Serum pneumoproteins and biomarkers of exposure to urban air pollution: a cross-sectional comparison of policemen and foresters

Very few biomarkers are available for the non-invasive detection of effects of urban air pollution on the respiratory tract. The objective was to evaluate whether Clara cell protein (CC16) and surfactant-associated protein-A (SP-A), two pulmonary secretory proteins, were useful in the detection of effects of urban air pollutants on the pulmonary epithelium. These proteins were determined in the serum of 53 policemen working in Brussels, Belgium, and a control group of 59 foresters working in the countryside. Except for ozone (O₃), annual concentrations of the main air pollutants (PM₁₀, NO₂, CO, SO₂ and benzene) were significantly higher in Brussels than in the country. The proportion of smokers was lower in urban policemen compared with foresters, but they smoked on average a similar number of cigarettes per day as confirmed by their urinary excretion of cotinine. Muconic acid, a marker of benzene exposure, was significantly higher in urban policemen than in foresters, in both smokers and non-smokers. Multiple regression analysis showed that the type of work, smoking habits and time spent outdoors and in a car were significant determinants of benzene uptake. Tobacco smoking impaired lung function to a similar extent in urban policemen and foresters. The serum levels of SP-A were significantly increased in smokers but were not different between policemen and foresters. Serum CC16 was significantly reduced by tobacco smoking and slightly decreased in policemen compared with foresters. Interestingly, the reduction of serum CC16 was more pronounced in the subgroup of traffic compared with survey policemen, the latter being also less exposed to benzene. The results suggest that serum pneumoproteins and especially serum CC16 could be useful in the detection of chronic effects of urban air pollutants on the respiratory epithelium of populations particularly at risk.     

Effect of rioprostil and colchicine on CC14-acute liver damage in rats. Relationship with plasma membrane lipids

The effects of colchicine (10 g/day p.o. for 7 days) and rioprostil (2-decarboxy, 2-hydroxymethyl-15-deoxy-16-RS-hydroxy-16-methyl-prostaglandin-E1) (20 g/kg s.c., a single dose) on the enzymatic and histological markers of acute liver damage were studied in rats intoxicated with a single oral dose of CC1₄. The rats were sacrificed 24 h after CC1₄. The lipid composition of the liver plasma membranes was also determined. The increase in Alk. Phosp., GGTP and GPT activities and bilirubin concentration in serum as well as the histological images produced by CC1₄ were equally prevented by the treatments with colchicine or rioprostil. CC1₄ changed the lipid composition of the liver plasma membrane by increasing PI and PC and decreasing SM, PS and PEA. There was a decrease in the cholesterol/phospholipid ratio at the expense of a reduction of cholesterol/protein ratio and elevation in phospholipid/protein ratio. Colchicine and rioprostil also prevented these lipid alterations. The results suggest that the plasma membrane is an important site of action of CC1₄ and of the 2 drugs studied. We postulate that the plasma membrane rather than other organelles is the target for the cytoprotective actions of prostaglandins.     

Clara cell protein (CC16): characteristics and potential applications as biomarker of lung toxicity

Most biomarkers of lung toxicity presently available require a bronchoahreolar lavage (BAL). Such a procedure cannot be applied for monitoring populations at risk in the industry or environment nor for a regular follow-up of patients with lung disorders. A lung biomarker, measurable in serum, BAL fluid and sputum has recently been identified. This biomarker is a microptotein initially isolated from urine (Urine Protein 1) and subsequently identified as the major secretory product of lung Clara cells which are non-ciliated cells localized predominantly in terminal bronchioles. This protein called Clara cell protein (CC16) is a homodimer of 15.8 kDA. Several lines of evidence indicate that CC16 is a natural immunoregulator protecting the respiratory tract from unwanted inflammatory reactions. CC16 secreted in the respiratory tract diffuses passively by transudation into plasma from where it is rapidly eliminated by glomerular filtration before being taken up and catabolized in proximal tubule cells. Studies reviewed here suggest that CC16 in BAL fluid or serum is a sensitive indicator of acute or chronic bronchial epithelium injury. A significant reduction of CC16 has been found in serum and BAL fluid of asymptomatic smokers. On average serum CC16 decreases by 15% for each 10 pack-year smoking history. Serum CC16 was also found to be decreased in several occupational groups chronically exposed to different air pollutants (silica, dust, welding fumes). A dose—effect relationship with the intensity of exposure to dust has been found in one study on foundry workers. The concentration of CC16 in serum can also be used to detect an acute or chronic disruption of the bronchoalveolar/blood barrier integrity. While confirming the potential interest of CC16 as a lung biomarker, clinical investigations indicate that CC16 might be an important mediator in the development of lung injury. These findings open new perspectives in the assessment of lung toxicity by suggesting that readily diffusible lung-specific proteins may serve as peripheral markers of pneumotoxicity.     

