A comparative study of the effects of an inhaled corticosteroid, budesonide, and a β2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: A randomized, double-blind, parallel-group controlled trial

doi:10.1016/S0091-6749(06)80008-4

Journal of Allergy and Clinical Immunology

Volume 90, Issue 1, July 1992, Pages 32-42

https://doi.org/10.1016/S0091-6749(06)80008-4 Get rights and content

We compared the effect of an inhaled corticosteroid, budesonide, and an inhaled β₂-agonist, terbutaline, on clinical symptoms, lung function, and airway inflammation in 14 adult patients with newly diagnosed asthma. The study was conducted as a randomized, double-blind, parallel-group trial. Seven patients inhaled 600 μg, twice daily, of budesonide, the other seven patients inhaled 375 μg, twice daily, of terbutaline via identical metered-dose inhalers with a spacer. Bronchial biopsy specimens, obtained before randomization and after 3 months of treatment, were analyzed by electron microscopy. Both groups improved clinically budesonide was more effective than terbutaline in improving morning and evening peak expiratory flow rates, as well as bronchial responsiveness to inhaled histamine. Treatment with budesonide was accompanied by increased numbers of ciliated airway cells and intraepithelial nerves and fewer inflammatory cells, including eosinophils, especially in the epithelium, these changes were not observed in specimens from terbutaline-treated patients. We conclude that, in contrast to inhaled terbutaline, inhaled budesonide improved lung function and bronchial hyperreactivity in adult subjects with asthma treated for 3 months and that this corticosteroid was more effective in ameliorating abnormalities of the bronchial epithelium and decreasing inflammation in the airways.

References (25)

KraanJ et al.
Changes in bronchial hyperreactivity induced by 4 weeks of treatment with antiasthmatic drugs in patients with allergic asthma: a comparison between budesonide and terbutaline
J Allergy Clin Immunol
(1985)
SearsMR et al.
Regular inhaled β-agonist treatment in bronchial asthma
Lancet
(1990)
LaitinenLA et al.
Damage of the airway epithelium and bronchial reactivity in patients with asthma
Am Rev Respir Dis
(1985)
SöderbergM et al.
Bergh A. Structural characterization of bronchial mucosal biopsies from healthy volunteers: a light and electron microscopical study
Eur Respir J
(1990)
BeasleyR et al.
Cellular events in the bronchi in mild asthma and after bronchial provocation
Am Rev Respir Dis
(1989)
JefferyPK et al.
Bronchial biopsies in asthma
Am Rev Respir Dis
(1989)
BousquetJ et al.
Eosinophilic inflammation in asthma
N Engl J Med
(1990)
LaitinenLA et al.
Pathology of human asthma
BarnesPJ
A new approach to the treatment of asthma
N Engl J Med
(1989)
HaahtelaT et al.
Comparison of a β₂-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma
N Engl J Med
(1991)

LaitinenLA et al.

Inflammatory cell population in the airways of newly diagnosed asthmatic patients: a quantitative ultrastructural study

Eur Respir J

(1990)

JuniperEF et al.

Effect of long-term treatment with inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthm

Am Rev Respir Dis

(1990)

Cited by (532)

