Burden Of Inflammatory Disease Research Articles

Novel, computational IgE-clustering in a population-based cross-sectional study: Mapping the allergy burden.

Even though the prevalence of allergies is increasing, population-based data are still scarce. As a read-out for chronic inflammatory information, new methods are needed to integrate individual biological measurements and lifestyle parameters to mitigate the consequences and costs of allergic burden for society. More than 480.000 data points were collected from 1462 Luxembourg adults during the representative, cross-sectional European Health Examination Survey, spanning health and lifestyle reports. Deep IgE-profiles based on unsupervised clustering were correlated with data of the health survey. 42.6% of the participants reported a physician-diagnosed allergy and 44% were found to be IgE-positive to at least one allergen or extract. The main sensitization sources were tree pollens followed by grass pollens and mites (52.4%, 51.8% and 40.3% of sensitized participants respectively), suggesting seasonal as well as perennial burden. The youngest group of participants (25-34years old) showed the highest burden of sensitization, with 18.2% of them having IgE to 10 or more allergen groups. Unsupervised clustering revealed that the biggest cluster of 24.4% of participants was also the one with the highest medical need, marked by their multi-sensitization to respiratory sources. Our novel approach to analyzing large biosample datasets together with health information allows the measurement of the chronic inflammatory disease burden in the general population and led to the identification of the most vulnerable groups in need of better medical care.

More than skin-deep: visceral fat is strongly associated with disease activity, function and metabolic indices in psoriatic disease

ObjectiveTo compare body composition between patients with psoriatic disease (PsD), including cutaneous psoriasis (PsO) and psoriatic arthritis (PsA), and controls, and to explore associations between disease activity and measures of function and metabolic derangement.MethodsBody composition was assessed by air displacement plethysmography (ADP) and MRI-derived fat segmentation using an automated pipeline (FatSegNet). Function was assessed by Health Assessment Questionnaire (HAQ) and metabolic status by fasting lipid profile, insulin and adiponectin. Active and inactive PsO and PsA were defined by body surface area (BSA) and Psoriasis Area Severity Index (PASI) and minimal disease activity (MDA), respectively.ResultsThirty patients (median disease duration 15 years; median age 52 years) and 30 BMI-matched controls were enrolled. Compared with controls, all MRI-derived body composition parameters—whole-body volume, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), abdominal adipose tissue (AAT), VAT/AAT and VAT/SAT—were higher in the PsD group, specifically, those with active disease. Body mass, body fat, whole-body volume and whole-body VAT were correlated with higher triglycerides, cholesterol:HDL (high-density lipoprotein), insulin resistance and lower adiponectin as well as higher HAQ and lower MDA.ConclusionsIn this pilot study, patients with PsD revealed excessive total adipose tissue and a greater volume of metabolically unfavourable ectopic fat, including VAT, compared with BMI-matched controls, which also correlated with HAQ, disease activity and overall dysmetabolism. We also provide the first evidence in patients with PsD for the clinical application of FatSegNet: a novel, automated and rapid deep learning pipeline for providing accurate MRI-based measurement of fat segmentation. Our findings suggest the need for a more integrated approach to the management of PsD, which considers both the metabolic and inflammatory burden of disease. More specifically, visceral fat is a surrogate marker of uncontrolled PsD and may be an important future target for both pharmacological and lifestyle interventions.

Mean Platelet Volume as a Marker of Sepsis in Newborn

Introduction: Neonatal sepsis is the leading cause of death in developing country like India and we need early diagnosis and treatment to prevent mortality so we require better diagnostic marker for sepsis. Mean platelet volume (MPV) is a measure of average platelet volume which represents inflammatory burden of disease. In our study MPV rises in septic neonates significantly and can be helpful to diagnose sepsis early with other blood counts. Methods: This case-control study was done on 500 newborns, out of which 452 included in study are classified into two groups that is group A (n = 226): apparently healthy neonates, group B (n = 226): diagnosed with neonatal sepsis by septic screening positive. All patients in the study were go through adequate valuation of their history, clinical examination, complete blood count including MPV, C-reactive protein (CRP) and blood culture. Results: Septic neonates showed statistically higher values of MPV than the control group. The diagnostic cut-off value of MPV NS was 10.2 fl. Conclusions: MPV which is a platelet index obtained from complete blood count can be used an additional marker along with established septic screen to ensure early diagnosis in neonatal sepsis.

Pain experiences among those living with hidradenitis suppurativa: a qualitative study.

Pain is rated by patients with hidradenitis suppurativa (HS) as the disease's most impactful symptom. HS therapies are often insufficient to control inflammatory disease activity and pain. A better understanding of patient experiences with pain may improve patient-provider relationships and help identify strategies for addressing HS pain. This qualitative study sought to characterize lived pain experiences of those with HS. English-speaking patients ≥ 18 years old with a dermatologist-confirmed diagnosis of HS and an average numerical rating scale pain score of ≥ 1 over the preceding week were recruited from a single academic medical centre in Atlanta, Georgia, USA. Semistructured interviews were conducted from November 2019 to March 2020 to explore participants' HS pain experiences and the subsequent impact on their lives. Thematic saturation was reached after interviewing 21 participants. Interviews were audio recorded, transcribed, and analysed using thematic analysis. Among 21 study participants, the median 7-day average pain score was 6 (interquartile range 3-7; scale ranges from 0 to 10, with 10 being most pain). Participants' descriptions of pain were consistent with nociceptive pain, neuropathic pain and itch. Pain impacted multiple life domains, including physical limitations (decreased mobility and impaired sleep), decreased psychological wellbeing (irritability, depression, loss of control, and difficulty communicating pain experiences) and impaired social relationships (social isolation, intimacy problems and difficulty fulfilling social responsibilities). Although participants reported chronic discomfort, acutely painful and unpredictable HS disease flares caused more distress and quality-of-life (QoL) burden. Participants frequently treated their pain without input from the medical team, sometimes with unsafe medication doses or combinations. Factors contributing to self-management of pain included difficulty accessing timely outpatient care during disease flares and fear of stigma from healthcare providers. When present, HS-related pain may impact not only physical wellbeing but also mental health and relationships. In addition to therapies that target the inflammatory disease burden, treating the symptom of pain may improve patients' QoL and wellbeing. Because patients with HS have difficulty explaining their pain, proactively asking them about pain may identify unmet needs, facilitate better pain control and improve QoL. Further, the influence of HS-related pain on numerous aspects of QoL suggests the need for multidisciplinary, patient-centred approaches to HS pain management.

Nasal Nitric Oxide as a Biomarker in the Diagnosis and Treatment of Sinonasal Inflammatory Diseases: A Review of the Literature.

To critically review the literature on nasal nitric oxide (nNO) and its current clinical and research applicability in the diagnosis and treatment of different sinonasal inflammatory diseases, including acute bacterial rhinosinusitis (ABRS), allergic rhinitis (AR), and chronic rhinosinusitis (CRS). A search of the PubMed database was conducted to include articles on nNO and sinonasal diseases from January 2003 to January 2020. All article titles and abstracts were reviewed to assess their relevance to nNO and ABRS, AR, or CRS. After selection of the manuscripts, full-text reviews were performed to synthesize current understandings of nNO and its applications to the various sinonasal inflammatory diseases. A total of 79 relevant studies from an initial 559 articles were identified using our focused search and review criteria. nNO has been consistently shown to be decreased in ABRS and CRS, especially in cases with nasal polyps. While AR is associated with elevations in nNO, nNO levels have also been found to be lower in AR cases with higher symptom severity. The obstruction of the paranasal sinuses is speculated to be an important variable in the relationship between nNO and the sinonasal diseases. Treatment of these diseases appears to affect nNO through the reduction of inflammatory disease burden and also mitigation of sinus obstruction. nNO has been of increasing interest to researchers and clinicians over the last decade. The most compelling data for nNO as a clinical tool involve CRS. nNO can be used as a marker of ostiomeatal complex patency. Variations in measurement techniques and technology continue to impede standardized interpretation and implementation of nNO as a biomarker for sinonasal inflammatory diseases.

