Need For Oral Corticosteroids Research Articles

Immunobiologicals in severe asthma: case report

According to the Global Initiative for Asthma (GINA), asthma is a chronic-inflammatory respiratory disease, characterized by limitation of expiratory air flow, dyspnea, wheezing and tachypnea, especially at night or in contact with allergens, climate changes or presence of environmental pollution. Among its subtypes, severe asthma stands out, where the symptomatic condition persists despite optimized treatment at advanced levels. The present study is a case report associated with a literature review on the use of immunobiologicals in the clinical treatment of severe asthma. Female patient, 53 years old, history of late-onset asthma at age 25, with frequent exacerbations, using drug therapy based on inhaled corticosteroid (ICS), long-acting β2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) in a single inhaler associated with the use of oral corticosteroids. After confirming the diagnosis of severe non-allergic eosinophilic asthma of endotype T2, GINA 5, the patient started treatment with mepolizumab and months later she showed significant improvement with the use of the immunobiological 1x/month and use of ICS associated with LABA. 12/12h, without the need for oral corticosteroids and use of rescue medications less than 2x/week.

Comparative real-world outcomes of dupilumab versus endoscopic sinus surgery in the treatment of severe CRSwNP patients.

Management of severe chronic rhinosinusitis with nasal polyps (CRSwNP) has changed significantly in recent years, with different treatments now available including biologics and endoscopic sinus surgery (ESS), although there are still few comparative studies. We aimed to compare 1-year outcomes of patients with severe CRSwNP treated with dupilumab or ESS plus intranasal corticosteroids (INCS). In this retrospective, real-life, observational, cohort study, we enrolled 101 patients with severe CRSwNP who were treated with INCS and either ESS (n = 49) or dupilumab (n = 52). The following outcomes were considered: nasal polyp score (NPS), Sino Nasal Outcome Test-22 (SNOT-22), visual analogue scale (VAS) for specific symptoms, Sniffin' Sticks identification test (SSIT), need for oral corticosteroids (OCS) and local eosinophilia detected by nasal cytology. ΔNPS was significantly higher in the surgery group up to 12 months when the difference with dupilumab group was no longer significant (ΔNPS: 4 vs. 4.1). ΔVAS rhinorrhoea, ΔVAS smell and ΔSNOT-22 were significantly higher in the dupilumab group at 12 months (p < .05). SSIT scores were significantly better in the dupilumab group starting from the first month of follow-up (p < .05). In the dupilumab group, only 6.1% of patients had detectable local eosinophilia compared to 57% in the surgery group alongside with a lower need for OCS (16.3% vs. 61%). Both dupilumab and ESS were effective in improving outcomes in patients with severe CRSwNP over 12 months. Nevertheless, patients treated with dupilumab had greater improvement in terms of SNOT-22, VAS rhinorrhoea, VAS smell and SSIT scores, with better control of local inflammation and less need for OCS.

Clinical Remission in Patients Affected by Severe Eosinophilic Asthma on Dupilumab Therapy: A Long-Term Real-Life Study.

