Temporal data representation, normalization, extraction, and reasoning: A review from clinical domain.

Comput Methods Programs Biomed. 2016 May;128:52-68

Authors: Madkour M, Benhaddou D, Tao C

Abstract
BACKGROUND AND OBJECTIVE: We live our lives by the calendar and the clock, but time is also an abstraction, even an illusion. The sense of time can be both domain-specific and complex, and is often left implicit, requiring significant domain knowledge to accurately recognize and harness. In the clinical domain, the momentum gained from recent advances in infrastructure and governance practices has enabled the collection of tremendous amount of data at each moment in time. Electronic health records (EHRs) have paved the way to making these data available for practitioners and researchers. However, temporal data representation, normalization, extraction and reasoning are very important in order to mine such massive data and therefore for constructing the clinical timeline. The objective of this work is to provide an overview of the problem of constructing a timeline at the clinical point of care and to summarize the state-of-the-art in processing temporal information of clinical narratives.
METHODS: This review surveys the methods used in three important area: modeling and representing of time, medical NLP methods for extracting time, and methods of time reasoning and processing. The review emphasis on the current existing gap between present methods and the semantic web technologies and catch up with the possible combinations.
RESULTS: The main findings of this review are revealing the importance of time processing not only in constructing timelines and clinical decision support systems but also as a vital component of EHR data models and operations.
CONCLUSIONS: Extracting temporal information in clinical narratives is a challenging task. The inclusion of ontologies and semantic web will lead to better assessment of the annotation task and, together with medical NLP techniques, will help resolving granularity and co-reference resolution problems.

PMID: 27040831 [PubMed - indexed for MEDLINE]

Blending water- and nutrient-source wastewaters for cost-effective cultivation of high lipid content microalgal species Micractinium inermum NLP-F014.

Bioresour Technol. 2015 Dec;198:388-94

Authors: Park S, Kim J, Yoon Y, Park Y, Lee T

Abstract
The possibility of utilizing blended wastewaters from different streams was investigated for cost-efficient microalgal cultivation. The influent of a domestic wastewater treatment plant and the liquid fertilizer from a swine wastewater treatment plant were selected as water- and nutrient-source wastewaters, respectively. The growth of Micractinium inermum NLP-F014 in the blended wastewater medium without any pretreatment was comparable to that in Bold's Basal Medium. The optimum blending ratio of 5-15% (vv(-1)) facilitated biomass production up to 5.7 g-dry cell weight (DCW) L(-1), and the maximum biomass productivity (1.03 g-DCWL(-1)d(-1)) was achieved after three days of cultivation. Nutrient depletion induced lipid accumulation in the cell up to 39.1% (ww(-1)) and the maximum lipid productivity was 0.19 g-FAMEL(-1)d(-1). These results suggest that blending water- and nutrient-source wastewaters at a proper ratio without pretreatment can significantly cut costs in microalgae cultivation for biodiesel production.

PMID: 26409109 [PubMed - indexed for MEDLINE]

Public Understanding of Science in turbulent times III: Deficit to dialogue, champions to critics.

Public Underst Sci. 2016 Feb;25(2):186-97

Authors: Smallman M

Abstract
As part of the 20th Anniversary of the Public Understanding of Science journal, the journal has been reflecting on how the field and journal have developed. This research note takes a closer look at some of the trends, considering the journal's 50 most cited papers and using IRaMuTeQ, an open-source computer text analysis technique. The research note presents data that show that the move within public engagement from deficit to dialogue has been followed by a further shift from championing dialogue to criticising its practice. This shift has taken place alongside a continued, but changing, interest in media coverage, surveys and models of public understanding.

PMID: 25234052 [PubMed - indexed for MEDLINE]

Coronary artery disease in Eisenmenger's syndrome--Rare but not to be forgotten.

