Disease Severity In Adults Research Articles

Correlates of self-reported quality of life in adults and children with morphea

Determining a disease's impact on life quality is important in clinical decision making, research, and resource allocation. Determinants of quality of life (QOL) in morphea are poorly understood. We sought to ascertain demographic and clinical variables correlated with negative impact on self-reported QOL in morphea. We conducted a cross-sectional survey of the Morphea in Adults and Children cohort. Symptoms (pruritus and pain) and functional impairment were correlated with decreased QOL in children and adults. This was true in both sexes and was independent of subtype and age. Patient-reported QOL correlated with physician-based measures of disease severity in adults, but not in children. Patients with linear and generalized morphea had the greatest impact on QOL. Small sample size is a limitation. Symptoms and functional impairment were determinants of impaired life quality in both children and adults independent of morphea subtype. These results suggest that clinicians should consider suppressing the accumulation of new lesions (when rapidly accumulating) and symptoms (pain and pruritus) in the treatment of patients with morphea.

Association between pneumococcal load and disease severity in adults with pneumonia

Determination of pneumococcal load by quantitative PCR may be useful for diagnostic and prognostic purposes. We hypothesized that higher pneumococcal load would be associated with increased pneumonia severity. Therefore, we tested serum, sputum and urine specimens from 304 adults with community-acquired pneumonia by using a quantitative lytA pneumococcal real-time PCR assay. The association between pneumococcal load and disease severity was assessed using several markers of severity: CURBage score, PSI risk class, intensive care unit admission, in-hospital death and admission duration. For PCR-positive specimens, the bacterial loads were higher in sputum specimens [median 8.55×10(5) copies ml(-1); interquartile range (IQR) 4.70×10(4)-4.69×10(6) copies ml(-1)] than either serum (median 180 copies ml(-1); IQR 165-8970 copies ml(-1)) or urine (median 623 copies ml(-1); IQR 510-650 copies ml(-1)). Detection of pneumococcal DNA in serum was associated with severe disease, and there was evidence of a dose-response effect with increased bacterial load being associated with increased severity. The same observations were not observed for other specimen types. This study adds to an increasing body of evidence suggesting that determination of pneumococcal load has a clinical utility. Further work is needed to determine whether measuring pneumococcal load in respiratory specimens from adults will differentiate colonization from coincidental carriage.

Do Adult Disease Severity Subclassifications Predict Use of Cyclophosphamide in Children with ANCA-associated Vasculitis? An Analysis of ARChiVe Study Treatment Decisions

To determine whether adult disease severity subclassification systems for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are concordant with the decision to treat pediatric patients with cyclophosphamide (CYC). We applied the European Vasculitis Study (EUVAS) and Wegener's Granulomatosis Etanercept Trial (WGET) disease severity subclassification systems to pediatric patients with AAV in A Registry for Childhood Vasculitis (ARChiVe). Modifications were made to the EUVAS and WGET systems to enable their application to this cohort of children. Treatment was categorized into 2 groups, "cyclophosphamide" and "no cyclophosphamide." Pearson's chi-square and Kendall's rank correlation coefficient statistical analyses were used to determine the relationship between disease severity subgroup and treatment at the time of diagnosis. In total, 125 children with AAV were studied. Severity subgroup was associated with treatment group in both the EUVAS (chi-square 45.14, p < 0.001, Kendall's tau-b 0.601, p < 0.001) and WGET (chi-square 59.33, p < 0.001, Kendall's tau-b 0.689, p < 0.001) systems; however, 7 children classified by both systems as having less severe disease received CYC, and 6 children classified as having severe disease by both systems did not receive CYC. In this pediatric AAV cohort, the EUVAS and WGET adult severity subclassification systems had strong correlation with physician choice of treatment. However, a proportion of patients received treatment that was not concordant with their assigned severity subclass.