Background. Nowadays, highly selective biological drugs offer the possibility of treating severe type 2 asthma. However, in the real-life setting, it is crucial to confirm the validity of the chosen biological treatment by evaluating the achievement of clinical remission. Study purpose. The main aims of this real-life study were to evaluate the efficacy of dupilumab in terms of clinical, functional, and inflammatory outcomes at 6, 12, 18, and 24 months of treatment and to estimate the percentage of patients achieving partial or complete clinical remission at 12 and 24 months of treatment. In addition, we attempted to identify whether baseline clinical characteristics of patients could be associated with clinical remission at 24 months of treatment. Materials and methods. In this observational prospective study, 20 outpatients with severe uncontrolled eosinophilic asthma were prescribed dupilumab and followed-up after 6, 12, 18, and 24 months of treatment. At each patient visit, the need for oral corticosteroids (OCS) and corticosteroid required dose, number of exacerbations during the previous year or from the previous visit, asthma control test (ACT) score, pre-bronchodilator forced expiratory volume in the 1st second (FEV1), fractional exhaled nitric oxide at a flow rate of 50 mL/s (FeNO50), and blood eosinophil count were assessed. Results. The number of OCS-dependent patients was reduced from 10 (50%) at baseline to 5 (25%) at one year (T12) and 2 years (T24). The average dose of OCS required by patients demonstrated a significant reduction at T12 (12.5 ± 13.75 mg vs. 2.63 ± 3.94 mg, p = 0.015), remaining significant even at T24 (12.5 ± 13.75 mg vs. 2.63 ± 3.94 mg, p = 0.016). The number of exacerbators showed a statistically significant decrease at T24 (10 patients, 50% vs. 3 patients, 15%, p = 0.03). The mean number of exacerbations demonstrated a statistically significant reduction at T24 (1.45 ± 1.58 vs. 0.25 ± 0.43, p = 0.02). The ACT score improved in a statistically significant manner at T12 (15.30 ± 4.16 vs. 21.40 ± 2.35, p < 0.0001), improving further at T24 (15.30 ± 4.16 vs. 22.10 ± 2.59, p < 0.0001). The improvement in pre-bronchodilator FEV1 values reached statistical significance at T24 (79.5 ± 14.4 vs. 87.7 ± 13.8, p = 0.03). The reduction in flow at the level of the small airways (FEF25-75%) also demonstrated an improvement, although it did not reach statistical significance either at T12 or T24. A total of 11 patients (55%) showed clinical remission at T12 (6 complete + 5 partial) and 12 patients (60%) reached clinical remission at T24 (9 complete + 3 partial). Only obesity was associated with a negative odds ratio (OR) for achieving clinical remission at T24 (OR: 0.03, 95% CI: 0.002-0.41, p = 0.004). No other statistically significant differences in baseline characteristics emerged between patients who reached clinical remission at T24 and the group of patients who did not achieve this outcome. Conclusion. Dupilumab appears to be an effective drug in promoting achievement of clinical remission in patients with severe uncontrolled eosinophilic asthma. The achievement of clinical remission should be continuously evaluated during treatment. Further studies are needed to clarify whether certain baseline clinical characteristics can help predict dupilumab favorable outcomes.

Eosinophilia, asthma, NERD and the use of oral corticosteroids predict uncontrolled chronic rhinosinusitis with nasal polyps after surgery.

Severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) is a challenging condition to treat. The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS2020) has the following criteria when considering biological therapy for severe uncontrolled CRSwNP: eosinophilia, need for oral corticosteroids (OCS), symptom score, loss of sense of smell and co-morbid asthma. This study aimed at finding associations of baseline factors with uncontrolled CRSwNP after endoscopic sinus surgery (ESS). Electronic health record data of CRSwNP patients (N = 137) undergoing ESS in 2002-17 were used. Endpoints of uncontrolled CRSwNP were revision ESS, purchased OCS and antibiotic courses during follow up. Baseline factors were chosen based on EPOS2020 and the data available: nasal polyp (NP) eosinophilia, peripheral blood eosinophilia, co-existing asthma and/or non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD), need for OCS during the previous year, previous ESS, endoscopic NP score, and Lund-Mackay score of sinus computed tomography scans. During the follow-up of 10.1 ± 3.1 (mean ± standard deviation) years, 35 (25.5%) individuals underwent revision ESS. The best predictive model was obtained by a sum of baseline (1) blood eosinophilia ≥ 250 cells/≥l and/or NP eosinophilia ≥ 30% (Eos), (2) asthma/NERD, and (3) ≥ 1 OCS/year. It was significantly associated with revision ESS, purchased doctor-prescribed OCS and antibiotic courses during follow-up. We identified similar predictive variables for uncontrolled CRSwNP that are used in the EPOS2020 indications of biological therapy, thus suggesting that these estimates are usable in clinical practice.

Biologics for the treatment of severe asthma: Current status report 2023

Severe asthma is associated with increased use of healthcare services, significant deterioration in the quality of life, and high disease and economic burden on patients and societies. Additional treatments are required for severe forms of asthma. Biological agents are recommended for the treatment of severe asthma. In this current status report, we aimed to evaluate the efficacy, effectiveness, and safety data of approved biologics; omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, in the treatment of severe asthma and appropriate patient profiles for these biologics. Pubmed and Cochrane databases based on randomized controlled trials, posthoc analyses, meta-analyses, and real-life studies examining the efficacy and effectiveness of biologics in severe asthma were searched, and the results of these studies on important asthma outcomes were reviewed. Existing studies have shown that all the approved biologic agents targeting cells, receptors, and mediators involved in type 2 inflammation in the bronchial wall in severe asthma significantly reduce asthma exacerbations, reduce the need for oral corticosteroids, and improve asthma control, quality of life, and pulmonary functions. Characterizing the asthma endotype and phenotype in patients with severe asthma and determining which treatment would be more appropriate for a particular patient is an essential step in personalized treatment.

