Course Of Oral Steroids Research Articles

Comparative Study of Budesonide Inhalation Suspension and Montelukast in Young Children With Mild Persistent Asthma

Szefler SJ, Baker JW, Uryniak T, Goldman M, Silkoff PE. J Allergy Clin Immunol. 2007;120(5):1043–1050 PURPOSE OF THE STUDY. To evaluate the efficacy of budesonide inhalation suspension (Pulmicort respules) compared with montelukast (Singulair) for controlling asthma symptoms in young children with mild persistent asthma. STUDY POPULATION. This was a prospective study of 395 children, aged 2 to 8 years, diagnosed with mild persistent asthma recruited from 55 US centers. Approximately 12% of the subjects had previous histories of inhaled corticosteroid (ICS) use. METHODS. Subjects were randomly assigned to receive either budesonide 0.5 mg or montelukast 4 to 5 mg daily and were followed for 52 weeks. Compliance was assessed by daily electronic diary review. For mild asthma exacerbations, step-up therapy consisted of the addition of a morning dose of budesonide 0.5 mg in both arms. For severe asthma exacerbations, subjects received a 3- to 10-day standardized course of oral steroids. The primary end point was evaluated by using the intention-to-treat population and was defined as time to first additional medication for asthma worsening at 52 weeks. Secondary end points included the time to additional asthma medication and rates of occurrence of mild and severe asthma exacerbations. Changes in symptom scores, peak flows, rescue-medication use, and pulmonary-function test results were also evaluated. RESULTS. Kaplan-Meier probability curves showed that the primary outcome measurement, time to the first additional asthma medication, was not significantly different between the 2 groups at 52 weeks (P = .3). There was a significant increase in the time to first additional asthma medication in the budesonide group compared with the montelukast group at 12 weeks (P = .05). The percentage of subjects requiring step-up therapy in the budesonide group versus the montelukast group at 12 weeks was 29.1% versus 38.6% (not significant [NS]), at 26 weeks was 41.3% versus 48.2% (NS), and at 52 weeks was 52% versus 56.9% (NS), respectively. The budesonide group achieved significantly improved morning and evening peak flow values compared with the montelukast group at 12 weeks (P = .005–.007). The rate of mild and severe asthma exacerbations per subject per year in the budesonide and montelukast groups was 1.23 and 1.63, respectively (P = .034). There was no significant difference in the number of severe asthma exacerbations between the 2 groups. Both treatment groups showed nonsignificant improvements in changes from baseline asthma scores, 24-hour rescue-medication use, and medication- and asthma-free days. CONCLUSIONS. Both budesonide and montelukast are effective and well-tolerated as controller medications in children aged 2 to 8 years with mild persistent asthma. Results favored budesonide for several secondary outcome measures. REVIEWER COMMENTS. Previous studies have shown that ICSs are more effective asthma-controller medications compared with montelukast in children older than 6 years. Although this study failed to show statistical significance in the primary outcome, it provides data supporting certain treatment benefits of ICSs in children younger than 6 years (257 of 395 children were <5 years old). Compared with previous studies, these children had milder asthma, with only 12% having taken ICSs before enrollment.

Evidence‐based management of a patient with anosmia

Evidence‐based management of a patient with anosmia

Coccydynia Related to Calcium Crystal Deposition

Study of 4 cases of severe coccydynia revealing calcium deposits in the sacrococcygeal and intercoccygeal joints. To highlight calcium crystal deposition as a cause of sudden-onset coccydynia. Intervertebral disc calcification in the cervical, thoracic, or lumbar spine is well known, but calcifications in the sacrococcygeal or intercoccygeal joints with symptoms have never been reported. All 4 patients presented with severe, sudden-onset coccydynia. Radiographs of the coccygeal area showed calcific deposits in the sacrococcygeal or intercoccygeal joints. Patients received a short course of oral corticosteroids or steroid injections. Conservative management provided prompt relief in all but one case. In 2, the resolution of the calcific deposits as seen on follow-up radiography was highly suggestive of their apatite origin. Calcium crystal deposition in the sacrococcygeal or intercoccygeal joints can cause coccydynia. Conservative treatment is effective as a first-line approach.

