Effect of High Dose Inhaled Steroid on Cells, Cytokines, and Proteases in Induced Sputum in Chronic Obstructive Pulmonary Disease

Culpitt, Sarah V.; Maziak, Wasim; Loukidis, Stelios; Nightingale, Julia A.; Matthews, John L.; Barnes, Peter J.

doi:10.1164/ajrccm.160.5.9811058

Cited by 379 publications

(247 citation statements)

References 35 publications

Supporting

Mentioning

222

Contrasting

Unclassified

Order By: Relevance

“…At the same time this treatment can produce systemic adverse effects, including skin bruising, adrenal suppression or loss of bone density [142][143][144]. Not surprisingly the inflammation in COPD is scarcely suppressed by inhaled or oral glucocorticoids, even at high doses [66,145,146].…”

Section: Effects Of Inhaled Corticosteroids In Copdmentioning

confidence: 99%

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Chung

Caramori

Adcock

2009

Eur J Clin Pharmacol

123

106

View full text Add to dashboard Cite

International audienceInhaled corticosteroid (ICS) therapy in combination with long-acting β-adrenergic agonists represents the most important treatment for chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). ICS therapy forms the basis for treatment of asthma of all severities, improving asthma control, lung function and preventing exacerbations of disease. Use of ICS has also been established in the treatment of COPD, particularly symptomatic patients, who experience useful gains in quality of life, likely from an improvement in symptoms such as breathlessness and in reduction in exacerbations, and an attenuation of the yearly rate of deterioration in lung function. The addition of long-acting β-agonist (LABA) therapy with ICS increases the efficacy of ICS effects in moderate-to-severe asthma. Thus, a 800 μg daily dose of the ICS budesonide reduced severe exacerbation rates by 49% compared to a low dose of 200 μg daily, and addition of the LABA formoterol to budesonide (800 μg) led to a 63% reduction. In COPD, the effects of ICS are less prominent but there are beneficial effects on the decline in FEV and the rate of exacerbations. A reduction in the rate of decline in FEV of 16 ml/year with a 25% reduction in exacerbation rate has been reported with the salmeterol and fluticasone combination. A non-significant 17.5% reduction in all-cause mortality rate with ICS and LABA is reported. Chronic inflammation is a feature of both asthma and COPD, although there are site and characteristic differences. ICS targets this inflammation although this effect of ICS is less effective in patients with severe asthma and with COPD; however, addition of LABA may potentiate the anti-inflammatory effects of ICS. An important consideration is the presence of corticosteroid insensitivity in these patients. Currently available ICS have variably potent binding activities to specific glucocorticoid receptors, leading to inhibition of gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. Local side effects of ICS include oral candidiasis, hoarseness and dysphonia, while systemic side effects, such as easy bruising and reduction in growth velocity or bone mineral densitometry, are usually restricted to doses above maximally recommended doses. Use of LABA alone in patients with asthma increases the risk of asthma-related events including deaths, but this is less observed with the combination of ICS and LABA. Therefore, use of LABA alone is not recommended for asthma therapy. Future progress in ICS development will be characterised by the introduction of ICS with greater efficacy with a limited side-effect profile, and by longer-acting ICS that can be used in combination with once-daily LABAs. Other agents that could improve the efficacy of corticosteroids or reverse corticosteroid insensitivity may be added to ICS. ICS in combination with LABAs will continue to remain the main focus of treatment of airways diseases

show abstract

Section: Effects Of Inhaled Corticosteroids In Copdmentioning

confidence: 99%

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Chung

Caramori

Adcock

2009

Eur J Clin Pharmacol

123

106

View full text Add to dashboard Cite

show abstract

“…In COPD, inflammation is not suppressed by corticosteroids and there is no reduction in inflammatory cells, cytokines, or proteases in induced sputum, even with oral corticosteroids (63,64). Corticosteroids do not suppress neutrophilic inflammation in the airways, and corticosteroids may prolong the survival of neutrophils (65).…”

Section: Corticosteroid Resistance In Copdmentioning

confidence: 99%

“…There is a striking reduction in the activity and expression of HDACs in the peripheral lung of patients with COPD (68). Even in patients with COPD who have stopped smoking, the steroid resistance persists (63,64), and these patients are known to have continuing oxidative stress (69).…”

Section: Corticosteroid Resistance In Copdmentioning

confidence: 99%

How Do Corticosteroids Work in Asthma?

