed the swimming pool water was mutagenic at levels similar to that of drinking water but was more cytotoxic (could kill cells at a lower concentration) than drinking water. The researchers acknowledge the need for further research on a variety of swimming pools under various conditions of maintenance and use as well as more complete evaluations of the uptake and potential effects of the compounds present in pool water. They also note the importance of timing in the collection of biological samples—a parameter for which there was no precedent, given the lack of previous studies of this type with swimmers. Above all, they emphasize that positive health effects of swimming can be maintained by minimizing pool levels of DBPs.