Demyelinating Sensorimotor Polyneuropathy Associated With the Use of Sirolimus: A Case Report

Liver transplantation is associated with a number of neurological complications. We herein report a case of chronic inflammatory demyelinating polyneuropathy associated with the use of sirolimus-based immunosuppression. The patient was treated by converting the immunosuppression from sirolimus to cyclosporine and by a short course of oral steroids. Following this, we observed almost complete clinical and electrophysiologic resolution of this syndrome. We believe that this is the first described case of such a complication occurring in association with sirolimus. This immunosuppressive agent can, therefore, lead to neurological complications similar to the ones that have been observed with calcineurin inhibitors.

Actinomyces israelii endogenous endophthalmitis

Actinomyces species are anaerobic Gram-positive pleomorphic rods that are commensals of the oral flora and facultative pathogens.1 In ophthalmological practice, Actinomyces are typically associated with canaliculitis. Although these organisms have...

A case of scar sarcoidosis

Infiltration of sarcoid granuloma in old cutaneous scars is one of the uncommon cutaneous manifestations of sarcoidosis. Here, we report the case of a 47-year-old female who presented with swelling and irritation in 5 old scars. She had acquired these scars 9 years ago in a traffic accident. An incisional scar biopsy revealed noncaseating granulomas consistent with sarcoidosis. High-resolution CT (HRCT) revealed right paratracheal, both hilar, paraaortic, and subcarinal lymphadenopathy without any nodular densities in both lung fields. Successful regression of cutaneous inflammation was achieved using a short course of oral steroids.

Dietary modifications, nutritional supplements and alternative medicine in paediatric patients with inflammatory bowel disease

Data on use of complementary and alternative medicine in children with inflammatory bowel disease are scarce. To assess prevalence, predictors and parental attitude to the use of complementary and alternative medicine in a paediatric population with inflammatory bowel disease in the west of Scotland. Questionnaire survey encompassing alternative therapists, nutritional supplements and dietary modifications used in the management of inflammatory bowel disease was used. Demographics, disease and treatment data were also collected. 86 guardians completed the survey. 61% had used at least one type and 37% were using complementary and alternative medicine recently. The most common types were probiotics (44%) and dairy-free diet (28%). Higher parental education and young parental age were predictors of complementary and alternative medicine use. An increased number of oral steroid courses and prior use of complementary and alternative medicine for other health reasons were associated with use of alternative therapists. Personal recommendation and to complement conventional medicine were the main reasons for using complementary and alternative medicine. 48% judged complementary and alternative medicine at least partially effective. 86% agreed that doctors should be supportive of use. 89% would give complementary and alternative medicine to their children. Use of complementary and alternative medicine was higher in children with IBD than in adults with the same disease. The gastrointestinal nature of the disease could explain the high use of nutritional supplements and dietary modifications in this survey.

An exploratory, pragmatic, cluster randomised trial of practice nurse training in the use of asthma action plans

To investigate the feasibility of improving asthma management - in particular, the implementation of individualised asthma action plans (AAPs) for poorly-controlled adult asthma patients - by providing training in asthma-focused clinical and communication skills for practice nurses who deliver asthma clinics. A pragmatic, cluster randomised trial with an intervention (an interactive seminar) delivered at practice level (n=13 practices; 6=intervention, 7=control). The impact of the intervention was assessed against patient outcomes: routinely available asthma outcome measures (beta2-agonist prescription rate and number of oral steroid courses) for asthma patients identified as being poorly-controlled from practice records; and questionnaire data - Mini Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) - from a subset of consenting patients. Data was collected at baseline and at 6-month follow-up. ANALYSISs: Routine data was analysed for 629 patients. 236 (37%) of these patients consented to provide questionnaire data at baseline, with 75% returning questionnaires at follow-up. After adjustment for baseline and practice, there was a significant difference at followup between intervention and control practices on the Mini AQLQ only (p=0.03). Estimates for subsequent sample sizes to inform future trials of asthma training were identified. Training designed to support practice nurses in implementing individualised AAPs impacted on one patient outcome only. This disappointing outcome may have been due to many different factors such as outcome measure limitations, data collection problems, and underestimating the complexity of supporting practice nurses in behaviour change.

