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April 06, 2023
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Inhaled corticosteroids lower risk for all-cause mortality in patients with COPD

Fact checked byKristen Dowd
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Key takeaways:

  • Inhaled corticosteroids were associated with lower odds for mortality in patients with COPD.
  • An eosinophil count of 200 cells/μL or more was the greatest predictor of this association.

Patients with COPD treated with inhaled corticosteroids for more than 6 months had a decreased risk for all-cause mortality, according to study results published in CHEST.

Further, several demographic characteristics were identified as predictors of lower odds for mortality when receiving inhaled corticosteroids, according to researchers.

Infographic showing Peto odds ratio of all-cause mortality risk among patients with COPD receiving inhaled therapy with inhaled corticosteroids
Data were derived from Chen H, et al. CHEST. 2023;doi:10.1016/j.chest.2022.07.015.

“Inhaled therapy containing inhaled corticosteroids [ICSs], especially triple therapy, should be used in the maintenance treatment of patients with COPD, especially in those with eosinophil counts of [at least 200 cells/μL],” Hong Chen, MD, of the department of respiratory and critical care medicine at Chengdu Second People’s Hospital, and colleagues wrote.

In a systematic review and meta-analysis, Chen and colleagues found and assessed 60 randomized controlled trials from a database search that included a total of 103,034 patients with COPD to find out how inhaled therapy including ICSs and the risk for all-cause mortality are related to each other. Researchers also looked for predictors of this association.

Of the total cohort, 60,552 patients had inhaled therapy with ICSs and 42,482 patients had inhaled therapy without them.

Compared with inhaled therapy not containing ICSs, researchers found a decreased risk for all-cause mortality linked to therapy with ICSs (Peto OR = 0.9; 95% CI, 0.84-0.97). Specifically looking at intervention type, this risk was found to decrease with triple therapy (Peto OR = 0.73; 95% CI, 0.59-0.91) and ICS plus long-acting beta agonists (Peto OR = 0.89; 95% CI, 0.81-0.97). Mono-ICS therapy showed the smallest reduction (Peto OR = 0.97; 95% CI, 0.87-1.08), according to researchers.

When assessing treatment length, longer than 6 months (Peto OR = 0.9; 95% CI, 0.83-0.97) was related to a lower risk for mortality compared with 6 months or less (Peto OR = 0.91; 95% CI, 0.64-1.29).

In terms of different levels of dosing, researchers found a decreased risk for all-cause mortality with medium-dose ICSs (Peto OR = 0.71; 95% CI, 0.56-0.91) or low-dose ICSs (Peto OR = 0.88; 95% CI, 0.79-0.97) in therapy compared with high-dose ICSs (Peto OR = 0.95; 95% CI, 0.85-1.07).

Among fluticasone propionate, fluticasone furoate, budesonide, mometasone furoate and beclomethasone dipropionate, a lower risk for all-cause mortality was only found with budesonide (Peto OR = 0.75; 95% CI, 0.59-0.94).

Researchers also found that several demographics at baseline predicted a lower risk for mortality in patients who received therapy with ICSs. These included:

  • eosinophil count of 200 cells/μL or greater (Peto OR = 0.58; 95% CI, 0.36-0.95);
  • eosinophil percentage of 2% or greater (Peto OR = 0.61; 95% CI, 0.42-0.9);
  • history of at least two moderate or severe exacerbations in the year prior (Peto OR = 0.63; 95% CI, 0.49-0.83);
  • Global Initiative for Chronic Obstructive Lung Disease stage III or IV lung function (Peto OR = 0.87; 95% CI, 0.78-0.96);
  • aged younger than 65 years (Peto OR = 0.81; 95% CI, 0.7-0.94); and
  • BMI of 25 kg/m2 or greater (Peto OR = 0.91; 95% CI, 0.84-0.99).

These results were confirmed in sensitivity analyses that did not factor in randomized controlled trials with a high risk for bias, trials published prior to 2016 and trials that fell in the last 50% when put in descending order of sample size.

“More studies are needed to identify the exact subgroups of patients with COPD who could benefit from the inhaled therapy containing ICSs for a reduction in the all-cause mortality risk and the relevant mechanisms,” Chen and colleagues wrote.

This study by Chen and colleagues contributes to growing literature on mortality risk associations with ICS for patients with COPD, but it has several limitations that should be considered when viewing the findings, according to an accompanying editorial by Darcy D. Marciniuk, MD, professor of respirology, critical care and sleep medicine at the University of Saskatchewan, and Luigino Calzetta, PhD, of the department of medicine and surgery at the University of Parma.

“Although the results of this study were positive, the findings provided by Chen et al should be interpreted with thoughtfulness, because the analysis was affected by substantial heterogeneity resulting not only from the inclusion of several studies that enrolled heterogeneous populations of COPD patients, but also because several formulations characterized by different regimens of administrations (once daily vs. twice daily) were compared and administered via different inhaler devices,” Marciniuk and Calzetta wrote. “Moreover, several formulations were compared, although there was not consistency between the bronchodilators included in each combination.”

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