A Pooled Analysis of FEV 1 Decline in COPD Patients Randomized to Inhaled Corticosteroids or Placebo

Soriano, Joan B.; Sin, Don D.; Zhang, Xuekui; Camp, Pat G.; Anderson, Julie A.; Anthonisen, N. R.; Buist, A. Sonia; Burge, P. S.; Calverley, Peter M.A.; Connett, John E.; Petersson, Stefan; Postma, Dirkje S.; Szafrański, W; Vestbo, Jørgen

doi:10.1378/chest.06-1696

Cited by 119 publications

(71 citation statements)

References 43 publications

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“…Inhaled corticosteroids are anti-inflammatory medications that are widely used in COPD patients, but their clinical response is often relatively poor, 22 with failure to reduce levels of key COPD-related inflammatory cells (CD8 ϩ T lymphocytes, neutrophils) and the interaction suppression of cytokine relapse [23][24][25] after stimuli. As documented in peripheral lung tissue, alveolar macrophages, and bronchial biopsy specimens of COPD patients, a molecular mechanism of steroid resistance may be due to reduced levels of histone deacetylase-2 activity [26][27][28] ; this is a nuclear enzyme involved in corticosteroid deactivation of pro-inflammatory genes and in the repression of cytokine production.…”

Section: Discussionmentioning

confidence: 99%

Inhaled Corticosteroids Do Not Influence the Early Inflammatory Response and Clinical Presentation of Hospitalized Subjects With COPD Exacerbation

et al. 2014

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BACKGROUND: Inhaled corticosteroids are anti-inflammatory medications that can down-regulate the immunologic response in patients with COPD; however, their role at onset of COPD exacerbation is still not understood. The aim of this study was to assess the early inflammatory response and clinical presentation of patients with COPD exacerbation mediated by inhaled corticosteroids. METHODS: Prospective data were collected on 123 hospitalized subjects with COPD exacerbation over a 30-month period at 2 Spanish university hospitals. Based on domiciliary use, comparative analyses were performed between subjects who did not use inhaled corticosteroids (n ‫؍‬ 58) and subjects who did (n ‫؍‬ 65). Measurements of serum biomarkers were recorded on admission to the hospital (day 1) and on day 3; clinical, physiological, microbiological, and severity data and mortality/readmission rates were also recorded. RESULTS: At days 1 and 3, both groups showed a similar inflammatory response; fluticasone produced lower levels of interleukin-8 compared with budesonide (P < .01). All clinical features considered were similar in the 2 groups; multivariate analysis predicting clinical complications on hospitalization showed air-flow obstruction severity as the only predictive factor (odds ratio 3.13, 95% CI 1.13-8.63, P ‫؍‬ .02). CONCLUSIONS: Our study demonstrates a lack of inhaled corticosteroid influence in the early systemic inflammatory response to and clinical presentation of COPD exacerbation.

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Section: Discussionmentioning

confidence: 99%

Inhaled Corticosteroids Do Not Influence the Early Inflammatory Response and Clinical Presentation of Hospitalized Subjects With COPD Exacerbation

et al. 2014

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“…A pooling of seven randomised studies (,5,000 patients) found that ICS reduced COPD mortality by 27% relative to placebo, although none of the studies separately reached significance in favour of ICSs [63]. The beneficial effect, however, was particularly noticeable in exsmokers and females, and it is assumed that ICSs may potentially work better in ex-smokers than current smokers in COPD, through largely unknown mechanisms [64]. Surprisingly, the TORCH trial showed no survival benefit in patients randomised to ICSs alone.…”

Section: Mortalitymentioning

confidence: 99%

COPD-related morbidity and mortality after smoking cessation: status of the evidence

Godtfredsen¹,

Lam²,

Hansel³

et al. 2008

European Respiratory Journal

234

143

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The evidence base for the benefit of quitting smoking as regards morbidity and mortality outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) is limited.The present article is a review of the existing literature. A systematic literature search in medical databases was performed until March 2006, and subsequently until September 1, 2007. The outcomes examined were COPD-related morbidity and mortality (including all-cause mortality) in COPD patients in connection with smoking cessation.A total of 21 and 27 published articles on morbidity and mortality, respectively, were identified and reviewed. For both outcomes, only a few of the studies included patients with severe COPD. Most of the studies reported a beneficial effect of smoking cessation compared with continued smoking, whereas a few found no improvement. Methodological problems, including small study sizes, poor data quality, possibility of reverse causality and incomplete ascertainment of cause of death, limit interpretation of some of the studies.The evidence as a whole supports the conclusion that, even in severe chronic obstructive pulmonary disease, smoking cessation slows the accelerated rate of lung function decline and improves survival compared with continued smoking.

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“…Indeed, with recent concerns regarding the safety of LABA monotherapy in the treatment 91 of asthma, current guidance supports fixed dose combinations of LABA/ICS therapy from a 92 single inhaler [5][6][7]. Chronic obstructive pulmonary disease (COPD) is also characterized by 93 chronic airways inflammation, but unlike asthma, ICS treatment on its own has relatively little 94 effect on the accelerated decline in lung function seen in COPD patients [8,9]. However in 95 contrast, several large clinical trials of combination LABA/ICS therapy in patients with stable 96 COPD have shown better control of respiratory symptoms, lung function, quality of life, and 97 exacerbations with no greater risk of side-effects, compared to the use of either ICS alone or 98 LABA alone (10-13).…”

Section: Introduction 88mentioning

confidence: 99%

Inhaled long-acting β2 agonists enhance glucocorticoid receptor nuclear translocation and efficacy in sputum macrophages in COPD

Haque

Hakim

Moodley

et al. 2013

Journal of Allergy and Clinical Immunology

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A Pooled Analysis of FEV 1 Decline in COPD Patients Randomized to Inhaled Corticosteroids or Placebo

Cited by 119 publications

References 43 publications

Inhaled Corticosteroids Do Not Influence the Early Inflammatory Response and Clinical Presentation of Hospitalized Subjects With COPD Exacerbation

Inhaled Corticosteroids Do Not Influence the Early Inflammatory Response and Clinical Presentation of Hospitalized Subjects With COPD Exacerbation

COPD-related morbidity and mortality after smoking cessation: status of the evidence

Inhaled long-acting β2 agonists enhance glucocorticoid receptor nuclear translocation and efficacy in sputum macrophages in COPD

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