Steroid-treated Patients Research Articles

Increasing the Infliximab Dose Is Beneficial in Crohn’s Disease Patients Who Responded to a Lower Dose and Relapsed

Background: Relapse after an initial response to infliximab therapy poses a problem for maintenance treatment. Aim: To assess the effects of increasing the infliximab dosage in Crohn’s disease (CD) patients who initially responded but flared during maintenance therapy. Methods: This was an observational study. Twelve CD patients with both inflammatory and fistulizing manifestations were included. All patients initially responded to 5 mg/kg of infliximab, relapsed during maintenance therapy, and were treated with 10 mg/kg. The Harvey-Bradshaw index, the fistula activity, and steroid use were assessed before and after treatment with the increased dose of infliximab. Results: The mean Harvey-Bradshaw index score after flare-up during treatment with 5 mg/kg of infliximab was 13.5 ± 3.7. Treatment with 10 mg/kg, in a mean of 3.3 infusions, decreased the activity score to a mean of 8.8 ± 2.5. Two patients were weaned off prednisone, and a reduced dose was possible in the other steroid-treated patients. Conclusions: Increasing the infliximab dose may be beneficial in CD patients who initially responded to therapy, but relapsed during maintenance with the lower dosage.

A Cost-Effectiveness Analysis of Alternative Disease Management Strategies in Patients with Crohn's Disease Treated with Azathioprine or 6-Mercaptopurine

Azathioprine (AZA) is effective for the maintenance of a steroid free remission in Crohn's disease (CD). Thiopurine methyltransferase (TPMT) is important for the metabolism of AZA and influences the production of active AZA metabolites. AZA dose selection based on pharmacogenetic testing of TPMT and metabolite monitoring (MM) may offer a safety and efficacy advantage over traditional dosing strategies. We performed a decision analysis to estimate the potential costs and effectiveness of TPMT screening and MM as disease management strategies for CD. Strategies applying TPMT and/or MM to influence treatment decisions were compared to community care (CC). The impact on toxicity minimization and improved time to initial and sustained response was evaluated. A 1-yr model was developed from the third-party payer perspective for mild to moderately chronically active, steroid-treated CD patients. Effectiveness and toxicity defined by time to response CD activity index (CDAI <150, +/- steroids) or time to sustained response (CDAI <150, off steroids x 8 wk) and reduction in leukopenic events, respectively. One- and two-way sensitivity analyses were conducted to determine the effect of varying individual estimates from those used in the base-case analysis. MM, TPMT, and TPMT + MM strategies as compared to CC achieved an earlier time to initial response (18.66, 18.96, and 19.10 vs. 22.41 wk, respectively) and sustained response (39.83, 42.91, and 39.8 vs. 45.36 wk, respectively). The least costly strategy at 1 yr was TPMT ($3,861) and the most costly strategy was CC ($7,142). Each alternative strategy was shown to dominate CC (i.e., less costs and faster time to response or sustained response). The cost-effectiveness rankings were robust to sensitivity analyses on key variables. The addition of alternative strategies to CC may improve AZA outcomes and reduce the total cost of care for steroid treated chronically active CD patients, with TPMT being more beneficial for initial response to treatment and MM being more beneficial for sustained response to treatment.

Effects of Leukotriene Receptor Antagonists on Vascular Endothelial Growth Factor Levels in Asthma

Kanazawa et al1,2 have reported an interesting reduction in airway permeability with pranlukast that correlated with a reduction in airway vascular endothelial growth factor (VEGF) levels. However, no such reduction in VEGF levels was observed in steroid-treated asthmatics. In contrast, a clinical study2has shown a further benefit in symptoms and lung function in the combination of leukotriene receptor antagonists and inhaled steroids. It is therefore perhaps surprising that no further reduction in airway VEGF occurred with pranlukast added to the steroid-treated patients.

