Reply to Wang and Lai: The Role of Eosinophils during the Withdrawal of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease.
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SUBMITTER: Han MK
PROVIDER: S-EPMC7781138 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7781124 | biostudies-literature
Project description:Chronic obstructive pulmonary disease (COPD) guidelines suggest using inhaled corticosteroids (ICS) in patients with severe airflow limitation or those at high risk of exacerbations. This recommendation is based on evidence demonstrating that ICS, especially when prescribed in fixed-dose combinations (FDC) with long-acting β2 agonists (LABA), improve quality of life (QoL), decrease exacerbations and hospitalisations, and have been associated with a trend towards a reduction in all-cause mortality. Audit shows that routine prescribing practice frequently uses inhaler therapies outside current guidelines recommendations; severe to very severe disease constitutes about 20% of all COPD patients, but up to 75% of COPD patients are prescribed an ICS, with significant numbers given ICS/LABA as first-line maintenance therapy. The role of ICS in the treatment paradigm for COPD is changing, driven by the growing evidence of increased risk of pneumonia, and the introduction of a new class of FDC; LABA and long-acting muscarinic antagonists (LAMA), which simplify dual bronchodilation and present a plausible alternative therapy. As the evidence base for dual therapy bronchodilation expands, it is likely that maximal bronchodilation will move up the treatment algorithm and ICS reserved for those with more severe disease who are not controlled on dual therapy. This change has already manifested in local COPD algorithms, such as those at Tayside, and represents a significant change in recommended prescribing practice. This review reassesses the role of ICS in the shifting treatment paradigm, in the context of alternative treatment options that provide maximal bronchodilation.
| S-EPMC4776680 | biostudies-literature
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| S-EPMC7605197 | biostudies-literature
Project description: Not available
| S-EPMC7924572 | biostudies-literature
Project description:Rationale: Decreasing medication overuse represents an opportunity to avoid harm and costs in the era of value-based purchasing. Studies of inhaled corticosteroids (ICS) overuse in chronic obstructive pulmonary disease (COPD) have examined prevalent use. Understanding initiation of low-value ICS among complex patients with COPD may help shape deadoption efforts.Objectives: Examine ICS initiation among a cohort with low exacerbation risk COPD and test for associations with markers of patient and health system complexity.Methods: Between 2012 and 2016, we identified veterans with COPD from 21 centers. Our primary outcome was first prescription of ICS. We used the care assessment needs (CAN) score to assess patient-level complexity as the primary exposure. We used a time-to-event model with time-varying exposures over 1-year follow-up. We tested for effect modification using selected measures of health system complexity.Results: We identified 8,497 patients with COPD without an indication for ICS and did not have baseline use (inception cohort). Follow-up time was four quarters. Patient complexity by a continuous CAN score was associated with new dispensing of ICS (hazard ratio = 1.17 per 10-unit change; 95% confidence interval = 1.13-1.21). This association demonstrated a dose-response when examining quartiles of CAN score. Markers of health system complexity did not modify the association between patient complexity and first use of low-value ICS.Conclusions: Patient complexity may represent a symptom burden that clinicians are attempting to mitigate by initiating ICS. Lack of effect modification by health system complexity may reflect the paucity of structural support and low prioritization for COPD care.
| S-EPMC7193812 | biostudies-literature
Project description:IntroductionContinuing inhaled corticosteroid (ICS) use does not benefit all patients with COPD, yet it is difficult to determine which patients may safely sustain ICS withdrawal. Although eosinophil levels can facilitate this decision, better biomarkers could improve personalised treatment decisions.MethodsWe performed transcriptional profiling of sputum to explore the molecular biology and compared the predictive value of an unbiased gene signature versus sputum eosinophils for exacerbations after ICS withdrawal in COPD patients. RNA-sequencing data of induced sputum samples from 43 COPD patients were associated with the time to exacerbation after ICS withdrawal. Expression profiles of differentially expressed genes were summarised to create gene signatures. In addition, we built a Bayesian network model to determine coregulatory networks related to the onset of COPD exacerbations after ICS withdrawal.ResultsIn multivariate analyses, we identified a gene signature (LGALS12, ALOX15, CLC, IL1RL1, CD24, EMR4P) associated with the time to first exacerbation after ICS withdrawal. The addition of this gene signature to a multiple Cox regression model explained more variance of time to exacerbations compared to a model using sputum eosinophils. The gene signature correlated with sputum eosinophil as well as macrophage cell counts. The Bayesian network model identified three coregulatory gene networks as well as sex to be related to an early versus late/nonexacerbation phenotype.ConclusionWe identified a sputum gene expression signature that exhibited a higher predictive value for predicting COPD exacerbations after ICS withdrawal than sputum eosinophilia. Future studies should investigate the utility of this signature, which might enhance personalised ICS treatment in COPD patients.
