Need For Corticosteroid Treatment Research Articles

Expression of MMP-2, MMP-7, MMP-9, and TIMP-1 by Inflamed Mucosa in the Initial Diagnosis of Ulcerative Colitis as a Response Marker for Conventional Medical Treatment

Introduction: Experimental and clinical data involve matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) in the pathogenesis of inflammatory bowel diseases. However, the impact of MMPs/TIMPs expression by inflamed mucosa on medical response therapy has scarcely been investigated. Methods: The expression of MMP-2, MMP-7, MMP-9, and TIMP-1 was determined by immunohistochemical analysis in inflamed mucosa samples at diagnosis in 82 patients with ulcerative colitis (UC; 22 never-treated with corticosteroids, 28 nonresponders, and 32 responders to corticosteroid therapy) and 15 patients with acute diverticulitis (AD). The global expression (score value) of each factor was analyzed by computer-generated image analysis. Results: UC samples showed higher MMP-2 and MMP-9 expression but lower TIMP-1 expression than the AD samples (p < 0.0001, for all). High MMP-9 and TIMP-1 scores were significantly associated with no need for corticosteroid treatment (p < 0.001 and p = 0.017, respectively); whereas higher score in the MMP-7 expression was significantly associated with nonresponse to corticosteroid therapy (p = 0.037). In addition, in this latter UC subgroup, MMP-7 correlated positively with the younger age of the patients and with the extension of the disease (p = 0.030 and p = 0.010, respectively). Conclusion: Our results suggest the relevance of MMPs and TIMPs for predicting treatment response to both 5-aminosalicylates and corticosteroids in UC.

Role of serum immunoglobulins for predicting sarcoidosis outcome: A cohort study.

BackgroundSarcoidosis is a systemic granulomatous disease which carries variable outcomes. Serum protein electrophoresis is an easily accessible and routinely performed examination at diagnosis, in order to search for hypergammaglobulinemia, which is frequently found, and to rule out other granulomatous diseases such as common variable immunodeficiency. We aimed to assess the impact of baseline immunoglobulin level on the outcome of sarcoidosis.MethodsWe conducted a retrospective cohort-study, at Rennes University Hospital, in which all newly diagnosed patients for whom a serum protein electrophoresis had been performed at baseline were enrolled, from 2006 to 2014. The main outcome was the need for corticosteroid treatment within 2 years from diagnosis, the secondary outcome was the occurrence of relapse among treated patients.ResultsEighty patients were included in the study, and 41.25% of them exhibited an elevated globulins rate. In univariate analysis, an elevated ACE level >70 U/l, Afro-Caribbean origin, and extra-pulmonary involvement, were associated with the need for corticosteroid treatment. In multivariate analysis, only ACE elevation (OR = 1.03, IC95% 1.01–1.05, p = 0.009) and extra-pulmonary involvement (OR = 5.8, IC95% 1.4–24, p = 0.015) were significant. Immunoglobulin level was not associated with the main outcome. Regarding the secondary outcome, none of the studied features were predictive of relapse among the 34 treated patients followed for two years.ConclusionsThere was no relation between the immunoglobulin level at diagnosis and the evolution of sarcoidosis. An elevated ACE level and the presence of initial extra-pulmonary involvement were both associated with a more severe course of the disease necessitating a corticosteroid treatment.

P92 C reactive protein as a predictive indicator of treatment and disease progression in patients with sarcoidosis: a retrospective observational cohort study in the West of Ireland

IntroductionC reactive protein (CRP) is an acute-phase protein synthesised in response to tissue damage or inflammation. Previous studies evaluating the role of CRP in sarcoidosis have focussed on disease monitoring....

T cell activation profiles in different granulomatous interstitial lung diseases – a role for CD8+CD28null cells?

Lymphocytes play a crucial role in lung inflammation. Different interstitial lung diseases may show distinct lymphocyte activation profiles. The aim of this study was to examine the expression of a variety of activation markers on T lymphocyte subsets from blood and bronchoalveolar lavage fluid (BALF) of patients with different granulomatous interstitial lung diseases and healthy controls. Bronchoalveolar lavage cells and blood cells from 23 sarcoidosis patients, seven patients with hypersensitivity pneumonitis and 24 healthy controls were analysed. Lymphocyte activation status was determined by flow cytometry. Lymphocytes were stained with antibodies against CD3, CD4, CD8, CD25, CD28, CD69, very late antigen-1 (VLA)-1, VLA-4 and human leucocyte antigen D-related (HLA-DR). In general, CD28, CD69 and VLA-1 expression on BALF CD4+ lymphocytes and HLA-DR expression on BALF CD8+ lymphocytes was different in patients with hypersensitivity pneumonitis and sarcoidosis patients with parenchymal involvement. This BALF lymphocyte phenotype correlated with carbon monoxide diffusing lung capacity (Dlco) values across interstitial lung diseases (ILD) (r2 = 0.48, P = 0.0002). In sarcoidosis patients, CD8+CD28(null) blood lymphocytes correlated with lower Dlco values (r = -0.66, P = 0.004), chronic BALF lymphocyte activation phenotype (r2 = 0.65, P < 0.0001), radiographic staging (stage I versus stage II and higher, P = 0.006) and with the need for corticosteroid treatment (P = 0.001). Higher expression of CD69, VLA-1 and HLA-DR and lower expression of CD28 on BALF lymphocytes suggests prolonged stimulation and chronic lymphocyte activation in patients with ILD. In sarcoidosis, blood CD8+CD28(null) cells might be a new biomarker for disease severity but needs further investigation.