CIRCULATING LEVELS OF MACROPHAGE MIGRATION INHIBITORY FACTOR ARE ASSOCIATED WITH MILD PULMONARY DYSFUNCTION AFTER CARDIOPULMONARY BYPASS

Macrophage migration inhibitory factor (MIF) is a central mediator of inflammatory response and acute lung injury that is secreted in response to corticosteroids. A rise in systemic MIF levels was described after cardiac surgery in steroid-treated patients. This study aimed to investigate the circulating levels of MIF and the possible relationship of this cytokine to pulmonary dysfunction after cardiopulmonary bypass (CPB). We included 74 patients without previous organ dysfunction undergoing elective coronary artery bypass surgery (CABS). The same team performed all CABS via a standard technique adding methylprednisolone (15 mg/kg) to the CPB priming solution (Group MP, n = 37). In the remaining patients (Group NS, n = 37), methylprednisolone was withdrawn from the CPB priming. MIF, C-reactive protein (CRP), and total C3 were assayed in peripheral blood sampled immediately before anesthesia induction and 3, 6, and 24 h post-CPB. Preoperative risk scores and peri- and postoperative variables were documented. Postoperative kinetics of MIF and C3 were similar for both groups. Levels of CRP 24 h post-CPB were higher in Group MP (P = 0.003). Higher MIF levels were detected 6 h post-CPB, and returned to preoperative levels 24 h after CPB. MIF levels 6 h post-CPB were inversely related to the postoperative PaO2/FiO2 ratio (P = 0.0021) and were directly related to the duration of mechanical ventilation (P = 0.014). Perioperative use of methylprednisolone did not modify the MIF response to CPB, but it was related to an enhanced acute phase response. Higher circulating MIF levels 6 h post-CPB were associated with worse postoperative pulmonary short-course outcome.

Effects of Pranlukast Administration on Vascular Endothelial Growth Factor Levels in Asthmatic Patients

We have previously found that vascular endothelial growth factor (VEGF) levels in induced sputum were increased in asthmatic patients, and that its levels were closely associated with the degree of airway obstruction and microvascular permeability. Therefore, this study was designed to examine the effects of pranlukast, a selective leukotriene receptor antagonist, on VEGF levels in induced sputum from steroid-untreated or steroid-treated asthmatic patients. Double-blind, randomized, placebo-controlled, crossover study. University hospital. Twenty-three asthmatic patients (steroid-untreated, 13 patients; steroid-treated, 10 patients) and 10 healthy control subjects. All asthmatic patients received 4-weeks of therapy with pranlukast (225 mg bid), and sputum induction was performed before and after the 4-week treatment course. In steroid-untreated asthmatic patients, the mean percentage of eosinophils (%EOS) and mean eosinophil cationic protein (ECP) levels in induced sputum were significantly decreased after 4 weeks of pranlukast administration (%EOS: before, 16.7% [SD, 7.1%]; after, 12.3% [SD, 4.0%]; p = 0.03; ECP levels: before, 774 ng/mL [SD, 258 ng/mL]; after, 564 ng/mL [SD, 204 ng/mL]; p = 0.034). Moreover, VEGF levels in the induced sputum and the airway vascular permeability index also were decreased after pranlukast administration (VEGF levels: before, 5,670 pg/mL [SD, 1,780 pg/mL]; after, 4,380 pg/mL [SD, 1,540 pg/mL]; p = 0.026; airway vascular permeability index: before, 0.032 [SD, 0.012]; after, 0.017 [SD, 0.006]; p = 0.01). In addition, the change in airway vascular permeability index from before to after pranlukast administration was significantly correlated with the change in VEGF levels (r = 0.782; p = 0.007). However, in steroid-treated asthmatic patients there was no significant difference in mean VEGF levels in induced sputum between placebo administration (before, 3,640 pg/mL [SD, 1,020 pg/mL]; after, 3,640 pg/mL [SD, 960 pg/mL] and pranlukast administration (before, 3,660 pg/mL [SD, 940 pg/mL]; after, 2,950 pg/mL [SD, 890 pg/mL]). Pranlukast administration decreased airway microvascular permeability through, at least in part, a decrease in airway VEGF levels in steroid-untreated asthmatic patients. However, it is likely that pranlukast administration added little efficacy to inhaled corticosteroid therapy for reduction in airway VEGF levels.

Monitoring of ELISA for Anti‐BP180 Antibodies: Clinical and Therapeutic Analysis of Steroid‐Treated Patients with Bullous Pemphigoid

We studied the precise correlation between ELISA values for BP180 NC16A and the alternations of disease activity in 5 patients with bullous pemphigoid (BP) during various treatments and tried to answer the question of how we can use ELISA to determine the timing of prednisolone (PSL) tapering. Disease activity in some patients with BP, but not in all, was poorly correlated with ELISA values in short-term follow-up. However, all patients showed a good correlation of disease activity with ELISA values as a whole in long-term follow-up. Three patients with typical BP showed rapid and good responses to PSL for erosion and blister formation. Their ELISA values gradually decreased to 40% of initial values during PSL therapy after four weeks. Two patients with the vesicular type of BP did not show rapid and good responses to PSL for erosion and blister formation. In the cases with the vesicular type of BP, diaphenylsulfone in addition to PSL dramatically improved the clinical symptoms including erosion and blister formation, even though the ELISA values were as high as those before treatment. Relapses did not occur with the tapering of PSL dosage when the ELISA values decreased to 40% of initial values, although they were still not within the normal range.

Increased concentrations of glutathione in induced sputum of patients with mild or moderate allergic asthma

Oxidative stress is involved in the pathogenesis of allergic inflammatory diseases, such as rhinitis and asthma. Glutathione is a vital intracellular and extracellular protective pulmonary antioxidant. It plays a key role in regulating oxidant-induced lung epithelial cell function and also in the control of proinflammatory processes. To quantify oxidative stress in sputum of asthmatic patients compared with healthy subjects. We quantified induced sputum supernatant concentrations of total and oxidized glutathione in 20 patients with mild asthma without inhaled corticosteroid treatment, 19 patients with moderate-persistent asthma treated with inhaled corticosteroids (median dose, 900 microg/d of beclomethasone equivalent), and 15 healthy, nonatopic, nonsmoking subjects. Total glutathione levels were significantly increased in mild and persistent asthma compared with healthy subjects [geometric mean (95% confidence interval), 9.2 microM (7.1-12 microM) and 8.7 microM (5.9-12.5 microM) vs 4 microM (2.7-6 microM); P = .039 and .042, respectively]. In contrast, there were no differences in total and oxidized glutathione levels between steroid-naïve and steroid-treated asthmatic patients (P > .20 for all comparisons). Persistent, steroid-treated asthmatic patients had higher sputum counts of neutrophils than steroid-naïve asthmatic patients [geometric mean (95% confidence interval), 35.6% (28.2%-42.7%) vs 17.7% (11.7%-27.1%), P = .04]. There was a positive correlation of total glutathione with sputum total cells (rho = 0.32, P = .02). Total glutathione is increased in induced sputum of patients with mild and moderate asthma. These data underline the contribution of oxidative stress to the pathogenesis of allergic asthmatic inflammation.

Evaluation of exhaled nitric oxide and nitric oxide metabolites in exhaled breath condensate during asthma

Rationale The collection of exhaled breath condensate (EBC) represents a potentially important non-invasive diagnostic tool to sample non-volatile substances from the lower airways. The purpose of the present study was to evaluate whether there exists a relationship between exhaled nitric oxide (ENO) and NO metabolites in EBC in asthmatic patients. Methods We measured ENO (off-line and on-line) as well as nitrite (NO 2 −) and nitrate (NO 3 −) concentrations in exhaled breath condensates (EBC) from 10 normal individuals, 11 steroid-naïve, and 8 steroid-treated asthmatic patients. In all subjects, EBC was collected during tidal breathing using the Jaeger Ecoscreen system and nitrite/nitrate concentrations in EBC were measured using a chemiluminescence detector. Results ENO was elevated in steroid naïve asthmatic patients compared to healthy individuals (32 ± 23 vs 10 ± 6 ppb) and it was statistically significantly reduced in steroid treated individuals (11 ± 5 ppb, p<0.05). Nitrate but not nitrite concentrations showed an increase in steroid naïve and a reversal in steroid treated patients. Consistent with these findings, there was a positive linear correlation between ENO and nitrate but not nitrite. Conclusions Our results suggest that determination of nitrate but not nitrite might represent a relevant marker in asthma. In addition, there was a trend in increased interleukin-8 and decreased interferon-γ levels in steroid naïve asthmatic individuals. Overall, the utilization of EBC solutes as relevant diagnostic markers will rely on the rigorous standardization of sampling procedures.

Hand-Sewn versus Stapled Intestinal Anastomoses in a Chronically Steroid-Treated Porcine Model

Chronic steroid treatment is known to delay wound healing; however, there are no trials examining stapled intestinal anastomoses in subjects chronically treated with steroids. The current study compares mechanically stapled to manually sutured intestinal anastomoses in a steroid-treated porcine model. Twenty adult male pigs were treated with daily prednisolone (0.5 mg/kg IM) for 14 days. The pigs were divided between hand-sewn and stapled groups. All pigs underwent a laparotomy with construction of a jejunojejunostomy, an ileocecostomy, and a colocolostomy. Pigs were sacrificed on postoperative day 4. Bursting pressure, collagen content, and inflammatory scores were used to evaluate each anastomosis. Bursting pressure was greater for the hand-sewn group at the jejunojejunostomies only (1.52 vs 0.79 psi; P < 0.001). The collagen content and microscopic inflammatory scores were not significantly different at any location. The mean gross inflammatory score was greater for the hand-sewn colocolostomies only (5.20 vs 4.00; P < 0.01). Stapled ileocecostomies and colocolostomies appear to heal as well as hand-sewn anastomoses. This may not be true of the jejunojejunostomies as evidenced by the decreased bursting pressures. These data may provide evidence in support of the use of stapled anastomoses in steroid-treated patients.

Estudo comparativo da eficácia do uso de prednisolona e cetorolaco de trometamina tópicos após cirurgia de estrabismo

OBJETIVO: Avaliar os resultados do uso de antiinflamatório não hormonal (AINH) no controle da inflamação no pós-operatório de estrabismo, comparando-se com corticóide tópico. MÉTODOS: Selecionaram-se exclusivamente pacientes submetidos a recuo-ressecção em um só olho. Os dois grupos de pacientes usaram o mesmo antibiótico, sendo que para um grupo foi prescrito prednisolona 0,12% e para o outro cetorolaco de trometamina. Eles foram avaliados quanto a hiperemia, edema, conforto e variação da pressão intra-ocular, até o 21º dia de pós-operatório. RESULTADOS: Foram 27 pacientes, sendo 15 no grupo de AINH e 12 no de corticóide. Com relação a edema, conforto e PIO não houve variação entre os grupos. Porém, no grupo com AINH houve 5 (33,3%) casos de hiperemia conjuntival de ++/4 no 21º dia de pós-operatório e três (20%) de granuloma. Entre os pacientes com corticóide só se observou 1 (8,3%) caso de hiperemia de ++/4 ao término do tratamento e nenhum de granuloma. CONCLUSÃO: Para cirurgias de recuo-ressecção, procedimentos que parecem induzir maior resposta inflamatória, o uso de AINH não é aconselhável.

Prevention of posttraumatic hypoxaemia in isolated lower limb long bone fractures with a minimal prophylactic dose of corticosteroids

The efficacy of a minimum dose of methylprednisolone for the prevention of posttraumatic hypoxaemia and fat embolism syndrome (FES) was prospectively studied in 87 patients with isolated, closed or grade I open, femoral and tibial fractures. On admission, the patients were randomly allocated either to a control group given placebo (40 patients) or to a methylprednisolone-treated group (47 patients). A total dose of 6 mg/kg BW methylprednisolone (SoluMedrol ®, Upjohn) was administered intravenously, divided in six equal doses at 8 h intervals. Six patients (12.8%) in the control group and one patient (2.5%) in the trial group developed FES ( P=0.079) but the difference is not statistically significant. Twenty-four hours after admission, the steroid-treated patients displayed statistically significant higher p O 2 values compared to the control group ( P=0.035) and this difference persisted on the second and the third post-admission day as well ( P=0.008). No corticosteroid-related side-effects were noticed in any of the patients during hospitalisation. Our results support the prophylactic administration of methylprednisolone in small dosage to prevent posttraumatic hypoxaemia and probably FES in patients with isolated lower limb long bone fractures, especially when early fracture stabilisation is not possible.

Effect of Lamotrigine on Mood and Cognition in Patients Receiving Chronic Exogenous Corticosteroids

Mood changes, cognitive deficits, and psychosis have been reported during corticosteroid therapy. However, minimal data are available on the treatment of these side effects. This pilot study examined the effect of 12 weeks of open-label lamotrigine treatment (dose: mean=340 mg/day, SD=65) on mood and cognition in five patients receiving prescription corticosteroids continuously for at least 6 months before study entry. The participants showed significant improvement in cognition with lamotrigine. Two subjects who met criteria for a current major depressive episode at baseline had baseline-to-exit reductions in scores on the Hamilton Depression Rating Scale of more than 20 points. These pilot data suggest that lamotrigine may be associated with improved mood and performance on cognitive tasks in steroid-treated patients. Larger controlled trials are needed to confirm these preliminary findings.

Steroid effects on vestibular compensation in human

Vestibular neuritis (VN) rapidly damages unilateral vestibular periphery, inducing severe balance disorders. In most cases, such vestibular imbalance is gradually restored to within the normal level after clinical therapies. This successive clinical recovery occurs due to regeneration of vestibular periphery and/or accomplishment of central vestibular compensation. We experienced 36 patients with VN treated at our hospital, including cases in our previous preliminary report. To elucidate effects of steroid therapy both on the recovery of peripheral function and on the adaptation of central vestibular compensation, we examined caloric test and several questionnaires with two randomly divided groups, 18 steroid-treated and 18 nonsteroid-treated patients, over two years after the onset. These examinations revealed that steroid-treated patients had a tendency of better canal improvements (13/18, 72%) than nonsteroid-treated ones (10/18, 55.6%). However, there was no significant difference between these two groups. In cases with persistent canal paresis, steroid-treated patients (n = 5) reduced handicaps in their everyday life due to the dizziness induced by head and/or body movements and the disturbance of their mood, more effectively than those with nonsteroid therapy (n = 8). These findings suggest that steroid therapy with VN could be effective on not only vestibular periphery but central vestibular system, to restore the balance.

Infliximab in the treatment of Crohn's disease: a user's guide for clinicians.

Induction therapy with infliximab is indicated for treatment of signs and symptoms, and induction and maintenance of remission in patients with moderate to severely active inflammatory Crohn's disease with an inadequate response to conventional therapy, and for reduction in the number of draining fistulas in patients with fistulizing Crohn's disease. Emerging indications for infliximab therapy in patients with Crohn's disease include maintenance of fistula improvement (reduction in the number of draining perianal or enterocutaneous fistulas) and complete fistula response (no draining fistulas) in patients with fistulizing Crohn's disease, steroid sparing in steroid-treated patients, early use in hospitalized patients who have not failed conventional medical therapy where there is either a severe clinical presentation or a rapid onset of action is desired, and in a variety of unusual and extra-intestinal manifestations of Crohn's disease. An infliximab dose of 5 mg/kg is recommended initally, but some patients who require maintenance dosing may benefit from increasing the infliximab dose over a range of 5-10 mg/kg. An induction regimen of 3 doses at 0, 2, and 6 weeks is the preferred dosing strategy for inducing remission. The optimal dosing interval for patients who require retreatment appears to be every 8 weeks for most patients. Concomitant immunosuppressive therapy with azathioprine, 6-mercaptopurine, or methotrexate may result in improved outcomes due to a reduction in the frequency of human anti-chimeric antibody formation, acute infusion reactions, and a reduced risk of delayed hypersensitivity-like reactions and formation of antinuclear antibodies. Pretreatment with diphenhydramine (and in selected cases of acetaminophen and, rarely, corticosteroids) is recommended in patients with a history of infusion reactions and patients at risk for delayed hypersensitivity-like reactions. Patients with evidence of active infection should not receive infliximab until the infection is adequately treated, and all patients should be screened for tuberculosis prior to initiating infliximab therapy.

