Oral Corticosteroid Bursts Research Articles

Steroid bursts associated with severe adverse events

Yao TC, Wang JY, Chang SM, Chang YC, Tsai YF, Wu AC, et al. Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children. JAMA Pediatr 2021. https://doi.org/10.1001/jamapediatrics.2021.0433

Multidisciplinary consensus on a stepwise treatment algorithm for management of chronic rhinosinusitis with nasal polyps.

Multidisciplinary consensus on a stepwise treatment algorithm for management of chronic rhinosinusitis with nasal polyps.

Usage of long-acting muscarinic antagonists and biologics as add-on therapy for patients in the United States with moderate-to-severe asthma

Objective Many asthma patients remain uncontrolled on inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs), but guidance for selecting add-on therapies, including long-acting muscarinic antagonists (LAMAs) or biologics, is limited. We describe how prescribing practices for add-on LAMA and biologic therapy have changed with increased treatment options and revised treatment guidelines. We further identify differences in treatment initiation and discontinuation rates by patient characteristics, including concomitant COPD. Methods This retrospective cohort study analyzed insurance claims in the IBM Marketscan database for adult US asthma patients treated with medium- or high-dose ICS/LABA between 2012 and 2019 (n = 277,373). We used negative binomial regression models to evaluate LAMA and biologic initiation rates and their association with patient characteristics, and survival analysis methods for assessing discontinuation rates. Results Between 2012 and 2019, LAMA and biologic uptake increased approximately 5-fold and 20-fold, respectively. LAMA initiation was significantly higher among patients with concomitant COPD, a group typically unstudied in clinical trials, versus those with asthma only (rate ratio of 5.90, 95% CI: 5.76–6.04). High-dose ICS/LABA treatment and the need for oral corticosteroid (OCS) bursts had stronger associations with biologic initiation. Probability of discontinuation (i.e. non-persistence) in the first year was 40.5% and 22.7% for those initiating LAMAs and biologics, respectively, with higher LAMA discontinuation rates among patients with asthma only versus those with concomitant COPD. Conclusions Our results provide insights into how clinicians apply treatment guidelines for initiating add-on LAMA and biologic therapies in moderate-to-severe asthma patients and highlight patients who have an unmet treatment need after discontinuation.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, a mimicker of malignancy: a case report and review of the literature

BackgroundChronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a clinically and radiographically distinct inflammatory syndrome affecting multiple structures of the brain, including the cerebellum, brainstem, and spinal cord. The clinical presentation can be variable, including ataxia, nystagmus, dysarthria, dysphagia, and other subacute brainstem, cranial nerve, or cerebellar symptoms. These symptoms can be subacute to chronic, episodic, and progressive, making the diagnosis challenging. The hallmark radiographic magnetic resonance imaging findings are gadolinium-enhancing punctate lesions predominantly “peppering” the pons in a perivascular pattern.Case presentationHere, we describe a case and literature review of a 74-year-old Caucasian male who presented with subacute symptoms of ataxia, diplopia, and generalized fatigue. Physical examination was notable for horizontal nystagmus and wide-based gait. Magnetic resonance imaging revealed angiocentric enhancement predominantly in the brainstem and cerebellum, with involvement of the basal ganglia, thalami, and supratentorial white matter. Meanwhile, a screening computed tomography scan demonstrated a right upper lobe mass with biopsy proving primary lung cancer. Biopsy of one of the brain lesions showed perivascular infiltrate primarily composed of CD3+ T cells, scattered CD20+ B cells, and no signs of malignancy. The patient was started on high-dose glucocorticoids followed by a maintenance regimen with rapid improvement clinically and radiographically. Given extensive work-up was negative, these clinical and radiographic findings were consistent with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids.ConclusionsThis case illustrates the difficulty of diagnosing chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, given its variable presentation, lack of specific laboratory findings, and poorly understood pathogenesis. We demonstrate a case that responded well to oral corticosteroid burst followed by a taper to the lowest corticosteroid dose clinically possible. Failure to recognize this syndrome could result in permanent central nervous system morbidity. Therefore, earlier recognition is crucial for this treatable condition.

