Oral Steroid Requirement Research Articles

Effects of implants with steroids after endoscopic sinus surgery: A systematic review with meta-analysis of randomized controlled trials.

Chronic rhinosinusitis affects approximately 5%-2% of the general population worldwide. Steroid implants after endoscopic sinus surgery (ESS) have drawn considerable interest for their cost savings, but relevant guidelines indicate that evidence on this topic is of low quality with high heterogeneity. The purpose of this study was to examine the efficacy of steroid implants after ESS by synthesizing relevant randomized controlled trials (RCTs). Two authors independently assessed the eligibility of potential references from five biomedical databases. They further extracted relevant data from the included studies, including (a) mean, standard deviation, or standard error for Lund-Kennedy endoscopic (LKE) score and Perioperative Sinus Endoscopy (POSE) score and (b) events and sample sizes of each group for further intervention. Data were pooled in a random-effects model, and results were presented as the weighted mean difference (WMD) or risk ratio (RR) with 95% confidence interval (CI) and I2 . Eleven RCTs (n=853) were included and showed that the steroid implant group had lower LKE scores (WMD, -1.19; 95% CI, -1.75 to -0.62; I2 =0%) and POSE scores (WMD, -1.62; 95% CI, -2.47 to -0.76; I2 =48%) than the placebo implant group at postoperative week 2. Moreover, the reoperation rate in the steroid implant group was also lower than in the placebo implant group (RR, 0.49; 95% CI, 0.30 to 0.80; I2 =0%). However, no significant difference was observed in the postoperative oral steroid requirement between both groups. Collectively, steroid implant decreases LKE and POSE among patients receiving ESS in the short term, but long-term effects remain unclear. Patient-based outcomes are worth further discussion in the future.

Building Bridges for Asthma Care: Reducing School Absence for Inner-City Children With Health Disparities

To assess the effect of a school-based asthma care program on improving school attendance and asthma control.Researchers in this study included children ages 5 to 14 years in 28 schools within the Denver and Hartford public school systems who were managed for 2 consecutive school years.Students were identified by using school health and medication authorization forms; risk was assessed by using the Asthma Intake Form, which used self-reported criteria such as emergency department or hospital visits, oral steroid requirement, school absenteeism, and markers of uncontrolled asthma. Students and their caregivers received targeted case management, including asthma education, inhaler training, regular school nurse visits, assessment of asthma control, and coordination with primary care. The control group consisted of matched children who did not participate in the program. The primary outcome was rate of absences; secondary outcomes included rescue inhaler use and Asthma Control Test (ACT) scores.Of the 2178 students who were identified as having asthma, 1390 returned an Asthma Intake Form, and 781 met high-risk asthma criteria. A total of 463 high-risk students were enrolled in the Building Bridges for Asthma Care Program, 292 declined to participate, and 26 were lost to follow-up. The majority of Building Bridges program participants were Hispanic (69.5%) or black (20.5%); 59% were boys. Participants experienced a 22% absolute decrease in school absenteeism, which equates to 5.5 additional days of school attendance per student per year. Likewise, the number of children with ACT scores of less than the control threshold of 20 decreased from 42.7% to 28.8%. Bronchodilator use >2 times per week decreased from 35.8% to 22.9%, and ACT scores improved in 37.4%. School nurses spent ∼120 minutes per week implementing the program.School-based interventions with an emphasis on school nurse involvement can both reduce school absenteeism and improve asthma control by coordinating care with children, their caregivers, and clinicians. Time spent by school nurses in program implementation was manageable and may be justified by time saved in acute asthma management. Limitations of the study include nonrandomized selection of controls and lack of data regarding the actual reason for school absences.This study highlights how school-based asthma management programs can improve asthma control and reduce school absenteeism with the potential for far-reaching impact. Broad application of such programs should be considered.

