Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial

Vestbo, Jørgen; Søorensen, Torben; Lange, Peter; Brix, Anders; Torre, Piero; Viskum, K

doi:10.1016/s0140-6736(98)10019-3

Cited by 723 publications

(404 citation statements)

References 23 publications

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“…First, because of its anti-inflammatory effect, it was hoped that long-term ICS could alter the natural course of COPD such as the long-term decline in FEV 1 . However, no significant effects of ICS alone on slope has been shown [142,[147][148][149]. However, in two subsequent meta-analyses published, one concluded that ICS reduced FEV 1 decline by a small statistical mean rate of 7.7 ml/year [150], while another meta-analysis showed a non-significant 5.0 ml/year reduction [151].…”

Section: Effect Of Ics Alonementioning

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

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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

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Section: Effect Of Ics Alonementioning

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

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“…In contrast, in the Copenhagen City Lung Study long term treatment with inhaled steroids had no effect on decline in lung function in patients with mild to moderate irreversible airflow limitation. 6 In a recent study patients with COPD were treated with triamcinolone for 3 years. 7 A subgroup of the patients was hyperreactive.…”

Section: Discussionmentioning

confidence: 99%

“…The improvements in lung function parameters, which are characteristic of steroid treatment in asthma, have not been unequivocally found in patients with COPD. [4][5][6][7] It has been postulated that, if steroids are important in the treatment of COPD, they act via downregulation of cytokine and adhesion molecule expression with a consequent reduction in cell migration and activation. 8 To date, only a limited number of studies have examined the effect of steroid treatment on inflammation in COPD.…”

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confidence: 99%

Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness

Verhoeven

Hegmans²,

Mulder³

et al. 2002

Thorax

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Background: Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids does not appear to be as effective as similar treatment of asthma. It seems that only certain subgroups of patients with COPD benefit from steroid treatment. A study was undertaken to examine whether inhaled fluticasone propionate (FP) had an effect on lung function and on indices of inflammation in a subgroup of COPD patients with bronchial hyperresponsiveness (BHR). Methods: Twenty three patients with COPD were studied. Patients had to be persistent current smokers between 40 and 70 years of age. Non-specific BHR was defined as a PC 20 for histamine of <8 mg/ ml. Patients received either 2 × 500 µg FP or placebo for 6 months. Expiratory volumes were measured at monthly visits, BHR was determined at the start of the study and after 3 and 6 months, and bronchial biopsy specimens were taken at the start and after 6 months of treatment. Biopsy specimens from asymptomatic smokers served as controls. Results: In contrast to asthma, indices of BHR were not significantly influenced by treatment with FP. Forced expiratory volume in 1 second (FEV 1 ) showed a steep decline in the placebo group but remained stable in patients treated with FP. FEV 1 /FVC, and maximal expiratory flows at 50% and 25% FVC (MEF 50 , MEF 25 ) were significantly increased in the FP treated patients compared with the placebo group. Biopsy specimens were analysed for the presence of CD3+, CD4+, CD8+, MBP+, CD15+, CD68+, CD1a, and tryptase cells. FP treatment resulted in marginal reductions in these indices of inflammation. Conclusion: In patients with COPD and BHR, FP has a positive effect on indices of lung function compared with placebo. Bronchial inflammation analysed in bronchial biopsy specimens is only marginally reduced.

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“…[4][5][6][7][8][9][10][11] Surprisingly, the observed declines in FEV 1 in these trials and in observational cohorts of patients with COPD have been variable and smaller than anticipated, particularly among persons with the most severe airflow limitation. [4][5][6][7][8][9][10][11][12][13][14][15][16] These observations question the notion that COPD always follows a trajectory of rapid decline in FEV 1 and are consistent with the hypothesis that low maximally attained lung function in early adulthood can also result in COPD later in life, even when the rate of decline in FEV 1 is within the normal range. [17][18][19][20][21] In fact, this alternative course was already suggested by Fletcher and Peto 3 and emphasized by Burrows et al 22 but was never explored in a long-term, prospective investigation.…”

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confidence: 99%

Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease

et al. 2015

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BACKGROUNDChronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV 1 ) over time. Yet it is possible that a normal decline in FEV 1 could also lead to COPD in persons whose maximally attained FEV 1 is less than population norms. METHODSWe stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV 1 ≥80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV 1 over time among the participants according to their FEV 1 at cohort inception and COPD status at study end. RESULTSAmong 657 persons who had an FEV 1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV 1 of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (P<0.001). Approximately half the 332 persons with COPD at the end of the observation period had had a normal FEV 1 before 40 years of age and had a rapid decline in FEV 1 thereafter, with a mean (±SD) decline of 53±21 ml per year. The remaining half had had a low FEV 1 in early adulthood and a subsequent mean decline in FEV 1 of 27±18 ml per year (P<0.001), despite similar smoking exposure. CONCLUSIONSOur study suggests that low FEV 1 in early adulthood is important in the genesis of COPD and that accelerated decline in FEV 1 is not an obligate feature of COPD. (Funded by an unrestricted grant from GlaxoSmithKline and others.) a bs tr ac t

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Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial

Cited by 723 publications

References 23 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

Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness

Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease

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