Prediction of Very Short Survival in Patients with Brain Metastases from Breast Cancer

Aims Current prognostic models are not accurate enough to identify brain metastases patients with very short survival, i.e. <2 months, who are unlikely to derive major benefit from whole brain radiotherapy. Our aim was to develop a more reliable model. Materials and methods This was a retrospective analysis of a German database, which was used to develop a score, and an additional database from Norway, which was used for validation purposes. Results The groups included 67 and 32 patients, respectively. An analysis of prognostic factors resulted in a risk score based on performance status, extra-cranial metastases, the interval from breast cancer to brain metastases and a need for corticosteroid treatment, which classified 63 of 67 test patients correctly. However, the validation failed and unfortunately the risk score that performed best in the Norwegian patients (31 of 32 correctly predicted) was not applicable to the German patients. Conclusions The prediction of short survival is associated with several caveats and seems to result in an unacceptable risk of withholding radiotherapy in patients who actually survive for longer than 2 months.

Fatores preditivos da evolução da asma aguda em crianças

OBJETIVO: Identificar fatores preditivos da evolução da asma aguda, a partir de características clínicas e funcionais observadas no momento da admissão de crianças em unidade de emergência. MÉTODOS: Este estudo avaliou prospectivamente 130 crianças com asma aguda, na faixa etária de um a treze anos, no momento da admissão e durante a evolução em unidade de emergência, através de escore clínico e medidas de saturação arterial de oxigênio por oximetria de pulso e do pico de fluxo expiratório. RESULTADOS: Os valores iniciais de escore clínico, saturação arterial de oxigênio medida por oximetria de pulso e pico de fluxo expiratório apresentaram correlação com o número de inalações realizadas e a necessidade do uso de corticosteróide. As médias dos valores iniciais de escore clínico e da saturação arterial de oxigênio dos pacientes que foram internados foram estatisticamente diferentes das dos que não foram internados. Os valores iniciais de escore clínico e de saturação arterial de O2 e a existência de atendimento anterior pela mesma exacerbação foram preditivos da necessidade de hospitalização das crianças. CONCLUSÕES: A medida da saturação arterial de O2 e o escore clínico foram úteis para predizer a evolução da asma aguda em crianças. A medida do pico de fluxo expiratório é de difícil obtenção e interpretação nessa condição e demonstrou ter pouca aplicação prática.

Pimecrolimus Cream in the Long-Term Management of Atopic Dermatitis in Adults: A Six-Month Study

Background: Pimecrolimus cream (Elidel^®, SDZ ASM 981), a non-steroid inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms reduces the need for topical corticosteroids. Objective: To investigate the efficacy and safety of pimecrolimus cream 1% in the long-term management of adult AD. Methods: 192 adults with moderate to severe AD were randomised (1:1) for twice daily (b.i.d.) treatment of early signs or symptoms of AD with either pimecrolimus cream 1% or vehicle cream (control group) to prevent progression to flares. Treatment was given as needed for 24 weeks. In the event of flares, a moderately potent corticosteroid (prednicarbate 0.25% cream) was permitted as rescue medication in both groups. The percentage of days on which a topical corticosteroid was used to treat disease flares was the main outcome measure. Results: Corticosteroid medication was used on 14.2% (95% confidence interval, CI: 8.3–21.1) of the days of the 24-week treatment period in the pimecrolimus group and on 37.2% (95% CI: 30.4–44.0) of the days in the control group (p < 0.001). In total, 44.8% (43/96) of patients in the pimecrolimus group did not experience a flare compared with 18.8% (18/96) of patients in the control group. The median time to first flare was 144 days in the pimecrolimus group and 26 days in the control group (p < 0.001). Pimecrolimus treatment was also associated with improvement in signs and symptoms of AD, pruritus, patients’ self-assessment and quality of life. Conclusions: Pimecrolimus cream 1% b.i.d. is an effective, well-tolerated, long-term treatment for AD in adults, substantially reducing the number of flares compared to a conventional therapy and consequently reducing or eliminating the need for corticosteroid treatment.

