Secondary adrenal suppression related to high doses of inhaled corticosteroids in severe asthma patients

2022 ◽  
Author(s):  
Mariana Lobato ◽  
João Gaspar-Marques ◽  
Pedro Carreiro-Martins ◽  
Paula Leiria Pinto
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Adrenal Suppression ◽  
Asthma Patients ◽  
High Doses

scholarly journals Recent Advances in Asthma Management

2018 ◽  
Vol 4 (1) ◽  
pp. 15
Author(s):  
Peter J Barnes ◽  
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Asthma Management ◽  
European Respiratory Society ◽  
Systemic Corticosteroids ◽  
Expert Interview ◽  
Asthma Patients ◽  
Global Initiative ◽  
High Doses ◽  
Gina Guidelines

The treatment of asthma has improved greatly during the last two decades, and deaths from the disease have decreased.1 Despite these advances, many asthma patients fail to achieve optimal asthma control as defined by international guidelines.2,3 Severe asthma is associated with high risk of exacerbations and death.4 Definitions of severe asthma vary but, according to European Respiratory Society (ERS)/American Thoracic Society (ATS) and Global Initiative for Asthma (GINA) guidelines, severe asthma is asthma that requires treatment with high doses of inhaled corticosteroids plus a second controller, and/or systemic corticosteroids, to prevent it from becoming uncontrolled, or remains uncontrolled despite this therapy.2,5 In an expert interview, Professor Barnes discusses the latest advances in the management of both mild and severe asthma.

Diagnosis and Management of Severe Asthma

2018 ◽  
Vol 39 (01) ◽  
pp. 091-099 ◽  
Author(s):  
Kian Fan Chung
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
High Dose ◽  
Blood Eosinophil ◽  
Exhaled Breath ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Asthma Patients ◽  
Long Acting

AbstractSevere therapy-resistant asthma has been defined as “asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy”. Patients who usually present with ‘difficult-to-treat asthma’ should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.

scholarly journals Algorithm of biophenotyping and choice of medication for targeted therapy of severe uncontrolled asthma with eosinophilic type of airways inflammation

2017 ◽  
Vol 14 (3) ◽  
pp. 5-18
Author(s):  
N I Ilina ◽  
N M Nenasheva ◽  
S N Avdeev ◽  
Z R Aisanov ◽  
V V Arkhipov ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Clinical Studies ◽  
Inhaled Corticosteroids ◽  
Uncontrolled Asthma ◽  
Treatment Regimens ◽  
Expert Opinions ◽  
Beta Agonists ◽  
Biomarker Testing ◽  
High Doses ◽  
Long Acting

The article is based on the resolution of the Expert Council, including experts from Russian Association of Allergists and Clinical Immunologists (RAACI) and Russian Respiratory Society (RRS) dated November 20, 2016, and the review of clinical studies results and publications on the biomarker-based diagnosis and biological treatment of severe uncontrolled asthma. The aim of this work is to develop a phenotype-oriented algorithm of diagnostics and treatment of severe asthma, supported by the biomarker testing for subsequent selection of appropriate immunobiological treatment. The article constitutes the summary of results of clinical studies and expert opinions on the treatment of asthma in patients who do not achieve disease control with standard treatment regimens including high doses of inhaled corticosteroids in the combination with long-acting beta-agonists, tiotropium, and medications from other pharmacological groups according to Russian Respiratory Society (2016) and GINA (2016-2017) guidelines. The article summarizes the results of international randomized clinical studies performed to assess safety and efficacy of new class of biological treatments, monoclonal antibodies acting against major cytokines that are responsible for inflammation, in patients with severe asthma, including a new anti-IL-5 antibody, reslizumab (Cinqaero).

scholarly journals Local adverse effects associated with the use of inhaled corticosteroids in patients with moderate or severe asthma

2013 ◽  
Vol 39 (4) ◽  
pp. 409-417 ◽  
Author(s):  
Charleston Ribeiro Pinto ◽  
Natalie Rios Almeida ◽  
Thamy Santana Marques ◽  
Laira Lorena Lima Yamamura ◽  
Lindemberg Assuncao Costa ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Oral Candidiasis ◽  
Control Program ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Convenience Sample ◽  
Throat Clearing ◽  
Asthma Patients

OBJECTIVE: To describe and characterize local adverse effects (in the oral cavity, pharynx, and larynx) associated with the use of inhaled corticosteroids (ICSs) in patients with moderate or severe asthma. METHODS: This was a cross-sectional study involving a convenience sample of 200 asthma patients followed in the Department of Pharmaceutical Care of the Bahia State Asthma and Allergic Rhinitis Control Program Referral Center, located in the city of Salvador, Brazil. The patients were ≥ 18 years of age and had been using ICSs regularly for at least 6 months. Local adverse effects (irritation, pain, dry throat, throat clearing, hoarseness, reduced vocal intensity, loss of voice, sensation of thirst, cough during ICS use, altered sense of taste, and presence of oral candidiasis) were assessed using a 30-day recall questionnaire. RESULTS: Of the 200 patients studied, 159 (79.5%) were women. The mean age was 50.7 ± 14.4 years. In this sample, 55 patients (27.5%) were using high doses of ICS, with a median treatment duration of 38 months. Regarding the symptoms, 163 patients (81.5%) reported at least one adverse effect, and 131 (65.5%) had a daily perception of at least one symptom. Vocal and pharyngeal symptoms were identified in 57 (28.5%) and 154 (77.0%) of the patients, respectively. The most commonly reported adverse effects were dry throat, throat clearing, sensation of thirst, and hoarseness. CONCLUSIONS: Self-reported adverse effects related to ICS use were common among the asthma patients evaluated here.