P031 Montelukast antagonising underlying systemic illness

Abstract Background/Aims Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, multisystemic, autoimmune vasculitis involving small to medium-sized blood vessels. It has a well-established affiliation with atopic syndromes, typically adult-onset asthma and sinusitis. More rare associations are linked with drug side effects such as Montelukast. According to the ‘American College of Rheumatology 1990’, the following criteria yield a sensitivity of 84% in identifying a patient with EGPA. The criteria include: asthma, eosinophilia &amp;gt;10% on differential white cell count, mononeuropathy or polyneuropathy, transient pulmonary infiltrates on chest radiography, paranasal sinus abnormality, and blood vessel biopsy demonstrating extravascular eosinophilia, in a patient with symptoms of systemic vasculitis. The multisystemic involvement of EGPA makes both diagnosis and management difficult as presentations can vary. Methods We report the complex case of a 61 year-old gentleman diagnosed with EGPA. His relevant past medical history includes a diagnosis of Asthma in 2002 (managed with inhaled bronchodilators, corticosteroids, and montelukast), recurrent sinusitis, and lower respiratory tract infections. The patient presented with a one month history of abdominal cramping and bloating. This was associated with nausea, constipation, anorexia, and a week of ‘drenching’ night sweats. His full physical examination during this time was unremarkable. Results He had a normal CT Abdomen Pelvis and colonoscopy. His admission chest radiograph demonstrated bilateral parenchymal lung changes. This was followed by a CT Thorax showing bilateral upper and lower lobe bronchiectasis. Mediastinal and hilar adenopathy consistent with a diagnosis of allergic bronchopulmonary aspergillosis with associated reactive adenopathy. His laboratory investigations showed eosinophilia (21.68) and leucocytosis (32.7). In view of these results, an autoantibody screen was sent showing positive ANCA and positive anti-Myeloperoxidase antibodies(MPO titre 55). Two days into his admission he developed pain and paralysis of his right upper limb. He reported marked fatigue followed by a petechial, non-blanching, vasculitic rash on both ankles. Neurological examination reflected a subacute symmetrical sensory and motor polyneuropathy predominantly involving the right side with bilateral foot drop. MRI Brain demonstrated an established infarct in the left external capsule. He was commenced on high dose aspirin. Due to high suspicion for EGPA, methylprednisolone was commenced for 5 days, followed by tapering oral corticosteroid therapy and Rituximab therapy. A skin punch biopsy showed ‘ a vasculopathic type reaction with small vessel vasculitis, associated mixed inflammatory infiltrate which includes some eosinophils’ confirmed his diagnosis. Conclusion A topic of particular relevance to this case is the association between EGPA and montelukast. It has been hypothesised that there may be a relationship between Leukotriene Receptor Antagonist Therapy, specifically Montelukast, with the pathogenesis of EGPA. Some research suggests that treatment with Montelukast permits the decreased need for oral corticosteroids for asthma control. Therefore, suggesting that EGPA could have been masked by corticosteroid therapy. Disclosure Á. Connerton: None.

Real-Life Experience of Biologic Treatment for Asthma on Chronic Rhinosinusitis: A Finnish Cohort

Introduction: Biologics are used in the treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of this retrospective study was to evaluate the effects of biologics initiated for asthma on coexistent CRS and the influence of comorbid factors, including aspirin-exacerbated respiratory disease (AERD) and secretory otitis media (SOM). Methods: A review of electronic health records (2009–2020) at a Finnish tertiary center was conducted to identify CRS patients treated with biologics for their asthma. We identified the type of biologic and treatment response, by comparing nasal polyp score (NPS), sinonasal outcome test (SNOT)-22, need for oral corticosteroids (OCS) and antibiotics, frequency of visits, and endoscopic sinus surgeries (ESS) pretreatment and during treatment. Results: 55 patients were treated with anti-immunoglobulin E (IgE) (n = 18) or anti-interleukin-5/5-receptor (IL-5/5R) (n = 37) biologics. Treatment lasted for an average of 4.1 years. Seventy-five percent (n = 41) had CRSwNP and 25% (n = 14) had CRSsNP. Of all patients, 24% (n = 13) had comorbid AERD and 22% (n = 12) had SOM. Biologic therapy reduced the need for OCS courses (anti-IgE, n = 17, p = 0.03; anti-IL-5/5R, n = 35, p = 0.01) and for daily OCS in anti-IL-5/5R (n = 35, p = 0.001) but not in anti-IgE patients (n = 16, p = 0.07). Biologics also improved NPS by 0.5 point (n = 32, p = 0.009) and SNOT-22 by 14 points (n = 7, p = 0.02) in CRSwNP patients. The overall discontinuation rate was 37.7% (n = 20) and was independent of type of biologic. Conclusion: Treatment with anti-IgE and/or anti-IL-5/5R biologics reduced the overall need for OCS medication in individuals with asthma and concomitant CRS, but despite this, the discontinuation rate was high.