Association Between a Type 2 Inflammatory Disease Burden Score and Outcomes Among Patients with Asthma

BackgroundAlthough prevalence of co-existing type 2 inflammatory diseases (cT2) in asthma patients has been reported, limited data exist regarding their impact on asthma outcomes.ObjectiveTo assess the impact of cT2 burden on asthma outcomes and to evaluate patterns of clustering of cT2 in a real-world setting.MethodsFrom medical records of 4.5 million enrollees in 650 primary care practices in the UK (January 2010–December 2017), patients with ≥1 diagnosis code for asthma at any time pre-index date (date of most recent asthma-related medical encounter) and ≥2 asthma-related prescriptions during the year before index date were categorized into the Global Initiative of Asthma (GINA) guideline severity steps. A cT2 burden score (range 0–9) was assigned based on the total number of co-existing conditions (allergic conjunctivitis, allergic rhinitis, anaphylaxis, eczema/atopic dermatitis, chronic rhinosinusitis, eosinophilic esophagitis, food allergy, nasal polyps, or urticaria) for which patients received a medical diagnosis. Multivariate regression models evaluated associations between cT2 burden score and asthma exacerbations and asthma control. Factor analysis was performed to assess which cT2 comorbidities were correlated and exhibited patterns of clustering.ResultsOverall, 245,893 patients with asthma were included (mean [SD] age 44.8 [22.1] years; 43.8% male). Between 55% (GINA step 1) and 60% (GINA step 5) of asthma patients had a medical diagnosis for ≥1 other type2dx. Patients with increased cT2 burden were significantly more likely to experience asthma exacerbations and less likely to achieve asthma control.ConclusionAsthma patients with a higher cumulative cT2 burden score were more likely to experience worse asthma outcomes than those without any cT2 (burden score of 0).

692 Low Levels of Ustekinumab Despite Dose Escalation Is a Risk Factor for Surgery

INTRODUCTION: Ustekinumab is an IL-12/23 inhibitor used for the treatment of Crohn's disease (CD). Previous studies have suggested that dose escalation to every 4-week intervals can be beneficial in patients who do not achieve a clinical response on every 8-week maintenance dosing. However, safety and efficacy is unknown in CD patients escalated to more frequently than every 4-week intervals in patients who continue to have low trough drug levels. METHODS: We performed a retrospective chart review of patients on ustekinumab for CD who had dosing escalation to every two weeks (Q2) due to persistent low drug levels (<5 µg/mL) despite being on q4 weeks (Q4) maintenance dosing and clinically losing response. RESULTS: Out of 200 CD patients on ustekinumab 90 mg subcutaneous (SQ) maintenance in our IBD program, 112 underwent reactive therapeutic drug monitoring for loss of response or incomplete response to therapy. Of the 112 with drug levels, none had anti-drug antibodies, but 80 patients had levels <5 mcg/mL. All 80 patients were frequency escalated to q4 week dosing. Of these, 12 patients continued to have low ustekinumab trough levels at week 4 (<5 mcg/mL) and thus were escalated to Q2 week dosing. Eight of the 12 patients had IV reinduction dosing prior to dose escalation to Q2 frequency. Of the 12 patients, 6 (50%) required surgery for their active Crohn's disease. These patients were on Q2 week dosing for median of 16 weeks (range 1-68) prior to surgery. All 6 (100%) were able to be de-escalate to less frequent dosing after surgery. Two patients that were unable to de-escalate their dosing frequency are planning for surgery in the near future. The remaining four patients were able to de-escalate to Q4 dosing after clinical response. See full details in Table 1. No adverse events unrelated to their Crohn's disease, including infections or other safety markers were noted. CONCLUSION: Low levels of ustekinumab despite escalation of dosing to every 2 weeks may suggest a need for Crohn's disease related surgery. In our study, all patients who underwent surgery were able to de-escalate to lower dosing frequency suggesting that high inflammatory disease burden contributed to the low levels of ustekinumab. Further studies are needed to assess the safety and efficacy of high frequency dosing of ustekinumab.