Safety and Effectiveness of Bronchial Thermoplasty When FEV1 Is Less Than 50%

Randomized clinical trials of bronchial thermoplasty (BT) were conducted in patients with a baseline FEV1 greater than 50%. There is a paucity of data regarding BT in patients with more severe obstruction, and consequently these patients are often excluded from receiving BT. The purpose of this study was to compare safety and efficacy outcomes in a large cohort of patients with an FEV1 less than 50%with those of a cohort of less obstructed patients. Consecutive patients with severe asthma were drawn from the Australian BT Registry. Patients were grouped into (1) those with a baseline prebronchodilator FEV1 %predicted< 50%(n= 32) or (2) those with an FEV1≥ 50%(n= 36). Adverse outcomes were defined as (1) remaining in hospital longer than the planned 24-hour admission posttreatment or (2) being readmitted to hospital for any cause within 30days of a treatment. Efficacy outcomes were evaluated 6months after BT. More severely obstructed patients were no more likely to have experienced any adverse event. Significant improvements in Asthma Control Questionnaire score, exacerbation frequency, reliever medication use, and requirement for daily oral steroids were observed in both groups, and were of a similar degree. This study demonstrates that BT can confidently be offered to patients with asthma with an FEV1 that is 30%to 50%of predicted without risk of more frequent or more severe adverse events, and with the expectation of the same degree of response as patients with better lung function.

Omalizumab in the treatment of eosinophilic granulomatosis with polyangiitis (EGPA): single-center experience in 18 cases

Background Data are limited regarding the effectiveness of omalizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Our aim was to evaluate the clinical and functional effectiveness of omalizumab in patients with EGPA in long-term follow-up.Methods This study was a retrospective chart review of patients with EGPA who were treated with omalizumab injections between May 2012 and April 2018. Once treatment with omalizumab was started, data were collected at various time points: baseline, the 16th week, 1st year, and annually until the last evaluation.Results Eighteen patients (16F/2M) with a mean age of 48.61 ± 11.94 years were included. Data were available for all patients for the first year, 12 patients for the second year, 10 patients for the third year, 8 patients for the fourth year and 5 patients for the fifth year. All patients were on mean dosage of 15.77 ± 7.6 mg/day oral corticosteroid (OCS) as daily bases for mean 8.61 ± 4 years besides high-dose inhaler corticosteroid/long-acting beta agonist. Antineutrophil cytoplasmic antibodies (ANCA) were positive in 2 patients, and 8 patients were diagnosed as having vasculitis by skin biopsy, one patient had polyneuropathy, and one patient had cardiac involvement.By considering the individual responses of patients and the level of improvement at the last evalulation, 10 (55.6%) patients responded completely, 1 responded partially, and 7 (38.9%) had no improvement. Omalizumab worked as a steroid-sparing agent in all patients and the daily OCS dose was reduced with a mean dosage of 6.28 mg/day at the end of the first year. The mean OCS reduction time for the whole group was 4 months. A reduction in asthma exacerbations/hospitalizations, improvement in forced expiratory volume in 1 second, and no decrease in the eosinophil count during treatment with omalizumab were also observed.Conclusions Omalizumab improved asthma control in some patients with EGPA with uncontrolled asthma by reducing asthma exacerbations and oral steroid requirement. However, more data are needed before recommending widespread use of omalizumab in patients with EGPA.

Quantifying Exposure to Diagnostic Radiation and Factors Associated With Exposure to High Levels of Radiation in Korean Patients With Inflammatory Bowel Disease

