The feasibility of measuring calprotectin from a throat swab as a marker of infections caused by group A streptococcus: a case-control feasibility study.

BACKGROUND: Most people with sore throat do not benefit from antibiotic treatment, but nearly three-quarters of those presenting in primary care are prescribed antibiotics. A test that is predictive of bacterial infection could help guide antibiotic prescribing. Calprotectin is a biomarker of neutrophilic inflammation, and may be a useful marker of bacterial throat infections. AIM: To assess the feasibility of measuring calprotectin from throat swabs, and assess whether individuals with sore throats likely to be caused by streptococcal infections have apparently higher throat calprotectin levels than other individuals with sore throat and healthy volunteers. DESIGN & SETTING: A proof of concept case-control study was undertaken, which compared primary care patients with sore throats and healthy volunteers. METHOD: Baseline characteristics and throat swabs were collected from 30 primary care patients with suspected streptococcal sore throat, and throat swabs were taken from 10 volunteers without sore throat. Calprotectin level determination and rapid antigen streptococcal testing were conducted on the throat swab eluents. Calprotectin levels in the following groups were compared: volunteers without a sore throat; all patients with a sore throat; patients with a sore throat testing either negative or positive for streptococcal antigen; and those with lower and higher scores on clinical prediction rules for streptococcal sore throat. RESULTS: Calprotectin was detected in all throat swab samples. Mean calprotectin levels were numerically higher in patients with sore throat compared with healthy volunteers, and sore throat patients who had group A streptococci antigen detected compared with those who did not. CONCLUSION: Calprotectin can be measured from throat swab samples and levels are consistent with the hypothesis that streptococcal infection leads to higher throat calprotectin levels. This hypothesis will be tested in a larger study.

Identification of clinical and urine biomarkers for uncomplicated urinary tract infection using machine learning algorithms.

Women with uncomplicated urinary tract infection (UTI) symptoms are commonly treated with empirical antibiotics, resulting in overuse of antibiotics, which promotes antimicrobial resistance. Available diagnostic tools are either not cost-effective or diagnostically sub-optimal. Here, we identified clinical and urinary immunological predictors for UTI diagnosis. We explored 17 clinical and 42 immunological potential predictors for bacterial culture among women with uncomplicated UTI symptoms using random forest or support vector machine coupled with recursive feature elimination. Urine cloudiness was the best performing clinical predictor to rule out (negative likelihood ratio [LR-] = 0.4) and rule in (LR+ = 2.6) UTI. Using a more discriminatory scale to assess cloudiness (turbidity) increased the accuracy of UTI prediction further (LR+ = 4.4). Urinary levels of MMP9, NGAL, CXCL8 and IL-1ß together had a higher LR+ (6.1) and similar LR- (0.4), compared to cloudiness. Varying the bacterial count thresholds for urine culture positivity did not alter best clinical predictor selection, but did affect the number of immunological predictors required for reaching an optimal prediction. We conclude that urine cloudiness is particularly helpful in ruling out negative UTI cases. The identified urinary biomarkers could be used to develop a point of care test for UTI but require further validation.

The biological effects upon the cardiovascular system consequent to exposure to particulates of less than 500 nm in size.

CONTEXT: Ultrafine particulate matter contribution to cardiovascular disease is not known and not regulated. PM up to 500 nm are abundant in urban air and alveolar deposition is significant. OBJECTIVE: Effects beyond the alveolar barrier within the body or in vitro tissues exposed to particles <500 nm. DATABASES: MEDLINE; Ovid-MEDLINE PREM; Web of Science; PubMed (SciGlobe). 127 articles. Results in tables: "subject type exposed", "exposure type", "technique". CONCLUSION: Heart rate, vasoactivity, atherosclerotic advancement, oxidative stress, coagulability, inflammatory changes are affected. Production of reactive oxygen species is a useful target to limit outcomes associated with UFP exposure.

Characterization of the interactions between protein and carbon black.

A considerable amount of studies have been conducted to investigate the interactions of biological fluids with nanoparticle surfaces, which exhibit a high affinity for proteins and particles. However, the mechanisms underlying these interactions have not been elucidated, particularly as they relate to human health. Using bovine serum albumin (BSA) and mice bronchoalveolar lavage fluid (BALF) as models for protein-particle conjugates, we characterized the physicochemical modifications of carbon blacks (CB) with 23nm or 65nm in diameter after protein treatment. Adsorbed BALF-containing proteins were quantified and identified by pathways, biological analyses and protein classification. Significant modifications of the physicochemistry of CB were induced by the addition of BSA. Enzyme modulators and hydrolase predominately interacted with CB, with protein-to-CB interactions that were associated with the coagulation pathways. Additionally, our results revealed that an acute-phase response could be activated by these proteins. With regard to human health, the present study revealed that the CB can react with proteins (∼55kDa and 70kDa) after inhalation and may modify the functional structures of lung proteins, leading to the activation of acute-inflammatory responses in the lungs.

