Lack of Bacterial Colonization Measure in Randomized Controlled Trial on Inhaled Corticosteroids Effect in Patients with Chronic Obstructive Pulmonary Disease.
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ABSTRACT:
SUBMITTER: Martinez-Garcia MA
PROVIDER: S-EPMC7924565 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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
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: Not available
| S-EPMC7781124 | biostudies-literature
Project description:Background: Whether all types of inhaled corticosteroids (ICSs) would increase the pneumonia risk in patients with chronic obstructive pulmonary disease (COPD) remains controversial. We aimed to assess the association between ICSs treatment and pneumonia risk in COPD patients, and the impact of medication details and baseline characteristics of patients on the association. Methods: Four databases (PubMed, Embase, Cochrane Library, and Clinical Trials.gov) were searched to identify eligible randomized controlled trials (RCTs) comparing ICSs treatment with non-ICSs treatment on the pneumonia risk in COPD patients. Pooled results were calculated using Peto odds ratios (Peto ORs) with corresponding 95% confidence intervals (CIs). Results: A total of 59 RCTs enrolling 103,477 patients were analyzed. All types of ICSs significantly increased the pneumonia risk (Peto OR, 1.43; 95% CI, 1.34-1.53). Subgroup analysis showed that there was a dose-response relationship between ICSs treatment and pneumonia risk (low-dose: Peto OR, 1.33; 95% CI, 1.22-1.45; medium-dose: Peto OR, 1.50; 95% CI, 1.28-1.76; and high-dose: Peto OR, 1.64; 95% CI, 1.45-1.85). Subgroup analyses based on treatment durations and baseline characteristics (severity, age, and body mass index) of patients were consistant with the above results. Subgroup analysis based on severity of pneumonia showed that fluticasone (Peto OR, 1.75; 95% CI, 1.44-2.14) increased the risk of serious pneumonia, while budesonide and beclomethasone did not. Conclusions: ICSs treatment significantly increased the risk of pneumonia in COPD patients. There was a dose-response relationship between ICSs treatment and pneumonia risk. The pneumonia risk was related with COPD severity.
| S-EPMC8275837 | 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:ObjectivesTo identify clusters of patients who may benefit from treatment with an inhaled corticosteroid (ICS)/long-acting β2 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).DesignPost 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.SettingGlobal.Participants3255 patients with COPD (intent-to-treat populations) with a history of exacerbations in the past year.InterventionsFF/VI 50/25 µg, 100/25 µg or 200/25 µg, or VI 25 µg; all one time per day.Outcome measuresMean annual COPD exacerbation rate to identify clusters of patients who benefit from adding an ICS (FF) to VI bronchodilator therapy.ResultsThree 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.ConclusionsIn 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 numbersNCT01009463; NCT01017952; Post-results.
| S-EPMC4893846 | biostudies-literature
Project description:RationaleInflammation is now recognized as an integral part of the pathogenesis of chronic obstructive pulmonary disease (COPD). In contrast to the sterile airways of normal lungs, bacterial pathogens are often isolated from the airways in stable COPD. This "colonization" of the tracheobronchial tree, currently believed to be innocuous, could serve as an inflammatory stimulus, independent of current tobacco smoke exposure.ObjectiveTo test the hypothesis that bacterial colonization is associated with airway inflammation in stable COPD.MethodsBronchoscopy with bronchoalveolar lavage (BAL) was performed in three groups of subjects: 26 ex-smokers with stable COPD (COPD), 20 ex-smokers without COPD (ex-smokers), and 15 healthy nonsmokers (nonsmokers). Quantitative bacterial cultures, cell counts, chemokine, cytokine, proteinase/antiproteinase, and endotoxin levels in the BAL fluid were compared.ResultsPotentially pathogenic bacteria were recovered at > or = 100 cfu/ml in 34.6% of COPD, 0% of ex-smokers, and in 6.7% of nonsmokers (p = 0.003). All values are expressed as median (interquartile range). Subjects with colonized COPD had significantly greater relative (12.0 [28.4] vs. 3.0 [7.8]%, p = 0.03) and absolute (4.98 [5.26] x 10(4)/ml vs. 3.04 [2.82] x 10(4)/ml, p = 0.02) neutrophil counts, interleukin 8 (33.8 [189.8] vs. 16.9 [20.1] pg/ml, p = 0.005), active matrix metalloproteinase-9 (2.16 [4.30] vs. 0.84 [0.99] U/ml, p = 0.03), and endotoxin (36.0 [72.6] vs. 3.55 [7.17] mEU/ml, p = 0.004) levels in the BAL than the subjects with noncolonized COPD. These inflammatory constituents of BAL were also significantly elevated in subjects with colonized COPD when compared with ex-smokers and nonsmokers.ConclusionsBacterial colonization is associated with neutrophilic airway lumen inflammation in ex-smokers with COPD and could contribute to progression of airway disease in COPD.
| S-EPMC2662918 | biostudies-literature
Project description: Not available
| S-EPMC6543465 | biostudies-literature
Project description:BACKGROUND:We aimed to assess the association between inhaled corticosteroids (ICSs) and the risk of upper respiratory tract infection (URTI) in patients with chronic obstructive pulmonary disease (COPD). METHODS:PubMed, Embase, Cochrane Library and Clinical Trials.gov were searched from inception to October 2019. Randomized controlled trials (RCTs) of any ICSs vs control for COPD with reporting of URTI as an adverse event were included. The study was registered with PROSPERO prospectively (#CRD42020153134). RESULTS:Seventeen RCTs (20,478 patients) were included. ICSs significantly increased the risk of URTI in COPD patients (RR, 1.13; 95% CI 1.03-1.24; P?=?0.01; heterogeneity: I2?=?7%). Futher subgroup analyses suggested that short-term use of ICSs increased the risk of URTI (RR, 1.29; 95% CI 1.06-1.56; P?=?0.01; heterogeneity: I2?=?14%) but not for long-term use (RR, 1.08; 95% CI 0.97-1.2; P?=?0.14; heterogeneity: I2?=?0%). Short-term use of high-dose fluticasone increased the risk of URTI (RR, 1.33; 95% CI 1.03-1.71; P?=?0.03; heterogeneity: I2?=?0%) but not for long-term use (RR, 1.12; 95% CI 0.97-1.29; P?=?0.13; heterogeneity: I2?=?50%). Medium-dose (RR, 0.97; 95% CI 0.71-1.32; P?=?0.84; heterogeneity: I2?=?0%) and low-dose (RR, 1.39; 95% CI 0.92-2.1; P?=?0.12; heterogeneity: I2?=?30%) fluticasone did not increase the risk of URTI regardless of duration. Neither mometasone (RR, 1.05; 95% CI 0.87-1.26; P?=?0.61; heterogeneity: I2?=?0%) nor budesonide (RR, 1.08; 95% CI 0.77-1.5; P?=?0.67; heterogeneity: I2?=?46%) increased the risk of URTI, regardless of dosage or duration. CONCLUSIONS:Long-term use of ICSs does not increase the risk of URTI in patients with COPD. Short-term use of high-dose fluticasone increases the risk of URTI in patients with COPD, but not mometasone or budesonide.
| S-EPMC7594481 | biostudies-literature