Several recent studies have revealed that diagnostic imaging can result in exposure to potentially harmful levels of ionizing radiation in patients with inflammatory bowel disease (IBD). However, these studies have been conducted exclusively in Western countries, and no data are available in Asian populations. The aim of this study was to estimate the diagnostic radiation exposure in Korean patients with IBD and to determine the factors associated with high radiation exposure. Patients with an established diagnosis of IBD between July 1987 and January 2012 were investigated in 13 university hospitals in Korea. The cumulative effective dose (CED) was calculated retrospectively from standard tables. A total of 777 patients with Crohn's disease (CD) and 1422 patients with ulcerative colitis (UC) were included in the study. The mean CED for CD and UC were 53.6 and 16.4 mSv, respectively (P < 0.001). CTof CD and UC accounted for 81.6% and 71.2% of total effective dose, respectively. Importantly, 34.7% of patients with CD and 8.4% of patients with UC were exposed to high levels of radiation (CED > 50 mSv) (P < 0.001). High radiation exposure was associated with long disease duration, ileocolonic disease, upper gastrointestinal tract involvement, surgical intervention, hospitalization, and the requirement for oral steroids in CD, and with surgical intervention, hospitalization, and the requirement for infliximab in UC. A substantial proportion of patients with IBD, especially patients with CD, were exposed to significantly harmful amounts of diagnostic radiation, mainly as a result of CT examination. Given that IBD is a life-long illness, strategies to reduce radiation exposure from diagnostic imaging need to be considered.

Minocycline Blocks Asthma-associated Inflammation in Part by Interfering with the T Cell Receptor-Nuclear Factor κB-GATA-3-IL-4 Axis without a Prominent Effect on Poly(ADP-ribose) Polymerase

Minocycline protects against asthma independently of its antibiotic function and was recently reported as a potent poly(ADP-ribose) polymerase (PARP) inhibitor. In an animal model of asthma, a single administration of minocycline conferred excellent protection against ovalbumin-induced airway eosinophilia, mucus hypersecretion, and Th2 cytokine production (IL-4/IL-5/IL-12(p70)/IL-13/GM-CSF) and a partial protection against airway hyperresponsiveness. These effects correlated with pronounced reduction in lung and sera allergen-specific IgE. A reduction in poly(ADP-ribose) immunoreactivity in the lungs of minocycline-treated/ovalbumin-challenged mice correlated with decreased oxidative DNA damage. The effect of minocycline on PARP may be indirect, as the drug failed to efficiently block direct PARP activation in lungs of N-methyl-N'-nitro-N-nitroso-guanidine-treated mice or H(2)O(2)-treated cells. Minocycline blocked allergen-specific IgE production in B cells potentially by modulating T cell receptor (TCR)-linked IL-4 production at the mRNA level but not through a modulation of the IL-4-JAK-STAT-6 axis, IL-2 production, or NFAT1 activation. Restoration of IL-4, ex vivo, rescued IgE production by minocycline-treated/ovalbumin-stimulated B cells. IL-4 blockade correlated with a preferential inhibition of the NF-κB activation arm of TCR but not GSK3, Src, p38 MAPK, or ERK1/2. Interestingly, the drug promoted a slightly higher Src and ERK1/2 phosphorylation. Inhibition of NF-κB was linked to a complete blockade of TCR-stimulated GATA-3 expression, a pivotal transcription factor for IL-4 expression. Minocycline also reduced TNF-α-mediated NF-κB activation and expression of dependent genes. These results show a potentially broad effect of minocycline but that it may block IgE production in part by modulating TCR function, particularly by inhibiting the signaling pathway, leading to NF-κB activation, GATA-3 expression, and subsequent IL-4 production.

Prevalence of Bronchiectasis in Asthma according to Oral Steroid Requirement: Influence of Immunoglobulin Levels

