Molecular Mechanisms of RSV and Air Pollution Interaction: A Scoping Review.

RSV is one of the major infectious agents in paediatrics, and its relationship with air pollution is frequently observed. However, the molecular basis of this interaction is sparsely reported. We sought to systematically review the existing body of literature and identify the knowledge gaps to answer the question: which molecular mechanisms are implied in the air pollutants-RSV interaction? Online databases were searched for original studies published before August 2022 focusing on molecular mechanisms of the interaction. The studies were charted and a narrative synthesis was based upon three expected directions of influence: a facilitated viral entry, an altered viral replication, and an inappropriate host reaction. We identified 25 studies published between 1993 and 2020 (without a noticeable increase in the number of studies) that were performed in human (n = 12), animal (n = 10) or mixed (n = 3) models, and analysed mainly cigarette smoke (n = 11), particulate matter (n = 4), nanoparticles (n = 3), and carbon black (n = 2). The data on a damage to the epithelial barrier supports the hypothesis of facilitated viral entry; one study also reported accelerated viral entry upon an RSV conjugation to particulate matter. Air pollution may result in the predominance of necrosis over apoptosis, and, as an effect, an increased viral load was reported. Similarly, air pollution mitigates epithelium function with decreased IFN-γ and Clara cell secretory protein levels and decreased immune response. Immune response might also be diminished due to a decreased viral uptake by alveolar macrophages and a suppressed function of dendritic cells. On the other hand, an exuberant inflammatory response might be triggered by air pollution and provoke airway hyperresponsiveness (AHR), prolonged lung infiltration, and tissue remodeling, including a formation of emphysema. AHR is mediated mostly by increased IFN-γ and RANTES concentrations, while the risk of emphysema was related to the activation of the IL-17 → MCP-1 → MMP-9 → MMP-12 axis. There is a significant lack of evidence on the molecular basics of the RSV-air pollution interaction, which may present a serious problem with regards to future actions against air pollution effects. The major knowledge gaps concern air pollutants (mostly the influence of cigarette smoke was investigated), the mechanisms facilitating an acute infection or a worse disease course (since it might help plan short-term, especially non-pharmacological, interventions), and the mechanisms of an inadequate response to the infection (which may lead to a prolonged course of an acute infection and long-term sequelae). Thus far, the evidence is insufficient regarding the broadness and complexity of the interaction, and future studies should focus on common mechanisms stimulated by various air pollutants and a comparison of influence of the different contaminants at various concentrations.

Association of inflammation and lung function decline caused by personal PM2.5 exposure: a machine learning approach in time-series data.

Numerous studies focused on the association between lung function impairment and inflammation caused by fine particulate matter (PM2.5), but the causal relationships are difficult to clarify. In the current study, twenty healthy Chinese young adults who participated in 7 days of observation every four seasons were enrolled, and autoregression models (AM) and classification and regression trees (CART) in a machine learning framework were applied to analyze the association among PM2.5 exposure, inflammation, and lung function from a data structure perspective. There were strong cross-correlations between personal dose of PM2.5 (Dw) and lung functions (vital capacity (VC), forced vital capacity (FVC), etc.). These cross-correlation coefficients were associated with inflammatory indicators (uteroglobin (UG), serum amyloid (SAA), and fractional exhaled nitric oxide (FeNO)). CART reported that inflammatory indicators UG and SAA had the predictive ability of the directional association between Dw and FVC at 1-day lag and that high levels of UG and SAA predicted that PM2.5 exposure induced lung function decline. Consistently, lower lung function indicators at a 2-day lag after personal PM2.5 exposure predicted the high value of inflammatory indicator FeNO. Taken together, we applied machine learning algorithms to analyze repeated measurement data, finding that inflammation and lung function decline caused by PM2.5 could affect each other.

Traffic-related air pollution, biomarkers of metabolic dysfunction, oxidative stress, and CC16 in children.

