Impact of an increase in the inhaled corticosteroid dose on blood eosinophils in asthma

Here, we report that increasing treatment with inhaled corticosteroids (ICS) in patients with not well-controlled asthma from a medium to a high dose results in a profound reduction of blood eosinophils (median fall in blood eosinophil concentrations from 560 to 320 cells/µL). Therefore, ‘normal values’ of blood eosinophils in patients with asthma need to be considered in view of the individual ICS doses of the patients. In addition, increases in the dose of ICS may result in blood eosinophil concentrations which would formally preclude treatment with biologics targeting the interleukin-5 pathway.

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Benign intracranial hypertension associated with inhaled corticosteroids in a child with asthma

BMJ Case Reports ◽

10.1136/bcr-2021-242455 ◽

2021 ◽

Vol 14 (5) ◽

pp. e242455

Author(s):

James Trayer ◽

Declan O'Rourke ◽

Lorraine Cassidy ◽

Basil Elnazir

Keyword(s):

Cerebrospinal Fluid ◽

Intracranial Hypertension ◽

Inhaled Corticosteroids ◽

Benign Intracranial Hypertension ◽

Inhaled Corticosteroid ◽

Moderate Dose ◽

Opening Pressure ◽

Blurred Vision ◽

Corticosteroid Dose ◽

Steroid Side Effects

A 13-year-old male asthmatic presented to the general paediatric clinic with papilloedema identified following a check-up with his optician due to blurred vision. His asthma was well controlled on a moderate dose of inhaled corticosteroid and there had been no recent increase or decrease in the dose. A diagnosis of benign intracranial hypertension (BIH) was made based on a raised cerebrospinal fluid opening pressure, papilloedema, a normal neurological examination and normal neuroimaging. The only associated risk factor was his inhaled corticosteroids. He was commenced on acetazolamide and the inhaled corticosteroid dose was reduced, resulting in resolution of his papilloedema. This case serves to highlight that steroid side effects including BIH may occur at moderate doses of inhaled corticosteroids and that inhaled corticosteroid dose should be regularly reviewed and decreased to the lowest dose that maintains asthma control.

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Characterisation of patients with severe asthma in the UK Severe Asthma Registry in the biologic era

Thorax ◽

10.1136/thoraxjnl-2020-215168 ◽

2020 ◽

pp. thoraxjnl-2020-215168

Author(s):

David J Jackson ◽

John Busby ◽

Paul E Pfeffer ◽

Andrew Menzies-Gow ◽

Thomas Brown ◽

...

Keyword(s):

Asthma Control ◽

Severe Asthma ◽

Symptom Control ◽

Unmet Need ◽

High Dose ◽

Blood Eosinophil ◽

Biologic Therapies ◽

Exacerbation Rate ◽

The Uk ◽

Blood Eosinophils

BackgroundThe UK Severe Asthma Registry (UKSAR) is the world’s largest national severe asthma registry collecting standardised data on referrals to UK specialist services. Novel biologic therapies have transformed the management of type 2(T2)-high severe asthma but have highlighted unmet need in patients with persisting symptoms despite suppression of T2-cytokine pathways with corticosteroids.MethodsDemographic, clinical and treatments characteristics for patients meeting European Respiratory Society / American Thoracic Society severe asthma criteria were examined for 2225 patients attending 15 specialist severe asthma centres. We assessed differences in biomarker low patients (fractional exhaled nitric oxide (FeNO) <25 ppb, blood eosinophils <150/μL) compared with a biomarker high population (FeNO ≥25 ppb, blood eosinophils ≥150/µL).ResultsAge (mean 49.6 (14.3) y), age of asthma onset (24.2 (19.1) y) and female predominance (62.4%) were consistent with prior severe asthma cohorts. Poor symptom control (Asthma Control Questionnaire-6: 2.9 (1.4)) with high exacerbation rate (4 (IQR: 2, 7)) were common despite high-dose treatment (51.7% on maintenance oral corticosteroids (mOCS)). 68.9% were prescribed biologic therapies including mepolizumab (50.3%), benralizumab (26.1%) and omalizumab (22.6%). T2-low patients had higher body mass index (32.1 vs 30.2, p<0.001), depression/anxiety prevalence (12.3% vs 7.6%, p=0.04) and mOCS use (57.9% vs 42.1%, p<0.001). Many T2-low asthmatics had evidence of a historically elevated blood eosinophil count (0.35 (0.13, 0.60)).ConclusionsThe UKSAR describes the characteristics of a large cohort of asthmatics referred to UK specialist severe asthma services. It offers the prospect of providing novel insights across a range of research areas and highlights substantial unmet need with poor asthma control, impaired lung function and high exacerbation rates. T2-high phenotypes predominate with significant differences apparent from T2-low patients. However, T2-low patients frequently have prior blood eosinophilia consistent with possible excessive corticosteroid exposure.

