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Association between inhaled corticosteroids and upper respiratory tract infection in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials.

ABSTRACT: 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.

SUBMITTER: Chen H

PROVIDER: S-EPMC7594481 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Association between inhaled corticosteroids and upper respiratory tract infection in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials.

Chen Hong H Feng Yulin Y Wang Ke K Yang Jing J Du Yuejun Y

BMC pulmonary medicine 20201028 1

<h4>Background</h4>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).<h4>Methods</h4>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 pros ...[more]

PMID: 33115481

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Project description:BackgroundThe fracture risk of patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids is controversial. And some large-scale randomized controlled trials have not solved this problem. The purpose of our systematic review and meta-analysis including 44 RCTs is to reveal the effect of inhaled corticosteroids on the fracture risk of COPD patients.MethodsTwo reviewers independently retrieved randomized controlled trials of inhaled corticosteroids or combinations of inhaled corticosteroids in the treatment of COPD from PubMed, Embase, Medline, Cochrane Library, and Web of Science. The primary outcome was a fracture event. This study was registered at PROSPERO (CRD42022366778).ResultsForty-four RCTs were performed in 87,594 patients. Inhaled therapy containing ICSs (RR, 1.19; 95%CI, 1.04-1.37; P = 0.010), especially ICS/LABA (RR, 1.30; 95%CI, 1.10-1.53; P = 0.002) and triple therapy (RR, 1.49; 95%CI, 1.03-2.17; P = 0.04) were significantly associated with the increased risk of fracture in COPD patients when compared with inhaled therapy without ICSs. Subgroup analyses showed that treatment duration ≥ 12 months (RR, 1.19; 95%CI, 1.04-1.38; P = 0.01), budesonide therapy (RR, 1.64; 95%CI., 1.07-2.51; P = 0.02), fluticasone furoate therapy (RR, 1.37; 95%CI, 1.05-1.78; P = 0.02), mean age of study participants ≥ 65 (RR, 1.27; 95%CI, 1.01-1.61; P = 0.04), and GOLD stage III(RR, 1.18; 95%CI, 1.00-1.38; P = 0.04) were significantly associated with an increased risk of fracture. In addition, budesonide ≥ 320 ug bid via MDI (RR, 1.75; 95%CI, 1.07-2.87; P = 0.03) was significantly associated with the increased risk of fracture.ConclusionInhalation therapy with ICSs, especially ICS/LABA or triple therapy, increased the risk of fracture in patients with COPD compared with inhaled therapy without ICS. Treatment duration, mean age of participants, GOLD stage, drug dosage form, and drug dose participated in this association. Moreover, different inhalation devices of the same drug also had differences in risk of fracture.

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.

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.

Dataset Information

Association between inhaled corticosteroids and upper respiratory tract infection in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials.

Publications

Association between inhaled corticosteroids and upper respiratory tract infection in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials.

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