A Single Center Experience of Super-Responders Among Severe Asthma Patients Receiving Treatment with Mepolizumab.

OBJECTIVE:Anecdotal reports among clinicians treating severe asthma patients with novel add-on treatments such as mepolizumab suggest that a fraction of these patients may experience a much more dramatic benefit from these agents than reported in large, randomized controlled studies. Although these patients have been referred to as super-responders in some studies, currently, there is no consensus regarding the nomenclature. Therefore, our aim was to assess the real-life data among patients receiving mepolizumab treatment due to severe eosinophilic asthma, in an effort to determine potential clinical and laboratory differences between super-responders and other group of patients.MATERIAL AND METHODS:Data from adult patients who received at least four doses of mepolizumab due to persistent severe asthma between Janury 1, 2020, and December 31, 2021, in a Tertiary Allergy Clinic were evaluated in a retrospective manner.Results:A total of 57 patients with severe asthma receiving mepolizumab treatment were included [female: 38, male: 19]. At 4th- and 12th-month after initiation of mepolizumab treatment, significant differences in forced expiratory volume in 1 second, forced vital capacity, forced expiratory volume in 1 second/forced vital capacity, blood eosinophil count, and serum immunoglobulin E level were detected as compared to baseline (P < .001, P < 0.001, P = .027, P < .001, and P = .035). Also, at the 12th-month of treatment with mepolizumab, there were significant differences compared to baseline in asthma control test scores, number of asthma exacerbations, non-planned emergency room visits, hospitalizations, and daily need for oral corticosteroids (P < .001, for all parameters). Also, there was not a statistically significant difference between super-responders and responders groups in regard to age, gender, duration of disease, duration of mepolizumab treatment, allergen sensitivities, and comorbid conditions (chronic rhinosinusitis, nasal polyps, and aspirin sensitivity).Conclusion:Our results suggest that mepolizumab may be an effective therapeutic option in patients with severe asthma. On the other hand, patients who were considered to be super-responders to mepolizumab treatment were not significantly different from the remaining group of patients (responders). Obviously, further studies are warranted to better define the super-responders among patients with severe asthma who receive mepolizumab treatment.

Alpine altitude climate treatment for severe and uncontrolled asthma: An EAACI position paper.

Currently available European Alpine Altitude Climate Treatment (AACT) programs combine the physical characteristics of altitude with the avoidance of environmental triggers in the alpine climate and a personalized multidisciplinary pulmonary rehabilitation approach. The reduced barometric pressure, oxygen pressure, and air density, the relatively low temperature and humidity, and the increased UV radiation at moderate altitude induce several physiological and immunological adaptation responses. The environmental characteristics of the alpine climate include reduced aeroallergens such as house dust mites (HDM), pollen, fungi, and less air pollution. These combined factors seem to have immunomodulatory effects controlling pathogenic inflammatory responses and favoring less neuro‐immune stress in patients with different asthma phenotypes. The extensive multidisciplinary treatment program may further contribute to the observed clinical improvement by AACT in asthma control and quality of life, fewer exacerbations and hospitalizations, reduced need for oral corticosteroids (OCS), improved lung function, decreased airway hyperresponsiveness (AHR), improved exercise tolerance, and improved sinonasal outcomes. Based on observational studies and expert opinion, AACT represents a valuable therapy for those patients irrespective of their asthma phenotype, who cannot achieve optimal control of their complex condition despite all the advances in medical science and treatment according to guidelines, and therefore run the risk of falling into a downward spiral of loss of physical and mental health. In the light of the observed rapid decrease in inflammation and immunomodulatory effects, AACT can be considered as a natural treatment that targets biological pathways.