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Diagnosis and Management of Severe Asthma

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0037-1607391 ◽

2018 ◽

Vol 39 (01) ◽

pp. 091-099 ◽

Cited By ~ 5

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.

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Eosinophils Target Therapy for Severe Asthma: Critical Points

BioMed Research International ◽

10.1155/2018/7582057 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 13

Author(s):

L. Brussino ◽

E. Heffler ◽

C. Bucca ◽

S. Nicola ◽

G. Rolla

Keyword(s):

Severe Asthma ◽

Eosinophil Count ◽

Inhaled Corticosteroids ◽

Response To Treatment ◽

High Dose ◽

Blood Eosinophil ◽

Moderate Increase ◽

Eosinophilic Asthma ◽

Peripheral Blood Eosinophil ◽

Blood Eosinophil Count

Asthma is a chronic and heterogeneous disease, which is defined as severe disease whenever it requires treatment with a high dose of inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or if it remains ‘‘uncontrolled’’ despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma, which is characterized by sputum eosinophilia, associated with mild to moderate increase in blood eosinophil count, frequently adult-onset, and associated with chronic rhinosinusitis with nasal polyps in half of the cases. Eosinophilic asthma is driven by T2 inflammation, characterized, among the others, by interleukin-5 production. IL-5 plays a key role in the differentiation, survival, migration, and activation of eosinophils, and it has become an appealing therapeutic target for eosinophilic asthma. In recent years two monoclonal antibodies (mepolizumab and reslizumab) directed against IL-5 and one monoclonal antibody directed against the alpha-subunit of the IL-5 receptor (benralizumab) have been developed. All these IL-5 target drugs have been shown to reduce the number of exacerbation in patients with severe asthma selected on the basis of peripheral blood eosinophil count. There are still a number of unresolved issues related to the anti-IL5 strategy in eosinophilic asthma, which are here reviewed. These issues include the effects of such therapy on airway obstruction and asthmatic symptoms, the level of baseline eosinophils that predicts a response to treatment, the relationship between blood and airway eosinophilia, and, perhaps most importantly, how to elucidate the pathogenetic role played by eosinophils in the individual patient with severe eosinophilic asthma.

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Concurrent Use of Salmeterol with Inhaled Corticosteroids is More Effective than Inhaled Corticosteroid Dose Increases

Allergy and Asthma Proceedings ◽

10.2500/108854199778553028 ◽

1999 ◽

Vol 20 (3) ◽

pp. 173-180 ◽

Cited By ~ 59

Author(s):

John J. Murray ◽

Nina L. Church ◽

Wayne H. Anderson ◽

David I. Bernstein ◽

Sally E. Wenzel ◽

...

Keyword(s):

Inhaled Corticosteroids ◽

Inhaled Corticosteroid ◽

Corticosteroid Dose ◽

Concurrent Use

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COPD patients prescribed inhaled corticosteroid in primary care: time for re-assessment based on exacerbation rate and blood eosinophils?

Respiratory Research ◽

10.1186/s12931-021-01651-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Osman Savran ◽

Nina Godtfredsen ◽

Torben Sørensen ◽

Christian Jensen ◽

Charlotte Suppli Ulrik

Keyword(s):