Feasibility of using biomarkers in blood serum as markers of effect following exposure of the lungs to particulate matter air pollution.

Particulate matter (PM) air pollution has significant cardiopulmonary health effects. Serum biomarkers may elucidate the disease mechanisms involved and provide a means for biomonitoring exposed populations, thereby enabling accurate policy decisions on air quality standards to be made. For this review, research investigating association of blood serum biomarkers and exposure to PM was identified, finding 26 different biomarkers that were significantly associated with exposure. Recent evidence links different effects to different components of PM. Future research on biomarkers of effect will need to address exposure by all PM size fractions.

Maximal extent of translocation of single-walled carbon nanotubes from lung airways of the rat.

This study aimed to examine the extent of pulmonary translocation of single-walled carbon nanotubes (SWCNTs) from lung airways of rat. It utilised an ex vivo isolated perfused rat lung (IPRL) model that retains the intact lung architecture while eliminating the confounding issue of systemic pharmacokinetics. Doses (100 µg) of SWCNTs were instilled into the airways of the IPRL and the pulmonary translocation of SWCNTs quantified by inductively coupled plasma mass spectroscopy using CNT-associated nickel as the probe. SWCNT translocation from the airways across an intact pulmonary barrier into what would be the systemic circulation was no greater than 0.05% of the instilled dose over 90 min. Pharmacokinetic simulation incorporating a term for mucociliary clearance would predict over a 14 day an approximate cumulative pulmonary translocation from rat lung of no greater than 0.15% from a 100 µg deposited dose.

Differences in fungi present in induced sputum samples from asthma patients and non-atopic controls: a community based case control study.

BACKGROUND: There is emerging evidence for the presence of an extensive microbiota in human lungs. It is not known whether variations in the prevalence of species of microbiota in the lungs may have aetiological significance in respiratory conditions such as asthma. The aim of the study was to undertake semi-quantitative analysis of the differences in fungal species in pooled sputum samples from asthma patients and controls. METHODS: Induced sputum samples were collected in a case control study of asthma patients and control subjects drawn from the community in Wandsworth, London. Samples from both groups were pooled and then tested for eukaryotes. DNA was amplified using standard PCR techniques, followed by pyrosequencing and comparison of reads to databases of known sequences to determine in a semi-quantitative way the percentage of DNA from known species in each of the two pooled samples. RESULTS: A total of 136 fungal species were identified in the induced sputum samples, with 90 species more common in asthma patients and 46 species more common in control subjects. Psathyrella candolleana, Malassezia pachydermatis, Termitomyces clypeatus and Grifola sordulenta showed a higher percentage of reads in the sputum of asthma patients and Eremothecium sinecaudum, Systenostrema alba, Cladosporium cladosporioides and Vanderwaltozyma polyspora showed a higher percentage of reads in the sputum of control subjects. A statistically significant difference in the pattern of fungi that were present in the respective samples was demonstrated using the Phylogenetic (P) test (P < 0.0001). CONCLUSION: This study is novel in providing evidence for the widespread nature of fungi in the sputum of healthy and asthmatic individuals. Differences in the pattern of fungi present in asthma patients and controls merit further investigation. Of particular interest was the presence of Malassezia pachydermatis, which is known to be associated with atopic dermatitis.

Gene and protein responses of human lung tissue explants exposed to ambient particulate matter of different sizes.

CONTEXT: Exposure to ambient particulate air pollution is associated with increased cardiovascular and respiratory morbidity and mortality. It is necessary to understand causal pathways driving the observed health effects, particularly if they are differentially associated with particle size. OBJECTIVES: To investigate the effect of different size ranges of ambient particulate matter (PM) on gene and protein expression in an in vitro model. MATERIALS AND METHODS: Normal human tracheobronchial epithelium (NHTBE) three-dimensional cell constructs were exposed for 24 h to washed ambient PM of different sizes (size 1: 7-615 nm; size 2: 616 nm-2.39 µm; size 3: 2.4-10 µm) collected from a residential street. A human stress and toxicity PCR array was used to investigate gene expression and iTRAQ was used to perform quantitative proteomics. RESULTS: Eighteen different genes of the 84 on the PCR array were significantly dysregulated. Treatment with size 2 PM resulted in the greatest number of genes with altered expression, followed by size 1 and lastly size 3. ITRAQ identified 317 proteins, revealing 20 that were differentially expressed. Enrichment for gene ontology classification revealed potential changes to various pathways. DISCUSSION AND CONCLUSIONS: Different size fractions of ambient PM are associated with dysregulatory effects on the cellular proteome and on stress and toxicity genes of NHTBE cells. This approach not only provides an investigative tool to identify possible causal pathways but also permits the relationship between particle size and responses to be explored.