Int J Cardiol. 2016 Jan 15;203:276-7

Authors: Abraham D, Freeman LJ, Lewis C, O'Sullivan M

PMID: 26519685 [PubMed - indexed for MEDLINE]

Drug-drug interaction discovery and demystification using Semantic Web technologies.

J Am Med Inform Assoc. 2016 Dec 28;:

Authors: Noor A, Assiri A, Ayvaz S, Clark C, Dumontier M

Abstract
OBJECTIVE: To develop a novel pharmacovigilance inferential framework to infer mechanistic explanations for asserted drug-drug interactions (DDIs) and deduce potential DDIs.
MATERIALS AND METHODS: A mechanism-based DDI knowledge base was constructed by integrating knowledge from several existing sources at the pharmacokinetic, pharmacodynamic, pharmacogenetic, and multipathway interaction levels. A query-based framework was then created to utilize this integrated knowledge base in conjunction with 9 inference rules to infer mechanistic explanations for asserted DDIs and deduce potential DDIs.
RESULTS: The drug-drug interactions discovery and demystification (D3) system achieved an overall 85% recall rate in terms of inferring mechanistic explanations for the DDIs integrated into its knowledge base, while demonstrating a 61% precision rate in terms of the inference or lack of inference of mechanistic explanations for a balanced, randomly selected collection of interacting and noninteracting drug pairs.
DISCUSSION: The successful demonstration of the D3 system's ability to confirm interactions involving well-studied drugs enhances confidence in its ability to deduce interactions involving less-studied drugs. In its demonstration, the D3 system infers putative explanations for most of its integrated DDIs. Further enhancements to this work in the future might include ranking interaction mechanisms based on likelihood of applicability, determining the likelihood of deduced DDIs, and making the framework publicly available.
CONCLUSION: The D3 system provides an early-warning framework for augmenting knowledge of known DDIs and deducing unknown DDIs. It shows promise in suggesting interaction pathways of research and evaluation interest and aiding clinicians in evaluating and adjusting courses of drug therapy.

PMID: 28031284 [PubMed - as supplied by publisher]

Addressing the Crisis in the Treatment of Osteoporosis: A Path Forward.

J Bone Miner Res. 2016 Dec 29;:

Authors: Khosla S, Cauley JA, Compston J, Kiel DP, Rosen C, Saag KG, Shane E

Abstract
Considerable data and media attention have highlighted a potential "crisis" in the treatment of osteoporosis. Specifically, despite the availability of several effective drugs to prevent fractures, many patients who need pharmacological therapy are either not being prescribed these medications or if prescribed a medication, are simply not taking it. Although there are many reasons for this "gap" in the treatment of osteoporosis, a major factor is physician and patient concerns over the risk of side effects, especially atypical femur fractures (AFFs) related to bisphosphonate (and perhaps other anti-resorptive) drug therapy. In this perspective, we review the current state of under-treatment of patients at increased fracture risk and suggest possible short-, intermediate-, and long-term approaches to address patient concerns, specifically those related to AFF risk. We suggest improved patient and physician education on prodromal symptoms, extended femur scans using DXA to monitor patients on anti-resorptive treatment, better identification of high risk patients perhaps using geometrical parameters from DXA and other risk factors, and more research on pharmacogenomics to identify risk markers. Although not the only impediment to appropriate treatment of osteoporosis, concern over AFFs remains a major issue and one that needs to be resolved for effective dissemination of existing treatments to reduce fracture risk. This article is protected by copyright. All rights reserved.

PMID: 28032660 [PubMed - as supplied by publisher]

Rapid Naked-Eye Discrimination of Cytochrome P450 Genetic Polymorphism through Non-Crosslinking Aggregation of DNA-Functionalized Gold Nanoparticles.