| S-EPMC8255541 | biostudies-literature
Project description:OBJECTIVES:To identify clusters of patients who may benefit from treatment with an inhaled corticosteroid (ICS)/long-acting ?2 agonist (LABA) versus LABA alone, in terms of exacerbation reduction, and to validate previously identified clusters of patients with chronic obstructive pulmonary disease (COPD) (based on diuretic use and reversibility). DESIGN:Post hoc supervised cluster analysis using a modified recursive partitioning algorithm of two 1-year randomised, controlled trials of fluticasone furoate (FF)/vilanterol (VI) versus VI alone, with the primary end points of the annual rate of moderate-to-severe exacerbations. SETTING:Global. PARTICIPANTS:3255 patients with COPD (intent-to-treat populations) with a history of exacerbations in the past year. INTERVENTIONS:FF/VI 50/25?µg, 100/25?µg or 200/25?µg, or VI 25?µg; all one time per day. OUTCOME MEASURES:Mean annual COPD exacerbation rate to identify clusters of patients who benefit from adding an ICS (FF) to VI bronchodilator therapy. RESULTS:Three clusters were identified, including two groups that benefit from FF/VI versus VI: patients with blood eosinophils >2.4% (RR=0.68, 95% CI 0.58 to 0.79), or blood eosinophils ?2.4% and smoking history ?46 pack-years, experienced a reduced rate of exacerbations with FF/VI versus VI (RR=0.78, 95% CI 0.63 to 0.96), whereas those with blood eosinophils ?2.4% and smoking history >46 pack-years were identified as non-responders (RR=1.22, 95% CI 0.94 to 1.58). Clusters of patients previously identified in the fluticasone propionate/salmeterol (SAL) versus SAL trials of similar design were not validated; all clusters of patients tended to benefit from FF/VI versus VI alone irrespective of diuretic use and reversibility. CONCLUSIONS:In patients with COPD with a history of exacerbations, those with greater blood eosinophils or a lower smoking history may benefit more from ICS/LABA versus LABA alone as measured by a reduced rate of exacerbations. In terms of eosinophils, this finding is consistent with findings from other studies; however, the validity of the 2.4% cut-off and the impact of smoking history require further investigation. TRIAL REGISTRATION NUMBERS:NCT01009463; NCT01017952; Post-results.
| S-EPMC4893846 | biostudies-literature
Project description:Rate of FEV1 decline in COPD is heterogeneous and the extent to which inhaled corticosteroids (ICS) influence the rate of decline is unclear. The majority of previous reviews have investigated specific ICS and non-ICS inhalers and have consisted of randomised control trials (RCTs), which have specific inclusion and exclusion criteria and short follow up times. We aimed to investigate the association between change in FEV1 and ICS-containing medications in COPD patients over longer follow up times.MEDLINE and EMBASE were searched and literature comparing change in FEV1 in COPD patients taking ICS-containing medications with patients taking non-ICS-containing medications were identified. Titles, abstract, and full texts were screened and information extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool and a descriptive synthesis of the literature was carried out due to high heterogeneity of included studies.Seventeen studies met our inclusion criteria. We found that the difference in change in FEV1 in people using ICS and non-ICS containing medications depended on the study follow-up time. Shorter follow-up studies (1?year or less) were more likely to report an increase in FEV1 from baseline in both patients on ICS and in patients on non-ICS-containing medications, with the majority of these studies showing a greater increase in FEV1 in patients on ICS-containing medications. Longer follow-up studies (greater than 1?year) were more likely to report a decline in FEV1 from baseline in patients on ICS and in patients on non-ICS containing medications but rates of FEV1 decline were similar.Further studies are needed to better understand changes in FEV1 when ICS-containing medications are prescribed and to determine whether ICS-containing medications influence rate of decline in FEV1 in the long term. Results from inclusive trials and observational patient cohorts may provide information more generalisable to a population of COPD patients.
