Performance of the Roche IL-6 chemiluminescent immunoassay in patients with COVID-like respiratory symptoms.

INTRODUCTION: We evaluated the Roche Elecsys IL6 assay on the Cobas immunoassay analyser. METHOD: Serum IL6 of 144 controls were compared to 52 samples from patients with COVID-like respiratory symptoms (17 SARS-CoV-2 RT-PCR positive); 25 of these were from the intensive care unit (ICU). We compared the IL6 levels to C-reactive protein (CRP) and procalcitonin (PCT) levels in all cases. RESULTS: The IL6 assay had coefficient-of-variation (CV) of 2.3 % (34.1 pg/mL) and 2.5 % (222.5 pg/mL), a limit of quantitation <1.6 pg/mL, and was linear from 1.6 to 4948 pg/mL. There was a significant difference in IL6 values between patients with COVID-like respiratory symptoms versus controls (p < 0.001). ROC analysis showed that IL6 > 6.4 pg/mL identified symptomatic cases (AUC 0.94, sensitivity 88.2 %, specificity 97.2 %). There was a significant difference between the IL6 of symptomatic ICU/non-ICU cases (median IL6 228 vs 11 pg/mL, p < 0.0001); ROC analysis showed IL6 > 75 pg/mL (sensitivity 76.0 %, specificity 88.9 %) was superior to CRP and PCT in predicting ICU admission (AUC: IL6 0.83, CRP 0.71, PCT 0.82). CONCLUSION: The performance of Elecsys IL6 assay is in keeping with the manufacturer's claims. IL6 > 6.4 pg/mL differentiates healthy from suspected COVID-19 cases and appears to be raised earlier than the other inflammatory markers in some cases. IL6 > 75 pg/mL was a good predictor of ICU admission.

Procalcitonin and Interleukin-10 May Assist in Early Prediction of Bacteraemia in Children With Cancer and Febrile Neutropenia.

Objectives: Febrile neutropenia (FN) causes treatment disruption and unplanned hospitalization in children with cancer. Serum biomarkers are infrequently used to stratify these patients into high or low risk for serious infection. This study investigated plasma abundance of cytokines in children with FN and their ability to predict bacteraemia. Methods: Thirty-three plasma cytokines, C-reactive protein (CRP) and procalcitonin (PCT) were measured using ELISA assays in samples taken at FN presentation (n = 79) and within 8-24 h (Day 2; n = 31). Optimal thresholds for prediction of bacteraemia were identified and the predictive ability of biomarkers in addition to routinely available clinical variables was assessed. Results: The median age of included FN episodes was 6.0 years and eight (10%) had a bacteraemia. On presentation, elevated PCT, IL-10 and Mip1-beta were significantly associated with bacteraemia, while CRP, IL-6 and IL-8 were not. The combination of PCT (≥0.425 ng/ml) and IL-10 (≥4.37 pg/ml) had a sensitivity of 100% (95% CI 68.8-100%) and specificity of 89% (95% CI 80.0-95.0%) for prediction of bacteraemia, correctly identifying all eight bacteraemia episodes and classifying 16 FN episodes as high-risk. There was limited additive benefit of incorporating clinical variables to this model. On Day 2, there was an 11-fold increase in PCT in episodes with a bacteraemia which was significantly higher than that observed in the non-bacteraemia episodes. Conclusion: Elevated PCT and IL-10 accurately identified all bacteraemia episodes in our FN cohort and may enhance the early risk stratification process in this population. Prospective validation and implementation is required to determine the impact on health service utilisation.

Effects of age and comorbidities on serum levels of inflammatory markers in community-acquired pneumonia.

INTRODUCTION: Studies have suggested that an inappropriate inflammatory response is a major cause of treatment failure and mortality in patients with community-acquired pneumonia (CAP). We aimed to determine the effect of age and comorbidities on serum inflammatory markers in CAP. METHODS: We performed a prospective cohort study of adults hospitalized with CAP. For the purposes of this study, we compared patients according to comorbidities and age. Inflammatory markers were measured at hospital admission, focusing on acute phase proteins, cytokines and monocyte human leucocyte antigen DR (mHLA-DR) expression. RESULTS: In patients with chronic pulmonary disease (COPD), serum cytokines had significantly decreased levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and mHLA-DR expression, as well as the C-reactive protein (CRP), compared with patients who had no comorbidities. Similarly, patients with chronic heart disease had a significantly reduced CRP levels and mHLA-DR expression, whereas patients with chronic kidney disease had significantly higher serum levels of procalcitonin and TNF-α. Lower procalcitonin, IL-6 and IL-10 levels, as well as mHLA-DR expression, were documented in older patients, but with no significant differences compared to younger patients. Multimorbidity in older patients was associated with significant lower levels of CRP and mHLA-DR expression. CONCLUSIONS: The circulating inflammatory markers to CAP have profiles that differ with age and underlying comorbidities. Multimorbidity in the elderly is also associated with lower serum levels of some inflammatory markers. Our findings suggest that inflammatory markers in CAP should be interpreted after considering age and comorbid conditions.