The role of IL-18 in atopic dermatitis

Evaluation of: Kou K, Aihara M, Matsunaga T et al. Association of serum interleukin-18 and other biomarkers with disease severity in adults with atopic dermatitis. Arch. Dermatol. Res. doi:10.1007/s00403-011-1198-9 (2011) (Epub ahead of print).Atopic dermatitis (AD) is a frequent, chronic, inflammatory skin disease. Immunological and genetic factors followed by skin barrier dysfunction are the main causes of AD development. IL-18 is considered as a new factor involved in AD pathogenesis. The previous studies confirmed that the serum level of IL-18 is elevated in patients with AD, but its association with severity of the disease remains ambiguous. We review the recent paper by Kou et al. that identified biomarkers associated with clinical severity in adult AD patients. Results from this study indicate that IL-18 levels are significantly associated with Scoring Atopic Dermatitis (SCORAD) score, as well as TARC, total IgE and LDH levels. The authors suggest that a panel of these biomarkers may be a more usef...

Hypovitaminosis D in Adults with Inflammatory Bowel Disease: Potential Role of Ethnicity

Although vitamin D deficiency occurs in inflammatory bowel disease (IBD), it is currently unclear to what extent ethnicity affects vitamin D levels. Our aim was therefore to determine the ethnic variation in serum 25-hydroxyvitamin D status and its association with disease severity in adults with IBD. We conducted a prospective cohort study in ambulatory care IBD patients. Clinical disease severity was assessed through validated questionnaires. Serum 25-hydroxyvitamin D levels were used for vitamin D status. C-reactive protein (CRP), ferritin and hemoglobin (Hgb) levels were correlated with serum 25-hydroxyvitamin D levels. Sixty ulcerative colitis (UC) and forty Crohn's disease (CD) patients were enrolled comprising 65 % Caucasians and 29 % South Asians. However, South Asians had consistently lower average serum 25-hydroxyvitamin D levels (All 44.8 ± 18.1 nmol/L, UC 48.2 ± 18.3 nmol/L, CD 24.3 ± 13.3 nmol/L). Hypovitaminosis D was found in 39 % of All, 36.7 % of UC and 42.5 % of CD patients. A significantly higher proportion of South Asians were vitamin D deficient when compared to Caucasians in All and CD groups (58.6 % vs. 30.8 %, p = 0.01 and 85.7 % vs. 32.3 %, p < 0.01, respectively). A significantly higher percentage of South Asians had hypovitaminosis D when compared to Caucasians. Disease severity trended towards an inverse relationship with vitamin D status in all South Asian and Caucasian CD patients, although most patients in this study had only mild to moderate disease. We suggest that vitamin D supplementation should be considered in all adult IBD patients.

Association of serum interleukin-18 and other biomarkers with disease severity in adults with atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin for which there are no reliable biomarkers to assess clinical severity. Serum interleukin-18 (IL-18) levels may be associated with AD severity. To identify putative biomarkers associated with clinical severity in adult AD patients, we enrolled 121 adult AD patients (mean age 35.7years) and 50 healthy controls (mean age 31.7years). We compared these groups for blood eosinophils and serum levels of IL-18, thymus and activation-regulated chemokine (TARC), total IgE, and lactate dehydrogenase (LDH). We also determined S. aureus enterotoxin B (SEB) specific IgE levels and the SCORingAD (SCORAD) scores for AD patients. For AD patients, stepwise logistic regression was used to estimate odds ratios (OR) for each biomarker for the likelihood of having AD, and multiple linear regression was used to identify biomarkers associated with SCORAD scores. Compared with healthy controls, adult AD patients had higher levels of IL-18, TARC, total IgE, eosinophils, and LDH. TARC levels had the highest OR for AD occurrence, while the OR for IL-18 was insignificant. Also, IL-18 was not related to the presence of SEB-IgE. Notably, IL-18 levels were significantly associated with SCORAD scores, as were TARC, total IgE, and LDH levels. A panel of biomarkers (IL-18, TARC, total IgE, and LDH) may be more useful to accurately assess clinical severity in adult AD patients.