Purpose. To establish the prevalence of bronchiectasis in asthma in relation to patients' oral corticosteroid requirements and to explore whether the increased risk is due to blood immunoglobulin (Ig) concentration. Methods. Case-control cross-sectional study, including 100 sex- and age-matched patients, 50 with non-steroid-dependent asthma (NSDA) and 50 with steroid-dependent asthma (SDA). Study protocol: (a) measurement of Ig and gG subclass concentration; (b) forced spirometry; and (c) high-resolution thoracic computed tomography. When bronchiectasis was detected, a specific etiological protocol was applied to establish its etiology. Results. The overall prevalence of bronchiectasis was 12/50 in the SDA group and 6/50 in the NSDA group (p = ns). The etiology was documented in six patients (four NSDA and two SDA). After excluding these patients, the prevalence of bronchiectasis was 20% (10/50) in the SDA group and 2/50 (4%) in the NSDA group (P < 0.05). Patients with asthma-associated bronchiectasis presented lower FEV1 values than patients without bronchiectasis, but the levels of Ig and subclasses of IgG did not present differences. Conclusions. Steroid-dependent asthma seems to be associated with a greater risk of developing bronchiectasis than non-steroid-dependent asthma. This is probably due to the disease itself rather than to other influencing factors such as immunoglobulin levels.

Effect of Tetracyclines on IgE Allergic Responses and Asthma

There are no current therapies that specifically target IgE production in human allergic disease. We found that tetracyclines and chemically modified tetracyclines (CMT) that lack antibiotic activity prevent IgE production, making them ideal candidates for anti-allergy therapy. This is based on our findings that minocycline treatment of allergic asthmatic humans significantly improves their asthma symptoms, reduces their oral steroid requirements, and strongly suppresses their ongoing IgE responses. Tetracyclines and CMT also suppress ongoing IgE responses of BPO-KLH sensitized mice in vivo and in vitro and humans IgE responses in vitro. We also found that highly increased levels of phosphorylated p38 MAP kinase, but not phosphorylated JNK or ERK, are expressed by blood T and B cells and monocytes of allergic asthmatic humans. Levels of phosphorylated p38 MAP kinase, but not ERK or JNK, correlated with their IgE. Tetracyclines significantly suppressed expression of phosphorylated p38 MAP kinase by CD4+ and CD8+ T cells but not B cells or monocytes in vivo and in vitro. Our findings open the door to development of new drugs and patents, especially for CMTs that lack antibiotic activity (US 7649113), for treatment of human allergic disease.

Citron vert, bière et phytophotodermatose

Background Data are limited regarding the effectiveness of omalizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Our aim was to evaluate the clinical and functional effectiveness of omalizumab in patients with EGPA in long-term follow-up.Methods This study was a retrospective chart review of patients with EGPA who were treated with omalizumab injections between May 2012 and April 2018. Once treatment with omalizumab was started, data were collected at various time points: baseline, the 16th week, 1st year, and annually until the last evaluation.Results Eighteen patients (16F/2M) with a mean age of 48.61 ± 11.94 years were included. Data were available for all patients for the first year, 12 patients for the second year, 10 patients for the third year, 8 patients for the fourth year and 5 patients for the fifth year. All patients were on mean dosage of 15.77 ± 7.6 mg/day oral corticosteroid (OCS) as daily bases for mean 8.61 ± 4 years besides high-dose inhaler corticosteroid/long-acting beta agonist. Antineutrophil cytoplasmic antibodies (ANCA) were positive in 2 patients, and 8 patients were diagnosed as having vasculitis by skin biopsy, one patient had polyneuropathy, and one patient had cardiac involvement.By considering the individual responses of patients and the level of improvement at the last evalulation, 10 (55.6%) patients responded completely, 1 responded partially, and 7 (38.9%) had no improvement. Omalizumab worked as a steroid-sparing agent in all patients and the daily OCS dose was reduced with a mean dosage of 6.28 mg/day at the end of the first year. The mean OCS reduction time for the whole group was 4 months. A reduction in asthma exacerbations/hospitalizations, improvement in forced expiratory volume in 1 second, and no decrease in the eosinophil count during treatment with omalizumab were also observed.Conclusions Omalizumab improved asthma control in some patients with EGPA with uncontrolled asthma by reducing asthma exacerbations and oral steroid requirement. However, more data are needed before recommending widespread use of omalizumab in patients with EGPA.

