Association Between Inhaled Corticosteroids and Upper Respiratory Tract Infection in Patients With Chronic Obstructive Pulmonary Disease

A Meta-Analysis of Randomized Controlled Trials

Hong Chen; Yulin Feng; Ke Wang; Jing Yang; Yuejun Du


BMC Pulm Med. 2020;20(282) 

In This Article


Study Protocol

This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations.[18] And the study was registered with PROSPERO prospectively (#CRD42020153134).

Search Strategy

Two reviewers independently searched PubMed, Embase, Cochrane Library and Clinical for eligible articles from inception to May 10, 2019, and updated on October, 16, 2019. Both free words and MeSH terms referring to inhaled corticosteroid and the risk of URTI were used as search terms, including "Pulmonary Disease, Chronic Obstructive" OR "chronic obstructive pulmonary disease" OR "COPD" OR "airflow obstruction, chronic" OR "chronic airflow obstruction" OR "chronic obstructive airway disease" OR "chronic obstructive lung disease" OR "Bronchitis" OR "emphysema" AND "ICS" OR "inhaled corticosteroids" OR "fluticasone" OR "flunisolide" OR "budesonide" OR "beclomethasone" OR "triamcinolone" OR "mometasone" OR "ciclesonide". We also conducted a manual search using the reference lists of key articles.

Eligibility Criteria

Eligible studies were identified through the PICOS criteria (participants, interventions, comparators, outcomes and study design).[18] Inclusion criteria included: (1) patients with COPD; (2) The interventions included any type of inhaled corticosteroids, including ICSs alone or combined with long-acting bronchodilators; (3) non-ICSs treatment as control, including placebo or other inhaled drugs of corticosteroid free; (4) only trials reporting data on URTI as the outcome were included; (5) Only RCTs were included. Exclusion criteria included: (1) non-RCTs, such as observational studies, case series and reviews; (2) non-English articles; (3) Patients with asthma or unknown diagnosis; (4) ICSs was used in both the treatment group and the control group.

Data Collection Process

Two investigators independently extracted relevant data from the included RCTs into standardized collection forms for the outcomes and evidence. Disagreements between the two investigators were resolved by discussion, and a third investigator was consulted if necessary. The corresponding authors were contacted when relevant data were not available.

Risk of Bias Assessment and Quality of Evidence

Two investigators independently performed the risk assessment using the Cochrane Collaboration risk of bias tool.[19] Any disagreements between the two investigators were resolved by discussion, and a third investigator was consulted if necessary. The included RCTs were assessed according to the following features (1) random sequence generation; (2) allocation concealment; (3) blinding of participants and personnel; (4) blinding of outcome assessment;(5) selective reporting; (6) incomplete outcome data; (7) other bias. Each item was assessed as low, unclear, or high risk of bias.

Statistical Analysis

We performed meta-analyses for quantitative data synthesis using Revman Software (v.5.3, Cochrane Collaboration, London, UK). The weights of each study were estimated by Mantel-Haenszel method. We calculated the risk ratio (RR) and 95% confidence interval (CI) for the risk of URTI. A two-tailed p value < 0.05 was set for statistical significance. Heterogeneity was assessed using the I2 test, with I2 > 50% indicating a substantial heterogeneity.[20] A random-effect model would be used when a substantial level of heterogeneity was found, otherwise a fixed-effect model would be used.

Subgroup Analysis

Subgroup analyses were conducted according to the following variables: (1) duration (long [≥ 6 months] and short [< 6 months]); (2) dosage of ICSs[21] (high dose [defined as > 500 μg/day of fluticasone propionate or equivalent], medium dose [defined as > 250–500 μg/day of fluticasone propionate or equivalent] and low dose [defined as 100–250 μg/day of fluticasone propionate or equivalent]); (3) type of ICSs, including fluticasone, mometasone, budesonide, and beclomethasone.