Estimated burden of Chlamydia trachomatis female infection and consequent severe pelvic inflammatory disease, Italy, 2005-2016.

Chlamydia trachomatis (Ct) is the leading sexually transmitted infection (STI) across Europe. In Italy, Ct prevalence is low in general population, but predominance of asymptomatic infections, passive voluntary reporting, variable diagnostic criteria and coding practices can lead to considerable underestimation, preventing assessment of real burden of disease and health intervention. We analysed data on female genital Ct infection registered in STI sentinel surveillance systems in Italy from 2005 through 2016 and found 3305 women. Among them, those aged 20-24 years had the highest disability-adjusted life years (DALYs) estimation equal to 106.77 DALYs per 100 000-stratum specific population. Through the study period, incidence rate (IR) for female Ct infection increased significantly from 2.9 to 7.1 per 100 000 resident population. Besides, we analysed data on pelvic inflammatory disease (PID) reported from the National Hospital Information system (NHIS) in the same period. We found 287 women hospitalised with concurrent PID and Ct infection. We recommend targeted screening programmes in women aged 20-24, definition of nationwide active surveillance system, standardisation of diagnostic criteria and ICD-9CM coding practices.

Biomarker-Based Models Outperform Patient-Reported Scores in Predicting Endoscopic Inflammatory Disease Activity.

The Crohn's Disease Activity Index (CDAI), a scoring index including patient-reported outcomes (PROs), has known limitations for measuring intestinal inflammatory disease burden. Noninvasive markers of inflammation could prove more accurate than PROs; thus, regulatory authorities are exploring the use of PROs and endoscopic data as coprimary end points in clinical trials. The aim of this study was to assess the predictive ability of individual components of the CDAI, along with biomarker concentrations, to create models for predicting endoscopic disease activity. Between 2004 and 2006, 164 patients with established Crohn's disease (CD) undergoing clinically indicated ileocolonoscopy were recruited. Individual CDAI variables and fecal calprotectin (FC) were selected to explore their predictive accuracy for endoscopic disease activity, with the Simple Endoscopic Score-Crohn's Disease (SES-CD) as the outcome variable. Simple Poisson regression was performed on each variable, and 2 multivariate models were created (PRO-exclusive and PRO+FC [PRO+]). Additional analyses explored the patient-level agreement between models. Number of liquid stools, abdominal pain, hematocrit (Hct), FC, and high-sensitivity C-reactive protein (hsCRP) correlated significantly with the SES-CD. For the prediction of SES-CD (>7 vs ≤6), the area under the curve (AUC) was 0.81, with 63% and 88% sensitivity and specificity, for the PRO+ model, compared with a 0.56 AUC, with 61% and 55%, respectively, for the PRO model. Intra-individual comparison revealed the PRO+ model to be superior in the prediction of endoscopically active disease. The inclusion of biomarkers significantly improved predictive accuracy for endoscopic disease activity compared with PRO-exclusive models.