BACKGROUND: Previous research has revealed links between air pollution exposure and metabolic syndrome in adults; however, these associations are less explored in children. OBJECTIVE: This study aims to investigate the association between traffic-related air pollutants (TRAP) and biomarkers of metabolic dysregulation, oxidative stress, and lung epithelial damage in children. METHODS: We conducted cross-sectional analyses in a sample of predominantly Latinx, low-income children (n = 218) to examine associations between air pollutants (nitrogen dioxide (NO2), nitrogen oxides (NOx), elemental carbon, polycyclic aromatic hydrocarbons, carbon monoxide (CO), fine particulates (PM2.5)) and biomarkers of metabolic function (high-density lipoprotein (HDL), hemoglobin A1c (HbA1c), oxidative stress (8-isoprostane), and lung epithelial damage (club cell protein 16 (CC16)). RESULTS: HDL cholesterol showed an inverse association with NO2 and NOx, with the strongest relationship between HDL and 3-month exposure to NO2 (-15.4 mg/dL per IQR increase in 3-month NO2, 95% CI = -27.4, -3.4). 8-isoprostane showed a consistent pattern of increasing values with 1-day and 1-week exposure across all pollutants. Non-significant increases in % HbA1c were found during 1-month time frames and decreasing CC16 in 3-month exposure time frames. CONCLUSION: Our results suggest that TRAP is significantly associated with decreased HDL cholesterol in longer-term time frames and elevated 8-isoprostane in shorter-term time frames. TRAP could have the potential to influence lifelong metabolic patterns, through metabolic effects in childhood.

Measurement of Tryptase and CC16/Albumin in Nasal Lavage Fluid as a Screening Tool of Allergic Rhinitis.

BACKGROUND: There is no trial to make a diagnostic tool of allergic rhinitis (AR) utilizing biomarkers from nasal fluid. Base on previous studies, we selected following five biomarkers in nasal fluids that represent the characteristics of allergic reactions: tryptase, eosinophil cationic protein (ECP), interleukin 5 (IL-5), Clara cell protein 16 (CC16) and CC16-to-albumin ratio. OBJECTIVE: This study aimed to identify biomarkers in nasal discharge that may be used in biosensors to diagnose AR as an additional diagnostic tool. METHODS: Patients showed rhinorrhea and tested positive on allergic skin and specific immunoglobulin E (IgE) tests were included in the AR group. The non-AR group included individuals no dominant nasal symptoms and tested negative on allergy tests. Nasal lavage fluid samples were collected from all participants. Biomarkers in the samples were quantified using enzyme-linked immunosorbent assay. RESULTS: Forty-five patients with AR and 28 non-AR subjects were enrolled in this study. Comparing the concentrations of biomarkers, the concentrations of tryptase and IL-5 were significantly higher in the AR group than in the NAR group. And CC16 level and CC16-to-albumin ratio were significantly lower in the AR group. In the combination of tryptase or CC16-to-albumin ratio, the sensitivity was 90.7% and the specificity was 64.3% (p = 0.013). CONCLUSION: The combination of "tryptase or CC16-to-albumin" could be used as a screening tool for AR. Although this diagnostic method could not replace conventional diagnostic tools, we could consider the method we proposed as an additional screening tool for patients who could not undergo allergy tests.

Clara cell protein 16 release from the nasal mucosa in allergic rhinitis, chronic rhinosinusitis, and exposure to air pollutants.

Clara cell protein 16 (CC16) is a small protein mainly produced by non-ciliated Clara cells in the respiratory epithelium. It has an anti-inflammatory role in chronic upper and lower airway eosinophilic inflammations. Decreased levels of CC16 are found in the nasal secretions and plasma of patients with chronic eosinophilic inflammatory disorders, such as asthma, allergic rhinitis, and chronic rhinosinusitis with or without nasal polyps, as well as in people exposed to high levels of air pollutants. Intranasal corticosteroid administration suppresses chronic inflammation of the nasal mucosa driven by eosinophils and stimulates local CC16 production. CC16 can be a reliable biomarker of the beneficial effects of perennial allergic rhinitis and chronic rhinosinusitis therapy and of the functional recovery of the nasal mucosa after treatment with topical glucocorticoids.

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.

Biomarkers for patients with trauma associated acute respiratory distress syndrome.