Corticosteroid resistance in asthma: Cellular and molecular mechanisms
2022, Molecular Aspects of Medicine
Inhaled glucocorticoids (GCs) are drugs widely used as treatment for asthma patients. They prevent the recruitment and activation of lung immune and inflammatory cells and, moreover, have profound effects on airway structural cells to reverse the effects of disease on airway inflammation. GCs bind to a specific receptor, the glucocorticoid receptor (GR), which is a member of the nuclear receptor superfamily and modulates pro- and anti-inflammatory gene transcription through a number of distinct and complementary mechanisms. Targets genes include many pro-inflammatory mediators such as chemokines, cytokines, growth factors and their receptors. Inhaled GCs are very effective for most asthma patients with little, if any, systemic side effects depending upon the dose. However, some patients show poor asthma control even after the administration of high doses of topical or even systemic GCs. Several mechanisms relating to inflammation have been considered to be responsible for the onset of the relative GC resistance observed in these patients. In these patients, the side-effect profile of GCs prevent continued use of high doses and new drugs are needed. Targeting the defective pathways associated with GC function in these patients may also reactivate GC responsiveness.
Effect of long-term oral corticosteroid therapy in severe T2-weighted asthma patients
2020, Revue des Maladies Respiratoires Actualites
L’asthme est sévère lorsqu’il ne peut être contrôlé par des traitements inhalés à dose maximale (à condition qu’ils soient pris bien entendu), alors que la prise en charge des comorbidités et des autres facteurs précipitants ou aggravants ait été optimisée. Cette forme d’asthme ne concerne qu’environ 5 % des asthmatiques mais représente environ 60 % des dépenses.
Les corticostéroïdes ont révolutionné la prise en charge de l’asthme, confirmant la nature inflammatoire de cette maladie. L’identification des mécanismes d’action des corticoïdes dans cette maladie a permis de définir l’inflammation de type 2, ses acteurs clés (IL-4, IL-5, IL-13, TSLP, IL-33, IgE) et ses biomarqueurs non invasifs (éosinophiles de l’expectoration et/ou du sang et/ou tissulaires, FeNO, allergie à la fois clinique et biologique, polypose naso-sinusienne, possiblement l’intolérance aux AINS et à l’aspirine, cortico-dépendance) pour l’identifier chez les patients. On estime qu’au moins 60 à 80 % des asthmatiques ont ce profil.
Les stratégies d’épargne en corticostéroïdes oraux (CSO) suscitent un intérêt particulier en raison de leurs effets secondaires potentiels. Le recours aux CSO au-delà de 0,5 à 1 g/an expose de façon majeure aux complications des glucocorticoïdes et il s’agit d’un seuil facile à identifier pour déclencher l’adressage du patient à un centre expert de l’asthme sévère, car des solutions d’épargne cortisonique très efficaces sont maintenant disponibles.
© 2020 SPLF. Publié par Elsevier Masson SAS. Tous droits réservés.
Severe asthma is defined by a disease that remains partially controlled, or even uncontrolled, despite high dose of inhaled corticosteroid (ICS), while the management of comorbidities and other precipitating or aggravating factors has been optimized. Severe asthma represents only 5% of the asthma population but significant economic burden is associated with the disease and represents 60% of healthcare costs. Corticosteroids have completely revolutionized the management of asthma, confirming the inflammatory nature of this disease. Identification of corticosteroids biological mechanisms in asthma allows to define type 2 inflammation, the inflammatory mediators (IL-4, IL-5, IL-13, TSLP, IL-33, IgE) and the non-invasive biomarkers (sputum and/or blood eosinophilia and/or tissue inflammation, FeNO, clinical and biological allergy, nasal polyposis, aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) intolerance, corticosteroid dependent asthma). At least 60 to 80% of asthmatic patients have T2 inflammatory profile.
Options to achieve oral corticosteroid-sparing (OCS-sparing) have been increasing interest because of the side effects of oral corticosteroids (OCS), and this has now become achievable with biologics. In addition, a crucial message is that the need for OSCs above 0.5 to 1 g/year exposes to major complications and indicates the need for referral to secondary/tertiary care.
© 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.
Asthma maintenance and reliever therapy: Should this be the standard of care?
2020, Annals of Allergy, Asthma and Immunology
The goal of asthma management is to achieve optimal asthma control, defined by the absence of daytime symptoms, nighttime waking, reliever use, functional limitation, and lung function stability, and to also reduce the future risks of asthma exacerbations, deterioration in lung function, and the medication’s adverse effects. The most widely used maintenance therapy is inhaled corticosteroids (ICSs). This review considered the evidence in which the combination of the ICS budesonide and the rapid-onset long-acting β-agonist (LABA) formoterol can be used as a standard of care for maintenance and reliever therapy in moderate to severe asthma.
The archival literature of peer-reviewed studies on the efficacy and safety of budesonide-formoterol as maintenance and reliever therapy in moderate to severe asthma.
The ICS-LABA combination containing budesonide-formoterol reduces future risk of severe asthma exacerbations and provides similar levels of day-to-day asthma control when compared with using high-dose ICS alone, or combination ICS-LABA therapy and short-acting β₂-agonist as a reliever.
Budesonide-formoterol as a single combination maintenance and reliever inhaler is effective in reducing asthma exacerbation risk, requires a lower maintenance dose of ICS, and results in a simplified approach to asthma management.
A review of the burden and management of mild asthma in adults — Implications for clinical practice
2019, Respiratory Medicine
Mild asthma is present in 50–75% of patients with asthma and is defined by the Global Initiative for Asthma as asthma that can be well controlled with low-intensity treatments (Steps 1 and 2). Despite this definition, ‘mild’ asthma is often not well controlled in reality, and can have a significant impact on an individual's symptom burden and quality of life.
We performed a PubMed literature search to investigate the burden of ‘mild’ asthma in the lives of patients, including future risk and asthma control, and the current management strategies. While clinical guidelines recommend long-term, daily, low-dose inhaled corticosteroids (ICS) for ‘mild’ asthma, published data suggest that ICS are often under-prescribed or used intermittently as symptoms arise. Furthermore, patients and physicians tend to overestimate disease control, impacting the accuracy of diagnosing ‘mild asthma’ and subsequent management. This disconnect may be amplified by miscommunication between patients and physicians, limited objective assessment of control, and differences in guidelines.
As with moderate and severe asthma, current evidence supports early initiation of regular ICS in ‘mild’ asthma to address the underlying inflammation, achieve symptom control and reduce risk of exacerbations. Adherence to ICS treatment is key and can be improved by educating both patients and healthcare professionals. The results of this literature search challenge the term ‘mild’ asthma and suggest strategies to improve the proactive management of the disease to enable patients to live symptom-free.
Revisiting asthma therapeutics: focus on WNT signal transduction
2018, Drug Discovery Today
Asthma is a complex disease of the airways that develops as a consequence of both genetic and environmental factors. This interaction has highlighted genes important in early life, particularly those that control lung development, such as the Wingless/Integrase-1 (WNT) signalling pathway. Although aberrant WNT signalling is involved with an array of human conditions, it has received little attention within the context of asthma. Yet it is highly relevant, driving events involved with inflammation, airway remodelling, and airway hyper-responsiveness (AHR). In this review, we revisit asthma therapeutics by examining whether WNT signalling is a valid therapeutic target for asthma.
The Finnish experience to save asthma costs by improving care in 1987-2013
2017, Journal of Allergy and Clinical Immunology
The Finnish National Asthma Program 1994-2004 markedly improved asthma care in the 1990s. We evaluated the changes in costs during 26 years from 1987 to 2013. Direct and indirect costs were calculated by using data from national registries. Costs from both the societal and patient perspectives were included. The costs were based on patients with persistent, physician-diagnosed asthma verified by lung function measurements. We constructed minimum and maximum scenarios to assess the effect of improved asthma care on total costs. The number of patients with persistent asthma in the national drug reimbursement register increased from 83,000 to 247,583. Improved asthma control reduced health care use and disability, resulting in major cost savings. Despite a 3-fold increase in patients, the total costs decreased by 14%, from €222 million to €191 million. Costs for medication and primary care visits increased, but overall annual costs per patient decreased by 72%, from €2656 to €749. The theoretical total cost savings for 2013, comparing actual with predicted costs, were between €120 and €475 million, depending on the scenario used. The Finnish Asthma Program resulted in significant cost savings at both the societal and patient levels during a 26-year period.