Rituximab as successful therapy in a patient with refractory paroxysmal cold hemoglobinuria

Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia (AIHA) attributed to a biphasic hemolysin known as the Donath-Landsteiner (DL) antibody. It is most commonly encountered as an acute transient AIHA after a viral infection in children; the disease resolves after cessation of the infection. The rarest form of PCH is a chronic form in adults that is not (nowadays) associated with infection and is not responsive to conventional therapies. Rituximab has been found to be effective therapy in other forms of AIHA, such as cold agglutinin syndrome, that are refractory to conventional therapies. We describe a case of PCH refractory to steroids that responded to rituximab therapy on two separate occasions. A 64-year-old woman with fatigue was found to be profoundly anemic with laboratory findings consistent with AIHA. She was admitted for the workup and management of her disease after she failed to respond to a course of oral steroids. Laboratory evaluation demonstrated a positive DL test suggesting PCH. She was given a course of rituximab that resulted in normalization of her hemoglobin concentration. She presented 9 months later with recurrent hemolysis. She was given another course of rituximab that again resulted in termination of hemolysis. The patient remained in remission since her last dose of rituximab 19 months previously. To our knowledge, this is the first report of an adult case of refractory PCH successfully treated with rituximab.

An Unusual Case of Disseminated Histoplasmosis in an Immunocompetent Patient

Purpose: Although histoplasmosis in the immunocompetent patient has been reported, dissemination is rare. We report an unusual case of an immunocompetent patient with disseminated histoplasmosis who presented with abdominal pain and bloody diarrhea. Results: A 27 year old Caucasian male with a history of poor oral hygiene presented with tachycardia and daily fevers up to 103°F for nine months following a molar extraction. He initially developed a recurrent oral abscess despite treatment with clindamycin. He then failed to improve with a 10-day course of oral steroids. The patient presented to the emergency room with a temperature of 102.9°F, heart rate of 160/minute. On exam, ulcerated red lesions in the buccal mucosa and gingiva were noted. White blood cell count was 16.0 × 103/μL. The remainder of his blood tests including an HIV test was negative. Blood cultures were drawn and he was started on ampicillin/sulbactam and vancomycin. The patient was diagnosed with acute necrotizing ulcerative gingivitis and was taken for teeth extraction and debridement. Mandibular biopsy showed findings consistent with osteomyelitis. Biopsy culture was only positive for coagulase negative Staphylococcus. The patient continued to have sinus tachycardia and fevers despite a variety of antibiotic regimens. He then developed abdominal pain and bloody diarrhea. Pseudomembranous colitis was suspected and appropriate treatment was started with no improvement. A colonoscopy revealed numerous ulcerations throughout the colon. Biopsies of the ulcers revealed extensive infiltration with macrophages engorged with Histoplasma capsulatum. The previous mandibular biopsy slide was then reviewed and it demonstrated the same organism. Further history taking revealed that the patient was a former resident of Missouri, and had moved to California 3 years ago. Within several days of starting amphotericin B, his fevers subsided for the first time in nearly 10 months, and his tachycardia markedly improved. He was eventually discharged home with itraconazole. Conclusion: Approximately two-thirds of patients with disseminated histoplasmosis do not have a clear etiology for their hematogenous spread. In our patient, steroid therapy could have led to him being momentarily immunocompromised, promoting hematogenous spread of the fungal spores and consequently, disseminated disease.