Prognostic significance of low serum levels of Clara cell phospholipid-binding protein in occupational aluminium neurotoxicity

The relationship between respiratory and neurological effects of exposure to aluminium (Al) was investigated in a group of foundry workers exposed to Al at concentrations below the threshold limit value (TLV) binding in Poland (2.0 mg Al2O3 m(-3)). Neurological and neurophysiological parameters indicated subclinical effects of Al exposure on the nervous system. The measurement of serum anti-inflammatory Clara cell protein (CC16) was employed as a peripheral marker of the lung epithelium function. There was a strong inverse relationship between serum Al (Al-S) and CC16 concentrations (p = 0.006). The lowest CC16 concentrations were found in serum of workers characterised by subjective symptoms of the central nervous system (CNS) and abnormal results of neurophysiological examinations (EEG and VEP). Low serum CC16 concentrations and enhanced Al and iron (Fe) levels were also observed in the younger age group of workers with the subjective CNS symptoms and abnormal VEP results, which suggests that Fe is implicated in strengthening of the neurotoxic Al potential. The results of our study support the hypothesis that subclinical neurological symptoms (especially abnormal VEP) are most likely associated with internalisation of Al ions with lipid fractions of the lung epithelium, which in turn may help Al ions overcome the blood-brain barrier. Low serum CC16 concentrations (<10 microg L(-1)) were noted in workers with the abnormal results of neurological (CNS) and neurophysiological (EEG and VEP) examinations as well as with Al body burden manifested by urinary excretion (Al-U) below 60 microg L(-1) and Al-S concentration of 2 microg L(-1). This concentration may be considered as a threshold allowable biological concentration of aluminium.     

Comprehensive characterisation of pulmonary and serum surfactant protein D in COPD

Background

Pulmonary surfactant protein D (SP-D) is considered as a candidate biomarker for the functional integrity of the lung and for disease progression, which can be detected in serum. The origin of SP-D in serum and how serum concentrations are related to pulmonary concentrations under inflammatory conditions is still unclear.

Methods

In a cross-sectional study comprising non-smokers (n = 10), young - (n = 10), elderly smokers (n = 20), and smokers with COPD (n = 20) we simultaneously analysed pulmonary and serum SP-D levels with regard to pulmonary function, exercise, repeatability and its quaternary structure by native gel electrophoresis. Statistical comparisons were conducted by ANOVA and post-hoc testing for multiple comparisons; repeatability was assessed by Bland-Altman analysis.

Results

In COPD, median (IQR) pulmonary SP-D levels were lower (129(68) ng/ml) compared to smokers (young: 299(190), elderly: 296(158) ng/ml; p < 0.01) and non-smokers (967(708) ng/ml; p < 0.001). The opposite was observed in serum, with higher concentrations in COPD (140(89) ng/ml) as compared to non-smokers (76(47) ng/ml; p < 0.01). SP-D levels were reproducible and correlated with the degree of airway obstruction in all smokers. In addition, smoking lead to disruption of the quaternary structure.

Conclusions

Pulmonary and serum SP-D levels are stable markers influenced by smoking and related to airflow obstruction and disease state. Smaller subunits of pulmonary SP-D and the rapid increase of serum SP-D levels in COPD due to exercise support the translocation hypothesis and its use as a COPD biomarker.