Controller Medication Use and Exacerbations for Children and Adults With Asthma in High-Deductible Health Plans

High-deductible health plans (HDHPs) are increasingly common and associated with decreased medication use in some adult populations. How children are affected is less certain. To examine the association between HDHP enrollment and asthma controller medication use and exacerbations. For this longitudinal cohort study with a difference-in-differences design, data were obtained from a large, national, commercial (and Medicare Advantage) administrative claims database between January 1, 2002, and December 31, 2014. Children aged 4 to 17 years and adults aged 18 to 64 years with persistent asthma who switched from traditional plans to HDHPs or remained in traditional plans (control group) by employer choice during a 24-month period were identified. A coarsened exact matching technique was used to balance the groups on characteristics including employer and enrollee propensity to have HDHPs. In most HDHPs, asthma medications were exempt from the deductible and subject to copayments. Statistical analyses were conducted from August 13, 2019, to January 19, 2021. Employer-mandated HDHP transition. Thirty-day fill rates and adherence (based on proportion of days covered [PDC]) were measured for asthma controller medications (inhaled corticosteroid [ICS], leukotriene inhibitors, and ICS long-acting β-agonists [ICS-LABAs]). Asthma exacerbations were measured by rates of oral corticosteroid bursts and asthma-related emergency department visits among controller medication users. The HDHP group included 7275 children (mean [SD] age, 10.8 [3.3] years; 4402 boys [60.5%]; and 5172 non-Hispanic White children [71.1%]) and 17 614 adults (mean [SD] age, 41.1 [13.4] years; 10 464 women [59.4%]; and 12 548 non-Hispanic White adults [71.2%]). The matched control group included 45 549 children and 114 141 adults. Compared with controls, children switching to HDHPs experienced significant absolute decreases in annual 30-day fills only for ICS-LABA medications (absolute change, -0.04; 95% CI, -0.07 to -0.01). Adults switching to HDHPs did not have significant reductions in 30-day fills for any controllers. There were no statistically significant differences in PDC, oral steroid bursts, or asthma-related emergency department visits for children or adults. For the 9.9% of HDHP enrollees with health savings account-eligible HDHPs that subjected medications to the deductible, there was a significant absolute decrease in PDC for ICS-LABA compared with controls (-4.8%; 95% CI, -7.7% to -1.9%). This cohort study found that in a population where medications were exempt from the deductible for most enrollees, HDHP enrollment was associated with minimal or no reductions in controller medication use for children and adults and no change in asthma exacerbations. These findings suggest a potential benefit from exempting asthma medications from the deductible in HDHPs.

Do Short Oral Corticosteroid Bursts Have Adverse Effects

Unlike with chronic corticosteroid therapy, short bursts of oral corticosteroids in children have not been associated with adverse effects, but few

Oral corticosteroid bursts and severe adverse events: a critical appraisal.

Short-term corticosteroidsare commonly used to treat various dermatoses. Previous study has indicated oral corticosteroids < 30 days duration increased the risk of gastrointestinal (GI) bleedings, fractures, venous thromboembolism and sepsis.1 However, data on the risk of steroid bursts, defined as steroid use ≤ 14 days, remain scarce.

Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children

The adverse effects from the long-term use of oral corticosteroids are known, but, to our knowledge, few studies have reported the risk of corticosteroid bursts, particularly among children. To quantify the associations of corticosteroid bursts with severe adverse events, including gastrointestinal (GI) bleeding, sepsis, pneumonia, and glaucoma, in children. This study used data derived from the National Health Insurance Research Database in Taiwan from January 1, 2013, to December 31, 2017, on children younger than 18 years of age and used a self-controlled case series design. Data were analyzed from January 1 to July 30, 2020. Oral corticosteroid bursts (defined as oral corticosteroid use for ≤14 days). Incidence rates were calculated of 4 severe adverse events (GI bleeding, sepsis, pneumonia, and glaucoma) in children who did or did not receive corticosteroid bursts. Conditional fixed-effect Poisson regression was used to estimate incidence rate ratios (IRRs) of severe adverse events within 5 to 30 days and 31 to 90 days after initiation of corticosteroid bursts. Among 4 542 623 children, 23% (1 064 587; 544 268 boys [51.1%]; mean [SD] age, 9.7 [5.8] years) were prescribed a single corticosteroid burst. The most common indications were acute respiratory tract infections and allergic diseases. The incidence rate differences per 1000 person-years between children administered a single corticosteroid burst and those not prescribed corticosteroids were 0.60 (95% CI, 0.55-0.64) for GI bleeding, 0.03 (95% CI, 0.02-0.05) for sepsis, 9.35 (95% CI, 9.19-9.51) for pneumonia, and 0.01 (95% CI, 0.01-0.03) for glaucoma. The IRRs within 5 to 30 days after initiating corticosteroid bursts were 1.41 (95% CI, 1.27-1.57) for GI bleeding, 2.02 (95% CI, 1.55-2.64) for sepsis, 2.19 (95% CI, 2.13-2.25) for pneumonia, and 0.98 (95% CI, 0.85-1.13) for glaucoma; the IRRs within the subsequent 31 to 90 days were 1.10 (95% CI, 1.02-1.19) for GI bleeding, 1.08 (95% CI, 0.88-1.32) for sepsis, 1.09 (95% CI, 1.07-1.11) for pneumonia, and 0.95 (95% CI, 0.85-1.06) for glaucoma. This study suggests that corticosteroid bursts, which are commonly prescribed for children with respiratory and allergic conditions, are associated with a 1.4- to 2.2-fold increased risk of GI bleeding, sepsis, and pneumonia within the first month after initiation of corticosteroid therapy that is attenuated during the subsequent 31 to 90 days.

When medical treatments fail: Surgical interventions for allergic rhinitis

The current recommendations for the diagnosis, assessment, and treatment of rhinitis were recently published.1 These guidelines include a detailed algorithm for severe persistent symptoms of allergic rhinitis (AR), ultimately recommending that if there is a very severe presentation or if severe mucosal edema is still present even after the patient has received comprehensive medical therapies (antihistamines, intranasal corticosteroids, intranasal anticholinergics, and/or oral decongestants), then, at that point, an oral corticosteroid (CCS) burst would be warranted.

Real-World Reductions in Oral Corticosteroid Use in the USA Following Mepolizumab Therapy for Severe Asthma.

BackgroundPatients with severe asthma often require oral corticosteroid (OCS) treatment. Clinical trials have demonstrated that mepolizumab can reduce OCS dependence, but real-world data are limited.ObjectiveTo evaluate the impact of mepolizumab on OCS use, asthma exacerbations, and asthma exacerbation-related costs in a real-world setting.MethodsThis retrospective cohort study (GSK ID: 209642; HO-19-19597) analyzed data from the MarketScan® Commercial database (identification period: November 2015–September 2017). Patients were ≥12 years old at mepolizumab initiation (index date), had a baseline asthma diagnosis, and received ≥2 mepolizumab administrations in the first 6 months of follow-up. OCS use, asthma exacerbation rate, and asthma exacerbation-related costs were assessed in the 12-months before (baseline) and 12-months after (follow-up) mepolizumab initiation.ResultsMepolizumab was associated with a 14.7% reduction in the proportion of patients with ≥1 OCS claim from baseline to follow-up (93.4% vs 79.7%; P<0.001). The mean numbers of OCS claims/patient and OCS bursts (≥20 mg prednisone equivalents for 3‒28 days) between baseline and follow-up were also reduced by 29.1% (P<0.001) and 36.8% (P<0.001), respectively. Reductions in chronic OCS use were demonstrated during follow-up in patients with baseline mean OCS dose ≥5mg and those with a mean OCS dose ≥10mg 90 days before index; the proportion of patients with no OCS use also increased from 6.6% to 20.3% between baseline and follow-up.ConclusionOur findings demonstrate that mepolizumab therapy is associated with reduced OCS use in patients treated in a real-world setting, potentially mitigating adverse health sequelae caused by OCS use in these patients.