Self-administered prescriptions of oral steroids and antibiotics in chronic obstructive pulmonary disease: are we doing more harm than good?

Patients with chronic obstructive pulmonary disease (COPD) are often given a prescription for a short course of oral steroids and antibiotics for self-administration during an acute exacerbation. The main objective of this study was to determine the impact of such prescriptions on medical care utilization, and steroids and antibiotics intake. This retrospective cohort study included patients with moderate to severe COPD participating in a self-management programme. We compared the number of unplanned medical visits (including hospitalizations) and the utilization of systemic steroids (number of short courses, number of days on treatment) and antibiotics (number of treatments) over a period of six months following registration to the programme in patients who received such a prescription and those who did not. Data were collected from hospital and community pharmacy files. A total of 89 patients were included; 46 received a self-administered prescription. During the study period, we found no difference between the two groups in the number of unplanned medical visits. However, we observed small but significant differences in the number of short courses of Prednisone (P = 0.018) and antibiotics (P = 0.006). This translated in an important difference in the number of days on steroids over the same period (;Prescription' group: 26; controls: 8; P = 0.005). Self-administered prescriptions may increase steroids and antibiotics utilization in patients with moderate to severe COPD, without reducing the number of unplanned medical visits.

Association of control and risk of severe asthma‐related events in severe or difficult‐to‐treat asthma patients

Clinical tools for predicting poor outcomes in asthma patients are lacking. This study investigated the association of asthma control and subsequent severe asthma-related healthcare events in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. The extent of asthma control problems was determined from baseline values of the Asthma Therapy Assessment Questionnaire (ATAQ). Patients self-reported the presence of severe asthma-related events at 6- and 12-month follow up. Poisson regression models determined the adjusted association between baseline control and the likelihood of severe asthma-related events. At baseline, 2942 patients (mean age, 49.6 years; female, 71.9%) had an ATAQ score (no control problems, 17.0%; 1 control problem, 20.0%; 2 control problems, 30.8%; 3 or 4 control problems, 32.2%) and at least one severe asthma-related event. After adjustment, subjects with three or four control problems were at greater risk for unscheduled office visits [relative risk (RR) = 2.8; 95% confidence interval (CI): 2.4-3.2], course of oral steroids (RR = 2.9; 95% CI: 2.5-3.3), emergency room visits (RR = 4.1; 95% CI: 2.7-6.2) or hospitalization (RR = 13.6; 95% CI: 7.4-24.9), vs no control problems. Progressively poorer levels of asthma control are associated with increasing risk of severe asthma-related events. This study provides evidence of an association between poor asthma control and future severe asthma-related healthcare events. A validated questionnaire may help clinicians identify patients requiring intervention to prevent future severe asthma-related events.

Differential diagnosis in ptosis and ophthalmoplegia: mitochondrial disease or myasthenia?