ChemistryOpen. 2016 Dec;5(6):508-512

Authors: Akiyama Y, Wang G, Shiraishi S, Kanayama N, Takarada T, Maeda M

Abstract
Involvement of single-nucleotide polymorphism (SNP) genotyping in healthcare should allow for more effective use of pharmacogenomics. However, user-friendly assays without the requirement of a special instrument still remain unavailable. This study describes naked-eye SNP discrimination in exon 5 of the human cytochrome P450 2C19 monooxygenase gene, CYP2C19*1 (the wild-type allele) and CYP2C19*2 (the variant allele with G681A point mutation). The present assay is composed of allele-specific single-base primer extension and salt-induced aggregation of DNA-modified gold nanoparticles (DNA-AuNPs). Genetic samples extracted from human hair roots are subjected to this assay. The results are verified by direct sequencing. This study should promise the prospective use of DNA-AuNPs in gene diagnosis.

PMID: 28032016 [PubMed]

Pharmacogenetics of cancer therapy: breakthroughs from beyond?

Future Sci OA. 2015 Nov;1(4):FSO80

Authors: Lu DY, Lu TR, Xu B, Ding J

Abstract
'Pharmacogenetics or Pharmacogenomics' (PG) is one of the most practiced cancer therapeutic strategies, tailored for individualized patients. Despite its popularity and rapid advancements in the field, many obstacles for cancer therapy PG still need to be overcome. By borrowing scientific systems from other disciplines such as cancer diagnosis, and therapeutic information from the diversity of tumor origins, categories and stages, cancer therapy PG may hopefully be improved. Furthermore, to quickly acquire genetic and pathologic information and seek therapeutic interventions, possible breakthroughs may come from beyond - changing the cancer therapeutic landscapes. The next generations of PG protocols and hospital routines for searching deadly cancer pathogenic pathways versus drug-targeting predictions are of great clinical significance for the future. Yet, progress of cancer therapy PG is entering into a bottleneck stage owing to simple model of relevant techniques and routines. Promoting or even innovating present PG modular is very necessary. This perspective highlights this issue by introducing new initiatives and ideas.

PMID: 28031929 [PubMed]

Perception of first respiratory infection with Pseudomonas aeruginosa by people with cystic fibrosis and those close to them: an online qualitative study.

BMJ Open. 2016 Dec 28;6(12):e012303

Authors: Palser SC, Rayner OC, Leighton PA, Smyth AR

Abstract
BACKGROUND: People with cystic fibrosis (CF) are susceptible to respiratory infection with Pseudomonas aeruginosa (PA), which may become chronic if initial eradication fails. Environmental acquisition and person-to-person transmission can occur. Respiratory PA infection is associated with increased mortality and more hospitalisations. This may cause patients and families anxiety and lead them to adopt preventive measures which may be ineffectual and intrusive. It is not possible to hold a conventional focus group to explore these issues because people with CF cannot meet together due to the risk of cross-infection.
OBJECTIVE: To explore the perceptions of first respiratory infection with PA in people with CF and those close to them.
DESIGN: We designed an online survey, to maximise accessibility and avoid the risk of cross-infection. This established the respondent's relationship with CF, asked 3 open questions about perceptions of PA and a final question about the prioritisation of research. Responses were analysed using a structured, iterative process. We identified keywords, analysed these incontext and derived key themes.
SETTING: Promotion through social media allowed respondents from any country to participate.
PARTICIPANTS: People with CF and those close to them.
RESULTS: Responses were received from 393 people, including 266 parents and 97 people with CF. The key themes were the emotional burden of PA (fear in particular); the burden of treatment PA entails and the need for accurate knowledge about PA.
CONCLUSIONS: Lack of knowledge and the health beliefs of individuals may promote fear of infection and inappropriate avoidance measures. Uncertainty about the implications of PA infection and the treatment required may cause anxiety. Healthcare professionals should provide clear information about how PA might be acquired and the treatment necessary, making clear the limitations of current understanding and acknowledging health beliefs.

PMID: 28031208 [PubMed - in process]

Thromboelastogram as a Tool to Predict Hypercoagulability in Children With Cystic Fibrosis.

