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.     

Club cell protein (CC16) in plasma,bronchial brushes,BAL and urine following an inhaled allergen challenge in allergic asthmatics

Background: Club cell protein (CC16) is a pneumoprotein secreted by epithelial club cells. CC16 possesses anti-inflammatory properties and is a potential biomarker for airway epithelial damage. We studied the effect of inhaled allergen on pulmonary and systemic CC16 levels.

Methods: Thirty-four subjects with allergic asthma underwent an inhaled allergen challenge. Bronchoscopy with bronchoalveolar lavage (BAL) and brushings was performed before and 24?h after the challenge. CC16 was quantified in BAL and CC16 positive cells and CC16 mRNA in bronchial brushings. CC16 was measured in plasma and urine before and repeatedly after the challenge. Thirty subjects performed a mannitol inhalation challenge prior to the allergen challenge.

Results: Compared to baseline, CC16 in plasma was significantly increased in all subjects 0–1?h after the allergen challenge, while CC16 in BAL was only increased in subjects without a late allergic response. Levels of CC16 in plasma and in the alveolar fraction of BAL correlated significantly after the challenge. There was no increase in urinary levels of CC16 post-challenge. Mannitol responsiveness was greater in subjects with lower baseline levels of CC16 in plasma.

Conclusions: The increase in plasma CC16 following inhaled allergen supports the notion of CC16 as a biomarker of epithelial dysfunction.     

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.     

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.     

Metallic elements in exhaled breath condensate and serum of patients with exacerbation of chronic obstructive pulmonary disease

Biomarkers in exacerbated chronic obstructive pulmonary disease may be useful in aiding diagnosis, defining specific phenotypes of disease, monitoring the disease and evaluating the effects of drugs. The aim of this study was the characterization of metallic elements in exhaled breath condensate and serum as novel biomarkers of exposure and susceptibility in exacerbated chronic obstructive pulmonary disease using reference analytical techniques. C-Reactive protein and procalcitonin were assessed as previously validated diagnostic and prognostic biomarkers which have been associated with disease exacerbation, thus useful as a basis of comparison with metal levels. Exhaled breath condensate and serum were obtained in 28 patients at the beginning of an episode of disease exacerbation and when they recovered. Trace elements and toxic metals were measured by inductively coupled plasma-mass spectrometry. Serum biomarkers were measured by immunoassay. Exhaled manganese and magnesium levels were influenced by exacerbation of chronic obstructive pulmonary disease, an increase in their concentrations--respectively by 20 and 50%--being observed at exacerbation in comparison with values obtained at recovery; serum elemental composition was not modified by exacerbation; serum levels of C-reactive protein and procalcitonin at exacerbation were higher than values at recovery. In outpatients who experienced a mild-moderate chronic obstructive pulmonary disease exacerbation, manganese and magnesium levels in exhaled breath condensate are elevated at admission in comparison with values at recovery, whereas no other changes were observed in metallic elements at both the pulmonary and systemic level.     

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.     

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.     

Molecular and cellular mechanisms in the viral exacerbation of asthma

The aetiology of asthma associated with viral infection is complex. The dynamics that contribute to disease pathogenesis are multifactorial and involve overlapping molecular and cellular mechanisms, particularly the immune response to respiratory virus infection or allergen sensitization. This review summarizes the evidence associated with factors that may contribute to the development or exacerbation of asthma including age, host factors, genetic polymorphisms, altered immune responses, and aspects of viral antigen expression. This review also provides an important perspective of key events linked to the development of asthmatic disease and related pulmonary inflammation from human and animal studies, and discusses their relationship as targets for disease intervention strategies.     

Circulating surfactant protein D as a potential lung-specific biomarker of health outcomes in COPD: a pilot study

Background

There is a paucity of surrogate lung-specific biological markers that can be used to track disease progression and predict clinical outcomes in chronic obstructive pulmonary disease (COPD). The principal aim of this pilot study was to determine whether circulating surfactant protein D (SPD) or Clara Cell protein-16 (CC16) levels are associated with lung function or health status in patients with severe COPD.

Methods

We studied 23 patients with advanced COPD. Lung function measurements, Chronic Respiratory Disease Questionnaire (CRQ) scores, and serum levels of SPD, CC16, and C-reactive protein (CRP) were determined at baseline and at 3 months.

Results

At baseline, FEV₁ was inversely associated with serum SPD levels (P = 0.045) but not with CC16 (P = 0.675) or CRP levels (P = 0.549). Over a 3 month period, changes in SPD levels correlated significantly with changes in CRQ scores (adjusted P = 0.008) such that patients who had the largest declines in serum SPD levels experienced the largest gains in health status. The association was particularly notable between circulating SPD level and the dyspnea domain of the CRQ score (P = 0.018). Changes in CC16 or CRP levels did not correlate with changes in CRQ scores.

Conclusion

Changes in serum SPD levels tracked well with changes in health status over a 3 month period in patients with severe COPD. These data suggest that circulating SPD levels may be useful biomarkers to track health outcomes of COPD patients.     

Hyaluronan and Its Heavy Chain Modification in Asthma Severity and Experimental Asthma Exacerbation

Hyaluronan (HA) is a large (>1500 kDa) polysaccharide of the extracellular matrix that has been linked to severity and inflammation in asthma. During inflammation, HA becomes covalently modified with heavy chains (HC-HA) from inter-α-inhibitor (IαI), which functions to increase its avidity for leukocytes. Our murine model of allergic pulmonary inflammation suggested that HC-HA may contribute to inflammation, adversely effecting lower airway remodeling and asthma severity. Our objective was to characterize the levels of HA and HC-HA in asthmatic subjects and to correlate these levels with asthma severity. We determined the levels and distribution of HA and HC-HA (i) from asthmatic and control lung tissue, (ii) in bronchoalveolar lavage fluid obtained from non-severe and severe asthmatics and controls, and (iii) in serum and urine from atopic asthmatics after an experimental asthma exacerbation. HC-HA distribution was observed (i) in the thickened basement membrane of asthmatic lower airways, (ii) around smooth muscle cells of the asthmatic submucosa, and (iii) around reserve cells of the asthmatic epithelium. Patients with severe asthma had increased HA levels in bronchoalveolar lavage fluid that correlated with pulmonary function and nitric oxide levels, whereas HC-HA was only observed in a patient with non-severe asthma. After an experimental asthma exacerbation, serum HA was increased within 4 h after challenge and remained elevated through 5 days after challenge. Urine HA and HC-HA were not significantly different. These data implicate HA and HC-HA in the pathogenesis of asthma severity that may occur in part due to repetitive asthma exacerbations over the course of the disease.     

Serum surfactant protein D is increased in acute and chronic inflammation in mice

Surfactant protein A (SP-A) and surfactant protein D (SP-D) are important components of innate immunity that can modify the inflammatory response. However, alterations and regulation of SP-A and SP-D in acute and chronic inflammation are not well defined. In addition, serum SP-D may serve as a biomarker of lung inflammation. We determined the expression of SP-A and SP-D in murine models. To study acute inflammation, we instilled bleomycin intrabronchially. To study chronic lung inflammation, we used a transgenic mouse that overexpresses tumor necrosis factor (TNF)-alpha under the control of the SP-C promoter. These mice have a chronic mononuclear cell infiltration, airspace enlargement, pulmonary hypertension, and focal pulmonary fibrosis. In acute inflammation model, levels of mRNA for all surfactant proteins were reduced after bleomycin administration. However, serum SP-D was increased from days 7 to 28 after instillation. In chronic inflammation model, SP-D mRNA expression was increased, whereas the expression of SP-A, SP-B and SP-C was reduced. Both serum and lung SP-D concentrations were increased in chronic lung inflammation. These data clarified profile of SP-A and SP-D in acute and chronic inflammation and indicated that serum SP-D can serve as a biomarker of lung inflammation in both acute and chronic lung injury in mice.     

Lung epithelium injury biomarkers in workers exposed to sulphur dioxide in a non-ferrous smelter

Serum Clara cell protein (CC16) and surfactant-associated protein D (SP-D) were measured in 161 workers exposed to sulphur dioxide (SO₂) in a non-ferrous smelter. Seventy workers from a blanket manufacture served as referents. Exposure to SO₂ and tobacco smoking were associated with a decrease of CC16 and an increase of SP-D in serum. Tobacco smoking and exposure SO₂ interacted synergistically to decrease serum CC16 but not to increase serum SP-D. While further illustrating the potential of serum CC16 and SP-D, our study confirms that SO₂ can cause airways damage at exposure levels below current occupational exposure limits.     

Potential risk of asthma associated with in utero exposure to xenobiotics

The incidence of asthma, a complex disease and significant public health problem, has been increasing over the last 30 years for unknown reasons. Changes in environmental exposures or lifestyle may be involved. In some cases asthma may originate in utero or in early life. Associations have been found between in utero exposures to several xenobiotics and increased risk of asthma. There is convincing evidence that maternal smoking and/or in utero and perinatal exposure to environmental tobacco smoke are associated with increased risk of asthma. Similar effects have been demonstrated in animal models of allergic asthma. Evidence also suggests that in utero and/or early‐life exposures to various ambient air pollutants may increase the risk of asthma although supporting animal data are very limited. A few studies have suggested that in utero exposure to acetaminophen is associated with increased risk of asthma; however, animal data are lacking. Various vitamin deficiencies and supplements during pregnancy have been studied. In general, it appears that vitamins A, C, and E have protective effects and vitamins D and B may, in some instances, increase the risk, but the data are not conclusive. Some studies related to in utero exposures to polychlorinated biphenyls and bisphenol A and asthma risk are also reported. The underlying mechanisms for an association between xenobiotic exposures and asthma remain a matter of speculation. Genetic predisposition and epigenetic changes have been explored. The developing immune, respiratory, and nervous systems are potential targets. Oxidative stress and modulation of inflammation are thought to be involved. Birth Defects Research (Part C) 99:1–13, 2013. © 2013 Wiley Periodicals, Inc.     

Club Cell-16 and RelB as Novel Determinants of Arterial Stiffness in Exacerbating COPD Patients

Background

Exacerbations of chronic obstructive pulmonary disease (COPD) are acute events of worsened respiratory symptoms that may increase the risk of cardiovascular disease (CVD), a leading cause of mortality amongst COPD patients. The utility of lung-specific inflammatory mediators such as club cell protein-16 (CC-16) and surfactant protein D (SPD) and that of a novel marker of CV outcomes in COPD- RelB- in predicting adverse cardiovascular events during exacerbation is not known.

Methods

Thirty-eight subjects with COPD admitted to the hospital for severe exacerbation were included in this analysis. Clinical, physiological and arterial stiffness measurements were performed within 72 hours of admission; this was followed by measurements taken every 3 days until hospital discharge, then once a week until 30 days after discharge, and then again at 90 and 180 days. Plasma concentrations of inflammatory mediators were measured from peripheral venous blood taken at admission, and at days 15, 30, 90 and 180.

Results

CC-16 and RelB concentrations were increased at day 15 of exacerbations whereas SPD concentrations were decreased. The course of change in CC-16 and RelB levels over time was inversely associated with that of carotid-femoral pulse wave velocity, the gold-standard measure of arterial stiffness. Increases in CC-16 could predict a decreased number of subsequent exacerbations during follow-up.

Conclusions

Lung-specific (CC-16) and novel (RelB) biomarkers are associated with systemic cardiovascular changes over time. CC-16 can predict subsequent exacerbations in subjects with severe COPD and may be an important biomarker of pulmonary and systemic stress in COPD.     

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 (O(3)), annual concentrations of the main air pollutants (PM(10), NO(2), CO, SO(2) 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.     

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.     

Microbiota: A Missing Link in The Pathogenesis of Chronic Lung Inflammatory Diseases

Chronic respiratory diseases account for high morbidity and mortality, with asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) being the most prevalent globally. Even though the diseases increase in prevalence, the exact underlying mechanisms have still not been fully understood. Despite their differences in nature, pathophysiologies, and clinical phenotypes, a growing body of evidence indicates that the presence of lung microbiota can shape the pathogenic processes underlying chronic inflammation, typically observed in the course of the diseases. Therefore, the characterization of the lung microbiota may shed new light on the pathogenesis of these diseases. Specifically, in chronic respiratory tract diseases, the human microbiota may contribute to the disease’s development and severity. The present review explores the role of the microbiota in the area of chronic pulmonary diseases, especially COPD, asthma, and CF.     

重症慢性阻塞性肺病急性发作期患者血清PCT, hs-CRP及D-D的表达及意义

目的:探究重症慢性阻塞性肺病(COPD)急性发作期患者血清降钙素原(PCT)、超敏C反应蛋白(hs-CRP)和D-二聚体(D-D)的表达及意义。方法:选取2014年9月-2016年9月我院收治的146例COPD患者作为研究对象,其中73例COPD急性发作期(AECOPD)患者纳入急性期组,73例COPD缓解期患者纳入缓解期组,另选取同期来我院体检的40例健康者作为对照组。比较三组研究对象的血清PCT、hs-CRP和D-D水平,同时比较急性期组细菌感染与无细菌感染患者、不同肺功能分级的患者血清PCT、hs-CRP和D-D水平的差异。结果:急性期组与缓解期组患者的血清PCT、hs-CRP和D-D水平较对照组显著升高(P0.05),急性期组的血清PCT、hs-CRP和D-D水平较缓解期组显著升高,差异有统计学意义(P0.05)。合并细菌感染组血清PCT、hs-CRP水平均显著高于无细菌感染组(P0.05),而D-D水平则无统计学差异(P0.05)。不同肺功能分级患者间的血清PCT、hs-CRP和D-D水平比较差异显著(P0.05),且肺功能分级越高水平越高(P0.05)。结论:AECOPD患者的血清PCT、hs-CRP和D-D水平均显著的升高,三者联合检测能够有效反映患者病情严重程度,并有利于诊断患者是否存在有细菌感染。     

Influenza A virus infection inhibits the efficient recruitment of Th2 cells into the airways and the development of airway eosinophilia

Most infections with respiratory viruses induce Th1 responses characterized by the generation of Th1 and CD8(+) T cells secreting IFN-gamma, which in turn have been shown to inhibit the development of Th2 cells. Therefore, it could be expected that respiratory viral infections mediate protection against asthma. However, the opposite seems to be true, because viral infections are often associated with the exacerbation of asthma. For this reason, we investigated what effect an influenza A (flu) virus infection has on the development of asthma. We found that flu infection 1, 3, 6, or 9 wk before allergen airway challenge resulted in a strong suppression of allergen-induced airway eosinophilia. This effect was associated with strongly reduced numbers of Th2 cells in the airways and was not observed in IFN-gamma- or IL-12 p35-deficient mice. Mice infected with flu virus and immunized with OVA showed decreased IL-5 and increased IFN-gamma, eotaxin/CC chemokine ligand (CCL)11, RANTES/CCL5, and monocyte chemoattractant protein-1/CCL2 levels in the bronchoalveolar lavage fluid, and increased airway hyperreactivity compared with OVA-immunized mice. These results suggest that the flu virus infection reduced airway eosinophilia by inducing Th1 responses, which lead to the inefficient recruitment of Th2 cells into the airways. However, OVA-specific IgE and IgG1 serum levels, blood eosinophilia, and goblet cell metaplasia in the lung were not reduced by the flu infection. Flu virus infection also directly induced AHR and goblet cell metaplasia. Taken together, our results show that flu virus infections can induce, exacerbate, and suppress features of asthmatic disease in mice.