Sirs: One of the commonest phenotypes of mitochondrial disease is generalised fatigue with ptosis and a chronic progressive external ophthalmoplegia. The main differential diagnosis in these patients is with myasthenia gravis (MG). Ocular symptoms are the most common presentation of MG [1] and in up to 48% of patients are the only clinical manifestation [2]. Correct diagnosis is vital both to provide the best treatments and to avoid side effects from inappropriate ones [3]. We reviewed the records of 430 patients with proven mitochondrial disease on the basis of muscle histochemistry or mitochondrial DNA analysis to determine how many had originally been diagnosed with MG. Eighty-one of our patients had first presented with ptosis or ophthalmoplegia. Of these, a relatively small number, 15, had been investigated for possible MG as part of their diagnostic workup, and 5 (6.2%) had been given a primary diagnosis of MG. Table 1 shows the extra-ocular clinical features of the patients both at the time of diagnosis with MG and at subsequent diagnosis with mitochondrial disease. The average time between the initial diagnosis of MG and the subsequent diagnosis of mitochondrial disease was 3.6 years (range 1–9). Three of these patients had a single largescale deletion of mitochondrial DNA, and in two multiple deletions of the mitochondrial genome were found. All of the five patients initially diagnosed with MG had negative anti-acetylcholine receptor antibodies Table 2. Three patients were reported as having had a positive response to tensilon, although in one patient a repeat test was negative. Only three patients had undergone the more sensitive test of single fibre electromyography of orbicularis oculi. In one patient the initial result was reported as being consistent with myasthenia gravis on the basis of increased jitter (but with no blocking); this was subsequently repeated and reported as normal. All five patients had been treated with oral anticholinesterases. In one, an initial but shortlived symptomatic improvement was recorded. Three patients had received prolonged courses of oral steroids because of poor response to anticholinesterase treatment and one patient had undergone thymectomy. The differential diagnosis between mitochondrial disease presenting as ptosis and external ophthalmoplegia and myasthenia gravis can be difficult. The presenting clinical features of all the patients were entirely compatible with MG. Indeed, the majority reported variability in symptoms, often regarded as a hallmark of MG. Even those symptoms, which became apparent years later, such as proximal weakness and dysphagia, are common in MG. The investigations performed were similarly ambiguous; although all patients had negative anti-acetylcholine receptor antibodies, these are negative in up to 50% of ocular MG. Three had a positive tensilon test and one a suggestive single fibre EMG. Whilst all of these were probably false positives, an intriguing possibility is that these patients had disturbed neuromuscular transmission as a direct result of their mitochondrial disease. Blocking mitochondrial function in vitro leads to reduced phasic acetyl choline vesicle release [4] and changes in neuromuscular transmission similar to antibody mediated MG. Families with proven mitochondrial disease show minor but definite abnormalities on single fibre electromyography [5–7]. There are also anecdotal reports of symptomatic improvement in patients with mitochondrial disease given anticholinesterases [8], including one patient in this study. Although these drugs are as likely as any other to produce a placebo effect, these remain interesting observations. Our study emphasises the need to consider mitochondrial disease in the differential diagnosis of ocular MG, especially in those patients in whom symptoms do not respond well to treatment. R. G. Whittaker (&) AE A. M. Schaefer R. W. Taylor AE D. M. Turnbull Mitochondrial Research Group School of Neurology Neurobiology and Psychiatry University of Newcastle upon Tyne Newcastle upon Tyne NE2 4HH, UK Tel.: +1-91-2228334 Fax: +1-91-2228553 E-Mail: r.whittaker@ncl.ac.uk LETTER TO THE EDITORS J Neurol (2007) 254:1138– 1139 DOI 10.1007/s00415-006-0484-5

Clinical, functional, and epidemiological differences between atopic and nonatopic asthmatic children from a tertiary care hospital in a developing country

Differences between children with atopic asthma (AA) and nonatopic asthma (non-AA) have been shown in epidemiologic studies. In developing countries, even when non-AA is more prevalent than AA among schoolchildren, no data are available regarding clinical, functional, and epidemiological differences between these 2 groups. To evaluate differences between Chilean children with AA and non-AA. In this cross-sectional study, skin prick tests were performed on all patients (age range, 4-14 years) admitted to our tertiary care hospital with the diagnosis of asthma who were consequently classified as having AA or non-AA. Demographic characteristics, spirometry results, exercise bronchial challenge test results, and eosinophil counts measured in the last 12 months were recorded. Among the 237 asthmatic children, 62.5% had AA. Non-AA children had a significantly earlier onset of asthma and a more frequent history of pneumonia and tobacco consumption at home. Children with AA had higher nasal eosinophilia levels and a higher prevalence of dermatitis and severe exacerbation episodes of asthma in the past year (emergency department consultation and oral corticosteroids courses). Lung function was similar in both groups. After the multivariate analysis, only the number of oral steroid courses was significantly different between the groups and was associated with AA. In this selected population of asthmatic schoolchildren, the prevalence of non-AA (37.6%) is not negligible, and some differences between AA and non-AA children exist.