Severe asthma: One disease and multiple definitions

IntroductionThere is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. MethodsData collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. ConclusionsThe present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem.

THE ACUTE ASTHMA EXACERBATION ASSESSMENT SURVEY: VALIDATING A NEW SURVEY TOOL

THE ACUTE ASTHMA EXACERBATION ASSESSMENT SURVEY: VALIDATING A NEW SURVEY TOOL

Overuse of Oral Corticosteroids, Underuse of Inhaled Corticosteroids, and Implications for Biologic Therapy in Asthma

Background: Asthma patients using high cumulative doses of oral corticosteroids (OCSs) are at risk of serious adverse events and are increasingly being treated with steroid-sparing asthma biologics. However, it is unknown whether prescribing these expensive biologics is always justified. Objectives: This study aimed to (1) assess the prevalence of asthma patients using high cumulative doses of OCSs, (2) explore the role of suboptimal inhaler therapy, and (3) estimate the proportion of patients to whom asthma biologics might be prescribed unnecessarily. Methods: All adults (n = 5,002) with at least 1 prescription of high-dose inhaled corticosteroids (≥500–1,000 mcg/day fluticasone-equivalent) and/or OCSs (GINA step 4–5) in 2010 were selected from a pharmacy database including 500,500 Dutch inhabitants, and sent questionnaires. Of 2,312 patients who returned questionnaires, 929 had asthma. We calculated the annual cumulative OCS dose and prescription fillings and checked inhaler technique in a sample of 60 patients. Patients estimated to have good adherence and inhaler proficiency who still required high doses of OCSs (≥420 mg/year) were considered candidates for initiating biologic treatment. Results: 29.5% of asthma patients on GINA 4–5 therapy used high doses of OCSs, of which 78.1% were likely to have poor therapy adherence or inadequate inhaler technique. Only 21.9% were considered definitive candidates for biologic therapy. Conclusion: High OCS use in Dutch GINA 4–5 asthma patients was common. However, in 4 out of 5 patients adherence to inhaled corticosteroid therapy and/or inhalation technique was considered suboptimal. Since optimizing inhaler therapy may reduce the need for OCSs, this should be mandatory before prescribing expensive steroid-sparing drugs.

GLP-1 based therapies and disease course of inflammatory bowel disease.

BackgroundThe disease course of inflammatory bowel disease (IBD) following treatment with glucagon-like peptide (GLP)-1 based therapies is unclear. The aim of this study was to examine the disease course of IBD in patients treated with GLP-1 based therapies compared with treatment with other antidiabetics.MethodsUsing nationwide Danish registries, we identified patients with IBD and type 2 diabetes who received antidiabetic treatment between 1 January 2007 and 31 March 2019. The primary outcome was a composite of the need for oral corticosteroids, tumour necrosis factor-α inhibitors, IBD-related hospitalisation, or IBD-related surgery. In the setting of a new-user active comparator design, we used Poisson regression to estimate incidence rate ratios (IRR) comparing treatment with GLP-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors with other antidiabetic therapies. The analyses were adjusted for age, sex, calendar year, IBD severity, and metformin use.FindingsWe identified 3751 patients with a diagnosis of IBD and type 2 diabetes and with a prescription of an antidiabetic drug (GLP-1 receptor agonists/DPP-4 inhibitors: 982 patients; other antidiabetic treatment: 2769 patients). The adjusted IRR of the composite outcome was 0·52 (95% CI: 0·42–0·65) for patients exposed to GLP-1 receptor agonists/DPP-4 inhibitors compared with patients exposed to other antidiabetics.InterpretationIn patients with IBD and type 2 diabetes, we observed a lower risk of adverse clinical events amongst patients treated with GLP-1 based therapies compared with treatment with other antidiabetics. These findings suggest that treatment with GLP-1 based therapies may improve the disease course of IBD.