Non-antibiotic properties of tetracyclines as anti-allergy and asthma drugs

All available therapies for human allergic disease target IgE mediated pathologic responses after IgE has been produced. We are developing tetracyclines as anti-allergy drugs to prevent IgE production, based on our findings that minocycline or doxycycline treatment of allergic asthmatic humans significantly improves their asthma symptoms, reduces their oral steroid requirements, and strongly suppresses their ongoing IgE responses (ELISA, mast cell mediated cutaneous late phase responses); the tetracyclines also strongly suppress peak IgE responses of BPO-KLH sensitized mice (ELISPOT assay, ELISA, skin tests). The antibiotic activity of the tetracyclines is not required for suppression of IgE responses; inclusion of minocycline or doxycycline in sterile culture prevents anti-CD40/IL-4 mediated induction of memory IgE responses by PBMC of allergic asthmatic patients (ELISA), and induction of specific memory IgE responses by spleen cells of BPO-KLH sensitized mice (ELISPOT assay, ELISA). The tetracyclines affect an epsilon specific pathway because IgM, IgG and IgA responses did not decrease. Further, in humans, DTH responses to recall antigens did not decrease. In related studies, we found that two distinct T cell subsets: CD4+CD60 negative and CD8+CD60+ (CD60 is a ganglioside) (humans) and CD4+ Asialo GM1 ganglioside negative and CD8+Asialo GM1 ganglioside+ (mice), both are required for induction of memory IgE responses. Phosphorylated (phos) p38 MAP kinase, but not phos ERK or phos JNK expression by CD4+ and CD8+, including CD8+CD60+, T cells is increased in allergic asthmatic humans, as is IL-4 and IL-10 production. The tetracyclines appear to target T cell pathways to induce suppression of IgE responses because they suppress phos p38 MAP kinase expression by both CD4+ and CD8+, including CD8+CD60+, T cell subsets, and IL-4 and IL-10, while upregulating IL-2 and IFN gamma, and suppressing IgE responses. Our finding that tetracyclines do not require antibiotic activity to suppress IgE responses opens the door to development of new tetracycline-based and other therapeutics for human allergic disease.

Omalizumab in the management of oral corticosteroid-dependent IGE-mediated asthma patients

Background:Several studies have demonstrated the beneficial effects of omalizumab in asthma patients. Here we describe the drug’s tolerance and oral corticosteroid sparing capacity in a long-term observational study.Methods:Thirty-two patients aged ≥18 years with obstructive airway disease and FEV1 reversibility ≥12% and 200 mL, with an oral steroid requirement ≥7.5 mg per day of prednisolone during a period of ≥1 year, a positive prick test or in vitro reactivity (RAST) to at least one perennial aeroallergen and a baseline immunoglobulin E level ranking between 30–700 IU/mL were prospectively followed for 17.2 ± 8.5 months. Patients were visited once or twice a month, depending on their schedule for omalizumab administration. Intervention: blood analysis every six months; spirometry and nitric oxide measurement at every visit.Results:One patient who dropped out early was excluded. Follow-up period: the treatment benefited 83.9% (26/31) of the cohort; oral corticosteroids were reduced from 7.19 ± 11.1 to 3.29 ± 11.03 mg (p < 0.002) and withdrawn in 74.2% of patients. FEV1 (percent predicted) was 64.4 ± 22.7 at the beginning and 62.9 ± 24.3 at the end. IgE at entry was 322.2 ± 334.2 IU/mL and increased 2.34-fold. Respiratory function and NO did not present statistically significant changes. We identified three groups of patients: the first (n = 17) receiving oral steroid at entry in whom the accumulated dose of oral steroids progressively decreased; another (n = 10) including patients who had quit oral steroids before starting omalizumab although they had not been instructed to do so and whose oral steroid dose at the end of follow-up was zero; and a third group (n = 4) that did not benefit from omalizumab treatment. The only relevant side effect was a flu-like syndrome which required discontinuation of treatment in one patient.Conclusion:In our series, a substantial, safe decrease in oral corticosteroid requirements was observed due, at least to some extent, to omalizumab therapy. Oral corticosteroids were withdrawn in three-quarters of the patients. We were unable to identify a factor able to predict which patients would benefit most from omalizumab treatment.