Chronic cough and Holmes-Adie syndrome

In April, 2006, a 45-year-old white man—a lifelong nonsmoker—was referred to the Royal Brompton Hospital Cough Clinic. In October, 2002, he had presented to his general practitioner with a persistent dry cough. The cough had started in March, 2002, after a bout of pneumonia. In addition, he claimed to have night sweats but no systemic symptoms. Auscultation of his chest, and a chest radiograph were normal, and he had a negative (grade 1) tuberculin skin test. In January, 2003, he was referred to his local chest clinic, where further inves tigations including lung function and CT of the chest were normal. He was reassured and discharged. In June, 2004, he presented to his local eye clinic complaining of blurred vision. Anisocoria was noted with an enlarged tonic left pupil (fi gure) and near light dissociation. Ankle tendon arefl exia was present on the right and elicited on the left only with reinforcement. He was diagnosed with Holmes-Adie syndrome—a condition of unknown cause characterised by tonic pupillary reactions and absent tendon refl exes. In August 2004, he was re-referred back to his local chest clinic because his dry cough persisted. Empirical treatment with omeprazole 20 mg daily was started and he underwent a normal barium swallow. Over the course of the following year, with no improvement in symptoms, he was prescribed an inhaled antimuscarinic bronchodilator (oxitropium bromide), an oral H1-anti histamine (loratadine), and he was given a trial of an H2-receptor antagonist (ranitidine) for 1 month, with no eff ect. When seen by us in April, 2006, his cough had persisted and he reported that during one coughing paroxysm he had experienced syncope. Direct questioning revealed truncal and right arm hyperhydrosis with excessive sweating in the right armpit. Respiratory, nasopharyngeal, and cardiovascular examinations were unremarkable. In particular, the patient had no evidence of dry eyes, dry mouth, or skin changes that might suggest a diagnosis of Sjogren’s syndrome. VDRL, autoantibody screen, and fasting blood sugar were negative. CT of the chest, full lung function (including histamine challenge, nitric oxide, and reversibility testing), nasolaryngo scopy, cinevideo fl uoroscopy, and 24-hour oesophageal pH monitoring were all normal. The patient declined fi breoptic bronchoscopy and capsaicin cough challenge. Treatment with high-dose inhaled corticosteroid (fl uticasone propionate 1000 μg daily) delivered from a pressurised metered-dose inhaler and spacer attachment, induced paroxysms of cough. Two separate courses of high dose oral steroids provided no improvement in either symptomatology or diurnal peak expiratory fl ow rate measurements. The addition of a non-selective oral H1-antihistamine treatment (chlorphenamine maleate 4 mg four times a day) was of no additional benefi t. As of September, 2006, the patient is still symptomatic and awaiting neurological consultation including cardiovascular autonomic testing. Kimber and colleagues, have reported an association between Holmes-Adie syndrome and chronic cough. Our patient showed early signs of autonomic neuropathy as his cough developed, including anisocoria, hyperhydrosis and syncope. The mechanism behind the cough is poorly understood, but it has been proposed that selective loss of thinly myelinated aff erent nerves in the lung, trachea, and larynx leads to denervation hypersensitivity of secondary neurons in the nucleus solitarius. Although the patient undoubtedly had a trigger episode precipitating his chronic cough (the original episode of pneumonia), the presence of an autonomic neuropathy may well explain the persistence of his symptoms. This case also highlights the diffi culty in treating patients with no apparent cause for their cough. Although chronic idiopathic cough and Holmes-Adie syndrome are both of unknown cause, recognition of this association has led to a more accurate diagnosis and, in this case, an appropriate tertiary specialist opinion.

Use of the ProSeal LMA in the ICU to facilitate weaning from controlled ventilation in patients with severe two episodic bronchospasm

Use of the ProSeal LMA in the ICU to facilitate weaning from controlled ventilation in patients with severe two episodic bronchospasm

Topical Steroid Drops for the Treatment of Sinus Ostia Stenosis in the Postoperative Period

Chronic oral steroid use causes significant morbidity, including osteoporosis, immunosuppression, and adrenal insufficiency. Refractory chronic rhinosinusitis patients often take repeated oral steroid courses to treat polypoid disease or sinus ostia stenosis. This study evaluated topical steroid drop efficacy in treating recurrent sinus ostia stenosis in the postoperative period. The 5-year single institution experience with topical steroid drop use after endoscopic sinus surgery (ESS) was evaluated by retrospective review. Patients were included if they began topical dexamethasone ophthalmic, prednisolone ophthalmic, or ciprofloxacin/ dexamethasone otic intranasally (used off-label) within 3 months after ESS. Outcomes (i.e., ostia patency, oral steroid use, revision surgery, and complications) were assessed for a 6-month period after steroid drop initiation. Thirty-six patients met inclusion criteria. Forty-four surgeries were performed during the study period; 67 sides were treated postoperatively with topical steroid drops. In 86.6% of cases, steroid drops were used to treat frontal ostium stenosis or frontal recess edema; 93.2% of surgeries were revision procedures. Sixty-four percent of sinuses were treated successfully with topical steroid drops, 14.9% remained stable, and 20.9% failed. Reasons for failure included persistent/worsening edema, scarring, or noncompliance. Ten patients (27.8%) required oral steroids and 4 patients (6%) underwent revision surgery during the study period. One case of adrenal suppression occurred. Topical steroid drops are beneficial in preventing sinus ostia stenosis in the postoperative period and may decrease the propensity toward repeated oral steroid therapy. This is particularly noteworthy in this challenging cohort, largely composed of revision frontal sinus surgery patients.

Systemic Steroids for the Treatment of Acute Asthma

In Brief Despite over 50 years of clinical experience, many uncertainties persist with respect to the onset of action, dose–response characteristics, duration of treatment, and optimal route of administration of systemic steroids when used in the treatment of severe acute asthma. Studies show that treating severe acute asthma with systemic corticosteroids within 1 hour of presentation to the emergency department lowers hospitalization rates and improves pulmonary function. The onset of action may be seen in as little as 2 hours in studies using peak flow, but may be delayed as much as 6 hours in studies using forced expiratory volume in 1 second as the pulmonary function outcome measure. A clear dose–response is seen at doses below 40 mg per day of methylprednisolone or equivalent; however, there is limited evidence for any added efficacy when doses above 60 to 80 mg per day are administered. There is no clear benefit of intravenous systemic steroids over oral steroids for treatment of severe acute asthma. High-dose inhaled corticosteroids may have a potential role, but further studies are needed to confirm efficacy. There is good evidence that a short course of oral systemic steroids for 3 to 7 days after initial steroid therapy prevents rebound asthma symptoms; no steroid taper is required if the patient was receiving inhaled steroids. Intramuscular steroids are at least equally effective and may be useful in patients who poorly adhere to their medication regimens; however, they are associated with more side effects than oral therapy. After more than 50 years of clinical experience using systemic corticosteroids for severe, acute asthma, there remains considerable uncertainty as to the onset of action, dose–response characteristics, duration of treatment, and optimal route of administration. A review of the literature offers guidance but many questions remain.