Association of Intracellular TH1-TH2 Balance in CD4+ T-cells and MIP-1α in CD8+ T-cells with Disease Severity in Adults with Dengue

BackgroundWe tested the hypothesis that dengue haemorrhagic fever (DHF) is associated with a TH1-skewed immune response as opposed to dengue fever (DF).MethodsWe estimated intracellular (in T-cells) and serum levels of designate TH1/TH2 cytokines [interferon-γ (IFN-γ), interleukin-4 (IL-4), and tumor necrosis factor-α] and macrophage inflammatory protein-1α (MIP-1α) at admission, 48 h, and day 5 in 20 adults with dengue (DF=10, DHF=10) and 10 dengue-naïve healthy controls.ResultsAt admission, intracellular IFN-γ/IL-4 ratio in CD4+ T-cells and proportion of MIP-1α-positive CD8+ T-cells were significantly higher in patients with DHF [7.21 (5.36~10.81) vs. 3.04 (1.75~4.02); p=0.011 and 6.2% (3.2~8.2%) vs. 2.4% (2.0~3.6%); p=0.023]. The latter showed a significant positive correlation with IFN-γ/IL-4 ratio in CD4+ T-cells (Spearman's rho=0.64; p=0.003), percentage-change in haematocrit (rho=0.47; p=0.048), and serum alanine aminotransferase level (rho=0.61; p=0.009).ConclusionWe conclude that DHF is associated with a TH1-skewed immune response. Further, MIP-1α in CD8+ T-cells is an important immunologic correlate of disease severity in dengue.

Prevalence of Nocturnal Hypoxia and Its Association with Disease Severity in Adults with Sickle Cell Disease.

Abstract 261 Introduction:In children with sickle cell disease (SCD), obstructive sleep apnoea (OSA) is common and the degree of overnight hypoxia is closely correlated with disease severity, particularly frequency of painful crises, risk of stroke and presence of pulmonary hypertension. No studies have examined the prevalence or effects of OSA in adults with SCD. Methods:All adults with SCD attending routine sickle cell out-patient clinics were offered screening for OSA using the Epworth Sleepiness Score (ESS) questionnaire. All of those in whom the score was >10 or in whom there was a high clinical suspicion of OSA were offered overnight domiciliary oximetry. Oximetry traces were both analysed by computer and manually. Computerised analysis was used to quantify night time hypoxic load (mean nocturnal SpO2 and sleep time with SpO2 below 90%) and frequency of desaturation (number of times per hour the SpO2 dropped by >4%, or Overnight Desaturation Index, ODI). Manual analysis of each trace was performed by four independent sleep physicians who assigned a diagnosis of normal, OSA, non-OSA nocturnal hypoxia or inadequate based on the pattern of the oxygen saturation and heart rate traces. These parameters were then correlated with measures of disease severity and presence of complications taken from the patient's medical record. Statistical analysis was performed using the t-test and linear regression. Results:93 patients completed the ESS, with 34 patients identified for subsequent oximetry (26 ESS>10, 8 clinical suspicion). 22 patients went on to have subsequent oximetry. 17/22 of recordings (77%) were abnormal of which 11 showed OSA (65%) and 6 showed nocturnal hypoxia without OSA (35%). Nocturnal hypoxic load, measured as mean overnight oxygen saturation, was correlated with glomerular filtration rate (r=0.5; p=0.0008) and pulmonary artery systolic pressure estimated by echocardiography (r=0.71; p=0.0001). Furthermore, urine protein level correlated with ODI (r=0.5 p=0.0007) and mean overnight oxygen saturation (r=0.35; p=0.02). In addition, mean overnight oxygen saturation was 87% in male patients that experienced priapism and 94% in those who did not (p=0.004). Mean ODI was 10/hr in patients with priapism and 4 in those without (p=0.008). There were no correlations demonstrated between either hypoxic load or ODI with the frequency of painful crises, frequency of hospital admissions or avascular necrosis. Lung function test parameters, history of chest syndrome, hydroxyurea therapy and Epworth score did not predict either hypoxic load or ODI. However, daytime SpO2 were highly predictive of nocturnal hypoxic load (r=0.69 p=0.0000007) but not ODI. Conclusion:OSA and non-OSA nocturnal hypoxia are common in adults with sickle cell disease. The degree of nocturnal hypoxia is associated with impaired renal function, proteinuria, priapism and pulmonary hypertension. Daytime SpO2 appears to be a better predictor of night time hypoxic load than daytime somnolence. Further work is needed to investigate the effect of interventions such as nocturnal oxygen therapy or continuous positive airway pressure on the associations reported. Disclosures:No relevant conflicts of interest to declare.