Minocycline treatment results in reduced oral steroid requirements in adult asthma

The tetracycline antibiotics have pleiotropic anti-inflammatory properties that may explain their therapeutic benefit in rheumatoid arthritis and acne. As these agents suppress both cellular and humoral immune responses, they may be of benefit in treating asthma and other allergic disorders. The purpose of this study was to determine whether minocycline therapy of asthma has steroid sparing effects beyond its inherent antibiotic properties. Adult asthmatic patients (n = 17) were treated with minocycline 150 mg p.o. twice daily or placebo for 8 weeks in a randomized, double-blind, placebo-controlled crossover study. Patients were evaluated for clinical improvement in oral steroid requirements, spirometry, and symptom scores (Asthma Quality of Life Questionnaire). They underwent assessment for preexisting infection (CT facial sinuses, Chlamydia pneumoniae nasopharyngeal culture, and C. pneumoniae and Mycoplasma pneumoniae serology). Minocycline use was associated with a 30% reduction in mean daily prednisone use compared with placebo (8.8 mg versus 14.4 mg, respectively; p = 0.02). Pulmonary function testing showed improvement in forced vital capacity (FVC; percent predicted; p = 0.03) and improvement in actual FVC and forced expiratory volume in 1 second (percent predicted) approached statistical significance (p = 0.05 and 0.08, respectively). Minocycline treatment was associated with significant improvement in asthma symptoms brought on by environmental triggers (p = 0.01). This preliminary study of minocycline therapy showed oral steroid-sparing properties for those with moderate persistent and severe persistent asthma.

Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a condition associated with high morbidity, mortality and cost to the community. Patients often report symptomatic improvement with short-acting beta-2 agonists (SABA) and anticholinergic bronchodilator medications, and both are recommended in COPD guidelines. These medications have different mechanisms of action and therefore could have an additive effect when combined. To compare the relative efficacy and safety of regular long term use (at least four weeks) of ipratropium bromide and short- acting beta-2 agonist therapy in patients with stable COPD. The Cochrane Airways Group Specialised Register of Trials was searched. Bibliographies were checked to identify relevant cross-references. Drug companies were contacted for relevant trial data. The searches are current to August 2005. All randomised controlled trials comparing at least 4 weeks of treatment with an anticholinergic agent (ipratropium bromide) alone or in combination with a beta-2 agonist (short acting) versus the beta-2 agonist alone, delivered via metered dose inhaler or nebuliser, in non-asthmatic adult subjects with stable COPD. Data extraction and study quality assessment was performed independently by three reviewers. Authors of studies and relevant manufacturers were contacted if data were missing. Eleven studies (3912 participants) met the inclusion criteria of the review. Small benefits of ipratropium over a short-acting beta-2 agonist were demonstrated on lung function outcomes. There were small benefits in favour of ipratropium on quality of life (HRQL), as well as a reduction in the requirement for oral steroids. Combination therapy with ipratropium plus a short-acting beta-2 agonist conferred benefits over a short-acting beta-2 agonist alone in terms of post-bronchodilator lung function. There was no significant benefit of combination therapy in subjective improvements in HRQL, but again there was a reduction in the requirement for oral steroids. The available data from the trials included in this review suggest that the advantage of regular long term use of ipratropium alone or in combination with a short-acting beta-2 agonist or over a beta-2 agonist alone are small, if the aim is to improve lung function, symptoms and exercise tolerance. Until further data are available, the strategy of providing a short-acting beta-2 agonist on a PRN basis, and then either continuing with the short-acting beta-2 agonist regularly or conducting an "n of 1" trial of regular beta-2 agonist or regular anticholinergic to determine the treatment that gives the best relief of symptoms (and continuing with it), would seem cost effective. This strategy does need formal evaluation. Patient preference is also important, as is the relative importance of avoiding the use of systemic corticosteroids.

