Long-Term Treatment with Inhaled Budesonide in Persons with Mild Chronic Obstructive Pulmonary Disease Who Continue Smoking

Pauwels, Romain; Löfdahl, Claes-Göran; Laitinen, Lauri A.; Schouten, Jan P.; Postma, Dirkje S.; Pride, N. B.; Ohlsson, Stefan V.

doi:10.1056/nejm199906243402503

Cited by 940 publications

(574 citation statements)

References 28 publications

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“…There is no effective therapy to reduce the persistent pulmonary inflammation in chronic obstructive pulmonary disease patients and improve their prognosis, even in those patients who use inhaled corticosteroids [35,36]. Therefore, the disease is being targeted with new anti-inflammatory treatments.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-18 production and pulmonary function in COPD

Imaoka

Hoshino

Takei³

et al. 2008

European Respiratory Journal

121

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Interleukin (IL)-18 production and pulmonary function were evaluated in patients with chronic obstructive pulmonary disease (COPD) in order to determine the role of IL-18 in COPD.Immunohistochemical techniques were used to examine IL-18 production in the lungs of patients with very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV, n516), smokers (n527) and nonsmokers (n523). Serum cytokine levels and pulmonary function were analysed in patients with GOLD stage I-IV COPD (n562), smokers (n534) and nonsmokers (n547).Persistent and severe small airway inflammation was observed in the lungs of ex-smokers with very severe COPD. IL-18 proteins were strongly expressed in alveolar macrophages, CD8+ Tcells, and both the bronchiolar and alveolar epithelia in the lungs of COPD patients. Serum levels of IL-18 in COPD patients and smokers were significantly higher than those in nonsmokers. Moreover, serum levels of IL-18 in patients with GOLD stage III and IV COPD were significantly higher than in smokers and nonsmokers. There was a significant negative correlation between serum IL-18 level and the predicted forced expiratory volume in one second in patients with COPD. In contrast, serum levels of IL-4, IL-13 and interferon-c were not significantly increased in any of the three groups.In conclusion, overproduction of interleukin-18 in the lungs may be involved in the pathogenesis of chronic obstructive pulmonary disease.

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Section: Discussionmentioning

confidence: 99%

Interleukin-18 production and pulmonary function in COPD

Imaoka

Hoshino

Takei³

et al. 2008

European Respiratory Journal

121

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“…Variables showing a significant correlation (p ≤ 0.1) were included in the multivariate logistic regression analysis. Smoking (≥ 5 pack-years vs < 5 pack-years)[13,14], asthma duration (≥ 15 years vs < 15 years)[15], rhinitis, patient age (≥ 50 years old vs < 50 years old) [16,17], age at onset (≥ 40 years old vs < 40 years old)[18], and gender and atopic status which were selected for identification of the independent factors associated with FAO. Statistical analyses were performed using the SPSS statistical software package (version 18).…”

Section: Methodsmentioning

confidence: 99%

Smoking, longer disease duration and absence of rhinosinusitis are related to fixed airway obstruction in Koreans with severe asthma: findings from the COREA study

Lee

Bae

et al. 2011

Respir Res

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BackgroundThe clinical manifestations of severe asthma are heterogeneous. Some individuals with severe asthma develop irreversible fixed airway obstruction, which is associated with poor outcomes. We therefore investigated the factors associated with fixed airway obstruction in Korean patients with severe asthma.MethodsSevere asthma patients from a Korean adult asthma cohort were divided into two groups according to the results of serial pulmonary function tests. One group had fixed airway obstruction (FAO) [forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio < 0.7, n = 119] and the other had reversible airway obstruction (RAO) [FEV1/FVC ratio ≥ 0.7, n = 116]. Clinical and demographic parameters were compared between the two groups.ResultsMultivariate analysis showed that longer duration of disease, greater amount of cigarette smoking and absence of rhinosinusitis were significantly related to the development of FAO in severe asthmatics. Other parameters, including atopic status, pattern of airway inflammatory cells in induced sputum, and frequency of asthma exacerbations did not differ between the FAO and RAO groups.ConclusionSevere asthma patients with longer disease duration and the absence of rhinosinusitis are more likely to develop FAO. This study also demonstrates the importance of quitting smoking in order to prevent irreversible airway obstruction. Further investigation is required to determine the mechanism by which these factors can modify the disease course in Korean patients with severe asthma.

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“…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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Long-Term Treatment with Inhaled Budesonide in Persons with Mild Chronic Obstructive Pulmonary Disease Who Continue Smoking

Abstract: In patients with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline.

Cited by 940 publications

References 28 publications

Interleukin-18 production and pulmonary function in COPD

Interleukin-18 production and pulmonary function in COPD

Smoking, longer disease duration and absence of rhinosinusitis are related to fixed airway obstruction in Koreans with severe asthma: findings from the COREA study

Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness

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