scholarly journals The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Kenji Izuhara ◽  
Shoichi Suzuki ◽  
Masahiro Ogawa ◽  
Satoshi Nunomura ◽  
Yasuhiro Nanri ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inhaled Corticosteroids ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Apical Side ◽  
Asthma Patients ◽  
High Doses ◽  
Antithyroid Agents ◽  
Antiasthma Drugs

Inhaled corticosteroids (ICSs) are used as first-line drugs for asthma, and various novel antiasthma drugs targeting type 2 immune mediators are now under development. However, molecularly targeted drugs are expensive, creating an economic burden on patients. We and others previously found pendrin/SLC26A4 as a downstream molecule of IL-13, a signature type 2 cytokine critical for asthma, and showed its significance in the pathogenesis of asthma using model mice. However, the molecular mechanism of how pendrin causes airway inflammation remained elusive. We have recently demonstrated that hypothiocyanite (OSCN−) produced by the pendrin/DUOX/peroxidase pathway has the potential to cause airway inflammation. Pendrin transports thiocyanate (SCN−) into pulmonary lumens at the apical side. Peroxidases catalyze SCN− and H2O2 generated by DUOX into OSCN−. Low doses of OSCN− activate NF-κB in airway epithelial cells, whereas OSCN− in high doses causes necrosis of the cells, inducing the release of IL-33 and accelerating inflammation. OSCN− production is augmented in asthma model mice and possibly in some asthma patients. Heme peroxidase inhibitors, widely used as antithyroid agents, diminish asthma-like phenotypes in mice, indicating the significance of this pathway. These findings suggest the possibility of repositioning antithyroid agents as antiasthma drugs.

The Management of Mild Asthma

2020 ◽  
pp. 2003051
Author(s):  
Paul M. O'Byrne ◽  
Helen K. Reddel ◽  
Richard Beasley
Keyword(s):  
Severe Asthma ◽  
Maintenance Treatment ◽  
Inhaled Corticosteroids ◽  
Symptom Relief ◽  
Rapid Onset ◽  
Mild Asthma ◽  
Asthma Exacerbations ◽  
Reliever Medication ◽  
Asthma Patients ◽  
Long Acting

Inhaled corticosteroids (ICS) have been recommended as a maintenance treatment, either alone or together with long-acting inhaled β2-agonists, for all asthma patients. Short acting β2-agonists (SABA) are rapid onset bronchodilators, which provide symptom relief, but have no anti-inflammatory properties, yet are the most widely used as-needed reliever treatment for asthma, and often the only treatment prescribed. Asthma patients can find adhering to daily preventative medication with ICS difficult and will often revert to using as-needed SABA as their only treatment, increasing their risk of exacerbations. The purpose of this review was to evaluate the efficacy of reliever medications that contain an ICS when compared to SABA as a reliever, or to maintenance ICS and SABA as reliever, in mild asthma patients.Nine studies were identified which have evaluated the use of ICS as a component of an as-needed reliever in patients with mild asthma. Four of the most recent studies compared the combination of ICS/formoterol to SABA as reliever.An ICS containing reliever medication was superior to SABA as reliever alone, and was equivalent to maintenance ICS and SABA as reliever, particularly in reducing risks of severe asthma exacerbations, in studies which compared these reliever options.SABAs should not be used as a reliever without ICS. The concern about patients with mild asthma not being adherent to maintenance ICS, supports a recommendation that ICS/formoterol should be considered as a treatment option instead of maintenance ICS, to avoid the risk of patients reverting to SABA alone.

ВАРИАБЕЛЬНОСТЬ ОТВЕТА НА СТАНДАРТНУЮ ФАРМАКОТЕРАПИЮ У ПАЦИЕНТОВ С БРОНХИАЛЬНОЙ АСТМОЙ

2019 ◽  
pp. 20-24
Author(s):  
K.S. Pavlova ◽  
D.S. Mdinaradze ◽  
O.M. Kurbacheva
Keyword(s):  
Severe Asthma ◽  
Ipratropium Bromide ◽  
Tiotropium Bromide ◽  
Bronchial Obstruction ◽  
Asthma Phenotype ◽  
Basic Therapy ◽  
Asthma Symptoms ◽  
Asthma Patients ◽  
High Doses ◽  
Basic Treatment