GLP-1 Based Therapies and Disease Course of Inflammatory Bowel Disease

Background: The disease course of inflammatory bowel disease (IBD) following treatment with glucagon-like peptide (GLP)-1 based therapies is unclear. Objectives: To examine clinical outcomes of IBD in patients with IBD and type 2 diabetes treated with GLP-1 based therapies compared with treatment with other antidiabetics. Methods: Using nationwide Danish registries, we identified patients with IBD and type 2 diabetes who received antidiabetic treatment between 1 January 2007 and 31 March 2019. The primary outcome was a composite of the need for oral corticosteroids, tumour necrosis factor-α inhibitors, IBD-related hospitalisation, or IBD-related surgery. In the setting of a new-user active comparator design, we used Poisson regression to estimate incidence rate ratios (IRRs) comparing treatment with GLP-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors with other antidiabetic therapies. The analyses were adjusted for age, sex, calendar year, IBD severity, and metformin use. Results: We identified 3751 patients with a diagnosis of IBD and type 2 diabetes and with a prescription of an antidiabetic drug (GLP-1 receptor agonists/DPP-4 inhibitors: 982 patients; other antidiabetic treatment: 2769 patients). The adjusted IRR of the composite outcome was 0.52 (95% CI: 0.42-0.65) for patients exposed to GLP-1 receptor agonists/DPP-4 inhibitors compared with patients exposed to other antidiabetics. Conclusion: In patients with IBD and type 2 diabetes, treatment with GLP-1 receptor agonists/DPP-4 inhibitors are associated with a lower risk of adverse clinical events compared with treatment with other antidiabetics. Funding Information: The study was funded by the Novo Nordisk Foundation [grant number NNF16OC0022586 and NNF17OC0029768]. Declaration of Interests: None of the authors have any conflicts of interest to disclose. Ethics Approval Statement: The study was approved by the Danish Data Protection Agency, and data were analysed on a secure research server at the Danish Health Data Authority. In Denmark, ethical approval is not required for research using pre-existing, routinely collected data.

Anti-IL-5 treatments in severe eosinophilic asthma: real life datas

Randomized controlled studies have shown that anti-IL-5 treatments reduce the need for oral corticosteroids, annual asthma exacerbation and hospitalization rates, blood eosinophil count and increase FEV1 values, asthma control, and quality of life in patients with eosinophilic severe asthma. Although the number of real-life studies with anti-IL-5 is limited, there are 10 real life studies with mepolizumab, one real life study with benralizumab and one real life study with reslizumab in the current literature. Similar to randomized controlled trials, real-life studies reported that a reduction in the need for oral corticosteroids, annual asthma exacerbation and hospitalization rates, and blood eosinophil counts and increase FEV1 values, asthma control test and quality of life scores, Response criteria were defined in some of the real-life studies and although different response rates were given according to these criteria, most of the patients with severe eosinophilic asthma showed high response rates to anti-IL-5 treatments. In real-life studies evaluating the safety of anti-IL-5 treatments, the most common adverse effect is mild local injection site reaction that does not require treatment, in conclusion, real-life studies suggest that all three anti-IL-5 treatments in clinical practice are effective and well tolerated.

Impact of the COVID-19 pandemic in children with allergic asthma

Impact of the COVID-19 pandemic in children with allergic asthma

Which Child with Asthma is a Candidate for Biological Therapies?

In asthmatic adults, monoclonals directed against Type 2 airway inflammation have led to major improvements in quality of life, reductions in asthma attacks and less need for oral corticosteroids. The paediatric evidence base has lagged behind. All monoclonals currently available for children are anti-eosinophilic, directed against the T helper (TH2) pathway. However, in children and in low and middle income settings, eosinophils may have important beneficial immunological actions. Furthermore, there is evidence that paediatric severe asthma may not be TH2 driven, phenotypes may be less stable than in adults, and adult biomarkers may be less useful. Children being evaluated for biologicals should undergo a protocolised assessment, because most paediatric asthma can be controlled with low dose inhaled corticosteroid if taken properly and regularly. For those with severe therapy resistant asthma, and refractory asthma which cannot be addressed, the two options if they have TH2 inflammation are omalizumab and mepolizumab. There is good evidence of efficacy for omalizumab, particularly in those with multiple asthma attacks, but only paediatric safety, not efficacy, data for mepolizumab. There is an urgent need for efficacy data in children, as well as data on biomarkers to guide therapy, if the right children are to be treated with these powerful new therapies.