Adenosine in exhaled breath condensate in healthy volunteers and in patients with asthma.

Persistent airway inflammation may require the use of different markers for monitoring airway inflammation. In this study, the authors investigated whether adenosine, which may be produced in allergic inflammatory conditions, could be measured with good reproducibility in exhaled breath condensate (EBC), and whether its concentration was elevated in patients with asthma. EBC adenosine and exhaled nitric oxide (eNO), a noninvasive marker of asthmatic airway inflammation, were measured in 40 healthy volunteers and 43 patients with allergic bronchial asthma. Repeatability of adenosine measurement was checked in 20 pairs of samples collected from healthy control subjects. Adenosine was detectable in all EBC samples by the applied high-performance liquid chromatographic method. The mean difference between repeated measurements of adenosine was -0.1 nM and all differences were within the coefficient of repeatability. Adenosine concentration was higher in steroid-naive patients (n=23) compared with healthy control subjects and steroid-treated patients (n=20). In patients with worsening symptoms of asthma (n=23), adenosine concentration was elevated compared with those in a stable condition (n=20). Furthermore, adenosine concentrations were related to eNO levels in asthmatic patients. These results, showing good reproducibility of adenosine measurements and increased adenosine concentrations in steroid-naive patients and in patients with worsening of asthmatic symptoms, indicate that adenosine measurement in exhaled breath condensate might be an acceptable novel method to investigate the role of local production of adenosine in the airways.

Peripheral bone density in patients with rheumatoid arthritis and factors which influence it

Introduction: Patients with rheumatoid arthritis (RA) frequently possess a number of risk factors for osteoporosis. Additionally, oral steroids are often used to control active rheumatoid disease and may further potentiate bone loss. We wished to establish the degree of peripheral bone loss in RA and to assess the influence of oral steroids and other risk factors. Methods: We measured bone mineral density (BMD) in the non-dominant forearm using a DTX 200 osteometer in 191 RA patients who were receiving oral prednisone in a dose of at least 5 mg daily for over 3 months. We compared the results with those of two other groups: 165 RA patients who had never received oral prednisone and 242 normal controls without RA or any history of steroid therapy. Forward stepwise multiple regression analysis was used to determine the effects of age, disease variables and steroids on BMD. Results: Age ( P<0.001), RA ( P<0.02) and steroid therapy ( P<0.05) were all associated with reduced BMD using multiple regression analysis. Duration of RA was also associated with reduced BMD ( P<0.05), but activity of disease was not. By WHO criteria (BMD T score<−2.5 S.D.), 95 (50%) of the RA steroid-treated patients (RAS) had osteoporosis, while 48 (25%) of the RA patients not exposed to steroids (RAN) were osteoporotic. Among the normal controls (NC), 48 (20%) had osteoporosis. The mean (S.D.) BMD Z scores for the three groups were −0.8 (1.3) for RAS, −0.4 (1.3) for RAN and 0.0 (1.0) for NC ( P<0.01 for all differences). The percentages of patients with a Z score of −1 or less were 51% for RAS, 29% for RAN and 14% for NC. These differences were also significant ( P<0.01). Male sex was associated with reduced BMD when compared to female sex ( Z<−1) in the RAS (57 vs. 49%; P<0.05) but not in the RAN (25 vs. 31%) groups. For men with RA, the mean (S.D.) BMD Z scores were −1.3 (1.3) for RAS compared to −0.5 (1.3) for RAN ( P<0.005), while for women the differences were less marked at −0.7 (1.3) for RAS compared to −0.4 (1.3) for RAN ( P<0.05). Conclusions: In general, patients with RA have a significantly reduced forearm BMD, which correlates with increasing disease duration. Exposure to oral steroids increases bone loss, notably in male patients. Patients with RA on oral steroids need BMD measurements with a view to prophylactic therapy in those with a low result. Previous fractures and a daily dose of 15 mg or more of prednisone are also important factors in determining when prophylaxis is indicated.