Актуальность. Основанием для проведения данного исследования послужило наличие группы пациентов с бронхиальной астмой (БА), которые предпочитают для купирования приступов удушья использовать короткодействующие антихолинергические препараты (КДХП). Цель. Изучение возможной низкой эффективности длительно действующих Р2агонистов (ДДБА) у пациентов с БА, не имеющих достаточного ответа на КДБА, а также вероятности уменьшения бронхиальной обструкции с помощью длительно действующих антихолинергических препаратов (ДДХП) у этих пациентов. Материалы и методы. В исследовании приняли участие 12 взрослых некурящих пациентов с БА средней степени тяжести (IIIIV ступень по GINA), получавшие в качестве базисной терапии ИГКС в средних или высоких дозах в сочетании с ДДБА, при этом характеризовались отсутствием или неполным контролем над симптомами БА. В первую (n7) группу были определены пациенты с клинически и инструментально подтвержденной эффективностью сальбутамола, которые в то же время имели хороший ответ на ипратропия бромид (КДБАКДХП). Во вторую группу (n5) вошли пациенты с низким ответом на сальбутамол и положительным тестом с ипратропия бромидом (КДБАКДХП). Пациентам проводили серию исследований функции внешнего дыхания (ФВД) до и через 5, 10, 15, 30, 60, 120 и 240 мин после ингаляции бронхолитического средства (салметерола 50 мкг, формотерола 12 мкг и тиотропия бромида 18 мкг). Результаты. Было показано, что пациенты с БА и фенотипом КДБАКДХП имеют низкий ответ на ДДБА: максимальный прирост ОФВгпосле ингаляции сальметерола составил 7,641,67 и 156,0116,03 мл, а после формотерола 9,435,84, 166,71103,14 мл (в сравнении с группой КДБАКДХП, где ответ на сальметерол составил 20,812,42 и 551,4393,94 мл, а на формотерол 30,216,75 и 718,57140,78 мл), и хороший ответ на ДДХП (13,735,78 и 250,0361,61). Заключение. Результаты исследования дают основание к выделению отдельного фенотипа БА с низкой обратимостью бронхиальной обструкции в ответ на КДБА и достаточной обратимостью в ответ на КДХП (КДБАКДХП). Этой группе пациентов в качестве базисной терапии следует рассматривать сочетание ИГКСДДБА и ДДХП (тиотропия бромида).Background. The aim of this study was to analyse the group of patients with asthma, who prefer to use shortacting anticholinergics (SAMA) for relief of asthma attacks. At the same time, these patients are prescribed inhaled glucocorticosteroids (ICS) in combination with longacting P2agonists (LABA) as a basic therapy according to the standards. Tha aim. To study the cause of low efficacy of LABA in patients with asthma who do not have a sufficient response to SABA, as well as the probability of reducing of bronchial obstruction with LAMA. Materials and methods. 12 nonsmoking adults with moderate to severe asthma (IIIIV stage of GINA), receiving medium or high doses of ICS in combination with LABA as a basic therapy without adequate control over asthma symptoms were included in the study. First group of patients showed the efficacy of salbutamol (FEV1reversibility was more than 12 and more than 200 ml after 400 g of salbutamol) and ipratropium bromide (SABASAMA). Second group included patients with low response to salbutamol and positive test (FEVtreversibility) with ipratropium bromide (SABASAMA). Spirometry was performed at baseline point and in 5, 10, 15, 30, 60, 120 and 240 min after inhalation of bronchodilator (salmeterol 50 g, formoterol 12 g and tiotropium bromide 18 g in the different days). Results. It was shown that SABASAMA phenotype asthma patients demonstrated low response to LABA: FEV1increased up to 7.641.67, 156.016.0 ml after salmeterol inhalation and up to 9.45.8, 166.7103.1 ml after formoterol inhalation (compared with a group of SABASAMA, where the response to salmeterol was 20.812.42, 551.4393.94 ml and the response to formoterol was 30.216.75, 718.57140.78 ml, p0.05), and a good response to LAMA (13.75.8 and 250.061.6). Conclusion. The results of the study allowed to define asthma phenotype with low bronchial obstruction reversibility to SABA and sufficient reversibility to SAMA (SABASAMA). This group of asthma patients need the basic treatment with the combination of ICS and LABA and LAMA (tiotropium bromide).

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

Respiration ◽  
2021 ◽  
pp. 1-6
Author(s):  
Katrien Eger ◽  
Marijke Amelink ◽  
Simone Hashimoto ◽  
Pieter-Paul Hekking ◽  
Cristina Longo ◽  
...  
Keyword(s):  
Biologic Therapy ◽  
Inhaled Corticosteroids ◽  
Inhalation Technique ◽  
High Dose ◽  
Inhaler Technique ◽  
Biologic Treatment ◽  
Asthma Patients ◽  
Oral Corticosteroids ◽  
High Doses ◽  
Steroid Sparing

<b><i>Background:</i></b> 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. <b><i>Objectives:</i></b> 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. <b><i>Methods:</i></b> All adults (<i>n</i> = 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.

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