Clin Appl Thromb Hemost. 2016 Jan 01;:1076029616683045

Authors: Anıl H, Kılıç Yıldırım G, Harmancı K, Bozkurt Turhan A, Akay OM, Bör Ö, Aydoğdu S, Kocak A

Abstract
Increased thrombophilic tendency in patients with cystic fibrosis (CF) has recently been reported. The determinants of thrombosis in children with CF remain largely unknown. Our aim in this study was to evaluate the thromboelastography (TEG) profile of children with CF through ROTEM (whole blood rotation thromboelastometry). Nineteen patients with CF and 20 controls were included in the study. Whole blood count, prothrombin time, activated prothrombin time, fibrinogen, d-dimer levels, and ROTEM assays (INTEM, EXTEM) were performed. Clotting time, clot formation time (CFT), and maximum clot firmness (MCF) were determined by INTEM and EXTEM analysis. In INTEM assay, MCF ( P = .001) value was significantly increased and CFT ( P = .031) value was decreased in patients with CF compared with those of the control group. In the EXTEM assay, there was a similar significant increase in MCF ( P = .023) value in patients with CF compared with that of the control group. There was a significant positive correlation between fibrinogen levels and MCF in EXTEM ( r = .72) and INTEM ( r = .76) assays, whereas there was a negative correlation with CFT in EXTEM ( r = -.61) and INTEM ( r = -.67). The results of our study indicated that TEG profiles in patients with CF were more hypercoagulable compared with those of the control group.

PMID: 28030968 [PubMed - as supplied by publisher]

HMGB1 levels in children with atopic eczema/dermatitis syndrome (AEDS).

Pediatr Allergy Immunol. 2016 Feb;27(1):99-102

Authors: Cuppari C, Manti S, Salpietro A, Valenti S, Capizzi A, Arrigo T, Salpietro C, Leonardi S

PMID: 26388323 [PubMed - indexed for MEDLINE]

Clinical, Immune, and Microbiome Traits of Gingivitis and Peri-implant Mucositis.

J Dent Res. 2017 Jan;96(1):47-55

Authors: Schincaglia GP, Hong BY, Rosania A, Barasz J, Thompson A, Sobue T, Panagakos F, Burleson JA, Dongari-Bagtzoglou A, Diaz PI

Abstract
Tissues surrounding dental implants and teeth develop clinical inflammation in response to microbial stimuli. However, the literature suggests that differences exist in the microbial insult and inflammatory responses leading to gingivitis and peri-implant mucositis. In this pilot study, the authors use for the first time a systems biology approach to comprehensively evaluate clinical parameters, selected inflammatory markers, and the microbiome of subject-matched tooth and implant sites during native inflammation and in response to experimental plaque accumulation. Fifteen subjects with 2 posterior implants and corresponding contralateral teeth were examined at enrollment; at day 0, after reinstitution of gingival/mucosal health; at days 7, 14, and 21, during stent-mediated oral hygiene (OH) abstention; and at day 42, after resumption of OH. The subgingival microbiome was evaluated via 16S rRNA gene sequencing and 8 selected inflammatory markers measured in crevicular fluid. Comparison of teeth and implants via general linear models based on orthogonal polynomials showed similar responses in clinical parameters, inflammatory mediators, and proportions of individual microbial taxa during OH abstention. Implants, however, accumulated less plaque and underwent more heterogeneous shifts in microbiome structure. A multilevel, within-group, sparse partial least squares analysis of covariation of microbial, inflammatory, and clinical parameters throughout all study visits found inflammation around teeth and implants positively correlated with IL-1 alpha and IL-1 beta and with the proportions of Selenomonas, Prevotella, and 5 species-level phylotypes. Gingivitis, however, showed a stronger positive correlation with lactoferrin and IL-1ra and a stronger negative correlation with Rothia. Peri-implant mucositis, on the contrary, correlated positively with certain microbial taxa not associated with gingivitis by a previous study or the current one. In summary, differences existed between implants and tooth sites in microbiome evolution during OH abstention and in the correlation of specific inflammatory mediators and microbial taxa with clinical inflammation. Common biological features, however, were also identified for gingivitis and mucositis.