View all citing articles on Scopus

^*: Supported by a grant from the Swedish Heart and Lung Foundation (Hjärt-Lungfonden) and the Finnish Antituberculosis Association.

View full text

A comparative study of the effects of an inhaled corticosteroid, budesonide, and a β2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: A randomized, double-blind, parallel-group controlled trial*

J Allergy Clin Immunol

Lancet

Damage of the airway epithelium and bronchial reactivity in patients with asthma

Am Rev Respir Dis

Bergh A. Structural characterization of bronchial mucosal biopsies from healthy volunteers: a light and electron microscopical study

Eur Respir J

Cellular events in the bronchi in mild asthma and after bronchial provocation

Am Rev Respir Dis

Bronchial biopsies in asthma

Am Rev Respir Dis

Eosinophilic inflammation in asthma

N Engl J Med

Pathology of human asthma

A new approach to the treatment of asthma

N Engl J Med

Comparison of a β2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma

N Engl J Med

Inflammatory cell population in the airways of newly diagnosed asthmatic patients: a quantitative ultrastructural study

Eur Respir J

Effect of long-term treatment with inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthm

Am Rev Respir Dis

A comparative study of the effects of an inhaled corticosteroid, budesonide, and a β₂-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: A randomized, double-blind, parallel-group controlled trial*

Comparison of a β₂-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma