Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material

The x-ray contrast mediums used over the past three decades have been salts of iodinated acids administered in highly hypertonic concentrations. We conducted a multiinstitutional randomized study of the protective effects of pretreatment with corticosteroids against reactions to intravenous contrast material. We gave 6763 patients two doses of oral corticosteroids (methylprednisolone, 32 mg) approximately 12 hours and 2 hours before challenge with contrast material, one dose of oral prednisolone approximately 2 hours before challenge, or placebo in the same dosages. The two-dose corticosteroid regimen, but not the one-dose regimen, significantly reduced the incidence of reactions of all types (P less than 0.05) except a category of reactions dominated by hives, for which the reduction approached significance (P = 0.055). In recent years, several relatively expensive monomeric nonionic iodinated compounds having approximately half the osmolality of the corresponding ionic compounds and a lower reaction rate have become available. With our two-dose corticosteroid regimen, the incidence of reactions necessitating therapy in patients receiving the ionic medium approximated that reported in an unblinded nonrandomized study of patients receiving a newer intravenous nonionic medium without corticosteroid pretreatment. We conclude that the much less expensive ionic medium, if administered with corticosteroid pretreatment, may serve as a reasonable alternative to intravenous nonionic medium, without loss of safety.     

Efficacy of soluble IL-4 receptor for the treatment of adults with asthma

BACKGROUND: IL-4 mediates important proinflammatory functions in asthma, including induction of the IgE isotype switch, increased expression of vascular cell adhesion molecule 1 and promotion of eosinophil transmigration across the endothelium, stimulation of mucus production, and T(H)2 lymphocyte differentiation, leading to release of IL-4, IL-5, IL-9, and IL-13. OBJECTIVE: The current study evaluated the therapeutic potential of inhaled recombinant human soluble interleukin-4 receptor (IL-4R) as an IL-4 antagonist. METHODS: This study was a randomized, double-blind, placebo-controlled study in 62 subjects involving 12 once weekly nebulizations of 0.75, 1.5, or 3.0 mg of IL-4R or placebo. During screening, subjects documented dependence on inhaled corticosteroids by an exacerbation in asthma induced by one or two 50% dose reductions at 2-week intervals. After restabilization for 2 weeks on the dose above which their asthma flared, inhaled steroids were discontinued, patients were randomized, and study medication was started on day 0. RESULTS: IL-4R was well tolerated. Efficacy was demonstrated by a decline in FEV(1) observed in the placebo group (-0.4 L and -13% predicted), which did not occur in the group receiving 3.0 mg of IL-4R (-0.1 L and -2% predicted; P =.05 over the 3-month treatment period). Daily patient-measured morning FEV(1) also demonstrated a significant decline in the placebo group (-0.5 L and -18% predicted), which did not occur in the group receiving 3.0 mg of IL-4R (-0.1 L and -4% predicted; P =.02 over the 3-month treatment period). The efficacy of IL-4R was further confirmed by the absence of increase in asthma symptom scores in the group receiving 3.0 mg of IL-4R (Delta 0.1) compared with that seen in the placebo group (Delta 1.4 over 1 month; P =.07). Study discontinuation for asthma exacerbation was not significantly different between groups (placebo, 56%; 3.0 mg of IL-4R, 47%; P = not significant). CONCLUSION: These promising data suggest that IL-4R is safe and effective in the treatment of moderate persistent asthma.     

High-dose intramuscular triamcinolone in severe, chronic, life-threatening asthma

BACKGROUND. Despite oral corticosteroid therapy, some patients with asthma have frequent exacerbations requiring emergency room visits, hospitalization, and occasionally, mechanical ventilation. We compared the effects of high-dose intramuscular triamcinolone with oral prednisone in patients with severe chronic asthma. METHODS. In a double-blind, placebo-controlled, cross-over study that spanned all seasons, we treated 12 patients with high-dose intramuscular triamcinolone (360 mg over the first three days of the treatment period) or low-dose oral prednisone (median dose, 12.5 mg per day throughout the period; range 0 to 30). The two three-month treatment periods were separated by a three-month washout period. During all periods the patients were allowed to take additional doses of prednisone for acute exacerbations of asthma. RESULTS. After receiving triamcinolone, the patients had significantly better peak expiratory flow rates than while receiving prednisone (the average [+/- SEM] weekly percent of the predicted value during the triamcinolone period was 91.5 +/- 6.9, as compared with 75.0 +/- 5.9 for the prednisone period; P less than 0.05). During the prednisone period there were 21 emergency room visits and 10 hospitalizations, but there were none during the triamcinolone period (P less than 0.05). There were two episodes of ventilatory failure during the prednisone period. Total steroid doses were significantly smaller during the triamcinolone period than during the prednisone period (P less than 0.04). Steroidal side effects were more pronounced after treatment with triamcinolone than after treatment with prednisone (P less than 0.1). CONCLUSIONS. We conclude that high-dose intramuscular triamcinolone is more effective than low-dose prednisone in patients with severe, chronic, life-threatening asthma, but steroidal side effects are somewhat worse.     

Addition of salmeterol to low-dose fluticasone versus higher-dose fluticasone: an analysis of asthma exacerbations

BACKGROUND: Adding salmeterol to low-dose fluticasone propionate (FP) produces greater improvements in pulmonary function and symptom control than increasing the dose of FP in patients who remain symptomatic with low-dose FP. OBJECTIVE: We sought to compare the rates and characteristics of asthma exacerbations in patients after adding salmeterol to low-dose FP with the rates and characteristics of exacerbations in patients receiving higher dose FP. METHODS: In 2 multicenter, double-blind studies, 925 patients 12 years of age and older receiving 88 microg twice daily FP randomly received either 42 microg of salmeterol and 88 microg of FP or an increased dose of FP (220 microg) twice daily for 24 weeks. Exacerbation rates and clinical measures of asthma worsening were assessed for all patients who experienced an asthma exacerbation. RESULTS: The addition of salmeterol resulted in a significantly lower rate and number of exacerbations compared with higher dose FP. A total of 41 (8.8%) patients experienced 47 exacerbations with the addition of salmeterol compared with 63 (13.8%) patients with 75 exacerbations in the group receiving increased-dose FP (P =.017). Salmeterol plus low-dose FP was significantly more protective than increased-dose FP in preventing asthma exacerbations, as assessed by the time to first exacerbation (P <.05). In both groups clinical indicators of worsening asthma showed parallel changes before asthma exacerbation, and greater improvements were observed after exacerbation with salmeterol compared with higher dose FP. CONCLUSION: Salmeterol plus low-dose FP was more effective than higher dose FP alone in reducing asthma exacerbations in patients with persistent asthma. The ability to detect deteriorating asthma and the severity of exacerbation was similar between groups.     

The Patient with Asthma in the Emergency Department

Asthma is a highly prevalent disease that presents commonly to the emergency department (ED) in acute exacerbation. Recent asthma treatment guidelines have added content dedicated to the management of acute exacerbations. Effective management of an exacerbation requires rapid assessment of severity through physical examination, measurement of peak expiratory flow rate, and response to initial treatment. Most therapies are directed at alleviating bronchospasm and decreasing airway inflammation. While inhaled short-acting beta-agonists, systemic corticosteroids, and supplemental oxygen are the initial and often only therapies required for patients with mild moderate exacerbations, high-dose beta agonists and inhaled anti-cholinergics should also be given to patients with severe exacerbations. Adjunctive therapy with intravenous magnesium and Heliox-driven nebulization of bronchodilators should be considered for patients presenting with severe and very severe exacerbations. Early recognition and appropriate management of respiratory failure are required to mitigate the risk of complications including death. Disposition should be determined based on serial assessments of the response to therapy over the first 4 h in the ED. Patients stable for discharge should receive medications, asthma education including a written asthma action plan, and should have follow-up scheduled for them by ED staff. Rapid implementation of evidence-based, multi-disciplinary care is required to ensure the best possible outcomes for this potentially treatable disease.     