Assessing the cost-effectiveness of mepolizumab as add-on therapy to standard of care for severe eosinophilic asthma in Singapore

Objective To evaluate the cost-effectiveness of mepolizumab added to standard of care (SOC) compared with SOC alone among patients with severe uncontrolled eosinophilic asthma in the Singapore setting. Methods A Markov model with three health states (asthma on mepolizumab and SOC, asthma on SOC alone, and death) was developed from a healthcare system perspective over a lifetime horizon. During each 4-week cycle, patients in the non-death health states could experience asthma exacerbations requiring oral corticosteroid burst, emergency department visit, or hospitalization. Asthma-related mortality following an exacerbation or all-cause mortality could also occur at each cycle. The model was populated using local costs while utilities were derived from international literature. Transition probabilities were obtained from a mixture of Singapore-specific and internationally published data. Results The base-case analysis comparing mepolizumab plus SOC with SOC alone resulted in an incremental cost-effectiveness ratio (ICER) of SGD335 486 (USD238 195) per quality-adjusted life-year (QALY) gained. Sensitivity analysis demonstrated that the ICER was most sensitive to the price of mepolizumab, followed by the proportion of exacerbations which required hospital intensive care. Despite restricting mepolizumab use to patients with a higher baseline exacerbation rate (3 in the past year) in a scenario analysis, the ICER remained high at SGD238 876 (USD 169 602) per QALY gained. Conclusion At its current price, mepolizumab is not considered a cost-effective use of healthcare resources in Singapore. Substantial price reductions for mepolizumab are required to improve its cost-effectiveness to an acceptable range. These results will be useful to inform national funding decisions.

Chronic rhinosinusitis with nasal polyps management in the age of biologics

Background: Chronic rhinosinusitis is one of the most common medical conditions seen in the U.S. population. Chronic rhinosinusitis with nasal polyps (CRSwNP) in adults has predominately a type 2 inflammatory endotype that usually is treated with medical management that consists of inhaled corticosteroids, saline solution irrigation, oral corticosteroid bursts, and, at times, leukotriene antagonists and antibiotics. If medical management fails, then surgical intervention is usually recommended. Various biologics that target type 2 inflammation are now available, which have been or will be approved for use in these patients. Objective: To determine where biologics that affect the type 2 pathway fit into the algorithm of treatment for CRSwNP. Methods: A review of the literature on standard-of-care measures and surgical interventions in CRSwNP and an analysis of recent studies on the efficacy and safety of biologics in this condition. Results: Standard of care with medication and surgical interventions fail in some patients with CRSwNP. Biologics that affect the type 2 inflammatory pathway led to a decrease in nasal polyp size, improved nasal congestion, and improved quality of life both in patients who had surgery and those who had not had surgery for CRSwNP. Also, they showed efficacy and safety in patients whether or not they had comorbid asthma. These agents do not cure the patient with CRSwNP, and will be required chronically for control. Conclusion: Shared decision-making should be used in determining the use of certain medications, surgical management, and biologics in patients with CRSwNP. In patients for whom surgery has already failed and in patients with moderate-to-severe CRSwNP who have other type 2 comorbidities, e.g., asthma, a trial of biologics is a rational course.

Clinical Characterization of the Frequent Exacerbator Phenotype in Asthma.

