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Improving patient care via development of a protein-based diagnostic test for microbe-specific detection of chronic rhinosinusitis.

ABSTRACT: The hypothesis is that signature bacterial proteins can be identified in sinus secretions via high-throughput, proteomic based techniques. Nontypeable Haemophilus influenzae (NTHI) is the most common bacterial pathogen associated with sinusitis and serves as proof of principle pathogen for identifying biomarkers.In vitro and in vivo studies using proteomic-based analysis of cultures of NTHI and a novel, experimental chinchilla polymicrobial sinusitis model.Nano-liquid chromatography /tandem mass spectrometry (nano-LC-MS/MS) was performed to annotate the secretome from an NTHI biofilm. A model of NTHI-induced sinusitis was developed in a chinchilla, and NTHI proteins were detected in chinchilla secretions. A reference standard RT-PCR-based assay was adapted to allow for sensitivity and specificity testing of the identified signature biomarkers in human patients.Outer membrane proteins P2 (OMP-P2) and P5 (OMP-P5) were identified as promising candidates for the detection of NTHI biofilms and positively detected in nasopharyngeal secretions of chinchillas experimentally infected with NTHI. An RT-PCR based test for the presence of NTHI biofilms demonstrated 100% sensitivity and 100% specificity when tested against eight unique strains commonly found in human bacterial rhinosinusitis.Proteomic analysis was successful in identifying signature proteins for possible use as a biomarker for chronic rhinosinusitis (CRS). OMP-P2 and OMP-P5 were validated as promising candidates and were positively detected from nasopharyngeal secretions from chinchillas experimentally infected with NTHI. Collectively, these data support the use of OMP-P2 and OMP-P5 as biomarkers for a human clinical trial to develop a point-of-care medical diagnostic test to assist in the diagnosis and treatment of CRS.

SUBMITTER: Das S

PROVIDER: S-EPMC4020599 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Improving patient care via development of a protein-based diagnostic test for microbe-specific detection of chronic rhinosinusitis.

Das Subinoy S Rosas Lucia E LE Jurcisek Joseph A JA Novotny Laura A LA Green Kari B KB Bakaletz Lauren O LO

The Laryngoscope 20131002 3

<h4>Objectives/hypothesis</h4>The hypothesis is that signature bacterial proteins can be identified in sinus secretions via high-throughput, proteomic based techniques. Nontypeable Haemophilus influenzae (NTHI) is the most common bacterial pathogen associated with sinusitis and serves as proof of principle pathogen for identifying biomarkers.<h4>Study design</h4>In vitro and in vivo studies using proteomic-based analysis of cultures of NTHI and a novel, experimental chinchilla polymicrobial sinu ...[more]

PMID: 23904321

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Project description:ObjectivesThe concept of disease control incorporates independent disease characteristics that are longitudinally reflective of disease status and which can be used to make treatment decisions. Chronic rhinosinusitis (CRS) is a chronic condition for which the determination of disease control by both the patient and the treating physician is important. Our objectives were to determine CRS disease characteristics that are associated with patient-reported and physician-rated CRS disease control.Study typeCross-sectional.MethodsA total of 209 participants were prospectively recruited. Participants were asked to rate their global level of CRS control as "not at all," "a little," "somewhat," "very," and "completely." All participants completed a 22-item Sinonasal Outcome Test (SNOT-22) and also reported the number of sinus infections, CRS-related antibiotic courses taken, CRS-related oral corticosteroid courses taken, and missed days of work or school due to CRS, all in the last 3 months. Clinical and demographic characteristics were also collected from each participant. A Lund-Kennedy endoscopy score was calculated for each participant from nasal endoscopy. Two rhinologists were then given each participant's SNOT-22 score (as well as SNOT-22 nasal, sleep, otologic/facial pain, and emotional subdomain scores), endoscopy score, and the number of sinus infections, CRS-related antibiotics, CRS-related oral corticosteroid courses and missed days of work or school due to CRS in the preceding 3 months as reported by the patient. The two rhinologists were blinded to all other participant characteristics and each rhinologist independently rated every participant's global control level as "not at all," "a little," "somewhat," "very," and "completely." Associations were sought between CRS disease characteristics (SNOT-22 score, endoscopy score, sinus infections, CRS-related antibiotic usage, CRS-related oral corticosteroid usage, and lost productivity due to CRS) and patient-reported CRS control as well as mean physician-rated CRS control.ResultsPatient-reported global CRS control was associated only with SNOT-22 (adjusted relative risk [RR]?=?0.99, 95% CI: 0.98-0.99, P?<?.001) but no other CRS disease characteristic. Patient-reported CRS control was specifically associated only with nasal symptoms and not extra-nasal symptoms of CRS. Physician-rated CRS control was associated with SNOT-22 score (adjusted RR [for each 1-unit increase of SNOT-22]?=?0.99, 95% CI: 0.98-0.99, P?<?.001), number of acute bacterial CRS exacerbations-reflected by number of antibiotic courses taken (or sinus infections)-in the last 3 months (adjusted RR?=?0.89, 95% CI: 0.82-0.98, P?=?.014) and the number of CRS-related oral corticosteroid courses taken in the last 3 months (adjusted RR?=?0.87, 95% CI: 0.78-0.97, P?=?.012). Nasal, sleep, and otologic/facial pain symptoms were all associated with physician-rated CRS control. Having used at least one course of antibiotics or oral corticosteroids in the last 3 months was the optimal threshold for detecting poorly controlled CRS.ConclusionsPatients and physicians use different criteria to determine the level of CRS control. While both rely on the burden of CRS symptomatology, patients consider primarily nasal symptoms while physicians include nasal and extra-nasal symptoms of CRS in determining CRS control. Physicians also independently consider CRS-related antibiotic use, as a reflection of acute bacterial CRS exacerbations, and CRS-related oral corticosteroid use in the determination of global CRS control.Level of evidence2c.