Development of magnetic particle-based chemiluminescence immunoassay for measurement of human procalcitonin in serum.

BACKGROUND: Serum procalcitonin (PCT) has been recognized as a primary biomarker in bacterial infections, and monitoring its concentration could help to evaluate the prognosis of sepsis and guide the antibiotic administration. We aimed to establish a fast and accurate immunoassay for PCT quantitation. METHODS: Our newly developed monoclonal antibodies (mAbs) against human PCT were preliminarily evaluated by enzyme-linked immunosorbent assay and then used to develop a chemiluminescence enzyme immunoassay (CLEIA). The proposed CLEIA was assessed in analytical performance and applied to measurement of serum PCT. RESULTS: mAb 2D3 and mAb 8F6 were selected as capture and detection antibody respectively, due to the highest sensitivity for PCT detection with no cross reaction to calcitonin gene-related peptides. The proposed CLEIA based on mAb pair of 2D3/8F6-AP was characterized for a working range from 0.03 to 100 µg/L. An excellent correlation was observed between our proposed assay and the VIDAS BRAHMS PCT assay (r: 0.9825). CONCLUSION: Our newly developed mAbs and CLEIA can serve as important diagnostic tools for measurement of human PCT in serum.

Neglected Variables in the Interpretation of Serum Procalcitonin Levels in Patients With Septic Shock.

The interpretation of serum procalcitonin (PCT) levels in septic patients is facilitated by reviewing the known stimuli that activate the PCT family of genes. Herein we describe 7 pathways that, alone or in combination, can increase serum PCT levels. As a marker of activation of innate immunity, high PCT levels affect clinical diagnosis, can be trended as a measure of "source" control, and can guide duration of antibacterial therapy in septic patients. Low PCT levels reflect little to no activation of an innate immune response, influence the differential diagnosis, and support the discontinuation of empiric antibiotic therapy. Understanding the pathways that result in elevated serum PCT levels is necessary for interpretation and subsequent clinical management.

Using IL-2R/lymphocytes for predicting the clinical progression of patients with COVID-19.

Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease.

Immediate psychological distress in quarantined patients with COVID-19 and its association with peripheral inflammation: A mixed-method study.

Since the end of 2019, Corona Virus Disease 2019 (COVID-19) has been the cause of a worldwide pandemic. The mental status of patients with COVID-19 who have been quarantined and the interactions between their psychological distress and physiological levels of inflammation have yet to be analyzed. Using a mixed-method triangulation design (QUAN + QUAL), this study investigated and compared the mental status and inflammatory markers of 103 patients who, while hospitalized with mild symptoms, tested positive with COVID-19 and 103 matched controls that were COVID-19 negative. The severity of depression, anxiety, and post-traumatic stress symptoms (PTSS) was measured via an on-line survey. Using a convenience sampling technique, qualitative data were collected until the point of data saturation. In addition, a semi-structured interview was conducted among five patients with COVID-19. Peripheral inflammatory markers were also collected in patients, both at baseline and within ± three days of completing the on-line survey. Results revealed that COVID-19 patients, when compared to non-COVID controls, manifested higher levels of depression (P < 0.001), anxiety (P < 0.001), and post-traumatic stress symptoms (P < 0.001). A gender effect was observed in the score of "Perceived Helplessness", the subscale of PSS-10, with female patients showing higher scores compared to male patients (Z = 2.56, P = 0.010), female (Z = 2.37, P = 0.018) and male controls (Z = 2.87, P = 0.004). Levels of CRP, a peripheral inflammatory indicator, correlated positively with the PHQ-9 total score (R = 0.37, P = 0.003, Spearman's correlation) of patients who presented symptoms of depression. Moreover, the change of CRP level from baseline inversely correlated with the PHQ-9 total score (R = -0.31, P = 0.002), indicative of improvement of depression symptoms. Qualitative analysis revealed similar results with respect to patient reports of negative feelings, including fear, guilt, and helplessness. Stigma and uncertainty of viral disease progression were two main concerns expressed by COVID-19 patients. Our results indicate that significant psychological distress was experienced by hospitalized COVID-19 patients and that levels of depressive features may be related to the inflammation markers in these patients. Thus, we recommend that necessary measures should be provided to address depression and other psychiatric symptoms for COVID-19 patients and attention should be paid to patient perceived stigma and coping strategies when delivering psychological interventions.