Benefits of low weekly doses of methotrexate in steroid-dependent asthmatic patients. A double-blind, randomized, placebo-controlled study

Though several drugs have been tested, the choice of the ideal steroid-sparing agent in steroid-dependent asthmatic patients remains unclear. Our objective was to evaluate the efficacy and tolerance of methotrexate in low weekly doses in order to decrease chronic oral steroid requirements in asthmatic patients. double blind randomized placebo-controlled study. The study was performed in a 760-bed teaching hospital. 46 steroid-dependent asthmatic patients were randomized. PATIENTS received 10mg of methotrexate or placebo once weekly for a year. The 6-methylprednisolone was progressively tapered (2mg/day every two weeks) until FEV1 diminished by 5% or more; 6-methylprednisolone was then increased until the previous FEV1 was reached, and the procedure was repeated throughout follow-up. Blood and urine analyses and bone densitometry were performed at entry and at the end of the study. Pulmonary function was tested monthly during the first three months and then every three months until the end. Thirty-nine patients were evaluated at interim analysis. A 54.8% decrease (9.5+/-4.9 mg/day) in 6-methylprednisolone dose was observed in the methotrexate group and a 4.4% decrease (0.5+/-7.2 mg/day) in the placebo group (P<0.001). There was no significant decrease of FEV1 in either group. No changes in bone metabolism were observed except for a non-statistically significant increase in osteocalcin levels in the treated group compared to a decrease in the placebo group. Toxicity was mild. (1) Methotrexate is an effective steroid-sparing agent. (2) A dosage lower than the one recommended in the literature is effective. (3) Tolerance is good. (4) No benefit or detrimental effects in bone metabolism were observed after one year.

Minocycline treatment results in reduced oral steroid requirements and suppresses IgE responses in adult asthma

RATIONALE: The tetracycline antibiotics have pleiotropic anti-inflammatory properties and are used to treat acne and rheumatoid arthritis; minocycline therapy is oral steroid-sparing in the latter condition. The present studies investigated the oral steroid-sparing potential of minocycline in the treatment of asthma.

Use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth

Background Inhaled steroids are recommended for the treatment of persistent asthma during pregnancy, but their potential effects on intrauterine growth have been inadequately evaluated. Objective The purpose of this study was to evaluate the association between maternal use of specific inhaled steroids and inhaled steroid dose during pregnancy and the incidence of infants who are small for gestational age (SGA) and mean birth weight. Methods Pregnant asthmatic women being treated with inhaled steroids were enrolled in the study before delivery by their managing allergists. Information regarding the specific inhaled steroid and daily dose used, requirement for oral steroids, occurrence of acute asthmatic episodes, maternal race, birth weight, gestational age, and congenital malformations was obtained for each patient. SGA was defined through use of a published normative sample of American births. Results A total of 474 women were enrolled in the study; of the 451 enrolled participants whose pregnancy ended in a singleton live birth, 396 (88%) completed the study. The incidence of infants with low birth weight, preterm births, and congenital malformations in this cohort was not greater than expected in the general population. The incidence of SGA was 7.1% (95% CI, 5.0% to 10.1%). No significant relationships between specific inhaled steroid or dose of inhaled steroid used and either SGA or mean birth weight were observed. Conclusion These data suggest that the use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth and supports the recommendation that inhaled steroids should be used in the management of persistent asthma during pregnancy.