Background: Asthma exacerbation is episodic worsening of respiratory symptoms in conjunction with the deterioration of lung function, which may occur independently from the asthma severity hampering asthmatics’ quality of life. This study aimed to characterize the patient phenotype more prone to asthma exacerbation (oral corticosteroid burst ≥2 per year) to allow the proper identification of such patients. Methods: This real-life, observational, cross-sectional study evaluated 464 asthmatic patients stratified according to the asthma exacerbations experienced in the previous year. Clinical, functional, and blood parameters were retrieved from chart data and were representative of patients in stable conditions. Results: The frequent asthma exacerbator was more commonly female, suffered from chronic rhinosinusitis with nasal polyposis, had reduced lung function and peripheral oxygen saturation, and had increased daily activity limitations. These patients often had severe asthma and more frequently needed hospitalization in their lives. Furthermore, the frequent asthma exacerbator had higher concentrations of serum immunoglobulin E (IgE) and exhaled nitric oxide with cut-off risk values of 107.5 kU/L (OR = 4.1) and 43.35 ppb (OR = 3.8), respectively. Conclusions: This study illustrates the clinical features of the frequent asthma exacerbator phenotype. Nevertheless, serum IgE and exhaled nitric oxide could allow the identification of this phenotype and the establishment of an appropriate therapeutic approach.

Association Between Oral Corticosteroid Bursts and Severe Adverse Events : A Nationwide Population-Based Cohort Study.

Long-term use of oral corticosteroids has known adverse effects, but the risk from brief oral steroid bursts (≤14 days) is largely unknown. To examine the associations between steroid bursts and severe adverse events, specifically gastrointestinal (GI) bleeding, sepsis, and heart failure. Self-controlled case series. Entire National Health Insurance Research Database of medical claims records in Taiwan. Adults aged 20 to 64 years with continuous enrollment in the National Health Insurance program from 1 January 2013 to 31 December 2015. Incidence rates of severe adverse events in steroid burst users and non-steroid users, as well as incidence rate ratios (IRRs) for severe adverse events within 5 to 30 and 31 to 90 days after initiation of steroid therapy. Of 15859129 adult participants, 2623327 who received a single steroid burst were included. The most common indications were skin disorders and respiratory tract infections. The incidence rates per 1000 person-years in steroid bursts were 27.1 (95% CI, 26.7 to 27.5) for GI bleeding, 1.5 (CI, 1.4 to 1.6) for sepsis, and 1.3 (CI, 1.2 to 1.4) for heart failure. Rates of GI bleeding (IRR, 1.80 [CI, 1.75 to 1.84]), sepsis (IRR, 1.99 [CI, 1.70 to 2.32]), and heart failure (IRR, 2.37 [CI, 2.13 to 2.63]) significantly increased within 5 to 30 days after steroid therapy initiation and attenuated during the subsequent 31 to 90 days. Persons younger than 20 years or older than 64 years were not included. Oral corticosteroid bursts are frequently prescribed in the general adult population in Taiwan. The highest rates of GI bleeding, sepsis, and heart failure occurred within the first month after initiation of steroid therapy. National Health Research Institutes, Ministry of Science and Technology of Taiwan, Chang Gung Medical Foundation, and Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Oral corticosteroid bursts increase risk of severe AEs

Oral corticosteroid bursts increase risk of severe AEs

Real-Life Patterns of Exacerbations While on Inhaled Corticosteroids and Long-Acting Beta Agonists for Asthma over 15 Years

Asthma affects more than 300 million people in the world, costs over $80 billion annually in the United States, and is efficaciously treated with inhaled corticosteroids (ICS). To our knowledge, no studies have examined the real-world effectiveness of ICS, including the combination therapy consisting of ICS and long-acting beta agonists (LABAs), and patterns of use over a 15-year time period. We used data from the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort which comprises longitudinal electronic health record data of over 100,000 people. Data included longitudinal asthma-related events, such as ambulatory office visits, hospitalizations, emergency department (ED) visits, and fills of ICS and ICS–LABA combination. Asthma exacerbations were defined as an asthma-related ED visit, hospitalization, or oral corticosteroid (OCS) burst. We used an expected-value approach to determine ICS and ICS–LABA coverage over exacerbation events. We compared rates of exacerbation of subjects on ICS or ICS–LABAs to their own rates of exacerbation when off controller medications. We found ICS–LABA therapy had significant effects, reducing all types of exacerbations per day by a factor of 1.76 (95% CI (1.06, 2.93), p = 0.03) and, specifically, bursts per day by a factor of 1.91 (95% CI (1.04, 3.53), p = 0.037). In conclusion, ICS–LABA therapy was significantly associated with fewer asthma-related exacerbations in a large population of individuals with asthma who were followed for 15 years.