Trauma is a major factor that contributes to the risk for acute respiratory distress syndrome (ARDS). Biomarkers that predict the risk, diagnosis, treatment response and prognosis of ARDS after trauma have been widely investigated. In addition to their applications in clinical diagnosis and treatment, these biomarkers provide important insights into our understanding of the pathogenesis of ARDS. This review begins with a brief introduction regarding the incidence and pathogenesis of trauma-associated ARDS. Then, we focus on reviewing the clinical trials that have been designed to investigate the value of biomarkers in ARDS after trauma. Biomarkers with a confirmed value in ARDS have been organized on the basis of key pathogenic processes that are central to ARDS and are described in detail. Among these, angiopoietin 2 (Ang-2), L-selectin, Clara cell protein 16 (CC16), soluable receptor for advanced glycation end products (sRAGE), Surfactant protein D (SP-D), histones, mtDNAs and some biomarker panels had a certain association with the diagnosis and prognosis of trauma-related ARDS. Further investigations are needed regarding the design of trials, the best sampling approaches and the optimal combinations of the biomarker panels.

Clara Cell Protein Expression in Mechanically Ventilated Term and Preterm Infants with Respiratory Distress Syndrome and at Risk of Bronchopulmonary Dysplasia: A Pilot Study.

The aim of this pilot study was to determine Clara cell protein (CC16) concentration in bronchoalveolar lavages (BAL) fluid from full-term and preterm (<37 weeks' gestational age) neonates requiring respiratory support, having symptoms of neonatal respiratory distress syndrome, and at risk of bronchopulmonary dysplasia (BPD). We hypothesized that CC16 may be predictive of BPD diagnosis regardless of gestational age. BAL fluid CC16 was measured by ELISA at birth and at day 7 of life. Both groups that developed BPD showed significantly decreased BAL fluid CC16 levels compared to those infants that did not develop the disease. CC16 positively correlated with diagnosis of BPD and negatively with the severity of the disease. These results suggest that BAL fluid CC16 levels may have a diagnostic value at day 7 for BPD in both term and preterm infants. This study demonstrates the potential utility of BAL fluid CC16 levels as a biomarker for BPD in term infants.

Evaluation of Club Cell 10-kDa Protein (CC10) Levels in Full-Term Infants.

BACKGROUND: The club cell 10-kDa protein (CC10) is a homeostatic protein that is produced in the lung, diffuses into the blood, and is then excreted into the urine and stool. CC10 is known to have anti-inflammatory properties and to have lower endogenous production in preterm infants. OBJECTIVES: As recombinant human CC10 (rhCC10) is being studied in preterm infants to reduce lung injury, understanding CC10 levels in term infants with normal lungs is needed to establish appropriate target dosing ranges. METHODS: Serum, urine, and stool samples were collected from 24 healthy full-term infants, and CC10 levels were measured. Levels in term infants were then compared to those in preterm infants who were examined in our previous studies. RESULTS: The mean gestational age and birth weight of the term infants were 38.8 ±1.1 weeks and 3,257 ± 513 g, respectively. The mean gestational age of the preterm infants was 26.8 ± 1.4 weeks. The median serum [CC10] levels with minimum and maximum values in term infants (214.2 ng/mL [34.1, 428.1]) were >7-fold higher than in preterm infants (27.5 ng/mL [8.0, 760.0]; p < 0.05). A significant correlation was found between [CC10] in urine and stool as well as between gestational age and stool [CC10] (p < 0.05). CONCLUSIONS: CC10 is detectable in serum, urine, and stool in healthy term infants, with levels significantly higher than in preterm infants. This provides important data for ongoing therapeutic intervention trials with rhCC10 in high-risk preterm infants.

Effects of Intrauterine Devices in Mares: A Histomorphological and Immunohistochemical Evaluation of the Endometrium.

Oestrous suppression by intrauterine devices (IUDs) is caused by prolongation of luteal function, but the biological mechanism is unknown. The aim of the study was to investigate mechanisms which could explain the action of IUDs. Thirty mares were age-matched and either inseminated (AI, n = 15) or fitted with an IUD (IUD, n = 15) and subsequently divided into four groups: AI-P, pregnant (n = 8); AI-N, non-pregnant (n = 7); IUD-P, prolonged luteal phase (n = 7); and IUD-N, normal luteal phase (n = 8). The median ages were 5.5 and 7 years in AI-P and IUD-P groups and 14 and 11 years in AI-N and IUD-N groups, respectively. On Day 15 after ovulation, an endometrial biopsy was obtained to study histomorphological and immunohistochemical expression patterns of uterine proteins (uteroferrin, UF; uterocalin, UC; uteroglobin, UG), oestrogen and progesterone receptors (ER, PR), proliferation marker Ki-67 and content of inflammatory cells. Expression of UF was higher in IUD mares; the difference between pregnant and IUD-P mares was significant. Mares exhibiting a prolonged luteal phase (AI-P, IUD-P) showed only mild angiosclerosis and lower expression of both ER and PR than mares with a normal luteal phase (AI-N, IUD-N). No significant differences were detected in the numbers of inflammatory cells, with the exception of macrophages, which were more numerous in AI-P than AI-N mares. Although inflammatory cells were not detected in IUD mares, increased UF levels may indicate chronic inflammation. Young age and normality of the endometrial blood vessels may improve the efficacy of IUDs.