2003

View full text Add to dashboard Cite

“…Systemische Kortikosteroide sind daher nur für den begrenzten Zeitraum einer Exazerbation indiziert [36]. Die vierwö-chige Behandlung von Patienten mit leichter bis mittelschwerer COPD mit hochdosierten inhalativen Kortikosteroiden führt weder zu einer funktionellen Verbesserung noch zu einer Modulation der Entzündungsmarker im Sputum und Exhalat [37,38]. Vor dem Hintergrund dieser Daten sollte der Einsatz von systemischen Kortikosteroiden der Exazerbation vorbehalten bleiben [39].…”

Section: Antiinflammatorische Therapie Der Copdunclassified

COPD: Eine entzündliche Erkrankung der Atemwege?

Magnussen

2004

Pneumologie

View full text Add to dashboard Cite

EinleitungDie chronisch obstruktive Bronchitis und das Lungenemphysem werden aufgrund der Schwierigkeiten der Abgrenzung der bronchitischen und emphysematösen Komponente nach dem Vorschlag der Global Initiative for Chronic Obstructive Lung Disease (GOLD) mit COPD (chronic obstructive pulmonary disease) abgekürzt [1].Die COPD ist durch eine nicht vollständig reversible Begrenzung des Atemflusses charakterisiert. Die Limitation des Atemflusses ist meist fortschreitend und mit einer abnormen entzündlichen Reaktion der Lungen vergesellschaftet [1, 2].Die Pharmakotherapie der COPD beruht überwiegend auf den Substanzen, die bei der Behandlung des Asthma bronchiale eingesetzt werden. Die Atemwegsobstruktion kann erfolgreich mit Bronchodilatatoren behandelt werden, während für die Beeinflussung der abnormen entzündlichen Reaktion bislang vorwiegend Kortikosteroide zur Verfügung stehen. Die hervorragende Effektivität der Kortikosteroide beim Asthma bronchiale hat zu zahlreichen Studien geführt, die den Einsatz insbesondere von inhalativen Kortikosteroiden bei der COPD rechtfertigen sollen.Ich möchte mich in dem folgenden Beitrag mit einigen Aspekten auseinandersetzen, die den Zusammenhang zwischen den funktionellen Konsequenzen der COPD, der abnormen Entzündungs-reaktion und den therapeutischen Möglichkeiten betreffen. Funktionelle Konsequenzen der COPDDie COPD ist durch eine meist progressive Limitation der Strö-mung innerhalb der Atemwege gekennzeichnet. Dieses funktionelle Merkmal wird üblicherweise mit Hilfe der Spirometrie gemessen, die aufgrund der internationalen Übereinkommen nur das exspiratorische Manöver berücksichtigt [3]. Die forciert exspirierte Vitalkapazität, FVC, das forciert exspirierte Volumen in der ersten Sekunde der Ausatmung, FEV 1.0 und deren Verhältnis beschreiben die Atemwegsobstruktion in qualitativer und quantitativer Weise. Die Stadieneinteilung der COPD beruht auf dem Nachweis einer obstruktiven Ventilationsstörung durch eine Erniedrigung von FEV 1.0 /FVC < 70 % sowie einer definierten Erniedrigung von FEV 1.0 . Während die spirometrischen Parameter von den verschiedenen Expertengremien in gleicher Weise eingesetzt werden, unterscheiden sich die quantitativen Angaben, die zur Abschätzung der Schweregrade führen. Dieser Umstand erschwert unter anderem den Vergleich epidemiologischer Erhebungen zur Häufigkeit und Schwere der COPD in verschiedenen Ländern [4,5].Die Objektivierung der obstruktiven Ventilationsstörung durch die alleinige Auswertung der forcierten Exspiration stellt einen

show abstract

Effect of High Dose Inhaled Steroid on Cells, Cytokines, and Proteases in Induced Sputum in Chronic Obstructive Pulmonary Disease

Cited by 379 publications

References 35 publications

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

How Do Corticosteroids Work in Asthma?

COPD: Eine entzündliche Erkrankung der Atemwege?

Contact Info

Product

Resources

About