The inflammatory disease burden at presentation is a good indicator of early LDA/remission: A retrospective study

Background: Factors predicting early response to treatment in rheumatoid arthritis (RA) assist in optimizing treatment strategies. DAS28CRP is routinely used to measure treatment response, whereas the role of associated biomarkers has not been thoroughly assessed. Objective: To examine the clinical utility of baseline demographic, clinical, and immunological parameters as predictors of early response to treatment in RA patients. To develop an empirical equation to assess the probability of early remission. Methods: We included data from newly diagnosed RA patients who fulfilled ACR-EULAR 2010 classification criteria in an exploratory, retrospective observational study. Patients’ initial assessment and follow-up data were collected. Variables were assessed by t-test or Mann-Whitney test as appropriate, univariate regression and receiver operating characteristic (ROC) curve. A predictive equation was developed using multiple logistic regression. Model accuracy evaluated by ROC curve. The bootstrap procedure was used to assess internal validity. Results: The study included 159 patients after screening for inclusion and exclusion criteria. A multivariate logistic regression with age, hemoglobin percentage (Hb%), neutrophil-to-lymphocyte ratio (NLR) and DASCRP was performed. The discriminatory ability of the predictive model was fair, area under the curve (AUC) = 0.711 (95% CI- 0.630-0.792) with P-value <0.001 and calibration slope of 0.98. The corresponding sensitivity and specificity noted were 49.2%, and 78.7%. The bias-corrected C index was 0.683. Conclusion: This multivariate logistic equation improves on currently recommended methods of screening for remission. The baseline DAS28CRP score is a strong predictor and inclusion of additional factors like NLR and Hb% contribute to prediction. Further studies in a large cohort could improve and confirm these results.

Inflammation-a Critical Appreciation of the Role of Myeloid Cells.

What is inflammation's big idea? In this brief overview of the role of myeloid cells in inflammation, we will critically discuss what drives the initiation, amplification, and resolution of inflammation in different anatomical sites in response to different pathological stimuli. It can be argued that we have a good understanding of the basic principles that underlie myeloid cell activation and the mobilization of innate immune cells to sites of injury and infection in acute inflammation. The challenge now for inflammation biologists is to understand how resolution of this normal physiological response goes wrong in hyperacute and chronic inflammation. A better understanding of how inflammation is regulated will allow us to develop new anti-inflammatory drugs that will reduce the burden of inflammatory disease without compromising the patient's immune defenses against infectious disease. Ideally such drugs should encourage a return to homeostasis and enhance tissue repair processes.

Emerging Epidemic of Inflammatory Bowel Disease in a Middle Income Country: A Nation-wide Study from Iran.

The burden of inflammatory bowel disease (IBD) hasn't been reported in Iran. We aimed to estimate the prevalence and incidence of IBD and its trend in Iran at national and subnational level from 1990 to 2012. We conducted a systematic review of English and Persian databases about the epidemiology of IBD. We also collected outpatient data from 17 provinces of Iran using almost all public and private referral gastroenterology clinics. Prevalence and incidence rate was calculated at national and subnational levels. The Kriging method was used to extrapolate provinces with missing data and GPR model to calculate time trends of rates at subnational level. We found 16 case series, two population-based studies, and two review articles. We collected 11,000 IBD cases from outpatient databases. Among them, 9,269 (84.26%) had ulcerative colitis (UC), 1,646 (14.96%) had Crohn's disease (CD), and 85 had intermediate colitis (IC). A total of 5,452 (49.56%) patients were male. Mean age at diagnosis was 32.80 years (CI: 13 - 61) for UC and 29.98 years (CI: 11 - 58) for CD. Annual incidences of IBD, UC, and CD in 2012 were 3.11, 2.70, and 0.41 per 100,000 subjects respectively. Prevalence of IBD, UC, and CD in 2012 were 40.67, 35.52, and 5.03 per 100,000 subjects respectively. The incidence of UC and CD showed a significant increase during the study period (P for trend < 0.05). The incidence and prevalence of IBD are increasing in Iran. Establishing a national IBD registry seems necessary for comprehensive care of IBD patients in Iran.

Increased levels of circulating platelet-derived microparticles in psoriasis: Possible implications for the associated cardiovascular risk.