Eosinophil markers in blood, serum, and urine for monitoring the clinical course in childhood asthma: Impact of budesonide treatment and withdrawal

Background: Markers of airway inflammation are needed for prediction of asthma deterioration and evaluation of disease severity. Few studies have focused on the dynamics of airway inflammation as reflected by the activity of the eosinophils and their proteins after withdrawal of inhaled corticosteroids. Objective: Our goal was to investigate the effect of withdrawal of inhaled budesonide on eosinophil count in blood and eosinophil proteins in serum and urine and to relate the levels of these markers to the risk of symptoms of asthma, increased bronchial hyperresponsiveness, and deterioration of lung function. Methods: Thirty-three children were randomly selected to continue or discontinue use of inhaled budesonide in a double-blind, placebo-controlled study. They were followed up for 4 months with regular analysis of blood, serum, and urine samples; lung function; and methacholine challenges. Eosinophil activity markers were analyzed. Age-matched healthy children provided reference data for all parameters measured. Results: The eosinophil number in blood and eosinophil protein levels in serum (serum eosinophil cationic protein [ECP] and serum eosinophil peroxidase [EPO]) increased significantly in the withdrawal group, and the difference between the groups was significant (P = .02 for all). Twenty-nine percent of the children in the withdrawal group remained symptom free. This subgroup had eosinophil counts at baseline below 350/μL, a serum ECP level below 15 μg/L, and a serum EPO level below 25 μg/L, each of which was related to a low risk of exacerbation (relative risk = 0.37, 0.48, and 0.37 respectively; P < .05 for all). All eosinophil markers were lower in the healthy children than in the symptom-free children with asthma. Conclusion: Our data indicate that eosinophil count and/or ECP and EPO levels can be used to estimate the short-term risk of deterioration and the need for corticosteroid treatment in cases of mild and moderate allergic asthma. (J Allergy Clin Immunol 2001;107:812-7.)

Epidemiology of familial sarcoidosis in the UK.

The last comprehensive epidemiological studies on familial sarcoidosis in the UK were more than 25 years ago, reporting another affected family member in 1.7% of index cases. A significant proportion of like-sex over unlike-sex pairs, an excess of mother-child over father-child associations, and a preponderance of monozygous over dizygous twins was noted. Another study reported ethnic heterogeneity in familial disease. This study was undertaken to identify the risk ratio (lambda(S)) for siblings of familial sarcoidosis in the UK, to determine if the previous epidemiological findings have persisted, and to reassess whether ethnic heterogeneity prevails in familial disease. Questionnaires were sent to 406 index patients. Two hundred and sixty eight replies (66%) were received. Twenty four of the original 406 index patients (5.91%) were found to have at least one other relative (first, second or third degree) with biopsy proven sarcoidosis. A lambda(S) value of 36-73 was calculated indicating significant familial clustering of the disease. Ethnically the families comprised 62.5% Caucasian, 29.2% Afro-Caribbean, and 8.3% Asian. Mean age at diagnosis was 39.8 years for women and 40.9 years for men with a male to female ratio of 1:1.7. This differed for the Asian families in which all the affected members were male. Three sets of female twins (two monozygous and one dizygous) were included. There was an equal distribution of like-sex (primarily female) and unlike-sex families as well as mother-child and father-child pairs. Pulmonary involvement was predominant irrespective of ethnicity, as was the need for corticosteroid treatment. These results support the theory that a shared determinant (either genetic or environmental) is operating in familial sarcoidosis and suggest that this determinant is similar for all ethnic groups.

Treatment of recurrent pericarditis with colchicine

Corticosteroid therapy, because of its frequent and severe side effects should be avoided if possible, and colchicine may be an effective substitute in steroid-dependent recurrent pericarditis. The aim of our study was to assess the usefulness of colchicine in recurrent pericarditis before initiating corticosteroid treatment. Nineteen consecutive patients (10 males, nine females, age 46 +/- 7 years) with recurrent pericarditis (two episodes or more) were included in this prospective open-label study. Before the study, the patients suffered a total of 57 episodes of pericarditis (mean = 3.0 +/- 0.5 episodes.patient-1) despite the use of non-steroidal anti-inflammatory drugs. The mean interval time between the episodes was 7.3 +/- 5.3 months. Colchicine was given at a loading dose of 3 mg and a maintenance dose of 1 mg daily (for 1 to 27 months (mean = 7.7). During the clinical follow-up, the efficacy was estimated by the occurrence of new episodes of pericarditis and by the need for corticosteroid treatment. No recurrence occurred in 14 out of the 19 patients (74%) during a follow-up of 37.4 +/- 6.5 months. In four out of the 19 patients (21%), five recurrences occurred, which resolved without corticosteroids. Follow-up at 23.8 +/- 12.7 months was free of further recurrence. Only one patient (5%) had several recurrences and required corticosteroids for chronic rheumatism. Tolerance was good except for two cases of diarrhoea, one case of hypothyroidism due to associated long-term antidiarrhoeal therapy (containing iodine), and one case of mild leucopenia.(ABSTRACT TRUNCATED AT 250 WORDS)