| S-EPMC6894275 | biostudies-literature
Project description:OBJECTIVES:Inhaled corticosteroids (ICS) reduce exacerbation rates and the decline in lung function in people with chronic obstructive pulmonary disease (COPD). There is evidence that smoking causes 'steroid resistance' and thus reduces the effect of ICS. This systematic review aimed to investigate the effect of smoking on efficacy of ICS in COPD in terms of lung function and exacerbation rates. DESIGN:Systematic review. DATA SOURCES:An electronic database search of PubMed, Ovid MEDLINE, Ovid Embase and Cochrane Library (January 2000 to January 2020). ELIGIBILITY CRITERIA:Fully published randomised controlled trials (RCTs), in the English language, evaluating the use of ICS in COPD adults that stratified the participants by smoking status. Trials that included participants with asthma, lung cancer and pneumonia were excluded. The primary outcome measures were changes in lung function and yearly exacerbation rates. DATA EXTRACTION AND SYNTHESIS:Two independent reviewers extracted data and assessed risk of bias using the Cochrane Collaboration's tool. RESULTS:Seven studies were identified. Four trials (17 892 participants) recorded change in forced expiratory volume in one second (FEV1) from baseline to up to 30 months after starting treatment. Heavier smokers (>36 pack years) using ICS had a greater decline in FEV1 that ranged from -22 mL to -75 mL in comparison to lighter smokers. Smokers using ICS had mixed results in FEV1 change: -8 mL to +77 mL in comparison to ex-smokers. Four trials (21 270 participants) recorded difference in COPD exacerbation rates at 52 weeks. The rate ratios favoured more exacerbations in ICS users who were current or heavier smokers than those who were ex-smokers or lighter smokers (0.81 to 0.99 vs 0.92 to 1.29). CONCLUSIONS:In COPD, heavier or current smokers do not gain the same benefit from ICS use on lung function and exacerbation rates as lighter or ex-smokers do, however effects may not be clinically important. PROSPERO REGISTRATION NUMBER:CRD42019121833.
| S-EPMC7245617 | biostudies-literature
Project description:Inhaled corticosteroids (ICS) (in fixed combinations with long-acting ?2-agonists [LABAs]) are frequently prescribed for patients with chronic obstructive pulmonary disease (COPD), outside their labeled indications and recommended treatment strategies and guidelines, despite having the potential to cause significant side effects.Although the existence of asthma in patients with asthma-COPD overlap syndrome (ACOS) clearly supports the use of anti-inflammatory treatment (typically an ICS/LABA combination, as ICS monotherapy is usually not indicated for COPD), the current level of ICS/LABA use is not consistent with the prevalence of ACOS in the COPD population. Data have recently become available showing the comparative efficacy of fixed bronchodilator combinations (long-acting muscarinic antagonist [LAMA]/LABA with ICS/LABA combinations). Additionally, new information has emerged on ICS withdrawal without increased risk of exacerbations, under cover of effective bronchodilation.For patients with COPD who do not have ACOS, a LAMA/LABA combination may be an appropriate starting therapy, apart from those with mild disease who can be managed with a single long-acting bronchodilator. Patients who remain symptomatic or present with exacerbations despite effectively delivered LAMA/LABA treatment may require additional drug therapy, such as ICS or phosphodiesterase-4 inhibitors. When prescribing an ICS/LABA, the risk:benefit ratio should be considered in individual patients.
| S-EPMC4673525 | biostudies-other