Trial registration

no interventional trial     

Effect of sulphur dioxide exposure on human chromosomes

The genotoxic effects of an average concentration of 41.7 mg/m³ of SO₂ exposure on 42 workers of a fertilizer factory were investigated. Mitotic index (MI), chromosomal aberrations (CAs), sister-chromatid exchanges (SCEs) and satellite associations (SA) were observed. In SO₂-exposed workers, a higher mitotic index (7.09) was recorded in comparison to controls (4.34). The MI, however, declined with duration of exposure. Satellite associations showed a two-fold increase (17.1) as compared to controls (8.11). Among chromosomes, D-G group associations were the highest (7.43%), while 3D type associations were the lowest (0.4%). There was a significant difference (p < 0.05) in the mean frequency of CAs per cell in the exposed workers (3.262%) and the controls (0.833%). The mean frequency of SCEs per cell increased from 3.32 ± 0.1 in controls to 7.72 ± 0.19 in the exposed group. The difference was significant (p < 0.05). In smokers, alcoholics and smoker-alcoholics, the frequency of CAs and SCEs per cell was significantly higher than the non-smokers and non-alcoholics, both in the controls and the SO₂-exposed workers and showed a correlation with the duration of exposure. SO₂ is therefore a clastogenic and genotoxic agent for which necessary precautions must be taken.     

Serum pneumoproteins and biomarkers of exposure to urban air pollution: a cross-sectional comparison of policemen and foresters

Very few biomarkers are available for the non-invasive detection of effects of urban air pollution on the respiratory tract. The objective was to evaluate whether Clara cell protein (CC16) and surfactant-associated protein-A (SP-A), two pulmonary secretory proteins, were useful in the detection of effects of urban air pollutants on the pulmonary epithelium. These proteins were determined in the serum of 53 policemen working in Brussels, Belgium, and a control group of 59 foresters working in the countryside. Except for ozone (O₃), annual concentrations of the main air pollutants (PM₁₀, NO₂, CO, SO₂ and benzene) were significantly higher in Brussels than in the country. The proportion of smokers was lower in urban policemen compared with foresters, but they smoked on average a similar number of cigarettes per day as confirmed by their urinary excretion of cotinine. Muconic acid, a marker of benzene exposure, was significantly higher in urban policemen than in foresters, in both smokers and non-smokers. Multiple regression analysis showed that the type of work, smoking habits and time spent outdoors and in a car were significant determinants of benzene uptake. Tobacco smoking impaired lung function to a similar extent in urban policemen and foresters. The serum levels of SP-A were significantly increased in smokers but were not different between policemen and foresters. Serum CC16 was significantly reduced by tobacco smoking and slightly decreased in policemen compared with foresters. Interestingly, the reduction of serum CC16 was more pronounced in the subgroup of traffic compared with survey policemen, the latter being also less exposed to benzene. The results suggest that serum pneumoproteins and especially serum CC16 could be useful in the detection of chronic effects of urban air pollutants on the respiratory epithelium of populations particularly at risk.     

七氟烷吸入麻醉对单肺通气患者血清IL-6、IL-10、MIP-2、SP-D及HMGB1水平的影响

目的:探讨七氟烷吸入麻醉对单肺通气患者血白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、巨噬细胞炎性蛋白-2(MIP-2)、人肺表面活性特异蛋白(SP-D)及高迁移率族蛋白1(HMGB1)水平的影响。方法:选择2014年9月~2016年9月于我院行单肺通气的患者108例,参照抽签法分为两组,每组各54例。对照组行常规麻醉,实验组采用七氟烷麻醉,比较两组通气前后血清IL-6、IL-10、MIP-2、SP-D、HMGB1、丙二醇(MDA)、超氧化物歧化醇(SOD)、平均动脉压(MAP)、心率(HR)水平的变化及并发症的发生情况。结果:通气前,两组血清IL-6、IL-10、MIP-2、SP-D、HMGB1、MDA、SOD、MAP、HR水平比较差异均无统计学意义(P0.05)。通气后,两组血清IL-6、IL-10、MIP-2、SP-D、HMGB1、MDA水平均较治疗前显著上升,而实验组以上指标均明显低于对照组;两组血清SOD、MAP、HR均较治疗前显著降低,且研究组低于对照组,差异均有统计学意义(P0.05)。结论:七氟烷吸入麻醉能够抑制单肺通气患者血清IL-6、IL-10、MIP-2、SP-D及HMGB1水平上升,改善机体的氧化应激状态,利于血流动力学的稳定,发挥肺部保护作用。     

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

Background

Respiratory 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.

Methods

The 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.