Plasma concentration of thymus and activation-regulated chemokine is elevated in childhood asthma.

Thymus and activation-regulated chemokine (TARC) is responsible for the trafficking of T(H)2 lymphocytes into sites of allergic inflammation. Serum TARC levels correlate with the severity of atopic dermatitis. The relationship between this marker and the occurrence and severity of asthma has not been evaluated. We tested whether plasma TARC level is a useful marker for asthma and atopy in children. Plasma total IgE levels were measured by means of microparticle immunoassay, and specific IgE levels to common aeroallergens were measured by using a fluorescent enzyme immunoassay. We used a sandwich enzyme immunoassay to measure plasma TARC concentrations. Sixty asthmatic children and 28 age- and sex-matched control subjects were recruited, with mean logarithmic plasma total IgE levels of 2.66 +/- 0.60 kIU/L and 1.74 +/- 0.58 kIU/L, respectively (P <.0001). The median plasma TARC concentration was higher in asthmatic patients without inhaled corticosteroid treatment (131.0 pg/mL) compared with those seen in steroid-treated patients (97.5 pg/mL) and control subjects (76.0 pg/mL; P =.01 and P <.0001, respectively). Plasma TARC concentration was found to correlate with total IgE level in plasma (r = 0.219, P =.04). This marker was also increased in subjects who were sensitized to cat allergen (P =.001) but not in subjects sensitized to other aeroallergens. Disease severity score, FEV(1) value, and atopy were not associated with increased plasma TARC levels. Our results suggest that plasma TARC concentrations are elevated in childhood asthma. This marker is also linked to plasma total IgE levels and cat allergen sensitization.

Increased exhaled cysteinyl-leukotrienes and 8-isoprostane in aspirin-induced asthma.

The pathogenesis of aspirin-induced asthma (AIA) has not yet been clearly elucidated, although eicosanoid metabolites appear to play an important role. We hypothesized that levels of eicosanoids in exhaled air condensate are abnormal in patients with AIA and that they change in patients receiving steroid therapy. We measured cysteinyl-leukotrienes (cys-LTs), prostaglandin E(2) (PGE(2)), and leukotriene B(4) (LTB(4)), and also 8-isoprostane as a marker of oxidative stress, by enzyme immunoassay in exhaled breath condensate from patients with AIA (17 steroid naive; mean age, 41 +/- 23 years; FEV(1), 63%pred), 26 patients with aspirin-tolerant asthma (ATA) (11 steroid naive; mean age, 47 +/- 18 years; FEV(1), 69%pred), and 16 healthy subjects (mean age, 45 +/- 17 years; FEV(1), 93%pred). Cys-LTs were significantly higher in steroid-naive patients with AIA compared with steroid-naive patients with ATA and healthy subjects (152.3 +/- 30.4 and 36.6 +/- 7.1 versus 19.4 +/- 2.8 pg/ml; p < 0.05 and p < 0.05, respectively). Steroid-naive patients with AIA also had higher levels of 8-isoprostane than normal subjects (131.8 +/- 31.0 versus 21.9 +/- 4.5 pg/ml; p < 0.05). There were significantly lower levels of both cys-LTs and 8-isoprostanes in steroid-treated patients with AIA. There was no difference in either the PGE(2) or LTB(4) level between the patient groups. This is the first study to show that cys-LTs and 8-isoprostanes are elevated in expired breath condensate of steroid-naive patients with AIA, and that cys-LTs are decreased in steroid-treated patients. Exhaled PGE(2) levels are not reduced, so that it is unlikely that a deficiency of PGE(2) is an important mechanism, whereas exhaled LTB(4) levels are unchanged, indicating an abnormality beyond 5-lipoxygenase.

Immunosuppressive treatment in dialysis patients.