Examining the Effects of External or Internal Radiation Exposure of Juvenile Mice on Late Morbidity after Infection with Influenza A.

A number of investigators have suggested that exposure to low-dose radiation may pose a potentially serious health risk. However, the majority of these studies have focused on the short-term rather than long-term effects of exposure to fixed source radiation, and few have examined the effects of internal contamination. Additionally, very few studies have focused on exposure in juveniles, when organs are still developing and could be more sensitive to the toxic effects of radiation. To specifically address whether early-life radiation injury may affect long-term immune competence, we studied 14-day-old juvenile pups that were either 5 Gy total-body irradiated or injected internally with 50 µCi soluble (137)Cs, then infected with influenza A virus at 26 weeks after exposure. After influenza infection, all groups demonstrated immediate weight loss. We found that externally irradiated, infected animals failed to recover weight relative to age-matched infected controls, but internally (137)Cs contaminated and infected animals had a weight recovery with a similar rate and degree as controls. Externally and internally irradiated mice demonstrated reduced levels of club cell secretory protein (CCSP) message in their lungs after influenza infection. The externally irradiated group did not recover CCSP expression even at the two-week time point after infection. Although the antibody response and viral titers did not appear to be affected by either radiation modality, there was a slight increase in monocyte chemoattractant protein (MCP)-1 expression in the lungs of externally irradiated animals 14 days after influenza infection, with increased cellular infiltration present. Notably, an increase in the number of regulatory T cells was seen in the mediastinal lymph nodes of irradiated mice relative to uninfected mice. These data confirm the hypothesis that early-life irradiation may have long-term consequences on the immune system, leading to an altered antiviral response.

Distribution and morphology of Clara cells in common marmosets (Callithrix jacchus).

BACKGROUND: The objective of this investigation was to define the phenotype and spatial distribution of Clara cells within the respiratory tract of common marmosets and to distinguish them from other non-ciliated cells (goblet cells, mixed type secretory cells). METHODS: Non-ciliated cells were identified immunohistochemically using antibodies against Clara cell secretory protein and mucin 5AC. Transmission electron microscopy and scanning electron microscopy were performed to characterize Clara cells ultrastructurally. RESULTS: Clara cells were present throughout the tracheobronchial tree, with lowest numbers in the trachea and highest numbers in bronchioles. Goblet cells and mixed type cells were scarce in the upper conducting airways and virtually absent within bronchioles. Ultrastructurally, Clara cells showed typical apical electron-dense granules and a prominent granular endoplasmatic reticulum. CONCLUSIONS: Clara cells of common marmosets have species-specific morphological characteristics, which suggest grouping the common marmoset phenotypically between primates and rodents.

Clara cell 10-kD protein in inflammatory upper airway diseases.

PURPOSE OF REVIEW: To discuss the role of Clara cell 10-kD protein (CC10), an anti-inflammatory and immunomodulatory molecule, in inflammatory upper airway diseases, particularly in allergic rhinitis and chronic rhinosinusitis (CRS). RECENT FINDINGS: CC10 expression is downregulated in allergic rhinitis and CRS. CC10 can inhibit the expression of chitinase 3-like 1 protein and osteopontin in eosinophilic CRS and allergic rhinitis, respectively. CC10 can also suppress osteopontin-induced expression of Th2 and proinflammatory cytokines in airway epithelial cells, and CC10 gene transfection can inhibit NF-κB activity in airway epithelial cells. Proinflammatory and Th2 cytokines can diminish CC10 production, whereas Th1 cytokines and interleukin-10 can promote CC10 production in sinonasal mucosa. Allergen exposure leads to a transdifferentiation of CC10 secreting cells into trefoil factor family 1 secreting cells and/or goblet cells in upper airways, resulting in the diminished expression of CC10. SUMMARY: Allergen exposure and Th2 milieu can suppress the expression of CC10 in upper airways. CC10 can inhibit Th2-dominated eosinophilic inflammation in upper airways via multiple pathways.