Project description:ObjectivesTo explore patient views and perspectives of current management of chronic rhinosinusitis (CRS) in primary and secondary care.DesignSemistructured qualitative telephone interviews as part of the MACRO programme (Defining best Management for Adults with Chronic RhinOsinusitis).SettingPrimary care and secondary care ear, nose and throat outpatient clinics in the UK.ParticipantsTwenty-five patients consented to in-depth telephone interviews. Transcribed recordings were managed using NVivo software and analysed using inductive thematic analysis.ResultsCRS has a significant impact on patients' quality of life, affecting their ability to work effectively, their social interactions and daily living. Patients seek help when symptoms become unmanageable, but can become frustrated with the primary care system with difficulties obtaining an appointment, and lack of continuity of care. Patients perceive that general practitioners can be dismissive of CRS symptoms, and patients often prioritise other concerns when they consult. Health system barriers and poor communication can result in delays in accessing appropriate treatment and referral. Adherence to intranasal steroids is a problem and patients are uncertain about correct technique. Nasal irrigation can be time-consuming and difficult for patients to use. Secondary care consultations can appear rushed, and patients would like specialists to take a more 'holistic' approach to their management. Surgery is often considered a temporary solution, appropriate when medical options have been explored.ConclusionsPatients are frustrated with the management of their CRS, and poor communication can result in delays in receiving appropriate treatment and timely referral. Patients seek better understanding of their condition and guidance to support treatments decisions in light of uncertainties around the different medical and surgical options. Better coordinated care between general practice and specialist settings and consistency of advice has the potential to increase patient satisfaction and improve outcomes.

Project description:BackgroundThe aetiology of chronic rhinosinusitis (CRS) is multifactorial with a complex interplay between environmental, microbial endogenous and genetic factors. The impact of outdoor air pollution on prevalence or severity of CRS remains largely unknown.MethodsReal-life geolocation data (2017-2018, Belgium) from 278 CRS patients (2576 health records) using the mySinusitisCoach mobile application were analysed to calculate the patients' individual exposure to outdoor air pollutants (ozone (O3), black carbon (BC), nitrogen dioxide (NO2) and particulate matter with diameter < 2.5 μm (PM2.5)) and to associate these pollutants with the patients' sinus related symptoms measured at multiple occasions by visual analogue scale (VAS).ResultsThe adjusted seasonal model for the spring-summer (n = 1000 health entries, N = 83 patients) population revealed an increase of 6.07 (p < 0.0001) in overall CRS symptom scoring for an interquartile range (IQR) increase in exposure to O3 (26.9 μg/m3). An increase of 1.69 (p = 0.05) in total CRS symptom scoring was observed for an IQR increase of PM2.5 (7.1 µg/m3) exposure. Sex-stratified analysis in the spring-summer population showed significant interaction between air pollution and sex with male patients having higher total CRS symptom scores for an IQR increase in exposure to PM2.5 (3.52, p = 0.001), and O3 (8.33, p < 0.0001), while no significant association with symptom severity was seen in the female patients. In the analysis stratified by comorbid asthma, CRS patients with comorbid asthma had higher total CRS symptoms for an IQR increase in exposure to PM2.5 (2.58, p = 0.04) and O3 (7.72, p < 0.0001) while the patients without comorbid asthma had no significant symptom increases.ConclusionExposure to outdoor air pollution is associated with increased symptom severity in CRS patients. The extent to which CRS patients are sensitive to outdoor air pollution exposure varies per season and depends on their sex and comorbid asthma status. mHealth technology has the potential to reveal novel insights on the patients' exposome and disease severity in the real-life situation.

Dataset Information

Improving patient care via development of a protein-based diagnostic test for microbe-specific detection of chronic rhinosinusitis.

Publications

Improving patient care via development of a protein-based diagnostic test for microbe-specific detection of chronic rhinosinusitis.

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