Results

Asthma 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.

Conclusions

Regular 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.     

Biomarkers and Bacterial Pneumonia Risk in Patients with Treated HIV Infection: A Case-Control Study

Background

Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist.

Methods

We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1∶1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls.

Results

Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm³. Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 µg/mL in cases vs. 1.93 µg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively).

Conclusions

In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk.     

A critical review of the use of Clara cell secretory protein (CC16) as a biomarker of acute or chronic pulmonary effects

Biomarkers associated with asthma aetiology and exacerbation have been sought to shed light on this multifactorial disease. One candidate is the serum concentration of the Clara cell secretory protein (CC16, sometimes referred to as CC10 or uteroglobin). In this review, we examine serum CC16's relation to asthma aetiology and exacerbation. There is evidence that acute exposures to certain pulmonary irritants can cause a transient increase in serum CC16 levels, and limited evidence also suggests that a transient increase in serum CC16 levels can be caused by a localized pulmonary inflammation. Research also indicates that a transient increase in serum CC16 is not associated with measurable pulmonary damage or impairment of pulmonary function. The biological interpretation of chronic changes in serum CC16 is less clear. Changes in serum CC16 concentrations (either transient or chronic) are not specific to any one agent, disease state, or aetiology. This lack of specificity limits the use of serum CC16 as a biomarker of specific exposures. To date, many of the critical issues that must be understood before serum CC16 levels can have an application as a biomarker of effect or exposure have not been adequately addressed.     

Clara cell protein (CC16) in serum and bronchoalveolar lavage fluid of subjects exposed to asbestos

The Clara cell protein (CC16) is a small and readily diffusible protein of 16kDa secreted by bronchiolar Clara cells in the distal airspaces. These epithelial cells are altered in several pulmonary pathological processes induced by various lung toxicants. In the search for a new biomarker of asbestos-induced lung impairment, we used a sensitive immunoassay to determine the levels of CC16 in bronchoalveolar fluid (BALF) and serum of subjects exposed to asbestos compared with a group of healthy controls. In the BALF of asbestos-exposed subjects there was an insignificant trend towards CC16 elevation compared with controls, with a (mean ±SD of 0.81 ±0.65mg l^-1 for asbestos-exposed subjects (n = 23) versus 0.39 ±0.19mg l^-1 for controls (n = 11) (p = 0.09). In serum, CC16 concentration was significantly increased among asbestos-exposed subjects, with values of 27.2 ±24.0 µg l^-1 for asbestos-exposed subjects (n = 34) versus 16.1 ±7.6 µg l^-1 for controls (n = 34) (p = 0.01). Regarding the effects of smoking, there were significant differences between generally lower CC16 levels in serum and BALF (p = 0.05 and 0.001, respectively) of smokers compared with the higher levels in non-smokers. Serum CC16 levels positively correlated with those in BALF, which is consistent with a diffusional transfer of CC16 from the bronchoalveolar space into the serum. No association, however, emerged between the levels of CC16 in serum or BALF and either the duration of asbestos exposure or the severity of the lung impairment as assessed by chest X-ray. These findings suggest that exposure to asbestos elicits early changes in the local and, importantly, also the systemic levels of CC16. This pneumoprotein therefore appears as a promising non-invasive biomarker of asbestos-induced lung injury and occupational disease in both smoking and non-smoking exposed subjects.     

A critical review of the use of Clara cell secretory protein (CC16) as a biomarker of acute or chronic pulmonary effects

Biomarkers associated with asthma aetiology and exacerbation have been sought to shed light on this multifactorial disease. One candidate is the serum concentration of the Clara cell secretory protein (CC16, sometimes referred to as CC10 or uteroglobin). In this review, we examine serum CC16's relation to asthma aetiology and exacerbation. There is evidence that acute exposures to certain pulmonary irritants can cause a transient increase in serum CC16 levels, and limited evidence also suggests that a transient increase in serum CC16 levels can be caused by a localized pulmonary inflammation. Research also indicates that a transient increase in serum CC16 is not associated with measurable pulmonary damage or impairment of pulmonary function. The biological interpretation of chronic changes in serum CC16 is less clear. Changes in serum CC16 concentrations (either transient or chronic) are not specific to any one agent, disease state, or aetiology. This lack of specificity limits the use of serum CC16 as a biomarker of specific exposures. To date, many of the critical issues that must be understood before serum CC16 levels can have an application as a biomarker of effect or exposure have not been adequately addressed.     