A comparison of inhaled fluticasone and oral prednisone for children with severe acute asthma

BACKGROUND: Inhaled corticosteroids are effective in the treatment of children with asthma. It is uncertain how inhaled corticosteroids compare with oral corticosteroids in the management of severe acute disease. METHODS: We performed a double-blind, randomized trial involving 100 children five years of age or older who had severe acute asthma (indicated by a forced expiratory volume in one second [FEV1] that was less than 60 percent of the predicted value) and in whom the results could be evaluated. All were treated with an aggressive bronchodilator regimen and received one dose of either 2 mg of inhaled fluticasone through a metered-dose inhaler with a spacer or 2 mg of oral prednisone per kilogram of body weight. They were assessed hourly for up to four hours. RESULTS: The mean (+/-SD) base-line FEV1 as a percentage of the predicted value was 46.3+/-12.5 in the fluticasone group (51 subjects) and 43.9+/-9.9 in the prednisone group (49 subjects). The FEV1 increased by a mean of 9.4+/-12.5 percentage points in the fluticasone group and by 18.9+/-9.8 percentage points in the prednisone group four hours after therapy (P< 0.001). None of the children in the prednisone group had a reduction in FEV1 as a percentage of the predicted value from base line to four hours, as compared with 25 percent of those in the fluticasone group (P<0.001). Sixteen (31 percent) of the children treated with fluticasone were hospitalized, as compared with five (10 percent) of those treated with prednisone (P=0.01). CONCLUSIONS: Children with severe acute asthma should be treated with oral prednisone and not with inhaled fluticasone or a similar inhaled corticosteroid.     

Effect of single dose of prednisolone on hospitalisation in patients of acute bronchial asthma

The present study was undertaken to assess the effect of stat dose of oral prednisolone on rate of hospitalisation in patients of acute bronchial asthma. 259 patients, aged 1-65 years presenting with acute exacerbation of asthma were randomised in a double blind fashion to receive a stat dose of oral prednisolonev (30 mg if age < 5 years; 60 mg if age > 5 years) or equivalent placebo. Then, nebulbutamol (0.15 mg/kg in 2 m/l normal saline) was given to all patients and patients were re-examined after 4 hours to decide about the hospitalisation. The study revealed that only 37 (26.42%) patients required hospitalisation and further management in prednisolone group compared to 50 (42.01%) patients in placebo group (p < 0.01). This suggests that prompt use of single oral dose of prednisolone along with routine bronchodilator therapy can significantly reduce morbidity and need for hospital admission in patients of acute bronchial asthma.     

Step-down and step-up therapy in moderate persistent asthma

BACKGROUND: A step-down therapy may be more beneficial for the management of asthma than a step-up therapy. METHODS: Eighty-two asthmatic patients with moderate persistent asthma were enrolled in the study and randomized into three groups. One group of patients received 400 microg/day of beclomethasone dipropionate (BDP) for 4 weeks and then 800 microg/day for another 4 weeks (step-up group). The other two groups of patients received 1,200 microg/day of BDP for 4 weeks with or without short-term oral steroid (prednisolone, 0.5 mg/day for 1 week) and then 800 microg/day for another 4 weeks (step-down group). Severe exacerbation of asthma, asthma symptoms, respiratory function and rescue use of inhaled beta(2)-agonists were monitored. If asthma was well controlled, the dose of BDP was decreased every 3 months and if asthma was exacerbated, the dose of BDP was increased until 8 months after the initial treatment. RESULTS: Twenty-two patients during the run-in period, 4 patients in the step-up group, 2 patients in the step-down group treated with a high dose of BDP and no patients in the step-down group with oral steroids during first 4 weeks dropped out because of severe exacerbation of asthma. Although asthma symptoms and respiratory function significantly improved 8 weeks after the therapy in all groups, more significant and prompt improvements of these parameters were observed in patients of the step-down group than in patients of the step-up group after the first 2 weeks of treatment. Furthermore, step-down therapy with short-term oral steroid resulted in the lowest maintenance doses of BDP at 8 months of the three groups. CONCLUSIONS: These results suggest that step-down therapy starting with a high dose of inhaled steroid and short-term oral steroid is more effective in gaining prompt control of asthma and reducing the severe exacerbation of asthma and the maintenance dose of inhaled steroids than a step-up therapy starting with a low dose of inhaled steroids in patients with moderate persistent asthma.     

Warning nonrespiratory symptoms in asthma: catastrophic abdominal involvement in a case of Churg-Strauss syndrome.