Primary Care ◽

Eosinophil Count ◽

Large Cohort ◽

Blood Eosinophil ◽

Study Cohort ◽

Inhaled Corticosteroid ◽

Exacerbation Rate ◽

Blood Eosinophil Count ◽

Copd Patients ◽

Blood Eosinophils

Abstract Background and objective Inhaled corticosteroid (ICS) therapy for COPD should be guided by exacerbations and blood-eosinophils according to the GOLD 2020 strategy document. In the present study, we applied these recent recommendations in a large cohort of COPD patients recruited from general practice. Methods The participating general practitioners (n = 144) recruited patients with a diagnosis of COPD currently prescribed ICS and reported data on exacerbation history and blood-eosinophils. Clinical variables were compared using two-sample t-tests. Results The study cohort comprised 1,567 COPD patients (44% males and mean age 72 years). In the past 12 months, 849 (54%) of the COPD patients currently prescribed ICS had no exacerbation, whereas 383 (24%) and 328 (21%) patients, respectively, had a history of one exacerbation and two or more exacerbations. Compared to patients with one or no exacerbation, patients with ≥ 2 exacerbations (21%) per year reported more dyspnea (p < 0.001) and had higher degree of airflow obstruction (p < 0.001). Among patients with no and at least one exacerbation within the preceding 12 months, 30% and 26%, respectively, had a blood-eosinophil count ≥ 0.3 × 109/L. In patients with two or more exacerbations within the last 12 months, 77% had a blood-eosinophil count of ≥ 0.1 × 109/L. Furthermore, 166 patients (11%) had at least one hospital admission due to COPD exacerbation, and a blood-eosinophil count of ≥ 0.1 × 109/L. Conclusion This study of a large cohort of COPD patients currently prescribed inhaled corticosteroids suggests the need for re-evaluating the management strategy to increase benefit and reduce adverse effects of ICS treatment in COPD patients managed in primary care.

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COPD patients prescribed inhaled corticosteroid in primary care – Time for re-assessment based on exacerbation rate and blood eosinophils?

10.21203/rs.3.rs-51349/v3 ◽

2021 ◽

Author(s):

Osman Savran ◽

Nina Skavlan Godtfredsen ◽

Torben Sørensen ◽

Christian Jensen ◽

Charlotte Ulrik

Keyword(s):

Primary Care ◽

Eosinophil Count ◽

Large Cohort ◽

Blood Eosinophil ◽

Study Cohort ◽

Inhaled Corticosteroid ◽

Exacerbation Rate ◽

Blood Eosinophil Count ◽

Copd Patients ◽

Blood Eosinophils

Abstract Background and objective: Inhaled corticosteroid (ICS) therapy for COPD should be guided by exacerbations and blood-eosinophils according to the GOLD 2020 strategy document. In the present study, we applied these recent recommendations in a large cohort of COPD patients recruited from general practice. Methods: The participating general practitioners (n = 144) recruited patients with a diagnosis of COPD currently prescribed ICS and reported data on exacerbation history and blood-eosinophils. Clinical variables were compared using two-sample t-tests. Results: The study cohort comprised 1,567 COPD patients (44% males and mean age 72 years). In the past 12 months, 849 (54%) of the COPD patients currently prescribed ICS had no exacerbation, whereas 383 (24%) and 328 (21%) patients, respectively, had a history of one exacerbation and two or more exacerbations. Compared to patients with one or no exacerbation, patients with ≥2 exacerbations (21%) per year reported more dyspnea (p<0.001) and had higher degree of airflow obstruction (p<0.001). Among patients with no and at least one exacerbation within the preceding 12 months, 30% and 26%, respectively, had a blood-eosinophil count ≥ 0.3 x 109/L. In patients with two or more exacerbations within the last 12 months, 77% had a blood-eosinophil count of ≥ 0.1 x 109/L. Furthermore, 166 patients (11%) had at least one hospital admission due to COPD exacerbation, and a blood-eosinophil count of ≥ 0.1 x 109/L.Conclusion: This study of a large cohort of COPD patients currently prescribed inhaled corticosteroids suggests the need for re-evaluating the management strategy to increase benefit and reduce adverse effects of ICS treatment in COPD patients managed in primary care.

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Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD

European Respiratory Journal ◽

10.1183/13993003.00451-2017 ◽

2017 ◽

Vol 50 (4) ◽

pp. 1700451 ◽

Cited By ~ 49

Author(s):

Marco Contoli ◽

Alessia Pauletti ◽

Maria Rita Rossi ◽

Antonio Spanevello ◽

Paolo Casolari ◽

...