AIMTo evaluate platelet activation markers in psoriasis patients, compared to controls, and investigate their association with the inflammatory burden of psoriasis.METHODSForty psoriatic patients without cardiovascular disease, and 12 healthy controls were subjected to measurement of baseline platelet CD62P, CD63 and CD42b expression, platelet-leukocyte complexes, i.e., platelet-monocyte complexes (PMC), platelet-neutrophil complexes (PNC) and platelet-lymphocyte complexes, and concentrations of platelet-derived microparticles (PMPs) using flow cytometry. Both larger-size (0.5-0.9 μm) and smaller-size (< 0.5 μm) PMPs were determined. Serum interleukin (IL)-12 and IL-17 levels were also measured by enzyme-linked immunosorbent assay. The severity of psoriasis was evaluated by the Psoriasis Area Severity Index (PASI).RESULTSPMP concentrations were significantly higher in psoriasis patients than controls [mean ± standard error of mean (SEM): 22 ± 5/μL vs 11 ± 6/μL; P = 0.018), for both smaller-size (10 ± 2/μL vs 4 ± 2/μL; P = 0.033) and larger-size (12 ± 3/μL vs 6 ± 4/μL; P = 0.014) PMPs. Platelet CD62P, CD63 and CD42b expression and circulating PMC and PNC were similar between the two groups. Lower circulating PLC were observed in psoriasis patients compared to controls (mean ± SEM: 16% ± 3% vs 23% ± 6%; P = 0.047). Larger-size PMPs were related with IL-12 levels (P < 0.001) and smaller-size PMPs with both IL-12 and IL-17 levels (P < 0.001). Total PMPs also correlated with IL-12 (P < 0.001). CD63 expression was positively correlated with both IL-12 and IL-17 (P < 0.05). Increased PASI score was associated with increased levels of larger-size PMPs (r = 0.45; P = 0.011) and increased CD63 expression (r = 0.47; P < 0.01).CONCLUSIONPMPs, known to be predictive of cardiovascular outcomes, are increased in psoriasis patients, and associated with high inflammatory disease burden. Enhanced platelet activation may be the missing link leading to cardiovascular events in psoriatic patients.

Objectifying the Crohnʼs Disease Activity Index (CDAI): Can We Teach an Old Score New Tricks?: Presidential Poster

Purpose: The CDAI has known limitations, but is still a widely used and accepted instrument in the conduct of clinical trials. Advances in disease assessment and monitoring have led to the development of non-invasive, objective biomarkers of inflammatory disease activity. The CDAI's utility for accurately measuring inflammatory disease burden in CD is questionable. The objective of this study was to compare the predictive ability of patient-reported outcome (PRO)-based and biomarker-based models for endoscopic inflammatory disease activity in subjects with CD. Methods: Between 2004 and 2006, 164 adults with established CD undergoing clinically indicated ileocolonoscopy were recruited to participate in this study. Demographic (gender, age, smoking status, BMI), disease-related (CDAI, number of resections), endoscopic (SES-CD), and biomarker (fecal calprotectin [FC[, IL-6, hsCRP) variables were collected. Endoscopists were blinded to biomarker and CDAI values. The SES-CD was the independent variable against which CDAI was compared. Eight variables from the original CDAI, along with 6 new variables (BMI, smoking status, surgical resection, FC, IL-6, hsCRP) were selected to explore their influence on predictive accuracy for endoscopic disease activity. Simple Poisson regression was performed on each of the variables individually. A robust multivariate model was built using a cross-validated bootstrapping approach. Results: In univariate pre-screening, antidiarrheal/opiate use, smoking status, and presence of resection correlated weakly with the SES-CD score. Abdominal mass, IL-6, and standardized weight were dropped from the model. The remaining variables were added to a bootstrapaggregating (bagging) Poisson regression model. Five variables significantly and consistently related to SES-CD in a multivariate Poisson regression model: number of liquid or soft stools, sum of 7-day abdominal pain ratings, hematocrit (Hct), FC, and hsCRP. For the prediction of SES-CD ≥3 versus ≤ 2, the area under the curve (AUC) was 0.552 (95% CI: [0.543, 0.562]), with sensitivity and specificity of 65.2% and 51.8% for CDAI, compared to 0.682 AUC (95% CI: [0.673, 0.691]) with sensitivity and specificity of 51.1% and 82.9% for the new model, and 0.598 AUC (95% CI: [0.590, 0.608]) with sensitivity and specificity values of 34.2% and 86.4% for a PRO-exclusive model. Conclusion: The CDAI correlates poorly with SES-CD. Incorporation of inflammatory biomarkers into models can improve predictive accuracy for endoscopically active disease. PRO-exclusive models remain inferior to biomarker-based models. Model adaptation to account for variability in SES-CD subcomponents related to inter-subject variability will be explored in the future.