BACKGROUND: Churg-Strauss syndrome (CSS) is a systemic vasculitis that occurs in the setting of asthma or allergic rhinitis with eosinophilia. The development of systemic manifestations in these allergic patients needs to be recognized as a likely sign of CSS. OBJECTIVE: To describe a patient with limb paresthesia and abdominal complaints related to CSS. METHODS: Blood leukocyte count, nerve conduction study, ultrasound and computed tomography of the abdomen, laparoscopic cholecystectomy and ileum resection, and histopathologic examination of ileum and gallbladder samples. RESULTS: A 55-year-old man with chronic asthma and rhinosinusitis had acute acalculous cholecystitis after he experienced lower limb paresthesia subsequently recognized as being due to mononeuritis multiplex. His eosinophil count was 1,860/microL. Three days after laparoscopic cholecystectomy the patient developed sudden severe diffuse abdominal pain with hypotension due to perforation of the ileum. The peripheral eosinophil count increased to 14,000/microL. Ileal resection was performed. Histopathologic examination showed necrotizing vasculitis with eosinophilic infiltration of the ileum and granulomatous vasculitis with eosinophilic infiltration of the gallbladder. He was treated with pulse intravenous methylprednisolone, 1 g for 3 consecutive days, followed by pulse intravenous cyclophosphamide, 750 mg/m(2), and recovered uneventfully. He received 6 additional monthly infusions of cyclophosphamide, and oral prednisone was tapered. When last seen, 2 years later, the patient was in good clinical condition, continuing alternate-day use of oral prednisone (10 mg). CONCLUSIONS: Nonrespiratory symptoms, such as paresthesia and acalculous cholecystitis, in a patient with asthma should alert the physician to consider CSS. If the neuropathic complaints had prompted the consideration of vasculitis, medical management might have avoided one or both surgical procedures.     

Elevated complement C3a in plasma from patients with severe acute asthma

BACKGROUND: Complement component C3a, an anaphylatoxin, provokes acute inflammatory responses, including smooth muscle contraction, mucus hypersecretion, increase in vascular permeability, and recruitment of inflammatory cells. Thus C3a may be related to airway inflammation and bronchoconstriction in acute asthma exacerbation. OBJECTIVE: We sought to determine whether plasma C3a is elevated in patients presenting for emergency treatment of acute asthma exacerbations and to correlate C3a concentrations with response to therapy. METHODS: Plasma C3a and serum eosinophil cationic protein were measured in 52 patients with acute asthma with peak expiratory flow of < or =50% the predicted value. Control subjects were 42 patients with stable chronic asthma. Patients with severe acute asthma were classified into 2 groups (admitted and discharged), according to how effective inhaled bronchodilators and systemic corticosteroids were in the first 2 hours of treatment. RESULTS: Concentrations of C3a in plasma from subjects in the admitted group (median, 256 ng/mL; range, 94 to 454) were significantly higher than those in the discharged group (197 ng/mL; 72 to 300) or those in patients with stable chronic asthma (166 ng/mL; 89 to 254; P <.0001). Elevated plasma C3a concentrations in admitted asthmatic patients decreased significantly by 7 days after admission (P =.0005). No significant difference was evident in serum eosinophil cationic protein concentration between the admitted group (33.1 microg/L; 6.3 to 143) and the discharged group (32.7 microg/L; 14.6 to 160; P =.99). CONCLUSIONS: Concentrations of C3a, which can induce airway inflammation and bronchoconstriction, were associated with differences in response to emergency treatment of severe asthma exacerbation.     

Effects of inhaled beclomethasone dipropionate and alternate-day prednisone on pituitary-adrenal function in children with chronic asthma.

Two corticosteroid regimens, alternate-day prednisone and inhaled beclomethasone dipropionate, have been more acceptable than daily oral corticosteroids for treatment of chronic asthma. To compare the effect of these regimens on hypothalamic-pituitary-adrenal function, 20 children with asthma were evaluated while receiving 20 to 40 mg of prednisone on alternate mornings or 400 to 800 microgram per day of inhaled beclomethasone dipropionate in divided daily doses; seven children requiring only non-corticosteroid medication served as controls. Early-morning serum cortisol concentration, urinary free-cortisol excretion and the 11-desoxycortisol response to metyrapone were decreased to a similar degree among children receiving both corticosteroid regimens in comparison with the control patients and were lowest when alternate-day prednisone and inhaled beclomethasone dipropionate were given together. Thus, inhaled beclomethasone dipropionate appears similar to alternate-day prednisone in its effect on hypothalamic-pituitary-adrenal function when used alone; the effect is additive when the two are used together.     