Parasite-Dependent Expansion of TNF Receptor II–Positive Regulatory T Cells with Enhanced Suppressive Activity in Adults with Severe Malaria

Severe Plasmodium falciparum malaria is a major cause of global mortality, yet the immunological factors underlying progression to severe disease remain unclear. CD4+CD25+ regulatory T cells (Treg cells) are associated with impaired T cell control of Plasmodium spp infection. We investigated the relationship between Treg cells, parasite biomass, and P. falciparum malaria disease severity in adults living in a malaria-endemic region of Indonesia. CD4+CD25+Foxp3+CD127lo Treg cells were significantly elevated in patients with uncomplicated (UM; n = 17) and severe malaria (SM; n = 16) relative to exposed asymptomatic controls (AC; n = 10). In patients with SM, Treg cell frequency correlated positively with parasitemia (r = 0.79, p = 0.0003) and total parasite biomass (r = 0.87, p<0.001), both major determinants for the development of severe and fatal malaria, and Treg cells were significantly increased in hyperparasitemia. There was a further significant correlation between Treg cell frequency and plasma concentrations of soluble tumor necrosis factor receptor II (TNFRII) in SM. A subset of TNFRII+ Treg cells with high expression of Foxp3 was increased in severe relative to uncomplicated malaria. In vitro, P. falciparum–infected red blood cells dose dependently induced TNFRII+Foxp3hi Treg cells in PBMC from malaria-unexposed donors which showed greater suppressive activity than TNFRII− Treg cells. The selective enrichment of the Treg cell compartment for a maximally suppressive TNFRII+Foxp3hi Treg subset in severe malaria provides a potential link between immune suppression, increased parasite biomass, and malaria disease severity. The findings caution against the induction of TNFRII+Foxp3hi Treg cells when developing effective malaria vaccines.

Aminoterminal Pro B-Type Natriuretic Peptide (NT-proBNP) Levels for Monitoring Interventions in Paediatric Cardiac Patients with Stenotic Lesions

Background. Serum concentration of NT-proBNP correlates well with the severity of cardiac disease in adults. Few studies have been performed on the applicability of NT-proBNP for monitoring children with congenital heart disease. Objective. To assess the potential of NT-proBNP for monitoring the success of interventions in children with stenotic cardiac lesions. Methods. NT-proBNP was measured in 42 children aged 1 day to 17 years (y) before and 6 to 12 weeks after surgical or interventional correction of obstructive lesions of the heart. Comparison is made with the clinical status and echocardiographic data of the child. Results. NT-proBNP levels (median 280, range 10–263,000 pg/mL) were above the reference value in all but 6 patients (pts) prior to the intervention. Higher levels were found in more compromised patients. The 35 children with clinical improvement after the procedure showed a decline of their NT-proBNP level in all but 4 patients, whose levels remained unchanged. Five patients with unchanged gradients despite a therapeutic intervention also demonstrated unchanged NT-proBNP levels after the intervention. Thus, the success rate of the procedure correlated well to clinical and echocardiographic findings. Conclusion. NT-proBNP can be used to assess the efficiency of an intervention.

Association of high Orientia tsutsugamushi DNA loads with disease of greater severity in adults with scrub typhus.