THU0114 Abatacept as an effective treatment in the management of poor prognosis ACPA negative undifferentiated arthritis

BackgroundA goal in the management of undifferentiated arthritis (UA) is to prevent its progression to rheumatoid arthritis (RA). A preliminary study suggested abatacept may delay progression of ACPA positive UA...

Examining the Risk of Cardiovascular Disease in Patients with Psoriasis: A Critical Review

Increased prevalence of cardiovascular disease (CVD) in psoriasis patients could be due to a greater prevalence of traditional cardiovascular (CV) risk factors or increased inflammatory disease burden. To critically evaluate evidence on the etiology and magnitude of CV risk in psoriasis patients. A total of 497 articles were identified for review through a PubMed search using the terms "CVD and psoriasis"; 43 were selected. Data measuring the risk of comorbidities and CV risk factors in psoriasis were retrieved. Psoriasis patients have an increased prevalence of CV risk factors. Evidence suggests an increased risk of CV morbidity and mortality associated with psoriasis itself. Risk estimates vary across studies (OR range 1.13-6.48), possibly due to heterogeneous study design and incomplete data. Although additional data are required, increased awareness of the association of psoriasis with CV risk factors could lead to early diagnosis and treatment of comorbidities, with resultant improvement in morbidity and mortality.

Periodontal Disease Burden and Pathological Changes in Organs of Dogs

Bacterial plaque associated periodontal disease is the most common chronic infection in man and dogs. In man, there is an association between periodontal disease and myocardial infarction and stroke, while in dogs it has also been associated with changes in internal organs. Inflamed periodontal tissues present a 'periodontal disease burden' to the host and the extent of this inflammatory disease burden is likely to affect the degree of associated pathological change in distant organs. This hypothesis was investigated in dogs with naturally occurring periodontal disease. Post-mortem investigations including periodontal assessment, standard necropsy, and organ histology were performed on 44 mature toy and miniature Poodles (related, periodontitis predisposed breeds) that died naturally or were euthanized based on clinical disease. Animals with gross primary organ pathology were excluded. The periodontal disease burden was estimated from the total surface area of periodontal pocket epithelium using six measurements of probing depth for each tooth and the tooth circumferences. Ordinal logistic regression (OR) analysis established that for each square centimeter of periodontal disease burden there was a 1.4-times higher likelihood of greater changes being present in the left atrio-ventricular valves (OR = 1.43), plus 1.2 and 1.4 times higher likelihoodfor greater liver and kidney pathology (OR = 1.21; OR = 1.42), respectively The results show that there is a link between the estimated 'periodontal disease burden' resulting from plaque-bacteria associated periodontal disease and the level of internal pathology in this population, implying that periodontitis might contribute to the development of systemic pathology in dogs.