Methylprednisolone pulse therapy in acute severe asthma

Methylprednisolone pulse therapy (MPPT) has been shown to possess a long-lasting effect in other immune-inflammatory diseases without the well-known side effects caused by long-term treatment with glucocorticosteroids. In an attempt to reduce the long-term use of oral steroids in asthmatics, we conducted this double-blind, double-dummy study to compare the use of MPPT (1 g of methylprednisolone intravenously) (8 patients) with a short course of oral prednisolone (10 patients) in asthmatics presenting with acute severe asthma. Both treatments were effective in relieving the acute attack of asthma. The MPPT-treated patients did not show a faster resolution than did the orally treated group. No patients needed assisted ventilation, and no deaths occurred. One week after the treatment FEV1 tended to decrease in the methylprednisolone group compared with the oral prednisolone group (P = 0.06). The patients initially receiving MPPT needed supplementary prednisolone earlier and in higher doses than did the patients receiving oral prednisolone as initial treatment. At the end of the 12 weeks' study period, the groups reached identical FEV1. In conclusion, we did not find intravenous methylprednisolone superior to oral prednisolone in the treatment of acute attacks of severe asthma, but methylprednisolone pulse therapy had a shorter duration as regards protection against future asthma attacks.     

The effectiveness of high-dose inhaled budesonide therapy in the treatment of acute asthma exacerbations in children.

BACKGROUND: International guidelines recommend the use of systemic steroids for the treatment of acute asthma attack if it has not been resolved within 24 to 36 hours of home management with regular beta2 mimetic inhalation. Such therapy for infrequent exacerbations is unlikely to have serious systemic effects. Unfortunately, many patients receiving frequent courses are potentially at risk for corticosteroid-induced side effects such as adrenal suppression, depression of linear growth, and osteoporosis. OBJECTIVE: To decrease the use of frequent oral corticosteroid courses in children, this study was designed to evaluate the efficacy of high-dose inhaled steroids in comparison with oral steroids, in the therapy of acute asthma exacerbations in children. METHODS: Sixty children who have experienced an acute exacerbation of asthma unresponsive to home management with regular use of inhaled beta2 mimetics, yet not severe enough to hospitalize, were randomized to be treated with either high-dose inhaled budesonide (1,600 microg daily) or oral methylprednisolone (1 mg/kg daily) plus medium-dose inhaled budesonide (800 microg daily, both in addition to inhaled terbutaline, 2,000 microg daily). Pre- and posttreatment pulmonary index scores, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow 25% to 75% (FEF25%-75%) were evaluated. RESULTS: The mean number of decrease in pulmonary index score was 2.61 +/- 1.12 in the high-dose budesonide-receiving group (group I) and 1.90 +/- 1.08 in the oral steroid-receiving group (group II). There was a statistically significant difference between the two groups, in favor of group I (P = .038). No statistically significant difference was detected between the two groups with respect to the increase in lung function test measurements (FEV1, FEV1/FVC, FEF25%-75%; P = .790, .959, .819, respectively). CONCLUSIONS: Short-term high-dose budesonide therapy can be considered an alternative for children who are experiencing an acute asthma attack that is unresponsive to home management with regular use of an inhaled beta2 mimetic, yet who are not severe enough to hospitalize.     

In vivo effects of corticosteroids on human allergic responses. I. Effects of systemic administrations of steroids

In order to better understand the effects of corticosteroids in allergic disease, the relative degrees of allergen-induced cutaneous histamine release and granulocyte accumulation were evaluated in atopic volunteers following intravenous placebo or methylprednisolone administration. In nine subjects, a single intravenous dose of methylprednisolone (1 mg/kg) did not inhibit histamine release but did significantly reduce granulocyte accumulation at both allergen and buffer-challenged sites during five and one-half to six and one-half hours following steroid injection. These findings suggest that the corticosteroid-induced anti-inflammatory effects at allergic reaction sites do not include inhibition of local mediator release. Furthermore, the steroid-induced inhibition of inflammatory cell accumulation is not specific for the allergic reaction.     