Inflammatory markers in saliva for diagnosis of sepsis of hospitalizes patients.

BACKGROUND: Inflammatory/immunological serum markers are useful for the early detection of organ dysfunction, helping the diagnosis of sepsis. Although the detection of blood biomarkers is a standard practice, the use of noninvasive samples (eg saliva) would be beneficial. AIM: To investigate the saliva of hospitalized patients with and without sepsis and identify the levels of inflammatory markers such as C-reactive protein (CRP), procalcitonin (PCT), interleukin 6 (IL-6) and nitric oxide (NO). METHODS: Saliva samples were collected from 26 patients in intensive care unit with diagnosis of sepsis and from 26 without sepsis (control). The levels of CRP were determined by using latex agglutination test, whereas those of procalcitonin and IL-6 by ELISA and NO by the Griess reaction. RESULTS: Of 26 patients with sepsis, 14 were males (54%) with a mean age of 63.81 ± 3.48 years. The control group had the same distribution for gender, with mean age 65.04 ± 4.07 years. Sepsis group showed higher salivary concentrations of CRP, PCT, IL-6 and NO, with only levels of IL-6 being statistically different (P = .0001). CONCLUSIONS: Patients with sepsis had significantly higher levels of IL-6 in their saliva, suggesting that this biological sample could be useful in the diagnosis of this condition.

Quench-Type Electrochemiluminescence Immunosensor Based on Resonance Energy Transfer from Carbon Nanotubes and Au-Nanoparticles-Enhanced g-C3N4 to CuO@Polydopamine for Procalcitonin Detection.

A new type of sandwich electrochemiluminescence (ECL) immunosensor dependent on ECL resonance energy transfer (ECL-RET) to achieve sensitive detection of procalcitonin (PCT) has been designed. In brief, carbon nanotubes (CNT) and Au-nanoparticles-functionalized graphitic carbon nitride (g-C3N4-CNT@Au) and CuO nanospheres covered with polydopamine (PDA) layer (CuO@PDA) were synthesized and applied as ECL donor and receptor, respectively. g-C3N4-CNT nanomaterials were in situ prepared on the basis of π-π conjugation, and the CNT content in the composite were optimized to achieve a strong and stable ECL signal. At the same time, Au nanoparticles were used to functionalize g-C3N4-CNT to further increase the ECL intensity and the loading amount of primary antibody (Ab1). Moreover, CuO@PDA was first used to successfully quench the ECL signal of g-C3N4-CNT@Au. Under the optimum experimental conditions, the linear detection range for PCT concentration was within 0.0001-10 ng mL-1 and the detection limit was 25.7 fg mL-1 (S/N = 3). Considering prominent specificity, reproducibility, and stability, the prepared immunosensor was used to assess recovery rate of PCT in human serum according to the standard addition method and the result was satisfactory. In addition, it is worth mentioning that a novel ECL-RET pair of g-C3N4-CNT@Au (donor)/CuO@PDA (acceptor) was first developed, which offered an effective analytical tool for sensitive detection of biomarkers in early disease diagnostics.

Determination of Melatonin Deprivation Impact on Sepsis With Acute Phase Reactants.