Starting early

Multiple sclerosis (MS) is considered an inflammatory autoimmune disease of CNS white matter. Quantitative MRI measures of visible white matter lesion load, however, have shown that the burden of inflammatory disease is a relatively insensitive metric of physical disability, cognitive impairment, or long-term prognosis. While MRI has proven to be an invaluable tool for MS diagnosis and response to anti-inflammatory based therapies, 1 the relatively poor correlation between measures of inflammation and clinical sequelae has prompted revitalized recognition of the neurodegenerative aspects of MS. Pathologic studies have emphasized the extensive network of axonal transactions and neuronal cell loss in lesional and normal-appearing white matter (NAWM), and have confirmed that a significant aspect of MS pathology also resides in cortical and subcortical gray matter. Advances in MR imaging are ever-increasingly able to detect lesions in the cerebral mantle and in deep gray structures,2 gray matter loss can be detected even at the time of an initial demyelinating event,3 and apparently NAWM in patients with MS has been shown to have reduced structural integrity. …

Visualization of pulmonary inflammation using noninvasive fluorescence molecular imaging

The ability to visualize molecular processes and cellular regulators of complex pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), or adult respiratory distress syndrome (ARDS), would aid in the diagnosis, differentiation, therapy assessment and in small animal-based drug-discovery processes. Herein we report the application of normalized transillumination and fluorescence molecular tomography (FMT) for the noninvasive quantitative imaging of the mouse lung in vivo. We demonstrate the ability to visualize and quantitate pulmonary response in a murine model of LPS-induced airway inflammation. Twenty-four hours prior to imaging, BALB/c female mice were injected via tail vein with 2 nmol of a cathepsin-sensitive activatable fluorescent probe (excitation: 750 nm; emission: 780 nm) and 2 nmol of accompanying intravascular agent (excitation: 674 nm; emission: 694 nm). Six hours later, the mice were anesthetized with isoflurane and administered intranasal LPS in sterile 0.9% saline in 25 microl aliquots (one per nostril). Fluorescence molecular imaging revealed the in vivo profile of cysteine protease activation and vascular distribution within the lung typifying the inflammatory response to LPS insult. Results were correlated with standard in vitro laboratory tests (Western blot, bronchoalveolar lavage or BAL analysis, immunohistochemistry) and revealed good correlation with the underlying activity. We demonstrated the capacity of fluorescence tomography to noninvasively and longitudinally characterize physiological, cellular, and subcellular processes associated with inflammatory disease burden in the lung. The data presented herein serve to further evince fluorescence molecular imaging as a technology highly appropriate for the biomedical laboratory.

Chronic Inflammatory Autoimmune Disorders and Atherosclerosis

Rheumatoid arthritis (RA), periodontal disease (PD), and coronary artery disease (CAD) are common chronic inflammatory diseases. RA is associated with accelerated vascular risk resulting in an increased prevalence of CAD with attendant early mortality and excess morbidity. RA and PD have a common pathobiology. Accordingly, the aim of this study was to evaluate the association between RA, PD, and CAD and the influence of systemic inflammatory factors. A total of 100 active RA patients of which 50 had established CAD and 50 had no CAD were assessed for PD. All subjects underwent a clinical, cardiac, dental, laboratory, and radiological evaluation. Blood samples were obtained and the level of high-sensitivity C-reactive protein (hs-CRP), total white blood counts (WBC), erythrocyte sedimentation rate (ESR), fibrinogen and tumor necrosis alpha (TNF-alpha), total cholesterol (TC), and high-density lipoprotein (HDL) were assayed. The findings of this study demonstrated an association between RA, PD, and CAD. The RA patients with CAD had significantly more PD than RA patients without CAD, P < 0.001. The inflammatory markers hs-CRP, ESR, WBC, fibrinogen, and TNF-alpha were raised in all patients but were significantly higher in RA patients with CAD who also had PD, that is, in those with more inflammatory disease burden. HDL levels were lower in RA patients with CAD when compared to RA patients without CAD, P < 0.005. Evidence from this study shows an association between RA, PD, CAD, and systemic levels of the inflammatory mediators. The implication is that inflammation may be the central link between the chronic inflammatory autoimmune disorders and atherosclerosis.