Steroid-resistant asthma: immunologic and pharmacologic features.

Glucocorticoids play an important role in asthma therapy; however, a subset of patients are poorly responsive. We evaluated immunologic and pharmacologic features of 17 patients with steroid-resistant (SR) asthma (six male and 11 female patients) between the ages of 16 and 69 years (mean age, 29 years). SR asthma was defined as failure to improve morning prebronchodilator FEV1 greater than 60% predicted after a 2-week course of oral prednisone (mean dose, 45 mg/day). These patients were compared to 24 steroid-sensitive (SS) patients, aged 5 to 70 years (mean age, 17 years; 17 male and seven female patients), and 47 healthy control subjects, aged 20 to 40 years. Mean prednisone dose in SS patients was 25 mg/day. Steroid pharmacokinetics were evaluated in six patients with SR asthma. All studies were within normal limits. Peripheral blood mononuclear cells (PBMCs) from all subjects were stimulated with 10 micrograms/ml of phytohemagglutinin and incubated for 72 hours with 10(-5) to 10(-9) mol/L of methylprednisolone (Mpn). The Mpn dose-response curve for PBMCs from patients with SR asthma demonstrated a significant (p less than 0.05) increase in DNA synthesis, that is, more T cell proliferation than PBMCs stimulated with phytohemagglutinin in the presence of Mpn, as compared to SS patients and normal subjects. This augmentation of DNA synthesis was reversible with 10 micrograms/ml of troleandomycin in vitro. We conclude that PBMCs from patients with SR asthma demonstrate altered response to Mpn in the presence of a T cell mitogen. This abnormality in cellular response may contribute to persistent airway inflammation in patients with SR asthma despite glucocorticoid therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anaphylaxis-like reactions to corticosteroid therapy

This is a report of a 17-year-old male patient with a history of reactions characterized by the precipitous onset of urticaria, angioedema, and increased bronchospasm following therapy for status asthmaticus with either Solu-Medrol or Solu-Cortef. Intravenous challenge with 40 mg. of Solu-Medrol and methylprednisolone sodium succinate and oral challenge with 40 mg. of methylprednisolone produced dramatic confirmation of his history within 2, 11, and 35 minutes, respectively. Intravenous challenge with 4 mg. of Solu-Medrol and methylprednisolone sodium succinate, and oral challenges with 40 mg. of prednisolone and prednisone and 6 mg. of dexamethasone produced no adverse reactions. Direct skin testing revealed positive immediate reactions to pure methylprednisolone and hydrocortisone, whereas on passive transfer these reactions were negative for 4 and 48 hours. Negative skin test reactions were obtained to Solu-Medrol, methylprednisolone sodium succinate, methylprednisolone sodium acetate, prednisolone, prednisone, triamcinolone, dexamethasone, Solu-Cortef, hyrocortisone sodium succinate, and cortisone actate. Serial measurements during two intravenous challenges which produced anaphylaxis revealed no significant changes in 6 components of the complement system, fibrinogen, or the presence of split products.     

Exhaled carbon monoxide levels after a course of oral prednisone in children with asthma exacerbation