PMID: 28033066 [PubMed - in process]

A unique large-scale undergraduate research experience in molecular systems biology for non-mathematics majors.

Biochem Mol Biol Educ. 2016 Dec 28;:

Authors: Kappler U, Rowland SL, Pedwell RK

Abstract
Systems biology is frequently taught with an emphasis on mathematical modeling approaches. This focus effectively excludes most biology, biochemistry, and molecular biology students, who are not mathematics majors. The mathematical focus can also present a misleading picture of systems biology, which is a multi-disciplinary pursuit requiring collaboration between biochemists, bioinformaticians, and mathematicians. This article describes an authentic large-scale undergraduate research experience (ALURE) in systems biology that incorporates proteomics, bacterial genomics, and bioinformatics in the one exercise. This project is designed to engage students who have a basic grounding in protein chemistry and metabolism and no mathematical modeling skills. The pedagogy around the research experience is designed to help students attack complex datasets and use their emergent metabolic knowledge to make meaning from large amounts of raw data. On completing the ALURE, participants reported a significant increase in their confidence around analyzing large datasets, while the majority of the cohort reported good or great gains in a variety of skills including "analysing data for patterns" and "conducting database or internet searches." An environmental scan shows that this ALURE is the only undergraduate-level system-biology research project offered on a large-scale in Australia; this speaks to the perceived difficulty of implementing such an opportunity for students. We argue however, that based on the student feedback, allowing undergraduate students to complete a systems-biology project is both feasible and desirable, even if the students are not maths and computing majors. © 2016 by The International Union of Biochemistry and Molecular Biology, 2016.

PMID: 28032403 [PubMed - as supplied by publisher]

BluePen Biomarkers LLC: integrated biomarker solutions.

Future Sci OA. 2016 Jun;2(2):FSO124

Authors: Blair IA, Mesaros C, Lilley P, Nunez M

Abstract
BluePen Biomarkers provides a unique comprehensive multi-omics biomarker discovery and validation platform. We can quantify, integrate and analyze genomics, proteomics, metabolomics and lipidomics biomarkers, alongside clinical data, demographics and other phenotypic data. A unique bio-inspired signal processing analytic approach is used that has the proven ability to identify biomarkers in a wide variety of diseases. The resulting biomarkers can be used for diagnosis, prognosis, mechanistic studies and predicting treatment response, in contexts from core research through clinical trials. BluePen Biomarkers provides an additional groundbreaking research goal: identifying surrogate biomarkers from different modalities. This not only provides new biological insights, but enables least invasive, least-cost tests that meet or exceed the predictive quality of current tests.

PMID: 28031971 [PubMed]

Detection of clinically important colorectal surgical site infection using Bayesian network.

J Surg Res. 2016 Oct 05;209:168-173

Authors: Sohn S, Larson DW, Habermann EB, Naessens JM, Alabbad JY, Liu H

Abstract
BACKGROUND: Despite extensive efforts to monitor and prevent surgical site infections (SSIs), real-time surveillance of clinical practice has been sparse and expensive or nonexistent. However, natural language processing (NLP) and machine learning (i.e., Bayesian network analysis) may provide the methodology necessary to approach this issue in a new way. We investigated the ability to identify SSIs after colorectal surgery (CRS) through an automated detection system using a Bayesian network.
MATERIALS AND METHODS: Patients who underwent CRS from 2010 to 2012 and were captured in our institutional American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) comprised our cohort. A Bayesian network was applied to detect SSIs using risk factors from ACS-NSQIP data and keywords extracted from clinical notes by NLP. Two surgeons provided expertise informing the Bayesian network to identify clinically meaningful SSIs (CM-SSIs) occurring within 30 d after surgery.
RESULTS: We used data from 751 CRS cases experiencing 67 (8.9%) SSIs and 78 (10.4%) CM-SSIs. Our Bayesian network detected ACS-NSQIP-captured SSIs with a receiver operating characteristic area under the curve of 0.827, but this value increased to 0.892 when using surgeon-identified CM-SSIs.
CONCLUSIONS: A Bayesian network coupled with NLP has the potential to be used in real-time SSI surveillance. Moreover, surgeons identified CM-SSI not captured under current NSQIP definitions. Future efforts to expand CM-SSI identification may lead to improved and potentially automated approaches to survey for postoperative SSI in clinical practice.