Orientia tsutsugamushi, the cause of scrub typhus, is a major pathogen in the Asia-Pacific region. The severity of infection ranges from mild features to multiorgan failure and death. The aim of this prospective study was to define the O. tsutsugamushi loads in the blood samples of patients with scrub typhus on the day of hospital admission and to determine whether this was associated with disease severity. Quantitation was performed using a real-time PCR assay targeting the 16S rRNA gene of O. tsutsugamushi. A total of 155 patients with a confirmed diagnosis of scrub typhus had a median (interquartile range [IQR], range) O. tsutsugamushi DNA load in blood of 13 (0 to 334, 0 to 310,253) copies/ml. This included 74 patients who had undetectable bacterial loads. An analysis of bacterial load versus clinical features for all 155 patents demonstrated that duration of illness (P < 0.001), presence of eschar (P = 0.004), and concentrations of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase (P < 0.001 for all three) were positively correlated with bacterial load. Patients who died had a significantly higher bacterial load than those who survived (mean [standard deviation] values: 17,154 [12.7] versus 281 [5.2] copies/ml; P < 0.001). This study has demonstrated a relationship between bacterial load and disease severity in adults with scrub typhus.

Efficacy and Safety of Desloratadine in Adults with Chronic Idiopathic Urticaria

Chronic idiopathic urticaria (CIU), a condition characterized by pruritus and wheals, can cause patients physical and psychological distress. Desloratadine, a second-generation histamine H(1) receptor antagonist (antihistamine), is a first-line treatment option for CIU. The objective of this study was to evaluate the efficacy and safety of once-daily desloratadine 5mg versus placebo for the treatment of CIU symptoms and disease severity in adults. This was a randomized, placebo-controlled, multicenter trial of 137 adult patients with active CIU who received oral once-daily desloratadine 5mg or placebo for 6 weeks. Outcome measures included pruritus severity, number of wheals, and the size of the largest wheal. Patients assessed signs and symptoms on a four-point scale twice daily. The overall therapeutic response at the end of the 6-week treatment period was also rated. Desloratadine treatment was associated with significant improvements compared with placebo in pruritus scores and in the size of the largest wheals as early as day 1. These improvements continued through to the end of the trial. The mean score for the number of wheals was significantly lower in the desloratadine group than in the placebo group on days 14 and 42 (p < or = 0.016). Overall improvement in CIU (complete, marked, or moderate therapeutic response) was also greater at the end of the study in the desloratadine group compared with placebo (p < 0.001). Adverse events occurred with similar frequency among desloratadine- and placebo-treated patients. Once-daily desloratadine 5mg is well tolerated and superior to placebo in reducing pruritus and wheals associated with CIU. Desloratadine provided rapid and sustained relief of CIU symptoms as early as after the first dose and maintained this effect until the end of the 6-week treatment period.

RORα-Mediated Purkinje Cell Development Determines Disease Severity in Adult SCA1 Mice

Spinocerebellar ataxia type 1 (SCA1) is one of nine inherited, typically adult onset, polyglutamine neurodegenerative diseases. To examine whether development impacts SCA1, we used a conditional transgenic mouse model of SCA1 to delay the postnatal expression of mutant ATXN1 until after completion of cerebellar development. Delayed postnatal expression of mutant ATXN1 led to a substantial reduction in severity of disease in adults in comparison with early postnatal gene expression. This was linked to a destabilization of RORalpha, a transcription factor critical for cerebellar development. In SCA1 mice, there was a depletion of RORalpha and a reduction in expression of genes controlled by RORalpha. Partial loss of RORalpha enhanced mutant ATXN1 pathogenicity. Additionally, evidence points to the existence of a complex containing ATXN1, RORalpha, and the RORalpha coactivator Tip60. These studies indicate RORalpha and Tip60 have a role in SCA1 and suggest a mechanism by which compromising cerebellar development contributes to severity of neurodegeneration in an adult.