No lung function recovery in cystic fibrosis exacerbations with systemic corticosteroids

Key takeaways:

• Percent predicted FEV₁ did not improve after systemic corticosteroid treatment.
• This treatment was also not linked to getting baseline lung function back.

Pediatric patients with cystic fibrosis hospitalized with an exacerbation showed no lung function improvement with systemic corticosteroids, according to study results published in Annals of the American Thoracic Society.

“In contrast to our hypothesis, systemic corticosteroids were not associated with better pre- to post-pulmonary exacerbation percent predicted FEV₁ responses or a higher odds of returning to lung function baseline, but consistent with our hypothesis, systemic corticosteroids use was associated with a 9% reduced chance of future pulmonary exacerbation requiring intravenous antibiotics compared with pulmonary exacerbation treatment without systemic corticosteroids,” Chelsea S. Davis, MD, clinical assistant professor of pediatrics at the University of Washington, and colleagues wrote.

In a retrospective cohort study, Davis and colleagues evaluated 3,471 patients aged 6 to 21 years with cystic fibrosis admitted into the hospital between 2006 and 2018 with a pulmonary exacerbation event to figure out whether treatment with systemic corticosteroids or without is better in terms of improving clinical outcomes.

Patients who received systemic corticosteroids — including enteral/intravenous prednisone, prednisolone, methylprednisolone or dexamethasone — for at least 3 days were classified into the treatment group.

Researchers used Cox proportional hazards regression to analyze the amount of time that passed between hospital discharge and admission for another exacerbation that needed to be treated with intravenous antibiotics (time to next pulmonary exacerbation) between those treated with and without corticosteroids. In order to compare patients’ lung function after treatment, researchers utilized both linear mixed-effect models and generalized estimating equations.

The number of exacerbations varied across the cohort, with 39% of patients experiencing one, 22% experiencing two and 39% experiencing three or more.

Of the total cohort, researchers observed 9,787 pulmonary exacerbations, of which systemic corticosteroid treatment was given in 1,499 (15%) cases. In terms of patients, this meant 556 patients (median age, 11.8 years; 43% boys; 40% with asthma) treated with systemic corticosteroids and 2,915 (median age, 12.7 years; 46% boys; 29% with asthma) not receiving this treatment.

At hospital admission, those receiving corticosteroid treatment had worse percent predicted FEV₁ (65.7%) than those not receiving the treatment (69%).

Main analysis

In terms of changes in lung functions after treatment, researchers did not find improvement in percent predicted FEV₁ with systemic corticosteroids (mean difference, –0.36; 95% CI, –1.14 to 0.42). Further, patients receiving this treatment did not have increased chances of reaching 90% or more of baseline percent predicted FEV₁ (OR = 0.97; 95% CI, 0.84-1.12).

Despite no improvements found in lung function measures, researchers did observe a lower risk for future pulmonary exacerbations that would need to be treated with intravenous antibiotics in patients on systemic corticosteroids (HR = 0.91; 95% CI, 0.85-0.96; P = .002) than patients not on corticosteroids. Notably, researchers wrote that this finding is probably not clinically relevant since there was only a small difference in median time to next pulmonary exacerbation between those with corticosteroids and those without (difference, 17 days).

Sensitivity analysis

In a sensitivity analysis of only patients who took systemic corticosteroids from day 1 to day 6 in the hospital, researchers found one outcome difference from their main analysis with a 2.39 improvement in lung function (95% CI, 1.52-3.27; P < .001) following corticosteroid treatment vs. no corticosteroid treatment.

Another sensitivity analysis was conducted, but this time accounted for only the patient’s first pulmonary exacerbation.

In this assessment, researchers did not find a lower risk for future pulmonary exacerbations that would need intravenous antibiotics in patients on systemic corticosteroids (HR = 0.96; 95% CI, 0.86-1.07) vs. those not on this treatment, which was previously observed in the main analysis. Both lung function outcomes in this analysis were comparable with what was observed in the main analysis, according to researchers.

“Prospective studies are needed to determine whether the clinical benefits seen (timing of systemic corticosteroids use during pulmonary exacerbation treatment) outweigh the potential important adverse effects that may develop with short-term systemic corticosteroid treatment for pulmonary exacerbations,” Davis and colleagues wrote.