PMID: 28032554 [PubMed - as supplied by publisher]

Drug-Mediated Regulation of Glycosaminoglycan Biosynthesis.

Med Res Rev. 2016 Dec 28;:

Authors: Ghiselli G

Abstract
Glycosaminoglycans (GAGs) are a heterogeneous family of unbranched polysaccharides that exist in either a free state or attached to proteins and are found on the cell surface as well as in the extracellular matrix. GAGs play essential roles in cellular and tissue homeostasis, and their metabolism is altered in response to several pathological conditions. Despite strong experimental evidence supporting the function of GAGs in various diseases, little is known about the regulation of GAG biosynthesis via pharmacological intervention. In recent studies, the effects of several experimental drugs on GAG biosynthesis in animal models of disease were examined and key enzymes involved in GAG biosynthesis were found to be druggable. In addition to experimental small-molecule drugs that alter GAG biosynthesis, a number of clinically approved drugs modulate GAG metabolism, contributing to the therapeutic benefits associated with the use of these drugs. In this review article, we propose a classification scheme for drugs affecting GAG biosynthesis. Our goal is to present a rational approach to investigate the pharmacological regulation of these important biological molecules.

PMID: 28029167 [PubMed - as supplied by publisher]

Putative modifier genes in mevalonate kinase deficiency.

Mol Med Rep. 2016 Apr;13(4):3181-9

Authors: Marcuzzi A, Vozzi D, Girardelli M, Tricarico PM, Knowles A, Crovella S, Vuch J, Tommasini A, Piscianz E, Bianco AM

Abstract
Mevalonate kinase deficiency (MKD) is an autosomal recessive auto‑inflammatory disease, caused by impairment of the mevalonate pathway. Although the molecular mechanism remains to be elucidated, there is clinical evidence suggesting that other regulatory genes may be involved in determining the phenotype. The identification of novel target genes may explain non‑homogeneous genotype‑phenotype correlations, and provide evidence in support of the hypothesis that novel regulatory genes predispose or amplify deregulation of the mevalonate pathway in this orphan disease. In the present study, DNA samples were obtained from five patients with MKD, which were then analyzed using whole exome sequencing. A missense variation in the PEX11γ gene was observed in homozygosis in P2, possibly correlating with visual blurring. The UNG rare gene variant was detected in homozygosis in P5, without correlating with a specific clinical phenotype. A number of other variants were found in the five analyzed DNA samples from the MKD patients, however no correlation with the phenotype was established. The results of the presents study suggested that further analysis, using next generation sequencing approaches, is required on a larger sample size of patients with MKD, who share the same MVK mutations and exhibit 'extreme' clinical phenotypes. As MVK mutations may be associated with MKD, the identification of specific modifier genes may assist in providing an earlier diagnosis.

PMID: 26935981 [PubMed - indexed for MEDLINE]

Socio-economic burden of rare diseases: A systematic review of cost of illness evidence.

Health Policy. 2015 Jul;119(7):964-79

Authors: Angelis A, Tordrup D, Kanavos P

Abstract
Cost-of-illness studies, the systematic quantification of the economic burden of diseases on the individual and on society, help illustrate direct budgetary consequences of diseases in the health system and indirect costs associated with patient or carer productivity losses. In the context of the BURQOL-RD project ("Social Economic Burden and Health-Related Quality of Life in patients with Rare Diseases in Europe") we studied the evidence on direct and indirect costs for 10 rare diseases (Cystic Fibrosis [CF], Duchenne Muscular Dystrophy [DMD], Fragile X Syndrome [FXS], Haemophilia, Juvenile Idiopathic Arthritis [JIA], Mucopolysaccharidosis [MPS], Scleroderma [SCL], Prader-Willi Syndrome [PWS], Histiocytosis [HIS] and Epidermolysis Bullosa [EB]). A systematic literature review of cost of illness studies was conducted using a keyword strategy in combination with the names of the 10 selected rare diseases. Available disease prevalence in Europe was found to range between 1 and 2 per 100,000 population (PWS, a sub-type of Histiocytosis, and EB) up to 42 per 100,000 population (Scleroderma). Overall, cost evidence on rare diseases appears to be very scarce (a total of 77 studies were identified across all diseases), with CF (n=29) and Haemophilia (n=22) being relatively well studied, compared to the other conditions, where very limited cost of illness information was available. In terms of data availability, total lifetime cost figures were found only across four diseases, and total annual costs (including indirect costs) across five diseases. Overall, data availability was found to correlate with the existence of a pharmaceutical treatment and indirect costs tended to account for a significant proportion of total costs. Although methodological variations prevent any detailed comparison between conditions and based on the evidence available, most of the rare diseases examined are associated with significant economic burden, both direct and indirect.

PMID: 25661982 [PubMed - indexed for MEDLINE]

Clinical Impact of Pharmacogenomics of Clopidogrel in Stroke.

Circulation. 2017 Jan 03;135(1):34-37

Authors: Simon T, Danchin N

PMID: 28028061 [PubMed - in process]

A High Level of Soluble CD40L Is Associated with P. aeruginosa Infection in Patients with Cystic Fibrosis.

PLoS One. 2016;11(12):e0168819

Authors: Bustamante AE, Jaime-Pérez JC, Cordero-Pérez P, Galindo-Rodríguez G, Muñoz-Espinosa LE, Villarreal-Villarreal CD, Mercado-Longoria R

Abstract
OBJECTIVE: The aim of this study was to evaluate whether the concentration of sCD40L, a product of platelet activation, correlates with the presence of Pseudomonas aeruginosa in the airway of patients with cystic fibrosis (CF) and to determine its possible clinical association.
METHODS: Sixty patients with CF, ranging in age from 2 months to 36 years, were studied. The demographics, cystic fibrosis transmembrane conductance regulator (CFTR) genotype, spirometry measurements, radiographic and tomographic scans, platelet count in peripheral blood, sCD40L, IL-6, TNF-α and ICAM1 data were collected. Infection-colonization of the airway was evaluated using sputum and throat swab cultures; the levels of anti-Pseudomonas aeruginosa antibodies (Anti-PaAb) were evaluated.
RESULTS: Patients with CF and chronic colonization had anti-PaAb values of 11.6 ± 2.1 ELISA units (EU) and sCD40L in plasma of 1530.9 ±1162.3 pg/mL; those with intermittent infection had 5.7 ± 2.7 EU and 2243.6 ± 1475.9 pg/mL; and those who were never infected had 3.46 ± 1.8 EU (p≤0.001) and 1008.1 ± 746.8 pg/mL (p≤0.01), respectively. The cutoff value of sCD40L of 1255 pg/mL was associated with an area under the ROC (receiver operating characteristic curve) of 0.84 (95% CI, 0.71 to 0.97), reflecting P. aeruginosa infection with a sensitivity of 73% and a specificity of 89%. Lung damage was determined using the Brasfield Score, the Bhalla Score, and spirometry (FVC%, FEV1%) and found to be significantly different among the groups (p≤0.001).
CONCLUSION: Circulating sCD40L levels are increased in patients with cystic fibrosis and P. aeruginosa infection. Soluble CD40L appears to reflect infection and provides a tool for monitoring the evolution of lung deterioration.

PMID: 28030642 [PubMed - in process]