Association between protozoa in sputum and asthma: a case-control study.

BACKGROUND: Atypical infectious agents have been proposed as potential contributors to asthma. A novel set of morphological and staining criteria permit the identification of flagellated protozoa in sputum. This case-control study was designed to use this novel method and to assess: (1) are protozoa more common in asthmatics than in non-asthmatics; (2) is the presence of protozoa associated with the use of steroid inhalers; and (3) is the presence of protozoa associated with living in damp housing? METHODS: Induced sputum samples were collected from asthma patients and local non-atopic, non-smoking controls. Questionnaires assessed asthma severity and housing conditions. Sputum was examined for flagellated protozoa using a previously described staining technique. RESULTS: 96 participants were recruited for this study; 54 asthma patients and 42 controls, age range 21-62 years, 70% female participants. Limiting results to those who were clearly positive or negative for flagellated protozoa, 66.7% (20/30) of asthmatics and 30.8% (4/13) of controls had protozoa (p = 0.046). Among the asthma patients, prevalence of protozoa was not significantly different between those who had (10/18), and those who had not (10/12), used steroid inhaler in the preceding two weeks (p = 0.11). Similarly, the prevalence of protozoa was not significantly different between those who did (6/11) and those who did not (18/32), live in damp homes (p = 0.92). CONCLUSIONS: This case-control study demonstrates an association between flagellated protozoa in sputum and asthma. It is now necessary to confirm and characterise the protozoa using genetic techniques based on 18S ribosomal RNA. Once tis is established it would be worthwhile to determine if asthma symptoms improve when treated by anti-protozoal agents.

Airborne particles in Swansea, UK: their collection and characterization.

Urban air particulate matter (PM) has previously been associated with a variety of adverse health effects. It is now believed that the smallest particles, ultrafine or nanoparticles, are linked to the greatest health effects. The physicochemistry of these particles is likely to provide information regarding their toxicity. Therefore, the aim of this study was to further the understanding of the heterogeneous and changing particle concentrations in urban air, in conjunction with gaining an understanding of the physicochemistry of the particles. A Dekati electrical low-pressure impactor was used to collect the particles and real-time data in a busy traffic corridor in Swansea, Wales, over a period of 10 nonconsecutive weeks. Particle concentrations in the street canyon were analyzed and particle physicochemistries investigated using a variety of techniques. Particle number concentrations were found to vary both diurnally and from day to day in the traffic corridor. Of all particles, the nano to fine size fraction was consistently identified in the highest concentrations (maximum: 140,000 particles cm(-3)). Particle physicochemistry was found to vary as a function of size, with larger particles exhibiting a greater variety of morphologies (and consequently particle types) and associated metals.

Outdoor and indoor respirable air particulate concentrations in differing urban traffic microenvironments.

To study the adverse health effects associated with ambient respirable particulates it is necessary to assess population exposure. However, measurements are usually carried out by fixed-site air monitoring units and do not take into consideration the range of urban microenvironments. In particular, vehicular emissions are a major source of particulates in cities and it is therefore necessary to consider traffic density when investigating the adverse health effects of air particulates. This study assessed both PM(5) and total particle number (TPN) in areas of high and low traffic flow within the city of Cardiff, UK. Daytime measurements were made outdoors throughout the period January 2004-June 2005. Simultaneous indoor measurements were made in 73 participating households in areas of high traffic flow (exposed) and 50 households in areas of low traffic flow (controls). The median outdoor PM(5) concentration in the exposed area (16.7 microg cm(-3)) was 45% significantly higher than that in the unexposed area (11.5 microg cm(-3)) and the median TPN in the exposed area (18,130 particles cm(-3)) was almost double that in the unexposed area (9951 particles cm(-3)). The median indoor concentration of PM(5) in the exposed area (13.2 microg cm(-3)) was also 40% significantly higher than that in the unexposed area (9.4 microg cm(-3)), but there was almost no difference in indoor median TPN between the two areas: 8999 particles cm(-3) and 8549 particles cm(-3), respectively. The observed differences in respirable particles between areas of high and low traffic flow underline the importance of obtaining exposure measurements in microenvironments.