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

Abstract

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.     

An integrated approach to biomonitoring exposure to styrene and styrene-(7,8)-oxide using a repeated measurements sampling design

Abstract

The aim of this work was to investigate urinary analytes and haemoglobin and albumin adducts as biomarkers of exposure to airborne styrene (Sty) and styrene-(7,8)-oxide (StyOX) and to evaluate the influence of smoking habit and genetic polymorphism of metabolic enzymes GSTM1 and GSTT1 on these biomarkers. We obtained three or four air and urine samples from each exposed worker (eight reinforced plastics workers and 13 varnish workers), one air and urine samples from 22 control workers (automobile mechanics) and one blood sample from all subjects. Median levels of exposure to Sty and StyOX, respectively, were 18.2 mg m^?3 and 133 µg m^?3 for reinforced plastics workers, 3.4 mg m^?3 and 12 µg m^?3 for varnish workers, and <0.3 mg m^?3 and <5 µg m^?3 for controls. Urinary levels of styrene, mandelic acid, phenylglyoxylic acid, phenylglycine (PHG), 4-vinylphenol (VP) and mercapturic acids (M1+M2), as well as cysteinyl adducts of serum albumin (but not those of haemoglobin) were significantly associated with exposure status (controls相似文献   

支原体肺炎患者治疗后血清SP-A、SP-D与hs-CRP的变化趋势及临床意义

目的:研究支原体肺炎(MP)患者血清肺表面活性蛋白-A(SP-A)、肺表面活性蛋白-D(SP-D)与超敏C反应蛋白(hs-CRP)的变化趋势及临床意义。方法:选择从2015年9月到2016年9月在我院治疗的MP患者56例纳入本次研究,将其记为观察组,给予常规治疗后,有效者49例,无效者7例。另选同期在我院进行健康体检的志愿者55例作为对照组,对比两组血清SP-A、SP-D及hs-CRP的变化趋势,比较观察组不同治疗结果患者的血清SP-A、SP-D及hs-CRP水平,并分析患者的血清SP-A、SP-D与hs-CRP的相关性。结果:治疗后3d及治疗后7d观察组的血清SP-A、SP-D及hs-CRP水平较治疗前依次降低,但均高于对照组(P0.05),在治疗后14d血清SP-A、SP-D及hs-CRP水平较治疗前降低(P0.05),但与对照组比较差异无统计学意义(P0.05)。治疗后14 d有效组血清SP-A、SP-D及hs-CRP水平均明显低于无效组,差异有统计学意义(P0.05)。根据Spearman相关性分析结果显示,MP患者的血清SP-A、SP-D与hs-CRP均呈正相关(r=0.713、0.699,P=0.000、0.000)。结论:MP患者的血清SP-A、SP-D及hs-CRP水平可伴随治疗过程的进行而逐渐回落,最终基本恢复至正常范围,且血清SP-A、SP-D水平与hs-CRP水平呈正相关,临床治疗时可针对上述3种指标进行监测以判断患者病情及治疗效果。     

Synergistic Impaired Effect between Smoking and Manganese Dust Exposure on Pulmonary Ventilation Function in Guangxi Manganese-Exposed Workers Healthy Cohort (GXMEWHC)

