Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials

Bafadhel, Mona; Peterson, Stefan; Blas, Miguel A De; Calverley, Peter M.A.; Rennard, Stephen I.; Richter, Kai; Fagerås, Malin

doi:10.1016/s2213-2600(18)30006-7

Cited by 349 publications

(347 citation statements)

References 24 publications

(26 reference statements)

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“…The INCONTROL study showed that for patients with blood-eosinophil counts ≥100 cells/µL, exacerbations were reduced significantly more with budesonide–formoterol compared with formoterol alone ( P =0.015) 42. The higher the blood-eosinophil count, the greater the exacerbation rate without ICSs and the greater the reduction in exacerbations with ICSs, which tends to reach a plateau around eosinophil counts of 400 cells/µL.…”

Section: Predictors Of Responsementioning

confidence: 99%

“…Differences in study populations could account for the disparate findings, as the INCONTROL study had a larger number of smokers with more exacerbations compared with the SPIROMICS cohort 42,48…”

Section: Predictors Of Responsementioning

confidence: 99%

“…Sputum eosinophils may be reduced in smokers as a result of the nitric oxide and carbon monoxide present in cigarette smoke 54. A recent post hoc analysis of budesonide–formoterol studies in patients with COPD (INCONTROL) found that among current smokers, a greater reduction in exacerbation rate was observed with ICS-LABA therapy vs LABA alone at higher peripheral blood-eosinophil counts 42. These cell- and tissue-specific responses may be related to the heterogeneous nature of COPD, and suggest that reduced steroid responsiveness is not a general characteristic of the disease 42,55.…”

Section: Effect Of Smoking Status On Ics Responsementioning

confidence: 99%

“…A recent post hoc analysis of budesonide–formoterol studies in patients with COPD (INCONTROL) found that among current smokers, a greater reduction in exacerbation rate was observed with ICS-LABA therapy vs LABA alone at higher peripheral blood-eosinophil counts 42. These cell- and tissue-specific responses may be related to the heterogeneous nature of COPD, and suggest that reduced steroid responsiveness is not a general characteristic of the disease 42,55. These findings highlight the need for further evaluation of appropriate biomarkers of disease severity and treatment selection and their relationship to smoking status.…”

Section: Effect Of Smoking Status On Ics Responsementioning

confidence: 99%

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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: Predictors Of Responsementioning

confidence: 99%

Section: Predictors Of Responsementioning

confidence: 99%

Section: Effect Of Smoking Status On Ics Responsementioning

confidence: 99%

Section: Effect Of Smoking Status On Ics Responsementioning

confidence: 99%

See 2 more Smart Citations

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

Tashkin¹,

Strange²

2018

COPD

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“…However, improvements in lung function, exacerbation risk and all-cause mortality with ICS treatment when used in combination with long-acting beta-agonist (LABA) bronchodilators have been reported recently (7,8). In addition, some patients with COPD with no previous history of asthma can benefit from ICS, such as those with high blood eosinophil counts (9)(10)(11)(12)(13)(14). It has previously been shown that gene expression profiling in bronchial biopsies in COPD may identify those with asthma-COPD overlap, as reflected by a Th2-high inflammatory profile and a favorable shortand long-term ICS treatment response (3).…”

Section: Introductionmentioning

confidence: 99%

Novel Type 2-high gene clusters associated with corticosteroid sensitivity in COPD

Faiz

Pavlidis

Kuo

et al. 2020

Preprint

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RationaleSevere asthma and COPD share common pathophysiologic traits such as relative corticosteroid insensitivity. We recently published three transcriptome-associated clusters (TACs) using hierarchical analysis of the sputum transcriptome in asthmatics from the U-BIOPRED cohort with one Type 2-high signature (TAC1) and 2 Type 2-low signatures. ObjectiveWe examined whether gene-expression signatures obtained in asthma can be used to identify the subgroup of COPD patients with steroid sensitivity. MethodsUsing gene set variation analysis (GSVA), we examined the distribution and enrichment scores (ES) of the 3 TACs in the transcriptome of bronchial biopsies from 46 patients who participated in the GLUCOLD COPD study that received 30 months of treatment with inhaled corticosteroids (ICS) with and without an added long-acting β-agonist (LABA). The identified signatures were then associated with longitudinal clinical variables after treatment. Measurements and main resultsBronchial biopsies in COPD patients at baseline showed a wide range of expression of the 3 TACs. After ICS±LABA treatment, the ES of TAC1 was significantly reduced at 30 months, but those of TAC2 and TAC3 were unaffected. A corticosteroid-sensitive TAC1 (sub)signature was developed from the TAC1 ICS-responsive genes. This signature consisted of mast cellspecific genes identified by single-cell RNA-seq and positively correlated with bronchial biopsy mast cell numbers following ICS±LABA. Baseline levels of gene transcription predicted change in FEV1 %predicted following 30-month ICS±LABA. ConclusionsSputum-derived transcriptomic signatures from an asthma cohort can be recapitulated in bronchial biopsies of COPD patients and identified airway wall mast cells as a predictor of those COPD patients who will benefit from inhaled corticosteroids.Abbreviations: FEV 1 = Forced Expiratory Volume in 1second and RV/TLC= residual volume/total lung capacity .

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Diagnosis and Outpatient Management of Chronic Obstructive Pulmonary Disease

Riley

Sciurba

2019

JAMA

179

128

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CONCLUSIONS AND RELEVANCE Chronic obstructive pulmonary disease is a complicated disease requiring intensive treatment. Appropriate use of long-acting maintenance bronchodilators, inhaled corticosteroids, and pulmonary rehabilitation decreases symptoms, optimizes functional performance, and reduces exacerbation frequency. Supplemental oxygen in patients with resting hypoxemia prolongs life, and other advanced treatments are available based on specific patient characteristics.

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Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials

Abstract: AstraZeneca.

Cited by 349 publications

References 24 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?

Novel Type 2-high gene clusters associated with corticosteroid sensitivity in COPD

Diagnosis and Outpatient Management of Chronic Obstructive Pulmonary Disease

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