COPD exacerbations: the importance of a standard definition

Efforts to assess the efficacy of new therapies in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) have been hampered by the lack of a widely agreed and consistently used definition. A variety of definitions have been used in clinical studies, based on changes in patient symptoms or the requirement for antibiotic therapy, oral steroids or hospitalisation. To date, none of these definitions have been assessed in detail for their reliability, responsiveness and validity determined. Considerable heterogeneity in the aetiology and manifestation of COPD exacerbations makes identification and quantification of defining symptoms extremely difficult. New approaches are therefore being sought with a view to identifying a serum or tissue marker that can be used as a valuable diagnostic tool. Improvements in data recording will also contribute to the accuracy of data retrieval and assessment. If we are to progress to a level of sophistication seen in the diagnosis and management of other diseases, it is evident that considerable research efforts will be required to improve our understanding of COPD exacerbations and develop a standard definition for these events, thereby facilitating the assessment of therapeutic approaches.

Role of intravenous immunoglobulin in severe steroid-dependent asthma.

Subgroups of asthma patients have extremely severe respiratory symptoms that require chronic use of steroids for disease control. These patients are at risk of significant side-effects from chronic exposure to high doses of oral steroids. Intravenous immunoglobulin (IVIG) has immunomodulatory properties as shown by its use in some immune disorders. A few trials have suggested a possible benefit in individuals with severe asthma. To evaluate the role of IVIG as an adjunctive therapy in steroid-dependent asthma, monitoring the outcomes of lung function and measured reduction in oral steroid requirement. Seven patients with severe steroid-dependent asthma were given IVIG at a dose of 1 g/kg each month for 6 months. Baseline pulmonary function tests and immunoglobulin levels were obtained. At the end of 6 months, the end-points observed were lung function and the degree of reduction in the dose of oral steroids. The number of hospital admissions during the 12 months following commencement of IVIG was compared with the preceding 12 months. There was a significant reduction in daily prednisolone dose from 56 +/- 31 mg to 39 +/- 35 mg (P=0.04, Wilcoxon rank sum test) and a decrease in the number of hospital admissions from 5.9 +/- 2.9 to 3.6 +/- 3.5 (P=0.04). No significant improvement occurred in lung function. IVIG provides a potentially important adjunctive therapy in severe steroid-dependent asthma, reducing steroid requirement and decreasing hospital admissions, but not improving lung function.

European Consensus Lupus Activity Measurement is sensitive to change in disease activity in childhood-onset systemic lupus erythematosus.

To evaluate the European Consensus Lupus Activity Measurement (ECLAM) for responsiveness to change in disease activity when used in childhood-onset systemic lupus erythematosus (cSLE). To confirm the construct validity and to characterize the measurement properties of the ECLAM by assessing its ability to predict damage and steroid requirements. The disease courses of 66 newly diagnosed cSLE patients were reviewed. The ECLAM and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were scored for all clinic visits and hospitalizations. Damage was assessed at the end of the followup period using the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index. Disease activity at the time of diagnosis, 6 months after diagnosis, at the time of first flare, and 6 months after first flare was used to estimate responsiveness of the measures. Responsiveness was measured by the effect size, the effect size index, the standardized response mean, and the relative efficiency index (REI). The measurement properties of the ECLAM and SLEDAI over time were examined by comparing the ability of both measures to predict damage and oral steroid requirement. The ECLAM and SLEDAI are both responsive to change in disease activity irrespective of the statistic used. The ECLAM is more sensitive than the SLEDAI using the REI (all >1.9). Cumulative disease activity as measured by the SLEDAI or the ECLAM are important predictors of damage. There are no statistically important differences between the 2 measures with regard to their ability to predict steroid requirements. The ECLAM has construct validity in cSLE and, like the SLEDAI, is highly sensitive to clinically important change in disease activity. The ECLAM may be more responsive. The quantitative properties of the 2 measures are very similar. The SLEDAI likely remains the preferable disease activity measure for cSLE given its overall measurement properties and ease of use.

Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering β2agonists bronchodilators in asthma

Objectives: To determine the clinical effectiveness of pressurised metered dose inhalers compared with other hand held inhaler devices for delivering short acting β2 agonists in stable asthma.Design: Systematic review of...