BACKGROUND: Fractional exhaled nitric oxide (FE(NO)) and exhaled carbon monoxide (ECO) have been proposed as markers of airway inflammation and oxidative stress. OBJECTIVE: The aim of this study was to assess the effect of oral prednisone treatment on FE(NO) and ECO levels in a group of 30 asthmatic children with asthma exacerbation. METHODS: Thirty asthmatic children with asthma exacerbation were treated with oral prednisone for 5 days (1 mg/kg/day). Before and after prednisone therapy, ECO was measured by means of a chemical analyzer and FE(NO) was measured by means of a chemiluminescence analyzer. ECO and FE(NO) were also measured in a group of healthy nonatopic children. RESULTS: Before therapy, both ECO values and FE(NO) values were higher in asthmatic children (ECO, 3.2 +/- 0.2 ppm; FE(NO) online, 74.9 +/- 6.2 ppb; FE(NO) offline, 20.2 +/- 1.4 ppb) than in healthy controls (ECO, 2.0 +/- 0.2 ppm [P <.01]; FE(NO) online, 10.1 +/- 0.8 [P <.0001]; FE(NO) offline, 5.9 +/- 0.4 ppb [P <.0001]). An overlap in ECO values was found between healthy controls and asthmatic children. After prednisone therapy, there was a significant reduction in FE(NO) values (FE(NO) online, 40.6 +/- 4.6 ppb [P <.0001]; FE(NO) offline, 11.1 +/- 0.8 ppb [P < 0.0001]) and a slight but nonsignificant decrease in ECO values (2.7 +/- 0.2 ppm [P = not significant]) in the asthmatic group. No significant correlation between ECO values and FE(NO) values was found in either the asthmatic children or the controls. CONCLUSIONS: After a course of prednisone therapy, in children with asthma exacerbation there is a significant decrease in FE(NO) but no significant change in ECO levels. This possibly suggests that ECO is less sensitive than FE(NO) to inhibition by corticosteroids.     

Inhaled budesonide for the treatment of acute wheezing and dyspnea in children up to 24 months old receiving intravenous hydrocortisone

BACKGROUND: Inhaled corticosteroids are highly effective in the treatment of asthma at all ages, and their use in younger children is increasing. There are no data currently available on the treatment of infants with acute wheeze and dyspnea with nebulized budesonide. OBJECTIVE: Our purpose was to assess the clinical effect of nebulized budesonide in infants with acute wheeze and dyspnea. METHODS: A prospective study was performed comparing the addition of nebulized budesonide 0.25 mg every 6 hours (group A, n = 32) and nebulized ipratropium bromide 0.1 mg every 6 hours (group B, n = 39) with the normal treatment regimen with intravenous fluid, hydrocortisone, and nebulized fenoterol. A clinical score was made at admission and every 12 hours. The score included wheezing and costal retraction (0-6) and respiratory rate (counts per minute). RESULTS: Seventy-one infants aged 3 to 24 months were studied (42 boys). A statistically significant reduction was seen in clinical score and respiratory rate in both groups 12 hours after admission. The children who received budesonide improved significantly faster than the children who received ipratropium bromide, and the hospitalization period was significantly lower in the budesonide group (66.4 hours) compared with the ipratropium bromide group (93 hours) (P <.01). Three patients from the budesonide group and 2 from the ipratropium bromide group were readmitted within the first 4 weeks. CONCLUSION: Treatment of infants with acute wheeze with nebulized budesonide is associated with faster clinical improvement and reduction in hospital stay period.     

Inhibition of methylprednisolone elimination in the presence of clarithromycin therapy

BACKGROUND: Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma. Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance. OBJECTIVE: We sought to determine whether clarithromycin, a newer macrolide antibiotic, can alter the pharmacokinetic profile of oral glucocorticoids and thereby increase the risk of steroid-induced adverse effects. METHODS: An open-label study in a paired design (before and after treatment) was conducted in a hospital-based outpatient clinic. Participants were 6 adult patients (mean age, 30 years) with mild-to-moderate asthma. Prednisone (40 mg/1.73 m2) and methylprednisolone (40 mg/1.73 m2) were given as single randomized doses on consecutive study days before and on days 8 and 9 of a clarithromycin (500 mg twice daily) course. Twelve-hour pharmacokinetic profiles with measurement of plasma methylprednisolone and prednisolone levels were taken before and after clarithromycin therapy. RESULTS: Clarithromycin therapy resulted in a 65% reduction of methylprednisolone clearance and significantly higher mean plasma methylprednisolone concentrations compared with preclarithromycin concentrations but had no significant effect on prednisolone clearance or mean prednisolone plasma concentrations. CONCLUSIONS: Clinicians must be aware of potential drug interactions that could place patients at increased risk for steroid-induced adverse effects. Such an effect has been demonstrated between clarithromycin and methylprednisolone, two drugs that may be administered concomitantly in asthma. To avoid potential steroid-enhancing effects, prednisone should be substituted for methylprednisolone during prolonged courses of clarithromycin therapy.