Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort

Han, MeiLan K.; Quibrera, P. Miguel; Carretta, Elizabeth E.; Barr, R. Graham; Bleecker, Eugene R.; Bowler, Russell P.; Cooper, Christopher B.; Couper, David J.; Curtis, Jeffrey L.; Dransfield, Mark T.; Hansel, Nadia N.; Hoffman, Eric A.; Kanner, Richard E.; Krishnan, Jerry A.; Martínez, Carlos H.; Pirozzi, Cheryl; O’Neal, Wanda K.; Rennard, Stephen I.; Tashkin, Donald P.; Wedzicha, Jadwiga A.; Paine, Robert; Martínez, Fernando J.; Alexis, Neil E.; Anderson, Wayne H.; Boucher, Richard C.; Christenson, Stephanie A.; Comellas, A.P.; Criner, Gerard J.; Crystal, Ronald G.; Doerschuk, Claire M.; Freeman, Christine M.; Hastie, Annette T.; Kaner, Robert J.; Kleerup, Eric C.; LaVange, Lisa M.; Lazarus, Stephen C.; Meyers, Deborah A.; Newell, John D.; Oelsner, Elizabeth C.; Putcha, Nirupama; Scholand, Mary Beth; Wells, James M.; Wise, Robert A.; Woodruff, Prescott G.

doi:10.1016/s2213-2600(17)30207-2

Cited by 247 publications

(231 citation statements)

References 18 publications

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“…National Institute for Health and Care Excellence guidelines state that triple therapy is cost-effective only in patients who have FEV 1 <50% predicted and frequent exacerbations (two or more in past 12 months) 86,90. In this regard, it is interesting that only 2.1% of patients in the SPIROMICS cohort, of whom 30% had severe airflow obstruction, had two or more exacerbations in each year over a 3-year period 91. Therefore, the frequent exacerbator phenotype appears to be much less common than reported in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study 92.…”

Section: Future Directions: Triple Therapy and Beyondmentioning

confidence: 95%

Inhaled corticosteroids for chronic obstructive pulmonary disease: what is their role in therapy?

Tashkin¹,

Strange²

2018

COPD

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Inhaled corticosteroids (ICSs) are a mainstay of COPD treatment for patients with a history of exacerbations. Initial studies evaluating their use as monotherapy failed to show an effect on rate of pulmonary function decline in COPD, despite improvements in symptoms and reductions in exacerbations. Subsequently, ICS use in combination with long-acting β2-agonists (LABAs) was shown to provide improved reductions in exacerbations, lung function, and health status. ICS-LABA combination therapy is currently recommended for patients with a history of exacerbations despite treatment with long-acting bronchodilators alone. The presence of eosinophilic bronchial inflammation, detected by high blood eosinophil levels or a history of asthma or asthma–COPD overlap, may define a population of patients in whom ICSs may be of particular benefit. Prospective clinical studies to determine an appropriate threshold of eosinophil levels for predicting the beneficial effects of ICSs are needed. Further study is also required in COPD patients who continue to smoke to assess the impact of cell- and tissue-specific changes on ICS responsiveness. The safety profile of ICSs in COPD patients is confounded by comorbidities, age, and prior use of systemic corticosteroids. The risk of pneumonia in patients with COPD is increased, particularly with more advanced age and worse disease severity. ICS-containing therapy also has been shown to increase pneumonia risk; however, differences in study design and the definition of pneumonia events have led to substantial variability in risk estimates, and some data indicate that pneumonia risk may differ by the specific ICS used. In summary, treatment with ICSs has a role in dual and triple therapy for COPD to reduce exacerbations and improve symptoms. Careful assessment of COPD phenotypes related to risk factors, triggers, and comorbidities may assist in individualizing treatment while maximizing the benefit-to-risk ratio of ICS-containing COPD treatment.

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Section: Future Directions: Triple Therapy and Beyondmentioning

confidence: 95%

Inhaled corticosteroids for chronic obstructive pulmonary disease: what is their role in therapy?