PurposeThe aims of this study were to investigate the effects of manganese (Mn) dust exposure on lung functions and evaluate the potential synergistic effect between smoking and Mn dust exposure among refinery workers.MethodsA retrospective study including 1658 workers in a ferromanganese refinery was conducted, with subjects who were from the Guangxi manganese-exposed workers healthy cohort (GXMEWHC). Based on the Mn manganese cumulative exposure index (Mn-CEI), all subjects were divided into the low exposure group (n = 682) and the high exposure group (n = 976). A pulmonary function test was performed using an electronic spirometer, including the values and percentages of FVC, FEV₁, FEV₁/FVC, MMEF, PEFR, MVV, respectively.ResultsNo significant effect of Mn dust exposure on the pulmonary function was found in the female workers (all p>0.05). However, there was an obvious decrease in the male workers in the high exposure group compared with those in the low exposure group (FVC -60 ml, FEV₁ -120 ml, MMEF -260 ml/s, MVV -5.06 L, all p<0.05). In the high exposure group, the reduction in FVC% predicted, MMEF and MMEF% predicted was 1.0%, 210 mL/s, and 4.9%, respectively. In particular, among the exposed subjects smokers had a statistically significant decrease in lung function compared with non-smokers and the reduction in FVC% predicted, MMEF and MMEF% predicted was 1.0%, 210 mL/s, and 4.9%, respectively (p<0.05). Partial correlation analysis showed that there was also negative correlation between Mn-CEI and decreased changes in MMEF (r = -0.159, p = 0.018) and also MMEF% predicted (r = -0.163, p = 0.015).ConclusionsMn dust can impair the pulmonary ventilation function of male workers but not females, and individual smoking habits and manganese exposure had a synergistic effect on the lung function decrease.     

Serum heat shock protein 47 levels in patients with drug-induced lung disease

Background

Heat shock protein (HSP) 47 is a collagen-specific molecular chaperone that is required for molecular maturation of various types of collagens. We recently reported that HSP47 serum levels were markedly higher in patients with acute exacerbations of idiopathic pulmonary fibrosis (IPF) when compared with patients with stable IPF, suggesting that serum HSP47 levels correlate with interstitial pneumonia activity. The aim of this study was to evaluate serum HSP47 levels in patients with drug-induced lung disease (DILD).

Methods

Findings from high-resolution computed tomographic chest scans of 47 patients with DILD were classified into one of four predominant patterns: organizing pneumonia (OP) (n = 4), nonspecific interstitial pneumonia (NSIP) (n = 24), hypersensitivity pneumonitis (HP) (n = 11), and diffuse alveolar damage (DAD) (n = 8). Serum levels of HSP47, Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-A, and SP-D were measured in these patients.

Results

The PaO₂/fraction of inspired oxygen (FiO₂) (P/F) ratios were significantly lower and the alveolar-arterial difference of oxygen (A-a DO₂) was significantly higher in the DAD group than in the other groups. Patients with DAD had the worst outcomes among the different subgroups. Patients in the DAD group had significantly higher serum HSP47 levels than those in other groups. Receiver operating characteristic curves revealed that HSP47 was superior to KL-6, SP-A, and SP-D for discriminating between the DAD group and the other groups. The cut-off level for HSP47 that resulted in the highest diagnostic accuracy was 1711.5 pg/mL. The sensitivity, specificity, and diagnostic accuracy were 87.5%, 97.4%, and 95.7%, respectively. Serum levels of HSP47 in the group of patients requiring glucocorticoids were significantly higher than those in patients who experienced clinical improvement without glucocorticoid administration. Serum HSP47 levels also significantly correlated with various respiratory parameters.

Conclusion

This study demonstrated that serum HSP47 levels were elevated in patients with DILD with a DAD pattern who had the worst outcomes among the different subgroups, and that this was correlated with P/F ratio and A-a DO₂.     

Effects of SO(2) on Stomatal Metabolism in Pisum sativum L

Pea (Pisum sativum L. cv `Little Marvel') plants were exposed to SO₂ for short term (3 hours) and long term (2 days) at 0.2 and at 0.5 microliter per liter (ppm) levels. The effect of this treatment on the activity of phosphoenolpyruvate carboxylase, NAD- and NADP-malate dehydrogenases, and alanine aminotransferase from epidermis and whole leaves was investigated. Short-term exposure to SO₂ at 0.2 or 0.5 ppm decreased the activity of the carboxylase and the dehydrogenases in the epidermis. In contrast, the activity of the same three enzymes increased in whole leaves with either short- or long-term exposure to SO₂. Alanine aminotransferase in epidermis or whole leaves was not much affected by short-term exposure, but the epidermal activity was decreased and whole leaf activity was increased with long-term exposure. SO₂ exposure which was initiated prior to illumination decreased the free thiol content of both epidermis and of whole leaf. Net photosynthesis was reversibly inhibited by long-term exposure to SO₂ at 0.5 ppm. No effect of 0.5 ppm SO₂ on stomatal conductance was detectable after 3 hours. Stomatal conductance appeared to decrease after longer exposure times (2 days) at 0.5 ppm.