Serum and nasal lavage fluid Clara cell protein decreases in children with allergic rhinitis.

BACKGROUND: Allergic rhinitis is among the most common chronic disorders of childhood with prevalence of up to 40% in children. Clara cell secretory protein (CCSP) is secreted by Clara cells in the lining fluid of airways. It has an immune-modulatory and anti-inflammatory activity. AIM OF WORK: Study aimed at evaluating CCSP as a biomarker in serum and nasal lavage fluid of children with allergic rhinitis. METHODS: A case-control study was conducted on sera and nasal lavage fluid samples from 15 children with allergic rhinitis and 15 healthy children as a control group. RESULTS: Children with allergic rhinitis had a male to female ratio 2 to 1, with a mean age of 9.47±2.75 years, while among the healthy group, six were males and nine were females, with a mean age of 8.63±2.28 years. Rhinorrhea and nasal obstruction were the most frequent symptoms (100%) followed by itching (93.3%) then sneezing (73.3%). Among allergic rhinitis patients serum CCSP mean±SD was 2.03±0.59µg/l; it was reliable to predict allergic rhinitis (P<0.0001); while nasal lavage CCSP mean±SD was 12.73±8.25µg/l and it was not reliable to predict allergic rhinitis. Its best cut-off value was 3.75µg/l with a sensitivity of 100%, specificity 80%, with a diagnostic accuracy of 90%. CONCLUSION: Clara cell secretory protein is a new peripheral sensitive marker of airway injury. Furthermore, serum CCSP level is a predictor of allergic rhinitis but not nasal lavage fluid CCSP.

Biomarkers in obstructive respiratory diseases: an update.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, with the involvement of many inflammatory cells and mediators. Traditionally, this inflammation is thought to spread to a systemic level, thus inducing damage of different organs. However, other pathogenetic mechanisms could take part to the above-described process, and some open questions need to be solved. Due to the burden and increasing prevalence of COPD, the opportunity to find biomarkers that can potentially be useful in identifying individuals with the disease, or better, prior to symptoms onset, to diagnose and properly manage the respiratory symptoms, as well as to evaluate the response to treatment and to select specific subtypes of patients for tailored treatments is strongly advocated. Several mediators, enzymes, hormones and cells have been claimed to adhere to this objective. Moreover, the presence of comorbid or concomitant diseases can variably influence the concentration of specific biomarkers in samples of individuals with COPD, and age-related functional and structural changes (inflammaging) can further confuse the biological pattern. Several observations have been performed in the last decades; nevertheless, no biomarker is currently considered as satisfying all the above-mentioned issues. The "Evaluation of COPD longitudinally to identify predictive surrogates and points (ECLIPSE)" study has specifically explored the possibility to identify novel biomarkers that correlate with clinically relevant COPD subtypes and with markers of disease progression. Among the thirty-four biomarkers considered, 15 resulted to be increased in COPD patients rather than in smoker and non-smoker controls. Specific lung proteins such as CC-16 and SPD are promising in detecting lung damage, exacerbation susceptibility or responsiveness to treatment. The ECLIPSE findings confirm that, to date, the use of a single biomarker is not sufficient, but the combination of novel biomarkers with the already existing tools could improve our skills in optimizing treatment of COPD patients.

Respiratory effects associated with wood fuel use: a cross-sectional biomarker study among adolescents.

The use of wood as heating and cooking fuel can result in elevated levels of indoor air pollution, but to what extent this is related to respiratory diseases and allergies is still inconclusive. Here, we report a cross-sectional study among 744 school adolescents (median age 15 years) using as main outcomes respiratory symptoms and diseases, exhaled nitric oxide, total and aeroallergen-specific IgE in serum, and two epithelial biomarkers in nasal lavage fluid (NALF) or serum, that is, Clara cell protein (CC16) and surfactant-associated protein D (SPD). Information about the wood fuel use and potential confounders was collected via a personal interview of the adolescent and a questionnaire filled out by the parents. Two approaches were used to limit the possible influence of confounders, that is, multivariate analysis using the complete study population or pairwise analysis of matched sub-populations obtained using an automated procedure. Wood fuel use was associated with a decrease of CC16 and an increase of SPD in serum, which resulted in a decreased serum CC16/SPD ratio (median -9%, P = 0.001). No consistent differences were observed for the biomarkers measured in exhaled breath or NALF. Wood fuel use was also associated with increased odds for asthma [odds ratio (OR) 2.2, 95% CI: 1.1-4.4, P = 0.02], hay fever (OR = 2.4, 95% CI: 1.4-4.3, P = 0.002), and sensitization against pollen allergens (OR = 2.1, 95% CI: 1.3-3.4, P = 0.002). The risks of respiratory tract infections, self-reported symptoms, and sensitization against house-dust mite were not increased by wood fuel use. The increased risks of asthma, hay fever and aeroallergen sensitization, and the changes of lung-specific biomarkers consistently pointed towards respiratory effects associated with the use of wood fuel.

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.

Biological markers and diagnosis of ventilator-associated pneumonia.

Evaluation of a new biomarker from bronchoalveolar fluid, the Clara cell protein 10, adds data to the search for a diagnostic marker for ventilator-associated pneumonia (VAP). For more than 15 years, investigators tried to identify such a marker for predicting or diagnosing VAP. Unfortunately, the results of a number of these studies are disappointing. For optimal management of critically ill, ventilated patients with clinical suspicion of VAP, clinicians need accurate microbiological information to decide to treat in case of confirmed infection and to guide the initial choice of antibiotic therapy with identification of the responsible pathogen(s). Thus, today, the potential advantages of biomarkers are to improve the rapidity and performance of current diagnostic procedures and to reduce antibiotic exposure and selective pressure.

Clara cell protein in bronchoalveolar lavage fluid: a predictor of ventilator-associated pneumonia?

INTRODUCTION: Clara cell protein 10 (CC-10) has been associated with inflammatory and infectious pulmonary diseases. This study evaluates CC-10 concentrations in bronchoalveolar lavage (BAL) fluid as a potential marker of ventilator-associated pneumonia (VAP). METHODS: Between January 2003 and December 2007, BAL fluid samples obtained from critically ill patients at the intensive care unit of the Maastricht University Medical Centre clinically suspected of having VAP were included. Patients were divided into two groups: (1) microbiologically confirmed VAP (the VAP group) and (2) microbiologically unconfirmed VAP (the non-VAP group). The concentration of CC-10 was measured by means of a commercially available enzyme-linked immunosorbent assay kit, and retrospective analysis was performed. Areas under the curve of receiver operating characteristic curves were calculated for CC-10 concentrations. RESULTS: A total of 196 patients (122 men, 74 women) were included. A total of 79 (40%) of 196 cases of suspected VAP were microbiologically confirmed. The median CC-10 concentration in the VAP group was 3,019 ng/mL (range, 282 to 65,546 ng/mL) versus 2,504 ng/mL (range, 62 to 30,240 ng/mL) in the non-VAP group (P = 0.03). There was no significant difference in CC-10 concentrations between patients treated with or without corticosteroids (P = 0.26) or antibiotic therapy (P = 0.9). The CC-10 concentration did not differ significantly between patients with Gram-positive versus Gram-negative bacteria that caused the VAP (P = 0.06). However, CC-10 concentrations did differ significantly between the late-onset VAP group and the non-VAP group. CONCLUSIONS: The CC-10 concentration in BAL fluid yielded low diagnostic accuracy in confirming the presence of VAP.

Immunohistochemical expression and correlation of mammaglobin with the grading system of breast carcinoma.

OBJECTIVES: In this study it was intended to study mammaglobin expression as a marker for the detection of breast cancer and correlate it with the Bloom-Richardson grading system of breast carcinoma. MATERIALS AND METHODS: The study was conducted from May 2007 to May 2008. Tissue samples were collected from 50 patients of breast cancer in the various stages of their disease and correlated histologically with the Bloom-Richardson grading system for breast carcinoma. The clinical data of the patients were obtained from their respective files. RESULTS: Positive immunostaining for mammaglobin was seen in 84% of breast carcinoma cases. This immunoreactivity did not correlate with histological and nuclear grades of the tumors, yet it varied according to the histological type of the tumor with ductal carcinoma showing stronger and diffuse staining than other varieties. CONCLUSION: These results elicit that mammaglobin is overexpressed in carcinoma breast as compared to the normal breast epithelium. This mammaglobin expression can act as a useful tool in the diagnosis of women with breast cancer.