Trabecular Bone Score Is More Sensitive to Asthma Severity and Glucocorticoid Treatment Than Bone Mineral Density in Asthmatics.

PurposeIn asthmatic patients, treatment with corticosteroids, in addition to conventional risk factors for osteoporosis, may lead to bone loss. Trabecular bone score (TBS) is an indirect new parameter of bone quality. This study aimed to evaluate TBS in asthmatics in comparison to propensity score-matched controls and to investigate correlations between TBS and cumulative systemic and inhaled corticosteroid doses 1 year prior to bone mineral density (BMD) measurement in patients with asthma.MethodsIn total, 627 patients with asthma and the same number of non-asthmatic controls matched for sex and age were included in this retrospective cohort study. TBS was calculated in the lumbar region, based on 2 dimensional projections of dual-energy X-ray absorptiometry.ResultsPatients with severe asthma exhibited lower vertebral TBS values (1.32 ± 0.1) than those with non-severe asthma (1.36 ± 0.1, P = 0.001), with non-active asthma (1.38 ± 0.1, P < 0.001), and without asthma (1.39 ± 0.1, P < 0.001). No significant differences in BMD were noted among the study groups. TBS was significantly correlated with cumulative systemic and inhaled corticosteroid doses as well as asthma duration, lung function and airway hyper-responsiveness. A generalized linear model revealed that age, severe asthma, and frequency of oral corticosteroid burst were significant predictors for TBS levels.ConclusionsTBS can be used as an early indicator of altered bone quality stemming from glucocorticoid therapy or, possibly, more severe asthma.

CHANGES IN FRACTIONAL NITRIC OXIDE CONCENTRATION IN EXHALED BREATH WITH THE USE OF ICS/LABA INHALERS

Background and Aims: Real-world patients' medication adherence and inhalation techniques severely impact asthma clinical and economic outcomes, but have not been incorporated into previous asthma costeffectiveness models. Advancements in smart, digital and eHealth-based inhalers development could offer new opportunities. This study aims to develop a model incorporating adherence and inhalation technique and determine the potential cost-effectiveness of adherence and inhalation technique enhancing interventions. Methods: A Markov model with 6 health-states which consists of combinations of 2 asthma control status (controlled vs uncontrolled) along with 2 mortality states (asthma-related vs other cause) and exacerbation states (i.e. oral-corticosteroid burst, emergency department visit, and hospitalization) was developed for simulating the cost-effectiveness of adherence and inhalation improvement programs for patients with uncontrolled asthma. Bi-weekly health state transitions were used along with a lifetime horizon to determine the incremental cost-effectiveness ratio of three hypothetical scenarios (1. full adherence/good technique 2. full adherence/poor technique and 3. poor adherence/good technique) vs usual care (poor adherence/poor technique) within the U.S. payer perspective. Results: Over a 60-year period, the full adherence and good technique group was associated with (discounted) $107, 309 costs and 18.82 quality-adjusted life years (QALYs), the full adherence and poor technique group was associated with $107,936 costs and 18.80 QALYs, the poor adherence and good technique group was associated with $106,517 costs and 18.74 QALYs, and the poor adherence and technique group was associated with $103,667 costs and 18.74 QALYs. The incremental cost-effectiveness ratio of the full adherence good technique (full adherence poor technique and poor adherence good technique) vs usual care was $41,831 ($66,826 and $1,056,016) per QALY. Conclusion: Given the growing development of adherence and inhalation technique improving interventions (e.g. smart inhalers) in asthma, this study shows that attempts in improving adherence and inhalation technique for uncontrolled asthma patients can be associated with significant gains in QALYs at the standard willingness-to-pay threshold.