BACKGROUND: The aim of the present study is to determine the association of melatonin hormone level on CRP, Total Antioxidant Status, Leukocyte, Procalcitonin, and Malondialdehyde, all acute phase reactants in the dark and light cycle of rats with sepsis model. MATERIALS AND METHODS: In this study, 54 rats were divided into three groups. Whereas the first and third groups had a 12 h dark-light cycle, the second group was exposed to light for 24 h at 21°C-22°C for 10 d without any water and food restrictions. In the second and third groups, sepsis model was formed by cecal ligation and puncture (CLP) method at the end of 10th day, and blood samples were taken at the end of the 10th day. C-reactive protein, Malondialdehyde, Procalcitonin in the blood samples were analyzed by ELISA, and the levels of Total Antioxidant Status and leukocyte were determined by colorimetric method in the subsequent 12 and 24 h. RESULTS: CRP values increased in the second group rats, which were kept continuously under light and had undergone CLP, from 288.8 mg/L to 584.0 mg/L at the end of the 12 h and the end of the 24 h, approximately, two times. In rats, which were kept under 12 h of light, 12 h of darkness, and applied CLP (group 3), these values increased from 416.9 to 619.1; an increase of 1.5 times. When assessed for MDA, it was determined that the differences between Group 2 and Group 3 were more prominent between 0 h and 12 h. While the MDA values in group 2 increased from 16.53 nmol/mL at the 12 h to 17.66 nmol/mL at the 24 h. However, MDA values did not yield statistically significant changes in the third group. Changes in the in PCT values were similar to the MDA values obtained. Increase coefficient of the PCT values between 0 h and 12 h in the second group 2 was 1.26; however, in the third group, it was negligible. CONCLUSIONS: An increase in the oxidative stress was observed in the rats that underwent CLP and melatonin deprivation via continuous 24 h light exposure for 10 d. Accordingly, deprivation of light is considered to be effective in sepsis treatment due to the increase in melatonin levels in intensive care unit patients.

Quantitative detection of procalcitonin using an electrochemical immunosensor based on MoO3/Au@rGO nanocomposites.

In this work, a sandwich-type electrochemical immunosensor for the detection of procalcitonin (PCT) is constructed layer-by-layer with a novel label based on MoO3/Au@rGO nanocomposites. The high surface area and electroconductivity of graphene contributes to the transfer of electrons. Besides, the introduction of Au modulates the morphology of the MoO3@rGO nanocomposites from hexagonal prisms to agglomerated particles. Compared to rGO, Au@rGO and MoO3@rGO, the synergistic effect of MoO3/Au@rGO nanocomposites leads to the highest electrocatalytic activity towards H2O2 reduction. The electrochemical immunosensor exhibits a wide working range from 0.01 pg mL-1 to 10 ng mL-1 and a detection limit of 0.002 pg mL-1 at a signal-to-noise ratio of 3. Additionally, we also obtain excellent sensing performance for the immunosensor, including excellent selectivity, good reproducibility and stability. This work will give insight into the application of the nanocomposites based on noble metals combined with transition metal oxides in the fields of electroanalytical chemistry and biosensors.

Two-center comparison of 10 fully-automated commercial procalcitonin (PCT) immunoassays.

Background This two-center study was designed to verify comparability of procalcitonin (PCT) values among 10 different commercial immunoassays. Methods A total number of 176 routine lithium-heparin plasma samples were divided in identical aliquots and simultaneously analyzed with 10 different PCT immunoassays, including Kryptor BRAHMS PCT sensitive, Abbott Architect BRAHMS PCT, Beckman Coulter Access PCT (on Access and DXI), BioMérieux Vidas BRAHMS PCT, Diasorin Liaison BRAHMS PCT, Fujirebio Lumipulse G BRAHMS PCT, Roche BRAHMS PCT (on Cobas E801), Diazyme PCT (on Roche Cobas C702) and SNIBE Maglumi PCT. Results Highly significant correlation was always found across multiple comparisons, with correlation coefficients comprised between 0.918 and 0.997 (all p < 0.001). Bland and Altman plots analysis revealed highly variable bias among immunoassays, ranging between ±0.2% and ±38.6%. Diazyme PCT on Roche Cobas C702 and SNIBE Maglumi PCT displayed the larger overestimation, whilst PCT values were underestimated by Cobas BRAHAMS PCT. The agreement was always >80% (all p < 0.001), but varied largely across multiple comparisons, ranging between 90%-99% at 0.1 µg/L, 81%-99% at 0.25 µg/L, 83%-100% at 0.5 µg/L, 94%-100% at 2.0 µg/L and 90%-99% at 10 µg/L, respectively. The larger disagreement was observed comparing Diazyme PCT and Maglumi PCT with the other methods. Conclusions Although we found acceptable correlation among 10 commercial PCT immunoassays, the limited agreement at clinical decision thresholds remains a major issue, especially at lower end of PCT concentration, thus potentially contributing to jeopardize the clinical value of this biomarker.

Bioactivity-Protected Electrochemiluminescence Biosensor Using Gold Nanoclusters as the Low-Potential Luminophor and Cu2S Snowflake as Co-reaction Accelerator for Procalcitonin Analysis.