Prospective optical coherence tomographic evaluation of the efficacy of oral and posterior subtenon corticosteroids in patients with intermediate uveitis

To prospectively evaluate the efficacy of oral corticosteroids and posterior subtenon injection in the treatment of macular edema in patients with intermediate uveitis using optical coherence tomography (OCT). Twenty-two patients with intermediate uveitis were treated with posterior subtenon injection when the disease was unilateral (group A, n=11) or with oral steroids when the disease was bilateral (group B, n=11). Changes in macular thickness from baseline was determined using OCT in both groups at day 0, day 3, day 14, 6 weeks and 12 weeks. Statistically significant improvement in Snellen visual acuity in group A was seen at 6 weeks and in group B at 2 weeks. In patients receiving oral corticosteroids, foveal thickness decreased by 63% by day 3. In those treated with posterior subtenon injection, even at day 14 only a 55% reduction of foveal thickness was evident. Spearman's correlation coefficient for visual acuity and foveal thickness was found to be significant. OCT confirms a significantly more rapid decrease in macular edema in patients treated with oral corticosteroids. A short course of oral steroids may be useful in enabling earlier visual recovery in patients treated with posterior subtenon injection for unilateral uveitic macular edema.

Budesonide/Formoterol Combination Therapy as Both Maintenance and Reliever Medication in Asthma

Purpose of the Study. Previous studies have shown that the combination of inhaled corticosteroids (ICSs) with long-acting β2 agonists improves asthma control and reduces exacerbations. The authors hypothesized that in patients already receiving daily budesonide/formoterol (B/F), replacing conventional short-acting β2 agonist (SABA) rescue with the B/F combination drug would increase antiinflammatory therapy while simultaneously giving rapid relief of symptoms. The investigators reasoned that using the B/F combination drug in this manner might reduce asthma exacerbations and improve asthma control compared with other possible regimens. Study Population. Subjects were 2760 patients with asthma (aged 4–80 years), all previously on ICSs. Methods. A double-blind parallel-group study was performed with subjects randomly assigned to 3 groups: B/F (80 mg/4.5 μg) twice daily for maintenance and also for rescue; B/F (80 mg/4.5 μg) twice daily with terbutaline 0.4 mg for rescue; or budesonide 320 μg twice daily with terbutaline 0.4 mg for rescue. Pediatric patients (11%–13% of each group) received half of the above-stated doses for maintenance. The primary outcome was time to first severe exacerbation, defined as asthma symptoms requiring an emergency department visit or hospitalization; an increase in ICS dose; use of oral steroids; or a morning peak expiratory flow rate ≤70% of baseline on 2 consecutive days. Results. Multiple positive outcomes were seen in the group using B/F for maintenance and rescue: a significant increase in the time to the first severe and mild exacerbations (P < .001); a 45% to 50% decrease in the number of severe exacerbations; significant decreases in the use of rescue medication, nighttime symptom score, and the number of nighttime awakenings; and fewer courses of oral steroids per year. The average daily dose of ICS received per patient was lower in the 2 B/F groups. All of the medications were well tolerated. Pediatric subjects receiving B/F demonstrated greater linear growth than those on higher-dose budesonide. Conclusions. Use of B/F for both maintenance and rescue is associated with a lower asthma-exacerbation rate and an improvement in several other indicators of asthma control. In addition, subjects using B/F in this manner have a decreased exposure to oral steroids and require less use of rescue medication. The authors suggest that the timing of the increase in ICS use for asthma exacerbations, rather than the total ICS dose administered, provides the greater improvement in efficacy. Reviewer Comments. The rapid onset of action of the β2-agonist formoterol suggests that it could be used as a rescue medication, although this is not a licensed indication. Use of the B/F combination as controller and rescue presents an attractive option because of the decrease in asthma morbidity compared with either B/F and SABA or ICS and SABA. Even with the use of B/F for rescue, the mean dose of ICS received was lower than in the ICS-and-SABA group (240 vs 640 μg/day in the adults) and only slightly higher than in the B/F-and-SABA group (240 vs 160 μg/day in the adults). This combination product is not yet licensed in the United States, but if approved, B/F used in this fashion will offer a novel treatment alternative for asthmatic patients. In addition, B/F maintenance and rescue therapy may provide a significant benefit for patients for whom adherence to 2 separate drugs may present serious difficulties or confusion.