Tashkin¹,

Strange²

2018

COPD

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“…This favorable difference is unexpected, as compliance is unlikely to be a major issue in a clinical trial where adherence levels are usually high, although this, of course, is a potential advantage for single-inhaler triple therapy in real life. The SPIROMICS data33 show that patients who are used to exacerbation have higher small airways impairment than the other patients, providing a possible explanation for the reason why extrafine BDP/FF/GLY was more effective in this population than large-particle formulations.…”

Section: Introductionmentioning

confidence: 96%

“…A recent analysis from the SPIROMICS study showed an association between small airways disease and the consistent exacerbator phenotype (defined as patient with one exacerbation every year for the 3-year follow-up). The increased computed tomography-defined small airways abnormality was one of the most important variables associated with patients who consistently had acute exacerbations together with previous acute exacerbations and increased CAT score 33. In the TRILOGY study both interventions were delivered by the same inhaler type (pMDI), both formulations were extrafine, and the drugs were inhaled via the same device.…”

Section: Introductionmentioning

confidence: 99%

Triple therapy in COPD: new evidence with the extrafine fixed combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide

Singh¹,

Corradi²,

Spinola

et al. 2017

COPD

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The goals of COPD therapy are to prevent and control symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance. The triple combination therapy of inhaled corticosteroids (ICSs), long-acting beta2 agonists (LABAs), and long-acting muscarinic antagonists (LAMAs) has become an option for maintenance treatment of COPD and as a “step-up” therapy from single or double combination treatments. There is evidence that triple combination ICS/LABA/LAMA with different inhalers improves lung function, symptoms, and health status and reduces exacerbations. A new triple fixed-dose combination of extrafine beclomethasone dipropionate (100 µg/puff)/formoterol fumarate (6 µg/puff)/glycopyrronium bromide (12.5 µg/puff) has been developed as a hydrofluoroalkane pressurized metered dose inhaler. Two large pivotal studies showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms of lung function and exacerbation prevention in COPD patients at risk of exacerbation. This review considers the new information provided by these clinical trials of extrafine triple therapy and the implications for the clinical management of COPD patients.

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“…Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation affecting the airway, lung parenchyma and pulmonary vascular system (1). Infiltration of inflammatory cells such as alveolar macrophages, T lymphocytes, particularly CD8 + T cells, and neutrophils leads to the release of inflammatory mediators, including leukotriene B4 (LTB4), interleukin-8 (IL-8) and tumor necrosis factor (TNF)-α (2,3).…”

Section: Introductionmentioning

confidence: 99%

Jinwei Tang modulates HDAC2 expression in a rat model of COPD

Wu¹,

Yang³

et al. 2018

Exp Ther Med

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Abstract. The aim of the present study was to investigate the effect of a Traditional Chinese Herbal Medicine (TCHM), named Jinwei Tang on histone deacetylase 2 (HDAC2) and its role in the regulation of corticosteroid resistance in a rat model of chronic obstructive pulmonary disease (COPD). Male Wistar rats were divided into five groups (each n=10): COPD group, established by the intratracheal instillation of lipopolysaccharide and passive smoke exposure, and control, budesonide, theophylline + budesonide and Jinwei Tang + budesonide groups. Lung function was measured, lung tissue histopathology was examined and HDAC2 expression in the lung was assessed by immunohistochemistry. In addition, protein levels of interleukin-8 (IL-8), tumor necrosis factor (TNF)-α and HDAC2 in lung homogenate were quantified by ELISA. The rat COPD model exhibited alterations of the ratio of forced expiratory volume in 0.2 sec (FEV 0.2 ) to the forced vital capacity, FEV 0.2 , dynamic compliance and airway resistance. HDAC2 expression was markedly reduced in the lung tissue of the COPD group compared with the control group, and treatment with Jinwei Tang + budesonide or theophylline + budesonide resulted in significant attenuation of the reduction of HDAC2 expression in the lungs (P<0.05). However, treatment with budesonide alone did not significantly alter HDAC2 expression. In the Jinwei Tang + budesonide and theophylline + budesonide groups, IL-8 and TNF-α expression was significantly decreased (P<0.05) and the HDAC2 level increased (P<0.05) compared with that in the COPD group.In conclusion, Jinwei Tang modulates airway inflammation and may enhance the anti-inflammatory effect of glucocorticoid through the upregulation of HADC2 expression in a rat model of COPD.

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Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort

Cited by 247 publications

References 18 publications

Inhaled corticosteroids for chronic obstructive pulmonary disease: what is their role in therapy?

Inhaled corticosteroids for chronic obstructive pulmonary disease: what is their role in therapy?

Triple therapy in COPD: new evidence with the extrafine fixed combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide

Jinwei Tang modulates HDAC2 expression in a rat model of COPD

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