The expansion of electrochemiluminescence (ECL) technology to immunoassay at the core of care emphasizes all immune molecules will not be inactivated in the analysis process. That poses a major challenge to ECL-based biosensors due to the deoxynucleotide sequences of an antigen or antibody could be oxidized through a route of excessive cyclic potential. Herein, an ultrasensitive ECL biosensor was developed based on a novel bioactivity-protected sensing strategy utilizing Au nanoclusters (Au NCs) as low-potential luminophor for detection of procalcitonin (PCT). Bovine serum albumin (BSA)-templated Au NCs exhibited a low-potential anodic ECL signal in triethylamine (TEA) solution at 0.87 V, where it is suitable for the survival of immune molecules. Taking advantage of good conductivity and high surface area, a Cu2S snowflake not only functions as a satisfying substrate for connecting immune molecules but also acts as co-reaction accelerator to produce more cationic radicals TEA•+, which could improve the ECL intensity needed to meet the requirements of trace analysis. Otherwise, HWRGWVC (HC-7) heptapeptide as specific antibody immobilizer for site-oriented fixation was introduced to further maintain the bioactivity of an antibody. In view of the preceding discussion, the obtained biosensor exhibited ultrahigh immune recognition to targets so that the detection limit was as low as an unprecedented value of 2.36 fg/mL, which will be of great significance to the application and development of a biosensor in the future.

A semi-quantitative rapid multi-range gradient lateral flow immunoassay for procalcitonin.

A rapid semi-quantitative gradient lateral flow immunoassay (LFIA) of procalcitonin (PCT), a peptide precursor of the hormone calcitonin, was developed. The method is based on particular analyte cut-offs by immobilizing specific antibodies on the test strip with a consistent (gradient) increase in concentration from line to line. Semi-quantitative multi-range analysis is evaluated visually by counting the number of colored test lines corresponding to a certain concentration range of sepsis marker: [PCT]˂0.25; 0.25 ≤ [PCT] < 0.5; 0.5 ≤ [PCT] < 2; 2 ≤ [PCT] < 10; [PCT] ≥ 10 ng·mL-1. This multi-range gradient LFIA was implemented by using two types of label: spherical gold nanoparticles (35 nm) and hierarchical popcorn-like gold nanoparticles (100 nm). The comparison of this LFIA with an ELISA (for n = 82) yielded 87.5% and 76.6% sensitivities, and 92.3% and 92.3% specificities, respectively. Thus, multi-range gradient LFIA performs well at PCT thresholds, which is important for early diagnosis of sepsis and severe bacterial infection. In our perception, this method has a wide scope in that it may be implemented in numerous other LFIA based test systems. Graphical abstract Schematic of the gradient lateral flow immunoassay for determination of clinically relevant procalcitonin ranges. It allows to reach the correlation between the number of developed test lines and procalcitonin concentration range in serum by pre-immobilization of capture antibodies in a consistently (gradient) increasing concentration.

An ultrasensitive electrochemical immunosensor for procalcitonin detection based on the gold nanoparticles-enhanced tyramide signal amplification strategy.

In this study, we established an ultrasensitive electrochemical immunosensor based on the gold nanoparticles-enhanced tyramide signal amplification (AuNPs-TSA) for the detection of procalcitonin (PCT, for discriminating bacterial infections from nonbacterial infections). Firstly, a facilely prepared, well-conducting reduced graphene oxide nanosheets/GNP (rGO-AuNPs) nanocomposite was synthesized and immobilized on the electrode surface to absorb more capture antibodies (Ab1). Next another nanocomposite, acting as a signal tool, was modified with detection antibody (Ab2) and horseradish peroxidase (HRP), and then backfilled by bovine serum albumin (BSA). Because a single AuNP is able to load multiple HRPs and BSAs, a number of tyramine labeled biotins (T-B) could be deposited on the proteins adhering to the surface of AuNPs. Moreover, the high affinity between streptavidin (SA) and biotins significantly increases the loading of streptavidin labeled horseradish peroxidase (SA-HRP). The amplification system which was based on the two nanocomposites mentioned above, effectively amplified the electric current signals. This immunosensor exhibits a wide dynamic detection range from 0.05 ng mL-1 to 100 ng mL-1 and with an ultralow detection limit of 0.1 pg mL-1. We have successfully utilized this immunosensor to quantify the concentration of PCT in human serum samples, and the results suggest its potential use in clinical application.

A Robust and User-Friendly Alternative to Densitometry Using Origami Biosensors and Digital Logic.

Colorimetric detection with smartphones is ideal for point-of-care measurements because the signal reader is easily available. Densitometric detection schemes enable semiquantitative measurements but require a lightproof box to control photographic conditions and/or extensive data treatment to extract information. Approaches based on pattern recognition are not so sensitive to light artifacts but can only yield a yes/no type of answer when the signal is above or below a certain threshold. Here, we introduce a new method for detecting different concentrations of proteins as well as light artifacts with origami immunosensors and digital logic. The origami design consists of a folded piece of paper with three identical biorecognition sites so that one drop of sample generates three colorimetric signals simultaneously. The three colorimetric signals are then evaluated with an augmented reality app that generates a virtual semaphore that sequentially turns on its green, yellow, and red lights depending on the concentration of analyte. These three Boolean variables pass through "and" and "not" logic gates in a 3-to-8 decoder that enables the semiquantitative detection of proteins and adds a failsafe against erroneous results. The proposed method can detect the model analyte mouse IgG with a limit of detection and sensitivity comparable to densitometry performed under light-controlled conditions. It can also detect the sepsis biomarker procalcitonin at clinically relevant concentrations. With our approach, the detection is performed in real time, and signal processing is not required, which makes it suitable for rapid analyses by nonspecialists at the point of need.

Value of Exhaled Nitric Oxide (FeNO) And Eosinophilia During the Exacerbations of Chronic Obstructive Pulmonary Disease Requiring Hospital Admission.

The aim of this study was to analyze whether FeNO levels in acute exacerbation of COPD (AECOPD) with hospital admission have better diagnostic value than eosinophilia in blood, and to evaluate its usefulness in predicting a better clinical response. An observational prospective study of patients with AECOPD was carried out. FeNO determinations were made on arrival at the emergency room (ER), at discharge and during stability 3-6 months after discharge. Co-morbidities, bronchodilators, inhaled (IGC) and systemic (SGC) glucocorticoids, eosinophils, systemic inflammation markers (procalcitonin, C-reactive protein), eosinophil cationic protein, and total IgE were collected. Fifty consecutive patients (92% men, mean age 75 ± 6 years) were included in this study. Phenotypes were 26% Asthma-COPD Overlap Syndrome (ACOS), 42% chronic bronchitis (CB) and 32% emphysema. ACOS patients showed significantly higher levels of FeNO (73 ppb) and eosinophils (508 cells/mm3) than the rest (CB: 23 ppb, 184 cells/mm3, emphysema: 27 ppb, 159 cells/mm3; p < 0.05). A significant correlation between FeNO levels measured in ER and eosinophils was observed (r = 0.7; p < 0.001), but not at discharge or in stable phase. No significant association was found with parameters of systemic inflammation and mean stay. In conclusion, the determination of FeNO in AECOPD does not offer advantages over the evaluation of eosinophilia. These parameters rise at arrival in ER, descend at discharge, and remain unchanged in the stable phase. Both present similar diagnostic utility and are able to better identify the ACOS phenotype, which helps select a population that could benefit from a glucocorticoids therapy.

Label-Free Sandwich Imaging Ellipsometry Immunosensor for Serological Detection of Procalcitonin.

Analysis of trace low molecular weight (LMW) proteins in serum using the label-free imaging ellipsometry (IE) immunosensor is still a challenge due to the lack of an effective signal amplification strategy and the serious nonspecific adsorption. Herein we have developed a sandwich strategy-mediated IE (SSIE) immunosensor to enable the immunodetection of LMW protein biomarkers in serum samples. We have first found that the weak binding affinity and the insufficient surface amount density of the ligand are two important factors which hinder the detection of LMW proteins in serum using the IE immunosensor. Then we have deduced that the sandwich strategy can amplify the detection signal of IE and avoid the nonspecific adsorption in serum. As a validation of the serological detection of LMW proteins, the SSIE immunosensor has been used to accomplish the quantitative detection of procalcitonin (PCT) in serum. Compared with other PCT analysis methodologies, the SSIE immunosensor enjoys the advantages of simplicity, rapidity, and sufficient sensitivity. Furthermore, we have proposed the criteria to predict the ability of the SSIE immunosensor for the detection of LMW protein biomarkers in serum, which can make the detection of LMW proteins smart and efficient.