A Predictive Model for Clinical Asthma Exacerbations Using Albuterol eMDPI (ProAir Digihaler): A Twelve-Week, Open-Label Study

Background The ability to identify an impending clinical asthma exacerbation (CAE) would improve asthma action plans and provide opportunities for pre-emptive treatment. Increased use of inhaled rescue medications, such as albuterol, has been observed in the days prior to a CAE, but other potential predictive factors are poorly understood. Approved by the US Food and Drug Administration (FDA) in late 2018, ProAir Digihaler with built-in sensors registers when patients use the inhaler and has been shown previously to accurately measure both peak inspiratory flow and inhalation volume, confirming the device’s ability to reliably record objective information on inhaler usage and technique. Objective Data collected from the ProAir Digihaler provides, for the first time, a more complete picture of patients’ use of inhaled medication, and thereby offers an opportunity to develop a predictive model of an impending CAE, and the potential to better implement asthma action plans and facilitate early treatment. Methods Patients (≥18 years old) with exacerbation-prone asthma were recruited to a 12-week, open-label study. Patients used the ProAir Digihaler (albuterol 90 µg 1–2 inhalations q4 hours) as needed. The electronic component of Digihaler recorded each use and inhalation variables (peak inspiratory flow, volume inhaled, time to peak flow, and inhalation duration). Data were downloaded from the inhalers and, together with clinical data, subjected to a machine-learning algorithm to develop models predictive of an impending CAE as defined by the need for oral corticosteroids. The generated model was evaluated by receiver operating characteristic (ROC) curve analysis. Results Three hundred and sixty patients made ≥1 valid inhalation from the Digihaler and were included in the analysis. Of these, 64 patients experienced a total of 78 CAEs. The strongest predictive factor during the 5 days before a CAE was the average number of albuterol inhalations per day. The predictive model was strengthened by supplementing these data with other inhalation features collected by Digihaler, including peak inhalation flow, inhalation volume, night-time usage, and trends of these parameters over time. This model predicted an impending exacerbation over the 5 days with a ROC AUC value of 0.75. Conclusions This study represents, to our knowledge, the first successful attempt to develop a model to predict CAE derived from the use of a rescue medication inhaler device equipped with an integrated sensor and capable of measuring inhalation parameters. The predictive power of the model would benefit from further development with larger populations of asthma patients.

Implementing Health Care Technology Research into Practice to Improve Adult Asthma Management

Use of health technology has shown potential to improve asthma adherence and outcomes. Few studies have looked at the implementation of such research within larger asthma populations. This report examines the process of translating results from a pragmatic trial using speech recognition (SR) in children with persistent asthma into the standard operating procedure within a large health maintenance organization. Medication adherence and outcomes in adults with asthma were examined. The SR protocol was implemented for the total Kaiser Permanente Colorado (KPCO) patient population of 480,142, of whom 36,356 had asthma. Patients had persistent asthma, filled 1 or more inhaled corticosteroid prescriptions in the prior 6 months, and remained continuously enrolled with KPCO for 2 years. Documented exacerbations included the presence of a hospitalization, emergency department visit, or course of oral corticosteroid where asthma was the principal diagnosis. Adherence and exacerbation events were compared 1 year before and 1 year after intervention for 4,510 adults aged 19 to64. Patient adherence demonstrated a small but significant improvement from 39.5% to 41.7% (P < .0001). Although not significant, data trends suggested greater improvement for patients with lower socioeconomic status. When an outlier month was removed from both the pre- and postintervention time periods, courses of oral corticosteroids decreased. Emergency department visits and hospitalizations were infrequent in both time periods and did not decrease over time. A low-cost SR intervention reminding patients to fill and take their daily controller asthma medication can improve treatment adherence and decrease the need for oral corticosteroids due to asthma exacerbations, but not decrease emergency department visits or hospitalizations.

Diagnostic yield of allergy testing in Pediatric Eosinophilic Esophagitis: a 10 year experience at a tertiary care centre

Background Eosinophilic Esophagitis (EoE) is a disease in children characterized by esophageal dysfunction and eosinophilic infiltration [1]. Patients frequently present with an atopic history; therefore, allergy testing by both skin prick and food patch testing are often performed. However, the utility of allergy testing remains unclear [1,3]. Treatment with topical corticosteroids may be needed for clinical and histologic improvement if allergic triggers are not identified [1,2]. However, the natural history of EoE suggests that this condition is chronic and may recur when corticosteroids are withdrawn [2]. Therefore, treatment with dietary/aeroallergen avoidance is preferable to reduce the need for oral corticosteroids, while preventing exacerbation of EoE [3]. This study aims to describe the atopic characteristics of a pediatric cohort with EoE over a 10 year period at a tertiary care center.