Keyword(s):

Pathogenic Bacteria ◽

Inhaled Corticosteroids ◽

Respiratory Infections ◽

Bacterial Load ◽

Blood Eosinophil ◽

Inhaled Corticosteroid ◽

Long Term Effects ◽

Open Label ◽

Microbial Composition

Inhaled corticosteroid-containing medications reduce the frequency of COPD exacerbations (mainly infectious in origin) while paradoxically increasing the risk of other respiratory infections.The aim was to determine the effects of inhaled corticosteroids on airway microbial load in COPD patients and evaluate the influence of the underlying inflammatory profile on airway colonisation and microbiome.This is a proof-of-concept prospective, randomised, open-label, blinded endpoint study. Sixty patients with stable moderate COPD were randomised to receive one inhalation twice daily of either a combination of salmeterol 50 μg plus fluticasone propionate 500 μg or salmeterol 50 μg for 12 months. The primary outcome was the change of sputum bacterial loads over the course of treatment.Compared with salmeterol, 1-year treatment with salmeterol plus fluticasone was associated with a significant increase in sputum bacterial load (p=0.005), modification of sputum microbial composition and increased airway load of potentially pathogenic bacteria. The increased bacterial load was observed only in inhaled corticosteroid-treated patients with lower baseline sputum or blood eosinophil (≤2%) levels but not in patients with higher baseline eosinophils.Long-term inhaled corticosteroid treatment affects bacterial load in stable COPD. Lower eosinophil counts are associated with increased airway bacterial load.

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Inhaled corticosteroid dose-response on blood eosinophils in asthma

The Lancet Respiratory Medicine ◽

10.1016/s2213-2600(15)00504-4 ◽

2016 ◽

Vol 4 (1) ◽

pp. e1 ◽

Cited By ~ 2

Author(s):

Brian Lipworth ◽

Sunny Jabbal ◽

Arvind Manoharan ◽

William Anderson ◽

Philip Short

Keyword(s):

Dose Response ◽

Inhaled Corticosteroid ◽

Corticosteroid Dose ◽

Blood Eosinophils

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Predictors of Loss of Asthma Control Induced by Corticosteroid Withdrawal

Canadian Respiratory Journal ◽

10.1155/2006/189127 ◽

2006 ◽

Vol 13 (3) ◽

pp. 129-133 ◽

Cited By ~ 29

Author(s):

Jose Belda ◽

Krishnan Parameswaran ◽

Catherine Lemière ◽

Dennis Kamada ◽

Paul M O'Byrne ◽

...

Keyword(s):

Nitric Oxide ◽

Asthma Control ◽

Eosinophil Count ◽

Inhaled Corticosteroids ◽

Forced Expiratory Volume ◽

Exhaled Nitric Oxide ◽

Baseline Risk ◽

Blood Eosinophil ◽

Inhaled Corticosteroid ◽

Sputum Eosinophil

BACKGROUND: Asthma guidelines recommend reducing the dose of inhaled corticosteroids after establishing control.OBJECTIVE: To identify predictors of loss of control and the kinetics of symptoms, and inflammatory and physiological measurements when inhaled corticosteroids are reduced in patients with stable asthma.PATIENTS AND METHODS: In a single-blind study, the daily dose of inhaled corticosteroid was reduced by one-half at intervals of 20±2 days in 17 adults with controlled asthma until loss of asthma control occurred or until the corticosteroid was replaced with placebo for 20 days. The patients recorded symptoms and peak expiratory flow each day, and forced expiratory volume in 1 s (FEV1), the provocative concentration of methacholine causing a 20% fall in FEV1(PC20), exhaled nitric oxide, and eosinophils in sputum and blood were measured every 10 days. A loss of asthma control was defined as a worsening of the symptoms score of at least 20%, and either a decrease in FEV1of at least 15% or a decrease in PC20of at least fourfold.RESULTS: Two patients had a respiratory infection and were withdrawn from the study. In eight patients, asthma became uncontrolled after a mean of 33 days (range 13 to 48 days). This was accurately reflected by a worsening of all parameters. The first parameter to change was the sputum eosinophil percentage (20 days before the loss of asthma control). Significant changes in exhaled nitric oxide, FEV1and methacholine PC20were observed only when the symptoms became uncontrolled. A high blood eosinophil count at baseline (risk ratio of 2.5, 95% CI 1.0 to 6.5) and an increase in sputum eosinophil count after the reduction of corticosteroids were predictors of loss of asthma control.CONCLUSION: In patients whose asthma is controlled on inhaled corticosteroid, it is prudent not to reduce the dose further if the blood eosinophils are increased or if the sputum eosinophils increase by as little as 1% after the reduction of corticosteroids.

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