Depression symptoms and quality of life among individuals with aspirin-exacerbated respiratory disease

Objective: Patients with aspirin-exacerbated respiratory disease (AERD) have high disease burden due to the severity of asthma and sinonasal symptoms. There is limited research on the psychological well-being and subjective experiences of patients with AERD. This study examined levels of depression symptoms, asthma-related quality of life and asthma control among AERD patients. Methods: Thirty-two adults with AERD and 39 patients without AERD (asthma-only) were recruited from outpatient asthma/allergy clinics. The sample was largely comprised of ethnic minority, inner-city patients who ranged in age from 19 to 84 years old. Participants completed the Beck Depression Inventory (BDI), the Mini Asthma Quality of Life Questionnaire (Mini AQLQ), a self-report rating of asthma severity and spirometry testing. Asthma control and severity were determined following national guidelines. Results: AERD patients reported lower levels of depression symptoms (p = 0.049), better overall asthma-related quality of life (p < 0.001), and perceived their asthma to be less severe (p = 0.01) compared to asthma-only patients. However, clinician ratings of asthma severity were more severe for AERD than asthma-only patients (p = 0.006). No significant differences were found between the groups on asthma controller medications or oral corticosteroid bursts for asthma. Conclusions: AERD patients may be resilient given their low levels of depression symptoms and positive views of asthma-related impairment despite higher clinician-rated asthma severity. The adult onset nature of asthma in AERD might be a protective factor on mental health. Future studies should explore mechanisms linking AERD and positive psychological health outcomes and subjective perception of asthma.

Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part II-Use of Immunomodulatory Therapies.

Introduction: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a clinically heterogeneous disorder with a number of different etiologies and disease mechanisms. Inflammatory and postinfectious autoimmune presentations of PANS occur frequently, with some clinical series documenting immune abnormalities in 75%-80% of patients. Thus, comprehensive treatment protocols must include immunological interventions, but their use should be reserved only for PANS cases in which the symptoms represent underlying neuroinflammation or postinfectious autoimmunity, as seen in the PANDAS subgroup (Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections). Methods: The PANS Research Consortium (PRC) immunomodulatory task force is comprised of immunologists, rheumatologists, neurologists, infectious disease experts, general pediatricians, psychiatrists, nurse practitioners, and basic scientists with expertise in neuroimmunology and PANS-related animal models. Preliminary treatment guidelines were created in the Spring of 2014 at the National Institute of Health and refined over the ensuing 2 years over conference calls and a shared web-based document. Seven pediatric mental health practitioners, with expertise in diagnosing and monitoring patients with PANS, were consulted to create categories in disease severity and critically review final recommendations. All authors played a role in creating these guidelines. The views of all authors were incorporated and all authors gave final approval of these guidelines. Results: Separate guidelines were created for the use of immunomodulatory therapies in PANS patients with (1) mild, (2) moderate-to-severe, and (3) extreme/life-threatening severity. For mildly impairing PANS, the most appropriate therapy may be "tincture of time" combined with cognitive behavioral therapy and other supportive therapies. If symptoms persist, nonsteroidal anti-inflammatory drugs and/or short oral corticosteroid bursts are recommended. For moderate-to-severe PANS, oral or intravenous corticosteroids may be sufficient. However, intravenous immunoglobulin (IVIG) is often the preferred treatment for these patients by most PRC members. For more severe or chronic presentations, prolonged corticosteroid courses (with taper) or repeated high-dose corticosteroids may be indicated. For PANS with extreme and life-threatening impairment, therapeutic plasma exchange is the first-line therapy given either alone or in combination with IVIG, high-dose intravenous corticosteroids, and/or rituximab. Conclusions: These recommendations will help guide the use of anti-inflammatory and immunomodulatory therapy in the treatment of PANS.