Immunosuppressive treatment is a critical procedure in dialysis patients, in whom an increased risk of infection is already present. Haemodialytic treatment increases the patient's susceptibility to bacterial infection, mainly by impairing polymorphonuclear leukocyte phagocytosis, but it can also restore the patient's immunological defences by improving the T-cell function, which is reduced by pre-dialysis uraemia. Patients on dialysis usually continue the immunosuppressive treatment that had been established for the illness that caused their renal failure [e.g. systemic lupus erythematosus (SLE) or renal vasculitis]. Less frequently, patients on dialysis need immunosuppression for immunological or inflammatory diseases that appear 'de novo' after initiation of dialysis. SLE and antineutrophil cytoplasmic antibody (ANCA)-related vasculitides are immunological illnesses that frequently cause end-stage renal failure (ESRF). A reduction in serological and/or clinical activity is usually observed in SLE patients after they reach ESRF, but a similar or increased frequency of extrarenal relapse episodes in lupus patients after the beginning of the dialysis, compared with the pre-dialysis period, has also been described. Frequency of relapse episodes in patients on dialysis treatment for ANCA-related vasculitides varies from 10 to 30% per patient/year in different reports, and it is higher than the frequency of relapses after renal transplantation; anti-rejection therapy seems to be the most likely protective factor in these conditions. The treatment of relapse episodes in SLE or ANCA vasculitis in dialysis-dependent patients is usually not different from treatment of relapses in patients with dialysis-independent renal function. However, the risk of severe infection caused by immunosuppressive treatment is relevantly higher in dialysis patients. Furthermore, there is a lack of prospective controlled studies indicating the optimal management of immunosuppressive protocols in dialysis patients. A particularly careful assessment of the patient's risks and benefits is necessary in deciding how long immunosuppressive treatment should last after acute or rapidly progressive renal damage, that should require dialysis treatment, in patients with SLE or ANCA vasculitis. In the above conditions, the risks of prolonging immunosuppressive treatment must be balanced against the relatively good prognosis offered to these patients by dialysis and renal transplantation. In a retrospective review of 24 patients receiving long-term steroid therapy (>3 months) in our dialysis unit in the past 5 years, we found relevant clinical differences in the patients receiving steroid treatment compared with 24 controls. Steroid-treated patients showed less favourable nutritional conditions, with lower serum albumin and body mass index vs non-steroid-treated patients; moreover, C-reactive protein values were persistently higher in the steroid-treated group. Steroid treatment in these patients was usually performed at the beginning of regular dialysis, as a continuation of the treatment that started before the initiation of dialysis. Only two patients, who needed a prolonged low-dose steroidal treatment to control a malnutrition-inflammation-atherosclerosis (MIA) syndrome, started steroids many years after beginning dialysis. Steroid treatment was effective in improving the nutritional condition and inflammatory symptoms in these two patients after all conventional measures had failed.

Safety, tolerability and acceptability of two dry powder inhalers in the administration of budesonide in steroid-treated asthmatic patients

The purpose of this randomized, double-blind parallel group study was to compare the safety, tolerability and acceptability of Easyhaler® and Turbuhaler® dry powder inhalers for the delivery of budesonide 800 μ g day−1 in adult asthmatic patients who had already been treated with inhaled corticosteroids for at least 6 months prior to the study. Additionally the efficacy of the products was evaluated. The main objective was to evaluate the systemic safety of budesonide inhaled from Easyhaler® (Giona® Easyhaler®, Orion Pharma, Finland) as determined by serum and urine cortisol measurements. The secondary objective was to compare the tolerability, acceptability and efficacy of the two devices in the administration of budesonide. After a 2-week run-in period (baseline), patients were randomized on a 2:1 basis to receive budesonide from Easyhaler® (n=103) or from Turbuhaler® (Pulmicort® Turbuhaler®, AstraZeneca, Sweden) (n=58) 200 μ g dose−1, two inhalations twice daily for 12 weeks. There was no statistically significant change in morning serum cortisol values from baseline to the end of treatment in either group. Urine free cortisol and urine cortisol/creatinine ratio increased from baseline in both groups. There were no significant differences between the groups in terms of morning serum cortisol, urine cortisol, adverse events or efficacy variables, but Easyhaler® was generally considered more acceptable to the patients. In conclusion, at 800 μ g day−1, Giona® Easyhaler® is as safe and efficacious as Pulmicort® Turbuhaler® in adult asthmatic patients previously treated with corticosteroids, but more acceptable to patients.