Steroid use may increase mortality in acute exacerbation of fibrotic interstitial lung disease

A high mortality risk hounds patients with acute exacerbation (AE) of fibrotic interstitial lung disease (FILD) despite treatment with corticosteroids, reports a study, noting that such risk is similar to that seen in those with AE of idiopathic pulmonary fibrosis (IPF).

“AEs of IPF carry a high risk of mortality and this multicentre study demonstrates [that] there is also a considerable risk of increased mortality in exacerbations of other FILDs despite the use of corticosteroids,” the investigators said.

In this study, a code-based algorithm was used followed by individual case evaluation to filter patients with AE-FILD over a 10-year period. The investigators performed a binary logistic regression analysis to explore the association between corticosteroid treatment (≥0.5 mg/kg/day of prednisolone-equivalent for ≥3 days within the first 72 h of admission) and in-hospital mortality or need for lung transplantation.

Other outcomes assessed were as follows: readmission, overall survival, requirement for domiciliary oxygen, and rehabilitation.

One hundred seven patients with AE-FILD across two centres met the inclusion criteria, of whom 46 (43 percent) received acute steroid therapy. Those treated with steroids were younger, had fewer comorbidities but had higher oxygen requirements. [Respirology 2024;29:795-802]

Preadmission forced vital capacity and diffusing capacity for carbon monoxide, distribution of diagnoses, and smoking history were similar between cohorts.

The mean steroid dose was 4.59 mg/kg/day. Use of steroid appeared to contribute to a higher risk of inpatient mortality or transplantation (odds ratio, 4.11, 95 percent confidence interval [CI], 1.00‒16.83; p=0.049). However, in the steroid cohort, a reduced risk of all-cause mortality was observed in non-IPF patients (hazard ratio [HR], 0.21, 95 percent CI, 0.04‒0.96; p=0.04) compared with those with IPF.

Overall, the steroid group showed a lower median survival (221 vs 520.5 days), with a higher risk of all-cause mortality (HR, 3.25, 95 percent CI, 1.56‒6.77; p<0.01).

“This retrospective cohort study suggests that steroid use in patients with AEs of FILD may not reduce inpatient mortality and, in fact, may be potentially associated with increased risk of death or transplant, although there are several additional factors that may have contributed to this,” the investigators said.

Maladaptive response

While there have been several mechanisms proposed to explain the development of AEs, the predominant theme is that of maladaptive response to injury, which involved fibroblastic formation mediated by inflammatory cytokines. [Am J Respir Crit Care Med 2016;194:265-275]

Moreover, corticosteroids are considered as effective anti-inflammatory agents, but recent studies suggest that upregulation of cytokines, such as interleukin-17, in IPF-affected lung tissue may cancel the anti-inflammatory effect of corticosteroids, resulting in lack of clinical response. [Front Immunol 2022;13:905727]

“Although significant differences in disease severity and our study's retrospective design may act as confounders, these findings challenge the current paradigm to treat exacerbations of all FILD with immunosuppression,” the investigators said.

“Clinicians should consider other precipitating factors for exacerbations and use steroids judiciously,” they added.